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Vonoprazan promising for erosive esophagitis
, according to results of the phase 3 PHALCON-EE trial.
Vonoprazan achieved higher rates of healing and maintenance of healing than lansoprazole, with the benefit seen primarily in patients with more severe esophagitis.
The differences in healing rates were evident after 2 weeks of therapy and were maintained throughout the 24-week study, report Loren Laine, MD, Yale University, New Haven, Conn., and colleagues.
The study was published online in Gastroenterology.
More potent acid suppression
Gastroesophageal reflux disease is one of the most common disorders of the gastrointestinal tract, and erosive esophagitis is its most common complication.
Although standard PPI therapy is effective for healing erosive esophagitis, some patients do not achieve success with this conventional treatment.
Studies suggest that lack of healing of erosive esophagitis with 8 weeks of PPI therapy can be expected in roughly 5%-20% of patients, with rates up to 30% reported in patients with more severe esophagitis.
The PCAB vonoprazan provides more potent inhibition of gastric acid than PPIs and is seen as a potential alternative. However, data on its efficacy for erosive esophagitis are limited, the authors note.
The PHALCON-EE trial enrolled 1,024 adults from the United States and Europe with erosive esophagitis without Helicobacter pylori infection or Barrett esophagus.
Participants were randomized to receive once-daily vonoprazan 20 mg or lansoprazole 30 mg for up to 8 weeks in the healing phase.
The 878 patients with healing were then rerandomized to receive once-daily vonoprazan 10 mg, vonoprazan 20 mg, or lansoprazole 15 mg for 24 weeks in the maintenance phase.
For healing by week 8, vonoprazan was noninferior to lansoprazole in the primary analysis and superior to lansoprazole in a predefined exploratory analysis (92.9% vs. 84.6%; P < .0001).
Secondary analyses showed that vonoprazan was noninferior to lansoprazole in mean 24-hour heartburn-free days and superior in healing at week 2 for grade C/D esophagitis (70.2% vs. 52.6%; P = .0008).
For maintenance of healing at week 24, vonoprazan was noninferior to lansoprazole in the primary analysis and superior on secondary analysis of healing (80.7% for vonoprazan 20 mg and 79.2% for vonoprazan 10 mg vs. 72.0% for lansoprazole; P < .0001 for both comparisons).
The most common adverse event reported in the healing phase was diarrhea and in the maintenance phase was COVID-19. Two deaths occurred, both from COVID-19, during the maintenance phase in the vonoprazan 20-mg group.
As expected, serum gastrin increased to a greater extent with vonoprazan than lansoprazole, with levels > 500 pg/mL in 16% of those taking 20 mg at the end of maintenance therapy, the authors report. After stopping vonoprazan, gastrin levels dropped by roughly 60%-65% within 4 weeks.
Promising new option
“PCABs are a promising new option,” Avin Aggarwal, MD, who was not involved in the study, told this news organization.
They have a “more potent acid inhibitory effect” and have shown “superior healing of erosive esophagitis,” said Dr. Aggarwal, a gastroenterologist and medical director of Banner Health’s South Campus endoscopy services and clinical assistant professor at the University of Arizona in Tucson.
The results of the PHALCON-EE trial “validate noninferiority of PCABs compared to standard PPI therapy in the Western population after being proven in multiple Asian studies,” he said.
Dr. Aggarwal noted that PCABs work the same way as PPIs, by blocking the proton pumps, but “the longer half-life of PCABs and action on both active and inactive proton channels result in greater acid inhibition.”
Long-term effects of PCAB therapy from stronger acid inhibition and resulting hypergastrinemia still remain to be determined, he said.
Earlier this year, the U.S. Food and Drug Administration accepted Phathom Pharmaceuticals’ new drug application for vonoprazan for the treatment of erosive esophagitis.
Last May, the FDA approved two vonoprazan-based therapies for the treatment of H. pylori infection.
The study was funded by Phathom Pharmaceuticals. Dr. Laine and several coauthors have disclosed financial relationships with the company. Dr. Aggarwal reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, according to results of the phase 3 PHALCON-EE trial.
Vonoprazan achieved higher rates of healing and maintenance of healing than lansoprazole, with the benefit seen primarily in patients with more severe esophagitis.
The differences in healing rates were evident after 2 weeks of therapy and were maintained throughout the 24-week study, report Loren Laine, MD, Yale University, New Haven, Conn., and colleagues.
The study was published online in Gastroenterology.
More potent acid suppression
Gastroesophageal reflux disease is one of the most common disorders of the gastrointestinal tract, and erosive esophagitis is its most common complication.
Although standard PPI therapy is effective for healing erosive esophagitis, some patients do not achieve success with this conventional treatment.
Studies suggest that lack of healing of erosive esophagitis with 8 weeks of PPI therapy can be expected in roughly 5%-20% of patients, with rates up to 30% reported in patients with more severe esophagitis.
The PCAB vonoprazan provides more potent inhibition of gastric acid than PPIs and is seen as a potential alternative. However, data on its efficacy for erosive esophagitis are limited, the authors note.
The PHALCON-EE trial enrolled 1,024 adults from the United States and Europe with erosive esophagitis without Helicobacter pylori infection or Barrett esophagus.
Participants were randomized to receive once-daily vonoprazan 20 mg or lansoprazole 30 mg for up to 8 weeks in the healing phase.
The 878 patients with healing were then rerandomized to receive once-daily vonoprazan 10 mg, vonoprazan 20 mg, or lansoprazole 15 mg for 24 weeks in the maintenance phase.
For healing by week 8, vonoprazan was noninferior to lansoprazole in the primary analysis and superior to lansoprazole in a predefined exploratory analysis (92.9% vs. 84.6%; P < .0001).
Secondary analyses showed that vonoprazan was noninferior to lansoprazole in mean 24-hour heartburn-free days and superior in healing at week 2 for grade C/D esophagitis (70.2% vs. 52.6%; P = .0008).
For maintenance of healing at week 24, vonoprazan was noninferior to lansoprazole in the primary analysis and superior on secondary analysis of healing (80.7% for vonoprazan 20 mg and 79.2% for vonoprazan 10 mg vs. 72.0% for lansoprazole; P < .0001 for both comparisons).
The most common adverse event reported in the healing phase was diarrhea and in the maintenance phase was COVID-19. Two deaths occurred, both from COVID-19, during the maintenance phase in the vonoprazan 20-mg group.
As expected, serum gastrin increased to a greater extent with vonoprazan than lansoprazole, with levels > 500 pg/mL in 16% of those taking 20 mg at the end of maintenance therapy, the authors report. After stopping vonoprazan, gastrin levels dropped by roughly 60%-65% within 4 weeks.
Promising new option
“PCABs are a promising new option,” Avin Aggarwal, MD, who was not involved in the study, told this news organization.
They have a “more potent acid inhibitory effect” and have shown “superior healing of erosive esophagitis,” said Dr. Aggarwal, a gastroenterologist and medical director of Banner Health’s South Campus endoscopy services and clinical assistant professor at the University of Arizona in Tucson.
The results of the PHALCON-EE trial “validate noninferiority of PCABs compared to standard PPI therapy in the Western population after being proven in multiple Asian studies,” he said.
Dr. Aggarwal noted that PCABs work the same way as PPIs, by blocking the proton pumps, but “the longer half-life of PCABs and action on both active and inactive proton channels result in greater acid inhibition.”
Long-term effects of PCAB therapy from stronger acid inhibition and resulting hypergastrinemia still remain to be determined, he said.
Earlier this year, the U.S. Food and Drug Administration accepted Phathom Pharmaceuticals’ new drug application for vonoprazan for the treatment of erosive esophagitis.
Last May, the FDA approved two vonoprazan-based therapies for the treatment of H. pylori infection.
The study was funded by Phathom Pharmaceuticals. Dr. Laine and several coauthors have disclosed financial relationships with the company. Dr. Aggarwal reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, according to results of the phase 3 PHALCON-EE trial.
Vonoprazan achieved higher rates of healing and maintenance of healing than lansoprazole, with the benefit seen primarily in patients with more severe esophagitis.
The differences in healing rates were evident after 2 weeks of therapy and were maintained throughout the 24-week study, report Loren Laine, MD, Yale University, New Haven, Conn., and colleagues.
The study was published online in Gastroenterology.
More potent acid suppression
Gastroesophageal reflux disease is one of the most common disorders of the gastrointestinal tract, and erosive esophagitis is its most common complication.
Although standard PPI therapy is effective for healing erosive esophagitis, some patients do not achieve success with this conventional treatment.
Studies suggest that lack of healing of erosive esophagitis with 8 weeks of PPI therapy can be expected in roughly 5%-20% of patients, with rates up to 30% reported in patients with more severe esophagitis.
The PCAB vonoprazan provides more potent inhibition of gastric acid than PPIs and is seen as a potential alternative. However, data on its efficacy for erosive esophagitis are limited, the authors note.
The PHALCON-EE trial enrolled 1,024 adults from the United States and Europe with erosive esophagitis without Helicobacter pylori infection or Barrett esophagus.
Participants were randomized to receive once-daily vonoprazan 20 mg or lansoprazole 30 mg for up to 8 weeks in the healing phase.
The 878 patients with healing were then rerandomized to receive once-daily vonoprazan 10 mg, vonoprazan 20 mg, or lansoprazole 15 mg for 24 weeks in the maintenance phase.
For healing by week 8, vonoprazan was noninferior to lansoprazole in the primary analysis and superior to lansoprazole in a predefined exploratory analysis (92.9% vs. 84.6%; P < .0001).
Secondary analyses showed that vonoprazan was noninferior to lansoprazole in mean 24-hour heartburn-free days and superior in healing at week 2 for grade C/D esophagitis (70.2% vs. 52.6%; P = .0008).
For maintenance of healing at week 24, vonoprazan was noninferior to lansoprazole in the primary analysis and superior on secondary analysis of healing (80.7% for vonoprazan 20 mg and 79.2% for vonoprazan 10 mg vs. 72.0% for lansoprazole; P < .0001 for both comparisons).
The most common adverse event reported in the healing phase was diarrhea and in the maintenance phase was COVID-19. Two deaths occurred, both from COVID-19, during the maintenance phase in the vonoprazan 20-mg group.
As expected, serum gastrin increased to a greater extent with vonoprazan than lansoprazole, with levels > 500 pg/mL in 16% of those taking 20 mg at the end of maintenance therapy, the authors report. After stopping vonoprazan, gastrin levels dropped by roughly 60%-65% within 4 weeks.
Promising new option
“PCABs are a promising new option,” Avin Aggarwal, MD, who was not involved in the study, told this news organization.
They have a “more potent acid inhibitory effect” and have shown “superior healing of erosive esophagitis,” said Dr. Aggarwal, a gastroenterologist and medical director of Banner Health’s South Campus endoscopy services and clinical assistant professor at the University of Arizona in Tucson.
The results of the PHALCON-EE trial “validate noninferiority of PCABs compared to standard PPI therapy in the Western population after being proven in multiple Asian studies,” he said.
Dr. Aggarwal noted that PCABs work the same way as PPIs, by blocking the proton pumps, but “the longer half-life of PCABs and action on both active and inactive proton channels result in greater acid inhibition.”
Long-term effects of PCAB therapy from stronger acid inhibition and resulting hypergastrinemia still remain to be determined, he said.
Earlier this year, the U.S. Food and Drug Administration accepted Phathom Pharmaceuticals’ new drug application for vonoprazan for the treatment of erosive esophagitis.
Last May, the FDA approved two vonoprazan-based therapies for the treatment of H. pylori infection.
The study was funded by Phathom Pharmaceuticals. Dr. Laine and several coauthors have disclosed financial relationships with the company. Dr. Aggarwal reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM GASTROENTEROLOGY
Dupilumab improves eosinophilic esophagitis up to 24 weeks
Dupilumab appears to improve clinical, symptomatic, histologic, and endoscopic aspects of eosinophilic esophagitis (EoE) up to 24 weeks, according to findings presented at the annual meeting of the American College of Gastroenterology.
The drug was also well tolerated, demonstrating consistency with the known dupilumab safety profile, said Evan S. Dellon, MD, a gastroenterologist at the University of North Carolina at Chapel Hill.
In May, the Food and Drug Administration approved dupilumab (Dupixent) for the treatment of EoE in adults and adolescents who are 12 years and older and weigh at least 40 kg (about 88 pounds), based on safety and efficacy data previously presented by Dr. Dellon and colleagues as part of the phase 3 LIBERTY-EoE-TREET study (NCT03633617).
“Dupilumab is now the only medication FDA approved to treat EoE in the U.S.,” Dr. Dellon said. “The findings here are that the pooled efficacy and safety data for parts A and B of the phase 3 trial are consistent with the results of the individual parts of the study that were previously reported, and which led to the drug being approved for EoE.”
EoE is a chronic, progressive, type 2 inflammatory disease of the esophagus, which can lead to symptoms of esophageal dysfunction that affect quality of life. Current treatment options often lack specificity, present adherence challenges, and provide suboptimal long-term disease control, Dr. Dellon said.
Dupilumab, a fully human monoclonal antibody manufactured by Regeneron Pharmaceuticals, blocks the shared receptor component for interleukin-4 and IL-13, which are central drivers of type 2 inflammation in EoE.
Study population difficult to treat
In the three-part, double-blind, placebo-controlled, phase 3 study, dupilumab was administered to 122 patients as 300-mg weekly doses through subcutaneous injection. In parts A and B, dupilumab demonstrated statistically significant and clinically meaningful improvement in adults and adolescents up to 24 weeks. In patients from part A who continued to an extended active treatment period called part C, efficacy was sustained to week 52.
Participants were included if they had EoE that hadn’t responded to high-dose proton pump inhibitors, had baseline esophageal biopsies with a peak intraepithelial eosinophilic count of 15 eosinophils per high-power field (eos/HPF) or higher in two or more esophageal regions, had a history of an average of two or more episodes of dysphagia per week in the 4 weeks prior to screening, had four or more episodes of dysphagia in the 2 weeks prior to randomization with two or more episodes that required liquids or medical attention, and had a baseline Dysphagia Symptom Questionnaire (DSQ) score of 10 or higher.
On the other hand, participants were excluded if they initiated or changed a food-elimination diet regimen or reintroduced a previously eliminated food group in the 6 weeks before screening, had other causes of esophageal eosinophilia, had a history of other inflammatory diseases such as Crohn’s disease or ulcerative colitis, or were treated with swallowed topical corticosteroids within 8 weeks prior to baseline.
Dr. Dellon and colleagues focused on co–primary endpoints: The proportion of patients who achieved peak esophageal intraepithelial eosinophil count of 6 eos/HPF or less, and the absolute change in DSQ score from baseline to week 24.
Key secondary endpoints included percentage change in eos/HPF, absolute change in EoE-Endoscopic Reference Score (EREFS), absolute change in EoE-Histologic Scoring System (EoE-HSS) grade score, and EoE-HSS stage score. Other secondary endpoints included percentage change in DSQ score and proportion of patients achieving less than 15 eos/HPF.
The baseline demographics and clinical characteristics were similar between the treatment and placebo groups. Importantly, about 70% had been treated with topical corticosteroids, and about 40% had a history of esophageal dilation, Dr. Dellon said. The DSQ scores, peak eosinophil counts, and EREFS scores were high, indicating an inflamed, symptomatic, and difficult-to-treat population.
Pooled parts A and B findings
Overall, dupilumab reduced peak esophageal intraepithelial eosinophil counts at week 24. In the dupilumab group, 59% of patients were down to 6 eos/HPF or less, compared with 5.9% in the placebo group. In a secondary endpoint, 77% of dupilumab patients were down to 15 eos/HPF, compared with 7.6% in the placebo group. The dupilumab group saw an 80% drop in baseline change, compared with 1.5% in the placebo group.
Dupilumab also reduced dysphagia symptoms and improved endoscopic features of EoE at week 24. The absolute change in DSQ score was –23.21 in the dupilumab group, compared with –12.69 in the placebo group. The percent change in DSQ score was –65.5% in the dupilumab group, compared with –38.2% in the placebo group. The absolute change in EREFS score was –3.95 in the dupilumab group, compared with –0.41 in the placebo group.
In addition, dupilumab reduced histologic scores at week 24. The absolute change in EoE-HSS grade score was –0.82 in the dupilumab group, compared with –0.1 in the placebo group. The absolute change in EoE-HSS stage score was –0.79 in the dupilumab group, compared with –0.09 in the placebo group.
Dupilumab demonstrated an acceptable safety profile, and no new safety signals were noted, Dr. Dellon said. The most common adverse events was injection-site reaction at 37.5% in the dupilumab group and 33.3% in the placebo group. The severe adverse events were not related to the medication.
“If patients have EoE, dupilumab might be an option for treatment. However, it’s important to realize that, in the phase 3 study, all patients were PPI nonresponders, most had been treated with topical steroids [and many were not responsive], and many had prior esophageal dilation,” Dr. Dellon said. “We don’t have a lot of data in more mild EoE patients, and insurances are currently requiring a series of authorization before patients might be able to get this medication. It’s best to talk to their doctor about whether the medication is a good fit for not.”
The study was sponsored by Sanofi and Regeneron Pharmaceuticals. Three of the authors are employees for and have stock options with Regeneron or Sanofi. The other authors reported consultant roles, advisory roles, and research support from numerous pharmaceutical companies, including Regeneron and Sanofi.
Dupilumab appears to improve clinical, symptomatic, histologic, and endoscopic aspects of eosinophilic esophagitis (EoE) up to 24 weeks, according to findings presented at the annual meeting of the American College of Gastroenterology.
The drug was also well tolerated, demonstrating consistency with the known dupilumab safety profile, said Evan S. Dellon, MD, a gastroenterologist at the University of North Carolina at Chapel Hill.
In May, the Food and Drug Administration approved dupilumab (Dupixent) for the treatment of EoE in adults and adolescents who are 12 years and older and weigh at least 40 kg (about 88 pounds), based on safety and efficacy data previously presented by Dr. Dellon and colleagues as part of the phase 3 LIBERTY-EoE-TREET study (NCT03633617).
“Dupilumab is now the only medication FDA approved to treat EoE in the U.S.,” Dr. Dellon said. “The findings here are that the pooled efficacy and safety data for parts A and B of the phase 3 trial are consistent with the results of the individual parts of the study that were previously reported, and which led to the drug being approved for EoE.”
EoE is a chronic, progressive, type 2 inflammatory disease of the esophagus, which can lead to symptoms of esophageal dysfunction that affect quality of life. Current treatment options often lack specificity, present adherence challenges, and provide suboptimal long-term disease control, Dr. Dellon said.
Dupilumab, a fully human monoclonal antibody manufactured by Regeneron Pharmaceuticals, blocks the shared receptor component for interleukin-4 and IL-13, which are central drivers of type 2 inflammation in EoE.
Study population difficult to treat
In the three-part, double-blind, placebo-controlled, phase 3 study, dupilumab was administered to 122 patients as 300-mg weekly doses through subcutaneous injection. In parts A and B, dupilumab demonstrated statistically significant and clinically meaningful improvement in adults and adolescents up to 24 weeks. In patients from part A who continued to an extended active treatment period called part C, efficacy was sustained to week 52.
Participants were included if they had EoE that hadn’t responded to high-dose proton pump inhibitors, had baseline esophageal biopsies with a peak intraepithelial eosinophilic count of 15 eosinophils per high-power field (eos/HPF) or higher in two or more esophageal regions, had a history of an average of two or more episodes of dysphagia per week in the 4 weeks prior to screening, had four or more episodes of dysphagia in the 2 weeks prior to randomization with two or more episodes that required liquids or medical attention, and had a baseline Dysphagia Symptom Questionnaire (DSQ) score of 10 or higher.
On the other hand, participants were excluded if they initiated or changed a food-elimination diet regimen or reintroduced a previously eliminated food group in the 6 weeks before screening, had other causes of esophageal eosinophilia, had a history of other inflammatory diseases such as Crohn’s disease or ulcerative colitis, or were treated with swallowed topical corticosteroids within 8 weeks prior to baseline.
Dr. Dellon and colleagues focused on co–primary endpoints: The proportion of patients who achieved peak esophageal intraepithelial eosinophil count of 6 eos/HPF or less, and the absolute change in DSQ score from baseline to week 24.
Key secondary endpoints included percentage change in eos/HPF, absolute change in EoE-Endoscopic Reference Score (EREFS), absolute change in EoE-Histologic Scoring System (EoE-HSS) grade score, and EoE-HSS stage score. Other secondary endpoints included percentage change in DSQ score and proportion of patients achieving less than 15 eos/HPF.
The baseline demographics and clinical characteristics were similar between the treatment and placebo groups. Importantly, about 70% had been treated with topical corticosteroids, and about 40% had a history of esophageal dilation, Dr. Dellon said. The DSQ scores, peak eosinophil counts, and EREFS scores were high, indicating an inflamed, symptomatic, and difficult-to-treat population.
Pooled parts A and B findings
Overall, dupilumab reduced peak esophageal intraepithelial eosinophil counts at week 24. In the dupilumab group, 59% of patients were down to 6 eos/HPF or less, compared with 5.9% in the placebo group. In a secondary endpoint, 77% of dupilumab patients were down to 15 eos/HPF, compared with 7.6% in the placebo group. The dupilumab group saw an 80% drop in baseline change, compared with 1.5% in the placebo group.
Dupilumab also reduced dysphagia symptoms and improved endoscopic features of EoE at week 24. The absolute change in DSQ score was –23.21 in the dupilumab group, compared with –12.69 in the placebo group. The percent change in DSQ score was –65.5% in the dupilumab group, compared with –38.2% in the placebo group. The absolute change in EREFS score was –3.95 in the dupilumab group, compared with –0.41 in the placebo group.
In addition, dupilumab reduced histologic scores at week 24. The absolute change in EoE-HSS grade score was –0.82 in the dupilumab group, compared with –0.1 in the placebo group. The absolute change in EoE-HSS stage score was –0.79 in the dupilumab group, compared with –0.09 in the placebo group.
Dupilumab demonstrated an acceptable safety profile, and no new safety signals were noted, Dr. Dellon said. The most common adverse events was injection-site reaction at 37.5% in the dupilumab group and 33.3% in the placebo group. The severe adverse events were not related to the medication.
“If patients have EoE, dupilumab might be an option for treatment. However, it’s important to realize that, in the phase 3 study, all patients were PPI nonresponders, most had been treated with topical steroids [and many were not responsive], and many had prior esophageal dilation,” Dr. Dellon said. “We don’t have a lot of data in more mild EoE patients, and insurances are currently requiring a series of authorization before patients might be able to get this medication. It’s best to talk to their doctor about whether the medication is a good fit for not.”
The study was sponsored by Sanofi and Regeneron Pharmaceuticals. Three of the authors are employees for and have stock options with Regeneron or Sanofi. The other authors reported consultant roles, advisory roles, and research support from numerous pharmaceutical companies, including Regeneron and Sanofi.
Dupilumab appears to improve clinical, symptomatic, histologic, and endoscopic aspects of eosinophilic esophagitis (EoE) up to 24 weeks, according to findings presented at the annual meeting of the American College of Gastroenterology.
The drug was also well tolerated, demonstrating consistency with the known dupilumab safety profile, said Evan S. Dellon, MD, a gastroenterologist at the University of North Carolina at Chapel Hill.
In May, the Food and Drug Administration approved dupilumab (Dupixent) for the treatment of EoE in adults and adolescents who are 12 years and older and weigh at least 40 kg (about 88 pounds), based on safety and efficacy data previously presented by Dr. Dellon and colleagues as part of the phase 3 LIBERTY-EoE-TREET study (NCT03633617).
“Dupilumab is now the only medication FDA approved to treat EoE in the U.S.,” Dr. Dellon said. “The findings here are that the pooled efficacy and safety data for parts A and B of the phase 3 trial are consistent with the results of the individual parts of the study that were previously reported, and which led to the drug being approved for EoE.”
EoE is a chronic, progressive, type 2 inflammatory disease of the esophagus, which can lead to symptoms of esophageal dysfunction that affect quality of life. Current treatment options often lack specificity, present adherence challenges, and provide suboptimal long-term disease control, Dr. Dellon said.
Dupilumab, a fully human monoclonal antibody manufactured by Regeneron Pharmaceuticals, blocks the shared receptor component for interleukin-4 and IL-13, which are central drivers of type 2 inflammation in EoE.
Study population difficult to treat
In the three-part, double-blind, placebo-controlled, phase 3 study, dupilumab was administered to 122 patients as 300-mg weekly doses through subcutaneous injection. In parts A and B, dupilumab demonstrated statistically significant and clinically meaningful improvement in adults and adolescents up to 24 weeks. In patients from part A who continued to an extended active treatment period called part C, efficacy was sustained to week 52.
Participants were included if they had EoE that hadn’t responded to high-dose proton pump inhibitors, had baseline esophageal biopsies with a peak intraepithelial eosinophilic count of 15 eosinophils per high-power field (eos/HPF) or higher in two or more esophageal regions, had a history of an average of two or more episodes of dysphagia per week in the 4 weeks prior to screening, had four or more episodes of dysphagia in the 2 weeks prior to randomization with two or more episodes that required liquids or medical attention, and had a baseline Dysphagia Symptom Questionnaire (DSQ) score of 10 or higher.
On the other hand, participants were excluded if they initiated or changed a food-elimination diet regimen or reintroduced a previously eliminated food group in the 6 weeks before screening, had other causes of esophageal eosinophilia, had a history of other inflammatory diseases such as Crohn’s disease or ulcerative colitis, or were treated with swallowed topical corticosteroids within 8 weeks prior to baseline.
Dr. Dellon and colleagues focused on co–primary endpoints: The proportion of patients who achieved peak esophageal intraepithelial eosinophil count of 6 eos/HPF or less, and the absolute change in DSQ score from baseline to week 24.
Key secondary endpoints included percentage change in eos/HPF, absolute change in EoE-Endoscopic Reference Score (EREFS), absolute change in EoE-Histologic Scoring System (EoE-HSS) grade score, and EoE-HSS stage score. Other secondary endpoints included percentage change in DSQ score and proportion of patients achieving less than 15 eos/HPF.
The baseline demographics and clinical characteristics were similar between the treatment and placebo groups. Importantly, about 70% had been treated with topical corticosteroids, and about 40% had a history of esophageal dilation, Dr. Dellon said. The DSQ scores, peak eosinophil counts, and EREFS scores were high, indicating an inflamed, symptomatic, and difficult-to-treat population.
Pooled parts A and B findings
Overall, dupilumab reduced peak esophageal intraepithelial eosinophil counts at week 24. In the dupilumab group, 59% of patients were down to 6 eos/HPF or less, compared with 5.9% in the placebo group. In a secondary endpoint, 77% of dupilumab patients were down to 15 eos/HPF, compared with 7.6% in the placebo group. The dupilumab group saw an 80% drop in baseline change, compared with 1.5% in the placebo group.
Dupilumab also reduced dysphagia symptoms and improved endoscopic features of EoE at week 24. The absolute change in DSQ score was –23.21 in the dupilumab group, compared with –12.69 in the placebo group. The percent change in DSQ score was –65.5% in the dupilumab group, compared with –38.2% in the placebo group. The absolute change in EREFS score was –3.95 in the dupilumab group, compared with –0.41 in the placebo group.
In addition, dupilumab reduced histologic scores at week 24. The absolute change in EoE-HSS grade score was –0.82 in the dupilumab group, compared with –0.1 in the placebo group. The absolute change in EoE-HSS stage score was –0.79 in the dupilumab group, compared with –0.09 in the placebo group.
Dupilumab demonstrated an acceptable safety profile, and no new safety signals were noted, Dr. Dellon said. The most common adverse events was injection-site reaction at 37.5% in the dupilumab group and 33.3% in the placebo group. The severe adverse events were not related to the medication.
“If patients have EoE, dupilumab might be an option for treatment. However, it’s important to realize that, in the phase 3 study, all patients were PPI nonresponders, most had been treated with topical steroids [and many were not responsive], and many had prior esophageal dilation,” Dr. Dellon said. “We don’t have a lot of data in more mild EoE patients, and insurances are currently requiring a series of authorization before patients might be able to get this medication. It’s best to talk to their doctor about whether the medication is a good fit for not.”
The study was sponsored by Sanofi and Regeneron Pharmaceuticals. Three of the authors are employees for and have stock options with Regeneron or Sanofi. The other authors reported consultant roles, advisory roles, and research support from numerous pharmaceutical companies, including Regeneron and Sanofi.
FROM ACG 2022
Risk factors ID’d for acute pancreatitis from weight-loss drugs
CHARLOTTE, N.C. – a new study has found.
Type 2 diabetes, advanced chronic kidney disease, and tobacco use were associated with greater risk for acute pancreatitis, researchers report.
On the other hand, a higher body mass index (BMI) – 36 kg/m2 or higher – appeared to protect people against developing the condition.
“As this class of medications becomes increasingly popular in the United States, it is important for providers to know which patients are at a higher or lower risk of developing acute pancreatitis after being started on them,” said lead study author Robert Postlethwaite, MD, a gastroenterology resident at the University of Texas Southwestern Medical Center, Dallas.
The findings were presented at the annual meeting of the American College of Gastroenterology in Charlotte, N.C., being held in person and virtually.
Popularity comes at a price
The U.S. Food and Drug Administration has approved two GLP-1s for weight management – liraglutide (Victoza) in 2014 and semaglutide (Wegovy) in 2021. They work by targeting areas of the brain that control food intake and appetite. Other GLP-1s approved to treat type 2 diabetes include dulaglutide (Trulicity) and two other formulations of semaglutide (Rybelsus and Ozempic).
The demand for Wegovy has been so great that there is an ongoing shortage of the medication in the United States.
Although GLP-1s demonstrate a favorable side-effect profile, compared with other types of antiobesity medications, acute pancreatitis remains a serious and sometimes life-threatening complication, the researchers note. Some patients require hospitalization.
Dr. Postlethwaite and colleagues performed a retrospective, single-center study of 2,245 patients who attended an academic medical center’s Weight Wellness program from 2015 to 2019. The average age was about 50 years, and 81% were female. The average BMI of all patients was 39.7 kg/m2.
The study only included patients starting GLP-1s for treating obesity, not for diabetes.
Of the 2,245 patients, 49 (2.2%) developed acute pancreatitis after starting a GLP-1.
A history of type 2 diabetes mellitus made acute pancreatitis twice as likely (95% confidence interval, 1.04-3.96; P = .04).
Stage 3 or higher chronic kidney disease increased risk 2.3 times (95% CI, 1.18-4.55; P = .01), while tobacco use upped it 3.3 times (95% CI, 1.70-6.50; P < .001).
In contrast, researchers found those with a BMI of 36-40 kg/m2 were 88% less likely to develop acute pancreatitis (95% CI, 0.07-0.67; P = .007), compared with patients with a BMI of less than or equal to 30 kg/m2. Patients with a BMI of greater than 40 kg/m2 had a 73% lower risk (95% CI, 0.10-0.73; P = .01).
Dr. Postlethwaite and colleagues found no association with age, sex, or history of bariatric surgery or acute pancreatitis.
Because a history of acute pancreatitis was not a risk factor, he advised that clinicians not withhold these medications for this reason, “especially given the significant glycemic, cardiovascular, and weight-loss effects.”
“We hope that we can arm clinicians with evidence in order to risk stratify their patients and determine who is at high risk of developing pancreatitis,” Dr. Postlethwaite said.
“Hopefully, we can prevent the development of pancreatitis in some patients, especially high-risk individuals, or at least allow clinicians to be aware of it in higher-risk patients to identify it early enough to prevent complications of acute pancreatitis,” he added.
Larger studies needed
The study is “promising,” said session comoderator Baharak Moshiree, MD, a gastroenterologist at Atrium Health, Charlotte, N.C., who was not affiliated with the research.
However, because the study was retrospective and relatively small, it needs to be validated in larger, prospective studies, she added.
“With obesity being such a global issue, there are many patients on these GLP-1 agonists,” Dr. Moshiree said.
Generally, these medications are prescribed by endocrinologists, not gastroenterologists, she noted, and she said that gastroenterologists should be aware of the risks associated with them, including minor gastrointestinal side effects, like nausea and vomiting, that can occur because of delayed gastric emptying.
Dr. Postlethwaite noted that being unable to assess how much alcohol or tobacco individuals used was a limitation. The relatively low proportion of people who developed acute pancreatitis in the study also means larger studies are warranted, he added.
Going forward, Dr. Postlethwaite and colleagues want to study the risks for each individual GLP-1 and other therapies used to control high blood sugar in people with type 2 diabetes, such as DPP4 (dipeptidyl-peptidase 4) inhibitors.
The study was independently supported. Dr. Postlethwaite and Dr. Moshiree report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
CHARLOTTE, N.C. – a new study has found.
Type 2 diabetes, advanced chronic kidney disease, and tobacco use were associated with greater risk for acute pancreatitis, researchers report.
On the other hand, a higher body mass index (BMI) – 36 kg/m2 or higher – appeared to protect people against developing the condition.
“As this class of medications becomes increasingly popular in the United States, it is important for providers to know which patients are at a higher or lower risk of developing acute pancreatitis after being started on them,” said lead study author Robert Postlethwaite, MD, a gastroenterology resident at the University of Texas Southwestern Medical Center, Dallas.
The findings were presented at the annual meeting of the American College of Gastroenterology in Charlotte, N.C., being held in person and virtually.
Popularity comes at a price
The U.S. Food and Drug Administration has approved two GLP-1s for weight management – liraglutide (Victoza) in 2014 and semaglutide (Wegovy) in 2021. They work by targeting areas of the brain that control food intake and appetite. Other GLP-1s approved to treat type 2 diabetes include dulaglutide (Trulicity) and two other formulations of semaglutide (Rybelsus and Ozempic).
The demand for Wegovy has been so great that there is an ongoing shortage of the medication in the United States.
Although GLP-1s demonstrate a favorable side-effect profile, compared with other types of antiobesity medications, acute pancreatitis remains a serious and sometimes life-threatening complication, the researchers note. Some patients require hospitalization.
Dr. Postlethwaite and colleagues performed a retrospective, single-center study of 2,245 patients who attended an academic medical center’s Weight Wellness program from 2015 to 2019. The average age was about 50 years, and 81% were female. The average BMI of all patients was 39.7 kg/m2.
The study only included patients starting GLP-1s for treating obesity, not for diabetes.
Of the 2,245 patients, 49 (2.2%) developed acute pancreatitis after starting a GLP-1.
A history of type 2 diabetes mellitus made acute pancreatitis twice as likely (95% confidence interval, 1.04-3.96; P = .04).
Stage 3 or higher chronic kidney disease increased risk 2.3 times (95% CI, 1.18-4.55; P = .01), while tobacco use upped it 3.3 times (95% CI, 1.70-6.50; P < .001).
In contrast, researchers found those with a BMI of 36-40 kg/m2 were 88% less likely to develop acute pancreatitis (95% CI, 0.07-0.67; P = .007), compared with patients with a BMI of less than or equal to 30 kg/m2. Patients with a BMI of greater than 40 kg/m2 had a 73% lower risk (95% CI, 0.10-0.73; P = .01).
Dr. Postlethwaite and colleagues found no association with age, sex, or history of bariatric surgery or acute pancreatitis.
Because a history of acute pancreatitis was not a risk factor, he advised that clinicians not withhold these medications for this reason, “especially given the significant glycemic, cardiovascular, and weight-loss effects.”
“We hope that we can arm clinicians with evidence in order to risk stratify their patients and determine who is at high risk of developing pancreatitis,” Dr. Postlethwaite said.
“Hopefully, we can prevent the development of pancreatitis in some patients, especially high-risk individuals, or at least allow clinicians to be aware of it in higher-risk patients to identify it early enough to prevent complications of acute pancreatitis,” he added.
Larger studies needed
The study is “promising,” said session comoderator Baharak Moshiree, MD, a gastroenterologist at Atrium Health, Charlotte, N.C., who was not affiliated with the research.
However, because the study was retrospective and relatively small, it needs to be validated in larger, prospective studies, she added.
“With obesity being such a global issue, there are many patients on these GLP-1 agonists,” Dr. Moshiree said.
Generally, these medications are prescribed by endocrinologists, not gastroenterologists, she noted, and she said that gastroenterologists should be aware of the risks associated with them, including minor gastrointestinal side effects, like nausea and vomiting, that can occur because of delayed gastric emptying.
Dr. Postlethwaite noted that being unable to assess how much alcohol or tobacco individuals used was a limitation. The relatively low proportion of people who developed acute pancreatitis in the study also means larger studies are warranted, he added.
Going forward, Dr. Postlethwaite and colleagues want to study the risks for each individual GLP-1 and other therapies used to control high blood sugar in people with type 2 diabetes, such as DPP4 (dipeptidyl-peptidase 4) inhibitors.
The study was independently supported. Dr. Postlethwaite and Dr. Moshiree report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
CHARLOTTE, N.C. – a new study has found.
Type 2 diabetes, advanced chronic kidney disease, and tobacco use were associated with greater risk for acute pancreatitis, researchers report.
On the other hand, a higher body mass index (BMI) – 36 kg/m2 or higher – appeared to protect people against developing the condition.
“As this class of medications becomes increasingly popular in the United States, it is important for providers to know which patients are at a higher or lower risk of developing acute pancreatitis after being started on them,” said lead study author Robert Postlethwaite, MD, a gastroenterology resident at the University of Texas Southwestern Medical Center, Dallas.
The findings were presented at the annual meeting of the American College of Gastroenterology in Charlotte, N.C., being held in person and virtually.
Popularity comes at a price
The U.S. Food and Drug Administration has approved two GLP-1s for weight management – liraglutide (Victoza) in 2014 and semaglutide (Wegovy) in 2021. They work by targeting areas of the brain that control food intake and appetite. Other GLP-1s approved to treat type 2 diabetes include dulaglutide (Trulicity) and two other formulations of semaglutide (Rybelsus and Ozempic).
The demand for Wegovy has been so great that there is an ongoing shortage of the medication in the United States.
Although GLP-1s demonstrate a favorable side-effect profile, compared with other types of antiobesity medications, acute pancreatitis remains a serious and sometimes life-threatening complication, the researchers note. Some patients require hospitalization.
Dr. Postlethwaite and colleagues performed a retrospective, single-center study of 2,245 patients who attended an academic medical center’s Weight Wellness program from 2015 to 2019. The average age was about 50 years, and 81% were female. The average BMI of all patients was 39.7 kg/m2.
The study only included patients starting GLP-1s for treating obesity, not for diabetes.
Of the 2,245 patients, 49 (2.2%) developed acute pancreatitis after starting a GLP-1.
A history of type 2 diabetes mellitus made acute pancreatitis twice as likely (95% confidence interval, 1.04-3.96; P = .04).
Stage 3 or higher chronic kidney disease increased risk 2.3 times (95% CI, 1.18-4.55; P = .01), while tobacco use upped it 3.3 times (95% CI, 1.70-6.50; P < .001).
In contrast, researchers found those with a BMI of 36-40 kg/m2 were 88% less likely to develop acute pancreatitis (95% CI, 0.07-0.67; P = .007), compared with patients with a BMI of less than or equal to 30 kg/m2. Patients with a BMI of greater than 40 kg/m2 had a 73% lower risk (95% CI, 0.10-0.73; P = .01).
Dr. Postlethwaite and colleagues found no association with age, sex, or history of bariatric surgery or acute pancreatitis.
Because a history of acute pancreatitis was not a risk factor, he advised that clinicians not withhold these medications for this reason, “especially given the significant glycemic, cardiovascular, and weight-loss effects.”
“We hope that we can arm clinicians with evidence in order to risk stratify their patients and determine who is at high risk of developing pancreatitis,” Dr. Postlethwaite said.
“Hopefully, we can prevent the development of pancreatitis in some patients, especially high-risk individuals, or at least allow clinicians to be aware of it in higher-risk patients to identify it early enough to prevent complications of acute pancreatitis,” he added.
Larger studies needed
The study is “promising,” said session comoderator Baharak Moshiree, MD, a gastroenterologist at Atrium Health, Charlotte, N.C., who was not affiliated with the research.
However, because the study was retrospective and relatively small, it needs to be validated in larger, prospective studies, she added.
“With obesity being such a global issue, there are many patients on these GLP-1 agonists,” Dr. Moshiree said.
Generally, these medications are prescribed by endocrinologists, not gastroenterologists, she noted, and she said that gastroenterologists should be aware of the risks associated with them, including minor gastrointestinal side effects, like nausea and vomiting, that can occur because of delayed gastric emptying.
Dr. Postlethwaite noted that being unable to assess how much alcohol or tobacco individuals used was a limitation. The relatively low proportion of people who developed acute pancreatitis in the study also means larger studies are warranted, he added.
Going forward, Dr. Postlethwaite and colleagues want to study the risks for each individual GLP-1 and other therapies used to control high blood sugar in people with type 2 diabetes, such as DPP4 (dipeptidyl-peptidase 4) inhibitors.
The study was independently supported. Dr. Postlethwaite and Dr. Moshiree report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ACG 2022
Time to ditch clarithromycin for H. pylori?
Rates of resistance to clarithromycin among Helicobacter pylori isolates in the United States and Europe are high enough to warrant discontinuation of empiric use of proton pump inhibitor (PPI)–based triple therapy that includes the antibiotic in these regions, a new study has found.
Overall, 22.2% of participants were resistant to clarithromycin – a rate that is above the currently recommended threshold of 15% or higher for avoidance of PPI-based triple therapy that includes clarithromycin.
, study investigator William Chey, MD, professor and chief, Division of Gastroenterology and Hepatology, Michigan Medicine, Ann Arbor, said in an interview.
Judith Kim, MD, a gastroenterologist at NYU Langone Health and clinical instructor of medicine at NYU Grossman School of Medicine, who wasn’t involved in the study, agrees.
“The use of PPI-based triple therapy is still common practice despite recent recommendations to avoid clarithromycin in areas with high resistance rates,” Dr. Kim told this news organization.
“This study shows that multiple parts of the United States and Europe have high resistance rates,” rendering clarithromycin-based regimens “more likely to ineffectively eradicate H pylori,” Dr. Kim said.
The study was published online in The American Journal of Gastroenterology.
Better options now available
Guidelines advise against the use of PPI-based triple regimens with clarithromycin for H. pylori infection in areas where resistance is 15% or higher or for patients who have previously received macrolides. However, up-to-date information on H. pylori antimicrobial resistance patterns is limited, especially in the United States.
Dr. Chey and colleagues assessed resistance rates to antibiotics commonly used to treat H. pylori in isolates from 907 adults with the infection in the United States and Europe. They included four U.S. subregions and five participating European countries.
In all U.S. subregions and European countries, clarithromycin resistance rates were above 15% except possibly in the United Kingdom, where the sample size was too small to provide a reliable estimate.
Three-quarters of the clarithromycin-resistant isolates were also resistant to metronidazole.
The study also found that, overall, 1.2% of patients had isolates that were resistant to amoxicillin, and 69.2% had isolates resistant to metronidazole. Resistance patterns were similar in the United States and Europe; metronidazole resistance was the most common (50%-79% of isolates), and amoxicillin was the least common (≤ 5%).
“Overall, these data provide robust evidence to support a shift away from the default empiric prescription of triple combinations containing a PPI and clarithromycin for H. pylori infection in the United States and Europe,” the study team writes.
The high prevalence of resistance, including dual resistance, highlights the need for antibiotic stewardship and resistance surveillance, as well as novel treatment strategies for H. pylori infection, they add.
Last spring, as previously reported, the United States Food and Drug Administration approved two vonoprazan-based treatments for H. pylori: Voquezna Triple Pak (vonoprazan, amoxicillin, clarithromycin) and Voquezna Dual Pak (vonoprazan, amoxicillin), both from Phathom Pharmaceuticals.
“Vonoprazan-based treatment may be superior to standard PPI triple therapy for clarithromycin-resistant infections based on prior studies and is a potential good option,” Dr. Kim said.
Still, she added, she “would most likely first recommend regimens that do not have clarithromycin, such as bismuth quadruple therapy.”
Study’s importance
Because the study drew upon the largest dataset to date on U.S. resistance rates, it should be used to more precisely guide first-line therapy decisions, said Richard Peek, Jr., MD, professor of medicine and director of gastroenterology at Vanderbilt University Medical Center, Nashville, Tenn.
“To date, there has been a dearth of information in the United States regarding H. pylori resistance rates, which has often led to the use of ineffective empiric therapies and inappropriate exposure to antibiotics,” Dr. Peek, who wasn’t involved in the study, told this news organization.
“These data are particularly exciting when viewed within the context of new genomic sequencing tests that can determine H. pylori resistance patterns using DNA isolated from the stomach or the stool,” he said.
Dr. Peek agreed that the recent approval of vonoprazan-based therapies “adds another regimen to the therapeutic armamentarium available for eradicating H. pylori, and its value seems to be particularly beneficial for eradication failures.”
The research was funded by Phathom Pharmaceuticals. Dr. Chey is a board member of the American College of Gastroenterology, GI on Demand, the International Foundation of Functional GI Disorders, and the Rome Foundation. He has received compensation as a consultant from AbbVie, Alfasigma, Allakos, Alnylam, Bayer, BioAmerica, Cosmo, Intrinsic Medicine, Ironwood Pharmaceuticals, QOL Medical, Nestle, Phathom Pharmaceuticals, RedHill Biopharma, Salix/Valeant, Takeda, Urovant, and Vibrant; grant/research support from BioAmerica, Commonwealth Diagnostics International, QOL Medical, Salix, and Vibrant; owns stock/stock options in GI on Demand and Modify Health; and owns patents relating to methods and kits for identifying food sensitivities and intolerances, digital manometry, and a rectal expulsion device. Dr. Peek and Dr. Kim report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Rates of resistance to clarithromycin among Helicobacter pylori isolates in the United States and Europe are high enough to warrant discontinuation of empiric use of proton pump inhibitor (PPI)–based triple therapy that includes the antibiotic in these regions, a new study has found.
Overall, 22.2% of participants were resistant to clarithromycin – a rate that is above the currently recommended threshold of 15% or higher for avoidance of PPI-based triple therapy that includes clarithromycin.
, study investigator William Chey, MD, professor and chief, Division of Gastroenterology and Hepatology, Michigan Medicine, Ann Arbor, said in an interview.
Judith Kim, MD, a gastroenterologist at NYU Langone Health and clinical instructor of medicine at NYU Grossman School of Medicine, who wasn’t involved in the study, agrees.
“The use of PPI-based triple therapy is still common practice despite recent recommendations to avoid clarithromycin in areas with high resistance rates,” Dr. Kim told this news organization.
“This study shows that multiple parts of the United States and Europe have high resistance rates,” rendering clarithromycin-based regimens “more likely to ineffectively eradicate H pylori,” Dr. Kim said.
The study was published online in The American Journal of Gastroenterology.
Better options now available
Guidelines advise against the use of PPI-based triple regimens with clarithromycin for H. pylori infection in areas where resistance is 15% or higher or for patients who have previously received macrolides. However, up-to-date information on H. pylori antimicrobial resistance patterns is limited, especially in the United States.
Dr. Chey and colleagues assessed resistance rates to antibiotics commonly used to treat H. pylori in isolates from 907 adults with the infection in the United States and Europe. They included four U.S. subregions and five participating European countries.
In all U.S. subregions and European countries, clarithromycin resistance rates were above 15% except possibly in the United Kingdom, where the sample size was too small to provide a reliable estimate.
Three-quarters of the clarithromycin-resistant isolates were also resistant to metronidazole.
The study also found that, overall, 1.2% of patients had isolates that were resistant to amoxicillin, and 69.2% had isolates resistant to metronidazole. Resistance patterns were similar in the United States and Europe; metronidazole resistance was the most common (50%-79% of isolates), and amoxicillin was the least common (≤ 5%).
“Overall, these data provide robust evidence to support a shift away from the default empiric prescription of triple combinations containing a PPI and clarithromycin for H. pylori infection in the United States and Europe,” the study team writes.
The high prevalence of resistance, including dual resistance, highlights the need for antibiotic stewardship and resistance surveillance, as well as novel treatment strategies for H. pylori infection, they add.
Last spring, as previously reported, the United States Food and Drug Administration approved two vonoprazan-based treatments for H. pylori: Voquezna Triple Pak (vonoprazan, amoxicillin, clarithromycin) and Voquezna Dual Pak (vonoprazan, amoxicillin), both from Phathom Pharmaceuticals.
“Vonoprazan-based treatment may be superior to standard PPI triple therapy for clarithromycin-resistant infections based on prior studies and is a potential good option,” Dr. Kim said.
Still, she added, she “would most likely first recommend regimens that do not have clarithromycin, such as bismuth quadruple therapy.”
Study’s importance
Because the study drew upon the largest dataset to date on U.S. resistance rates, it should be used to more precisely guide first-line therapy decisions, said Richard Peek, Jr., MD, professor of medicine and director of gastroenterology at Vanderbilt University Medical Center, Nashville, Tenn.
“To date, there has been a dearth of information in the United States regarding H. pylori resistance rates, which has often led to the use of ineffective empiric therapies and inappropriate exposure to antibiotics,” Dr. Peek, who wasn’t involved in the study, told this news organization.
“These data are particularly exciting when viewed within the context of new genomic sequencing tests that can determine H. pylori resistance patterns using DNA isolated from the stomach or the stool,” he said.
Dr. Peek agreed that the recent approval of vonoprazan-based therapies “adds another regimen to the therapeutic armamentarium available for eradicating H. pylori, and its value seems to be particularly beneficial for eradication failures.”
The research was funded by Phathom Pharmaceuticals. Dr. Chey is a board member of the American College of Gastroenterology, GI on Demand, the International Foundation of Functional GI Disorders, and the Rome Foundation. He has received compensation as a consultant from AbbVie, Alfasigma, Allakos, Alnylam, Bayer, BioAmerica, Cosmo, Intrinsic Medicine, Ironwood Pharmaceuticals, QOL Medical, Nestle, Phathom Pharmaceuticals, RedHill Biopharma, Salix/Valeant, Takeda, Urovant, and Vibrant; grant/research support from BioAmerica, Commonwealth Diagnostics International, QOL Medical, Salix, and Vibrant; owns stock/stock options in GI on Demand and Modify Health; and owns patents relating to methods and kits for identifying food sensitivities and intolerances, digital manometry, and a rectal expulsion device. Dr. Peek and Dr. Kim report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Rates of resistance to clarithromycin among Helicobacter pylori isolates in the United States and Europe are high enough to warrant discontinuation of empiric use of proton pump inhibitor (PPI)–based triple therapy that includes the antibiotic in these regions, a new study has found.
Overall, 22.2% of participants were resistant to clarithromycin – a rate that is above the currently recommended threshold of 15% or higher for avoidance of PPI-based triple therapy that includes clarithromycin.
, study investigator William Chey, MD, professor and chief, Division of Gastroenterology and Hepatology, Michigan Medicine, Ann Arbor, said in an interview.
Judith Kim, MD, a gastroenterologist at NYU Langone Health and clinical instructor of medicine at NYU Grossman School of Medicine, who wasn’t involved in the study, agrees.
“The use of PPI-based triple therapy is still common practice despite recent recommendations to avoid clarithromycin in areas with high resistance rates,” Dr. Kim told this news organization.
“This study shows that multiple parts of the United States and Europe have high resistance rates,” rendering clarithromycin-based regimens “more likely to ineffectively eradicate H pylori,” Dr. Kim said.
The study was published online in The American Journal of Gastroenterology.
Better options now available
Guidelines advise against the use of PPI-based triple regimens with clarithromycin for H. pylori infection in areas where resistance is 15% or higher or for patients who have previously received macrolides. However, up-to-date information on H. pylori antimicrobial resistance patterns is limited, especially in the United States.
Dr. Chey and colleagues assessed resistance rates to antibiotics commonly used to treat H. pylori in isolates from 907 adults with the infection in the United States and Europe. They included four U.S. subregions and five participating European countries.
In all U.S. subregions and European countries, clarithromycin resistance rates were above 15% except possibly in the United Kingdom, where the sample size was too small to provide a reliable estimate.
Three-quarters of the clarithromycin-resistant isolates were also resistant to metronidazole.
The study also found that, overall, 1.2% of patients had isolates that were resistant to amoxicillin, and 69.2% had isolates resistant to metronidazole. Resistance patterns were similar in the United States and Europe; metronidazole resistance was the most common (50%-79% of isolates), and amoxicillin was the least common (≤ 5%).
“Overall, these data provide robust evidence to support a shift away from the default empiric prescription of triple combinations containing a PPI and clarithromycin for H. pylori infection in the United States and Europe,” the study team writes.
The high prevalence of resistance, including dual resistance, highlights the need for antibiotic stewardship and resistance surveillance, as well as novel treatment strategies for H. pylori infection, they add.
Last spring, as previously reported, the United States Food and Drug Administration approved two vonoprazan-based treatments for H. pylori: Voquezna Triple Pak (vonoprazan, amoxicillin, clarithromycin) and Voquezna Dual Pak (vonoprazan, amoxicillin), both from Phathom Pharmaceuticals.
“Vonoprazan-based treatment may be superior to standard PPI triple therapy for clarithromycin-resistant infections based on prior studies and is a potential good option,” Dr. Kim said.
Still, she added, she “would most likely first recommend regimens that do not have clarithromycin, such as bismuth quadruple therapy.”
Study’s importance
Because the study drew upon the largest dataset to date on U.S. resistance rates, it should be used to more precisely guide first-line therapy decisions, said Richard Peek, Jr., MD, professor of medicine and director of gastroenterology at Vanderbilt University Medical Center, Nashville, Tenn.
“To date, there has been a dearth of information in the United States regarding H. pylori resistance rates, which has often led to the use of ineffective empiric therapies and inappropriate exposure to antibiotics,” Dr. Peek, who wasn’t involved in the study, told this news organization.
“These data are particularly exciting when viewed within the context of new genomic sequencing tests that can determine H. pylori resistance patterns using DNA isolated from the stomach or the stool,” he said.
Dr. Peek agreed that the recent approval of vonoprazan-based therapies “adds another regimen to the therapeutic armamentarium available for eradicating H. pylori, and its value seems to be particularly beneficial for eradication failures.”
The research was funded by Phathom Pharmaceuticals. Dr. Chey is a board member of the American College of Gastroenterology, GI on Demand, the International Foundation of Functional GI Disorders, and the Rome Foundation. He has received compensation as a consultant from AbbVie, Alfasigma, Allakos, Alnylam, Bayer, BioAmerica, Cosmo, Intrinsic Medicine, Ironwood Pharmaceuticals, QOL Medical, Nestle, Phathom Pharmaceuticals, RedHill Biopharma, Salix/Valeant, Takeda, Urovant, and Vibrant; grant/research support from BioAmerica, Commonwealth Diagnostics International, QOL Medical, Salix, and Vibrant; owns stock/stock options in GI on Demand and Modify Health; and owns patents relating to methods and kits for identifying food sensitivities and intolerances, digital manometry, and a rectal expulsion device. Dr. Peek and Dr. Kim report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Experts refine nomenclature for eosinophilic GI diseases
A new international consensus paper is recommending that eosinophilic GI diseases (EGIDs) should be named according to more specific criteria. The paper seeks to update nomenclature to improve research and bolster clinical clarity.
The involved part of the GI tract should be specifically named, and the abbreviation “Eo” should be used. Furthermore, the umbrella term should be EGID instead of the currently used “eosinophilic gastroenteritis,” according to the statement published in Clinical Gastroenterology and Hepatology. The statement included 91 authors from five continents who filled out two rounds of surveys. In total, 93% completed the first and 90% completed the second. The paper produced 22 statements, with a consensus reached on all but 2.
EGIDs are chronic, immune-driven disorders that produce gastrointestinal symptoms and are characterized by eosinophil-dominant inflammation in specific GI regions. Although eosinophilic esophagitis (EoE) is the most well known of these conditions, other EGIDs have become more commonly recognized in recent years and are the subject of intense study. Other affected areas include the stomach, small bowel, and colon, where it can occur individually or in combination.
Efforts are underway to develop guidelines for diagnosis and treatment of EGIDs, but there was initial confusion surrounding the term eosinophilic gastroenteritis since its definition varied significantly in different clinical and research settings, according to the authors. That term varyingly referred to stomach alone, small bowel alone, stomach and small bowel, or any region of the GI tract.
“This nonstandardized use of nomenclature highlighted a need for a common language for non-EoE eosinophilic GI disease names, not only for clinical practice, but also for the consistent data collection required for research to continue to advance the field,” co–first authors Evan S. Dellon, MD, MPH, AGAF, from the University of North Carolina at Chapel Hill, and Nirmala Gonsalves, MD, from Northwestern University, Chicago, and colleagues wrote. “This step, while seemingly rudimentary, was essential to inform the guideline efforts that are now underway.”
After responses to the surveys were analyzed, respondents participated in one of two scheduled meetings held on a video conferencing platform in May 2021. Feedback from these meetings was then used to create a second round of 29 statements which were again distributed, and participants were asked to either agree or disagree with each statement. Agreement was set a priori at 70%. In all, 38% of the participants were women, and 91% worked in academic or university settings.
In routine clinical practice, conditions with eosinophil-dominant inflammation in the absence of secondary causes outside of the esophagus can collectively be referred to clinically as non-EoE EGID. Stomach involvement should be called eosinophilic gastritis (EoG), small bowel involvement eosinophilic enteritis (EoN), and colon involvement eosinophilic colitis (EoC).
For research use, and clinical use if desired, the authors called for greater granularity in description of the conditions, with each location named. For example, if the stomach and small bowel are both involved, the condition should be termed eosinophilic gastritis and enteritis. The authors could not reach a consensus for terminology when the esophagus is also involved, leading to the recommendation that it can be included using the phrase “with esophageal involvement” or by using EoE, although they note that this could be confusing since EoE is the current term for eosinophilia isolated in the esophagus.
The authors came to universal agreement in many areas, but there were exceptions that mostly centered on how to name conditions that affect multiple areas of the GI tract. It remains uncertain whether eosinophilia in different regions is caused by the same pathogenesis. Some experts felt that a “primary” location of EGID should be identified using predominant symptoms, endoscopic features, and complications. However, the authors anticipate that this nomenclature will change over time.
The authors noted that the clinical manifestation of the disease should remain the driving factor behind classification. Testing should be driven by clinically relevant questions, and overtesting should be avoided. More details on this are likely to be forthcoming in future guidelines.
The consensus statement is limited by the fact that most participants were from academic settings. These recommendations do not apply to eosinophilic disorders of the gallbladder, liver, or pancreas. Application of the recommendations to the small bowel may be too general or specific, but are meant primarily as a starting point for further refinement.
These limitations should help to drive further research. For example, molecular and pathogenic data could help distinguish EoE from “esophageal involvement” by determining if pathogenic mechanisms are the same or different, which would in turn lead to lumping the conditions into a single term or keeping them separate.
“The iterative and collaborative process led to agreement on nearly all aspects of the proposed nomenclature framework, and has identified future research directions. It is expected that as more data are collected, the nomenclature will again be updated to reflect best practices and the underlying pathogenesis of these disorders,” the authors concluded.
The authors disclosed relationships with various industry companies, including AstraZeneca, Celgene, GlaxoSmithKline, Regeneron, Sanofi, and Takeda.
Eosinophilic conditions of the gastrointestinal tract have risen in incidence, leading to significant patient symptoms and morbidity, but thankfully there have been tremendous innovations in identification, management, treatment, and drug development. In this excellent article, an international consensus was created to reflect this rapidly changing understanding of the phenotypes with updated diagnostic nomenclature.
Redefinition of these conditions will help in many aspects. First, advances in therapy targeted as eosinophilic trafficking have been approved with many biologic therapies in the pipeline, and understanding their treatment effects and targets will help our patients. Second, improved nomenclature will help better understand the genetic, phenotypic, and therapeutic options for these conditions providing our patients with personalized care. As the understanding of eosinophilic conditions expands with the growth of genetic associations and drug therapies, we are matching our inflammatory bowel disease colleagues in their successes to provide our patients with personalized care.
Rishi D. Naik, MD, MSCI, is an assistant professor, department of medicine, section of gastroenterology & hepatology, Esophageal Center at Vanderbilt University Medical Center, Nashville, Tenn.
Eosinophilic conditions of the gastrointestinal tract have risen in incidence, leading to significant patient symptoms and morbidity, but thankfully there have been tremendous innovations in identification, management, treatment, and drug development. In this excellent article, an international consensus was created to reflect this rapidly changing understanding of the phenotypes with updated diagnostic nomenclature.
Redefinition of these conditions will help in many aspects. First, advances in therapy targeted as eosinophilic trafficking have been approved with many biologic therapies in the pipeline, and understanding their treatment effects and targets will help our patients. Second, improved nomenclature will help better understand the genetic, phenotypic, and therapeutic options for these conditions providing our patients with personalized care. As the understanding of eosinophilic conditions expands with the growth of genetic associations and drug therapies, we are matching our inflammatory bowel disease colleagues in their successes to provide our patients with personalized care.
Rishi D. Naik, MD, MSCI, is an assistant professor, department of medicine, section of gastroenterology & hepatology, Esophageal Center at Vanderbilt University Medical Center, Nashville, Tenn.
Eosinophilic conditions of the gastrointestinal tract have risen in incidence, leading to significant patient symptoms and morbidity, but thankfully there have been tremendous innovations in identification, management, treatment, and drug development. In this excellent article, an international consensus was created to reflect this rapidly changing understanding of the phenotypes with updated diagnostic nomenclature.
Redefinition of these conditions will help in many aspects. First, advances in therapy targeted as eosinophilic trafficking have been approved with many biologic therapies in the pipeline, and understanding their treatment effects and targets will help our patients. Second, improved nomenclature will help better understand the genetic, phenotypic, and therapeutic options for these conditions providing our patients with personalized care. As the understanding of eosinophilic conditions expands with the growth of genetic associations and drug therapies, we are matching our inflammatory bowel disease colleagues in their successes to provide our patients with personalized care.
Rishi D. Naik, MD, MSCI, is an assistant professor, department of medicine, section of gastroenterology & hepatology, Esophageal Center at Vanderbilt University Medical Center, Nashville, Tenn.
A new international consensus paper is recommending that eosinophilic GI diseases (EGIDs) should be named according to more specific criteria. The paper seeks to update nomenclature to improve research and bolster clinical clarity.
The involved part of the GI tract should be specifically named, and the abbreviation “Eo” should be used. Furthermore, the umbrella term should be EGID instead of the currently used “eosinophilic gastroenteritis,” according to the statement published in Clinical Gastroenterology and Hepatology. The statement included 91 authors from five continents who filled out two rounds of surveys. In total, 93% completed the first and 90% completed the second. The paper produced 22 statements, with a consensus reached on all but 2.
EGIDs are chronic, immune-driven disorders that produce gastrointestinal symptoms and are characterized by eosinophil-dominant inflammation in specific GI regions. Although eosinophilic esophagitis (EoE) is the most well known of these conditions, other EGIDs have become more commonly recognized in recent years and are the subject of intense study. Other affected areas include the stomach, small bowel, and colon, where it can occur individually or in combination.
Efforts are underway to develop guidelines for diagnosis and treatment of EGIDs, but there was initial confusion surrounding the term eosinophilic gastroenteritis since its definition varied significantly in different clinical and research settings, according to the authors. That term varyingly referred to stomach alone, small bowel alone, stomach and small bowel, or any region of the GI tract.
“This nonstandardized use of nomenclature highlighted a need for a common language for non-EoE eosinophilic GI disease names, not only for clinical practice, but also for the consistent data collection required for research to continue to advance the field,” co–first authors Evan S. Dellon, MD, MPH, AGAF, from the University of North Carolina at Chapel Hill, and Nirmala Gonsalves, MD, from Northwestern University, Chicago, and colleagues wrote. “This step, while seemingly rudimentary, was essential to inform the guideline efforts that are now underway.”
After responses to the surveys were analyzed, respondents participated in one of two scheduled meetings held on a video conferencing platform in May 2021. Feedback from these meetings was then used to create a second round of 29 statements which were again distributed, and participants were asked to either agree or disagree with each statement. Agreement was set a priori at 70%. In all, 38% of the participants were women, and 91% worked in academic or university settings.
In routine clinical practice, conditions with eosinophil-dominant inflammation in the absence of secondary causes outside of the esophagus can collectively be referred to clinically as non-EoE EGID. Stomach involvement should be called eosinophilic gastritis (EoG), small bowel involvement eosinophilic enteritis (EoN), and colon involvement eosinophilic colitis (EoC).
For research use, and clinical use if desired, the authors called for greater granularity in description of the conditions, with each location named. For example, if the stomach and small bowel are both involved, the condition should be termed eosinophilic gastritis and enteritis. The authors could not reach a consensus for terminology when the esophagus is also involved, leading to the recommendation that it can be included using the phrase “with esophageal involvement” or by using EoE, although they note that this could be confusing since EoE is the current term for eosinophilia isolated in the esophagus.
The authors came to universal agreement in many areas, but there were exceptions that mostly centered on how to name conditions that affect multiple areas of the GI tract. It remains uncertain whether eosinophilia in different regions is caused by the same pathogenesis. Some experts felt that a “primary” location of EGID should be identified using predominant symptoms, endoscopic features, and complications. However, the authors anticipate that this nomenclature will change over time.
The authors noted that the clinical manifestation of the disease should remain the driving factor behind classification. Testing should be driven by clinically relevant questions, and overtesting should be avoided. More details on this are likely to be forthcoming in future guidelines.
The consensus statement is limited by the fact that most participants were from academic settings. These recommendations do not apply to eosinophilic disorders of the gallbladder, liver, or pancreas. Application of the recommendations to the small bowel may be too general or specific, but are meant primarily as a starting point for further refinement.
These limitations should help to drive further research. For example, molecular and pathogenic data could help distinguish EoE from “esophageal involvement” by determining if pathogenic mechanisms are the same or different, which would in turn lead to lumping the conditions into a single term or keeping them separate.
“The iterative and collaborative process led to agreement on nearly all aspects of the proposed nomenclature framework, and has identified future research directions. It is expected that as more data are collected, the nomenclature will again be updated to reflect best practices and the underlying pathogenesis of these disorders,” the authors concluded.
The authors disclosed relationships with various industry companies, including AstraZeneca, Celgene, GlaxoSmithKline, Regeneron, Sanofi, and Takeda.
A new international consensus paper is recommending that eosinophilic GI diseases (EGIDs) should be named according to more specific criteria. The paper seeks to update nomenclature to improve research and bolster clinical clarity.
The involved part of the GI tract should be specifically named, and the abbreviation “Eo” should be used. Furthermore, the umbrella term should be EGID instead of the currently used “eosinophilic gastroenteritis,” according to the statement published in Clinical Gastroenterology and Hepatology. The statement included 91 authors from five continents who filled out two rounds of surveys. In total, 93% completed the first and 90% completed the second. The paper produced 22 statements, with a consensus reached on all but 2.
EGIDs are chronic, immune-driven disorders that produce gastrointestinal symptoms and are characterized by eosinophil-dominant inflammation in specific GI regions. Although eosinophilic esophagitis (EoE) is the most well known of these conditions, other EGIDs have become more commonly recognized in recent years and are the subject of intense study. Other affected areas include the stomach, small bowel, and colon, where it can occur individually or in combination.
Efforts are underway to develop guidelines for diagnosis and treatment of EGIDs, but there was initial confusion surrounding the term eosinophilic gastroenteritis since its definition varied significantly in different clinical and research settings, according to the authors. That term varyingly referred to stomach alone, small bowel alone, stomach and small bowel, or any region of the GI tract.
“This nonstandardized use of nomenclature highlighted a need for a common language for non-EoE eosinophilic GI disease names, not only for clinical practice, but also for the consistent data collection required for research to continue to advance the field,” co–first authors Evan S. Dellon, MD, MPH, AGAF, from the University of North Carolina at Chapel Hill, and Nirmala Gonsalves, MD, from Northwestern University, Chicago, and colleagues wrote. “This step, while seemingly rudimentary, was essential to inform the guideline efforts that are now underway.”
After responses to the surveys were analyzed, respondents participated in one of two scheduled meetings held on a video conferencing platform in May 2021. Feedback from these meetings was then used to create a second round of 29 statements which were again distributed, and participants were asked to either agree or disagree with each statement. Agreement was set a priori at 70%. In all, 38% of the participants were women, and 91% worked in academic or university settings.
In routine clinical practice, conditions with eosinophil-dominant inflammation in the absence of secondary causes outside of the esophagus can collectively be referred to clinically as non-EoE EGID. Stomach involvement should be called eosinophilic gastritis (EoG), small bowel involvement eosinophilic enteritis (EoN), and colon involvement eosinophilic colitis (EoC).
For research use, and clinical use if desired, the authors called for greater granularity in description of the conditions, with each location named. For example, if the stomach and small bowel are both involved, the condition should be termed eosinophilic gastritis and enteritis. The authors could not reach a consensus for terminology when the esophagus is also involved, leading to the recommendation that it can be included using the phrase “with esophageal involvement” or by using EoE, although they note that this could be confusing since EoE is the current term for eosinophilia isolated in the esophagus.
The authors came to universal agreement in many areas, but there were exceptions that mostly centered on how to name conditions that affect multiple areas of the GI tract. It remains uncertain whether eosinophilia in different regions is caused by the same pathogenesis. Some experts felt that a “primary” location of EGID should be identified using predominant symptoms, endoscopic features, and complications. However, the authors anticipate that this nomenclature will change over time.
The authors noted that the clinical manifestation of the disease should remain the driving factor behind classification. Testing should be driven by clinically relevant questions, and overtesting should be avoided. More details on this are likely to be forthcoming in future guidelines.
The consensus statement is limited by the fact that most participants were from academic settings. These recommendations do not apply to eosinophilic disorders of the gallbladder, liver, or pancreas. Application of the recommendations to the small bowel may be too general or specific, but are meant primarily as a starting point for further refinement.
These limitations should help to drive further research. For example, molecular and pathogenic data could help distinguish EoE from “esophageal involvement” by determining if pathogenic mechanisms are the same or different, which would in turn lead to lumping the conditions into a single term or keeping them separate.
“The iterative and collaborative process led to agreement on nearly all aspects of the proposed nomenclature framework, and has identified future research directions. It is expected that as more data are collected, the nomenclature will again be updated to reflect best practices and the underlying pathogenesis of these disorders,” the authors concluded.
The authors disclosed relationships with various industry companies, including AstraZeneca, Celgene, GlaxoSmithKline, Regeneron, Sanofi, and Takeda.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Experts refine nomenclature for eosinophilic GI disorders
A new international consensus paper is recommending that eosinophilic GI diseases (EGIDs) should be named according to more specific criteria. The paper seeks to update nomenclature to improve research and bolster clinical clarity.
The involved part of the GI tract should be specifically named, and the abbreviation “Eo” should be used. Furthermore, the umbrella term should be EGID instead of the currently used “eosinophilic gastroenteritis,” according to the statement published in Clinical Gastroenterology and Hepatology. The statement included 91 authors from five continents who filled out two rounds of surveys. In total, 93% completed the first and 90% completed the second. The paper produced 22 statements, with a consensus reached on all but 2.
EGIDs are chronic, immune-driven disorders that produce gastrointestinal symptoms and are characterized by eosinophil-dominant inflammation in specific GI regions. Although eosinophilic esophagitis (EoE) is the most well known of these conditions, other EGIDs have become more commonly recognized in recent years and are the subject of intense study. Other affected areas include the stomach, small bowel, and colon, where it can occur individually or in combination.
Efforts are underway to develop guidelines for diagnosis and treatment of EGIDs, but there was initial confusion surrounding the term eosinophilic gastroenteritis since its definition varied significantly in different clinical and research settings, according to the authors. That term varyingly referred to stomach alone, small bowel alone, stomach and small bowel, or any region of the GI tract.
“This nonstandardized use of nomenclature highlighted a need for a common language for non-EoE eosinophilic GI disease names, not only for clinical practice, but also for the consistent data collection required for research to continue to advance the field,” co–first authors Evan S. Dellon, MD, MPH, AGAF, from the University of North Carolina at Chapel Hill, and Nirmala Gonsalves, MD, from Northwestern University, Chicago, and colleagues wrote. “This step, while seemingly rudimentary, was essential to inform the guideline efforts that are now underway.”
After responses to the surveys were analyzed, respondents participated in one of two scheduled meetings held on a video conferencing platform in May 2021. Feedback from these meetings was then used to create a second round of 29 statements which were again distributed, and participants were asked to either agree or disagree with each statement. Agreement was set a priori at 70%. In all, 38% of the participants were women, and 91% worked in academic or university settings.
In routine clinical practice, conditions with eosinophil-dominant inflammation in the absence of secondary causes outside of the esophagus can collectively be referred to clinically as non-EoE EGID. Stomach involvement should be called eosinophilic gastritis (EoG), small bowel involvement eosinophilic enteritis (EoN), and colon involvement eosinophilic colitis (EoC).
For research use, and clinical use if desired, the authors called for greater granularity in description of the conditions, with each location named. For example, if the stomach and small bowel are both involved, the condition should be termed eosinophilic gastritis and enteritis. The authors could not reach a consensus for terminology when the esophagus is also involved, leading to the recommendation that it can be included using the phrase “with esophageal involvement” or by using EoE, although they note that this could be confusing since EoE is the current term for eosinophilia isolated in the esophagus.
The authors came to universal agreement in many areas, but there were exceptions that mostly centered on how to name conditions that affect multiple areas of the GI tract. It remains uncertain whether eosinophilia in different regions is caused by the same pathogenesis. Some experts felt that a “primary” location of EGID should be identified using predominant symptoms, endoscopic features, and complications. However, the authors anticipate that this nomenclature will change over time.
The authors noted that the clinical manifestation of the disease should remain the driving factor behind classification. Testing should be driven by clinically relevant questions and overtesting should be avoided. More details on this are likely to be forthcoming in future guidelines.
The consensus statement is limited by the fact that most participants were from academic settings. These recommendations do not apply to eosinophilic disorders of gallbladder, liver, or pancreas. Application of the recommendations to the small bowel may be too general or specific, but are meant primarily as a starting point for further refinement.
These limitations should help to drive further research. For example, molecular and pathogenic data could help distinguish EoE from “esophageal involvement” by determining if pathogenic mechanisms are the same or different, which would in turn lead to lumping the conditions into a single term or keeping them separate.
“The iterative and collaborative process led to agreement on nearly all aspects of the proposed nomenclature framework, and has identified future research directions. It is expected that as more data are collected, the nomenclature will again be updated to reflect best practices and the underlying pathogenesis of these disorders,” the authors concluded.
The authors disclosed relationships with various industry companies, include AstraZeneca, Celgene, GlaxoSmithKline, Regeneron, Sanofi, and Takeda.
Eosinophilic conditions of the gastrointestinal tract have risen in incidence leading to significant patient symptom and morbidity, but thankfully there have been tremendous innovations in identification, management, treatment, and drug development. In this excellent article, an international consensus was created to reflect these rapidly changing understanding of the phenotypes with updated diagnostic nomenclature.
Redefinition of these conditions will help in many aspects. First, advances in therapy targeted as eosinophilic trafficking have been approved with many biologic therapies in the pipeline and understanding their treatment effects and targets will help our patients. Second, improved nomenclature will help better understand the genetic, phenotypic, and therapeutic options for these conditions providing our patients with personalized care. As the understanding of eosinophilic conditions expands with the growth of genetic associations and drug therapies, we are matching our inflammatory bowel disease colleagues in their successes to provide our patients with personalized care.
Rishi D. Naik, MD, MSCI, is an assistant professor, department of medicine, section of gastroenterology & hepatology, Esophageal Center at Vanderbilt University Medical Center, Nashville, Tenn.
Eosinophilic conditions of the gastrointestinal tract have risen in incidence leading to significant patient symptom and morbidity, but thankfully there have been tremendous innovations in identification, management, treatment, and drug development. In this excellent article, an international consensus was created to reflect these rapidly changing understanding of the phenotypes with updated diagnostic nomenclature.
Redefinition of these conditions will help in many aspects. First, advances in therapy targeted as eosinophilic trafficking have been approved with many biologic therapies in the pipeline and understanding their treatment effects and targets will help our patients. Second, improved nomenclature will help better understand the genetic, phenotypic, and therapeutic options for these conditions providing our patients with personalized care. As the understanding of eosinophilic conditions expands with the growth of genetic associations and drug therapies, we are matching our inflammatory bowel disease colleagues in their successes to provide our patients with personalized care.
Rishi D. Naik, MD, MSCI, is an assistant professor, department of medicine, section of gastroenterology & hepatology, Esophageal Center at Vanderbilt University Medical Center, Nashville, Tenn.
Eosinophilic conditions of the gastrointestinal tract have risen in incidence leading to significant patient symptom and morbidity, but thankfully there have been tremendous innovations in identification, management, treatment, and drug development. In this excellent article, an international consensus was created to reflect these rapidly changing understanding of the phenotypes with updated diagnostic nomenclature.
Redefinition of these conditions will help in many aspects. First, advances in therapy targeted as eosinophilic trafficking have been approved with many biologic therapies in the pipeline and understanding their treatment effects and targets will help our patients. Second, improved nomenclature will help better understand the genetic, phenotypic, and therapeutic options for these conditions providing our patients with personalized care. As the understanding of eosinophilic conditions expands with the growth of genetic associations and drug therapies, we are matching our inflammatory bowel disease colleagues in their successes to provide our patients with personalized care.
Rishi D. Naik, MD, MSCI, is an assistant professor, department of medicine, section of gastroenterology & hepatology, Esophageal Center at Vanderbilt University Medical Center, Nashville, Tenn.
A new international consensus paper is recommending that eosinophilic GI diseases (EGIDs) should be named according to more specific criteria. The paper seeks to update nomenclature to improve research and bolster clinical clarity.
The involved part of the GI tract should be specifically named, and the abbreviation “Eo” should be used. Furthermore, the umbrella term should be EGID instead of the currently used “eosinophilic gastroenteritis,” according to the statement published in Clinical Gastroenterology and Hepatology. The statement included 91 authors from five continents who filled out two rounds of surveys. In total, 93% completed the first and 90% completed the second. The paper produced 22 statements, with a consensus reached on all but 2.
EGIDs are chronic, immune-driven disorders that produce gastrointestinal symptoms and are characterized by eosinophil-dominant inflammation in specific GI regions. Although eosinophilic esophagitis (EoE) is the most well known of these conditions, other EGIDs have become more commonly recognized in recent years and are the subject of intense study. Other affected areas include the stomach, small bowel, and colon, where it can occur individually or in combination.
Efforts are underway to develop guidelines for diagnosis and treatment of EGIDs, but there was initial confusion surrounding the term eosinophilic gastroenteritis since its definition varied significantly in different clinical and research settings, according to the authors. That term varyingly referred to stomach alone, small bowel alone, stomach and small bowel, or any region of the GI tract.
“This nonstandardized use of nomenclature highlighted a need for a common language for non-EoE eosinophilic GI disease names, not only for clinical practice, but also for the consistent data collection required for research to continue to advance the field,” co–first authors Evan S. Dellon, MD, MPH, AGAF, from the University of North Carolina at Chapel Hill, and Nirmala Gonsalves, MD, from Northwestern University, Chicago, and colleagues wrote. “This step, while seemingly rudimentary, was essential to inform the guideline efforts that are now underway.”
After responses to the surveys were analyzed, respondents participated in one of two scheduled meetings held on a video conferencing platform in May 2021. Feedback from these meetings was then used to create a second round of 29 statements which were again distributed, and participants were asked to either agree or disagree with each statement. Agreement was set a priori at 70%. In all, 38% of the participants were women, and 91% worked in academic or university settings.
In routine clinical practice, conditions with eosinophil-dominant inflammation in the absence of secondary causes outside of the esophagus can collectively be referred to clinically as non-EoE EGID. Stomach involvement should be called eosinophilic gastritis (EoG), small bowel involvement eosinophilic enteritis (EoN), and colon involvement eosinophilic colitis (EoC).
For research use, and clinical use if desired, the authors called for greater granularity in description of the conditions, with each location named. For example, if the stomach and small bowel are both involved, the condition should be termed eosinophilic gastritis and enteritis. The authors could not reach a consensus for terminology when the esophagus is also involved, leading to the recommendation that it can be included using the phrase “with esophageal involvement” or by using EoE, although they note that this could be confusing since EoE is the current term for eosinophilia isolated in the esophagus.
The authors came to universal agreement in many areas, but there were exceptions that mostly centered on how to name conditions that affect multiple areas of the GI tract. It remains uncertain whether eosinophilia in different regions is caused by the same pathogenesis. Some experts felt that a “primary” location of EGID should be identified using predominant symptoms, endoscopic features, and complications. However, the authors anticipate that this nomenclature will change over time.
The authors noted that the clinical manifestation of the disease should remain the driving factor behind classification. Testing should be driven by clinically relevant questions and overtesting should be avoided. More details on this are likely to be forthcoming in future guidelines.
The consensus statement is limited by the fact that most participants were from academic settings. These recommendations do not apply to eosinophilic disorders of gallbladder, liver, or pancreas. Application of the recommendations to the small bowel may be too general or specific, but are meant primarily as a starting point for further refinement.
These limitations should help to drive further research. For example, molecular and pathogenic data could help distinguish EoE from “esophageal involvement” by determining if pathogenic mechanisms are the same or different, which would in turn lead to lumping the conditions into a single term or keeping them separate.
“The iterative and collaborative process led to agreement on nearly all aspects of the proposed nomenclature framework, and has identified future research directions. It is expected that as more data are collected, the nomenclature will again be updated to reflect best practices and the underlying pathogenesis of these disorders,” the authors concluded.
The authors disclosed relationships with various industry companies, include AstraZeneca, Celgene, GlaxoSmithKline, Regeneron, Sanofi, and Takeda.
A new international consensus paper is recommending that eosinophilic GI diseases (EGIDs) should be named according to more specific criteria. The paper seeks to update nomenclature to improve research and bolster clinical clarity.
The involved part of the GI tract should be specifically named, and the abbreviation “Eo” should be used. Furthermore, the umbrella term should be EGID instead of the currently used “eosinophilic gastroenteritis,” according to the statement published in Clinical Gastroenterology and Hepatology. The statement included 91 authors from five continents who filled out two rounds of surveys. In total, 93% completed the first and 90% completed the second. The paper produced 22 statements, with a consensus reached on all but 2.
EGIDs are chronic, immune-driven disorders that produce gastrointestinal symptoms and are characterized by eosinophil-dominant inflammation in specific GI regions. Although eosinophilic esophagitis (EoE) is the most well known of these conditions, other EGIDs have become more commonly recognized in recent years and are the subject of intense study. Other affected areas include the stomach, small bowel, and colon, where it can occur individually or in combination.
Efforts are underway to develop guidelines for diagnosis and treatment of EGIDs, but there was initial confusion surrounding the term eosinophilic gastroenteritis since its definition varied significantly in different clinical and research settings, according to the authors. That term varyingly referred to stomach alone, small bowel alone, stomach and small bowel, or any region of the GI tract.
“This nonstandardized use of nomenclature highlighted a need for a common language for non-EoE eosinophilic GI disease names, not only for clinical practice, but also for the consistent data collection required for research to continue to advance the field,” co–first authors Evan S. Dellon, MD, MPH, AGAF, from the University of North Carolina at Chapel Hill, and Nirmala Gonsalves, MD, from Northwestern University, Chicago, and colleagues wrote. “This step, while seemingly rudimentary, was essential to inform the guideline efforts that are now underway.”
After responses to the surveys were analyzed, respondents participated in one of two scheduled meetings held on a video conferencing platform in May 2021. Feedback from these meetings was then used to create a second round of 29 statements which were again distributed, and participants were asked to either agree or disagree with each statement. Agreement was set a priori at 70%. In all, 38% of the participants were women, and 91% worked in academic or university settings.
In routine clinical practice, conditions with eosinophil-dominant inflammation in the absence of secondary causes outside of the esophagus can collectively be referred to clinically as non-EoE EGID. Stomach involvement should be called eosinophilic gastritis (EoG), small bowel involvement eosinophilic enteritis (EoN), and colon involvement eosinophilic colitis (EoC).
For research use, and clinical use if desired, the authors called for greater granularity in description of the conditions, with each location named. For example, if the stomach and small bowel are both involved, the condition should be termed eosinophilic gastritis and enteritis. The authors could not reach a consensus for terminology when the esophagus is also involved, leading to the recommendation that it can be included using the phrase “with esophageal involvement” or by using EoE, although they note that this could be confusing since EoE is the current term for eosinophilia isolated in the esophagus.
The authors came to universal agreement in many areas, but there were exceptions that mostly centered on how to name conditions that affect multiple areas of the GI tract. It remains uncertain whether eosinophilia in different regions is caused by the same pathogenesis. Some experts felt that a “primary” location of EGID should be identified using predominant symptoms, endoscopic features, and complications. However, the authors anticipate that this nomenclature will change over time.
The authors noted that the clinical manifestation of the disease should remain the driving factor behind classification. Testing should be driven by clinically relevant questions and overtesting should be avoided. More details on this are likely to be forthcoming in future guidelines.
The consensus statement is limited by the fact that most participants were from academic settings. These recommendations do not apply to eosinophilic disorders of gallbladder, liver, or pancreas. Application of the recommendations to the small bowel may be too general or specific, but are meant primarily as a starting point for further refinement.
These limitations should help to drive further research. For example, molecular and pathogenic data could help distinguish EoE from “esophageal involvement” by determining if pathogenic mechanisms are the same or different, which would in turn lead to lumping the conditions into a single term or keeping them separate.
“The iterative and collaborative process led to agreement on nearly all aspects of the proposed nomenclature framework, and has identified future research directions. It is expected that as more data are collected, the nomenclature will again be updated to reflect best practices and the underlying pathogenesis of these disorders,” the authors concluded.
The authors disclosed relationships with various industry companies, include AstraZeneca, Celgene, GlaxoSmithKline, Regeneron, Sanofi, and Takeda.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Updates in eosinophilic gastrointestinal diseases
Eosinophilic gastrointestinal diseases (EGIDs) are characterized by GI signs or symptoms occurring along with tissue eosinophilia. Eosinophilic esophagitis (EoE) is the more commonly recognized EGID as endoscopic and histopathologic diagnostic criteria have long been established. Because of a lack of consensus on biopsy protocols, poorly understood histopathologic diagnostic criteria, and vague, nonspecific gastrointestinal complaints, patients with non-EoE EGIDs go unrecognized for years. Because of this, there is increasing emphasis on better defining rare, distal eosinophilic gastrointestinal diseases (i.e., eosinophilic gastritis, enteritis, and colitis).
EGID nomenclature was standardized in 2022 in part to minimize vague terminology (i.e., eosinophilic gastroenteritis) and to provide more specific information about the location of eosinophilic disease. The 2022 nomenclature suggest that EGID be used as the umbrella term for all GI luminal eosinophilia (without a known cause) but with emphasis on the site of specific eosinophilic involvement (i.e., eosinophilic gastritis or eosinophilic gastritis and colitis). Importantly, there is much work to be done to adequately identify patients suffering from EGIDs. Symptoms are variable, ranging from abdominal pain, bloating, and nausea seen in proximal disease to loose stools and hematochezia in more distal involvement. Signs of disease, such as iron or other nutrient deficiencies and protein loss, may also occur. Endoscopic findings can vary from erythema, granularity, erosions, ulcerations, and blunting to even normal-appearing tissue. In eosinophilic gastritis, Ikuo Hirano, MD, and colleagues demonstrated that increasing endoscopic inflammatory findings in the stomach correlate with assessment of disease severity. Regardless of endoscopic findings, numerous biopsies are needed for the diagnosis of EGIDs because, as already established in EoE, eosinophil involvement is patchy. Nirmala Gonsalves, MD, and Evan Dellon, MD, found that a minimum of four biopsies each in the gastric antrum, gastric body, and small bowel are needed to detect disease. Optimal biopsy patterns have not yet been determined for eosinophilic ileitis or colitis.
Despite these advances, there is more work to be performed. Although these disease states are termed “eosinophilic,” the immunopathology driving these diseases is multifactorial, involving lymphocytes and mast cells and creating different phenotypes of disease in a similar fashion to inflammatory bowel disease. Current therapies being studied include eosinophil-depleting medications along with others targeting T2 immune pathways. Patients may need multiple therapeutic options, and personalized medicine will soon play a larger role in defining treatments. For now, researchers are fervently working on improved methods to identify, phenotype, and treat these morbid disorders.
Dr. Peterson is associate professor of gastroenterology at University of Utah Health, Salt Lake City. She has no relevant conflicts of interest. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2022.
Eosinophilic gastrointestinal diseases (EGIDs) are characterized by GI signs or symptoms occurring along with tissue eosinophilia. Eosinophilic esophagitis (EoE) is the more commonly recognized EGID as endoscopic and histopathologic diagnostic criteria have long been established. Because of a lack of consensus on biopsy protocols, poorly understood histopathologic diagnostic criteria, and vague, nonspecific gastrointestinal complaints, patients with non-EoE EGIDs go unrecognized for years. Because of this, there is increasing emphasis on better defining rare, distal eosinophilic gastrointestinal diseases (i.e., eosinophilic gastritis, enteritis, and colitis).
EGID nomenclature was standardized in 2022 in part to minimize vague terminology (i.e., eosinophilic gastroenteritis) and to provide more specific information about the location of eosinophilic disease. The 2022 nomenclature suggest that EGID be used as the umbrella term for all GI luminal eosinophilia (without a known cause) but with emphasis on the site of specific eosinophilic involvement (i.e., eosinophilic gastritis or eosinophilic gastritis and colitis). Importantly, there is much work to be done to adequately identify patients suffering from EGIDs. Symptoms are variable, ranging from abdominal pain, bloating, and nausea seen in proximal disease to loose stools and hematochezia in more distal involvement. Signs of disease, such as iron or other nutrient deficiencies and protein loss, may also occur. Endoscopic findings can vary from erythema, granularity, erosions, ulcerations, and blunting to even normal-appearing tissue. In eosinophilic gastritis, Ikuo Hirano, MD, and colleagues demonstrated that increasing endoscopic inflammatory findings in the stomach correlate with assessment of disease severity. Regardless of endoscopic findings, numerous biopsies are needed for the diagnosis of EGIDs because, as already established in EoE, eosinophil involvement is patchy. Nirmala Gonsalves, MD, and Evan Dellon, MD, found that a minimum of four biopsies each in the gastric antrum, gastric body, and small bowel are needed to detect disease. Optimal biopsy patterns have not yet been determined for eosinophilic ileitis or colitis.
Despite these advances, there is more work to be performed. Although these disease states are termed “eosinophilic,” the immunopathology driving these diseases is multifactorial, involving lymphocytes and mast cells and creating different phenotypes of disease in a similar fashion to inflammatory bowel disease. Current therapies being studied include eosinophil-depleting medications along with others targeting T2 immune pathways. Patients may need multiple therapeutic options, and personalized medicine will soon play a larger role in defining treatments. For now, researchers are fervently working on improved methods to identify, phenotype, and treat these morbid disorders.
Dr. Peterson is associate professor of gastroenterology at University of Utah Health, Salt Lake City. She has no relevant conflicts of interest. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2022.
Eosinophilic gastrointestinal diseases (EGIDs) are characterized by GI signs or symptoms occurring along with tissue eosinophilia. Eosinophilic esophagitis (EoE) is the more commonly recognized EGID as endoscopic and histopathologic diagnostic criteria have long been established. Because of a lack of consensus on biopsy protocols, poorly understood histopathologic diagnostic criteria, and vague, nonspecific gastrointestinal complaints, patients with non-EoE EGIDs go unrecognized for years. Because of this, there is increasing emphasis on better defining rare, distal eosinophilic gastrointestinal diseases (i.e., eosinophilic gastritis, enteritis, and colitis).
EGID nomenclature was standardized in 2022 in part to minimize vague terminology (i.e., eosinophilic gastroenteritis) and to provide more specific information about the location of eosinophilic disease. The 2022 nomenclature suggest that EGID be used as the umbrella term for all GI luminal eosinophilia (without a known cause) but with emphasis on the site of specific eosinophilic involvement (i.e., eosinophilic gastritis or eosinophilic gastritis and colitis). Importantly, there is much work to be done to adequately identify patients suffering from EGIDs. Symptoms are variable, ranging from abdominal pain, bloating, and nausea seen in proximal disease to loose stools and hematochezia in more distal involvement. Signs of disease, such as iron or other nutrient deficiencies and protein loss, may also occur. Endoscopic findings can vary from erythema, granularity, erosions, ulcerations, and blunting to even normal-appearing tissue. In eosinophilic gastritis, Ikuo Hirano, MD, and colleagues demonstrated that increasing endoscopic inflammatory findings in the stomach correlate with assessment of disease severity. Regardless of endoscopic findings, numerous biopsies are needed for the diagnosis of EGIDs because, as already established in EoE, eosinophil involvement is patchy. Nirmala Gonsalves, MD, and Evan Dellon, MD, found that a minimum of four biopsies each in the gastric antrum, gastric body, and small bowel are needed to detect disease. Optimal biopsy patterns have not yet been determined for eosinophilic ileitis or colitis.
Despite these advances, there is more work to be performed. Although these disease states are termed “eosinophilic,” the immunopathology driving these diseases is multifactorial, involving lymphocytes and mast cells and creating different phenotypes of disease in a similar fashion to inflammatory bowel disease. Current therapies being studied include eosinophil-depleting medications along with others targeting T2 immune pathways. Patients may need multiple therapeutic options, and personalized medicine will soon play a larger role in defining treatments. For now, researchers are fervently working on improved methods to identify, phenotype, and treat these morbid disorders.
Dr. Peterson is associate professor of gastroenterology at University of Utah Health, Salt Lake City. She has no relevant conflicts of interest. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2022.
Warfarin associated with higher upper GI bleeding rates, compared with DOACs
Warfarin is associated with higher rates of upper gastrointestinal bleeding but not overall or lower GI bleeding rates, compared with direct oral anticoagulants (DOACs), according to a new nationwide report from Iceland.
In addition, warfarin is associated with higher rates of major GI bleeding, compared with apixaban.
“Although there has been a myriad of studies comparing GI bleeding rates between warfarin and DOACs, very few studies have compared upper and lower GI bleeding rates specifically,” Arnar Ingason, MD, PhD, a gastroenterology resident at the University of Iceland and Landspitali University Hospital, Reykjavik, said in an interview.
“Knowing whether the risk of upper and lower GI bleeding differs between warfarin and DOACs is important, as it can help guide oral anticoagulant selection,” he said.
“Given that warfarin was associated with higher rates of upper GI bleeding compared to DOACs in our study, warfarin may not be optimal for patients with high risk of upper GI bleeding, such as patients with previous history of upper GI bleeding,” Dr. Ingason added.
The study was published online in Clinical Gastroenterology and Hepatology.
Analyzing bleed rates
Dr. Ingason and colleagues analyzed data from electronic medical records for more than 7,000 patients in Iceland who began a prescription for oral anticoagulants between 2014 and 2019. They used inverse probability weighting to yield balanced study groups and calculate the rates of overall, major, upper, and lower GI bleeding. All events of gastrointestinal bleeding were manually confirmed by chart review.
Clinically relevant GI bleeding was defined as bleeding that led to medical intervention, unscheduled physician contact, or temporary cessation of treatment. Upper GI bleeding was defined as hematemesis or a confirmed upper GI bleed site on endoscopy, whereas lower gastrointestinal bleeding was defined as hematochezia or a confirmed lower GI bleed site on endoscopy. Patients with melena and uncertain bleeding site on endoscopy were classified as having a gastrointestinal bleed of unknown location.
Major bleeding was defined as a drop in hemoglobin of at least 20 g/L, transfusion of two or more packs of red blood cells, or bleeding into a closed compartment such as the retroperitoneum.
In total, 295 gastrointestinal bleed events were identified, with 150 events (51%) classified as lower, 105 events (36%) classified as upper, and 40 events (14%) of an unknown location. About 71% required hospitalization, and 63% met the criteria for major bleeding. Five patients died, including three taking warfarin and the other two taking apixaban and rivaroxaban.
Overall, warfarin was associated with double the rate of upper GI bleeding, with 1.7 events per 100 person-years, compared with 0.8 events per 100 person-years for DOACs. The rates of lower GI bleeding were similar for the drugs.
Specifically, warfarin was associated with nearly 5.5 times higher rates of upper gastrointestinal bleeding, compared with dabigatran (Pradaxa, Boehringer Ingelheim), 2.6 times higher than apixaban (Eliquis, Bristol-Myers Squibb), and 1.7 times higher than rivaroxaban (Xarelto, Janssen). The risk for upper GI bleeding also was higher in men taking warfarin.
Warfarin was associated with higher rates of major bleeding, compared with apixaban, with 2.3 events per 100 person-years versus 1.5 events per 100 person-years. Otherwise, overall and major bleed rates were similar for users of warfarin and DOACs.
“GI bleeding among cardiac patients on anticoagulants and antiplatelets is the fastest growing group of GI bleeders,” Neena Abraham, MD, professor of medicine and a gastroenterologist at the Mayo Clinic in Scottsdale, Ariz., said in an interview.
Dr. Abraham, who wasn’t involved with this study, runs a dedicated cardiogastroenterology practice and has studied these patients’ bleeding risk for 20 years.
“This is a group that is ever increasing with aging baby boomers,” she said. “It is anticipated by 2040 that more than 40% of the U.S. adult population will have one or more cardiovascular conditions requiring the chronic prescription of anticoagulant or antiplatelet drugs.”
Considering future research
In this study, peptic ulcer disease was a proportionally less common cause of upper GI bleeding for warfarin at 18%, compared with DOACs at 39%. At the same time, the absolute propensity-weighted incidence rates of peptic ulcer–induced bleeding were similar, with 0.3 events per 100 person-years for both groups.
“As warfarin is not thought to induce peptic ulcer disease but rather promote bleeding from pre-existing lesions, one explanation may be that peptic ulcer disease almost always leads to overt bleeding in anticoagulated patients, while other lesions, such as mucosal erosions and angiodysplasias, may be more likely to lead to overt bleeding in warfarin patients due to a potentially more intense anticoagulation,” Dr. Ingason said.
Dr. Ingason and colleagues now plan to compare GI bleeding severity between warfarin and DOACs. Previous studies have suggested that GI bleeding may be more severe in patients receiving warfarin than in those receiving DOACs, he said.
In addition, large studies with manual verification of GI bleed events could better estimate the potential differences in the sources of upper and lower bleeding between warfarin and DOACs, Dr. Ingason noted.
“Some DOACs, specifically dabigatran, are known to have a mucosal effect on the luminal GI tract, as well as a systemic effect,” Dr. Abraham said. “This pharmacologic effect may contribute to an increase in lower gastrointestinal bleeding in the setting of colonic diverticulosis or mucosal injuries from inflammatory processes.”
Ongoing research should also look at different ways to reduce anticoagulant-related GI bleeding among cardiac patients, she noted.
“Our research group continues to study the risk of cardiac and bleeding adverse events in patients prescribed to DOACs compared to those patients who receive a left atrial appendage occlusion device,” Dr. Abraham said. “This device often permits patients at high risk of GI bleeding to transition off anticoagulant and antiplatelet drugs.”
The study was funded by the Icelandic Centre for Research and the Landspitali University Hospital Research Fund. The funders had no role in the design, conduct, or reporting of the study. The authors declared no competing interests. Dr. Abraham reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Warfarin is associated with higher rates of upper gastrointestinal bleeding but not overall or lower GI bleeding rates, compared with direct oral anticoagulants (DOACs), according to a new nationwide report from Iceland.
In addition, warfarin is associated with higher rates of major GI bleeding, compared with apixaban.
“Although there has been a myriad of studies comparing GI bleeding rates between warfarin and DOACs, very few studies have compared upper and lower GI bleeding rates specifically,” Arnar Ingason, MD, PhD, a gastroenterology resident at the University of Iceland and Landspitali University Hospital, Reykjavik, said in an interview.
“Knowing whether the risk of upper and lower GI bleeding differs between warfarin and DOACs is important, as it can help guide oral anticoagulant selection,” he said.
“Given that warfarin was associated with higher rates of upper GI bleeding compared to DOACs in our study, warfarin may not be optimal for patients with high risk of upper GI bleeding, such as patients with previous history of upper GI bleeding,” Dr. Ingason added.
The study was published online in Clinical Gastroenterology and Hepatology.
Analyzing bleed rates
Dr. Ingason and colleagues analyzed data from electronic medical records for more than 7,000 patients in Iceland who began a prescription for oral anticoagulants between 2014 and 2019. They used inverse probability weighting to yield balanced study groups and calculate the rates of overall, major, upper, and lower GI bleeding. All events of gastrointestinal bleeding were manually confirmed by chart review.
Clinically relevant GI bleeding was defined as bleeding that led to medical intervention, unscheduled physician contact, or temporary cessation of treatment. Upper GI bleeding was defined as hematemesis or a confirmed upper GI bleed site on endoscopy, whereas lower gastrointestinal bleeding was defined as hematochezia or a confirmed lower GI bleed site on endoscopy. Patients with melena and uncertain bleeding site on endoscopy were classified as having a gastrointestinal bleed of unknown location.
Major bleeding was defined as a drop in hemoglobin of at least 20 g/L, transfusion of two or more packs of red blood cells, or bleeding into a closed compartment such as the retroperitoneum.
In total, 295 gastrointestinal bleed events were identified, with 150 events (51%) classified as lower, 105 events (36%) classified as upper, and 40 events (14%) of an unknown location. About 71% required hospitalization, and 63% met the criteria for major bleeding. Five patients died, including three taking warfarin and the other two taking apixaban and rivaroxaban.
Overall, warfarin was associated with double the rate of upper GI bleeding, with 1.7 events per 100 person-years, compared with 0.8 events per 100 person-years for DOACs. The rates of lower GI bleeding were similar for the drugs.
Specifically, warfarin was associated with nearly 5.5 times higher rates of upper gastrointestinal bleeding, compared with dabigatran (Pradaxa, Boehringer Ingelheim), 2.6 times higher than apixaban (Eliquis, Bristol-Myers Squibb), and 1.7 times higher than rivaroxaban (Xarelto, Janssen). The risk for upper GI bleeding also was higher in men taking warfarin.
Warfarin was associated with higher rates of major bleeding, compared with apixaban, with 2.3 events per 100 person-years versus 1.5 events per 100 person-years. Otherwise, overall and major bleed rates were similar for users of warfarin and DOACs.
“GI bleeding among cardiac patients on anticoagulants and antiplatelets is the fastest growing group of GI bleeders,” Neena Abraham, MD, professor of medicine and a gastroenterologist at the Mayo Clinic in Scottsdale, Ariz., said in an interview.
Dr. Abraham, who wasn’t involved with this study, runs a dedicated cardiogastroenterology practice and has studied these patients’ bleeding risk for 20 years.
“This is a group that is ever increasing with aging baby boomers,” she said. “It is anticipated by 2040 that more than 40% of the U.S. adult population will have one or more cardiovascular conditions requiring the chronic prescription of anticoagulant or antiplatelet drugs.”
Considering future research
In this study, peptic ulcer disease was a proportionally less common cause of upper GI bleeding for warfarin at 18%, compared with DOACs at 39%. At the same time, the absolute propensity-weighted incidence rates of peptic ulcer–induced bleeding were similar, with 0.3 events per 100 person-years for both groups.
“As warfarin is not thought to induce peptic ulcer disease but rather promote bleeding from pre-existing lesions, one explanation may be that peptic ulcer disease almost always leads to overt bleeding in anticoagulated patients, while other lesions, such as mucosal erosions and angiodysplasias, may be more likely to lead to overt bleeding in warfarin patients due to a potentially more intense anticoagulation,” Dr. Ingason said.
Dr. Ingason and colleagues now plan to compare GI bleeding severity between warfarin and DOACs. Previous studies have suggested that GI bleeding may be more severe in patients receiving warfarin than in those receiving DOACs, he said.
In addition, large studies with manual verification of GI bleed events could better estimate the potential differences in the sources of upper and lower bleeding between warfarin and DOACs, Dr. Ingason noted.
“Some DOACs, specifically dabigatran, are known to have a mucosal effect on the luminal GI tract, as well as a systemic effect,” Dr. Abraham said. “This pharmacologic effect may contribute to an increase in lower gastrointestinal bleeding in the setting of colonic diverticulosis or mucosal injuries from inflammatory processes.”
Ongoing research should also look at different ways to reduce anticoagulant-related GI bleeding among cardiac patients, she noted.
“Our research group continues to study the risk of cardiac and bleeding adverse events in patients prescribed to DOACs compared to those patients who receive a left atrial appendage occlusion device,” Dr. Abraham said. “This device often permits patients at high risk of GI bleeding to transition off anticoagulant and antiplatelet drugs.”
The study was funded by the Icelandic Centre for Research and the Landspitali University Hospital Research Fund. The funders had no role in the design, conduct, or reporting of the study. The authors declared no competing interests. Dr. Abraham reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Warfarin is associated with higher rates of upper gastrointestinal bleeding but not overall or lower GI bleeding rates, compared with direct oral anticoagulants (DOACs), according to a new nationwide report from Iceland.
In addition, warfarin is associated with higher rates of major GI bleeding, compared with apixaban.
“Although there has been a myriad of studies comparing GI bleeding rates between warfarin and DOACs, very few studies have compared upper and lower GI bleeding rates specifically,” Arnar Ingason, MD, PhD, a gastroenterology resident at the University of Iceland and Landspitali University Hospital, Reykjavik, said in an interview.
“Knowing whether the risk of upper and lower GI bleeding differs between warfarin and DOACs is important, as it can help guide oral anticoagulant selection,” he said.
“Given that warfarin was associated with higher rates of upper GI bleeding compared to DOACs in our study, warfarin may not be optimal for patients with high risk of upper GI bleeding, such as patients with previous history of upper GI bleeding,” Dr. Ingason added.
The study was published online in Clinical Gastroenterology and Hepatology.
Analyzing bleed rates
Dr. Ingason and colleagues analyzed data from electronic medical records for more than 7,000 patients in Iceland who began a prescription for oral anticoagulants between 2014 and 2019. They used inverse probability weighting to yield balanced study groups and calculate the rates of overall, major, upper, and lower GI bleeding. All events of gastrointestinal bleeding were manually confirmed by chart review.
Clinically relevant GI bleeding was defined as bleeding that led to medical intervention, unscheduled physician contact, or temporary cessation of treatment. Upper GI bleeding was defined as hematemesis or a confirmed upper GI bleed site on endoscopy, whereas lower gastrointestinal bleeding was defined as hematochezia or a confirmed lower GI bleed site on endoscopy. Patients with melena and uncertain bleeding site on endoscopy were classified as having a gastrointestinal bleed of unknown location.
Major bleeding was defined as a drop in hemoglobin of at least 20 g/L, transfusion of two or more packs of red blood cells, or bleeding into a closed compartment such as the retroperitoneum.
In total, 295 gastrointestinal bleed events were identified, with 150 events (51%) classified as lower, 105 events (36%) classified as upper, and 40 events (14%) of an unknown location. About 71% required hospitalization, and 63% met the criteria for major bleeding. Five patients died, including three taking warfarin and the other two taking apixaban and rivaroxaban.
Overall, warfarin was associated with double the rate of upper GI bleeding, with 1.7 events per 100 person-years, compared with 0.8 events per 100 person-years for DOACs. The rates of lower GI bleeding were similar for the drugs.
Specifically, warfarin was associated with nearly 5.5 times higher rates of upper gastrointestinal bleeding, compared with dabigatran (Pradaxa, Boehringer Ingelheim), 2.6 times higher than apixaban (Eliquis, Bristol-Myers Squibb), and 1.7 times higher than rivaroxaban (Xarelto, Janssen). The risk for upper GI bleeding also was higher in men taking warfarin.
Warfarin was associated with higher rates of major bleeding, compared with apixaban, with 2.3 events per 100 person-years versus 1.5 events per 100 person-years. Otherwise, overall and major bleed rates were similar for users of warfarin and DOACs.
“GI bleeding among cardiac patients on anticoagulants and antiplatelets is the fastest growing group of GI bleeders,” Neena Abraham, MD, professor of medicine and a gastroenterologist at the Mayo Clinic in Scottsdale, Ariz., said in an interview.
Dr. Abraham, who wasn’t involved with this study, runs a dedicated cardiogastroenterology practice and has studied these patients’ bleeding risk for 20 years.
“This is a group that is ever increasing with aging baby boomers,” she said. “It is anticipated by 2040 that more than 40% of the U.S. adult population will have one or more cardiovascular conditions requiring the chronic prescription of anticoagulant or antiplatelet drugs.”
Considering future research
In this study, peptic ulcer disease was a proportionally less common cause of upper GI bleeding for warfarin at 18%, compared with DOACs at 39%. At the same time, the absolute propensity-weighted incidence rates of peptic ulcer–induced bleeding were similar, with 0.3 events per 100 person-years for both groups.
“As warfarin is not thought to induce peptic ulcer disease but rather promote bleeding from pre-existing lesions, one explanation may be that peptic ulcer disease almost always leads to overt bleeding in anticoagulated patients, while other lesions, such as mucosal erosions and angiodysplasias, may be more likely to lead to overt bleeding in warfarin patients due to a potentially more intense anticoagulation,” Dr. Ingason said.
Dr. Ingason and colleagues now plan to compare GI bleeding severity between warfarin and DOACs. Previous studies have suggested that GI bleeding may be more severe in patients receiving warfarin than in those receiving DOACs, he said.
In addition, large studies with manual verification of GI bleed events could better estimate the potential differences in the sources of upper and lower bleeding between warfarin and DOACs, Dr. Ingason noted.
“Some DOACs, specifically dabigatran, are known to have a mucosal effect on the luminal GI tract, as well as a systemic effect,” Dr. Abraham said. “This pharmacologic effect may contribute to an increase in lower gastrointestinal bleeding in the setting of colonic diverticulosis or mucosal injuries from inflammatory processes.”
Ongoing research should also look at different ways to reduce anticoagulant-related GI bleeding among cardiac patients, she noted.
“Our research group continues to study the risk of cardiac and bleeding adverse events in patients prescribed to DOACs compared to those patients who receive a left atrial appendage occlusion device,” Dr. Abraham said. “This device often permits patients at high risk of GI bleeding to transition off anticoagulant and antiplatelet drugs.”
The study was funded by the Icelandic Centre for Research and the Landspitali University Hospital Research Fund. The funders had no role in the design, conduct, or reporting of the study. The authors declared no competing interests. Dr. Abraham reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
10-year delay in one-third of EoE diagnoses has persisted for decades
It takes at least 10 years for one-third of patients with eosinophilic esophagitis (EoE) to receive a diagnosis and a median of 4 years for patients overall to get their diagnosis – numbers that haven’t budged in 3 decades, according to a study published online in the American Journal of Gastroenterology.
This delay has persisted despite more than 2,000 publications on the condition since 2014 and a variety of educational events about it, reported Fritz R. Murray, MD, of the department of gastroenterology and hepatology at University Hospital Zurich and his colleagues.
“Bearing in mind that eosinophilic esophagitis is a chronic and progressive disease, that, if left untreated, leads to esophageal structuring ultimately causing food impaction, the results of our analysis are a cause for concern,” the authors wrote.
“Substantial efforts are warranted to increase awareness for eosinophilic esophagitis and its hallmark symptom, solid-food dysphagia, as an age-independent red-flag symptom … in order to lower risk of long-term complications,” they added.
The researchers retrospectively analyzed prospectively collected data from 1,152 patients in a Swiss database. The patients (74% male; median age, 38 years) had all been diagnosed with EoE according to established criteria. The authors calculated the diagnostic delay from 1989 to 2021 and at three key time points: 1993 – first description of the condition, 2007 – first consensus recommendations, and 2011 – updated consensus recommendations
The median diagnostic delay over the 3 decades studied was 4 years overall and was at least 10 years in nearly one-third (32%) of the population. Diagnostic delay did not significantly change throughout the study period, year by year, or at or after any of the milestones included in the analysis, retaining the minimum 10-year delay in about one-third of all patients.
The median age at symptom onset was 30 years, with 51% of patients first experiencing symptoms between 10 and 30 years of age.
“Age at diagnosis showed a normal distribution with its peak between 30 and 40 years with 25% of the study population being diagnosed with EoE during that period,” the authors reported.
Although diagnostic delay did not differ between sexes, the length of time before diagnosis did vary on the basis of the patient’s age at diagnosis, increasing from a median of 0 years for those aged 10 years or younger to 5 years for those aged 31-40 years.
“When examining variation in diagnostic delay based on age at symptom onset, we observed an inverse association of age at symptom onset and diagnostic delay, with longest diagnostic delay observed in children,” they wrote.
Diagnostic delay was longer in those who needed an endoscopic disimpaction – a median of 6 years – before being diagnosed, compared with those who did not require this procedure, who had a median delay of 3 years. Nearly one-third (31%) of participants had at least one food impaction requiring endoscopic removal before receiving their diagnosis.
Three in four participants (74%) had a confirmed atopic condition besides eosinophilic esophagitis, with 13% not having an atopic comorbidity and another 13% lacking information on whether they did or didn’t. Those with atopic conditions were younger (median age, 29 years) when symptoms began than were those without atopic conditions (median age, 34 years).
Similarly, those with atopic conditions were younger (median age, 38 years) than those without these conditions (median age, 41 years) at the time of diagnosis. Diagnostic delay was a median 2 years shorter – 3 years vs. 5 years – for patients with concomitant atopic conditions.
“Importantly, the length of diagnosis delay (untreated disease) directly correlates with the occurrence of esophageal strictures,” the authors wrote, citing previous research finding that the prevalence of strictures rose from 17% in patients with a delay of up to 2 years to 71% in patients with a delay of more than 20 years.
“Esophageal strictures were present in around 38% of patients with a delay between 8-11 years” in that study, “a delay that is prevalent in about one third of our study population,” the authors wrote. “However, even a median delay of 4 years resulted in strictures in around 31% of untreated patients.”
Other research has found that the risk for esophageal strictures increases an estimated 9% each year that eosinophilic esophagitis goes untreated.
The authors suggested that patients’ denying symptoms or attempting to address their symptoms with changes in diet or eating behavior may be one reason for the long diagnostic delay, given other findings showing that patient-dependent delay was 18 months, compared with 6 months for physician-dependent delay. Although the authors didn’t have the information in their dataset to assess patient- vs. physician-dependent delay, a subgroup analysis revealed that patients and nongastroenterologist doctors combined made up the largest proportion of diagnosis delay.
“This fact indicates that future efforts should target the general population, and potentially primary physicians, to strengthen the awareness for eosinophilic esophagitis as a potential underlying condition in patients with dysphagia,” the authors wrote.
“A change in eating behavior, especially in cases with prolonged chewing, slow swallowing or even the necessity of drinking fluids after swallowing of solid food, should raise suspicion also in the general population,” they added.
Dr. Murray received travel support from Janssen, and 9 of the other 11 authors reported consulting, speaking, research and/or travel fees from 23 various pharmaceutical and related companies.
A version of this article first appeared on Medscape.com.
It takes at least 10 years for one-third of patients with eosinophilic esophagitis (EoE) to receive a diagnosis and a median of 4 years for patients overall to get their diagnosis – numbers that haven’t budged in 3 decades, according to a study published online in the American Journal of Gastroenterology.
This delay has persisted despite more than 2,000 publications on the condition since 2014 and a variety of educational events about it, reported Fritz R. Murray, MD, of the department of gastroenterology and hepatology at University Hospital Zurich and his colleagues.
“Bearing in mind that eosinophilic esophagitis is a chronic and progressive disease, that, if left untreated, leads to esophageal structuring ultimately causing food impaction, the results of our analysis are a cause for concern,” the authors wrote.
“Substantial efforts are warranted to increase awareness for eosinophilic esophagitis and its hallmark symptom, solid-food dysphagia, as an age-independent red-flag symptom … in order to lower risk of long-term complications,” they added.
The researchers retrospectively analyzed prospectively collected data from 1,152 patients in a Swiss database. The patients (74% male; median age, 38 years) had all been diagnosed with EoE according to established criteria. The authors calculated the diagnostic delay from 1989 to 2021 and at three key time points: 1993 – first description of the condition, 2007 – first consensus recommendations, and 2011 – updated consensus recommendations
The median diagnostic delay over the 3 decades studied was 4 years overall and was at least 10 years in nearly one-third (32%) of the population. Diagnostic delay did not significantly change throughout the study period, year by year, or at or after any of the milestones included in the analysis, retaining the minimum 10-year delay in about one-third of all patients.
The median age at symptom onset was 30 years, with 51% of patients first experiencing symptoms between 10 and 30 years of age.
“Age at diagnosis showed a normal distribution with its peak between 30 and 40 years with 25% of the study population being diagnosed with EoE during that period,” the authors reported.
Although diagnostic delay did not differ between sexes, the length of time before diagnosis did vary on the basis of the patient’s age at diagnosis, increasing from a median of 0 years for those aged 10 years or younger to 5 years for those aged 31-40 years.
“When examining variation in diagnostic delay based on age at symptom onset, we observed an inverse association of age at symptom onset and diagnostic delay, with longest diagnostic delay observed in children,” they wrote.
Diagnostic delay was longer in those who needed an endoscopic disimpaction – a median of 6 years – before being diagnosed, compared with those who did not require this procedure, who had a median delay of 3 years. Nearly one-third (31%) of participants had at least one food impaction requiring endoscopic removal before receiving their diagnosis.
Three in four participants (74%) had a confirmed atopic condition besides eosinophilic esophagitis, with 13% not having an atopic comorbidity and another 13% lacking information on whether they did or didn’t. Those with atopic conditions were younger (median age, 29 years) when symptoms began than were those without atopic conditions (median age, 34 years).
Similarly, those with atopic conditions were younger (median age, 38 years) than those without these conditions (median age, 41 years) at the time of diagnosis. Diagnostic delay was a median 2 years shorter – 3 years vs. 5 years – for patients with concomitant atopic conditions.
“Importantly, the length of diagnosis delay (untreated disease) directly correlates with the occurrence of esophageal strictures,” the authors wrote, citing previous research finding that the prevalence of strictures rose from 17% in patients with a delay of up to 2 years to 71% in patients with a delay of more than 20 years.
“Esophageal strictures were present in around 38% of patients with a delay between 8-11 years” in that study, “a delay that is prevalent in about one third of our study population,” the authors wrote. “However, even a median delay of 4 years resulted in strictures in around 31% of untreated patients.”
Other research has found that the risk for esophageal strictures increases an estimated 9% each year that eosinophilic esophagitis goes untreated.
The authors suggested that patients’ denying symptoms or attempting to address their symptoms with changes in diet or eating behavior may be one reason for the long diagnostic delay, given other findings showing that patient-dependent delay was 18 months, compared with 6 months for physician-dependent delay. Although the authors didn’t have the information in their dataset to assess patient- vs. physician-dependent delay, a subgroup analysis revealed that patients and nongastroenterologist doctors combined made up the largest proportion of diagnosis delay.
“This fact indicates that future efforts should target the general population, and potentially primary physicians, to strengthen the awareness for eosinophilic esophagitis as a potential underlying condition in patients with dysphagia,” the authors wrote.
“A change in eating behavior, especially in cases with prolonged chewing, slow swallowing or even the necessity of drinking fluids after swallowing of solid food, should raise suspicion also in the general population,” they added.
Dr. Murray received travel support from Janssen, and 9 of the other 11 authors reported consulting, speaking, research and/or travel fees from 23 various pharmaceutical and related companies.
A version of this article first appeared on Medscape.com.
It takes at least 10 years for one-third of patients with eosinophilic esophagitis (EoE) to receive a diagnosis and a median of 4 years for patients overall to get their diagnosis – numbers that haven’t budged in 3 decades, according to a study published online in the American Journal of Gastroenterology.
This delay has persisted despite more than 2,000 publications on the condition since 2014 and a variety of educational events about it, reported Fritz R. Murray, MD, of the department of gastroenterology and hepatology at University Hospital Zurich and his colleagues.
“Bearing in mind that eosinophilic esophagitis is a chronic and progressive disease, that, if left untreated, leads to esophageal structuring ultimately causing food impaction, the results of our analysis are a cause for concern,” the authors wrote.
“Substantial efforts are warranted to increase awareness for eosinophilic esophagitis and its hallmark symptom, solid-food dysphagia, as an age-independent red-flag symptom … in order to lower risk of long-term complications,” they added.
The researchers retrospectively analyzed prospectively collected data from 1,152 patients in a Swiss database. The patients (74% male; median age, 38 years) had all been diagnosed with EoE according to established criteria. The authors calculated the diagnostic delay from 1989 to 2021 and at three key time points: 1993 – first description of the condition, 2007 – first consensus recommendations, and 2011 – updated consensus recommendations
The median diagnostic delay over the 3 decades studied was 4 years overall and was at least 10 years in nearly one-third (32%) of the population. Diagnostic delay did not significantly change throughout the study period, year by year, or at or after any of the milestones included in the analysis, retaining the minimum 10-year delay in about one-third of all patients.
The median age at symptom onset was 30 years, with 51% of patients first experiencing symptoms between 10 and 30 years of age.
“Age at diagnosis showed a normal distribution with its peak between 30 and 40 years with 25% of the study population being diagnosed with EoE during that period,” the authors reported.
Although diagnostic delay did not differ between sexes, the length of time before diagnosis did vary on the basis of the patient’s age at diagnosis, increasing from a median of 0 years for those aged 10 years or younger to 5 years for those aged 31-40 years.
“When examining variation in diagnostic delay based on age at symptom onset, we observed an inverse association of age at symptom onset and diagnostic delay, with longest diagnostic delay observed in children,” they wrote.
Diagnostic delay was longer in those who needed an endoscopic disimpaction – a median of 6 years – before being diagnosed, compared with those who did not require this procedure, who had a median delay of 3 years. Nearly one-third (31%) of participants had at least one food impaction requiring endoscopic removal before receiving their diagnosis.
Three in four participants (74%) had a confirmed atopic condition besides eosinophilic esophagitis, with 13% not having an atopic comorbidity and another 13% lacking information on whether they did or didn’t. Those with atopic conditions were younger (median age, 29 years) when symptoms began than were those without atopic conditions (median age, 34 years).
Similarly, those with atopic conditions were younger (median age, 38 years) than those without these conditions (median age, 41 years) at the time of diagnosis. Diagnostic delay was a median 2 years shorter – 3 years vs. 5 years – for patients with concomitant atopic conditions.
“Importantly, the length of diagnosis delay (untreated disease) directly correlates with the occurrence of esophageal strictures,” the authors wrote, citing previous research finding that the prevalence of strictures rose from 17% in patients with a delay of up to 2 years to 71% in patients with a delay of more than 20 years.
“Esophageal strictures were present in around 38% of patients with a delay between 8-11 years” in that study, “a delay that is prevalent in about one third of our study population,” the authors wrote. “However, even a median delay of 4 years resulted in strictures in around 31% of untreated patients.”
Other research has found that the risk for esophageal strictures increases an estimated 9% each year that eosinophilic esophagitis goes untreated.
The authors suggested that patients’ denying symptoms or attempting to address their symptoms with changes in diet or eating behavior may be one reason for the long diagnostic delay, given other findings showing that patient-dependent delay was 18 months, compared with 6 months for physician-dependent delay. Although the authors didn’t have the information in their dataset to assess patient- vs. physician-dependent delay, a subgroup analysis revealed that patients and nongastroenterologist doctors combined made up the largest proportion of diagnosis delay.
“This fact indicates that future efforts should target the general population, and potentially primary physicians, to strengthen the awareness for eosinophilic esophagitis as a potential underlying condition in patients with dysphagia,” the authors wrote.
“A change in eating behavior, especially in cases with prolonged chewing, slow swallowing or even the necessity of drinking fluids after swallowing of solid food, should raise suspicion also in the general population,” they added.
Dr. Murray received travel support from Janssen, and 9 of the other 11 authors reported consulting, speaking, research and/or travel fees from 23 various pharmaceutical and related companies.
A version of this article first appeared on Medscape.com.
FROM AMERICAN JOURNAL OF GASTROENTEROLOGY
Understanding GERD phenotypes
Approximately 30% of U.S. adults experience troublesome reflux symptoms of heartburn, regurgitation and noncardiac chest pain. Because the mechanisms driving symptoms vary across patients, phenotyping patients via a step-wise diagnostic framework effectively guides personalized management in GERD.
For instance, PPI trials are appropriate when esophageal symptoms are present, whereas up-front reflux monitoring rather than empiric PPI trials are recommended for evaluation of isolated extra-esophageal symptoms. All patients undergoing evaluation for GERD should receive counseling on weight management and lifestyle modifications as well as the brain-gut axis relationship. In the common scenario of inadequate symptom response to PPIs, upper GI endoscopy is recommended to assess for erosive reflux disease (which confirms a diagnosis of GERD) as well as the anti-reflux barrier integrity. For instance, the presence of a large hiatal hernia and/or grade III/IV gastro-esophageal flap valve may point to mechanical gastro-esophageal reflux as a driver of symptoms and lower the threshold for surgical referral. In the absence of erosive reflux disease the next recommended step is ambulatory reflux monitoring off PPI therapy, either as prolonged wireless telemetry (which can be done concurrently with index endoscopy as long as PPI was discontinued > 7 days) or 24-hour transnasal pH-impedance catheter-based testing. Studies suggest that 96-hour monitoring is optimal for diagnostic accuracy and to guide therapeutic strategies.
Patients without evidence of GERD on endoscopy or ambulatory reflux monitoring likely have a functional esophageal disorder for which therapy hinges on pharmacologic neuromodulation or behavioral interventions as well as PPI cessation.
Alternatively, management for GERD (erosive or nonerosive) aims to optimize lifestyle, PPI therapy and the individualized use of adjunctive therapy, which include H2-receptor antagonists, alginate antacids, GABA agonists, neuromodulation and/or behavioral interventions. Surgical or endoscopic antireflux interventions are also an option for refractory GERD. Prior to intervention, achalasia must be excluded (typically with esophageal manometry), and confirmation of PPI refractory GERD on pH-impedance monitoring on PPI is of value, particularly when the phenotype is unclear. Again, the choice of antireflux intervention (e.g., laparoscopic fundoplication, magnetic sphincter augmentation, transoral incisionless fundoplication, Roux-en-Y gastric bypass) should be individualized to the patient’s anatomy, physiology, and clinical profile.
A multitude of treatment options are available to manage GERD, including behavioral interventions, lifestyle modifications, pharmacotherapy, and endoscopic/surgical interventions. However, not every treatment strategy is appropriate for every patient. Data gathered from the step-down diagnostic approach, which starts with clinical presentation, then endoscopy, then reflux monitoring, then esophageal physiologic testing, helps determine the GERD phenotype and effectively guide therapy.
Dr. Yadlapati is associate professor of clinical medicine, and medical director, UCSD Center for Esophageal Diseases; director, GI Motility Lab, division of gastroenterology, University of California San Diego, La Jolla, Calif. She disclosed ties with Medtronic, Phathom Pharmaceuticals, StatLinkMD, Medscape, Ironwood Pharmaceuticals, and RJS Mediagnostix. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2022.
Approximately 30% of U.S. adults experience troublesome reflux symptoms of heartburn, regurgitation and noncardiac chest pain. Because the mechanisms driving symptoms vary across patients, phenotyping patients via a step-wise diagnostic framework effectively guides personalized management in GERD.
For instance, PPI trials are appropriate when esophageal symptoms are present, whereas up-front reflux monitoring rather than empiric PPI trials are recommended for evaluation of isolated extra-esophageal symptoms. All patients undergoing evaluation for GERD should receive counseling on weight management and lifestyle modifications as well as the brain-gut axis relationship. In the common scenario of inadequate symptom response to PPIs, upper GI endoscopy is recommended to assess for erosive reflux disease (which confirms a diagnosis of GERD) as well as the anti-reflux barrier integrity. For instance, the presence of a large hiatal hernia and/or grade III/IV gastro-esophageal flap valve may point to mechanical gastro-esophageal reflux as a driver of symptoms and lower the threshold for surgical referral. In the absence of erosive reflux disease the next recommended step is ambulatory reflux monitoring off PPI therapy, either as prolonged wireless telemetry (which can be done concurrently with index endoscopy as long as PPI was discontinued > 7 days) or 24-hour transnasal pH-impedance catheter-based testing. Studies suggest that 96-hour monitoring is optimal for diagnostic accuracy and to guide therapeutic strategies.
Patients without evidence of GERD on endoscopy or ambulatory reflux monitoring likely have a functional esophageal disorder for which therapy hinges on pharmacologic neuromodulation or behavioral interventions as well as PPI cessation.
Alternatively, management for GERD (erosive or nonerosive) aims to optimize lifestyle, PPI therapy and the individualized use of adjunctive therapy, which include H2-receptor antagonists, alginate antacids, GABA agonists, neuromodulation and/or behavioral interventions. Surgical or endoscopic antireflux interventions are also an option for refractory GERD. Prior to intervention, achalasia must be excluded (typically with esophageal manometry), and confirmation of PPI refractory GERD on pH-impedance monitoring on PPI is of value, particularly when the phenotype is unclear. Again, the choice of antireflux intervention (e.g., laparoscopic fundoplication, magnetic sphincter augmentation, transoral incisionless fundoplication, Roux-en-Y gastric bypass) should be individualized to the patient’s anatomy, physiology, and clinical profile.
A multitude of treatment options are available to manage GERD, including behavioral interventions, lifestyle modifications, pharmacotherapy, and endoscopic/surgical interventions. However, not every treatment strategy is appropriate for every patient. Data gathered from the step-down diagnostic approach, which starts with clinical presentation, then endoscopy, then reflux monitoring, then esophageal physiologic testing, helps determine the GERD phenotype and effectively guide therapy.
Dr. Yadlapati is associate professor of clinical medicine, and medical director, UCSD Center for Esophageal Diseases; director, GI Motility Lab, division of gastroenterology, University of California San Diego, La Jolla, Calif. She disclosed ties with Medtronic, Phathom Pharmaceuticals, StatLinkMD, Medscape, Ironwood Pharmaceuticals, and RJS Mediagnostix. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2022.
Approximately 30% of U.S. adults experience troublesome reflux symptoms of heartburn, regurgitation and noncardiac chest pain. Because the mechanisms driving symptoms vary across patients, phenotyping patients via a step-wise diagnostic framework effectively guides personalized management in GERD.
For instance, PPI trials are appropriate when esophageal symptoms are present, whereas up-front reflux monitoring rather than empiric PPI trials are recommended for evaluation of isolated extra-esophageal symptoms. All patients undergoing evaluation for GERD should receive counseling on weight management and lifestyle modifications as well as the brain-gut axis relationship. In the common scenario of inadequate symptom response to PPIs, upper GI endoscopy is recommended to assess for erosive reflux disease (which confirms a diagnosis of GERD) as well as the anti-reflux barrier integrity. For instance, the presence of a large hiatal hernia and/or grade III/IV gastro-esophageal flap valve may point to mechanical gastro-esophageal reflux as a driver of symptoms and lower the threshold for surgical referral. In the absence of erosive reflux disease the next recommended step is ambulatory reflux monitoring off PPI therapy, either as prolonged wireless telemetry (which can be done concurrently with index endoscopy as long as PPI was discontinued > 7 days) or 24-hour transnasal pH-impedance catheter-based testing. Studies suggest that 96-hour monitoring is optimal for diagnostic accuracy and to guide therapeutic strategies.
Patients without evidence of GERD on endoscopy or ambulatory reflux monitoring likely have a functional esophageal disorder for which therapy hinges on pharmacologic neuromodulation or behavioral interventions as well as PPI cessation.
Alternatively, management for GERD (erosive or nonerosive) aims to optimize lifestyle, PPI therapy and the individualized use of adjunctive therapy, which include H2-receptor antagonists, alginate antacids, GABA agonists, neuromodulation and/or behavioral interventions. Surgical or endoscopic antireflux interventions are also an option for refractory GERD. Prior to intervention, achalasia must be excluded (typically with esophageal manometry), and confirmation of PPI refractory GERD on pH-impedance monitoring on PPI is of value, particularly when the phenotype is unclear. Again, the choice of antireflux intervention (e.g., laparoscopic fundoplication, magnetic sphincter augmentation, transoral incisionless fundoplication, Roux-en-Y gastric bypass) should be individualized to the patient’s anatomy, physiology, and clinical profile.
A multitude of treatment options are available to manage GERD, including behavioral interventions, lifestyle modifications, pharmacotherapy, and endoscopic/surgical interventions. However, not every treatment strategy is appropriate for every patient. Data gathered from the step-down diagnostic approach, which starts with clinical presentation, then endoscopy, then reflux monitoring, then esophageal physiologic testing, helps determine the GERD phenotype and effectively guide therapy.
Dr. Yadlapati is associate professor of clinical medicine, and medical director, UCSD Center for Esophageal Diseases; director, GI Motility Lab, division of gastroenterology, University of California San Diego, La Jolla, Calif. She disclosed ties with Medtronic, Phathom Pharmaceuticals, StatLinkMD, Medscape, Ironwood Pharmaceuticals, and RJS Mediagnostix. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2022.
AT DDW 2022