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Effective NASH medications are coming ‘sooner than you think’
SAN ANTONIO – The therapeutic Dark Ages of nonalcoholic steatohepatitis (NASH) are finally drawing to a close.
“NASH-specific therapies are coming soon – sooner than you think,” Naim Alkhouri, MD, predicted at the annual meeting of the American College of Gastroenterology.
And that, he added, has important implications for clinical practice. Physicians are going to need to step up their game with regard to screening and staging patients with nonalcoholic fatty liver disease to identify the right candidates for the coming effective treatments.
The new treatment era in NASH could dawn as soon as the spring of 2020, by which time the Food and Drug Administration is expected to issue a decision on obeticholic acid, an oral FXR agonist for which the agency has granted breakthrough therapy status. Intercept Pharmaceuticals has filed for marketing approval of obeticholic acid for NASH on the strength of the positive 18-month histologic results of the pivotal phase 3 REGENERATE trial, the first-ever successful phase 3 study of a medication for NASH, noted Dr. Alkhouri, a gastroenterologist at the University of Texas, San Antonio, and director of the Metabolic Health Center at the Texas Liver Institute.
At present there are no FDA-approved pharmacotherapies for NASH. The unmet medical need is huge, since NASH is now recognized to be a full-blown, burgeoning epidemic. NASH will soon become the No. 1 indication for liver transplantation in the United States. A full-throttle race is on to find effective therapies targeting the various dimensions of NASH, with more than 70 drugs now in phase 2 studies. These drugs collectively address all four mechanisms of the disease’s development and progression: the metabolic targets, perturbations in the gut-liver axis, liver inflammation, and fibrosis.
Moreover, even as the FDA considers the application for approval of obeticholic acid in NASH, at least four other investigational drugs are in pivotal phase 3 clinical trials. These include elafibranor, aramchol, resmetirom, and cenicriviroc.
Cenicriviroc is a dual CCR 2/5 receptor antagonist that targets the hepatic inflammation and fibrosis dimensions of NASH. It is now being evaluated in the phase 3 AURORA trial on the strength of the earlier positive phase 2b Centaur study, in which patients randomized to cenicriviroc were twice as likely to experience significant improvement in fibrosis as were placebo-treated controls.
Elafibranor, aramchol, and resmetirom employ different mechanisms of action to address the metabolic derangements of NASH. What they share in common is their aim to reduce the influx of free fatty acids from adipose tissue to the liver, and/or to inhibit lipogenesis from carbohydrate building blocks. In so doing, these medications should result in reduced hepatocyte injury and liver inflammation.
Elafibranor is a peroxisome proliferator-activated receptor alpha/delta agonist that achieved significant biopsy-proven reversal of NASH in moderate- or severely affected patients in the phase 2 GOLDEN study. The phase 3 RESOLVE IT trial is underway.
Aramchol is a first-in-class synthetic fatty acid/bile acid conjugate that inhibits stearoyl-CoA desaturate activity. It’s designed to improve insulin resistance and curb accumulation of triglycerides in hepatocytes. In the 52-week, phase 2 ARREST trial, oral aramchol at 600 mg/day was 4.7-fold more likely than was placebo to achieve NASH resolution without worsening of fibrosis. The drug is now in phase 3 in the ARMOR study.
Resmetirom is a selective thyroid hormone receptor–beta agonist. Activation of the beta receptor lowers LDL cholesterol, triglycerides, and liver fat, whereas activation of the alpha receptor has the unwanted effects of promoting bone loss, thyrotoxicosis, and arrhythmias. In phase 2, 75% of patients on high-dose resmetirom achieved at least a 30% reduction in hepatic fat by MRI at week 12, compared with 18% of placebo-treated controls. And 39% of the high-dose resmetirom group showed histologic resolution of NASH on a week-36 liver biopsy, as did a mere 6% of controls. The phase 3 MAESTRO randomized trial is underway.
Obeticholic acid addresses the gut-liver axis abnormalities present in NASH, especially the exuberant bile acid circulation.
Clinical implications of the coming wave of medications
In Dr. Alkhouri’s view, .
“These are the patients with a high chance of progressing to cirrhosis and end-stage liver disease,” the gastroenterologist said.
Patients with earlier-stage nonalcoholic fatty liver disease are best managed via lifestyle changes, with particular emphasis upon 10% weight loss accompanied by exercise. And patients with more advanced disease – NASH with cirrhosis – appear thus far to be beyond the reach of the next-generation therapies.
None of the coming drugs is a cure-all. In the landmark phase 3 REGENERATE trial, for example, the rate of the primary outcome – fibrosis improvement of at least one stage plus no worsening of NASH at 18 months – was 23% in patients randomized to obeticholic acid at 25 mg/day, compared to 12% with placebo.
“These are not like hepatitis C medications, with 97% efficacy, so combination therapy targeting upstream and downstream for NASH is rational,” Dr. Alkhouri observed.
He reported serving on advisory boards for Allergan, Gilead, and Intercept, and receiving research grants from those companies as well as from Galmed, Genfit, and Madrigal.
*This story was updated on 12/5/2019.
SAN ANTONIO – The therapeutic Dark Ages of nonalcoholic steatohepatitis (NASH) are finally drawing to a close.
“NASH-specific therapies are coming soon – sooner than you think,” Naim Alkhouri, MD, predicted at the annual meeting of the American College of Gastroenterology.
And that, he added, has important implications for clinical practice. Physicians are going to need to step up their game with regard to screening and staging patients with nonalcoholic fatty liver disease to identify the right candidates for the coming effective treatments.
The new treatment era in NASH could dawn as soon as the spring of 2020, by which time the Food and Drug Administration is expected to issue a decision on obeticholic acid, an oral FXR agonist for which the agency has granted breakthrough therapy status. Intercept Pharmaceuticals has filed for marketing approval of obeticholic acid for NASH on the strength of the positive 18-month histologic results of the pivotal phase 3 REGENERATE trial, the first-ever successful phase 3 study of a medication for NASH, noted Dr. Alkhouri, a gastroenterologist at the University of Texas, San Antonio, and director of the Metabolic Health Center at the Texas Liver Institute.
At present there are no FDA-approved pharmacotherapies for NASH. The unmet medical need is huge, since NASH is now recognized to be a full-blown, burgeoning epidemic. NASH will soon become the No. 1 indication for liver transplantation in the United States. A full-throttle race is on to find effective therapies targeting the various dimensions of NASH, with more than 70 drugs now in phase 2 studies. These drugs collectively address all four mechanisms of the disease’s development and progression: the metabolic targets, perturbations in the gut-liver axis, liver inflammation, and fibrosis.
Moreover, even as the FDA considers the application for approval of obeticholic acid in NASH, at least four other investigational drugs are in pivotal phase 3 clinical trials. These include elafibranor, aramchol, resmetirom, and cenicriviroc.
Cenicriviroc is a dual CCR 2/5 receptor antagonist that targets the hepatic inflammation and fibrosis dimensions of NASH. It is now being evaluated in the phase 3 AURORA trial on the strength of the earlier positive phase 2b Centaur study, in which patients randomized to cenicriviroc were twice as likely to experience significant improvement in fibrosis as were placebo-treated controls.
Elafibranor, aramchol, and resmetirom employ different mechanisms of action to address the metabolic derangements of NASH. What they share in common is their aim to reduce the influx of free fatty acids from adipose tissue to the liver, and/or to inhibit lipogenesis from carbohydrate building blocks. In so doing, these medications should result in reduced hepatocyte injury and liver inflammation.
Elafibranor is a peroxisome proliferator-activated receptor alpha/delta agonist that achieved significant biopsy-proven reversal of NASH in moderate- or severely affected patients in the phase 2 GOLDEN study. The phase 3 RESOLVE IT trial is underway.
Aramchol is a first-in-class synthetic fatty acid/bile acid conjugate that inhibits stearoyl-CoA desaturate activity. It’s designed to improve insulin resistance and curb accumulation of triglycerides in hepatocytes. In the 52-week, phase 2 ARREST trial, oral aramchol at 600 mg/day was 4.7-fold more likely than was placebo to achieve NASH resolution without worsening of fibrosis. The drug is now in phase 3 in the ARMOR study.
Resmetirom is a selective thyroid hormone receptor–beta agonist. Activation of the beta receptor lowers LDL cholesterol, triglycerides, and liver fat, whereas activation of the alpha receptor has the unwanted effects of promoting bone loss, thyrotoxicosis, and arrhythmias. In phase 2, 75% of patients on high-dose resmetirom achieved at least a 30% reduction in hepatic fat by MRI at week 12, compared with 18% of placebo-treated controls. And 39% of the high-dose resmetirom group showed histologic resolution of NASH on a week-36 liver biopsy, as did a mere 6% of controls. The phase 3 MAESTRO randomized trial is underway.
Obeticholic acid addresses the gut-liver axis abnormalities present in NASH, especially the exuberant bile acid circulation.
Clinical implications of the coming wave of medications
In Dr. Alkhouri’s view, .
“These are the patients with a high chance of progressing to cirrhosis and end-stage liver disease,” the gastroenterologist said.
Patients with earlier-stage nonalcoholic fatty liver disease are best managed via lifestyle changes, with particular emphasis upon 10% weight loss accompanied by exercise. And patients with more advanced disease – NASH with cirrhosis – appear thus far to be beyond the reach of the next-generation therapies.
None of the coming drugs is a cure-all. In the landmark phase 3 REGENERATE trial, for example, the rate of the primary outcome – fibrosis improvement of at least one stage plus no worsening of NASH at 18 months – was 23% in patients randomized to obeticholic acid at 25 mg/day, compared to 12% with placebo.
“These are not like hepatitis C medications, with 97% efficacy, so combination therapy targeting upstream and downstream for NASH is rational,” Dr. Alkhouri observed.
He reported serving on advisory boards for Allergan, Gilead, and Intercept, and receiving research grants from those companies as well as from Galmed, Genfit, and Madrigal.
*This story was updated on 12/5/2019.
SAN ANTONIO – The therapeutic Dark Ages of nonalcoholic steatohepatitis (NASH) are finally drawing to a close.
“NASH-specific therapies are coming soon – sooner than you think,” Naim Alkhouri, MD, predicted at the annual meeting of the American College of Gastroenterology.
And that, he added, has important implications for clinical practice. Physicians are going to need to step up their game with regard to screening and staging patients with nonalcoholic fatty liver disease to identify the right candidates for the coming effective treatments.
The new treatment era in NASH could dawn as soon as the spring of 2020, by which time the Food and Drug Administration is expected to issue a decision on obeticholic acid, an oral FXR agonist for which the agency has granted breakthrough therapy status. Intercept Pharmaceuticals has filed for marketing approval of obeticholic acid for NASH on the strength of the positive 18-month histologic results of the pivotal phase 3 REGENERATE trial, the first-ever successful phase 3 study of a medication for NASH, noted Dr. Alkhouri, a gastroenterologist at the University of Texas, San Antonio, and director of the Metabolic Health Center at the Texas Liver Institute.
At present there are no FDA-approved pharmacotherapies for NASH. The unmet medical need is huge, since NASH is now recognized to be a full-blown, burgeoning epidemic. NASH will soon become the No. 1 indication for liver transplantation in the United States. A full-throttle race is on to find effective therapies targeting the various dimensions of NASH, with more than 70 drugs now in phase 2 studies. These drugs collectively address all four mechanisms of the disease’s development and progression: the metabolic targets, perturbations in the gut-liver axis, liver inflammation, and fibrosis.
Moreover, even as the FDA considers the application for approval of obeticholic acid in NASH, at least four other investigational drugs are in pivotal phase 3 clinical trials. These include elafibranor, aramchol, resmetirom, and cenicriviroc.
Cenicriviroc is a dual CCR 2/5 receptor antagonist that targets the hepatic inflammation and fibrosis dimensions of NASH. It is now being evaluated in the phase 3 AURORA trial on the strength of the earlier positive phase 2b Centaur study, in which patients randomized to cenicriviroc were twice as likely to experience significant improvement in fibrosis as were placebo-treated controls.
Elafibranor, aramchol, and resmetirom employ different mechanisms of action to address the metabolic derangements of NASH. What they share in common is their aim to reduce the influx of free fatty acids from adipose tissue to the liver, and/or to inhibit lipogenesis from carbohydrate building blocks. In so doing, these medications should result in reduced hepatocyte injury and liver inflammation.
Elafibranor is a peroxisome proliferator-activated receptor alpha/delta agonist that achieved significant biopsy-proven reversal of NASH in moderate- or severely affected patients in the phase 2 GOLDEN study. The phase 3 RESOLVE IT trial is underway.
Aramchol is a first-in-class synthetic fatty acid/bile acid conjugate that inhibits stearoyl-CoA desaturate activity. It’s designed to improve insulin resistance and curb accumulation of triglycerides in hepatocytes. In the 52-week, phase 2 ARREST trial, oral aramchol at 600 mg/day was 4.7-fold more likely than was placebo to achieve NASH resolution without worsening of fibrosis. The drug is now in phase 3 in the ARMOR study.
Resmetirom is a selective thyroid hormone receptor–beta agonist. Activation of the beta receptor lowers LDL cholesterol, triglycerides, and liver fat, whereas activation of the alpha receptor has the unwanted effects of promoting bone loss, thyrotoxicosis, and arrhythmias. In phase 2, 75% of patients on high-dose resmetirom achieved at least a 30% reduction in hepatic fat by MRI at week 12, compared with 18% of placebo-treated controls. And 39% of the high-dose resmetirom group showed histologic resolution of NASH on a week-36 liver biopsy, as did a mere 6% of controls. The phase 3 MAESTRO randomized trial is underway.
Obeticholic acid addresses the gut-liver axis abnormalities present in NASH, especially the exuberant bile acid circulation.
Clinical implications of the coming wave of medications
In Dr. Alkhouri’s view, .
“These are the patients with a high chance of progressing to cirrhosis and end-stage liver disease,” the gastroenterologist said.
Patients with earlier-stage nonalcoholic fatty liver disease are best managed via lifestyle changes, with particular emphasis upon 10% weight loss accompanied by exercise. And patients with more advanced disease – NASH with cirrhosis – appear thus far to be beyond the reach of the next-generation therapies.
None of the coming drugs is a cure-all. In the landmark phase 3 REGENERATE trial, for example, the rate of the primary outcome – fibrosis improvement of at least one stage plus no worsening of NASH at 18 months – was 23% in patients randomized to obeticholic acid at 25 mg/day, compared to 12% with placebo.
“These are not like hepatitis C medications, with 97% efficacy, so combination therapy targeting upstream and downstream for NASH is rational,” Dr. Alkhouri observed.
He reported serving on advisory boards for Allergan, Gilead, and Intercept, and receiving research grants from those companies as well as from Galmed, Genfit, and Madrigal.
*This story was updated on 12/5/2019.
REPORTING FROM ACG 2019
Endoscopic radiofrequency ablation excels for pancreatic tumors
SAN ANTONIO – Endoscopic ultrasound-guided radiofrequency ablation is ready for a prime time proper definitive test in a randomized controlled trial for treatment of unresectable pancreatic tumors, Amaninder Dhaliwal, MD, declared at the annual meeting of the American College of Gastroenterology.
He backed this assertion by presenting his meta-analysis of 13 published studies of endoscopic ultrasound radiofrequency ablation (EUS-RFA) therapy applied to 127 patients with unresectable pancreatic tumors. Most of the studies were small, single center, and prospective, with a mean 5.2 months of follow-up. Fifty-three percent of the patients had locally advanced unresectable pancreatic ductal adenocarcinoma and 30% had pancreatic neuroendocrine tumors, with a smattering of rarer pancreatic tumors making up the balance. The median lesion size was 28.2 mm. The majority of target lesions were located on the pancreatic head.
EUS-RFA is a relatively new approach to the treatment of unresectable pancreatic tumors. It’s a minimally invasive treatment strategy guided by high-quality, real-time imaging. , according to Dr. Dhaliwal, a gastroenterology fellow at the University of Nebraska, Omaha.
The patients collectively underwent 156 EUS-RFA procedures, with a 98% technical success rate. The pooled clinical success rate was 84.5% as defined by reduction in lesion size, symptomatic improvement, and radiologic evidence of necrosis on imaging the day following the procedure.
”Symptoms improved as early as the next day, including hypoglycemia in patients with insulinomas,” he said.
The 7-day early adverse event rate was 13.4%, with mild to moderate abdominal pain accounting for nearly three-quarters of such events. Notably, no perforations or infections occurred. Late adverse events consisted of two cases of jaundice, two cases of mild pancreatitis, one duodenal stricture, and one cystic fluid pocket.
All of the studies utilized specialized 18- or 19-gauge needle electrodes. The mean energy delivered was 30 watts.
“I think [these] data give us some hope that we can go forward with multicenter trials in patients with unresectable pancreatic cancer and benign lesions. These patients are very sick and have limited options,” Dr. Dhaliwal observed.
He reported no financial conflicts regarding his study.
SOURCE: Dhaliwal A. ACG Abstract 30.
SAN ANTONIO – Endoscopic ultrasound-guided radiofrequency ablation is ready for a prime time proper definitive test in a randomized controlled trial for treatment of unresectable pancreatic tumors, Amaninder Dhaliwal, MD, declared at the annual meeting of the American College of Gastroenterology.
He backed this assertion by presenting his meta-analysis of 13 published studies of endoscopic ultrasound radiofrequency ablation (EUS-RFA) therapy applied to 127 patients with unresectable pancreatic tumors. Most of the studies were small, single center, and prospective, with a mean 5.2 months of follow-up. Fifty-three percent of the patients had locally advanced unresectable pancreatic ductal adenocarcinoma and 30% had pancreatic neuroendocrine tumors, with a smattering of rarer pancreatic tumors making up the balance. The median lesion size was 28.2 mm. The majority of target lesions were located on the pancreatic head.
EUS-RFA is a relatively new approach to the treatment of unresectable pancreatic tumors. It’s a minimally invasive treatment strategy guided by high-quality, real-time imaging. , according to Dr. Dhaliwal, a gastroenterology fellow at the University of Nebraska, Omaha.
The patients collectively underwent 156 EUS-RFA procedures, with a 98% technical success rate. The pooled clinical success rate was 84.5% as defined by reduction in lesion size, symptomatic improvement, and radiologic evidence of necrosis on imaging the day following the procedure.
”Symptoms improved as early as the next day, including hypoglycemia in patients with insulinomas,” he said.
The 7-day early adverse event rate was 13.4%, with mild to moderate abdominal pain accounting for nearly three-quarters of such events. Notably, no perforations or infections occurred. Late adverse events consisted of two cases of jaundice, two cases of mild pancreatitis, one duodenal stricture, and one cystic fluid pocket.
All of the studies utilized specialized 18- or 19-gauge needle electrodes. The mean energy delivered was 30 watts.
“I think [these] data give us some hope that we can go forward with multicenter trials in patients with unresectable pancreatic cancer and benign lesions. These patients are very sick and have limited options,” Dr. Dhaliwal observed.
He reported no financial conflicts regarding his study.
SOURCE: Dhaliwal A. ACG Abstract 30.
SAN ANTONIO – Endoscopic ultrasound-guided radiofrequency ablation is ready for a prime time proper definitive test in a randomized controlled trial for treatment of unresectable pancreatic tumors, Amaninder Dhaliwal, MD, declared at the annual meeting of the American College of Gastroenterology.
He backed this assertion by presenting his meta-analysis of 13 published studies of endoscopic ultrasound radiofrequency ablation (EUS-RFA) therapy applied to 127 patients with unresectable pancreatic tumors. Most of the studies were small, single center, and prospective, with a mean 5.2 months of follow-up. Fifty-three percent of the patients had locally advanced unresectable pancreatic ductal adenocarcinoma and 30% had pancreatic neuroendocrine tumors, with a smattering of rarer pancreatic tumors making up the balance. The median lesion size was 28.2 mm. The majority of target lesions were located on the pancreatic head.
EUS-RFA is a relatively new approach to the treatment of unresectable pancreatic tumors. It’s a minimally invasive treatment strategy guided by high-quality, real-time imaging. , according to Dr. Dhaliwal, a gastroenterology fellow at the University of Nebraska, Omaha.
The patients collectively underwent 156 EUS-RFA procedures, with a 98% technical success rate. The pooled clinical success rate was 84.5% as defined by reduction in lesion size, symptomatic improvement, and radiologic evidence of necrosis on imaging the day following the procedure.
”Symptoms improved as early as the next day, including hypoglycemia in patients with insulinomas,” he said.
The 7-day early adverse event rate was 13.4%, with mild to moderate abdominal pain accounting for nearly three-quarters of such events. Notably, no perforations or infections occurred. Late adverse events consisted of two cases of jaundice, two cases of mild pancreatitis, one duodenal stricture, and one cystic fluid pocket.
All of the studies utilized specialized 18- or 19-gauge needle electrodes. The mean energy delivered was 30 watts.
“I think [these] data give us some hope that we can go forward with multicenter trials in patients with unresectable pancreatic cancer and benign lesions. These patients are very sick and have limited options,” Dr. Dhaliwal observed.
He reported no financial conflicts regarding his study.
SOURCE: Dhaliwal A. ACG Abstract 30.
REPORTING FROM ACG 2019
Endoscopy-related occupational injuries run rampant in gastroenterology
SAN ANTONIO – Swati Pawa, MD, reported at the annual meeting of the American College of Gastroenterology.
Moreover, most respondents said they received zero training in ergonomic strategies for endoscopy-related injury (ERI) prevention during their fellowship training. And there’s been none since. Eighty-one percent of respondents indicated they would welcome such training, added Dr. Pawa, a gastroenterologist at Wake Forest University, Winston-Salem, N.C.
The survey results expose a glaring unmet need in clinical practice, she said: “There have been no published guidelines from any of the major professional GI societies to date addressing how to prevent endoscopy-related injuries.”
The 38-item survey was created by the ACG Women in GI Committee and sponsored by the ACG governing board.
Among the key findings was the identification of sex differences in the types of ERIs reported, which suggests different contributory mechanisms. For example, female gastroenterologists were more likely than were their male colleagues to have experienced ERIs involving the upper back, by a margin of 49% to 36%. Upper extremity pain was more common among the women, too, with 63% reporting hand or finger pain, compared with 53% of men. Twenty-four percent of women reported carpal tunnel syndrome and an equal percentage developed tendonitis, compared with 18% and 17% of men, respectively.
Seventy-one percent of women attributed their ERI to torquing with their right hand, as did 63% of men. Women also more frequently cited having to deal with a nonadjustable bed or monitor as contributing to injury. In contrast, roughly twice as many men as women attributed their ERI to wearing a lead apron or use of the elevator on the duodenoscope.
Equally common causes of ERIs in men and women included standing in awkward positions while supporting an endoscope, standing for a long time, and adjusting tip angulation with the left hand.
Male and female gastroenterologists differed in their practice patterns. The men had been performing endoscopy for a mean of 23 years, compared with 13 years for the women. Fifty-six percent of the men were in private practice, compared with 35% of the women. In contrast, 43% of the women worked in academic settings versus 28% of the men. Thirty percent of the male gastroenterologists characterized themselves as interventional specialists, a rate more than twice that in women, who more commonly specialized in inflammatory bowel disease.
The survey was sent to nearly 16,000 ACG members. It generated a 14% response rate. Roughly two-thirds of responses were provided by male gastroenterologists.
Dr. Pawa and her coinvestigators are now drilling down through the survey data in an effort to identify an appropriate endoscopy workload limit that’s associated with reduced ERI risk.
One audience member commented, “The incidence of ERI in your survey is much higher than most of us would expect.” He speculated that response bias might be at work, with gastroenterologists who have personally experienced an ERI being perhaps more highly motivated to be among the 14% who completed the 38-question survey. Dr. Pawa replied that the survey figures are in line with other, smaller studies.
She reported having no financial conflicts regarding her study.
Visit https://www.ddwnews.org/
SAN ANTONIO – Swati Pawa, MD, reported at the annual meeting of the American College of Gastroenterology.
Moreover, most respondents said they received zero training in ergonomic strategies for endoscopy-related injury (ERI) prevention during their fellowship training. And there’s been none since. Eighty-one percent of respondents indicated they would welcome such training, added Dr. Pawa, a gastroenterologist at Wake Forest University, Winston-Salem, N.C.
The survey results expose a glaring unmet need in clinical practice, she said: “There have been no published guidelines from any of the major professional GI societies to date addressing how to prevent endoscopy-related injuries.”
The 38-item survey was created by the ACG Women in GI Committee and sponsored by the ACG governing board.
Among the key findings was the identification of sex differences in the types of ERIs reported, which suggests different contributory mechanisms. For example, female gastroenterologists were more likely than were their male colleagues to have experienced ERIs involving the upper back, by a margin of 49% to 36%. Upper extremity pain was more common among the women, too, with 63% reporting hand or finger pain, compared with 53% of men. Twenty-four percent of women reported carpal tunnel syndrome and an equal percentage developed tendonitis, compared with 18% and 17% of men, respectively.
Seventy-one percent of women attributed their ERI to torquing with their right hand, as did 63% of men. Women also more frequently cited having to deal with a nonadjustable bed or monitor as contributing to injury. In contrast, roughly twice as many men as women attributed their ERI to wearing a lead apron or use of the elevator on the duodenoscope.
Equally common causes of ERIs in men and women included standing in awkward positions while supporting an endoscope, standing for a long time, and adjusting tip angulation with the left hand.
Male and female gastroenterologists differed in their practice patterns. The men had been performing endoscopy for a mean of 23 years, compared with 13 years for the women. Fifty-six percent of the men were in private practice, compared with 35% of the women. In contrast, 43% of the women worked in academic settings versus 28% of the men. Thirty percent of the male gastroenterologists characterized themselves as interventional specialists, a rate more than twice that in women, who more commonly specialized in inflammatory bowel disease.
The survey was sent to nearly 16,000 ACG members. It generated a 14% response rate. Roughly two-thirds of responses were provided by male gastroenterologists.
Dr. Pawa and her coinvestigators are now drilling down through the survey data in an effort to identify an appropriate endoscopy workload limit that’s associated with reduced ERI risk.
One audience member commented, “The incidence of ERI in your survey is much higher than most of us would expect.” He speculated that response bias might be at work, with gastroenterologists who have personally experienced an ERI being perhaps more highly motivated to be among the 14% who completed the 38-question survey. Dr. Pawa replied that the survey figures are in line with other, smaller studies.
She reported having no financial conflicts regarding her study.
Visit https://www.ddwnews.org/
SAN ANTONIO – Swati Pawa, MD, reported at the annual meeting of the American College of Gastroenterology.
Moreover, most respondents said they received zero training in ergonomic strategies for endoscopy-related injury (ERI) prevention during their fellowship training. And there’s been none since. Eighty-one percent of respondents indicated they would welcome such training, added Dr. Pawa, a gastroenterologist at Wake Forest University, Winston-Salem, N.C.
The survey results expose a glaring unmet need in clinical practice, she said: “There have been no published guidelines from any of the major professional GI societies to date addressing how to prevent endoscopy-related injuries.”
The 38-item survey was created by the ACG Women in GI Committee and sponsored by the ACG governing board.
Among the key findings was the identification of sex differences in the types of ERIs reported, which suggests different contributory mechanisms. For example, female gastroenterologists were more likely than were their male colleagues to have experienced ERIs involving the upper back, by a margin of 49% to 36%. Upper extremity pain was more common among the women, too, with 63% reporting hand or finger pain, compared with 53% of men. Twenty-four percent of women reported carpal tunnel syndrome and an equal percentage developed tendonitis, compared with 18% and 17% of men, respectively.
Seventy-one percent of women attributed their ERI to torquing with their right hand, as did 63% of men. Women also more frequently cited having to deal with a nonadjustable bed or monitor as contributing to injury. In contrast, roughly twice as many men as women attributed their ERI to wearing a lead apron or use of the elevator on the duodenoscope.
Equally common causes of ERIs in men and women included standing in awkward positions while supporting an endoscope, standing for a long time, and adjusting tip angulation with the left hand.
Male and female gastroenterologists differed in their practice patterns. The men had been performing endoscopy for a mean of 23 years, compared with 13 years for the women. Fifty-six percent of the men were in private practice, compared with 35% of the women. In contrast, 43% of the women worked in academic settings versus 28% of the men. Thirty percent of the male gastroenterologists characterized themselves as interventional specialists, a rate more than twice that in women, who more commonly specialized in inflammatory bowel disease.
The survey was sent to nearly 16,000 ACG members. It generated a 14% response rate. Roughly two-thirds of responses were provided by male gastroenterologists.
Dr. Pawa and her coinvestigators are now drilling down through the survey data in an effort to identify an appropriate endoscopy workload limit that’s associated with reduced ERI risk.
One audience member commented, “The incidence of ERI in your survey is much higher than most of us would expect.” He speculated that response bias might be at work, with gastroenterologists who have personally experienced an ERI being perhaps more highly motivated to be among the 14% who completed the 38-question survey. Dr. Pawa replied that the survey figures are in line with other, smaller studies.
She reported having no financial conflicts regarding her study.
Visit https://www.ddwnews.org/
REPORTING FROM ACG 2019
Endoscopy-related occupational injuries run rampant in gastroenterology
SAN ANTONIO – Swati Pawa, MD, reported at the annual meeting of the American College of Gastroenterology.
Moreover, most respondents said they received zero training in ergonomic strategies for endoscopy-related injury (ERI) prevention during their fellowship training. And there’s been none since. Eighty-one percent of respondents indicated they would welcome such training, added Dr. Pawa, a gastroenterologist at Wake Forest University, Winston-Salem, N.C.
The survey results expose a glaring unmet need in clinical practice, she said: “There have been no published guidelines from any of the major professional GI societies to date addressing how to prevent endoscopy-related injuries.”
The 38-item survey was created by the ACG Women in GI Committee and sponsored by the ACG governing board.
Among the key findings was the identification of sex differences in the types of ERIs reported, which suggests different contributory mechanisms. For example, female gastroenterologists were more likely than were their male colleagues to have experienced ERIs involving the upper back, by a margin of 49% to 36%. Upper extremity pain was more common among the women, too, with 63% reporting hand or finger pain, compared with 53% of men. Twenty-four percent of women reported carpal tunnel syndrome and an equal percentage developed tendonitis, compared with 18% and 17% of men, respectively.
Seventy-one percent of women attributed their ERI to torquing with their right hand, as did 63% of men. Women also more frequently cited having to deal with a nonadjustable bed or monitor as contributing to injury. In contrast, roughly twice as many men as women attributed their ERI to wearing a lead apron or use of the elevator on the duodenoscope.
Equally common causes of ERIs in men and women included standing in awkward positions while supporting an endoscope, standing for a long time, and adjusting tip angulation with the left hand.
Male and female gastroenterologists differed in their practice patterns. The men had been performing endoscopy for a mean of 23 years, compared with 13 years for the women. Fifty-six percent of the men were in private practice, compared with 35% of the women. In contrast, 43% of the women worked in academic settings versus 28% of the men. Thirty percent of the male gastroenterologists characterized themselves as interventional specialists, a rate more than twice that in women, who more commonly specialized in inflammatory bowel disease.
The survey was sent to nearly 16,000 ACG members. It generated a 14% response rate. Roughly two-thirds of responses were provided by male gastroenterologists.
Dr. Pawa and her coinvestigators are now drilling down through the survey data in an effort to identify an appropriate endoscopy workload limit that’s associated with reduced ERI risk.
One audience member commented, “The incidence of ERI in your survey is much higher than most of us would expect.” He speculated that response bias might be at work, with gastroenterologists who have personally experienced an ERI being perhaps more highly motivated to be among the 14% who completed the 38-question survey. Dr. Pawa replied that the survey figures are in line with other, smaller studies.
She reported having no financial conflicts regarding her study.
SAN ANTONIO – Swati Pawa, MD, reported at the annual meeting of the American College of Gastroenterology.
Moreover, most respondents said they received zero training in ergonomic strategies for endoscopy-related injury (ERI) prevention during their fellowship training. And there’s been none since. Eighty-one percent of respondents indicated they would welcome such training, added Dr. Pawa, a gastroenterologist at Wake Forest University, Winston-Salem, N.C.
The survey results expose a glaring unmet need in clinical practice, she said: “There have been no published guidelines from any of the major professional GI societies to date addressing how to prevent endoscopy-related injuries.”
The 38-item survey was created by the ACG Women in GI Committee and sponsored by the ACG governing board.
Among the key findings was the identification of sex differences in the types of ERIs reported, which suggests different contributory mechanisms. For example, female gastroenterologists were more likely than were their male colleagues to have experienced ERIs involving the upper back, by a margin of 49% to 36%. Upper extremity pain was more common among the women, too, with 63% reporting hand or finger pain, compared with 53% of men. Twenty-four percent of women reported carpal tunnel syndrome and an equal percentage developed tendonitis, compared with 18% and 17% of men, respectively.
Seventy-one percent of women attributed their ERI to torquing with their right hand, as did 63% of men. Women also more frequently cited having to deal with a nonadjustable bed or monitor as contributing to injury. In contrast, roughly twice as many men as women attributed their ERI to wearing a lead apron or use of the elevator on the duodenoscope.
Equally common causes of ERIs in men and women included standing in awkward positions while supporting an endoscope, standing for a long time, and adjusting tip angulation with the left hand.
Male and female gastroenterologists differed in their practice patterns. The men had been performing endoscopy for a mean of 23 years, compared with 13 years for the women. Fifty-six percent of the men were in private practice, compared with 35% of the women. In contrast, 43% of the women worked in academic settings versus 28% of the men. Thirty percent of the male gastroenterologists characterized themselves as interventional specialists, a rate more than twice that in women, who more commonly specialized in inflammatory bowel disease.
The survey was sent to nearly 16,000 ACG members. It generated a 14% response rate. Roughly two-thirds of responses were provided by male gastroenterologists.
Dr. Pawa and her coinvestigators are now drilling down through the survey data in an effort to identify an appropriate endoscopy workload limit that’s associated with reduced ERI risk.
One audience member commented, “The incidence of ERI in your survey is much higher than most of us would expect.” He speculated that response bias might be at work, with gastroenterologists who have personally experienced an ERI being perhaps more highly motivated to be among the 14% who completed the 38-question survey. Dr. Pawa replied that the survey figures are in line with other, smaller studies.
She reported having no financial conflicts regarding her study.
SAN ANTONIO – Swati Pawa, MD, reported at the annual meeting of the American College of Gastroenterology.
Moreover, most respondents said they received zero training in ergonomic strategies for endoscopy-related injury (ERI) prevention during their fellowship training. And there’s been none since. Eighty-one percent of respondents indicated they would welcome such training, added Dr. Pawa, a gastroenterologist at Wake Forest University, Winston-Salem, N.C.
The survey results expose a glaring unmet need in clinical practice, she said: “There have been no published guidelines from any of the major professional GI societies to date addressing how to prevent endoscopy-related injuries.”
The 38-item survey was created by the ACG Women in GI Committee and sponsored by the ACG governing board.
Among the key findings was the identification of sex differences in the types of ERIs reported, which suggests different contributory mechanisms. For example, female gastroenterologists were more likely than were their male colleagues to have experienced ERIs involving the upper back, by a margin of 49% to 36%. Upper extremity pain was more common among the women, too, with 63% reporting hand or finger pain, compared with 53% of men. Twenty-four percent of women reported carpal tunnel syndrome and an equal percentage developed tendonitis, compared with 18% and 17% of men, respectively.
Seventy-one percent of women attributed their ERI to torquing with their right hand, as did 63% of men. Women also more frequently cited having to deal with a nonadjustable bed or monitor as contributing to injury. In contrast, roughly twice as many men as women attributed their ERI to wearing a lead apron or use of the elevator on the duodenoscope.
Equally common causes of ERIs in men and women included standing in awkward positions while supporting an endoscope, standing for a long time, and adjusting tip angulation with the left hand.
Male and female gastroenterologists differed in their practice patterns. The men had been performing endoscopy for a mean of 23 years, compared with 13 years for the women. Fifty-six percent of the men were in private practice, compared with 35% of the women. In contrast, 43% of the women worked in academic settings versus 28% of the men. Thirty percent of the male gastroenterologists characterized themselves as interventional specialists, a rate more than twice that in women, who more commonly specialized in inflammatory bowel disease.
The survey was sent to nearly 16,000 ACG members. It generated a 14% response rate. Roughly two-thirds of responses were provided by male gastroenterologists.
Dr. Pawa and her coinvestigators are now drilling down through the survey data in an effort to identify an appropriate endoscopy workload limit that’s associated with reduced ERI risk.
One audience member commented, “The incidence of ERI in your survey is much higher than most of us would expect.” He speculated that response bias might be at work, with gastroenterologists who have personally experienced an ERI being perhaps more highly motivated to be among the 14% who completed the 38-question survey. Dr. Pawa replied that the survey figures are in line with other, smaller studies.
She reported having no financial conflicts regarding her study.
REPORTING FROM ACG 2019
Wide-area transepithelial sampling may be best method for detecting esophageal intestinal metaplasia
SAN ANTONIO – A wide-area transepithelial sampling (WATS) brush proved superior to standard forceps biopsies for detection of intestinal metaplasia (IM) in the esophagus and gastroesophageal junction in patients with no history of IM who had any visible columnar-lined esophagus on upper endoscopy in a large randomized trial.
“This suggests that WATS should in fact be the preferred method of sampling these patients,” Steven R. DeMeester, MD, commented in presenting the study results at the annual meeting of the American College of Gastroenterology.
With that specific exception, however, the two sampling methods proved similarly effective at detecting IM and dysplasia, suggesting either technology can otherwise reliably be used to detect these conditions, added Dr. DeMeester, a general and thoracic surgeon at the Oregon Clinic, Portland.
This is important new information for clinicians. A prior multicenter, randomized trial by other investigators demonstrated that adding WATS to biopsy sampling improved the detection rate of dysplasia and esophageal adenocarcinoma, compared with biopsies alone (Gastrointest Endosc. 2018 Feb;87[2]:348-55). However, this dual-sampling strategy is too time-consuming for routine use in a busy practice. Given the new evidence that the two sampling methods can reliably be used interchangeably except in patients with no history of IM who have endoscopically visible columnar-lined esophagus, WATS offers a clear advantage in that it’s much quicker, especially in patients with long-segment Barrett’s esophagus, the surgeon said.
Unlike brush cytology, which merely collects surface epithelial cells, the WATS brush collects sheets of esophageal mucosa, which then undergo computer-assisted three-dimensional analysis.
“When done appropriately, a wide area of the esophageal mucosa can be sampled with the WATS brush,” Dr. DeMeester explained.
He reported on 1,002 patients who presented at nine U.S. centers for upper endoscopy for Barrett’s esophagus surveillance or evaluation of foregut symptoms. They were randomized to WATS or forceps biopsies using the Seattle protocol. In the entire group, WATS and forceps biopsies were similarly effective, each finding IM – a potentially premalignant mucosal change – in about 21% of patients, and dysplasia or cancer in 0.8%. Among the 185 patients who underwent endoscopy for follow-up of Barrett’s esophagus or post ablation, the two sampling strategies also performed similarly, detecting IM in roughly 36% of the 151 patients with columnar-lined esophagus shorter than 3 cm and in 56% of those with columnar-lined esophagus of greater length.
However, in the 196 patients with no history of IM who had any length of visible columnar-lined esophagus on endoscopy, the frequency of IM detection was 32.7% with WATS, compared with 15.3% with biopsy.
Dr. DeMeester and coinvestigators were also eager to identify factors associated with detection of IM in the esophagus or gastroesophageal junction in patients undergoing elective endoscopy with no history of IM. They found that whites were at greater risk than blacks, by a margin of 10.1% (17.1% vs. 7%). Moreover, the 23% IM detection rate in patients aged over age 70 years was significantly higher than the 15.5% rate in those under age 70. And to their surprise, there was no significant difference between the IM detection rate in men and women.
Nearly 15% of study participants with no measurable columnar-lined esophagus turned out to have IM. And two patients with low-grade dysplasia and one with adenocarcinoma were found among the group with no history of IM and no visible columnar-lined esophagus on upper endoscopy.
“This demonstrates that the absence of a measurable columnar-lined esophagus does not exclude patients from the risk of having intestinal metaplasia, dysplasia, or cancer at the gastroesophageal junction. Therefore evaluation of the gastroesophageal junction by biopsy or WATS should be considered during upper endoscopy, particularly in patients at increased risk for having intestinal metaplasia,” he concluded.
Dr. DeMeester reported serving as a consultant to BARD and receiving research funding from and serving as a paid speaker for CDx Diagnostics, which funded the trial.
SAN ANTONIO – A wide-area transepithelial sampling (WATS) brush proved superior to standard forceps biopsies for detection of intestinal metaplasia (IM) in the esophagus and gastroesophageal junction in patients with no history of IM who had any visible columnar-lined esophagus on upper endoscopy in a large randomized trial.
“This suggests that WATS should in fact be the preferred method of sampling these patients,” Steven R. DeMeester, MD, commented in presenting the study results at the annual meeting of the American College of Gastroenterology.
With that specific exception, however, the two sampling methods proved similarly effective at detecting IM and dysplasia, suggesting either technology can otherwise reliably be used to detect these conditions, added Dr. DeMeester, a general and thoracic surgeon at the Oregon Clinic, Portland.
This is important new information for clinicians. A prior multicenter, randomized trial by other investigators demonstrated that adding WATS to biopsy sampling improved the detection rate of dysplasia and esophageal adenocarcinoma, compared with biopsies alone (Gastrointest Endosc. 2018 Feb;87[2]:348-55). However, this dual-sampling strategy is too time-consuming for routine use in a busy practice. Given the new evidence that the two sampling methods can reliably be used interchangeably except in patients with no history of IM who have endoscopically visible columnar-lined esophagus, WATS offers a clear advantage in that it’s much quicker, especially in patients with long-segment Barrett’s esophagus, the surgeon said.
Unlike brush cytology, which merely collects surface epithelial cells, the WATS brush collects sheets of esophageal mucosa, which then undergo computer-assisted three-dimensional analysis.
“When done appropriately, a wide area of the esophageal mucosa can be sampled with the WATS brush,” Dr. DeMeester explained.
He reported on 1,002 patients who presented at nine U.S. centers for upper endoscopy for Barrett’s esophagus surveillance or evaluation of foregut symptoms. They were randomized to WATS or forceps biopsies using the Seattle protocol. In the entire group, WATS and forceps biopsies were similarly effective, each finding IM – a potentially premalignant mucosal change – in about 21% of patients, and dysplasia or cancer in 0.8%. Among the 185 patients who underwent endoscopy for follow-up of Barrett’s esophagus or post ablation, the two sampling strategies also performed similarly, detecting IM in roughly 36% of the 151 patients with columnar-lined esophagus shorter than 3 cm and in 56% of those with columnar-lined esophagus of greater length.
However, in the 196 patients with no history of IM who had any length of visible columnar-lined esophagus on endoscopy, the frequency of IM detection was 32.7% with WATS, compared with 15.3% with biopsy.
Dr. DeMeester and coinvestigators were also eager to identify factors associated with detection of IM in the esophagus or gastroesophageal junction in patients undergoing elective endoscopy with no history of IM. They found that whites were at greater risk than blacks, by a margin of 10.1% (17.1% vs. 7%). Moreover, the 23% IM detection rate in patients aged over age 70 years was significantly higher than the 15.5% rate in those under age 70. And to their surprise, there was no significant difference between the IM detection rate in men and women.
Nearly 15% of study participants with no measurable columnar-lined esophagus turned out to have IM. And two patients with low-grade dysplasia and one with adenocarcinoma were found among the group with no history of IM and no visible columnar-lined esophagus on upper endoscopy.
“This demonstrates that the absence of a measurable columnar-lined esophagus does not exclude patients from the risk of having intestinal metaplasia, dysplasia, or cancer at the gastroesophageal junction. Therefore evaluation of the gastroesophageal junction by biopsy or WATS should be considered during upper endoscopy, particularly in patients at increased risk for having intestinal metaplasia,” he concluded.
Dr. DeMeester reported serving as a consultant to BARD and receiving research funding from and serving as a paid speaker for CDx Diagnostics, which funded the trial.
SAN ANTONIO – A wide-area transepithelial sampling (WATS) brush proved superior to standard forceps biopsies for detection of intestinal metaplasia (IM) in the esophagus and gastroesophageal junction in patients with no history of IM who had any visible columnar-lined esophagus on upper endoscopy in a large randomized trial.
“This suggests that WATS should in fact be the preferred method of sampling these patients,” Steven R. DeMeester, MD, commented in presenting the study results at the annual meeting of the American College of Gastroenterology.
With that specific exception, however, the two sampling methods proved similarly effective at detecting IM and dysplasia, suggesting either technology can otherwise reliably be used to detect these conditions, added Dr. DeMeester, a general and thoracic surgeon at the Oregon Clinic, Portland.
This is important new information for clinicians. A prior multicenter, randomized trial by other investigators demonstrated that adding WATS to biopsy sampling improved the detection rate of dysplasia and esophageal adenocarcinoma, compared with biopsies alone (Gastrointest Endosc. 2018 Feb;87[2]:348-55). However, this dual-sampling strategy is too time-consuming for routine use in a busy practice. Given the new evidence that the two sampling methods can reliably be used interchangeably except in patients with no history of IM who have endoscopically visible columnar-lined esophagus, WATS offers a clear advantage in that it’s much quicker, especially in patients with long-segment Barrett’s esophagus, the surgeon said.
Unlike brush cytology, which merely collects surface epithelial cells, the WATS brush collects sheets of esophageal mucosa, which then undergo computer-assisted three-dimensional analysis.
“When done appropriately, a wide area of the esophageal mucosa can be sampled with the WATS brush,” Dr. DeMeester explained.
He reported on 1,002 patients who presented at nine U.S. centers for upper endoscopy for Barrett’s esophagus surveillance or evaluation of foregut symptoms. They were randomized to WATS or forceps biopsies using the Seattle protocol. In the entire group, WATS and forceps biopsies were similarly effective, each finding IM – a potentially premalignant mucosal change – in about 21% of patients, and dysplasia or cancer in 0.8%. Among the 185 patients who underwent endoscopy for follow-up of Barrett’s esophagus or post ablation, the two sampling strategies also performed similarly, detecting IM in roughly 36% of the 151 patients with columnar-lined esophagus shorter than 3 cm and in 56% of those with columnar-lined esophagus of greater length.
However, in the 196 patients with no history of IM who had any length of visible columnar-lined esophagus on endoscopy, the frequency of IM detection was 32.7% with WATS, compared with 15.3% with biopsy.
Dr. DeMeester and coinvestigators were also eager to identify factors associated with detection of IM in the esophagus or gastroesophageal junction in patients undergoing elective endoscopy with no history of IM. They found that whites were at greater risk than blacks, by a margin of 10.1% (17.1% vs. 7%). Moreover, the 23% IM detection rate in patients aged over age 70 years was significantly higher than the 15.5% rate in those under age 70. And to their surprise, there was no significant difference between the IM detection rate in men and women.
Nearly 15% of study participants with no measurable columnar-lined esophagus turned out to have IM. And two patients with low-grade dysplasia and one with adenocarcinoma were found among the group with no history of IM and no visible columnar-lined esophagus on upper endoscopy.
“This demonstrates that the absence of a measurable columnar-lined esophagus does not exclude patients from the risk of having intestinal metaplasia, dysplasia, or cancer at the gastroesophageal junction. Therefore evaluation of the gastroesophageal junction by biopsy or WATS should be considered during upper endoscopy, particularly in patients at increased risk for having intestinal metaplasia,” he concluded.
Dr. DeMeester reported serving as a consultant to BARD and receiving research funding from and serving as a paid speaker for CDx Diagnostics, which funded the trial.
REPORTING FROM ACG 2019
Geriatric IBD hospitalization carries steep inpatient mortality
SAN ANTONIO – Jeffrey Schwartz, MD, reported at the annual meeting of the American College of Gastroenterology.
The magnitude of the age-related increased risk highlighted in this large national study was strikingly larger than the differential inpatient mortality between geriatric and nongeriatric patients hospitalized for conditions other than inflammatory bowel disease (IBD). It’s a finding that reveals a major unmet need for improved systems of care for elderly hospitalized IBD patients, according to Dr. Schwartz, an internal medicine resident at Beth Israel Deaconess Medical Center, Boston.
“Given the high prevalence of IBD patients that require inpatient admission, as well as the rapidly aging nature of the U.S. population, it’s our hope that this study will provide some insight to drive efforts to improve standardized guideline-directed therapy and propose interventions to help close what I think is a very important gap in clinical care,” he said.
It’s well established that a second peak of IBD diagnoses occurs in 50- to 70-year-olds. At present, roughly 30% of all individuals carrying the diagnosis of IBD are over age 65, and with the graying of the baby-boomer population, this proportion is climbing.
Dr. Schwartz presented a study of the National Inpatient Sample for 2016, which is a representative sample comprising 20% of all U.S. hospital discharges for that year, the most recent year for which the data are available. The study population included all 71,040 patients hospitalized for acute management of Crohn’s disease or its immediate complications, of whom 10,095 were aged over age 75 years, as well as the 35,950 patients hospitalized for ulcerative colitis, 8,285 of whom were over 75.
Inpatient mortality occurred in 1.5% of the geriatric admissions, compared with 0.2% of nongeriatric admissions for Crohn’s disease. Similarly, the inpatient mortality rate in geriatric patients with ulcerative colitis was 1.0% versus 0.1% in patients under age 75 hospitalized for ulcerative colitis.
There are lots of reasons why the management of geriatric patients with IBD is particularly challenging, Dr. Schwartz noted. They have a higher burden of comorbid conditions, worse nutritional status, and increased risks of infection and cancer. In a regression analysis that attempted to control for such confounders using the Elixhauser mortality index, the nongeriatric Crohn’s disease patients were an adjusted 75% less likely to die in the hospital than those who were older. Nongeriatric ulcerative colitis patients were 81% less likely to die than geriatric patients with the disease. In contrast, nongeriatric patients admitted for reasons other than IBD had only an adjusted 50% lower risk of inpatient mortality than those who were older than 75.
Of note, in this analysis adjusted for confounders, there was no difference between geriatric and nongeriatric IBD patients in terms of resource utilization as reflected in average length of stay and hospital charges, Dr. Schwartz continued.
Asked if he could shed light on any specific complications that drove the age-related disparity in inpatient mortality in the IBD population, the physician replied that he and his coinvestigators were thwarted in their effort to do so because the inpatient mortality of 1.0%-1.5% was so low that further breakdown as to causes of death would have been statistically unreliable. It might be possible to do so successfully by combining several years of National Inpatient Sample data. That being said, it’s reasonable to hypothesize that cardiovascular complications are an important contributor, he added.
Dr. Schwartz reported having no financial conflicts regarding his study, conducted free of commercial support.
SAN ANTONIO – Jeffrey Schwartz, MD, reported at the annual meeting of the American College of Gastroenterology.
The magnitude of the age-related increased risk highlighted in this large national study was strikingly larger than the differential inpatient mortality between geriatric and nongeriatric patients hospitalized for conditions other than inflammatory bowel disease (IBD). It’s a finding that reveals a major unmet need for improved systems of care for elderly hospitalized IBD patients, according to Dr. Schwartz, an internal medicine resident at Beth Israel Deaconess Medical Center, Boston.
“Given the high prevalence of IBD patients that require inpatient admission, as well as the rapidly aging nature of the U.S. population, it’s our hope that this study will provide some insight to drive efforts to improve standardized guideline-directed therapy and propose interventions to help close what I think is a very important gap in clinical care,” he said.
It’s well established that a second peak of IBD diagnoses occurs in 50- to 70-year-olds. At present, roughly 30% of all individuals carrying the diagnosis of IBD are over age 65, and with the graying of the baby-boomer population, this proportion is climbing.
Dr. Schwartz presented a study of the National Inpatient Sample for 2016, which is a representative sample comprising 20% of all U.S. hospital discharges for that year, the most recent year for which the data are available. The study population included all 71,040 patients hospitalized for acute management of Crohn’s disease or its immediate complications, of whom 10,095 were aged over age 75 years, as well as the 35,950 patients hospitalized for ulcerative colitis, 8,285 of whom were over 75.
Inpatient mortality occurred in 1.5% of the geriatric admissions, compared with 0.2% of nongeriatric admissions for Crohn’s disease. Similarly, the inpatient mortality rate in geriatric patients with ulcerative colitis was 1.0% versus 0.1% in patients under age 75 hospitalized for ulcerative colitis.
There are lots of reasons why the management of geriatric patients with IBD is particularly challenging, Dr. Schwartz noted. They have a higher burden of comorbid conditions, worse nutritional status, and increased risks of infection and cancer. In a regression analysis that attempted to control for such confounders using the Elixhauser mortality index, the nongeriatric Crohn’s disease patients were an adjusted 75% less likely to die in the hospital than those who were older. Nongeriatric ulcerative colitis patients were 81% less likely to die than geriatric patients with the disease. In contrast, nongeriatric patients admitted for reasons other than IBD had only an adjusted 50% lower risk of inpatient mortality than those who were older than 75.
Of note, in this analysis adjusted for confounders, there was no difference between geriatric and nongeriatric IBD patients in terms of resource utilization as reflected in average length of stay and hospital charges, Dr. Schwartz continued.
Asked if he could shed light on any specific complications that drove the age-related disparity in inpatient mortality in the IBD population, the physician replied that he and his coinvestigators were thwarted in their effort to do so because the inpatient mortality of 1.0%-1.5% was so low that further breakdown as to causes of death would have been statistically unreliable. It might be possible to do so successfully by combining several years of National Inpatient Sample data. That being said, it’s reasonable to hypothesize that cardiovascular complications are an important contributor, he added.
Dr. Schwartz reported having no financial conflicts regarding his study, conducted free of commercial support.
SAN ANTONIO – Jeffrey Schwartz, MD, reported at the annual meeting of the American College of Gastroenterology.
The magnitude of the age-related increased risk highlighted in this large national study was strikingly larger than the differential inpatient mortality between geriatric and nongeriatric patients hospitalized for conditions other than inflammatory bowel disease (IBD). It’s a finding that reveals a major unmet need for improved systems of care for elderly hospitalized IBD patients, according to Dr. Schwartz, an internal medicine resident at Beth Israel Deaconess Medical Center, Boston.
“Given the high prevalence of IBD patients that require inpatient admission, as well as the rapidly aging nature of the U.S. population, it’s our hope that this study will provide some insight to drive efforts to improve standardized guideline-directed therapy and propose interventions to help close what I think is a very important gap in clinical care,” he said.
It’s well established that a second peak of IBD diagnoses occurs in 50- to 70-year-olds. At present, roughly 30% of all individuals carrying the diagnosis of IBD are over age 65, and with the graying of the baby-boomer population, this proportion is climbing.
Dr. Schwartz presented a study of the National Inpatient Sample for 2016, which is a representative sample comprising 20% of all U.S. hospital discharges for that year, the most recent year for which the data are available. The study population included all 71,040 patients hospitalized for acute management of Crohn’s disease or its immediate complications, of whom 10,095 were aged over age 75 years, as well as the 35,950 patients hospitalized for ulcerative colitis, 8,285 of whom were over 75.
Inpatient mortality occurred in 1.5% of the geriatric admissions, compared with 0.2% of nongeriatric admissions for Crohn’s disease. Similarly, the inpatient mortality rate in geriatric patients with ulcerative colitis was 1.0% versus 0.1% in patients under age 75 hospitalized for ulcerative colitis.
There are lots of reasons why the management of geriatric patients with IBD is particularly challenging, Dr. Schwartz noted. They have a higher burden of comorbid conditions, worse nutritional status, and increased risks of infection and cancer. In a regression analysis that attempted to control for such confounders using the Elixhauser mortality index, the nongeriatric Crohn’s disease patients were an adjusted 75% less likely to die in the hospital than those who were older. Nongeriatric ulcerative colitis patients were 81% less likely to die than geriatric patients with the disease. In contrast, nongeriatric patients admitted for reasons other than IBD had only an adjusted 50% lower risk of inpatient mortality than those who were older than 75.
Of note, in this analysis adjusted for confounders, there was no difference between geriatric and nongeriatric IBD patients in terms of resource utilization as reflected in average length of stay and hospital charges, Dr. Schwartz continued.
Asked if he could shed light on any specific complications that drove the age-related disparity in inpatient mortality in the IBD population, the physician replied that he and his coinvestigators were thwarted in their effort to do so because the inpatient mortality of 1.0%-1.5% was so low that further breakdown as to causes of death would have been statistically unreliable. It might be possible to do so successfully by combining several years of National Inpatient Sample data. That being said, it’s reasonable to hypothesize that cardiovascular complications are an important contributor, he added.
Dr. Schwartz reported having no financial conflicts regarding his study, conducted free of commercial support.
REPORTING FROM ACG 2019
Key clinical point: A major unmet need exists for better guideline-directed management of geriatric patients hospitalized for inflammatory bowel disease.
Major finding: The inpatient mortality rate among patients aged over age 75 years hospitalized for management of inflammatory bowel disease is four to five times higher than in those who are younger.
Study details: This was a retrospective analysis of all 106,990 hospital admissions for management of inflammatory bowel disease included in the 2016 National Inpatient Sample.
Disclosures: The presenter reported having no financial conflicts regarding his study, conducted free of commercial support.
Source: Schwartz J. ACG 2019, Abstract 42.
Rifabutin-based triple therapy for H. pylori gets high marks
SAN ANTONIO – David Y. Graham, MD, asserted at the annual meeting of the American College of Gastroenterology.
The drug, recently approved as Talicia, is a rifabutin-based triple therapy. Each capsule contains 50 mg of rifabutin, 1,000 mg of amoxicillin, and 40 mg of omeprazole. As in the pivotal phase 3 trial led by Dr. Graham, the approved treatment regimen calls for adults to take four capsules every 8 hours for 14 days.
The impetus for developing the new therapy centers on the growing problem of resistance to long-standard agents for H. pylori eradication, including metronidazole and clarithromycin. The World Health Organization has declared H. pylori eradication to be a high priority for therapeutic development. Rifabutin resistance is rare: In one study, 413 of 414 strains of H. pylori were sensitive to the antibiotic, noted Dr. Graham, professor of medicine at Baylor College of Medicine, Houston.
He presented the results of the pivotal phase 3, double-blind, multicenter, active comparator trial, known as ERADICATE Hp2, in which 455 participants with confirmed H. pylori infection were randomized to a course of the all-in-one-capsule triple drug combo or to dual therapy with four capsules, each containing 1,000 mg of amoxicillin and 40 mg of omeprazole, every 8 hours for 14 days.
The primary endpoint was H. pylori eradication as documented by a negative urea breath test obtained 4-6 weeks after completing 14 days of treatment. The rate was 84% with the rifabutin-based combo, compared with 58% seen with the high-dose dual therapy. Moreover, in a prespecified secondary analysis restricted to the 391 participants who were confirmed to be actually taking their medication as evidenced by a positive blood level measured on day 13, the eradication rates rose to 90% and 65%, respectively.
The antimicrobial resistance rates documented in this study were eye opening: 17% of patients’ strains were resistant to clarithromycin, 44% to metronidazole, and 10.5% to both. Of concern, 6.4% of participants’ strains were amoxicillin resistant.
“For the first time we saw a low level – but a definite level – of amoxicillin resistance. That’s something we had not seen previously,” Dr. Graham said.
No rifabutin resistance was detected before or after treatment.
The side effect profiles of the two treatment regimens were similar. Diarrhea was reported by 9% of participants, headache by 7%, and nausea by 5%. No serious adverse events occurred in the 14-day study.
The efficacy of the rifabutin-based therapy wasn’t affected by metronidazole or clarithromycin resistance.
The ERADICATE Hp2 trial was sponsored by RedHill Biopharma of Tel Aviv. Dr. Graham reported having no financial conflicts.
SAN ANTONIO – David Y. Graham, MD, asserted at the annual meeting of the American College of Gastroenterology.
The drug, recently approved as Talicia, is a rifabutin-based triple therapy. Each capsule contains 50 mg of rifabutin, 1,000 mg of amoxicillin, and 40 mg of omeprazole. As in the pivotal phase 3 trial led by Dr. Graham, the approved treatment regimen calls for adults to take four capsules every 8 hours for 14 days.
The impetus for developing the new therapy centers on the growing problem of resistance to long-standard agents for H. pylori eradication, including metronidazole and clarithromycin. The World Health Organization has declared H. pylori eradication to be a high priority for therapeutic development. Rifabutin resistance is rare: In one study, 413 of 414 strains of H. pylori were sensitive to the antibiotic, noted Dr. Graham, professor of medicine at Baylor College of Medicine, Houston.
He presented the results of the pivotal phase 3, double-blind, multicenter, active comparator trial, known as ERADICATE Hp2, in which 455 participants with confirmed H. pylori infection were randomized to a course of the all-in-one-capsule triple drug combo or to dual therapy with four capsules, each containing 1,000 mg of amoxicillin and 40 mg of omeprazole, every 8 hours for 14 days.
The primary endpoint was H. pylori eradication as documented by a negative urea breath test obtained 4-6 weeks after completing 14 days of treatment. The rate was 84% with the rifabutin-based combo, compared with 58% seen with the high-dose dual therapy. Moreover, in a prespecified secondary analysis restricted to the 391 participants who were confirmed to be actually taking their medication as evidenced by a positive blood level measured on day 13, the eradication rates rose to 90% and 65%, respectively.
The antimicrobial resistance rates documented in this study were eye opening: 17% of patients’ strains were resistant to clarithromycin, 44% to metronidazole, and 10.5% to both. Of concern, 6.4% of participants’ strains were amoxicillin resistant.
“For the first time we saw a low level – but a definite level – of amoxicillin resistance. That’s something we had not seen previously,” Dr. Graham said.
No rifabutin resistance was detected before or after treatment.
The side effect profiles of the two treatment regimens were similar. Diarrhea was reported by 9% of participants, headache by 7%, and nausea by 5%. No serious adverse events occurred in the 14-day study.
The efficacy of the rifabutin-based therapy wasn’t affected by metronidazole or clarithromycin resistance.
The ERADICATE Hp2 trial was sponsored by RedHill Biopharma of Tel Aviv. Dr. Graham reported having no financial conflicts.
SAN ANTONIO – David Y. Graham, MD, asserted at the annual meeting of the American College of Gastroenterology.
The drug, recently approved as Talicia, is a rifabutin-based triple therapy. Each capsule contains 50 mg of rifabutin, 1,000 mg of amoxicillin, and 40 mg of omeprazole. As in the pivotal phase 3 trial led by Dr. Graham, the approved treatment regimen calls for adults to take four capsules every 8 hours for 14 days.
The impetus for developing the new therapy centers on the growing problem of resistance to long-standard agents for H. pylori eradication, including metronidazole and clarithromycin. The World Health Organization has declared H. pylori eradication to be a high priority for therapeutic development. Rifabutin resistance is rare: In one study, 413 of 414 strains of H. pylori were sensitive to the antibiotic, noted Dr. Graham, professor of medicine at Baylor College of Medicine, Houston.
He presented the results of the pivotal phase 3, double-blind, multicenter, active comparator trial, known as ERADICATE Hp2, in which 455 participants with confirmed H. pylori infection were randomized to a course of the all-in-one-capsule triple drug combo or to dual therapy with four capsules, each containing 1,000 mg of amoxicillin and 40 mg of omeprazole, every 8 hours for 14 days.
The primary endpoint was H. pylori eradication as documented by a negative urea breath test obtained 4-6 weeks after completing 14 days of treatment. The rate was 84% with the rifabutin-based combo, compared with 58% seen with the high-dose dual therapy. Moreover, in a prespecified secondary analysis restricted to the 391 participants who were confirmed to be actually taking their medication as evidenced by a positive blood level measured on day 13, the eradication rates rose to 90% and 65%, respectively.
The antimicrobial resistance rates documented in this study were eye opening: 17% of patients’ strains were resistant to clarithromycin, 44% to metronidazole, and 10.5% to both. Of concern, 6.4% of participants’ strains were amoxicillin resistant.
“For the first time we saw a low level – but a definite level – of amoxicillin resistance. That’s something we had not seen previously,” Dr. Graham said.
No rifabutin resistance was detected before or after treatment.
The side effect profiles of the two treatment regimens were similar. Diarrhea was reported by 9% of participants, headache by 7%, and nausea by 5%. No serious adverse events occurred in the 14-day study.
The efficacy of the rifabutin-based therapy wasn’t affected by metronidazole or clarithromycin resistance.
The ERADICATE Hp2 trial was sponsored by RedHill Biopharma of Tel Aviv. Dr. Graham reported having no financial conflicts.
REPORTING FROM ACG 2019
Over-the-scope hemoclip prevails for upper GI bleeding
SAN ANTONIO – Use of a large over-the-scope hemoclip for initial endoscopic treatment of severe nonvariceal upper gastrointestinal bleeding resulted in a markedly lower 30-day rebleeding rate compared with standard endoscopic hemostasis in the first-ever randomized prospective clinical trial addressing the issue, Dennis M. Jensen, MD, reported at the annual meeting of the American College of Gastroenterology.
The over-the-scope clip also resulted in significantly fewer complications and cut the red blood cell transfusion rate in half, added Dr. Jensen, professor of medicine at the University of California, Los Angeles.
“The results appear to relate to the clip’s superior ability to obliterate critical arterial blood flow underneath the stigmata of hemorrhage and thereby reduce lesion rebleeding,” according to Dr. Jensen.
However, he emphasized a couple of caveats regarding this highly effective intervention.
First, it’s best reserved for patients with major stigmata of hemorrhage: that is, active arterial bleeding, a nonbleeding visible vessel, and/or adherent clot. That’s where all the benefit lies. Study participants with minor stigmata of hemorrhage – mere oozing bleeding or flat spots with arterial flow by Doppler – did just fine with standard endoscopic hemostasis, and in that setting the over-the-scope clip offered no additional benefit.
Second, there’s a significant learning curve involved in successful use of the clip.
“If someone’s going to be using this they have to get additional training. There’s a lot of tricks to using this,” the gastroenterologist cautioned.
The two-center prospective trial included 49 patients with severe nonvariceal upper GI bleeding who were randomized double-blind to the over-the-scope clip or standard hemostasis with hemoclips and/or application of a multipolar probe with epinephrine pre-injection as initial therapy. The severe bleeding was due to peptic ulcers in 40 patients and Dieulafoy’s lesions in the rest. All participants received high-dose proton pump inhibitor therapy after randomization.
The primary endpoint was clinically significant rebleeding within 30 days following initial therapy. This occurred in 7 of 25 patients (28%) on standard treatment and in 1 of 24 (4%) treated with the over-the-scope clip. This translated to an 85% relative risk reduction, with an impressive low number-needed-to-treat of 4.2.
Among the 35 patients with major stigmata of hemorrhage, the rebleeding rate was 35% in the over-the-scope clip group, compared with 6.3% with standard therapy, with a number-needed-to-treat of 3.5.
All four severe complications – a stroke, aspiration pneumonia, a case of severe heart failure, and a bleeding ischemic ulcer secondary to angiographic embolization – occurred in the standard therapy group. Patients in that group also averaged a 1.3-day-longer hospital length of stay and 2.8 more days in the ICU; however, those trends didn’t achieve statistical significance because of the small study size.
One audience member leapt to his feet to declare: “This is the study we’ve all been waiting for.” He pressed Dr. Jensen for technical details about the procedure.
Dr. Jensen explained that the large clip goes over an 11-mm-diameter endoscope with a 3-mm hood and no teeth. But he cautioned that some gastroenterologists in a busy community practice may find the procedure too time- and labor-intensive for their liking.
“It really takes two people to treat a duodenal ulcer. Somebody has to push quite firmly and suction very hard as you try to deploy this. By suctioning hard, the clip will burrow in so long as it’s centered on the stigmata of hemorrhage; that’s really key,” according to Dr. Jensen.
The procedure takes longer than standard endoscopic hemostasis because the over-the-scope clip limits visualization. So the patient must be scoped twice: the first time with a clipless diagnostic endoscope, so the operator can get his or her bearings; then that scope needs to be taken out, the patient is reintubated, and the over-the-scope clip is brought to bear.
“You shouldn’t just grab this off the shelf and try to use it in an emergency. You’ll really have problems. People have to be taught with porcine models and they need to review the stigmata,” Dr. Jensen said.
He reported having no financial conflicts regarding this study, conducted free of commercial support.
SOURCE: Jensen DM. ACG 2019, Abstract 8.
SAN ANTONIO – Use of a large over-the-scope hemoclip for initial endoscopic treatment of severe nonvariceal upper gastrointestinal bleeding resulted in a markedly lower 30-day rebleeding rate compared with standard endoscopic hemostasis in the first-ever randomized prospective clinical trial addressing the issue, Dennis M. Jensen, MD, reported at the annual meeting of the American College of Gastroenterology.
The over-the-scope clip also resulted in significantly fewer complications and cut the red blood cell transfusion rate in half, added Dr. Jensen, professor of medicine at the University of California, Los Angeles.
“The results appear to relate to the clip’s superior ability to obliterate critical arterial blood flow underneath the stigmata of hemorrhage and thereby reduce lesion rebleeding,” according to Dr. Jensen.
However, he emphasized a couple of caveats regarding this highly effective intervention.
First, it’s best reserved for patients with major stigmata of hemorrhage: that is, active arterial bleeding, a nonbleeding visible vessel, and/or adherent clot. That’s where all the benefit lies. Study participants with minor stigmata of hemorrhage – mere oozing bleeding or flat spots with arterial flow by Doppler – did just fine with standard endoscopic hemostasis, and in that setting the over-the-scope clip offered no additional benefit.
Second, there’s a significant learning curve involved in successful use of the clip.
“If someone’s going to be using this they have to get additional training. There’s a lot of tricks to using this,” the gastroenterologist cautioned.
The two-center prospective trial included 49 patients with severe nonvariceal upper GI bleeding who were randomized double-blind to the over-the-scope clip or standard hemostasis with hemoclips and/or application of a multipolar probe with epinephrine pre-injection as initial therapy. The severe bleeding was due to peptic ulcers in 40 patients and Dieulafoy’s lesions in the rest. All participants received high-dose proton pump inhibitor therapy after randomization.
The primary endpoint was clinically significant rebleeding within 30 days following initial therapy. This occurred in 7 of 25 patients (28%) on standard treatment and in 1 of 24 (4%) treated with the over-the-scope clip. This translated to an 85% relative risk reduction, with an impressive low number-needed-to-treat of 4.2.
Among the 35 patients with major stigmata of hemorrhage, the rebleeding rate was 35% in the over-the-scope clip group, compared with 6.3% with standard therapy, with a number-needed-to-treat of 3.5.
All four severe complications – a stroke, aspiration pneumonia, a case of severe heart failure, and a bleeding ischemic ulcer secondary to angiographic embolization – occurred in the standard therapy group. Patients in that group also averaged a 1.3-day-longer hospital length of stay and 2.8 more days in the ICU; however, those trends didn’t achieve statistical significance because of the small study size.
One audience member leapt to his feet to declare: “This is the study we’ve all been waiting for.” He pressed Dr. Jensen for technical details about the procedure.
Dr. Jensen explained that the large clip goes over an 11-mm-diameter endoscope with a 3-mm hood and no teeth. But he cautioned that some gastroenterologists in a busy community practice may find the procedure too time- and labor-intensive for their liking.
“It really takes two people to treat a duodenal ulcer. Somebody has to push quite firmly and suction very hard as you try to deploy this. By suctioning hard, the clip will burrow in so long as it’s centered on the stigmata of hemorrhage; that’s really key,” according to Dr. Jensen.
The procedure takes longer than standard endoscopic hemostasis because the over-the-scope clip limits visualization. So the patient must be scoped twice: the first time with a clipless diagnostic endoscope, so the operator can get his or her bearings; then that scope needs to be taken out, the patient is reintubated, and the over-the-scope clip is brought to bear.
“You shouldn’t just grab this off the shelf and try to use it in an emergency. You’ll really have problems. People have to be taught with porcine models and they need to review the stigmata,” Dr. Jensen said.
He reported having no financial conflicts regarding this study, conducted free of commercial support.
SOURCE: Jensen DM. ACG 2019, Abstract 8.
SAN ANTONIO – Use of a large over-the-scope hemoclip for initial endoscopic treatment of severe nonvariceal upper gastrointestinal bleeding resulted in a markedly lower 30-day rebleeding rate compared with standard endoscopic hemostasis in the first-ever randomized prospective clinical trial addressing the issue, Dennis M. Jensen, MD, reported at the annual meeting of the American College of Gastroenterology.
The over-the-scope clip also resulted in significantly fewer complications and cut the red blood cell transfusion rate in half, added Dr. Jensen, professor of medicine at the University of California, Los Angeles.
“The results appear to relate to the clip’s superior ability to obliterate critical arterial blood flow underneath the stigmata of hemorrhage and thereby reduce lesion rebleeding,” according to Dr. Jensen.
However, he emphasized a couple of caveats regarding this highly effective intervention.
First, it’s best reserved for patients with major stigmata of hemorrhage: that is, active arterial bleeding, a nonbleeding visible vessel, and/or adherent clot. That’s where all the benefit lies. Study participants with minor stigmata of hemorrhage – mere oozing bleeding or flat spots with arterial flow by Doppler – did just fine with standard endoscopic hemostasis, and in that setting the over-the-scope clip offered no additional benefit.
Second, there’s a significant learning curve involved in successful use of the clip.
“If someone’s going to be using this they have to get additional training. There’s a lot of tricks to using this,” the gastroenterologist cautioned.
The two-center prospective trial included 49 patients with severe nonvariceal upper GI bleeding who were randomized double-blind to the over-the-scope clip or standard hemostasis with hemoclips and/or application of a multipolar probe with epinephrine pre-injection as initial therapy. The severe bleeding was due to peptic ulcers in 40 patients and Dieulafoy’s lesions in the rest. All participants received high-dose proton pump inhibitor therapy after randomization.
The primary endpoint was clinically significant rebleeding within 30 days following initial therapy. This occurred in 7 of 25 patients (28%) on standard treatment and in 1 of 24 (4%) treated with the over-the-scope clip. This translated to an 85% relative risk reduction, with an impressive low number-needed-to-treat of 4.2.
Among the 35 patients with major stigmata of hemorrhage, the rebleeding rate was 35% in the over-the-scope clip group, compared with 6.3% with standard therapy, with a number-needed-to-treat of 3.5.
All four severe complications – a stroke, aspiration pneumonia, a case of severe heart failure, and a bleeding ischemic ulcer secondary to angiographic embolization – occurred in the standard therapy group. Patients in that group also averaged a 1.3-day-longer hospital length of stay and 2.8 more days in the ICU; however, those trends didn’t achieve statistical significance because of the small study size.
One audience member leapt to his feet to declare: “This is the study we’ve all been waiting for.” He pressed Dr. Jensen for technical details about the procedure.
Dr. Jensen explained that the large clip goes over an 11-mm-diameter endoscope with a 3-mm hood and no teeth. But he cautioned that some gastroenterologists in a busy community practice may find the procedure too time- and labor-intensive for their liking.
“It really takes two people to treat a duodenal ulcer. Somebody has to push quite firmly and suction very hard as you try to deploy this. By suctioning hard, the clip will burrow in so long as it’s centered on the stigmata of hemorrhage; that’s really key,” according to Dr. Jensen.
The procedure takes longer than standard endoscopic hemostasis because the over-the-scope clip limits visualization. So the patient must be scoped twice: the first time with a clipless diagnostic endoscope, so the operator can get his or her bearings; then that scope needs to be taken out, the patient is reintubated, and the over-the-scope clip is brought to bear.
“You shouldn’t just grab this off the shelf and try to use it in an emergency. You’ll really have problems. People have to be taught with porcine models and they need to review the stigmata,” Dr. Jensen said.
He reported having no financial conflicts regarding this study, conducted free of commercial support.
SOURCE: Jensen DM. ACG 2019, Abstract 8.
REPORTING FROM ACG 2019
Topical budesonide effective for eosinophilic esophagitis in pivotal trial
SAN ANTONIO – An investigational muco-adherent swallowed formulation of budesonide developed specifically for treatment of eosinophilic esophagitis aced all primary and secondary endpoints in a pivotal, phase 3, double-blind, placebo-controlled randomized trial, Ikuo Hirano, MD, reported at the annual scientific meeting of the American College of Gastroenterology.
This is welcome news for patients with this chronic immune-mediated disease, for which no Food and Drug Administration–approved drug therapy exists yet.
“This is the first phase 3 trial to demonstrate efficacy using the validated Dysphagia Symptom Questionnaire, the first completed phase 3 trial of any medical therapeutic for eosinophilic esophagitis, and the largest clinical trial for eosinophilic esophagitis conducted to date,” declared Dr. Hirano, professor of medicine at Northwestern University in Chicago.
This was a 12-week induction therapy study including 318 adolescents and adults randomized 2:1 to 2 mg of budesonide oral suspension (BOS) or placebo twice daily. Patients were instructed not to eat or drink anything for 30 minutes afterward to avoid washing away the medication.
This was a severely affected patient population with high-level inflammatory activity: their mean baseline peak eosinophil count was 75 cells per high-power field, well above the diagnostic threshold of 50 eosinophils per high-power field. In keeping with a requirement for study participation, all patients had failed to respond to at least 6 weeks of high-dose proton pump inhibitor therapy. They also had to experience solid food dysphagia on at least 4 days per 2 weeks. More than 40% of subjects had previously undergone esophageal dilation.
One coprimary endpoint addressed histologic response, defined as 6 or fewer eosinophils per high-power field after 12 weeks of double-blind treatment. The histologic response rate was 53% in the BOS group and 1% in placebo-treated controls.
The other coprimary endpoint was symptom response as defined by at least a 30% reduction from baseline in the Dysphagia Symptom Questionnaire score. This was achieved in 53% of patients on BOS and 39% of controls.
The prespecified key secondary endpoint was the absolute reduction in Dysphagia Symptom Questionnaire score through week 12. From a mean baseline score of 30 out of a possible 84, the swallowed steroid recipients experienced a mean 13-point improvement, compared with a 9.1-improvement for those on placebo.
The topical budesonide group also did significantly better than placebo in terms of all other secondary endpoints. Endoscopic improvement as reflected in the mean Eosinophilic Esophagitis Reference Score was greater in the BOS group by a margin of 4 versus 2.2 points. A high-bar histologic response rate of no more than a single eosinophil per high-power field at week 12 was achieved in one-third of the BOS group and zero controls. The overall peak eosinophil count from baseline to week 12 dropped by an average of 55.2 cells per high-power field in the budesonide group, compared to a 7.6-eosinophil decrease in controls. And the proportion of patients with no more than 15 eosinophils per high-power field at week 12 was 62% with BOS, compared with 1% with placebo.
Treatment-emergent adverse events were similar in the two study arms and were mild to moderate in severity. Of note, however, the 3.8% incidence of esophageal candidiasis rate in the topical corticosteroid group was twice that seen in the placebo arm. Adrenal function as assessed by ACTH stimulation testing at baseline and 12 weeks was normal in 88% of the BOS group and 94% of controls.
Dr. Hirano noted that adrenal function will continue to be carefully monitored during an ongoing, phase 3, double-blind, placebo-controlled BOS maintenance study.
He reported receiving research funding from and serving as a consultant to Takeda, the study sponsor, as well as a handful of other pharmaceutical companies.
This is an exciting abstract from Hirano et al. highlighting the results of the first phase 3 trial for an eosinophilic esophagitis (EoE) treatment. Furthermore, the trial design, which included histologic and symptom-based endpoints, may be critical to attaining Food and Drug Administration approval. Given the lack of any FDA-approved therapies for EoE, the results of this trial are welcome news for clinicians who treat patients with EoE.
This study of a topical muco-adherent steroid formulation (budesonide oral suspension) specifically designed to treat EoE significantly improved histologic, symptom, and endoscopic endpoints, compared with placebo. Of note, 62% of patients on the drug achieved a histologic response of less than 15 eosinophils per high-power field (53% achieved less than 6), compared with 1% in the placebo group. This study supplements the existing data supporting the use of swallowed topical steroids in EoE.
It is important to note that the subjects in this study had fairly severe disease, with more than 40% having previously undergone esophageal dilation and all patients experiencing dysphagia, on average, multiple times per week. Given the disease severity in the subject population, there can be even greater enthusiasm regarding the response rates for the budesonide group. Also notable is the relatively high dose of budesonide used in this study (2 mg twice daily), which may have contributed to the 3.8% incidence of esophageal candidiasis. Importantly, adrenal function was assessed during the study and will be monitored during the ongoing maintenance portion of the study.
These last points do highlight the challenges of treating more severe EoE given 38% of patients did not achieve histologic remission (less than 15 eosinophils per high-power field) despite the doses of budesonide used in this study. This emphasizes the need for other treatment options for steroid nonresponders.
Taken together, these results are very exciting and will lead to an FDA-approved EoE treatment in short order.
Paul Menard-Katcher, MD, is associate professor of medicine in the division of gastroenterology and hepatology at the University of Colorado at Denver, Aurora. He has no conflicts of interest.
This is an exciting abstract from Hirano et al. highlighting the results of the first phase 3 trial for an eosinophilic esophagitis (EoE) treatment. Furthermore, the trial design, which included histologic and symptom-based endpoints, may be critical to attaining Food and Drug Administration approval. Given the lack of any FDA-approved therapies for EoE, the results of this trial are welcome news for clinicians who treat patients with EoE.
This study of a topical muco-adherent steroid formulation (budesonide oral suspension) specifically designed to treat EoE significantly improved histologic, symptom, and endoscopic endpoints, compared with placebo. Of note, 62% of patients on the drug achieved a histologic response of less than 15 eosinophils per high-power field (53% achieved less than 6), compared with 1% in the placebo group. This study supplements the existing data supporting the use of swallowed topical steroids in EoE.
It is important to note that the subjects in this study had fairly severe disease, with more than 40% having previously undergone esophageal dilation and all patients experiencing dysphagia, on average, multiple times per week. Given the disease severity in the subject population, there can be even greater enthusiasm regarding the response rates for the budesonide group. Also notable is the relatively high dose of budesonide used in this study (2 mg twice daily), which may have contributed to the 3.8% incidence of esophageal candidiasis. Importantly, adrenal function was assessed during the study and will be monitored during the ongoing maintenance portion of the study.
These last points do highlight the challenges of treating more severe EoE given 38% of patients did not achieve histologic remission (less than 15 eosinophils per high-power field) despite the doses of budesonide used in this study. This emphasizes the need for other treatment options for steroid nonresponders.
Taken together, these results are very exciting and will lead to an FDA-approved EoE treatment in short order.
Paul Menard-Katcher, MD, is associate professor of medicine in the division of gastroenterology and hepatology at the University of Colorado at Denver, Aurora. He has no conflicts of interest.
This is an exciting abstract from Hirano et al. highlighting the results of the first phase 3 trial for an eosinophilic esophagitis (EoE) treatment. Furthermore, the trial design, which included histologic and symptom-based endpoints, may be critical to attaining Food and Drug Administration approval. Given the lack of any FDA-approved therapies for EoE, the results of this trial are welcome news for clinicians who treat patients with EoE.
This study of a topical muco-adherent steroid formulation (budesonide oral suspension) specifically designed to treat EoE significantly improved histologic, symptom, and endoscopic endpoints, compared with placebo. Of note, 62% of patients on the drug achieved a histologic response of less than 15 eosinophils per high-power field (53% achieved less than 6), compared with 1% in the placebo group. This study supplements the existing data supporting the use of swallowed topical steroids in EoE.
It is important to note that the subjects in this study had fairly severe disease, with more than 40% having previously undergone esophageal dilation and all patients experiencing dysphagia, on average, multiple times per week. Given the disease severity in the subject population, there can be even greater enthusiasm regarding the response rates for the budesonide group. Also notable is the relatively high dose of budesonide used in this study (2 mg twice daily), which may have contributed to the 3.8% incidence of esophageal candidiasis. Importantly, adrenal function was assessed during the study and will be monitored during the ongoing maintenance portion of the study.
These last points do highlight the challenges of treating more severe EoE given 38% of patients did not achieve histologic remission (less than 15 eosinophils per high-power field) despite the doses of budesonide used in this study. This emphasizes the need for other treatment options for steroid nonresponders.
Taken together, these results are very exciting and will lead to an FDA-approved EoE treatment in short order.
Paul Menard-Katcher, MD, is associate professor of medicine in the division of gastroenterology and hepatology at the University of Colorado at Denver, Aurora. He has no conflicts of interest.
SAN ANTONIO – An investigational muco-adherent swallowed formulation of budesonide developed specifically for treatment of eosinophilic esophagitis aced all primary and secondary endpoints in a pivotal, phase 3, double-blind, placebo-controlled randomized trial, Ikuo Hirano, MD, reported at the annual scientific meeting of the American College of Gastroenterology.
This is welcome news for patients with this chronic immune-mediated disease, for which no Food and Drug Administration–approved drug therapy exists yet.
“This is the first phase 3 trial to demonstrate efficacy using the validated Dysphagia Symptom Questionnaire, the first completed phase 3 trial of any medical therapeutic for eosinophilic esophagitis, and the largest clinical trial for eosinophilic esophagitis conducted to date,” declared Dr. Hirano, professor of medicine at Northwestern University in Chicago.
This was a 12-week induction therapy study including 318 adolescents and adults randomized 2:1 to 2 mg of budesonide oral suspension (BOS) or placebo twice daily. Patients were instructed not to eat or drink anything for 30 minutes afterward to avoid washing away the medication.
This was a severely affected patient population with high-level inflammatory activity: their mean baseline peak eosinophil count was 75 cells per high-power field, well above the diagnostic threshold of 50 eosinophils per high-power field. In keeping with a requirement for study participation, all patients had failed to respond to at least 6 weeks of high-dose proton pump inhibitor therapy. They also had to experience solid food dysphagia on at least 4 days per 2 weeks. More than 40% of subjects had previously undergone esophageal dilation.
One coprimary endpoint addressed histologic response, defined as 6 or fewer eosinophils per high-power field after 12 weeks of double-blind treatment. The histologic response rate was 53% in the BOS group and 1% in placebo-treated controls.
The other coprimary endpoint was symptom response as defined by at least a 30% reduction from baseline in the Dysphagia Symptom Questionnaire score. This was achieved in 53% of patients on BOS and 39% of controls.
The prespecified key secondary endpoint was the absolute reduction in Dysphagia Symptom Questionnaire score through week 12. From a mean baseline score of 30 out of a possible 84, the swallowed steroid recipients experienced a mean 13-point improvement, compared with a 9.1-improvement for those on placebo.
The topical budesonide group also did significantly better than placebo in terms of all other secondary endpoints. Endoscopic improvement as reflected in the mean Eosinophilic Esophagitis Reference Score was greater in the BOS group by a margin of 4 versus 2.2 points. A high-bar histologic response rate of no more than a single eosinophil per high-power field at week 12 was achieved in one-third of the BOS group and zero controls. The overall peak eosinophil count from baseline to week 12 dropped by an average of 55.2 cells per high-power field in the budesonide group, compared to a 7.6-eosinophil decrease in controls. And the proportion of patients with no more than 15 eosinophils per high-power field at week 12 was 62% with BOS, compared with 1% with placebo.
Treatment-emergent adverse events were similar in the two study arms and were mild to moderate in severity. Of note, however, the 3.8% incidence of esophageal candidiasis rate in the topical corticosteroid group was twice that seen in the placebo arm. Adrenal function as assessed by ACTH stimulation testing at baseline and 12 weeks was normal in 88% of the BOS group and 94% of controls.
Dr. Hirano noted that adrenal function will continue to be carefully monitored during an ongoing, phase 3, double-blind, placebo-controlled BOS maintenance study.
He reported receiving research funding from and serving as a consultant to Takeda, the study sponsor, as well as a handful of other pharmaceutical companies.
SAN ANTONIO – An investigational muco-adherent swallowed formulation of budesonide developed specifically for treatment of eosinophilic esophagitis aced all primary and secondary endpoints in a pivotal, phase 3, double-blind, placebo-controlled randomized trial, Ikuo Hirano, MD, reported at the annual scientific meeting of the American College of Gastroenterology.
This is welcome news for patients with this chronic immune-mediated disease, for which no Food and Drug Administration–approved drug therapy exists yet.
“This is the first phase 3 trial to demonstrate efficacy using the validated Dysphagia Symptom Questionnaire, the first completed phase 3 trial of any medical therapeutic for eosinophilic esophagitis, and the largest clinical trial for eosinophilic esophagitis conducted to date,” declared Dr. Hirano, professor of medicine at Northwestern University in Chicago.
This was a 12-week induction therapy study including 318 adolescents and adults randomized 2:1 to 2 mg of budesonide oral suspension (BOS) or placebo twice daily. Patients were instructed not to eat or drink anything for 30 minutes afterward to avoid washing away the medication.
This was a severely affected patient population with high-level inflammatory activity: their mean baseline peak eosinophil count was 75 cells per high-power field, well above the diagnostic threshold of 50 eosinophils per high-power field. In keeping with a requirement for study participation, all patients had failed to respond to at least 6 weeks of high-dose proton pump inhibitor therapy. They also had to experience solid food dysphagia on at least 4 days per 2 weeks. More than 40% of subjects had previously undergone esophageal dilation.
One coprimary endpoint addressed histologic response, defined as 6 or fewer eosinophils per high-power field after 12 weeks of double-blind treatment. The histologic response rate was 53% in the BOS group and 1% in placebo-treated controls.
The other coprimary endpoint was symptom response as defined by at least a 30% reduction from baseline in the Dysphagia Symptom Questionnaire score. This was achieved in 53% of patients on BOS and 39% of controls.
The prespecified key secondary endpoint was the absolute reduction in Dysphagia Symptom Questionnaire score through week 12. From a mean baseline score of 30 out of a possible 84, the swallowed steroid recipients experienced a mean 13-point improvement, compared with a 9.1-improvement for those on placebo.
The topical budesonide group also did significantly better than placebo in terms of all other secondary endpoints. Endoscopic improvement as reflected in the mean Eosinophilic Esophagitis Reference Score was greater in the BOS group by a margin of 4 versus 2.2 points. A high-bar histologic response rate of no more than a single eosinophil per high-power field at week 12 was achieved in one-third of the BOS group and zero controls. The overall peak eosinophil count from baseline to week 12 dropped by an average of 55.2 cells per high-power field in the budesonide group, compared to a 7.6-eosinophil decrease in controls. And the proportion of patients with no more than 15 eosinophils per high-power field at week 12 was 62% with BOS, compared with 1% with placebo.
Treatment-emergent adverse events were similar in the two study arms and were mild to moderate in severity. Of note, however, the 3.8% incidence of esophageal candidiasis rate in the topical corticosteroid group was twice that seen in the placebo arm. Adrenal function as assessed by ACTH stimulation testing at baseline and 12 weeks was normal in 88% of the BOS group and 94% of controls.
Dr. Hirano noted that adrenal function will continue to be carefully monitored during an ongoing, phase 3, double-blind, placebo-controlled BOS maintenance study.
He reported receiving research funding from and serving as a consultant to Takeda, the study sponsor, as well as a handful of other pharmaceutical companies.
REPORTING FROM ACG 2019