Upper GI Tract

Antireflux surgery may be no more effective than antireflux medication for reducing risk of esophageal adenocarcinoma (EAC) among patients with Barrett’s esophagus, according to a Nordic retrospective study.

Risk of EAC was higher among patients who underwent surgery, and risk appeared to increase over time, suggesting that postoperative patients should continue to participate in surveillance programs, reported lead author Jesper Lagergren, MD, PhD, of the Karolinska Institutet, Stockholm, and colleagues.

Karolinska Institutet

“Antireflux surgery with fundoplication increases the ability of the gastroesophageal anatomic and physiological barrier to prevent reflux, and can thus prevent any carcinogenic gastric content from reaching the esophagus, including both acid and bile,” the investigators wrote in Gastroenterology, noting that surgery reduces esophageal acid exposure to a greater degree than medication. “Antireflux surgery may thus prevent esophageal adenocarcinoma better than antireflux medication.”

Three meta-analyses to date, however, have failed to provide consistent support for this hypothesis.

“Most of the studies included in these meta-analyses came from single centers, were of small sample size, examined only one treatment arm, and had a short or incomplete follow-up, and ... were hampered by heterogeneity among the included studies,” they noted.

For the present study, Dr. Lagergren and colleagues analyzed national registry data from 33,939 patients with Barrett’s esophagus in Denmark, Finland, Norway, and Sweden. Out of this group, 542 patients (1.6%) had undergone antireflux surgery, while the remainder were managed with antireflux medication.

In both groups, approximately two-thirds of the patients were men. The median age at enrollment was about a decade higher in the medication group (66 vs. 54 years), and this group also tended to have more comorbidities.

After a follow-up period as long as 32 years, the absolute rates of EAC were 1.3% and 2.6% in the medication and surgery groups, respectively. Multivariate analysis, with adjustments for sex, age, year, comorbidities, and age, revealed that postsurgical patients had a 90% increased risk of EAC (hazard ratio [HR], 1.9; 95% CI, 1.1-3.5), versus patients treated with antireflux medication alone.

The relatively higher risk of EAC appeared to increase over time, based on a nonsignificant hazard ratio of 1.8 during the 1- to 4-year follow-up period (HR, 1.8; 95% CI, 0.6-5.0), versus a significant, fourfold risk elevation during the 10- to 32-year follow-up period (HR, 4.4; 95% CI, 1.4-13.5).

“In this cohort of patients with Barrett’s esophagus, the risk of esophageal adenocarcinoma did not decrease after antireflux surgery compared with antireflux medication,” the investigators wrote. “Instead, the risk was increased throughout the follow-up among patients having undergone antireflux surgery.”

Dr. Lagergren and colleagues suggested that the reason for relatively higher cancer risk in the group that underwent surgery likely stems from early and prolonged acid exposure.

“[P]erforming antireflux surgery after years of GERD may be too late to enable a cancer-preventative effect, and most of the patients first diagnosed with Barrett’s esophagus reported a history of many years of GERD symptoms,” they wrote, suggesting that carcinogenic processes had already been set in motion by the time surgery was performed.

“[P]atients with Barrett’s esophagus who undergo antireflux surgery remain at an increased risk of esophageal adenocarcinoma and should continue taking part in surveillance programs,” the investigators concluded.

The study was funded by the Swedish Cancer Society, Swedish Research Council, and Stockholm County Council. The investigators disclosed no conflicts of interest.

Antireflux surgery may be no more effective than antireflux medication for reducing risk of esophageal adenocarcinoma (EAC) among patients with Barrett’s esophagus, according to a Nordic retrospective study.

Risk of EAC was higher among patients who underwent surgery, and risk appeared to increase over time, suggesting that postoperative patients should continue to participate in surveillance programs, reported lead author Jesper Lagergren, MD, PhD, of the Karolinska Institutet, Stockholm, and colleagues.

Karolinska Institutet

“Antireflux surgery with fundoplication increases the ability of the gastroesophageal anatomic and physiological barrier to prevent reflux, and can thus prevent any carcinogenic gastric content from reaching the esophagus, including both acid and bile,” the investigators wrote in Gastroenterology, noting that surgery reduces esophageal acid exposure to a greater degree than medication. “Antireflux surgery may thus prevent esophageal adenocarcinoma better than antireflux medication.”

Three meta-analyses to date, however, have failed to provide consistent support for this hypothesis.

“Most of the studies included in these meta-analyses came from single centers, were of small sample size, examined only one treatment arm, and had a short or incomplete follow-up, and ... were hampered by heterogeneity among the included studies,” they noted.

For the present study, Dr. Lagergren and colleagues analyzed national registry data from 33,939 patients with Barrett’s esophagus in Denmark, Finland, Norway, and Sweden. Out of this group, 542 patients (1.6%) had undergone antireflux surgery, while the remainder were managed with antireflux medication.

In both groups, approximately two-thirds of the patients were men. The median age at enrollment was about a decade higher in the medication group (66 vs. 54 years), and this group also tended to have more comorbidities.

After a follow-up period as long as 32 years, the absolute rates of EAC were 1.3% and 2.6% in the medication and surgery groups, respectively. Multivariate analysis, with adjustments for sex, age, year, comorbidities, and age, revealed that postsurgical patients had a 90% increased risk of EAC (hazard ratio [HR], 1.9; 95% CI, 1.1-3.5), versus patients treated with antireflux medication alone.

The relatively higher risk of EAC appeared to increase over time, based on a nonsignificant hazard ratio of 1.8 during the 1- to 4-year follow-up period (HR, 1.8; 95% CI, 0.6-5.0), versus a significant, fourfold risk elevation during the 10- to 32-year follow-up period (HR, 4.4; 95% CI, 1.4-13.5).

“In this cohort of patients with Barrett’s esophagus, the risk of esophageal adenocarcinoma did not decrease after antireflux surgery compared with antireflux medication,” the investigators wrote. “Instead, the risk was increased throughout the follow-up among patients having undergone antireflux surgery.”

Dr. Lagergren and colleagues suggested that the reason for relatively higher cancer risk in the group that underwent surgery likely stems from early and prolonged acid exposure.

“[P]erforming antireflux surgery after years of GERD may be too late to enable a cancer-preventative effect, and most of the patients first diagnosed with Barrett’s esophagus reported a history of many years of GERD symptoms,” they wrote, suggesting that carcinogenic processes had already been set in motion by the time surgery was performed.

“[P]atients with Barrett’s esophagus who undergo antireflux surgery remain at an increased risk of esophageal adenocarcinoma and should continue taking part in surveillance programs,” the investigators concluded.

The study was funded by the Swedish Cancer Society, Swedish Research Council, and Stockholm County Council. The investigators disclosed no conflicts of interest.

Antireflux surgery may be no more effective than antireflux medication for reducing risk of esophageal adenocarcinoma (EAC) among patients with Barrett’s esophagus, according to a Nordic retrospective study.

Risk of EAC was higher among patients who underwent surgery, and risk appeared to increase over time, suggesting that postoperative patients should continue to participate in surveillance programs, reported lead author Jesper Lagergren, MD, PhD, of the Karolinska Institutet, Stockholm, and colleagues.

Karolinska Institutet

“Antireflux surgery with fundoplication increases the ability of the gastroesophageal anatomic and physiological barrier to prevent reflux, and can thus prevent any carcinogenic gastric content from reaching the esophagus, including both acid and bile,” the investigators wrote in Gastroenterology, noting that surgery reduces esophageal acid exposure to a greater degree than medication. “Antireflux surgery may thus prevent esophageal adenocarcinoma better than antireflux medication.”

Three meta-analyses to date, however, have failed to provide consistent support for this hypothesis.

“Most of the studies included in these meta-analyses came from single centers, were of small sample size, examined only one treatment arm, and had a short or incomplete follow-up, and ... were hampered by heterogeneity among the included studies,” they noted.

For the present study, Dr. Lagergren and colleagues analyzed national registry data from 33,939 patients with Barrett’s esophagus in Denmark, Finland, Norway, and Sweden. Out of this group, 542 patients (1.6%) had undergone antireflux surgery, while the remainder were managed with antireflux medication.

In both groups, approximately two-thirds of the patients were men. The median age at enrollment was about a decade higher in the medication group (66 vs. 54 years), and this group also tended to have more comorbidities.

After a follow-up period as long as 32 years, the absolute rates of EAC were 1.3% and 2.6% in the medication and surgery groups, respectively. Multivariate analysis, with adjustments for sex, age, year, comorbidities, and age, revealed that postsurgical patients had a 90% increased risk of EAC (hazard ratio [HR], 1.9; 95% CI, 1.1-3.5), versus patients treated with antireflux medication alone.

The relatively higher risk of EAC appeared to increase over time, based on a nonsignificant hazard ratio of 1.8 during the 1- to 4-year follow-up period (HR, 1.8; 95% CI, 0.6-5.0), versus a significant, fourfold risk elevation during the 10- to 32-year follow-up period (HR, 4.4; 95% CI, 1.4-13.5).

“In this cohort of patients with Barrett’s esophagus, the risk of esophageal adenocarcinoma did not decrease after antireflux surgery compared with antireflux medication,” the investigators wrote. “Instead, the risk was increased throughout the follow-up among patients having undergone antireflux surgery.”

Dr. Lagergren and colleagues suggested that the reason for relatively higher cancer risk in the group that underwent surgery likely stems from early and prolonged acid exposure.

“[P]erforming antireflux surgery after years of GERD may be too late to enable a cancer-preventative effect, and most of the patients first diagnosed with Barrett’s esophagus reported a history of many years of GERD symptoms,” they wrote, suggesting that carcinogenic processes had already been set in motion by the time surgery was performed.

“[P]atients with Barrett’s esophagus who undergo antireflux surgery remain at an increased risk of esophageal adenocarcinoma and should continue taking part in surveillance programs,” the investigators concluded.

The study was funded by the Swedish Cancer Society, Swedish Research Council, and Stockholm County Council. The investigators disclosed no conflicts of interest.

Use of fluticasone and budesonide for eosinophilic esophagitis during pregnancy had no significant adverse effect on maternal or fetal outcomes, according to new research presented at the annual meeting of the American College of Gastroenterology.

“Currently, there are no specific recommendations about the safe use of steroids in pregnant women with eosinophilic esophagitis (EoE), Julton Tomanguillo Chumbe, MD, said in an interview. “Our recommendations about the use of steroids among this population are based on the safety data extrapolated mainly from pregnant women with asthma.”

West Virginia University

In the study, Dr. Chumbe, an internal medicine resident at Charleston Area Medical Center, West Virginia University, Charleston, and colleagues identified pregnant patients aged 18 years and older with a diagnosis of EoE between January 2011 and December 2022 through the TriNetx Global Collaborative Network, which includes 101 health care organizations in 14 countries. The study population consisted of 1,263 individuals.

The researchers used propensity score matching (PSM) to compare the rates of spontaneous abortion, placenta previa, preeclampsia, premature delivery, HELLP syndrome, eclampsia, hyperemesis gravidarum, and major congenital abnormalities between women with EoE who did and did not use steroids during pregnancy. The PSM cohorts included 268 women in each group.

Overall, pregnant women who used steroids were not significantly more likely than were those who did not use steroids to experience spontaneous abortion (3.73% vs. 4.85%, P = .52). Rates of placenta previa, preeclampsia, premature delivery, HELLP syndrome, and hyperemesis gravidarum were equal between the groups (3.73% vs. 3.73%, P = 1.00 for all). No cases of eclampsia occurred in the steroid group, compared with a 3.73% rate in women who did not use steroids.

Incidence of major congenital abnormalities including but not limited to malformations of the eye, ear, face, neck, skull and face bones, and of the circulatory, respiratory, and digestive systems, were similar between the steroid and no steroid groups (7.09% vs. 8.20%, P = .62)

Dr. Chumbe said he was not surprised by the findings, given the robust data about the safe use of steroids in pregnant women with asthma, in terms of pregnancy outcomes and fetal outcomes.

“The findings of this study provide reassurance that the use of steroids in pregnant patients with eosinophilic esophagitis is not significantly associated with an increased risk of worse maternal or fetal outcomes,” he said. “During pregnancy, some patients may discontinue treatment due to safety concerns. However, this study suggests that this may not be necessary.” Consequently, patients can maintain EoE management while reducing the risk of complications.

Looking ahead, “it will be important to have some data about the safe use of dupilumab during pregnancy in patients with eosinophilic esophagitis,” he said.
 

Pregnant patients can maintain EoE management

“This study is able to address an important concern that many patients have regarding the safety of steroid therapy for EoE, particularly during pregnancy,” said Anita Afzali, MD, MPH, AGAF, a gastroenterologist specializing in inflammatory bowel disease and executive vice chair of internal medicine at the University of Cincinnati. “As EoE impacts over 40% of women, most who are in childbearing age, it is important to review the safety of treatment and management of EoE so a mother does not have to choose between EoE management and pregnancy.”

The results from this study were certainly reassuring, though not surprising, Dr. Afzali said. “Previously, the safety profile of steroids during pregnancy was mostly extrapolated from asthma, and other diseases such as inflammatory bowel disease. The results from this study confirm that there are no significant associations with adverse maternal or birth outcomes among women with EoE treated with steroids during pregnancy,” she said.

The study has some limitations, including the retrospective design and potential for selection bias, Dr. Afzali noted. “Further research is needed for the evaluation of newer therapies in the pipeline for treatment of EoE and its safety profile with pregnancy,” she said.

However, “sharing this information in clinical practice “will allow our patients to feel comfortable with continuation of appropriate steroid therapy for treatment and management of their EoE, without having to choose between family planning or pregnancy and EoE care management,” Dr. Afzali said.

The study received no outside funding. Dr. Chumbe an Dr. Afzali indicated having no relevant financial conflicts to disclose.

Use of fluticasone and budesonide for eosinophilic esophagitis during pregnancy had no significant adverse effect on maternal or fetal outcomes, according to new research presented at the annual meeting of the American College of Gastroenterology.

“Currently, there are no specific recommendations about the safe use of steroids in pregnant women with eosinophilic esophagitis (EoE), Julton Tomanguillo Chumbe, MD, said in an interview. “Our recommendations about the use of steroids among this population are based on the safety data extrapolated mainly from pregnant women with asthma.”

West Virginia University

In the study, Dr. Chumbe, an internal medicine resident at Charleston Area Medical Center, West Virginia University, Charleston, and colleagues identified pregnant patients aged 18 years and older with a diagnosis of EoE between January 2011 and December 2022 through the TriNetx Global Collaborative Network, which includes 101 health care organizations in 14 countries. The study population consisted of 1,263 individuals.

The researchers used propensity score matching (PSM) to compare the rates of spontaneous abortion, placenta previa, preeclampsia, premature delivery, HELLP syndrome, eclampsia, hyperemesis gravidarum, and major congenital abnormalities between women with EoE who did and did not use steroids during pregnancy. The PSM cohorts included 268 women in each group.

Overall, pregnant women who used steroids were not significantly more likely than were those who did not use steroids to experience spontaneous abortion (3.73% vs. 4.85%, P = .52). Rates of placenta previa, preeclampsia, premature delivery, HELLP syndrome, and hyperemesis gravidarum were equal between the groups (3.73% vs. 3.73%, P = 1.00 for all). No cases of eclampsia occurred in the steroid group, compared with a 3.73% rate in women who did not use steroids.

Incidence of major congenital abnormalities including but not limited to malformations of the eye, ear, face, neck, skull and face bones, and of the circulatory, respiratory, and digestive systems, were similar between the steroid and no steroid groups (7.09% vs. 8.20%, P = .62)

Dr. Chumbe said he was not surprised by the findings, given the robust data about the safe use of steroids in pregnant women with asthma, in terms of pregnancy outcomes and fetal outcomes.

“The findings of this study provide reassurance that the use of steroids in pregnant patients with eosinophilic esophagitis is not significantly associated with an increased risk of worse maternal or fetal outcomes,” he said. “During pregnancy, some patients may discontinue treatment due to safety concerns. However, this study suggests that this may not be necessary.” Consequently, patients can maintain EoE management while reducing the risk of complications.

Looking ahead, “it will be important to have some data about the safe use of dupilumab during pregnancy in patients with eosinophilic esophagitis,” he said.
 

Pregnant patients can maintain EoE management

“This study is able to address an important concern that many patients have regarding the safety of steroid therapy for EoE, particularly during pregnancy,” said Anita Afzali, MD, MPH, AGAF, a gastroenterologist specializing in inflammatory bowel disease and executive vice chair of internal medicine at the University of Cincinnati. “As EoE impacts over 40% of women, most who are in childbearing age, it is important to review the safety of treatment and management of EoE so a mother does not have to choose between EoE management and pregnancy.”

The results from this study were certainly reassuring, though not surprising, Dr. Afzali said. “Previously, the safety profile of steroids during pregnancy was mostly extrapolated from asthma, and other diseases such as inflammatory bowel disease. The results from this study confirm that there are no significant associations with adverse maternal or birth outcomes among women with EoE treated with steroids during pregnancy,” she said.

The study has some limitations, including the retrospective design and potential for selection bias, Dr. Afzali noted. “Further research is needed for the evaluation of newer therapies in the pipeline for treatment of EoE and its safety profile with pregnancy,” she said.

However, “sharing this information in clinical practice “will allow our patients to feel comfortable with continuation of appropriate steroid therapy for treatment and management of their EoE, without having to choose between family planning or pregnancy and EoE care management,” Dr. Afzali said.

The study received no outside funding. Dr. Chumbe an Dr. Afzali indicated having no relevant financial conflicts to disclose.

Use of fluticasone and budesonide for eosinophilic esophagitis during pregnancy had no significant adverse effect on maternal or fetal outcomes, according to new research presented at the annual meeting of the American College of Gastroenterology.

“Currently, there are no specific recommendations about the safe use of steroids in pregnant women with eosinophilic esophagitis (EoE), Julton Tomanguillo Chumbe, MD, said in an interview. “Our recommendations about the use of steroids among this population are based on the safety data extrapolated mainly from pregnant women with asthma.”

West Virginia University

In the study, Dr. Chumbe, an internal medicine resident at Charleston Area Medical Center, West Virginia University, Charleston, and colleagues identified pregnant patients aged 18 years and older with a diagnosis of EoE between January 2011 and December 2022 through the TriNetx Global Collaborative Network, which includes 101 health care organizations in 14 countries. The study population consisted of 1,263 individuals.

The researchers used propensity score matching (PSM) to compare the rates of spontaneous abortion, placenta previa, preeclampsia, premature delivery, HELLP syndrome, eclampsia, hyperemesis gravidarum, and major congenital abnormalities between women with EoE who did and did not use steroids during pregnancy. The PSM cohorts included 268 women in each group.

Overall, pregnant women who used steroids were not significantly more likely than were those who did not use steroids to experience spontaneous abortion (3.73% vs. 4.85%, P = .52). Rates of placenta previa, preeclampsia, premature delivery, HELLP syndrome, and hyperemesis gravidarum were equal between the groups (3.73% vs. 3.73%, P = 1.00 for all). No cases of eclampsia occurred in the steroid group, compared with a 3.73% rate in women who did not use steroids.

Incidence of major congenital abnormalities including but not limited to malformations of the eye, ear, face, neck, skull and face bones, and of the circulatory, respiratory, and digestive systems, were similar between the steroid and no steroid groups (7.09% vs. 8.20%, P = .62)

Dr. Chumbe said he was not surprised by the findings, given the robust data about the safe use of steroids in pregnant women with asthma, in terms of pregnancy outcomes and fetal outcomes.

“The findings of this study provide reassurance that the use of steroids in pregnant patients with eosinophilic esophagitis is not significantly associated with an increased risk of worse maternal or fetal outcomes,” he said. “During pregnancy, some patients may discontinue treatment due to safety concerns. However, this study suggests that this may not be necessary.” Consequently, patients can maintain EoE management while reducing the risk of complications.

Looking ahead, “it will be important to have some data about the safe use of dupilumab during pregnancy in patients with eosinophilic esophagitis,” he said.
 

Pregnant patients can maintain EoE management

“This study is able to address an important concern that many patients have regarding the safety of steroid therapy for EoE, particularly during pregnancy,” said Anita Afzali, MD, MPH, AGAF, a gastroenterologist specializing in inflammatory bowel disease and executive vice chair of internal medicine at the University of Cincinnati. “As EoE impacts over 40% of women, most who are in childbearing age, it is important to review the safety of treatment and management of EoE so a mother does not have to choose between EoE management and pregnancy.”

The results from this study were certainly reassuring, though not surprising, Dr. Afzali said. “Previously, the safety profile of steroids during pregnancy was mostly extrapolated from asthma, and other diseases such as inflammatory bowel disease. The results from this study confirm that there are no significant associations with adverse maternal or birth outcomes among women with EoE treated with steroids during pregnancy,” she said.

The study has some limitations, including the retrospective design and potential for selection bias, Dr. Afzali noted. “Further research is needed for the evaluation of newer therapies in the pipeline for treatment of EoE and its safety profile with pregnancy,” she said.

However, “sharing this information in clinical practice “will allow our patients to feel comfortable with continuation of appropriate steroid therapy for treatment and management of their EoE, without having to choose between family planning or pregnancy and EoE care management,” Dr. Afzali said.

The study received no outside funding. Dr. Chumbe an Dr. Afzali indicated having no relevant financial conflicts to disclose.

The Food and Drug Administration has approved vonoprazan 10-mg and 20-mg tablets (Voquezna, Phathom Pharmaceuticals) for the healing and maintenance of all grades of erosive esophagitis, also known as erosive gastroesophageal reflux disease (GERD), as well as relief of associated heartburn, the company has announced.

Vonoprazan, an oral potassium-competitive acid blocker (PCAB), provides more potent inhibition of gastric acid than do proton pump inhibitors (PPIs) and is seen as a potential alternative.

Olivier Le Moal/Getty Images

The approval of vonoprazan for erosive GERD was based on results from the phase 3 PHALCON-EE study.

The randomized, double-blind, multicenter study enrolled 1,024 patients with erosive GERD in the United States and Europe and compared vonoprazan with the PPI lansoprazole (Prevacid) in the healing and maintenance of healing of erosive GERD and associated heartburn symptom relief.

Vonoprazan 20 mg was noninferior to lansoprazole 30 mg for complete healing by week 8 in patients with all grades of erosive GERD, with healing rates of 93% vs. 85% for lansoprazole.

In addition, vonoprazan showed superior rates of healing in patients with moderate to severe disease (LA Grade C/D) at week 2 (70% vs. 53% with lansoprazole). Vonoprazan was also noninferior to lansoprazole in terms of heartburn-free days over the healing period.

In the maintenance phase of the trial, vonoprazan 10 mg was superior to lansoprazole 15 mg in maintaining healing at 6 months in all patients who were randomly assigned (79% vs. 72%) and in the subset of patients with moderate to severe erosive GERD (75% vs. 61%).

Adverse event (AE) rates for vonoprazan were comparable to lansoprazole. The most common AEs in the healing phase (≥ 2% with vonoprazan) were gastritis, diarrhea, abdominal distention, abdominal pain, and nausea.

The most common AEs in the maintenance phase (≥ 3% with vonoprazan) were gastritis, abdominal pain, dyspepsia, hypertension, and urinary tract infection.

“For many GERD patients with erosive esophagitis, the response to current treatment is suboptimal, leaving them with incomplete healing and ongoing symptoms,” Colin W. Howden, MD, professor emeritus, University of Tennessee, Memphis, said in the news release.

Vonoprazan provides clinicians with a “new first-in-class therapeutic option that demonstrated faster healing in the more difficult-to-treat GERD patients with erosive esophagitis,” Dr. Howden added.

Vonoprazan is expected to be available in the United States in December.

The FDA also recently approved reformulated vonoprazan tablets for Voquezna Triple Pak (vonoprazan, amoxicillin, clarithromycin) and Voquezna Dual Pak (vonoprazan, amoxicillin) for the treatment of Helicobacter pylori infection in adults, Phathom Pharmaceuticals announced.

In February, the FDA had put both the vonoprazan new drug application for erosive esophagitis and the postapproval supplement for H. pylori on hold until the company addressed concerns over the presence of nitrosamine impurities.

Dr. Howden is a former editor-in-chief of GI&Hepatology News. A version of this article appeared on Medscape.com.

The Food and Drug Administration has approved vonoprazan 10-mg and 20-mg tablets (Voquezna, Phathom Pharmaceuticals) for the healing and maintenance of all grades of erosive esophagitis, also known as erosive gastroesophageal reflux disease (GERD), as well as relief of associated heartburn, the company has announced.

Vonoprazan, an oral potassium-competitive acid blocker (PCAB), provides more potent inhibition of gastric acid than do proton pump inhibitors (PPIs) and is seen as a potential alternative.

Olivier Le Moal/Getty Images

The approval of vonoprazan for erosive GERD was based on results from the phase 3 PHALCON-EE study.

The randomized, double-blind, multicenter study enrolled 1,024 patients with erosive GERD in the United States and Europe and compared vonoprazan with the PPI lansoprazole (Prevacid) in the healing and maintenance of healing of erosive GERD and associated heartburn symptom relief.

Vonoprazan 20 mg was noninferior to lansoprazole 30 mg for complete healing by week 8 in patients with all grades of erosive GERD, with healing rates of 93% vs. 85% for lansoprazole.

In addition, vonoprazan showed superior rates of healing in patients with moderate to severe disease (LA Grade C/D) at week 2 (70% vs. 53% with lansoprazole). Vonoprazan was also noninferior to lansoprazole in terms of heartburn-free days over the healing period.

In the maintenance phase of the trial, vonoprazan 10 mg was superior to lansoprazole 15 mg in maintaining healing at 6 months in all patients who were randomly assigned (79% vs. 72%) and in the subset of patients with moderate to severe erosive GERD (75% vs. 61%).

Adverse event (AE) rates for vonoprazan were comparable to lansoprazole. The most common AEs in the healing phase (≥ 2% with vonoprazan) were gastritis, diarrhea, abdominal distention, abdominal pain, and nausea.

The most common AEs in the maintenance phase (≥ 3% with vonoprazan) were gastritis, abdominal pain, dyspepsia, hypertension, and urinary tract infection.

“For many GERD patients with erosive esophagitis, the response to current treatment is suboptimal, leaving them with incomplete healing and ongoing symptoms,” Colin W. Howden, MD, professor emeritus, University of Tennessee, Memphis, said in the news release.

Vonoprazan provides clinicians with a “new first-in-class therapeutic option that demonstrated faster healing in the more difficult-to-treat GERD patients with erosive esophagitis,” Dr. Howden added.

Vonoprazan is expected to be available in the United States in December.

The FDA also recently approved reformulated vonoprazan tablets for Voquezna Triple Pak (vonoprazan, amoxicillin, clarithromycin) and Voquezna Dual Pak (vonoprazan, amoxicillin) for the treatment of Helicobacter pylori infection in adults, Phathom Pharmaceuticals announced.

In February, the FDA had put both the vonoprazan new drug application for erosive esophagitis and the postapproval supplement for H. pylori on hold until the company addressed concerns over the presence of nitrosamine impurities.

Dr. Howden is a former editor-in-chief of GI&Hepatology News. A version of this article appeared on Medscape.com.

The Food and Drug Administration has approved vonoprazan 10-mg and 20-mg tablets (Voquezna, Phathom Pharmaceuticals) for the healing and maintenance of all grades of erosive esophagitis, also known as erosive gastroesophageal reflux disease (GERD), as well as relief of associated heartburn, the company has announced.

Vonoprazan, an oral potassium-competitive acid blocker (PCAB), provides more potent inhibition of gastric acid than do proton pump inhibitors (PPIs) and is seen as a potential alternative.

Olivier Le Moal/Getty Images

The approval of vonoprazan for erosive GERD was based on results from the phase 3 PHALCON-EE study.

The randomized, double-blind, multicenter study enrolled 1,024 patients with erosive GERD in the United States and Europe and compared vonoprazan with the PPI lansoprazole (Prevacid) in the healing and maintenance of healing of erosive GERD and associated heartburn symptom relief.

Vonoprazan 20 mg was noninferior to lansoprazole 30 mg for complete healing by week 8 in patients with all grades of erosive GERD, with healing rates of 93% vs. 85% for lansoprazole.

In addition, vonoprazan showed superior rates of healing in patients with moderate to severe disease (LA Grade C/D) at week 2 (70% vs. 53% with lansoprazole). Vonoprazan was also noninferior to lansoprazole in terms of heartburn-free days over the healing period.

In the maintenance phase of the trial, vonoprazan 10 mg was superior to lansoprazole 15 mg in maintaining healing at 6 months in all patients who were randomly assigned (79% vs. 72%) and in the subset of patients with moderate to severe erosive GERD (75% vs. 61%).

Adverse event (AE) rates for vonoprazan were comparable to lansoprazole. The most common AEs in the healing phase (≥ 2% with vonoprazan) were gastritis, diarrhea, abdominal distention, abdominal pain, and nausea.

The most common AEs in the maintenance phase (≥ 3% with vonoprazan) were gastritis, abdominal pain, dyspepsia, hypertension, and urinary tract infection.

“For many GERD patients with erosive esophagitis, the response to current treatment is suboptimal, leaving them with incomplete healing and ongoing symptoms,” Colin W. Howden, MD, professor emeritus, University of Tennessee, Memphis, said in the news release.

Vonoprazan provides clinicians with a “new first-in-class therapeutic option that demonstrated faster healing in the more difficult-to-treat GERD patients with erosive esophagitis,” Dr. Howden added.

Vonoprazan is expected to be available in the United States in December.

The FDA also recently approved reformulated vonoprazan tablets for Voquezna Triple Pak (vonoprazan, amoxicillin, clarithromycin) and Voquezna Dual Pak (vonoprazan, amoxicillin) for the treatment of Helicobacter pylori infection in adults, Phathom Pharmaceuticals announced.

In February, the FDA had put both the vonoprazan new drug application for erosive esophagitis and the postapproval supplement for H. pylori on hold until the company addressed concerns over the presence of nitrosamine impurities.

Dr. Howden is a former editor-in-chief of GI&Hepatology News. A version of this article appeared on Medscape.com.

COPENHAGEN – A real-time, blood-sensing capsule that detects upper gastrointestinal bleeding (UGIB) is safe and effective for patients before undergoing upper endoscopy, according to results from the first U.S.-based open-label, single-arm comparative clinical trial of a novel bleeding sensor for patients with suspected UGIB. It is also the largest such trial.

The capsule (PillSense, EnteraSense) is rapidly deployed, safe to use, and easy to interpret, study researchers say. In under 7 minutes, it correctly detected the presence of blood in 26 of 28 patients and its absence in 87 of 96 patients, as confirmed afterward by esophagogastroduodenoscopy (EGD).

“The use of the PillSense system will positively impact patient outcomes by providing early diagnosis, triaging, and directing care for UGIB,” said Karl Akiki, MD, study lead, who is in the division of gastroenterology and hepatology at the Mayo Clinic, Rochester, Minn. He presented the results at the annual United European Gastroenterology Week.

“Due to its ability to rapidly diagnose UGIB, it helps us, as doctors, expedite accurate clinical decision-making while also optimizing services to ensure the maximum number of patients obtain the best outcome,” he told this news organization.

“There are some pre-endoscopic assessment scores, like the Rockell or the Glasgow-Blatchford score, but they have limited clinical utility in predicting and confirming bleeding in suspected patients,” explained Dr. Akiki. He highlighted the need for a novel device that is rapid, accurate, and safe to use. He also pointed out that despite being the gold standard for diagnosis, EGD remains challenging in terms of time, personnel, and resources.

“The results of our study show the PillSense is a good diagnostic tool that will aid triage,” he said. He noted that PillSense and EGD supplement each other in patient care.

It’s not a device to replace the EGD itself,” he explained, but given the results from the capsule, it will act “as a kind of a bridge that helps us to determine which patients should undergo EGD.”

Optical sensing technology

The researchers aimed to assess the safety and efficacy of the PillSense system for patients with suspected UGIB. They enrolled 131 patients (mean age, 62 years), 60% of whom were men. The most common presenting symptoms for UGIB were melena (52%), anemia (41%), and hematemesis (15%). Five participants withdrew consent before capsule ingestion, and for two patients, primary endpoint data were missing. This left an intent-to-treat population of 124 patients; 110 completed the study.

Patients were asked to swallow the capsule and to lay on their left side. The PillSense is based on optical sensing technology that uses an optical signature of blood in the gut. The device differentiates blood from any other liquids that may be present. After 5-7 minutes, the device gathers and transmits data wirelessly to an external, handheld receiver that processes binary data and indicates either “blood detected” or “no blood detected” in the upper GI tract, explained Dr. Akiki.

Following the capsule reading, patients underwent EGD within 4 hours. This enabled the researchers to compare data between the two modalities. Follow-up visits were conducted on days 7, 14, and 21 to ensure the capsule had passed from the body. Endoscopists were blinded to the capsule result when reading the EGD.

Primary endpoints were the sensitivity and specificity of the device; secondary endpoints were positive predictive value, negative predictive value, successful passage of the capsule, and safety.
 

Rapid and accurate

The researchers determined the efficiency of the capsule in correctly detecting a UGIB. The capsule’s positive and negative predictive values were 74.3% and 97.8%, respectively.

“We achieved a sensitivity of around 93% (92.9%; P = 0.024) with the PillSense capsule and a specificity of 91% (90.6%; P < .001]), which were pretty good. We also detected a range from minimal bleeding – so, speckles of blood to large amounts of active bleeding covering the entire stomach,” reported Dr. Akiki.

There were no differences in terms of patient demographics, laboratory results, or concomitant use of medications. PillSense recording time was a mean of 6.71 minutes, the time from capsule ingestion to EGD was a mean of 55 minutes, and the time to capsule passage through the GI tract was 3.6 days. Most bleeds were found to be in the stomach (18/30; 60%), followed by the duodenum (5/30; 16.6%).

Various capsules for detecting UGIB are under development or are already available, but unlike some of the others, “[the PillSense] is not a video capsule,” said Dr. Akiki. “It does not take pictures at all but is more of a photo sensor capsule that measures the absorption of wavelengths.”

This explains why the PillSense was so rapid – results were available in around 7 minutes and did not require an interpretation by a physician, he explained. “Trained non-physician personnel can use it, and this is where it differs from other devices, such as video capsules that require someone highly trained to interpret the output. It’s an easy procedure and process to follow.”

The PillSense has value in improving workflow, Dr. Akiki said. “If we had someone come in during the night with a suspected upper GI bleed, we could give them the capsule, determine if they need an EGD or not, and potentially postpone it to a time – say, the morning, when more resources are available – freeing up the night for emergency cases. It helps me, as a physician, to determine which patients to send to EGD immediately or which to wait.”

He added that more studies are needed in the postmarketing phase to understand optimal use of the device and to define the exact clinical pathway for optimal implementation.

The device was approved by the U.S. Food and Drug Administration in February. Dr. Akiki noted that there were no adverse events or deaths related to the capsule.

Co-moderator, Philip Chiu, MD, a gastroenterologist from the Chinese University of Hong Kong, said, “It’s an interesting study, because sometimes we can’t differentiate by clinical symptoms as to whether this is a problem of continuous bleeding or something else. The capsule might help us in our decision-making in this respect and help determine whether we should scope the patients or just manage conservatively.”

Dr. Akiki and Dr. Chiu have disclosed no relevant financial relationships.

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

COPENHAGEN – A real-time, blood-sensing capsule that detects upper gastrointestinal bleeding (UGIB) is safe and effective for patients before undergoing upper endoscopy, according to results from the first U.S.-based open-label, single-arm comparative clinical trial of a novel bleeding sensor for patients with suspected UGIB. It is also the largest such trial.

The capsule (PillSense, EnteraSense) is rapidly deployed, safe to use, and easy to interpret, study researchers say. In under 7 minutes, it correctly detected the presence of blood in 26 of 28 patients and its absence in 87 of 96 patients, as confirmed afterward by esophagogastroduodenoscopy (EGD).

“The use of the PillSense system will positively impact patient outcomes by providing early diagnosis, triaging, and directing care for UGIB,” said Karl Akiki, MD, study lead, who is in the division of gastroenterology and hepatology at the Mayo Clinic, Rochester, Minn. He presented the results at the annual United European Gastroenterology Week.

“Due to its ability to rapidly diagnose UGIB, it helps us, as doctors, expedite accurate clinical decision-making while also optimizing services to ensure the maximum number of patients obtain the best outcome,” he told this news organization.

“There are some pre-endoscopic assessment scores, like the Rockell or the Glasgow-Blatchford score, but they have limited clinical utility in predicting and confirming bleeding in suspected patients,” explained Dr. Akiki. He highlighted the need for a novel device that is rapid, accurate, and safe to use. He also pointed out that despite being the gold standard for diagnosis, EGD remains challenging in terms of time, personnel, and resources.

“The results of our study show the PillSense is a good diagnostic tool that will aid triage,” he said. He noted that PillSense and EGD supplement each other in patient care.

It’s not a device to replace the EGD itself,” he explained, but given the results from the capsule, it will act “as a kind of a bridge that helps us to determine which patients should undergo EGD.”

Optical sensing technology

The researchers aimed to assess the safety and efficacy of the PillSense system for patients with suspected UGIB. They enrolled 131 patients (mean age, 62 years), 60% of whom were men. The most common presenting symptoms for UGIB were melena (52%), anemia (41%), and hematemesis (15%). Five participants withdrew consent before capsule ingestion, and for two patients, primary endpoint data were missing. This left an intent-to-treat population of 124 patients; 110 completed the study.

Patients were asked to swallow the capsule and to lay on their left side. The PillSense is based on optical sensing technology that uses an optical signature of blood in the gut. The device differentiates blood from any other liquids that may be present. After 5-7 minutes, the device gathers and transmits data wirelessly to an external, handheld receiver that processes binary data and indicates either “blood detected” or “no blood detected” in the upper GI tract, explained Dr. Akiki.

Following the capsule reading, patients underwent EGD within 4 hours. This enabled the researchers to compare data between the two modalities. Follow-up visits were conducted on days 7, 14, and 21 to ensure the capsule had passed from the body. Endoscopists were blinded to the capsule result when reading the EGD.

Primary endpoints were the sensitivity and specificity of the device; secondary endpoints were positive predictive value, negative predictive value, successful passage of the capsule, and safety.
 

Rapid and accurate

The researchers determined the efficiency of the capsule in correctly detecting a UGIB. The capsule’s positive and negative predictive values were 74.3% and 97.8%, respectively.

“We achieved a sensitivity of around 93% (92.9%; P = 0.024) with the PillSense capsule and a specificity of 91% (90.6%; P < .001]), which were pretty good. We also detected a range from minimal bleeding – so, speckles of blood to large amounts of active bleeding covering the entire stomach,” reported Dr. Akiki.

There were no differences in terms of patient demographics, laboratory results, or concomitant use of medications. PillSense recording time was a mean of 6.71 minutes, the time from capsule ingestion to EGD was a mean of 55 minutes, and the time to capsule passage through the GI tract was 3.6 days. Most bleeds were found to be in the stomach (18/30; 60%), followed by the duodenum (5/30; 16.6%).

Various capsules for detecting UGIB are under development or are already available, but unlike some of the others, “[the PillSense] is not a video capsule,” said Dr. Akiki. “It does not take pictures at all but is more of a photo sensor capsule that measures the absorption of wavelengths.”

This explains why the PillSense was so rapid – results were available in around 7 minutes and did not require an interpretation by a physician, he explained. “Trained non-physician personnel can use it, and this is where it differs from other devices, such as video capsules that require someone highly trained to interpret the output. It’s an easy procedure and process to follow.”

The PillSense has value in improving workflow, Dr. Akiki said. “If we had someone come in during the night with a suspected upper GI bleed, we could give them the capsule, determine if they need an EGD or not, and potentially postpone it to a time – say, the morning, when more resources are available – freeing up the night for emergency cases. It helps me, as a physician, to determine which patients to send to EGD immediately or which to wait.”

He added that more studies are needed in the postmarketing phase to understand optimal use of the device and to define the exact clinical pathway for optimal implementation.

The device was approved by the U.S. Food and Drug Administration in February. Dr. Akiki noted that there were no adverse events or deaths related to the capsule.

Co-moderator, Philip Chiu, MD, a gastroenterologist from the Chinese University of Hong Kong, said, “It’s an interesting study, because sometimes we can’t differentiate by clinical symptoms as to whether this is a problem of continuous bleeding or something else. The capsule might help us in our decision-making in this respect and help determine whether we should scope the patients or just manage conservatively.”

Dr. Akiki and Dr. Chiu have disclosed no relevant financial relationships.

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

COPENHAGEN – A real-time, blood-sensing capsule that detects upper gastrointestinal bleeding (UGIB) is safe and effective for patients before undergoing upper endoscopy, according to results from the first U.S.-based open-label, single-arm comparative clinical trial of a novel bleeding sensor for patients with suspected UGIB. It is also the largest such trial.

The capsule (PillSense, EnteraSense) is rapidly deployed, safe to use, and easy to interpret, study researchers say. In under 7 minutes, it correctly detected the presence of blood in 26 of 28 patients and its absence in 87 of 96 patients, as confirmed afterward by esophagogastroduodenoscopy (EGD).

“The use of the PillSense system will positively impact patient outcomes by providing early diagnosis, triaging, and directing care for UGIB,” said Karl Akiki, MD, study lead, who is in the division of gastroenterology and hepatology at the Mayo Clinic, Rochester, Minn. He presented the results at the annual United European Gastroenterology Week.

“Due to its ability to rapidly diagnose UGIB, it helps us, as doctors, expedite accurate clinical decision-making while also optimizing services to ensure the maximum number of patients obtain the best outcome,” he told this news organization.

“There are some pre-endoscopic assessment scores, like the Rockell or the Glasgow-Blatchford score, but they have limited clinical utility in predicting and confirming bleeding in suspected patients,” explained Dr. Akiki. He highlighted the need for a novel device that is rapid, accurate, and safe to use. He also pointed out that despite being the gold standard for diagnosis, EGD remains challenging in terms of time, personnel, and resources.

“The results of our study show the PillSense is a good diagnostic tool that will aid triage,” he said. He noted that PillSense and EGD supplement each other in patient care.

It’s not a device to replace the EGD itself,” he explained, but given the results from the capsule, it will act “as a kind of a bridge that helps us to determine which patients should undergo EGD.”

Optical sensing technology

The researchers aimed to assess the safety and efficacy of the PillSense system for patients with suspected UGIB. They enrolled 131 patients (mean age, 62 years), 60% of whom were men. The most common presenting symptoms for UGIB were melena (52%), anemia (41%), and hematemesis (15%). Five participants withdrew consent before capsule ingestion, and for two patients, primary endpoint data were missing. This left an intent-to-treat population of 124 patients; 110 completed the study.

Patients were asked to swallow the capsule and to lay on their left side. The PillSense is based on optical sensing technology that uses an optical signature of blood in the gut. The device differentiates blood from any other liquids that may be present. After 5-7 minutes, the device gathers and transmits data wirelessly to an external, handheld receiver that processes binary data and indicates either “blood detected” or “no blood detected” in the upper GI tract, explained Dr. Akiki.

Following the capsule reading, patients underwent EGD within 4 hours. This enabled the researchers to compare data between the two modalities. Follow-up visits were conducted on days 7, 14, and 21 to ensure the capsule had passed from the body. Endoscopists were blinded to the capsule result when reading the EGD.

Primary endpoints were the sensitivity and specificity of the device; secondary endpoints were positive predictive value, negative predictive value, successful passage of the capsule, and safety.
 

Rapid and accurate

The researchers determined the efficiency of the capsule in correctly detecting a UGIB. The capsule’s positive and negative predictive values were 74.3% and 97.8%, respectively.

“We achieved a sensitivity of around 93% (92.9%; P = 0.024) with the PillSense capsule and a specificity of 91% (90.6%; P < .001]), which were pretty good. We also detected a range from minimal bleeding – so, speckles of blood to large amounts of active bleeding covering the entire stomach,” reported Dr. Akiki.

There were no differences in terms of patient demographics, laboratory results, or concomitant use of medications. PillSense recording time was a mean of 6.71 minutes, the time from capsule ingestion to EGD was a mean of 55 minutes, and the time to capsule passage through the GI tract was 3.6 days. Most bleeds were found to be in the stomach (18/30; 60%), followed by the duodenum (5/30; 16.6%).

Various capsules for detecting UGIB are under development or are already available, but unlike some of the others, “[the PillSense] is not a video capsule,” said Dr. Akiki. “It does not take pictures at all but is more of a photo sensor capsule that measures the absorption of wavelengths.”

This explains why the PillSense was so rapid – results were available in around 7 minutes and did not require an interpretation by a physician, he explained. “Trained non-physician personnel can use it, and this is where it differs from other devices, such as video capsules that require someone highly trained to interpret the output. It’s an easy procedure and process to follow.”

The PillSense has value in improving workflow, Dr. Akiki said. “If we had someone come in during the night with a suspected upper GI bleed, we could give them the capsule, determine if they need an EGD or not, and potentially postpone it to a time – say, the morning, when more resources are available – freeing up the night for emergency cases. It helps me, as a physician, to determine which patients to send to EGD immediately or which to wait.”

He added that more studies are needed in the postmarketing phase to understand optimal use of the device and to define the exact clinical pathway for optimal implementation.

The device was approved by the U.S. Food and Drug Administration in February. Dr. Akiki noted that there were no adverse events or deaths related to the capsule.

Co-moderator, Philip Chiu, MD, a gastroenterologist from the Chinese University of Hong Kong, said, “It’s an interesting study, because sometimes we can’t differentiate by clinical symptoms as to whether this is a problem of continuous bleeding or something else. The capsule might help us in our decision-making in this respect and help determine whether we should scope the patients or just manage conservatively.”

Dr. Akiki and Dr. Chiu have disclosed no relevant financial relationships.

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

TOPLINE:

Dupilumab provides histologic, endoscopic, and symptomatic improvement in patients with severe, treatment-refractory, fibrostenotic eosinophilic esophagitis (EoE), new research shows.

METHODOLOGY:

• The researchers conducted a retrospective cohort study of 46 patients with severe, treatment-refractory fibrostenotic EoE who were prescribed dupilumab 300 mg subcutaneously every other week or weekly.
• Histologic response, endoscopic severity, and symptom improvement were assessed using the results of esophagogastroduodenoscopy (EGD) conducted before and after dupilumab therapy.

TAKEAWAY:

• Most patients demonstrated endoscopic, histologic, and symptomatic improvement on dupilumab, compared with predupilumab EGD results.
• The average peak eosinophil count improved from 70 eosinophils/high-power field to 9 eosinophils/HPF while on dupilumab, and 80% of patients achieved histologic remission (< 15 eosinophils/HPF), compared with 11% before dupilumab.
• Endoscopic features also improved on dupilumab, with a significant reduction in exudates, rings, edema, and furrows. The total EoE Endoscopic Reference Score decreased from 4.62 to 1.89 (P < .001).
• With dupilumab, a significant increase in predilation esophageal diameter (from 13.9 to 16 mm; P < .001) was observed, with no change in the proportion of strictures.
• Global symptom improvement was reported in 91% of patients while on dupilumab versus 2% before dupilumab.

IN PRACTICE:

“These results echo the results from the prior phase 3 study, but in a population where most subjects would likely have been excluded due to stricture severity and need for dilation,” the authors wrote. “Dupilumab has real-world efficacy for a patient population with severe fibrostenotic EoE. Further studies are needed to determine not only long-term efficacy of dupilumab for this group of EoE patients, but whether dupilumab could be moved earlier in the treatment algorithm for this severe subgroup.”

SOURCE:

The study, by Christopher Lee, MD, and Evan Dellon, MD, MPH, with the Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, was published online in Clinical Gastroenterology and Hepatology.

LIMITATIONS:

The study involved a single tertiary care center, which could limit the generalizability of the findings. The patients were primarily adults, so the results may not be able to be extended to younger children.

DISCLOSURES:

The study had no specific funding. Dr. Dellon has received research funding and consulting fees from multiple pharmaceutical companies. Dr. Lee has no relevant disclosures.

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

TOPLINE:

Dupilumab provides histologic, endoscopic, and symptomatic improvement in patients with severe, treatment-refractory, fibrostenotic eosinophilic esophagitis (EoE), new research shows.

METHODOLOGY:

• The researchers conducted a retrospective cohort study of 46 patients with severe, treatment-refractory fibrostenotic EoE who were prescribed dupilumab 300 mg subcutaneously every other week or weekly.
• Histologic response, endoscopic severity, and symptom improvement were assessed using the results of esophagogastroduodenoscopy (EGD) conducted before and after dupilumab therapy.

TAKEAWAY:

• Most patients demonstrated endoscopic, histologic, and symptomatic improvement on dupilumab, compared with predupilumab EGD results.
• The average peak eosinophil count improved from 70 eosinophils/high-power field to 9 eosinophils/HPF while on dupilumab, and 80% of patients achieved histologic remission (< 15 eosinophils/HPF), compared with 11% before dupilumab.
• Endoscopic features also improved on dupilumab, with a significant reduction in exudates, rings, edema, and furrows. The total EoE Endoscopic Reference Score decreased from 4.62 to 1.89 (P < .001).
• With dupilumab, a significant increase in predilation esophageal diameter (from 13.9 to 16 mm; P < .001) was observed, with no change in the proportion of strictures.
• Global symptom improvement was reported in 91% of patients while on dupilumab versus 2% before dupilumab.

IN PRACTICE:

“These results echo the results from the prior phase 3 study, but in a population where most subjects would likely have been excluded due to stricture severity and need for dilation,” the authors wrote. “Dupilumab has real-world efficacy for a patient population with severe fibrostenotic EoE. Further studies are needed to determine not only long-term efficacy of dupilumab for this group of EoE patients, but whether dupilumab could be moved earlier in the treatment algorithm for this severe subgroup.”

SOURCE:

The study, by Christopher Lee, MD, and Evan Dellon, MD, MPH, with the Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, was published online in Clinical Gastroenterology and Hepatology.

LIMITATIONS:

The study involved a single tertiary care center, which could limit the generalizability of the findings. The patients were primarily adults, so the results may not be able to be extended to younger children.

DISCLOSURES:

The study had no specific funding. Dr. Dellon has received research funding and consulting fees from multiple pharmaceutical companies. Dr. Lee has no relevant disclosures.

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

TOPLINE:

Dupilumab provides histologic, endoscopic, and symptomatic improvement in patients with severe, treatment-refractory, fibrostenotic eosinophilic esophagitis (EoE), new research shows.

METHODOLOGY:

• The researchers conducted a retrospective cohort study of 46 patients with severe, treatment-refractory fibrostenotic EoE who were prescribed dupilumab 300 mg subcutaneously every other week or weekly.
• Histologic response, endoscopic severity, and symptom improvement were assessed using the results of esophagogastroduodenoscopy (EGD) conducted before and after dupilumab therapy.

TAKEAWAY:

• Most patients demonstrated endoscopic, histologic, and symptomatic improvement on dupilumab, compared with predupilumab EGD results.
• The average peak eosinophil count improved from 70 eosinophils/high-power field to 9 eosinophils/HPF while on dupilumab, and 80% of patients achieved histologic remission (< 15 eosinophils/HPF), compared with 11% before dupilumab.
• Endoscopic features also improved on dupilumab, with a significant reduction in exudates, rings, edema, and furrows. The total EoE Endoscopic Reference Score decreased from 4.62 to 1.89 (P < .001).
• With dupilumab, a significant increase in predilation esophageal diameter (from 13.9 to 16 mm; P < .001) was observed, with no change in the proportion of strictures.
• Global symptom improvement was reported in 91% of patients while on dupilumab versus 2% before dupilumab.

IN PRACTICE:

“These results echo the results from the prior phase 3 study, but in a population where most subjects would likely have been excluded due to stricture severity and need for dilation,” the authors wrote. “Dupilumab has real-world efficacy for a patient population with severe fibrostenotic EoE. Further studies are needed to determine not only long-term efficacy of dupilumab for this group of EoE patients, but whether dupilumab could be moved earlier in the treatment algorithm for this severe subgroup.”

SOURCE:

The study, by Christopher Lee, MD, and Evan Dellon, MD, MPH, with the Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, was published online in Clinical Gastroenterology and Hepatology.

LIMITATIONS:

The study involved a single tertiary care center, which could limit the generalizability of the findings. The patients were primarily adults, so the results may not be able to be extended to younger children.

DISCLOSURES:

The study had no specific funding. Dr. Dellon has received research funding and consulting fees from multiple pharmaceutical companies. Dr. Lee has no relevant disclosures.

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

Most available drugs for eosinophilic esophagitis (EoE) demonstrate greater efficacy than placebo, but data are too heterogenous to determine a reliable therapeutic hierarchy, shows a meta-analysis published in Gut.

Among agents available outside of clinical trials, the corticosteroid budesonide had the broadest evidence base for efficacy, while EoE-specific topical steroids typically outperformed adapted asthma formulations, wrote authors who were led by Edoardo Savarino, MD, PhD, of the department of surgery, oncology and gastroenterology at the University of Padua, Italy.

The AGA Institute and the Joint Task Force on Allergy-Immunology Practice Parameters published clinical practice guidelines for eosinophilic esophagitis in 2020. The group issued 12 recommendations with only 1, the topical use of glucocorticosteroids over no treatment, being a “strong recommendation.” Both the AGA/JTF guidelines and guidelines issued May 23, 2022 , by the British Society of Gastroenterology and British Society of Pediatric Gastroenterology, Hepatology and Nutrition, recommend the use of proton pump inhibitors (PPIs) and topical glucocorticosteroids in certain cases. Neither set of guidelines addresses the use of dupilumab, which was approved in the United States on May 20, 2022, for adults and pediatric patients 12 years and older, and in January of this year by the European Commission for the same condition.

The current study is a meta-analysis that compared data from 1,813 subjects with active EoE who participated in 15 randomized controlled trials. All drugs tested in EoE were included, each compared against one another and placebo. Efficacy was characterized by induction of histological remission, symptomatic response, and endoscopic response. Topical steroids formulated for EoE were evaluated separately from off-label topical steroids for asthma.

This approach yielded a litany of efficacy findings.

Of note, budesonide orally disintegrating tablets ranked first for histological remission defined by no more than 15 eosinophils/high-powered field (HPF), while lirentelimab was best at achieving the lesser used histological remission threshold of 6 eosinophils/HPF. On the same topic of inducing histological remission, EoE-specific steroid formulations, along with dupilumab, showed greater efficacy than off-label topical steroids.

The investigators also highlighted that budesonide suspension and tablets were significantly better than placebo in terms of failure to achieve symptom improvement and failure to achieve endoscopic improvement according to EoE Endoscopic Reference Score.

Collectively, the analysis showed that most available drugs are significantly more effective than placebo for treating EoE, yet differences in study designs and population characteristics stand in the way of a clear road map to treatment selection.

“In summary, this network meta-analysis supports the efficacy of most available drugs over placebo for the treatment of EoE. All EoE-specific steroid formulations and dupilumab ranked higher than off-label topical steroids for the induction of histological remission in active EoE, and most EoE-specific steroid formulations and dupilumab ranked higher than esomeprazole, despite having comparable safety,” the authors wrote. “These results prompt further research to better understand the mechanisms underlying symptom generation in EoE, to target their cause and achieve better outcomes.”

Michigan Medicine

Joy Weiling Chang, MD, a gastroenterologist and assistant professor of medicine at the University of Michigan Medicine, Ann Arbor, offered a similar perspective.

“This study tells us that we still need more data to establish this clear hierarchy of medication treatments,” she said in an interview.

Still, Dr. Chang added, these findings are applicable to clinical practice. Because most EoE drugs demonstrate significant efficacy over placebo, and the best starting option remains unclear, then shared decision-making should focus on patient preferences, she said in an interview.

“As clinicians, we need to be working with our patients to consider which strategies work best for their lifestyles,” Dr. Chang said.

The investigators disclosed relationships with AbbVie, Biogen, Sanofi, and others. Dr. Chang reported consulting fees for Sanofi-Regeneron, the maker of Dupixent.
 

Most available drugs for eosinophilic esophagitis (EoE) demonstrate greater efficacy than placebo, but data are too heterogenous to determine a reliable therapeutic hierarchy, shows a meta-analysis published in Gut.

Among agents available outside of clinical trials, the corticosteroid budesonide had the broadest evidence base for efficacy, while EoE-specific topical steroids typically outperformed adapted asthma formulations, wrote authors who were led by Edoardo Savarino, MD, PhD, of the department of surgery, oncology and gastroenterology at the University of Padua, Italy.

The AGA Institute and the Joint Task Force on Allergy-Immunology Practice Parameters published clinical practice guidelines for eosinophilic esophagitis in 2020. The group issued 12 recommendations with only 1, the topical use of glucocorticosteroids over no treatment, being a “strong recommendation.” Both the AGA/JTF guidelines and guidelines issued May 23, 2022 , by the British Society of Gastroenterology and British Society of Pediatric Gastroenterology, Hepatology and Nutrition, recommend the use of proton pump inhibitors (PPIs) and topical glucocorticosteroids in certain cases. Neither set of guidelines addresses the use of dupilumab, which was approved in the United States on May 20, 2022, for adults and pediatric patients 12 years and older, and in January of this year by the European Commission for the same condition.

The current study is a meta-analysis that compared data from 1,813 subjects with active EoE who participated in 15 randomized controlled trials. All drugs tested in EoE were included, each compared against one another and placebo. Efficacy was characterized by induction of histological remission, symptomatic response, and endoscopic response. Topical steroids formulated for EoE were evaluated separately from off-label topical steroids for asthma.

This approach yielded a litany of efficacy findings.

Of note, budesonide orally disintegrating tablets ranked first for histological remission defined by no more than 15 eosinophils/high-powered field (HPF), while lirentelimab was best at achieving the lesser used histological remission threshold of 6 eosinophils/HPF. On the same topic of inducing histological remission, EoE-specific steroid formulations, along with dupilumab, showed greater efficacy than off-label topical steroids.

The investigators also highlighted that budesonide suspension and tablets were significantly better than placebo in terms of failure to achieve symptom improvement and failure to achieve endoscopic improvement according to EoE Endoscopic Reference Score.

Collectively, the analysis showed that most available drugs are significantly more effective than placebo for treating EoE, yet differences in study designs and population characteristics stand in the way of a clear road map to treatment selection.

“In summary, this network meta-analysis supports the efficacy of most available drugs over placebo for the treatment of EoE. All EoE-specific steroid formulations and dupilumab ranked higher than off-label topical steroids for the induction of histological remission in active EoE, and most EoE-specific steroid formulations and dupilumab ranked higher than esomeprazole, despite having comparable safety,” the authors wrote. “These results prompt further research to better understand the mechanisms underlying symptom generation in EoE, to target their cause and achieve better outcomes.”

Michigan Medicine

Joy Weiling Chang, MD, a gastroenterologist and assistant professor of medicine at the University of Michigan Medicine, Ann Arbor, offered a similar perspective.

“This study tells us that we still need more data to establish this clear hierarchy of medication treatments,” she said in an interview.

Still, Dr. Chang added, these findings are applicable to clinical practice. Because most EoE drugs demonstrate significant efficacy over placebo, and the best starting option remains unclear, then shared decision-making should focus on patient preferences, she said in an interview.

“As clinicians, we need to be working with our patients to consider which strategies work best for their lifestyles,” Dr. Chang said.

The investigators disclosed relationships with AbbVie, Biogen, Sanofi, and others. Dr. Chang reported consulting fees for Sanofi-Regeneron, the maker of Dupixent.
 

Most available drugs for eosinophilic esophagitis (EoE) demonstrate greater efficacy than placebo, but data are too heterogenous to determine a reliable therapeutic hierarchy, shows a meta-analysis published in Gut.

Among agents available outside of clinical trials, the corticosteroid budesonide had the broadest evidence base for efficacy, while EoE-specific topical steroids typically outperformed adapted asthma formulations, wrote authors who were led by Edoardo Savarino, MD, PhD, of the department of surgery, oncology and gastroenterology at the University of Padua, Italy.

The AGA Institute and the Joint Task Force on Allergy-Immunology Practice Parameters published clinical practice guidelines for eosinophilic esophagitis in 2020. The group issued 12 recommendations with only 1, the topical use of glucocorticosteroids over no treatment, being a “strong recommendation.” Both the AGA/JTF guidelines and guidelines issued May 23, 2022 , by the British Society of Gastroenterology and British Society of Pediatric Gastroenterology, Hepatology and Nutrition, recommend the use of proton pump inhibitors (PPIs) and topical glucocorticosteroids in certain cases. Neither set of guidelines addresses the use of dupilumab, which was approved in the United States on May 20, 2022, for adults and pediatric patients 12 years and older, and in January of this year by the European Commission for the same condition.

The current study is a meta-analysis that compared data from 1,813 subjects with active EoE who participated in 15 randomized controlled trials. All drugs tested in EoE were included, each compared against one another and placebo. Efficacy was characterized by induction of histological remission, symptomatic response, and endoscopic response. Topical steroids formulated for EoE were evaluated separately from off-label topical steroids for asthma.

This approach yielded a litany of efficacy findings.

Of note, budesonide orally disintegrating tablets ranked first for histological remission defined by no more than 15 eosinophils/high-powered field (HPF), while lirentelimab was best at achieving the lesser used histological remission threshold of 6 eosinophils/HPF. On the same topic of inducing histological remission, EoE-specific steroid formulations, along with dupilumab, showed greater efficacy than off-label topical steroids.

The investigators also highlighted that budesonide suspension and tablets were significantly better than placebo in terms of failure to achieve symptom improvement and failure to achieve endoscopic improvement according to EoE Endoscopic Reference Score.

Collectively, the analysis showed that most available drugs are significantly more effective than placebo for treating EoE, yet differences in study designs and population characteristics stand in the way of a clear road map to treatment selection.

“In summary, this network meta-analysis supports the efficacy of most available drugs over placebo for the treatment of EoE. All EoE-specific steroid formulations and dupilumab ranked higher than off-label topical steroids for the induction of histological remission in active EoE, and most EoE-specific steroid formulations and dupilumab ranked higher than esomeprazole, despite having comparable safety,” the authors wrote. “These results prompt further research to better understand the mechanisms underlying symptom generation in EoE, to target their cause and achieve better outcomes.”

Michigan Medicine

Joy Weiling Chang, MD, a gastroenterologist and assistant professor of medicine at the University of Michigan Medicine, Ann Arbor, offered a similar perspective.

“This study tells us that we still need more data to establish this clear hierarchy of medication treatments,” she said in an interview.

Still, Dr. Chang added, these findings are applicable to clinical practice. Because most EoE drugs demonstrate significant efficacy over placebo, and the best starting option remains unclear, then shared decision-making should focus on patient preferences, she said in an interview.

“As clinicians, we need to be working with our patients to consider which strategies work best for their lifestyles,” Dr. Chang said.

The investigators disclosed relationships with AbbVie, Biogen, Sanofi, and others. Dr. Chang reported consulting fees for Sanofi-Regeneron, the maker of Dupixent.
 

A new Clinical Practice Update from the AGA on belching, abdominal bloating, and distention offers practical management strategies for a class of disorders that, while highly prevalent, can be confusing to clinicians because of their nonspecific and overlapping symptomatology and wide range of possible causes.

The expert review, published online in Gastroenterology, is dedicated to these specific disorders, which, when not caused by bacteria, food intolerance, or autoimmune disease, are increasingly viewed as stemming from dysregulation of the brain-gut axis, and therefore responsive to interventions such as biofeedback therapy and central nervous system modulators, including antidepressants referred to as neuromodulators due to their pain modulating effects in the gut.

Baharak Moshiree, MD, of Atrium Health, Wake Forest Medical University, Charlotte, N.C., the lead author, said the guidance is aimed at GI specialists as much as primary care physicians and other providers who treat patients with these disorders.
 

Atrium Health

Clinicians may not always know which diagnostic studies to order for a patient with bloating, distention, or belching, Dr. Moshiree said, and since large randomized controlled trials in these patient groups are not available, making evidence-based treatment recommendations is challenging. Because the disorders are ubiquitous, “there’s a lot of social media attention around them, and these include fad diets and drugs labeled as medical foods, like probiotics, that patients will often try.”

The guidance includes 15 best practice advice statements along with two diagnostic and treatment algorithms, one for belching and the other for bloating and distention.

For belching, the authors stress discerning between gastric and supragastric belching using clinical history and examination, and if needed, impedance Ph monitoring. For supragastric belching, or esophageal belching, treatment considerations may include cognitive behavioral therapy, biofeedback training, and neuromodulator (antidepressant) drugs either alone or combined with psychological therapies.

Abdominal bloating and distention should be diagnosed using the Rome IV criteria, and in patients with suspected carbohydrate enzyme deficiencies, dietary restriction of potentially problematic carbohydrates or breath testing may be used to rule out intolerance. In a subset of at-risk patients, “small bowel aspiration and glucose- or lactulose-based hydrogen breath testing may be used to evaluate for small intestinal bacterial overgrowth,” the guidance says. Blood testing may be used to rule out celiac disease, and, if positive, a definitive diagnosis should be confirmed with small bowel tissue biopsy obtained during an upper endoscopy, Dr. Moshiree and her colleagues wrote.

Endoscopy and imaging should be restricted to patients with alarm features such as vomiting or weight loss, rapid worsening of symptoms, or an abnormal physical exam. Tests such as gastric emptying transit studies should not be routinely ordered unless nausea and vomiting are present. Similarly, whole-gut motility studies should be ordered only if there are symptoms suggestive of motility disorders, with testing carried out at specialized centers.

When constipation occurs with bloating, clinicians should use anorectal physiology testing to rule out a pelvic-floor disorder, which, if present, can be treated with pelvic floor biofeedback training. Constipation in the context of bloating may also be treated with laxatives. Probiotics are not advised as treatment for bloating and distention in this guidance, given a lack of robust studies. However, neuromodulators may help reduce visceral or gut hypersensitivity and improve psychological comorbidities if these are present, the authors wrote.

Conditions treated with dietary modifications should be overseen by dietitians, and diaphragmatic breathing and neuromodulators can be used to treat a condition called abdominophrenic dyssynergia, the guidance says.

“We tried to make it clinically useful,” Dr. Moshiree said of the practice update, which was not the result of systematic reviews or meta-analyses of multicenter randomized controlled trials. The update contains no ratings on its recommendations and does not grade the evidence used. Rather, the three coauthors looked to results from published randomized trials and observational studies, along with their own expert opinion.

For example, the guidance’s best practice advice on abdominophrenic dyssynergia came from single center studies in Italy where bloating improved with use of biofeedback therapy for this condition. Although this was a single center study, experts have found that biofeedback therapy is helpful for relaxing the pelvic floor muscles which can help bloating and distension symptoms.

Dr. Moshiree also pointed to a 2021 narrative review by Brian E. Lacy, MD. and David Cangemi, MD, of the Mayo Clinic in Jacksonville, Fla., that helped inform the framework for this clinical practice update.

Dr. Moshiree disclosed financial relationships with several pharmaceutical companies including Salix, AbbVie, Medtronic, and Takeda. Her two coauthors, Douglas Drossman, MD, of the Rome Foundation and the University of North Carolina, Chapel Hill, and Aasma Shaukat, MD, of New York University, also disclosed industry support.

A new Clinical Practice Update from the AGA on belching, abdominal bloating, and distention offers practical management strategies for a class of disorders that, while highly prevalent, can be confusing to clinicians because of their nonspecific and overlapping symptomatology and wide range of possible causes.

The expert review, published online in Gastroenterology, is dedicated to these specific disorders, which, when not caused by bacteria, food intolerance, or autoimmune disease, are increasingly viewed as stemming from dysregulation of the brain-gut axis, and therefore responsive to interventions such as biofeedback therapy and central nervous system modulators, including antidepressants referred to as neuromodulators due to their pain modulating effects in the gut.

Baharak Moshiree, MD, of Atrium Health, Wake Forest Medical University, Charlotte, N.C., the lead author, said the guidance is aimed at GI specialists as much as primary care physicians and other providers who treat patients with these disorders.
 

Atrium Health

Clinicians may not always know which diagnostic studies to order for a patient with bloating, distention, or belching, Dr. Moshiree said, and since large randomized controlled trials in these patient groups are not available, making evidence-based treatment recommendations is challenging. Because the disorders are ubiquitous, “there’s a lot of social media attention around them, and these include fad diets and drugs labeled as medical foods, like probiotics, that patients will often try.”

The guidance includes 15 best practice advice statements along with two diagnostic and treatment algorithms, one for belching and the other for bloating and distention.

For belching, the authors stress discerning between gastric and supragastric belching using clinical history and examination, and if needed, impedance Ph monitoring. For supragastric belching, or esophageal belching, treatment considerations may include cognitive behavioral therapy, biofeedback training, and neuromodulator (antidepressant) drugs either alone or combined with psychological therapies.

Abdominal bloating and distention should be diagnosed using the Rome IV criteria, and in patients with suspected carbohydrate enzyme deficiencies, dietary restriction of potentially problematic carbohydrates or breath testing may be used to rule out intolerance. In a subset of at-risk patients, “small bowel aspiration and glucose- or lactulose-based hydrogen breath testing may be used to evaluate for small intestinal bacterial overgrowth,” the guidance says. Blood testing may be used to rule out celiac disease, and, if positive, a definitive diagnosis should be confirmed with small bowel tissue biopsy obtained during an upper endoscopy, Dr. Moshiree and her colleagues wrote.

Endoscopy and imaging should be restricted to patients with alarm features such as vomiting or weight loss, rapid worsening of symptoms, or an abnormal physical exam. Tests such as gastric emptying transit studies should not be routinely ordered unless nausea and vomiting are present. Similarly, whole-gut motility studies should be ordered only if there are symptoms suggestive of motility disorders, with testing carried out at specialized centers.

When constipation occurs with bloating, clinicians should use anorectal physiology testing to rule out a pelvic-floor disorder, which, if present, can be treated with pelvic floor biofeedback training. Constipation in the context of bloating may also be treated with laxatives. Probiotics are not advised as treatment for bloating and distention in this guidance, given a lack of robust studies. However, neuromodulators may help reduce visceral or gut hypersensitivity and improve psychological comorbidities if these are present, the authors wrote.

Conditions treated with dietary modifications should be overseen by dietitians, and diaphragmatic breathing and neuromodulators can be used to treat a condition called abdominophrenic dyssynergia, the guidance says.

“We tried to make it clinically useful,” Dr. Moshiree said of the practice update, which was not the result of systematic reviews or meta-analyses of multicenter randomized controlled trials. The update contains no ratings on its recommendations and does not grade the evidence used. Rather, the three coauthors looked to results from published randomized trials and observational studies, along with their own expert opinion.

For example, the guidance’s best practice advice on abdominophrenic dyssynergia came from single center studies in Italy where bloating improved with use of biofeedback therapy for this condition. Although this was a single center study, experts have found that biofeedback therapy is helpful for relaxing the pelvic floor muscles which can help bloating and distension symptoms.

Dr. Moshiree also pointed to a 2021 narrative review by Brian E. Lacy, MD. and David Cangemi, MD, of the Mayo Clinic in Jacksonville, Fla., that helped inform the framework for this clinical practice update.

Dr. Moshiree disclosed financial relationships with several pharmaceutical companies including Salix, AbbVie, Medtronic, and Takeda. Her two coauthors, Douglas Drossman, MD, of the Rome Foundation and the University of North Carolina, Chapel Hill, and Aasma Shaukat, MD, of New York University, also disclosed industry support.

A new Clinical Practice Update from the AGA on belching, abdominal bloating, and distention offers practical management strategies for a class of disorders that, while highly prevalent, can be confusing to clinicians because of their nonspecific and overlapping symptomatology and wide range of possible causes.

The expert review, published online in Gastroenterology, is dedicated to these specific disorders, which, when not caused by bacteria, food intolerance, or autoimmune disease, are increasingly viewed as stemming from dysregulation of the brain-gut axis, and therefore responsive to interventions such as biofeedback therapy and central nervous system modulators, including antidepressants referred to as neuromodulators due to their pain modulating effects in the gut.

Baharak Moshiree, MD, of Atrium Health, Wake Forest Medical University, Charlotte, N.C., the lead author, said the guidance is aimed at GI specialists as much as primary care physicians and other providers who treat patients with these disorders.
 

Atrium Health

Clinicians may not always know which diagnostic studies to order for a patient with bloating, distention, or belching, Dr. Moshiree said, and since large randomized controlled trials in these patient groups are not available, making evidence-based treatment recommendations is challenging. Because the disorders are ubiquitous, “there’s a lot of social media attention around them, and these include fad diets and drugs labeled as medical foods, like probiotics, that patients will often try.”

The guidance includes 15 best practice advice statements along with two diagnostic and treatment algorithms, one for belching and the other for bloating and distention.

For belching, the authors stress discerning between gastric and supragastric belching using clinical history and examination, and if needed, impedance Ph monitoring. For supragastric belching, or esophageal belching, treatment considerations may include cognitive behavioral therapy, biofeedback training, and neuromodulator (antidepressant) drugs either alone or combined with psychological therapies.

Abdominal bloating and distention should be diagnosed using the Rome IV criteria, and in patients with suspected carbohydrate enzyme deficiencies, dietary restriction of potentially problematic carbohydrates or breath testing may be used to rule out intolerance. In a subset of at-risk patients, “small bowel aspiration and glucose- or lactulose-based hydrogen breath testing may be used to evaluate for small intestinal bacterial overgrowth,” the guidance says. Blood testing may be used to rule out celiac disease, and, if positive, a definitive diagnosis should be confirmed with small bowel tissue biopsy obtained during an upper endoscopy, Dr. Moshiree and her colleagues wrote.

Endoscopy and imaging should be restricted to patients with alarm features such as vomiting or weight loss, rapid worsening of symptoms, or an abnormal physical exam. Tests such as gastric emptying transit studies should not be routinely ordered unless nausea and vomiting are present. Similarly, whole-gut motility studies should be ordered only if there are symptoms suggestive of motility disorders, with testing carried out at specialized centers.

When constipation occurs with bloating, clinicians should use anorectal physiology testing to rule out a pelvic-floor disorder, which, if present, can be treated with pelvic floor biofeedback training. Constipation in the context of bloating may also be treated with laxatives. Probiotics are not advised as treatment for bloating and distention in this guidance, given a lack of robust studies. However, neuromodulators may help reduce visceral or gut hypersensitivity and improve psychological comorbidities if these are present, the authors wrote.

Conditions treated with dietary modifications should be overseen by dietitians, and diaphragmatic breathing and neuromodulators can be used to treat a condition called abdominophrenic dyssynergia, the guidance says.

“We tried to make it clinically useful,” Dr. Moshiree said of the practice update, which was not the result of systematic reviews or meta-analyses of multicenter randomized controlled trials. The update contains no ratings on its recommendations and does not grade the evidence used. Rather, the three coauthors looked to results from published randomized trials and observational studies, along with their own expert opinion.

For example, the guidance’s best practice advice on abdominophrenic dyssynergia came from single center studies in Italy where bloating improved with use of biofeedback therapy for this condition. Although this was a single center study, experts have found that biofeedback therapy is helpful for relaxing the pelvic floor muscles which can help bloating and distension symptoms.

Dr. Moshiree also pointed to a 2021 narrative review by Brian E. Lacy, MD. and David Cangemi, MD, of the Mayo Clinic in Jacksonville, Fla., that helped inform the framework for this clinical practice update.

Dr. Moshiree disclosed financial relationships with several pharmaceutical companies including Salix, AbbVie, Medtronic, and Takeda. Her two coauthors, Douglas Drossman, MD, of the Rome Foundation and the University of North Carolina, Chapel Hill, and Aasma Shaukat, MD, of New York University, also disclosed industry support.

Gastroesophageal reflux symptoms in women may increase the risk of poor sleep quality, shows a recent analysis of the Nurses’ Health Study II published in JAMA Network Open.

The findings suggest that treating gastroesophageal reflux may do more than offer symptomatic relief, but it could improve the chances of a good night’s rest by addressing comorbidities associated with poor sleep quality, wrote authors who were led by Andrew T. Chan, MD, MPH, of the Clinical and Translational Epidemiology Unit at Massachusetts General Hospital, Boston.

“Approximately 20% of the U.S. population experiences gastroesophageal reflux (GER) symptoms at least once a week, and the worldwide prevalence of GER disease (GERD) has been increasing. Beyond its association with quality of life, GERD is also associated with long-term complications, including Barrett esophagus and esophageal adenocarcinoma,” the authors wrote. “In this prospective cohort study, we found that GER symptoms were associated with an increase in subsequent risk of poor sleep quality. Although risk was somewhat attenuated among women who regularly used PPIs [proton pump inhibitors] and/or H₂RAs [histamine₂-receptor antagonists], the risk of poor sleep quality remained significantly higher among those who experienced GER symptoms at least once a week.”

A growing body of evidence suggests that GERD may be one of those lesser known risk factors of poor sleep quality (trouble falling asleep, sleep disturbance, daytime sleepiness, or restlessness of sleep). But data on the subject are scarce, compelling researchers to conduct the present investigation.

The analysis drew data from the Nurses’ Health Study II, an ongoing prospective study involving 116,429 female participants. Among the 48,536 women included in this analysis, 7,929 (16.3%) developed poor sleep quality during a 4-year follow-up period.

The multivariable relative risk for poor sleep quality among women who experienced GER symptoms more than once a week was 1.53 (95% confidence interval, 1.45-1.62). For those who experienced GER symptoms more than twice a week, the RR was 1.49 (95% CI, 1.39-1.58) for difficulty in falling asleep, 1.47 (95% CI, 1.39-1.56) for excessive daytime sleepiness, and 1.44 (95% CI, 1.36-1.53) for restlessness of sleep.

GER was more common in women who had higher body mass index, were less physically active, and had asthma and depression. Among women who experienced GER more than once a week, 48.2% regularly used PPIs and/or H₂RAs which are commonly prescribed for GERD. However, researchers found that frequent GER symptoms were significantly associated with higher risk of poor sleep quality regardless of whether patients used PPIs and/or H₂RAs. But poor sleep quality, in this case, was more common among those who did not use PPIs or H₂RAs.

In an interview, Bradley M. Morganstern, MD, medical director of the Inflammatory Bowel Disease Center at NYU Long Island, Mineola, N.Y., brought up the potential for confounding variables. For example, obesity could confound the analysis, he said, as people who are overweight have increased risk of reflux, but also sleep apnea, a strong risk factor for poor sleep.

Despite this possible limitation, Dr. Morganstern said the results are important because they point to a possible practice gap. Physicians typically screen for the classic symptoms of reflux like discomfort and burning, but not sleep quality.

“It’s not something we usually ask about unless the patient volunteers that they’re actually having reflux symptoms at nighttime,” Dr. Morganstern said. This possible link between reflux and poor sleep quality should be on the radar for both gastroenterologists and primary care providers, he added.

“I think different specialties could be asking about it for different reasons,” Dr. Morganstern said, suggesting that it may be worth discussing during diagnosis of reflux or detection of poor sleep quality, and when monitoring symptoms and responses to therapy.

Dr. Chan reported receiving grants from Pfizer, Zoe, and Freenome and receiving personal fees from Pfizer and Boehringer Ingelheim outside the submitted work. Other authors disclosed receiving fees and grants from a number of companies, but outside of the scope of this work.

Gastroesophageal reflux symptoms in women may increase the risk of poor sleep quality, shows a recent analysis of the Nurses’ Health Study II published in JAMA Network Open.

The findings suggest that treating gastroesophageal reflux may do more than offer symptomatic relief, but it could improve the chances of a good night’s rest by addressing comorbidities associated with poor sleep quality, wrote authors who were led by Andrew T. Chan, MD, MPH, of the Clinical and Translational Epidemiology Unit at Massachusetts General Hospital, Boston.

“Approximately 20% of the U.S. population experiences gastroesophageal reflux (GER) symptoms at least once a week, and the worldwide prevalence of GER disease (GERD) has been increasing. Beyond its association with quality of life, GERD is also associated with long-term complications, including Barrett esophagus and esophageal adenocarcinoma,” the authors wrote. “In this prospective cohort study, we found that GER symptoms were associated with an increase in subsequent risk of poor sleep quality. Although risk was somewhat attenuated among women who regularly used PPIs [proton pump inhibitors] and/or H₂RAs [histamine₂-receptor antagonists], the risk of poor sleep quality remained significantly higher among those who experienced GER symptoms at least once a week.”

A growing body of evidence suggests that GERD may be one of those lesser known risk factors of poor sleep quality (trouble falling asleep, sleep disturbance, daytime sleepiness, or restlessness of sleep). But data on the subject are scarce, compelling researchers to conduct the present investigation.

The analysis drew data from the Nurses’ Health Study II, an ongoing prospective study involving 116,429 female participants. Among the 48,536 women included in this analysis, 7,929 (16.3%) developed poor sleep quality during a 4-year follow-up period.

The multivariable relative risk for poor sleep quality among women who experienced GER symptoms more than once a week was 1.53 (95% confidence interval, 1.45-1.62). For those who experienced GER symptoms more than twice a week, the RR was 1.49 (95% CI, 1.39-1.58) for difficulty in falling asleep, 1.47 (95% CI, 1.39-1.56) for excessive daytime sleepiness, and 1.44 (95% CI, 1.36-1.53) for restlessness of sleep.

GER was more common in women who had higher body mass index, were less physically active, and had asthma and depression. Among women who experienced GER more than once a week, 48.2% regularly used PPIs and/or H₂RAs which are commonly prescribed for GERD. However, researchers found that frequent GER symptoms were significantly associated with higher risk of poor sleep quality regardless of whether patients used PPIs and/or H₂RAs. But poor sleep quality, in this case, was more common among those who did not use PPIs or H₂RAs.

In an interview, Bradley M. Morganstern, MD, medical director of the Inflammatory Bowel Disease Center at NYU Long Island, Mineola, N.Y., brought up the potential for confounding variables. For example, obesity could confound the analysis, he said, as people who are overweight have increased risk of reflux, but also sleep apnea, a strong risk factor for poor sleep.

Despite this possible limitation, Dr. Morganstern said the results are important because they point to a possible practice gap. Physicians typically screen for the classic symptoms of reflux like discomfort and burning, but not sleep quality.

“It’s not something we usually ask about unless the patient volunteers that they’re actually having reflux symptoms at nighttime,” Dr. Morganstern said. This possible link between reflux and poor sleep quality should be on the radar for both gastroenterologists and primary care providers, he added.

“I think different specialties could be asking about it for different reasons,” Dr. Morganstern said, suggesting that it may be worth discussing during diagnosis of reflux or detection of poor sleep quality, and when monitoring symptoms and responses to therapy.

Dr. Chan reported receiving grants from Pfizer, Zoe, and Freenome and receiving personal fees from Pfizer and Boehringer Ingelheim outside the submitted work. Other authors disclosed receiving fees and grants from a number of companies, but outside of the scope of this work.

Gastroesophageal reflux symptoms in women may increase the risk of poor sleep quality, shows a recent analysis of the Nurses’ Health Study II published in JAMA Network Open.

The findings suggest that treating gastroesophageal reflux may do more than offer symptomatic relief, but it could improve the chances of a good night’s rest by addressing comorbidities associated with poor sleep quality, wrote authors who were led by Andrew T. Chan, MD, MPH, of the Clinical and Translational Epidemiology Unit at Massachusetts General Hospital, Boston.

“Approximately 20% of the U.S. population experiences gastroesophageal reflux (GER) symptoms at least once a week, and the worldwide prevalence of GER disease (GERD) has been increasing. Beyond its association with quality of life, GERD is also associated with long-term complications, including Barrett esophagus and esophageal adenocarcinoma,” the authors wrote. “In this prospective cohort study, we found that GER symptoms were associated with an increase in subsequent risk of poor sleep quality. Although risk was somewhat attenuated among women who regularly used PPIs [proton pump inhibitors] and/or H₂RAs [histamine₂-receptor antagonists], the risk of poor sleep quality remained significantly higher among those who experienced GER symptoms at least once a week.”

A growing body of evidence suggests that GERD may be one of those lesser known risk factors of poor sleep quality (trouble falling asleep, sleep disturbance, daytime sleepiness, or restlessness of sleep). But data on the subject are scarce, compelling researchers to conduct the present investigation.

The analysis drew data from the Nurses’ Health Study II, an ongoing prospective study involving 116,429 female participants. Among the 48,536 women included in this analysis, 7,929 (16.3%) developed poor sleep quality during a 4-year follow-up period.

The multivariable relative risk for poor sleep quality among women who experienced GER symptoms more than once a week was 1.53 (95% confidence interval, 1.45-1.62). For those who experienced GER symptoms more than twice a week, the RR was 1.49 (95% CI, 1.39-1.58) for difficulty in falling asleep, 1.47 (95% CI, 1.39-1.56) for excessive daytime sleepiness, and 1.44 (95% CI, 1.36-1.53) for restlessness of sleep.

GER was more common in women who had higher body mass index, were less physically active, and had asthma and depression. Among women who experienced GER more than once a week, 48.2% regularly used PPIs and/or H₂RAs which are commonly prescribed for GERD. However, researchers found that frequent GER symptoms were significantly associated with higher risk of poor sleep quality regardless of whether patients used PPIs and/or H₂RAs. But poor sleep quality, in this case, was more common among those who did not use PPIs or H₂RAs.

In an interview, Bradley M. Morganstern, MD, medical director of the Inflammatory Bowel Disease Center at NYU Long Island, Mineola, N.Y., brought up the potential for confounding variables. For example, obesity could confound the analysis, he said, as people who are overweight have increased risk of reflux, but also sleep apnea, a strong risk factor for poor sleep.

Despite this possible limitation, Dr. Morganstern said the results are important because they point to a possible practice gap. Physicians typically screen for the classic symptoms of reflux like discomfort and burning, but not sleep quality.

“It’s not something we usually ask about unless the patient volunteers that they’re actually having reflux symptoms at nighttime,” Dr. Morganstern said. This possible link between reflux and poor sleep quality should be on the radar for both gastroenterologists and primary care providers, he added.

“I think different specialties could be asking about it for different reasons,” Dr. Morganstern said, suggesting that it may be worth discussing during diagnosis of reflux or detection of poor sleep quality, and when monitoring symptoms and responses to therapy.

Dr. Chan reported receiving grants from Pfizer, Zoe, and Freenome and receiving personal fees from Pfizer and Boehringer Ingelheim outside the submitted work. Other authors disclosed receiving fees and grants from a number of companies, but outside of the scope of this work.

The limited scope and depth of existing literature on childhood eosinophilic gastrointestinal disorders (EGIDs) beyond eosinophilic esophagitis (EoE) spurred an international group of researchers and clinicians to develop the first clinical practice guidelines for diagnosing and treating these rare conditions.

The consensus-based guidelines also aim to facilitate high-quality randomized controlled trials of various treatment modalities using a standardized nomenclature.

They were developed jointly by the European Society for Paediatric Gastroenterology, Hepatology and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.

Non-EoE EGIDs are rare chronic inflammatory disorders of the gastrointestinal tract, estimated at less than 200,000 cases annually in the United States, with unknown long-term consequences, Glenn Furuta, MD, professor of pediatrics at the University of Colorado at Denver and section head of gastroenterology at Children’s Hospital Colorado, both in Aurora, said in an interview 

“There are many unmet needs. Research has been limited and has not progressed at the pace we want it to,” added Dr. Furuta, who is corresponding author of the guidelines.

The guidelines were published online in the Journal of Pediatric Gastroenterology & Nutrition, by lead author Alexandra Papadopoulou, MD, division of gastroenterology and hepatology, first department of pediatrics, University of Athens, and Children’s Hospital Agia Sofia, also in Athens, and colleagues.

With these, we provide guidance for clinicians to better understand the conditions and also how to diagnose and initiate care for patients with these rare diseases, said Dr. Furuta. 
 

Difficult-to-diagnose conditions

Guideline development involved a working group of 26 pediatric gastroenterologists, adult gastroenterologists, allergists/immunologists, and pathologists from 16 countries across five continents. The consensus document includes 34 statements based on available evidence and 41 recommendations based on expert opinion and best clinical practices. In cases where the supporting evidence was weak but agreement was strong, the authors issued conditional recommendations.

The guidelines subdivide the non-EoE EGIDs according to inflammation location: eosinophilic gastritis, eosinophilic duodenitis (EoD), eosinophilic colitis, and eosinophilic enteritis. The latter can be further subdivided into EoD, eosinophilic jejunitis, and eosinophilic ileitis.

Non-EoE EGIDs are hard to diagnose because symptoms are relatively nonspecific and may include abdominal pain, vomiting, diarrhea, and bloody stools, all of which could have any number of underlying causes, Dr. Furuta said.

If you are treating a patient who is not getting better with such symptoms as persisting infections, acid-related problems, significant bleeding leading to anemia, intestinal perforation or obstruction, or low serum protein leading to swelling, then you should think that something else is going on that requires more of an evaluation, Dr. Furuta noted.

Patients with personal or family histories of eosinophilic or allergic disease should raise greater suspicion, Dr. Furuta said. “The next step requires an endoscopy and biopsy.”

Awareness of non-EoE EGIDs has been higher among pediatric gastroenterologists than among those treating adult disease because pediatric gastroenterologists have always obtained biopsies of the intestinal tract, Dr. Furuta noted.

The guidelines recommend that diagnosis of non-EoE EGIDs in children and adolescents must include signs or symptoms of gastrointestinal dysfunction, dense eosinophilic infiltrates found in mucosal or full-thickness biopsies above organ-specific threshold values included in the document, and absence of other diseases associated with GI mucosal eosinophilic inflammation.
 

Individualized treatment

The authors noted that the strength of recommendations varies with the often-modest availability of randomized controlled trial data on treatment efficacy. 

For example, they recommended that systemic steroids be considered to induce remission but only conditionally recommend topical steroids. They conditionally recommend consideration of empiric elimination diets and conditionally recommend against using food allergy testing to guide diet.

The choice of treatment should be individualized on the basis of the affected GI segment, severity of the disease, patient characteristics, and family resources and capabilities, the authors wrote.

“We’ve provided guidance on how to care for patients based on the consensus of experts who have the necessary experience and knowledge base,” Dr. Furuta said. “Our ability to say: ‘Here are the established treatments,’ is lacking, though. We need research studies to verify that our recommended approaches are indeed correct.”

The authors conditionally recommended that treatment goals include achieving symptom resolution, improving gross endoscopic and histologic abnormalities, promoting normal childhood growth and development, and preventing disease complications.

No pediatric study has determined the natural history of non-EoE EGIDs, and no study of maintenance therapy has been conducted, the authors noted. 

For this reason, they conditionally recommended that the clinical decision to continue therapy should be discussed with patients and their parents/caregivers, and those discussions include the benefits and risk of long-term treatment, its cost, and its impact on health-related quality of life.
 

A starting point for patient management

In a comment, Vincent Mukkada, MD, professor of pediatrics at the University of Cincinnati and an attending physician in gastroenterology, hepatology, and nutrition at Cincinnati Children’s Hospital and Medical Center, observed that, though improved awareness among pediatric gastroenterologists may account for some of the increase in GI eosinophil disease, the incidence is also likely growing. 

“We’re looking for them much more,” said Dr. Mukkada.

“But I also think they’re increasing, just like all other atopic diseases. We’re not sure why,” he added.

“The hope is that these guidelines will allow nonsubspecialized gastroenterologists and allergists feel comfortable to at least start on the journey of managing these patients. And, for pediatricians who learn that their patient has received a non-EoE EGID diagnosis, they can go to the summary figures in this one document and very quickly get an overview of the disease and its course,” Dr. Mukkada said.

Guideline development was funded by the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology and Nutrition. The authors and Dr. Mukkada reported no relevant financial relationships.

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

The limited scope and depth of existing literature on childhood eosinophilic gastrointestinal disorders (EGIDs) beyond eosinophilic esophagitis (EoE) spurred an international group of researchers and clinicians to develop the first clinical practice guidelines for diagnosing and treating these rare conditions.

The consensus-based guidelines also aim to facilitate high-quality randomized controlled trials of various treatment modalities using a standardized nomenclature.

They were developed jointly by the European Society for Paediatric Gastroenterology, Hepatology and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.

Non-EoE EGIDs are rare chronic inflammatory disorders of the gastrointestinal tract, estimated at less than 200,000 cases annually in the United States, with unknown long-term consequences, Glenn Furuta, MD, professor of pediatrics at the University of Colorado at Denver and section head of gastroenterology at Children’s Hospital Colorado, both in Aurora, said in an interview 

“There are many unmet needs. Research has been limited and has not progressed at the pace we want it to,” added Dr. Furuta, who is corresponding author of the guidelines.

The guidelines were published online in the Journal of Pediatric Gastroenterology & Nutrition, by lead author Alexandra Papadopoulou, MD, division of gastroenterology and hepatology, first department of pediatrics, University of Athens, and Children’s Hospital Agia Sofia, also in Athens, and colleagues.

With these, we provide guidance for clinicians to better understand the conditions and also how to diagnose and initiate care for patients with these rare diseases, said Dr. Furuta. 
 

Difficult-to-diagnose conditions

Guideline development involved a working group of 26 pediatric gastroenterologists, adult gastroenterologists, allergists/immunologists, and pathologists from 16 countries across five continents. The consensus document includes 34 statements based on available evidence and 41 recommendations based on expert opinion and best clinical practices. In cases where the supporting evidence was weak but agreement was strong, the authors issued conditional recommendations.

The guidelines subdivide the non-EoE EGIDs according to inflammation location: eosinophilic gastritis, eosinophilic duodenitis (EoD), eosinophilic colitis, and eosinophilic enteritis. The latter can be further subdivided into EoD, eosinophilic jejunitis, and eosinophilic ileitis.

Non-EoE EGIDs are hard to diagnose because symptoms are relatively nonspecific and may include abdominal pain, vomiting, diarrhea, and bloody stools, all of which could have any number of underlying causes, Dr. Furuta said.

If you are treating a patient who is not getting better with such symptoms as persisting infections, acid-related problems, significant bleeding leading to anemia, intestinal perforation or obstruction, or low serum protein leading to swelling, then you should think that something else is going on that requires more of an evaluation, Dr. Furuta noted.

Patients with personal or family histories of eosinophilic or allergic disease should raise greater suspicion, Dr. Furuta said. “The next step requires an endoscopy and biopsy.”

Awareness of non-EoE EGIDs has been higher among pediatric gastroenterologists than among those treating adult disease because pediatric gastroenterologists have always obtained biopsies of the intestinal tract, Dr. Furuta noted.

The guidelines recommend that diagnosis of non-EoE EGIDs in children and adolescents must include signs or symptoms of gastrointestinal dysfunction, dense eosinophilic infiltrates found in mucosal or full-thickness biopsies above organ-specific threshold values included in the document, and absence of other diseases associated with GI mucosal eosinophilic inflammation.
 

Individualized treatment

The authors noted that the strength of recommendations varies with the often-modest availability of randomized controlled trial data on treatment efficacy. 

For example, they recommended that systemic steroids be considered to induce remission but only conditionally recommend topical steroids. They conditionally recommend consideration of empiric elimination diets and conditionally recommend against using food allergy testing to guide diet.

The choice of treatment should be individualized on the basis of the affected GI segment, severity of the disease, patient characteristics, and family resources and capabilities, the authors wrote.

“We’ve provided guidance on how to care for patients based on the consensus of experts who have the necessary experience and knowledge base,” Dr. Furuta said. “Our ability to say: ‘Here are the established treatments,’ is lacking, though. We need research studies to verify that our recommended approaches are indeed correct.”

The authors conditionally recommended that treatment goals include achieving symptom resolution, improving gross endoscopic and histologic abnormalities, promoting normal childhood growth and development, and preventing disease complications.

No pediatric study has determined the natural history of non-EoE EGIDs, and no study of maintenance therapy has been conducted, the authors noted. 

For this reason, they conditionally recommended that the clinical decision to continue therapy should be discussed with patients and their parents/caregivers, and those discussions include the benefits and risk of long-term treatment, its cost, and its impact on health-related quality of life.
 

A starting point for patient management

In a comment, Vincent Mukkada, MD, professor of pediatrics at the University of Cincinnati and an attending physician in gastroenterology, hepatology, and nutrition at Cincinnati Children’s Hospital and Medical Center, observed that, though improved awareness among pediatric gastroenterologists may account for some of the increase in GI eosinophil disease, the incidence is also likely growing. 

“We’re looking for them much more,” said Dr. Mukkada.

“But I also think they’re increasing, just like all other atopic diseases. We’re not sure why,” he added.

“The hope is that these guidelines will allow nonsubspecialized gastroenterologists and allergists feel comfortable to at least start on the journey of managing these patients. And, for pediatricians who learn that their patient has received a non-EoE EGID diagnosis, they can go to the summary figures in this one document and very quickly get an overview of the disease and its course,” Dr. Mukkada said.

Guideline development was funded by the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology and Nutrition. The authors and Dr. Mukkada reported no relevant financial relationships.

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

The limited scope and depth of existing literature on childhood eosinophilic gastrointestinal disorders (EGIDs) beyond eosinophilic esophagitis (EoE) spurred an international group of researchers and clinicians to develop the first clinical practice guidelines for diagnosing and treating these rare conditions.

The consensus-based guidelines also aim to facilitate high-quality randomized controlled trials of various treatment modalities using a standardized nomenclature.

They were developed jointly by the European Society for Paediatric Gastroenterology, Hepatology and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.

Non-EoE EGIDs are rare chronic inflammatory disorders of the gastrointestinal tract, estimated at less than 200,000 cases annually in the United States, with unknown long-term consequences, Glenn Furuta, MD, professor of pediatrics at the University of Colorado at Denver and section head of gastroenterology at Children’s Hospital Colorado, both in Aurora, said in an interview 

“There are many unmet needs. Research has been limited and has not progressed at the pace we want it to,” added Dr. Furuta, who is corresponding author of the guidelines.

The guidelines were published online in the Journal of Pediatric Gastroenterology & Nutrition, by lead author Alexandra Papadopoulou, MD, division of gastroenterology and hepatology, first department of pediatrics, University of Athens, and Children’s Hospital Agia Sofia, also in Athens, and colleagues.

With these, we provide guidance for clinicians to better understand the conditions and also how to diagnose and initiate care for patients with these rare diseases, said Dr. Furuta. 
 

Difficult-to-diagnose conditions

Guideline development involved a working group of 26 pediatric gastroenterologists, adult gastroenterologists, allergists/immunologists, and pathologists from 16 countries across five continents. The consensus document includes 34 statements based on available evidence and 41 recommendations based on expert opinion and best clinical practices. In cases where the supporting evidence was weak but agreement was strong, the authors issued conditional recommendations.

The guidelines subdivide the non-EoE EGIDs according to inflammation location: eosinophilic gastritis, eosinophilic duodenitis (EoD), eosinophilic colitis, and eosinophilic enteritis. The latter can be further subdivided into EoD, eosinophilic jejunitis, and eosinophilic ileitis.

Non-EoE EGIDs are hard to diagnose because symptoms are relatively nonspecific and may include abdominal pain, vomiting, diarrhea, and bloody stools, all of which could have any number of underlying causes, Dr. Furuta said.

If you are treating a patient who is not getting better with such symptoms as persisting infections, acid-related problems, significant bleeding leading to anemia, intestinal perforation or obstruction, or low serum protein leading to swelling, then you should think that something else is going on that requires more of an evaluation, Dr. Furuta noted.

Patients with personal or family histories of eosinophilic or allergic disease should raise greater suspicion, Dr. Furuta said. “The next step requires an endoscopy and biopsy.”

Awareness of non-EoE EGIDs has been higher among pediatric gastroenterologists than among those treating adult disease because pediatric gastroenterologists have always obtained biopsies of the intestinal tract, Dr. Furuta noted.

The guidelines recommend that diagnosis of non-EoE EGIDs in children and adolescents must include signs or symptoms of gastrointestinal dysfunction, dense eosinophilic infiltrates found in mucosal or full-thickness biopsies above organ-specific threshold values included in the document, and absence of other diseases associated with GI mucosal eosinophilic inflammation.
 

Individualized treatment

The authors noted that the strength of recommendations varies with the often-modest availability of randomized controlled trial data on treatment efficacy. 

For example, they recommended that systemic steroids be considered to induce remission but only conditionally recommend topical steroids. They conditionally recommend consideration of empiric elimination diets and conditionally recommend against using food allergy testing to guide diet.

The choice of treatment should be individualized on the basis of the affected GI segment, severity of the disease, patient characteristics, and family resources and capabilities, the authors wrote.

“We’ve provided guidance on how to care for patients based on the consensus of experts who have the necessary experience and knowledge base,” Dr. Furuta said. “Our ability to say: ‘Here are the established treatments,’ is lacking, though. We need research studies to verify that our recommended approaches are indeed correct.”

The authors conditionally recommended that treatment goals include achieving symptom resolution, improving gross endoscopic and histologic abnormalities, promoting normal childhood growth and development, and preventing disease complications.

No pediatric study has determined the natural history of non-EoE EGIDs, and no study of maintenance therapy has been conducted, the authors noted. 

For this reason, they conditionally recommended that the clinical decision to continue therapy should be discussed with patients and their parents/caregivers, and those discussions include the benefits and risk of long-term treatment, its cost, and its impact on health-related quality of life.
 

A starting point for patient management

In a comment, Vincent Mukkada, MD, professor of pediatrics at the University of Cincinnati and an attending physician in gastroenterology, hepatology, and nutrition at Cincinnati Children’s Hospital and Medical Center, observed that, though improved awareness among pediatric gastroenterologists may account for some of the increase in GI eosinophil disease, the incidence is also likely growing. 

“We’re looking for them much more,” said Dr. Mukkada.

“But I also think they’re increasing, just like all other atopic diseases. We’re not sure why,” he added.

“The hope is that these guidelines will allow nonsubspecialized gastroenterologists and allergists feel comfortable to at least start on the journey of managing these patients. And, for pediatricians who learn that their patient has received a non-EoE EGID diagnosis, they can go to the summary figures in this one document and very quickly get an overview of the disease and its course,” Dr. Mukkada said.

Guideline development was funded by the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology and Nutrition. The authors and Dr. Mukkada reported no relevant financial relationships.

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

A new study published in Neurology found an association between long–term proton-pump inhibitors (PPI) use and dementia. This was an observational study and does not prove that acid reflux drugs cause dementia.

“In this study, the authors note that long-term PPI use, defined as more than 4.5 years of use, was associated with dementia. It is important to note, however, that this does not necessarily mean that PPIs cause dementia. With observational studies, there is an inherent risk of bias and confounding, as the authors report. Some of these confounders include Helicobacter pylori status, vitamin B₁₂ deficiency, depression, and socioeconomic status,” said Fouad J. Moawad, MD, graduate of the AGA FORWARD Program and gastroenterologist at Scripps Health in San Diego. A 2017 study led by Andrew T. Chan, MD, MPH, of Mass General Brigham, Boston, examined the association between proton pump inhibitor use and cognitive function in women. The investigators found no “convincing association between PPI use and cognitive function. Our data do not support the suggestion that PPI use increases dementia risk.”

A new article in press in Gastroenterology by Raaj S. Mehta and colleagues also studied this issue and concluded that in adults 65 years of age or older, PPIs were not associated with dementia or decline in cognition over time. These data provide reassurance about the safety of long-term use of PPIs among older adults.

The headlines may be confusing for patients. Here are AGA’s three talking points for communicating with patients about PPIs:

Talk to your doctor, before making any changes to your medication.

You have been prescribed PPIs for a reason, to treat a diagnosed medical condition. We can discuss the reason for your prescription, the dose and the timeframe for treatment.

Consider lifestyle modifications. 

These may reduce or eliminate the need for PPIs for long-term use. These may include weight loss, avoiding tobacco or a change in your eating patterns. We can work together to determine the changes that are right for you.

Keep in touch.

Research continues to be done on PPI use. Current research recommends that patients who have a diagnosed condition that is helped by PPIs should stay on them, as benefits can outweigh risks.

A new study published in Neurology found an association between long–term proton-pump inhibitors (PPI) use and dementia. This was an observational study and does not prove that acid reflux drugs cause dementia.

“In this study, the authors note that long-term PPI use, defined as more than 4.5 years of use, was associated with dementia. It is important to note, however, that this does not necessarily mean that PPIs cause dementia. With observational studies, there is an inherent risk of bias and confounding, as the authors report. Some of these confounders include Helicobacter pylori status, vitamin B₁₂ deficiency, depression, and socioeconomic status,” said Fouad J. Moawad, MD, graduate of the AGA FORWARD Program and gastroenterologist at Scripps Health in San Diego. A 2017 study led by Andrew T. Chan, MD, MPH, of Mass General Brigham, Boston, examined the association between proton pump inhibitor use and cognitive function in women. The investigators found no “convincing association between PPI use and cognitive function. Our data do not support the suggestion that PPI use increases dementia risk.”

A new article in press in Gastroenterology by Raaj S. Mehta and colleagues also studied this issue and concluded that in adults 65 years of age or older, PPIs were not associated with dementia or decline in cognition over time. These data provide reassurance about the safety of long-term use of PPIs among older adults.

The headlines may be confusing for patients. Here are AGA’s three talking points for communicating with patients about PPIs:

Talk to your doctor, before making any changes to your medication.

You have been prescribed PPIs for a reason, to treat a diagnosed medical condition. We can discuss the reason for your prescription, the dose and the timeframe for treatment.

Consider lifestyle modifications. 

These may reduce or eliminate the need for PPIs for long-term use. These may include weight loss, avoiding tobacco or a change in your eating patterns. We can work together to determine the changes that are right for you.

Keep in touch.

Research continues to be done on PPI use. Current research recommends that patients who have a diagnosed condition that is helped by PPIs should stay on them, as benefits can outweigh risks.

A new study published in Neurology found an association between long–term proton-pump inhibitors (PPI) use and dementia. This was an observational study and does not prove that acid reflux drugs cause dementia.

“In this study, the authors note that long-term PPI use, defined as more than 4.5 years of use, was associated with dementia. It is important to note, however, that this does not necessarily mean that PPIs cause dementia. With observational studies, there is an inherent risk of bias and confounding, as the authors report. Some of these confounders include Helicobacter pylori status, vitamin B₁₂ deficiency, depression, and socioeconomic status,” said Fouad J. Moawad, MD, graduate of the AGA FORWARD Program and gastroenterologist at Scripps Health in San Diego. A 2017 study led by Andrew T. Chan, MD, MPH, of Mass General Brigham, Boston, examined the association between proton pump inhibitor use and cognitive function in women. The investigators found no “convincing association between PPI use and cognitive function. Our data do not support the suggestion that PPI use increases dementia risk.”

A new article in press in Gastroenterology by Raaj S. Mehta and colleagues also studied this issue and concluded that in adults 65 years of age or older, PPIs were not associated with dementia or decline in cognition over time. These data provide reassurance about the safety of long-term use of PPIs among older adults.

The headlines may be confusing for patients. Here are AGA’s three talking points for communicating with patients about PPIs:

Talk to your doctor, before making any changes to your medication.

You have been prescribed PPIs for a reason, to treat a diagnosed medical condition. We can discuss the reason for your prescription, the dose and the timeframe for treatment.

Consider lifestyle modifications. 

These may reduce or eliminate the need for PPIs for long-term use. These may include weight loss, avoiding tobacco or a change in your eating patterns. We can work together to determine the changes that are right for you.

Keep in touch.

Research continues to be done on PPI use. Current research recommends that patients who have a diagnosed condition that is helped by PPIs should stay on them, as benefits can outweigh risks.