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Dabigatran, rivaroxaban linked to slight increase in GI bleeding risk
Compared with conventional anticoagulants, both dabigatran and rivaroxaban conferred small but statistically significant increases in the risk of major gastrointestinal bleeding in a systematic review and meta-analysis of randomized trials reported in the November issue of Clinical Gastroenterology and Hepatology. (doi: 10.1016/j.cgh.2017.04.031)
But other novel oral anticoagulants (NOACs) showed no such effect compared with warfarin, aspirin, or placebo, reported Corey S. Miller, MD, of McGill University, Montreal, and his associates. “The potentially increased risk of GI bleeding associated with dabigatran and rivaroxaban observed in some of our subgroup analyses merits further consideration,” they wrote.
The NOACs (also known as non–vitamin K antagonist oral anticoagulants) help prevent stroke in patients with atrial fibrillation and prevent and treat venous thromboembolism. However, large AF trials have linked all except apixaban to an increased risk of major GI bleeding compared with warfarin. Dabigatran currently is the only NOAC with an approved reversal agent, “making the question of GI bleeding risk even more consequential,” the authors wrote.
They searched the MEDLINE, EMBASE, Cochrane, and ISI Web of Knowledge databases for reports of randomized trials of NOACs for approved indications published between 1980 and January 2016, which identified 43 trials of 166,289 patients. Most used warfarin as the comparator, but one study compared apixaban with aspirin and six studies compared apixaban, rivaroxaban, or dabigatran with placebo. Fifteen trials failed to specify bleeding sources and therefore could not be evaluated for the primary endpoint, the reviewers noted.
In the remaining 28 trials, 1.5% of NOAC recipients developed major GI bleeding, compared with 1.3% of recipients of conventional anticoagulants (odds ratio, 0.98; 95% confidence interval, 0.80-1.21). Five trials of dabigatran showed a 2% risk of major GI bleeding, compared with 1.4% with conventional anticoagulation, a slight but significant increase (OR, 1.27; 95% CI, 1.04-1.55). Eight trials of rivaroxaban showed a similar trend (bleeding risk, 1.7% vs. 1.3%; OR, 1.40; 95% CI, 1.15-1.70). In contrast, subgroup analyses of apixaban and edoxaban found no difference in risk of major GI bleeding versus conventional treatment.
Subgroup analyses by region found no differences except in Asia, where NOACs were associated with a significantly lower odds of major GI bleeding (0.5% and 1.2%, respectively; OR, 0.45; 95% CI, 0.22-0.91).
Most studies did not report minor or nonsevere bleeds or specify bleeding location within the GI tract, the reviewers noted. Given those caveats, NOACs and conventional anticoagulants conferred similar risks of clinically relevant nonmajor bleeding (0.6% and 0.6%, respectively), upper GI bleeding (1.5% and 1.6%), and lower GI bleeding (1.0% and 1.0%).
A post hoc analysis using a random-effects model found no significant difference in risk of major GI bleeding between either rivaroxaban or dabigatran and conventional therapy, the reviewers said. In addition, the increased risk of bleeding with dabigatran was confined to the RELY and ROCKET trials of AF, both of which exposed patients to longer treatment periods. Dabigatran is coated with tartaric acid, which might have a “direct caustic effect on the intestinal lumen,” they wrote. Also, NOACs are incompletely absorbed across the GI mucosa and therefore have some anticoagulant activity in the GI lumen, unlike warfarin or parenteral anticoagulants.
The reviewers disclosed no funding sources. Dr. Miller and another author reported having no conflicts of interest. One author received research grants and speaker honoraria from Boehringer Ingelheim Canada, Bayer Canada, Daiichi Sankyo, Bristol Myers Squibb, and Pfizer Canada; another author disclosed serving as a consultant to Pendopharm, Boston Scientific, and Cook.
Novel oral anticoagulants (NOACs) receive a lot of press now. In randomized controlled trials (RCTs) comparing NOACs to warfarin for prevention of strokes and thromboembolism in atrial fibrillation (AF) and venous thromboembolism (VTE), fewer thromboembolisms are reported, but risks of gastrointestinal bleeding vary. To expand analyses for gastrointestinal bleeding, several systematic reviews and meta-analyses are reported, including this one by CS Miller et al. Their goals were to delineate risks of gastrointestinal bleeding for different NOACs compared with warfarin. What can GI clinicians now recommend about gastrointestinal bleeding for patients requiring anticoagulants? While we lack RCTs to give the highest quality of evidence about GIB as a primary outcome, conclusions now depend on the weight of evidence from recent secondary data analyses and I have some recommendations. First, although there may be differences among NOACs in risks of bleeding, all are likely to increase the risk of GI bleeding, comparable with warfarin. Some report that dabigatran and rivaroxaban have a higher risk of GI bleeding than other NOACs or warfarin, but differences are small. Second, some patients who need NOACs/warfarin have increased risks of ulcer bleeds including elderly patients and those with a history of upper GI bleeding, renal or hepatic impairment, low body weight, and concomitant antiplatelet agents. Such high-risk patients warrant treatment with a proton pump inhibitor or histamine2-receptor agonists for primary prevention while on anticoagulants. Finally, for patients with severe ulcer bleeding who require anticoagulation, warfarin or NOACs should be restarted after successful endoscopic hemostasis and proton pump inhibitors, usually within 3-5 days.
Dr. Jensen is professor of medicine at the University of California, Los Angeles; associate director of the CURE: DDRC, where he directs the Human Studies Core; a full-time staff physician in the UCLA division of digestive diseases; and a part-time staff physician in the GI section of the VA Greater Los Angeles Healthcare Center.
Novel oral anticoagulants (NOACs) receive a lot of press now. In randomized controlled trials (RCTs) comparing NOACs to warfarin for prevention of strokes and thromboembolism in atrial fibrillation (AF) and venous thromboembolism (VTE), fewer thromboembolisms are reported, but risks of gastrointestinal bleeding vary. To expand analyses for gastrointestinal bleeding, several systematic reviews and meta-analyses are reported, including this one by CS Miller et al. Their goals were to delineate risks of gastrointestinal bleeding for different NOACs compared with warfarin. What can GI clinicians now recommend about gastrointestinal bleeding for patients requiring anticoagulants? While we lack RCTs to give the highest quality of evidence about GIB as a primary outcome, conclusions now depend on the weight of evidence from recent secondary data analyses and I have some recommendations. First, although there may be differences among NOACs in risks of bleeding, all are likely to increase the risk of GI bleeding, comparable with warfarin. Some report that dabigatran and rivaroxaban have a higher risk of GI bleeding than other NOACs or warfarin, but differences are small. Second, some patients who need NOACs/warfarin have increased risks of ulcer bleeds including elderly patients and those with a history of upper GI bleeding, renal or hepatic impairment, low body weight, and concomitant antiplatelet agents. Such high-risk patients warrant treatment with a proton pump inhibitor or histamine2-receptor agonists for primary prevention while on anticoagulants. Finally, for patients with severe ulcer bleeding who require anticoagulation, warfarin or NOACs should be restarted after successful endoscopic hemostasis and proton pump inhibitors, usually within 3-5 days.
Dr. Jensen is professor of medicine at the University of California, Los Angeles; associate director of the CURE: DDRC, where he directs the Human Studies Core; a full-time staff physician in the UCLA division of digestive diseases; and a part-time staff physician in the GI section of the VA Greater Los Angeles Healthcare Center.
Novel oral anticoagulants (NOACs) receive a lot of press now. In randomized controlled trials (RCTs) comparing NOACs to warfarin for prevention of strokes and thromboembolism in atrial fibrillation (AF) and venous thromboembolism (VTE), fewer thromboembolisms are reported, but risks of gastrointestinal bleeding vary. To expand analyses for gastrointestinal bleeding, several systematic reviews and meta-analyses are reported, including this one by CS Miller et al. Their goals were to delineate risks of gastrointestinal bleeding for different NOACs compared with warfarin. What can GI clinicians now recommend about gastrointestinal bleeding for patients requiring anticoagulants? While we lack RCTs to give the highest quality of evidence about GIB as a primary outcome, conclusions now depend on the weight of evidence from recent secondary data analyses and I have some recommendations. First, although there may be differences among NOACs in risks of bleeding, all are likely to increase the risk of GI bleeding, comparable with warfarin. Some report that dabigatran and rivaroxaban have a higher risk of GI bleeding than other NOACs or warfarin, but differences are small. Second, some patients who need NOACs/warfarin have increased risks of ulcer bleeds including elderly patients and those with a history of upper GI bleeding, renal or hepatic impairment, low body weight, and concomitant antiplatelet agents. Such high-risk patients warrant treatment with a proton pump inhibitor or histamine2-receptor agonists for primary prevention while on anticoagulants. Finally, for patients with severe ulcer bleeding who require anticoagulation, warfarin or NOACs should be restarted after successful endoscopic hemostasis and proton pump inhibitors, usually within 3-5 days.
Dr. Jensen is professor of medicine at the University of California, Los Angeles; associate director of the CURE: DDRC, where he directs the Human Studies Core; a full-time staff physician in the UCLA division of digestive diseases; and a part-time staff physician in the GI section of the VA Greater Los Angeles Healthcare Center.
Compared with conventional anticoagulants, both dabigatran and rivaroxaban conferred small but statistically significant increases in the risk of major gastrointestinal bleeding in a systematic review and meta-analysis of randomized trials reported in the November issue of Clinical Gastroenterology and Hepatology. (doi: 10.1016/j.cgh.2017.04.031)
But other novel oral anticoagulants (NOACs) showed no such effect compared with warfarin, aspirin, or placebo, reported Corey S. Miller, MD, of McGill University, Montreal, and his associates. “The potentially increased risk of GI bleeding associated with dabigatran and rivaroxaban observed in some of our subgroup analyses merits further consideration,” they wrote.
The NOACs (also known as non–vitamin K antagonist oral anticoagulants) help prevent stroke in patients with atrial fibrillation and prevent and treat venous thromboembolism. However, large AF trials have linked all except apixaban to an increased risk of major GI bleeding compared with warfarin. Dabigatran currently is the only NOAC with an approved reversal agent, “making the question of GI bleeding risk even more consequential,” the authors wrote.
They searched the MEDLINE, EMBASE, Cochrane, and ISI Web of Knowledge databases for reports of randomized trials of NOACs for approved indications published between 1980 and January 2016, which identified 43 trials of 166,289 patients. Most used warfarin as the comparator, but one study compared apixaban with aspirin and six studies compared apixaban, rivaroxaban, or dabigatran with placebo. Fifteen trials failed to specify bleeding sources and therefore could not be evaluated for the primary endpoint, the reviewers noted.
In the remaining 28 trials, 1.5% of NOAC recipients developed major GI bleeding, compared with 1.3% of recipients of conventional anticoagulants (odds ratio, 0.98; 95% confidence interval, 0.80-1.21). Five trials of dabigatran showed a 2% risk of major GI bleeding, compared with 1.4% with conventional anticoagulation, a slight but significant increase (OR, 1.27; 95% CI, 1.04-1.55). Eight trials of rivaroxaban showed a similar trend (bleeding risk, 1.7% vs. 1.3%; OR, 1.40; 95% CI, 1.15-1.70). In contrast, subgroup analyses of apixaban and edoxaban found no difference in risk of major GI bleeding versus conventional treatment.
Subgroup analyses by region found no differences except in Asia, where NOACs were associated with a significantly lower odds of major GI bleeding (0.5% and 1.2%, respectively; OR, 0.45; 95% CI, 0.22-0.91).
Most studies did not report minor or nonsevere bleeds or specify bleeding location within the GI tract, the reviewers noted. Given those caveats, NOACs and conventional anticoagulants conferred similar risks of clinically relevant nonmajor bleeding (0.6% and 0.6%, respectively), upper GI bleeding (1.5% and 1.6%), and lower GI bleeding (1.0% and 1.0%).
A post hoc analysis using a random-effects model found no significant difference in risk of major GI bleeding between either rivaroxaban or dabigatran and conventional therapy, the reviewers said. In addition, the increased risk of bleeding with dabigatran was confined to the RELY and ROCKET trials of AF, both of which exposed patients to longer treatment periods. Dabigatran is coated with tartaric acid, which might have a “direct caustic effect on the intestinal lumen,” they wrote. Also, NOACs are incompletely absorbed across the GI mucosa and therefore have some anticoagulant activity in the GI lumen, unlike warfarin or parenteral anticoagulants.
The reviewers disclosed no funding sources. Dr. Miller and another author reported having no conflicts of interest. One author received research grants and speaker honoraria from Boehringer Ingelheim Canada, Bayer Canada, Daiichi Sankyo, Bristol Myers Squibb, and Pfizer Canada; another author disclosed serving as a consultant to Pendopharm, Boston Scientific, and Cook.
Compared with conventional anticoagulants, both dabigatran and rivaroxaban conferred small but statistically significant increases in the risk of major gastrointestinal bleeding in a systematic review and meta-analysis of randomized trials reported in the November issue of Clinical Gastroenterology and Hepatology. (doi: 10.1016/j.cgh.2017.04.031)
But other novel oral anticoagulants (NOACs) showed no such effect compared with warfarin, aspirin, or placebo, reported Corey S. Miller, MD, of McGill University, Montreal, and his associates. “The potentially increased risk of GI bleeding associated with dabigatran and rivaroxaban observed in some of our subgroup analyses merits further consideration,” they wrote.
The NOACs (also known as non–vitamin K antagonist oral anticoagulants) help prevent stroke in patients with atrial fibrillation and prevent and treat venous thromboembolism. However, large AF trials have linked all except apixaban to an increased risk of major GI bleeding compared with warfarin. Dabigatran currently is the only NOAC with an approved reversal agent, “making the question of GI bleeding risk even more consequential,” the authors wrote.
They searched the MEDLINE, EMBASE, Cochrane, and ISI Web of Knowledge databases for reports of randomized trials of NOACs for approved indications published between 1980 and January 2016, which identified 43 trials of 166,289 patients. Most used warfarin as the comparator, but one study compared apixaban with aspirin and six studies compared apixaban, rivaroxaban, or dabigatran with placebo. Fifteen trials failed to specify bleeding sources and therefore could not be evaluated for the primary endpoint, the reviewers noted.
In the remaining 28 trials, 1.5% of NOAC recipients developed major GI bleeding, compared with 1.3% of recipients of conventional anticoagulants (odds ratio, 0.98; 95% confidence interval, 0.80-1.21). Five trials of dabigatran showed a 2% risk of major GI bleeding, compared with 1.4% with conventional anticoagulation, a slight but significant increase (OR, 1.27; 95% CI, 1.04-1.55). Eight trials of rivaroxaban showed a similar trend (bleeding risk, 1.7% vs. 1.3%; OR, 1.40; 95% CI, 1.15-1.70). In contrast, subgroup analyses of apixaban and edoxaban found no difference in risk of major GI bleeding versus conventional treatment.
Subgroup analyses by region found no differences except in Asia, where NOACs were associated with a significantly lower odds of major GI bleeding (0.5% and 1.2%, respectively; OR, 0.45; 95% CI, 0.22-0.91).
Most studies did not report minor or nonsevere bleeds or specify bleeding location within the GI tract, the reviewers noted. Given those caveats, NOACs and conventional anticoagulants conferred similar risks of clinically relevant nonmajor bleeding (0.6% and 0.6%, respectively), upper GI bleeding (1.5% and 1.6%), and lower GI bleeding (1.0% and 1.0%).
A post hoc analysis using a random-effects model found no significant difference in risk of major GI bleeding between either rivaroxaban or dabigatran and conventional therapy, the reviewers said. In addition, the increased risk of bleeding with dabigatran was confined to the RELY and ROCKET trials of AF, both of which exposed patients to longer treatment periods. Dabigatran is coated with tartaric acid, which might have a “direct caustic effect on the intestinal lumen,” they wrote. Also, NOACs are incompletely absorbed across the GI mucosa and therefore have some anticoagulant activity in the GI lumen, unlike warfarin or parenteral anticoagulants.
The reviewers disclosed no funding sources. Dr. Miller and another author reported having no conflicts of interest. One author received research grants and speaker honoraria from Boehringer Ingelheim Canada, Bayer Canada, Daiichi Sankyo, Bristol Myers Squibb, and Pfizer Canada; another author disclosed serving as a consultant to Pendopharm, Boston Scientific, and Cook.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: Compared with conventional anticoagulants, novel oral anticoagulants (NOACs) were not associated with increased risk of major gastrointestinal bleeding, with the possible exception of dabigatran and rivaroxaban.
Major finding: In the overall analysis, risk of major GI bleeding was 1.5% with NOACs and 1.3% with conventional anticoagulants (OR, 0.98; 95% CI, 0.80-1.21). In subgroup analyses, dabigatran conferred a 2% risk of major GI bleeding (OR, 1.3; 95% CI, 1.04-1.55), rivaroxaban conferred a 1.7% risk (OR, 1.40; 95% CI, 1.15-1.70).
Data source: A systematic review and meta-analysis of 43 randomized trials, comprising 166,289 patients.
Disclosures: The reviewers disclosed no funding sources. Dr. Miller and another author reported having no conflicts of interest. One author received research grants and speaker honoraria from Boehringer Ingelheim Canada, Bayer Canada, Daiichi Sankyo, Bristol Myers Squibb, and Pfizer Canada; another author disclosed serving as a consultant to Pendopharm, Boston Scientific, and Cook.
VIDEO: Trial posts null results for Helicobacter screening, eradication
Compared with usual care, screening for and the eradication of Helicobacter pylori infection did not significantly improve the risk of dyspepsia or peptic ulcer disease, use of health care services, or quality of life in a large randomized, controlled trial reported in the November issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.06.006).
After 13 years of follow-up, the prevalence of dyspepsia was 19% in both arms (adjusted odds ratio, 0.93; 95% confidence interval, 0.82-1.04), reported Maria Bomme, MD, of University of Southern Denmark (Odense), and her associates. The cumulative risk of the coprimary endpoint, peptic ulcer disease, was 3% in both groups (risk ratio, 0.93; 95% confidence interval, 0.79-1.09). Screening and eradication also did not affect secondary endpoints such as rates of gastroesophageal reflux, endoscopy, antacid use, or health care utilization, or mental and physical quality of life.
The study “was designed to provide evidence on the effect of H. pylori screening at a population scale,” the researchers wrote. “It showed no significant long-term effect of population screening when compared with current clinical practice in a low-prevalence area.”
SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION
Prior studies have suggested that eradicating H. pylori infection might help prevent peptic ulcers and dyspepsia and could reduce the risk of gastric cancer, the researchers noted. For this trial, they randomly assigned 20,011 adults aged 40-65 years from a single county in Denmark to receive H. pylori screening or usual care. Screening consisted of an outpatient blood test for H. pylori, which was confirmed by 13C-urea breath test (UBT) if positive. Individuals with confirmed infections were offered triple eradication therapy (20 mg omeprazole, 500 mg clarithromycin, and either 1 g amoxicillin or 500 mg metronidazole) twice daily for 1 week. This regimen eradicated 95% of infections, based on UBT results from a subset of 200 individuals.
Compared with nonparticipants, the 12,530 (63%) study enrollees were significantly more likely to be female, 50 years or older, married, and to have a history of peptic ulcer disease. Rates of follow-up were 92% at 1 year, 83% at 5 years, and 69% (8,658 individuals) at 13 years. Among 5,749 screened participants, 17.5% tested positive for H. pylori. Nearly all underwent eradication therapy. At 5 years, screening and eradication were associated with a significant reduction in the incidence of peptic ulcers and associated complications and with modest improvements in dyspepsia, health care visits for dyspepsia, and sick leave days, compared with usual care. But the prevalence of dyspepsia waned in both groups over time and did not significantly differ between groups at 13 years in either the intention-to-treat or per-protocol analysis. Likewise, annual rates of peptic ulcer disease were very similar (1.9 cases/1,000 screened individuals and 2.2 cases/1,000 controls; incidence rate ratio, 0.87; 95% CI, 0.69-1.10). Rates of gastroesophageal cancer also were similar among groups throughout the study.
Screening for and eradicating H. pylori also did not affect the likelihood of dyspepsia or peptic ulcer disease at 13 years among individuals who were dyspeptic at baseline, the researchers said. The relatively low prevalence of H. pylori infection in Denmark might have diluted the effects of screening and eradication, they added.
Funders included the Region of Southern Denmark, the department of clinical research at the University of Southern Denmark, the Odense University Hospital research board, and the Aase and Ejnar Danielsens Foundation, Beckett- Fonden, and Helsefonden. The researchers reported having no conflicts of interest.
Compared with usual care, screening for and the eradication of Helicobacter pylori infection did not significantly improve the risk of dyspepsia or peptic ulcer disease, use of health care services, or quality of life in a large randomized, controlled trial reported in the November issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.06.006).
After 13 years of follow-up, the prevalence of dyspepsia was 19% in both arms (adjusted odds ratio, 0.93; 95% confidence interval, 0.82-1.04), reported Maria Bomme, MD, of University of Southern Denmark (Odense), and her associates. The cumulative risk of the coprimary endpoint, peptic ulcer disease, was 3% in both groups (risk ratio, 0.93; 95% confidence interval, 0.79-1.09). Screening and eradication also did not affect secondary endpoints such as rates of gastroesophageal reflux, endoscopy, antacid use, or health care utilization, or mental and physical quality of life.
The study “was designed to provide evidence on the effect of H. pylori screening at a population scale,” the researchers wrote. “It showed no significant long-term effect of population screening when compared with current clinical practice in a low-prevalence area.”
SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION
Prior studies have suggested that eradicating H. pylori infection might help prevent peptic ulcers and dyspepsia and could reduce the risk of gastric cancer, the researchers noted. For this trial, they randomly assigned 20,011 adults aged 40-65 years from a single county in Denmark to receive H. pylori screening or usual care. Screening consisted of an outpatient blood test for H. pylori, which was confirmed by 13C-urea breath test (UBT) if positive. Individuals with confirmed infections were offered triple eradication therapy (20 mg omeprazole, 500 mg clarithromycin, and either 1 g amoxicillin or 500 mg metronidazole) twice daily for 1 week. This regimen eradicated 95% of infections, based on UBT results from a subset of 200 individuals.
Compared with nonparticipants, the 12,530 (63%) study enrollees were significantly more likely to be female, 50 years or older, married, and to have a history of peptic ulcer disease. Rates of follow-up were 92% at 1 year, 83% at 5 years, and 69% (8,658 individuals) at 13 years. Among 5,749 screened participants, 17.5% tested positive for H. pylori. Nearly all underwent eradication therapy. At 5 years, screening and eradication were associated with a significant reduction in the incidence of peptic ulcers and associated complications and with modest improvements in dyspepsia, health care visits for dyspepsia, and sick leave days, compared with usual care. But the prevalence of dyspepsia waned in both groups over time and did not significantly differ between groups at 13 years in either the intention-to-treat or per-protocol analysis. Likewise, annual rates of peptic ulcer disease were very similar (1.9 cases/1,000 screened individuals and 2.2 cases/1,000 controls; incidence rate ratio, 0.87; 95% CI, 0.69-1.10). Rates of gastroesophageal cancer also were similar among groups throughout the study.
Screening for and eradicating H. pylori also did not affect the likelihood of dyspepsia or peptic ulcer disease at 13 years among individuals who were dyspeptic at baseline, the researchers said. The relatively low prevalence of H. pylori infection in Denmark might have diluted the effects of screening and eradication, they added.
Funders included the Region of Southern Denmark, the department of clinical research at the University of Southern Denmark, the Odense University Hospital research board, and the Aase and Ejnar Danielsens Foundation, Beckett- Fonden, and Helsefonden. The researchers reported having no conflicts of interest.
Compared with usual care, screening for and the eradication of Helicobacter pylori infection did not significantly improve the risk of dyspepsia or peptic ulcer disease, use of health care services, or quality of life in a large randomized, controlled trial reported in the November issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.06.006).
After 13 years of follow-up, the prevalence of dyspepsia was 19% in both arms (adjusted odds ratio, 0.93; 95% confidence interval, 0.82-1.04), reported Maria Bomme, MD, of University of Southern Denmark (Odense), and her associates. The cumulative risk of the coprimary endpoint, peptic ulcer disease, was 3% in both groups (risk ratio, 0.93; 95% confidence interval, 0.79-1.09). Screening and eradication also did not affect secondary endpoints such as rates of gastroesophageal reflux, endoscopy, antacid use, or health care utilization, or mental and physical quality of life.
The study “was designed to provide evidence on the effect of H. pylori screening at a population scale,” the researchers wrote. “It showed no significant long-term effect of population screening when compared with current clinical practice in a low-prevalence area.”
SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION
Prior studies have suggested that eradicating H. pylori infection might help prevent peptic ulcers and dyspepsia and could reduce the risk of gastric cancer, the researchers noted. For this trial, they randomly assigned 20,011 adults aged 40-65 years from a single county in Denmark to receive H. pylori screening or usual care. Screening consisted of an outpatient blood test for H. pylori, which was confirmed by 13C-urea breath test (UBT) if positive. Individuals with confirmed infections were offered triple eradication therapy (20 mg omeprazole, 500 mg clarithromycin, and either 1 g amoxicillin or 500 mg metronidazole) twice daily for 1 week. This regimen eradicated 95% of infections, based on UBT results from a subset of 200 individuals.
Compared with nonparticipants, the 12,530 (63%) study enrollees were significantly more likely to be female, 50 years or older, married, and to have a history of peptic ulcer disease. Rates of follow-up were 92% at 1 year, 83% at 5 years, and 69% (8,658 individuals) at 13 years. Among 5,749 screened participants, 17.5% tested positive for H. pylori. Nearly all underwent eradication therapy. At 5 years, screening and eradication were associated with a significant reduction in the incidence of peptic ulcers and associated complications and with modest improvements in dyspepsia, health care visits for dyspepsia, and sick leave days, compared with usual care. But the prevalence of dyspepsia waned in both groups over time and did not significantly differ between groups at 13 years in either the intention-to-treat or per-protocol analysis. Likewise, annual rates of peptic ulcer disease were very similar (1.9 cases/1,000 screened individuals and 2.2 cases/1,000 controls; incidence rate ratio, 0.87; 95% CI, 0.69-1.10). Rates of gastroesophageal cancer also were similar among groups throughout the study.
Screening for and eradicating H. pylori also did not affect the likelihood of dyspepsia or peptic ulcer disease at 13 years among individuals who were dyspeptic at baseline, the researchers said. The relatively low prevalence of H. pylori infection in Denmark might have diluted the effects of screening and eradication, they added.
Funders included the Region of Southern Denmark, the department of clinical research at the University of Southern Denmark, the Odense University Hospital research board, and the Aase and Ejnar Danielsens Foundation, Beckett- Fonden, and Helsefonden. The researchers reported having no conflicts of interest.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: Screening for and eradicating H. pylori infections did not significantly improve long-term prevalence of dyspepsia, incidence of peptic ulcer disease, use of health care services, or quality of life.
Major finding: At 13-year follow-up, both arms had a 19% prevalence of dyspepsia (aOR, 0.93; 95% CI, 0.82-1.04) and a 3% cumulative incidence of peptic ulcer disease (RR, 0.93; 95% CI, 0.79-1.09).
Data source: A randomized controlled trial of 8,658 adults aged 40-65 years
Disclosures: Funders included the Region of Southern Denmark, the department of clinical research at the University of Southern Denmark, the Odense University Hospital research board, and the Aase and Ejnar Danielsens Foundation, Beckett- Fonden, and Helsefonden. The researchers reported having no conflicts of interest.
Leukocyte activation test–based elimination diet improves IBS symptoms
Elimination diets guided by leukocyte activation tests reduced symptoms in patients with irritable bowel syndrome (IBS) in a parallel-group, double-blind, randomized controlled trial.
Study participants were randomized to a 4-week diet with individualized guidance to either eliminate foods with positive assay results and to allow foods with negative assay results (intervention group), or to eliminate foods with negative assay results and allow foods with positive assay results (comparison group). The 29 patients in the intervention group had significantly greater increases in mean IBS Global Improvement Scale scores at 4 weeks and 8 weeks vs. the 29 patients in the comparison group (mean between-group differences, 0.86 and 1.22 points, respectively), reported Ather Ali, ND, of Yale University, New Haven, Conn., and colleagues (BMJ Open Gastro. 2017;0:e000164. doi: 10.1136/bmjgast-2017-000164).
Improvements were seen in IBS Adequate Relief and Quality of Life scores in the intervention group, but the differences between the groups were not statistically significant. No adverse effects related to the intervention were reported, they said.
Of note, strong responders in the intervention group experienced significant reductions in neutrophil elastase.
IBS is a prevalent, costly, and often disabling condition, but assessing food intolerance in clinical practice is challenging, the investigators said, adding that while a number of commercially available blood tests claim to diagnose food intolerance – including leukocyte activation tests, which are among the most widely used for this purpose – no rigorous studies of the tests have been published.
For the current study, adults aged 18-75 years who met Rome III criteria for any subtype of IBS and had active symptoms were enrolled from an academic health center in Connecticut. The leukocyte activation test was used to culture peripheral blood leukocytes with standardized individual food extracts, producing either a positive or negative result, which then guided the food elimination.
The findings demonstrate that “a diet guided by leukocyte activation testing results in demonstrable clinical improvement in IBS,” they wrote, noting that dietary changes based on a leukocyte activation test may be less restrictive than those associated with a low–fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (low FODMAPs) diet (which has also shown promise as “an efficacious, although burdensome, dietary intervention for IBS”), and may result in better long-term adherence.
“These clinical results, associated with a reduction in plasma neutrophil elastase, have implication for better understanding the role of food intolerance and the pathophysiology of IBS,” they said, adding that “future studies, ideally multisite and in larger samples, can assess comparative effects of other dietary interventions in IBS, the effects of restricting specific foods, and whether dietary changes guided by leukocyte activation testing affect other conditions.”
Cell Science Systems funded the study. The authors reported having no disclosures.
Elimination diets guided by leukocyte activation tests reduced symptoms in patients with irritable bowel syndrome (IBS) in a parallel-group, double-blind, randomized controlled trial.
Study participants were randomized to a 4-week diet with individualized guidance to either eliminate foods with positive assay results and to allow foods with negative assay results (intervention group), or to eliminate foods with negative assay results and allow foods with positive assay results (comparison group). The 29 patients in the intervention group had significantly greater increases in mean IBS Global Improvement Scale scores at 4 weeks and 8 weeks vs. the 29 patients in the comparison group (mean between-group differences, 0.86 and 1.22 points, respectively), reported Ather Ali, ND, of Yale University, New Haven, Conn., and colleagues (BMJ Open Gastro. 2017;0:e000164. doi: 10.1136/bmjgast-2017-000164).
Improvements were seen in IBS Adequate Relief and Quality of Life scores in the intervention group, but the differences between the groups were not statistically significant. No adverse effects related to the intervention were reported, they said.
Of note, strong responders in the intervention group experienced significant reductions in neutrophil elastase.
IBS is a prevalent, costly, and often disabling condition, but assessing food intolerance in clinical practice is challenging, the investigators said, adding that while a number of commercially available blood tests claim to diagnose food intolerance – including leukocyte activation tests, which are among the most widely used for this purpose – no rigorous studies of the tests have been published.
For the current study, adults aged 18-75 years who met Rome III criteria for any subtype of IBS and had active symptoms were enrolled from an academic health center in Connecticut. The leukocyte activation test was used to culture peripheral blood leukocytes with standardized individual food extracts, producing either a positive or negative result, which then guided the food elimination.
The findings demonstrate that “a diet guided by leukocyte activation testing results in demonstrable clinical improvement in IBS,” they wrote, noting that dietary changes based on a leukocyte activation test may be less restrictive than those associated with a low–fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (low FODMAPs) diet (which has also shown promise as “an efficacious, although burdensome, dietary intervention for IBS”), and may result in better long-term adherence.
“These clinical results, associated with a reduction in plasma neutrophil elastase, have implication for better understanding the role of food intolerance and the pathophysiology of IBS,” they said, adding that “future studies, ideally multisite and in larger samples, can assess comparative effects of other dietary interventions in IBS, the effects of restricting specific foods, and whether dietary changes guided by leukocyte activation testing affect other conditions.”
Cell Science Systems funded the study. The authors reported having no disclosures.
Elimination diets guided by leukocyte activation tests reduced symptoms in patients with irritable bowel syndrome (IBS) in a parallel-group, double-blind, randomized controlled trial.
Study participants were randomized to a 4-week diet with individualized guidance to either eliminate foods with positive assay results and to allow foods with negative assay results (intervention group), or to eliminate foods with negative assay results and allow foods with positive assay results (comparison group). The 29 patients in the intervention group had significantly greater increases in mean IBS Global Improvement Scale scores at 4 weeks and 8 weeks vs. the 29 patients in the comparison group (mean between-group differences, 0.86 and 1.22 points, respectively), reported Ather Ali, ND, of Yale University, New Haven, Conn., and colleagues (BMJ Open Gastro. 2017;0:e000164. doi: 10.1136/bmjgast-2017-000164).
Improvements were seen in IBS Adequate Relief and Quality of Life scores in the intervention group, but the differences between the groups were not statistically significant. No adverse effects related to the intervention were reported, they said.
Of note, strong responders in the intervention group experienced significant reductions in neutrophil elastase.
IBS is a prevalent, costly, and often disabling condition, but assessing food intolerance in clinical practice is challenging, the investigators said, adding that while a number of commercially available blood tests claim to diagnose food intolerance – including leukocyte activation tests, which are among the most widely used for this purpose – no rigorous studies of the tests have been published.
For the current study, adults aged 18-75 years who met Rome III criteria for any subtype of IBS and had active symptoms were enrolled from an academic health center in Connecticut. The leukocyte activation test was used to culture peripheral blood leukocytes with standardized individual food extracts, producing either a positive or negative result, which then guided the food elimination.
The findings demonstrate that “a diet guided by leukocyte activation testing results in demonstrable clinical improvement in IBS,” they wrote, noting that dietary changes based on a leukocyte activation test may be less restrictive than those associated with a low–fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (low FODMAPs) diet (which has also shown promise as “an efficacious, although burdensome, dietary intervention for IBS”), and may result in better long-term adherence.
“These clinical results, associated with a reduction in plasma neutrophil elastase, have implication for better understanding the role of food intolerance and the pathophysiology of IBS,” they said, adding that “future studies, ideally multisite and in larger samples, can assess comparative effects of other dietary interventions in IBS, the effects of restricting specific foods, and whether dietary changes guided by leukocyte activation testing affect other conditions.”
Cell Science Systems funded the study. The authors reported having no disclosures.
FROM BMJ OPEN GASTROENTEROLOGY
Key clinical point:
Major finding: Mean IBS Global Improvement Scale scores improved significantly more in the intervention vs. comparison group at 4 weeks and 8 weeks (mean between-group differences of 0.86 and 1.22 points, respectively).
Data source: A parallel-group, double-blind, randomized controlled trial of 58 IBS patients.
Disclosures: Cell Science Systems funded the study. The authors reported having no disclosures.
Study shows childhood IBD increased cancer risk in adulthood
Children who had developed inflammatory bowel disease had an 18-fold greater risk of gastrointestinal cancers in later life, a new study suggests.
The cohort study found that the risk of all cancers was elevated in individuals with childhood-onset inflammatory bowel disease, but particularly in those with primary sclerosing cholangitis and ulcerative colitis.
Researchers followed 9,405 patients with childhood-onset inflammatory bowel disease to a mean age of 27 years using a Swedish national patient register (BMJ. 2017 Sep 21. doi: 10.1136/bmj.j3951).
Analysis revealed that individuals with childhood-onset inflammatory bowel disease had double the risk of any cancer, compared with the general population (hazard ratio, 2.2; 95% confidence interval, 2.0-2.5), and a 2.7-fold greater risk of developing cancer before the age of 18 years.
Primary sclerosing cholangitis was associated with a sixfold greater risk of cancer, ulcerative colitis was associated with a 2.6-fold greater risk, and patients who had had colitis for 10 years or more had a nearly fourfold greater risk of cancer (HR, 3.9).
The study also found that childhood-onset inflammatory bowel disease was associated with an 18-fold greater risk of gastrointestinal cancer, compared with the general population, matched for age, sex, birth year, and county.
The risk was particularly high in patients with ulcerative colitis, who showed a 33-fold higher risk of colorectal cancer, while patients with Crohn’s disease had a nearly 6-fold higher risk.
“Colorectal cancer is a major cause of cancer mortality in the population, and even a moderately increased incidence is likely to have a large effect on patients with inflammatory bowel disease,” wrote Ola Olén, MD, of Karolinska Institutet, Stockholm, and coauthors.
When the researchers looked in more detail at the type of cancers, they saw the greatest increases in risk were for colorectal cancer (HR, 19.5) and small intestinal cancer (HR, 12.8), while the risk of liver cancer was 134 times higher (95% CI, 59.6-382).
The researchers also saw a 2.7-fold increased risk of lymphoid neoplasms associated with childhood inflammatory bowel disease, particularly in individuals with ulcerative colitis or Crohn’s disease. The most common lymphoid neoplasms were non-Hodgkin lymphomas, followed by Hodgkin lymphomas.
Commenting on possible explanations for the associations seen in the study, the authors said that patients with inflammatory bowel disease may have their gastrointestinal cancers diagnosed earlier than the general population because of regular endoscopies.
They also said that thiopurines and TNF inhibitors – both used to treat inflammatory bowel disease – could not be ruled out as a possible cause of the increase in cancer risk, but their study was not powered to pick up such an effect.
“Instead, we suggest that extent and duration of chronic inflammation might be the main driving mechanisms underlying the increased risk of cancer,” they wrote.
The authors noted that their study did not include data on the smoking status of individuals, which could be significant, because smoking is known to reduce the risk of ulcerative colitis and increase the risk of Crohn’s disease and cancer. However, they pointed out that the majority of patients would not have been smoking at the time of their initial inflammatory bowel disease diagnosis, and would have been unlikely to take up the habit after their diagnosis.
With the observation that the risk of cancer in inflammatory bowel disease was higher in patients who were younger when diagnosed with the disease, the authors suggested that age of onset be considered when designing surveillance strategies for cancer in this group.
The Stockholm County Council and the Karolinska Institutet, the Swedish Cancer Society, the Swedish Research Council, and the Swedish Foundation for Strategic Research supported the study. One author received grants from the Swedish Medical Society, Magtarmfonden, the Jane and Dan Olsson Foundation, the Mjölkdroppen Foundation, the Bengt Ihre Research Fellowship in gastroenterology, and the Karolinska Institutet Foundations. No conflicts of interest were declared.
Children who had developed inflammatory bowel disease had an 18-fold greater risk of gastrointestinal cancers in later life, a new study suggests.
The cohort study found that the risk of all cancers was elevated in individuals with childhood-onset inflammatory bowel disease, but particularly in those with primary sclerosing cholangitis and ulcerative colitis.
Researchers followed 9,405 patients with childhood-onset inflammatory bowel disease to a mean age of 27 years using a Swedish national patient register (BMJ. 2017 Sep 21. doi: 10.1136/bmj.j3951).
Analysis revealed that individuals with childhood-onset inflammatory bowel disease had double the risk of any cancer, compared with the general population (hazard ratio, 2.2; 95% confidence interval, 2.0-2.5), and a 2.7-fold greater risk of developing cancer before the age of 18 years.
Primary sclerosing cholangitis was associated with a sixfold greater risk of cancer, ulcerative colitis was associated with a 2.6-fold greater risk, and patients who had had colitis for 10 years or more had a nearly fourfold greater risk of cancer (HR, 3.9).
The study also found that childhood-onset inflammatory bowel disease was associated with an 18-fold greater risk of gastrointestinal cancer, compared with the general population, matched for age, sex, birth year, and county.
The risk was particularly high in patients with ulcerative colitis, who showed a 33-fold higher risk of colorectal cancer, while patients with Crohn’s disease had a nearly 6-fold higher risk.
“Colorectal cancer is a major cause of cancer mortality in the population, and even a moderately increased incidence is likely to have a large effect on patients with inflammatory bowel disease,” wrote Ola Olén, MD, of Karolinska Institutet, Stockholm, and coauthors.
When the researchers looked in more detail at the type of cancers, they saw the greatest increases in risk were for colorectal cancer (HR, 19.5) and small intestinal cancer (HR, 12.8), while the risk of liver cancer was 134 times higher (95% CI, 59.6-382).
The researchers also saw a 2.7-fold increased risk of lymphoid neoplasms associated with childhood inflammatory bowel disease, particularly in individuals with ulcerative colitis or Crohn’s disease. The most common lymphoid neoplasms were non-Hodgkin lymphomas, followed by Hodgkin lymphomas.
Commenting on possible explanations for the associations seen in the study, the authors said that patients with inflammatory bowel disease may have their gastrointestinal cancers diagnosed earlier than the general population because of regular endoscopies.
They also said that thiopurines and TNF inhibitors – both used to treat inflammatory bowel disease – could not be ruled out as a possible cause of the increase in cancer risk, but their study was not powered to pick up such an effect.
“Instead, we suggest that extent and duration of chronic inflammation might be the main driving mechanisms underlying the increased risk of cancer,” they wrote.
The authors noted that their study did not include data on the smoking status of individuals, which could be significant, because smoking is known to reduce the risk of ulcerative colitis and increase the risk of Crohn’s disease and cancer. However, they pointed out that the majority of patients would not have been smoking at the time of their initial inflammatory bowel disease diagnosis, and would have been unlikely to take up the habit after their diagnosis.
With the observation that the risk of cancer in inflammatory bowel disease was higher in patients who were younger when diagnosed with the disease, the authors suggested that age of onset be considered when designing surveillance strategies for cancer in this group.
The Stockholm County Council and the Karolinska Institutet, the Swedish Cancer Society, the Swedish Research Council, and the Swedish Foundation for Strategic Research supported the study. One author received grants from the Swedish Medical Society, Magtarmfonden, the Jane and Dan Olsson Foundation, the Mjölkdroppen Foundation, the Bengt Ihre Research Fellowship in gastroenterology, and the Karolinska Institutet Foundations. No conflicts of interest were declared.
Children who had developed inflammatory bowel disease had an 18-fold greater risk of gastrointestinal cancers in later life, a new study suggests.
The cohort study found that the risk of all cancers was elevated in individuals with childhood-onset inflammatory bowel disease, but particularly in those with primary sclerosing cholangitis and ulcerative colitis.
Researchers followed 9,405 patients with childhood-onset inflammatory bowel disease to a mean age of 27 years using a Swedish national patient register (BMJ. 2017 Sep 21. doi: 10.1136/bmj.j3951).
Analysis revealed that individuals with childhood-onset inflammatory bowel disease had double the risk of any cancer, compared with the general population (hazard ratio, 2.2; 95% confidence interval, 2.0-2.5), and a 2.7-fold greater risk of developing cancer before the age of 18 years.
Primary sclerosing cholangitis was associated with a sixfold greater risk of cancer, ulcerative colitis was associated with a 2.6-fold greater risk, and patients who had had colitis for 10 years or more had a nearly fourfold greater risk of cancer (HR, 3.9).
The study also found that childhood-onset inflammatory bowel disease was associated with an 18-fold greater risk of gastrointestinal cancer, compared with the general population, matched for age, sex, birth year, and county.
The risk was particularly high in patients with ulcerative colitis, who showed a 33-fold higher risk of colorectal cancer, while patients with Crohn’s disease had a nearly 6-fold higher risk.
“Colorectal cancer is a major cause of cancer mortality in the population, and even a moderately increased incidence is likely to have a large effect on patients with inflammatory bowel disease,” wrote Ola Olén, MD, of Karolinska Institutet, Stockholm, and coauthors.
When the researchers looked in more detail at the type of cancers, they saw the greatest increases in risk were for colorectal cancer (HR, 19.5) and small intestinal cancer (HR, 12.8), while the risk of liver cancer was 134 times higher (95% CI, 59.6-382).
The researchers also saw a 2.7-fold increased risk of lymphoid neoplasms associated with childhood inflammatory bowel disease, particularly in individuals with ulcerative colitis or Crohn’s disease. The most common lymphoid neoplasms were non-Hodgkin lymphomas, followed by Hodgkin lymphomas.
Commenting on possible explanations for the associations seen in the study, the authors said that patients with inflammatory bowel disease may have their gastrointestinal cancers diagnosed earlier than the general population because of regular endoscopies.
They also said that thiopurines and TNF inhibitors – both used to treat inflammatory bowel disease – could not be ruled out as a possible cause of the increase in cancer risk, but their study was not powered to pick up such an effect.
“Instead, we suggest that extent and duration of chronic inflammation might be the main driving mechanisms underlying the increased risk of cancer,” they wrote.
The authors noted that their study did not include data on the smoking status of individuals, which could be significant, because smoking is known to reduce the risk of ulcerative colitis and increase the risk of Crohn’s disease and cancer. However, they pointed out that the majority of patients would not have been smoking at the time of their initial inflammatory bowel disease diagnosis, and would have been unlikely to take up the habit after their diagnosis.
With the observation that the risk of cancer in inflammatory bowel disease was higher in patients who were younger when diagnosed with the disease, the authors suggested that age of onset be considered when designing surveillance strategies for cancer in this group.
The Stockholm County Council and the Karolinska Institutet, the Swedish Cancer Society, the Swedish Research Council, and the Swedish Foundation for Strategic Research supported the study. One author received grants from the Swedish Medical Society, Magtarmfonden, the Jane and Dan Olsson Foundation, the Mjölkdroppen Foundation, the Bengt Ihre Research Fellowship in gastroenterology, and the Karolinska Institutet Foundations. No conflicts of interest were declared.
FROM BMJ
Key clinical point: Childhood inflammatory bowel disease was associated with significant increases in the risk of cancer – particularly gastrointestinal cancer – in later life.
Major finding: Individuals diagnosed with inflammatory bowel disease in childhood have an 18-fold greater risk of gastrointestinal cancer, and a twofold higher risk of any cancer, compared with the general population.
Data source: A cohort study of 9,405 patients with childhood-onset inflammatory bowel disease.
Disclosures: The Stockholm County Council and the Karolinska Institutet, the Swedish Cancer Society, the Swedish Research Council, and the Swedish Foundation for Strategic Research supported the study. One author received grants from the Swedish Medical Society, Magtarmfonden, the Jane and Dan Olsson Foundation, the Mjölkdroppen Foundation, the Bengt Ihre Research Fellowship in gastroenterology, and the Karolinska Institutet Foundations. No conflicts of interest were declared.
It’s a beautiful day to discuss inflammatory bowel disease
Uma Mahadevan, MD, AGAF, and I moderated this session on IBD, and we were fortunate enough to secure four of the best IBD educators in the AGA.
David Rubin, MD, AGAF, opened with “Selecting the correct therapy for your outpatients with IBD: From mesalamine to biologics.” Treatment goals have evolved from symptom control to remission based on measures of inflammation (e.g., serum C-reactive protein, fecal calprotectin, or endoscopy). For ulcerative colitis (UC), high-risk markers include extensive disease, deep ulcers, younger age at diagnosis, elevated biomarkers, and early need for steroids or hospitalization. For Crohn’s disease (CD), these include younger age, extensive involvement, and fistulizing disease. The 5-aminosalicylate drugs remain a backbone in mild to moderate UC. Judicious use of corticosteroids is reasonable, but we need an exit strategy. The thiopurines are decent drugs, but studies have called into question their efficacy as monotherapy, and safety issues persist. Methotrexate is underutilized. The anti–tumor necrosis factor (TNF) biologics are excellent therapies but controversies persist as to whether these drugs require combination therapy or if they can be managed as “optimized monotherapy” with therapeutic drug monitoring (TDM). There are now two infliximab biosimilars available in the U.S.. Vedolizumab is an efficacious gut-selective anti-integrin (for both CD and UC). Ustekinumab, an anti-IL-12/23 antibody, is now available for moderate to severe CD, and has a favorable safety profile.
Fernando Velayos, MD, AGAF, discussed “Surveillance for dysplasia: What is the standard of care in 2017?” General principles for surveillance colonoscopy in IBD include having quiescent disease, since inflammation can reduce ability to detect lesions, and good colonic preparation. The three U.S. society guidelines recommend starting surveillance after 8 years of disease. Patients with concomitant primary schlerosing cholangitis should begin surveillance immediately. Frequency of surveillance ranges every 1-3 years depending on histology. A meta-analysis showed a higher incremental dysplasia yield with chromoendoscopy compared to standard white-light colonoscopy. If visible dysplasia can be endoscopically resected, then continued surveillance rather than colectomy is recommended.
Sunanda Kane, MD, AGAF, discussed “Managing special populations: the transitioning adolescent, the gravid, and the elderly.” The transition from pediatric to adult IBD care is a high-risk time because the patient may be lost to follow-up or not adhere to the medical regimen, resulting in increased risk of flare. Successful transition requires developmental maturity of the patient, a certain style of parental involvement, and care coordination of the medical team. For women with IBD considering pregnancy, active IBD at the time of conception significantly increases the risk of flare. Women with CD who have no history of perianal disease don’t have an increased risk of perianal disease with vaginal delivery. A meta-analysis of the risk of congenital malformations with thiopurines found no significant association. Infliximab levels were likely to rise in the mother during the second and third trimesters (versus no increase with adalimumab), so one could consider TDM to guide dosing. In the PIANO study, anti-TNF therapy in the third trimester was neither associated with adverse pregnancy outcomes nor with infections up to 1 year for children. Patients who develop IBD later in life are more likely to have colonic inflammation. Elderly UC patients are more likely to require surgery, and postop mortality is higher for both CD and UC.
This is a summary provided by the moderator of one of the AGA Postgraduate Courses held at DDW 2017. Dr. Loftus is a professor of medicine, division of gastroenterology and hepatology, Mayo Clinic, Rochester, Minn.
Uma Mahadevan, MD, AGAF, and I moderated this session on IBD, and we were fortunate enough to secure four of the best IBD educators in the AGA.
David Rubin, MD, AGAF, opened with “Selecting the correct therapy for your outpatients with IBD: From mesalamine to biologics.” Treatment goals have evolved from symptom control to remission based on measures of inflammation (e.g., serum C-reactive protein, fecal calprotectin, or endoscopy). For ulcerative colitis (UC), high-risk markers include extensive disease, deep ulcers, younger age at diagnosis, elevated biomarkers, and early need for steroids or hospitalization. For Crohn’s disease (CD), these include younger age, extensive involvement, and fistulizing disease. The 5-aminosalicylate drugs remain a backbone in mild to moderate UC. Judicious use of corticosteroids is reasonable, but we need an exit strategy. The thiopurines are decent drugs, but studies have called into question their efficacy as monotherapy, and safety issues persist. Methotrexate is underutilized. The anti–tumor necrosis factor (TNF) biologics are excellent therapies but controversies persist as to whether these drugs require combination therapy or if they can be managed as “optimized monotherapy” with therapeutic drug monitoring (TDM). There are now two infliximab biosimilars available in the U.S.. Vedolizumab is an efficacious gut-selective anti-integrin (for both CD and UC). Ustekinumab, an anti-IL-12/23 antibody, is now available for moderate to severe CD, and has a favorable safety profile.
Fernando Velayos, MD, AGAF, discussed “Surveillance for dysplasia: What is the standard of care in 2017?” General principles for surveillance colonoscopy in IBD include having quiescent disease, since inflammation can reduce ability to detect lesions, and good colonic preparation. The three U.S. society guidelines recommend starting surveillance after 8 years of disease. Patients with concomitant primary schlerosing cholangitis should begin surveillance immediately. Frequency of surveillance ranges every 1-3 years depending on histology. A meta-analysis showed a higher incremental dysplasia yield with chromoendoscopy compared to standard white-light colonoscopy. If visible dysplasia can be endoscopically resected, then continued surveillance rather than colectomy is recommended.
Sunanda Kane, MD, AGAF, discussed “Managing special populations: the transitioning adolescent, the gravid, and the elderly.” The transition from pediatric to adult IBD care is a high-risk time because the patient may be lost to follow-up or not adhere to the medical regimen, resulting in increased risk of flare. Successful transition requires developmental maturity of the patient, a certain style of parental involvement, and care coordination of the medical team. For women with IBD considering pregnancy, active IBD at the time of conception significantly increases the risk of flare. Women with CD who have no history of perianal disease don’t have an increased risk of perianal disease with vaginal delivery. A meta-analysis of the risk of congenital malformations with thiopurines found no significant association. Infliximab levels were likely to rise in the mother during the second and third trimesters (versus no increase with adalimumab), so one could consider TDM to guide dosing. In the PIANO study, anti-TNF therapy in the third trimester was neither associated with adverse pregnancy outcomes nor with infections up to 1 year for children. Patients who develop IBD later in life are more likely to have colonic inflammation. Elderly UC patients are more likely to require surgery, and postop mortality is higher for both CD and UC.
This is a summary provided by the moderator of one of the AGA Postgraduate Courses held at DDW 2017. Dr. Loftus is a professor of medicine, division of gastroenterology and hepatology, Mayo Clinic, Rochester, Minn.
Uma Mahadevan, MD, AGAF, and I moderated this session on IBD, and we were fortunate enough to secure four of the best IBD educators in the AGA.
David Rubin, MD, AGAF, opened with “Selecting the correct therapy for your outpatients with IBD: From mesalamine to biologics.” Treatment goals have evolved from symptom control to remission based on measures of inflammation (e.g., serum C-reactive protein, fecal calprotectin, or endoscopy). For ulcerative colitis (UC), high-risk markers include extensive disease, deep ulcers, younger age at diagnosis, elevated biomarkers, and early need for steroids or hospitalization. For Crohn’s disease (CD), these include younger age, extensive involvement, and fistulizing disease. The 5-aminosalicylate drugs remain a backbone in mild to moderate UC. Judicious use of corticosteroids is reasonable, but we need an exit strategy. The thiopurines are decent drugs, but studies have called into question their efficacy as monotherapy, and safety issues persist. Methotrexate is underutilized. The anti–tumor necrosis factor (TNF) biologics are excellent therapies but controversies persist as to whether these drugs require combination therapy or if they can be managed as “optimized monotherapy” with therapeutic drug monitoring (TDM). There are now two infliximab biosimilars available in the U.S.. Vedolizumab is an efficacious gut-selective anti-integrin (for both CD and UC). Ustekinumab, an anti-IL-12/23 antibody, is now available for moderate to severe CD, and has a favorable safety profile.
Fernando Velayos, MD, AGAF, discussed “Surveillance for dysplasia: What is the standard of care in 2017?” General principles for surveillance colonoscopy in IBD include having quiescent disease, since inflammation can reduce ability to detect lesions, and good colonic preparation. The three U.S. society guidelines recommend starting surveillance after 8 years of disease. Patients with concomitant primary schlerosing cholangitis should begin surveillance immediately. Frequency of surveillance ranges every 1-3 years depending on histology. A meta-analysis showed a higher incremental dysplasia yield with chromoendoscopy compared to standard white-light colonoscopy. If visible dysplasia can be endoscopically resected, then continued surveillance rather than colectomy is recommended.
Sunanda Kane, MD, AGAF, discussed “Managing special populations: the transitioning adolescent, the gravid, and the elderly.” The transition from pediatric to adult IBD care is a high-risk time because the patient may be lost to follow-up or not adhere to the medical regimen, resulting in increased risk of flare. Successful transition requires developmental maturity of the patient, a certain style of parental involvement, and care coordination of the medical team. For women with IBD considering pregnancy, active IBD at the time of conception significantly increases the risk of flare. Women with CD who have no history of perianal disease don’t have an increased risk of perianal disease with vaginal delivery. A meta-analysis of the risk of congenital malformations with thiopurines found no significant association. Infliximab levels were likely to rise in the mother during the second and third trimesters (versus no increase with adalimumab), so one could consider TDM to guide dosing. In the PIANO study, anti-TNF therapy in the third trimester was neither associated with adverse pregnancy outcomes nor with infections up to 1 year for children. Patients who develop IBD later in life are more likely to have colonic inflammation. Elderly UC patients are more likely to require surgery, and postop mortality is higher for both CD and UC.
This is a summary provided by the moderator of one of the AGA Postgraduate Courses held at DDW 2017. Dr. Loftus is a professor of medicine, division of gastroenterology and hepatology, Mayo Clinic, Rochester, Minn.
Bezlotoxumab may lower risk of C. difficile readmissions
Clostridium difficile infection (CDI) patients treated with bezlotoxumab were less likely to be readmitted for recurring symptoms within 30 days of discharge, according to a phase 3 trial funded by Merck.
Recurrent CDI is a burden on both patients and providers, increasing health risks with each recurrence and eating through hospital resources, according to Vimalanand S. Prabhu, PhD, associate principal scientist for Merck.
In a randomized, double-blind, placebo-controlled, study of 1,050 CDI patients, a total of 27 (5%) of 530 of those given bezlotoxumab were re-hospitalized 30 days after discharge, compared with 58 (11%) of 520 patients in the placebo group (Clin Infect Dis. 2017 Aug 11. doi. 10.1093/cid/cix523).
Patients were gathered from 322 sites across 30 countries between November 2011 and May 2015.
When measuring CDI-related readmissions, the investigators found use of bezlotoxumab reduced rCDI hospitalizations by 6%, and by approximately 8% in high-risk patients, such as those over 65 years old or with severe CDI.
Bezlotoxumab works by binding to CDI toxin B, a primary cause of CDI symptoms, according to Dr. Prabhu and fellow investigators. The researchers suggested that bezlotoxumab could be a prevailing factor in fighting the rate of CDI infections, which accounted for 29,000 deaths in 2011 (N Engl J Med. 2015 Jun 11;372[24]:2368-9).
Investigators acknowledged that patients admitted for the study may be healthier than the real-world CDI population.
All investigators reported some financial involvement, whether being a full-time employee or acting as a consultant, for Merck, which funded the study. Individually, investigators reported financial ties to similar medical companies, such as Pfizer and AstraZeneca.
AGA offers patient education materials on C. diff that can help your patients better understand the infection. Learn more at http://www.gastro.org/patient-care/conditions-diseases/clostridium-difficile-infection.
[email protected]
On Twitter @eaztweets
Clostridium difficile infection (CDI) patients treated with bezlotoxumab were less likely to be readmitted for recurring symptoms within 30 days of discharge, according to a phase 3 trial funded by Merck.
Recurrent CDI is a burden on both patients and providers, increasing health risks with each recurrence and eating through hospital resources, according to Vimalanand S. Prabhu, PhD, associate principal scientist for Merck.
In a randomized, double-blind, placebo-controlled, study of 1,050 CDI patients, a total of 27 (5%) of 530 of those given bezlotoxumab were re-hospitalized 30 days after discharge, compared with 58 (11%) of 520 patients in the placebo group (Clin Infect Dis. 2017 Aug 11. doi. 10.1093/cid/cix523).
Patients were gathered from 322 sites across 30 countries between November 2011 and May 2015.
When measuring CDI-related readmissions, the investigators found use of bezlotoxumab reduced rCDI hospitalizations by 6%, and by approximately 8% in high-risk patients, such as those over 65 years old or with severe CDI.
Bezlotoxumab works by binding to CDI toxin B, a primary cause of CDI symptoms, according to Dr. Prabhu and fellow investigators. The researchers suggested that bezlotoxumab could be a prevailing factor in fighting the rate of CDI infections, which accounted for 29,000 deaths in 2011 (N Engl J Med. 2015 Jun 11;372[24]:2368-9).
Investigators acknowledged that patients admitted for the study may be healthier than the real-world CDI population.
All investigators reported some financial involvement, whether being a full-time employee or acting as a consultant, for Merck, which funded the study. Individually, investigators reported financial ties to similar medical companies, such as Pfizer and AstraZeneca.
AGA offers patient education materials on C. diff that can help your patients better understand the infection. Learn more at http://www.gastro.org/patient-care/conditions-diseases/clostridium-difficile-infection.
[email protected]
On Twitter @eaztweets
Clostridium difficile infection (CDI) patients treated with bezlotoxumab were less likely to be readmitted for recurring symptoms within 30 days of discharge, according to a phase 3 trial funded by Merck.
Recurrent CDI is a burden on both patients and providers, increasing health risks with each recurrence and eating through hospital resources, according to Vimalanand S. Prabhu, PhD, associate principal scientist for Merck.
In a randomized, double-blind, placebo-controlled, study of 1,050 CDI patients, a total of 27 (5%) of 530 of those given bezlotoxumab were re-hospitalized 30 days after discharge, compared with 58 (11%) of 520 patients in the placebo group (Clin Infect Dis. 2017 Aug 11. doi. 10.1093/cid/cix523).
Patients were gathered from 322 sites across 30 countries between November 2011 and May 2015.
When measuring CDI-related readmissions, the investigators found use of bezlotoxumab reduced rCDI hospitalizations by 6%, and by approximately 8% in high-risk patients, such as those over 65 years old or with severe CDI.
Bezlotoxumab works by binding to CDI toxin B, a primary cause of CDI symptoms, according to Dr. Prabhu and fellow investigators. The researchers suggested that bezlotoxumab could be a prevailing factor in fighting the rate of CDI infections, which accounted for 29,000 deaths in 2011 (N Engl J Med. 2015 Jun 11;372[24]:2368-9).
Investigators acknowledged that patients admitted for the study may be healthier than the real-world CDI population.
All investigators reported some financial involvement, whether being a full-time employee or acting as a consultant, for Merck, which funded the study. Individually, investigators reported financial ties to similar medical companies, such as Pfizer and AstraZeneca.
AGA offers patient education materials on C. diff that can help your patients better understand the infection. Learn more at http://www.gastro.org/patient-care/conditions-diseases/clostridium-difficile-infection.
[email protected]
On Twitter @eaztweets
FROM CLINICAL INFECTIOUS DISEASES
Flashback to 2015
In the early 1970s, clindamycin had only been on the market for a few years when patients taking the antibiotic began to present with diarrhea and associated colitis. Initial attempts to culture a pathologic organism were unsuccessful, so other possible pathophysiologic mechanisms, including medication toxicity, altered bacterial flora, or the emergence of a new bacterial or viral pathogen were considered. Patients were initially given treatments similar to those for ulcerative colitis, with systemic and topical steroids and colectomy. Several years later, Clostridium difficile infection (CDI) was identified as the culprit, and these presentations became increasingly common in U.S. hospitals, and later in community settings.
Incidentally, the organism had been discovered years earlier, in 1935, by a group of scientists studying normal bacterial flora in neonates, but it was not known to be pathogenic in adults. By 2007, CDI had become the most common cause of health care–associated infection in U.S. hospitals. This prompted the Centers for Disease Control and Prevention to begin active population- and laboratory-based surveillance for C. difficile through its Emerging Infections Program (EIP) with the goal of more accurately assessing disease burden, incidence, recurrence, and mortality by capturing data across the spectrum of health care delivery settings. The April 2015 issue of GI & Hepatology News highlighted a report of 2011 CDC data from 10 EIP sites (N Engl J Med. 372;9:825-34), demonstrating that CDI was responsible for nearly half a million infections and 29,000 deaths in that year across sites, with the hypervirulent NAP1 strain found to be more prevalent among health care–associated than community-associated infections.
Treatment of CDI continues to evolve. With increased use of fecal microbiota transplantation, emerging evidence regarding the efficacy of other novel therapies such as the monoclonal antibodies actoxumab and bezlotoxumab (providing passive immunity to toxins A and B, respectively), and development of preventive vaccines (currently in phase 2 trials), there is hope on the horizon of being able to improve patient outcomes and reduce the burden of CDI on the health care system.
Megan A. Adams, MD, JD, MSc, is a clinical lecturer in the division of gastroenterology at the University of Michigan, a gastroenterologist at the Ann Arbor, Mich., VA, and an investigator in the VA Ann Arbor Center for Clinical Management Research. She is an associate editor of GI & Hepatology News.
In the early 1970s, clindamycin had only been on the market for a few years when patients taking the antibiotic began to present with diarrhea and associated colitis. Initial attempts to culture a pathologic organism were unsuccessful, so other possible pathophysiologic mechanisms, including medication toxicity, altered bacterial flora, or the emergence of a new bacterial or viral pathogen were considered. Patients were initially given treatments similar to those for ulcerative colitis, with systemic and topical steroids and colectomy. Several years later, Clostridium difficile infection (CDI) was identified as the culprit, and these presentations became increasingly common in U.S. hospitals, and later in community settings.
Incidentally, the organism had been discovered years earlier, in 1935, by a group of scientists studying normal bacterial flora in neonates, but it was not known to be pathogenic in adults. By 2007, CDI had become the most common cause of health care–associated infection in U.S. hospitals. This prompted the Centers for Disease Control and Prevention to begin active population- and laboratory-based surveillance for C. difficile through its Emerging Infections Program (EIP) with the goal of more accurately assessing disease burden, incidence, recurrence, and mortality by capturing data across the spectrum of health care delivery settings. The April 2015 issue of GI & Hepatology News highlighted a report of 2011 CDC data from 10 EIP sites (N Engl J Med. 372;9:825-34), demonstrating that CDI was responsible for nearly half a million infections and 29,000 deaths in that year across sites, with the hypervirulent NAP1 strain found to be more prevalent among health care–associated than community-associated infections.
Treatment of CDI continues to evolve. With increased use of fecal microbiota transplantation, emerging evidence regarding the efficacy of other novel therapies such as the monoclonal antibodies actoxumab and bezlotoxumab (providing passive immunity to toxins A and B, respectively), and development of preventive vaccines (currently in phase 2 trials), there is hope on the horizon of being able to improve patient outcomes and reduce the burden of CDI on the health care system.
Megan A. Adams, MD, JD, MSc, is a clinical lecturer in the division of gastroenterology at the University of Michigan, a gastroenterologist at the Ann Arbor, Mich., VA, and an investigator in the VA Ann Arbor Center for Clinical Management Research. She is an associate editor of GI & Hepatology News.
In the early 1970s, clindamycin had only been on the market for a few years when patients taking the antibiotic began to present with diarrhea and associated colitis. Initial attempts to culture a pathologic organism were unsuccessful, so other possible pathophysiologic mechanisms, including medication toxicity, altered bacterial flora, or the emergence of a new bacterial or viral pathogen were considered. Patients were initially given treatments similar to those for ulcerative colitis, with systemic and topical steroids and colectomy. Several years later, Clostridium difficile infection (CDI) was identified as the culprit, and these presentations became increasingly common in U.S. hospitals, and later in community settings.
Incidentally, the organism had been discovered years earlier, in 1935, by a group of scientists studying normal bacterial flora in neonates, but it was not known to be pathogenic in adults. By 2007, CDI had become the most common cause of health care–associated infection in U.S. hospitals. This prompted the Centers for Disease Control and Prevention to begin active population- and laboratory-based surveillance for C. difficile through its Emerging Infections Program (EIP) with the goal of more accurately assessing disease burden, incidence, recurrence, and mortality by capturing data across the spectrum of health care delivery settings. The April 2015 issue of GI & Hepatology News highlighted a report of 2011 CDC data from 10 EIP sites (N Engl J Med. 372;9:825-34), demonstrating that CDI was responsible for nearly half a million infections and 29,000 deaths in that year across sites, with the hypervirulent NAP1 strain found to be more prevalent among health care–associated than community-associated infections.
Treatment of CDI continues to evolve. With increased use of fecal microbiota transplantation, emerging evidence regarding the efficacy of other novel therapies such as the monoclonal antibodies actoxumab and bezlotoxumab (providing passive immunity to toxins A and B, respectively), and development of preventive vaccines (currently in phase 2 trials), there is hope on the horizon of being able to improve patient outcomes and reduce the burden of CDI on the health care system.
Megan A. Adams, MD, JD, MSc, is a clinical lecturer in the division of gastroenterology at the University of Michigan, a gastroenterologist at the Ann Arbor, Mich., VA, and an investigator in the VA Ann Arbor Center for Clinical Management Research. She is an associate editor of GI & Hepatology News.
FDA approves second adalimumab biosimilar for multiple conditions
The Food and Drug Administration has approved Cyltezo (adalimumab-adbm) for multiple conditions.
Cyltezo is an injectable tumor necrosis factor blocker, and is a biosimilar to adalimumab (Humira). The drug is indicated to treat moderate to severe active rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, moderate to severe active Crohn’s disease, moderate to severe active ulcerative colitis, moderately to severely active polyarticular juvenile idiopathic arthritis in patients 4 years of age and older, and moderate to severe plaque psoriasis.
Find the Cyltezo labeling information here.
The Food and Drug Administration has approved Cyltezo (adalimumab-adbm) for multiple conditions.
Cyltezo is an injectable tumor necrosis factor blocker, and is a biosimilar to adalimumab (Humira). The drug is indicated to treat moderate to severe active rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, moderate to severe active Crohn’s disease, moderate to severe active ulcerative colitis, moderately to severely active polyarticular juvenile idiopathic arthritis in patients 4 years of age and older, and moderate to severe plaque psoriasis.
Find the Cyltezo labeling information here.
The Food and Drug Administration has approved Cyltezo (adalimumab-adbm) for multiple conditions.
Cyltezo is an injectable tumor necrosis factor blocker, and is a biosimilar to adalimumab (Humira). The drug is indicated to treat moderate to severe active rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, moderate to severe active Crohn’s disease, moderate to severe active ulcerative colitis, moderately to severely active polyarticular juvenile idiopathic arthritis in patients 4 years of age and older, and moderate to severe plaque psoriasis.
Find the Cyltezo labeling information here.
All guts and glory – esophagus, stomach, small intestine
Prakash Gyawali, MD, led off the session with a lecture on functional heartburn, which he defined as burning retrosternal discomfort not relieved by antisecretory therapy, in a patient for whom endoscopy, esophageal pH monitoring, and manometry have revealed no evidence of gastroesophageal reflux disease (GERD), eosinophilic esophagitis (EoE), or major esophageal motility disorders. When performing pH monitoring to assess for functional heartburn, Dr. Gyawali advised that the test be done with patients off of proton pump inhibitors (PPIs). Despite similarity to the heartburn sensation of GERD, Dr. Gyawali pointed out how functional heartburn has features resembling irritable bowel syndrome, such as its association with anxiety and depression, and its response to neuromodulators (e.g., antidepressants). He discussed how new impedance-based esophageal metrics such as the postswallow-induced peristaltic wave index and measurement of mean nocturnal baseline impedance might be used to confirm a diagnosis of functional heartburn. Although neuromodulators remain the mainstay of management for functional heartburn, Dr. Gyawali discussed encouraging preliminary results of studies on psychotherapy, hypnotherapy, and alternative therapies such as acupuncture.
Rhonda Souza, MD, AGAF, discussed EoE, focusing especially on the controversial condition of PPI-responsive esophageal eosinophilia (PPI-REE) in which patients have typical EoE symptoms and histology, with no evidence of GERD by endoscopy or esophageal pH monitoring, yet they respond to PPI therapy. She discussed two possible explanations for PPI-REE: 1) the patients have subclinical GERD that responds to PPI antisecretory effects, or 2) the patients have EoE that responds to PPI anti-inflammatory effects. Dr. Souza reviewed data from her laboratory showing that omeprazole can block the secretion of eotaxin-3, a potent eosinophil chemoattractant in esophageal epithelial cells stimulated with allergic (Th2) cytokines in vitro. This potential anti-inflammatory PPI effect is entirely independent of any effect on gastric acid inhibition. After reviewing recent clinical and esophageal transcriptome data, Dr. Souza concluded that PPI-REE is probably just a subset of EoE, not an independent disorder.
John Inadomi, MD, AGAF, discussed Barrett’s esophagus and esophageal adenocarcinoma. He pointed out the inadequacy of current screening programs, noting studies showing that less than 10% of patients found to have esophageal adenocarcinoma had a prior diagnosis of Barrett’s esophagus. He estimated the annual incidence of adenocarcinoma at 0.12%-0.5% for patients with nondysplastic Barrett’s metaplasia. He discussed how current American College of Gastroenterology guidelines call for screening men who have chronic GERD symptoms with at least two other Barrett’s cancer risk factors (age greater than 50 years, white race, central obesity, cigarette smoking, family history of Barrett’s esophagus), and noted how the very low risk of esophageal adenocarcinoma in women (similar to the risk of breast cancer in men) supports the ACG recommendation not to screen women routinely for Barrett’s esophagus. Dr. Inadomi recommended endoscopic eradication as the preferred treatment for patients with confirmed dysplasia of any grade. He also noted that the removal of nodular lesions by endoscopic mucosal resection or endoscopic submucosal dissection is a crucial part of endoscopic eradication therapy.
In a lecture titled “The truth about PPIs,” Byron Cryer, MD, reviewed a number of potential adverse effects of PPIs, including Clostridium difficile–associated diarrhea, bone fractures, kidney disease, dementia, myocardial infarction, and interactions with clopidogrel. He pointed out that most of these putative adverse effects have been identified as modest increases in risks noted in observational studies, and the quality of this evidence is considered low or very low. In contrast, the benefits of PPIs for patients with complicated GERD and for patients at risk for NSAID complications have been established in high-quality, randomized controlled trials. Dr. Cryer concluded that, when PPIs are prescribed appropriately, their benefits likely outweigh their risks. However, he also noted that PPIs frequently are prescribed inappropriately, in which case they have no benefit and their potential for risk assumes greater importance.
Sheila Crowe, MD, AGAF, delivered the last lecture of the session, discussing celiac disease and gluten sensitivity. She reviewed recent data suggesting a role for infection with reovirus in triggering the development of celiac disease, and she noted that tissue transglutaminase IgA remains the best test to screen for the condition. She discussed the controversial topic of nonceliac gluten sensitivity, in which patients report symptoms or health alterations that they perceive to be the result of gluten ingestion. She pointed out difficulties in establishing an unequivocal diagnosis of nonceliac gluten sensitivity and, for patients without celiac disease, she highlighted a number of potential drawbacks of a gluten-free diet, including its expense, higher fat and sugar content, and increased levels of toxic metals such as arsenic and mercury.
Dr. Spechler is chief of the division of gastroenterology and co-director of the Center for Esophageal Diseases, Baylor University Medical Center at Dallas; he is an investigator/professor and co-director of the Center for Esophageal Research, Baylor Scott and White Research Institute, Dallas. This is a summary provided by the moderator of one of the AGA Postgraduate Courses held at DDW 2017.
Prakash Gyawali, MD, led off the session with a lecture on functional heartburn, which he defined as burning retrosternal discomfort not relieved by antisecretory therapy, in a patient for whom endoscopy, esophageal pH monitoring, and manometry have revealed no evidence of gastroesophageal reflux disease (GERD), eosinophilic esophagitis (EoE), or major esophageal motility disorders. When performing pH monitoring to assess for functional heartburn, Dr. Gyawali advised that the test be done with patients off of proton pump inhibitors (PPIs). Despite similarity to the heartburn sensation of GERD, Dr. Gyawali pointed out how functional heartburn has features resembling irritable bowel syndrome, such as its association with anxiety and depression, and its response to neuromodulators (e.g., antidepressants). He discussed how new impedance-based esophageal metrics such as the postswallow-induced peristaltic wave index and measurement of mean nocturnal baseline impedance might be used to confirm a diagnosis of functional heartburn. Although neuromodulators remain the mainstay of management for functional heartburn, Dr. Gyawali discussed encouraging preliminary results of studies on psychotherapy, hypnotherapy, and alternative therapies such as acupuncture.
Rhonda Souza, MD, AGAF, discussed EoE, focusing especially on the controversial condition of PPI-responsive esophageal eosinophilia (PPI-REE) in which patients have typical EoE symptoms and histology, with no evidence of GERD by endoscopy or esophageal pH monitoring, yet they respond to PPI therapy. She discussed two possible explanations for PPI-REE: 1) the patients have subclinical GERD that responds to PPI antisecretory effects, or 2) the patients have EoE that responds to PPI anti-inflammatory effects. Dr. Souza reviewed data from her laboratory showing that omeprazole can block the secretion of eotaxin-3, a potent eosinophil chemoattractant in esophageal epithelial cells stimulated with allergic (Th2) cytokines in vitro. This potential anti-inflammatory PPI effect is entirely independent of any effect on gastric acid inhibition. After reviewing recent clinical and esophageal transcriptome data, Dr. Souza concluded that PPI-REE is probably just a subset of EoE, not an independent disorder.
John Inadomi, MD, AGAF, discussed Barrett’s esophagus and esophageal adenocarcinoma. He pointed out the inadequacy of current screening programs, noting studies showing that less than 10% of patients found to have esophageal adenocarcinoma had a prior diagnosis of Barrett’s esophagus. He estimated the annual incidence of adenocarcinoma at 0.12%-0.5% for patients with nondysplastic Barrett’s metaplasia. He discussed how current American College of Gastroenterology guidelines call for screening men who have chronic GERD symptoms with at least two other Barrett’s cancer risk factors (age greater than 50 years, white race, central obesity, cigarette smoking, family history of Barrett’s esophagus), and noted how the very low risk of esophageal adenocarcinoma in women (similar to the risk of breast cancer in men) supports the ACG recommendation not to screen women routinely for Barrett’s esophagus. Dr. Inadomi recommended endoscopic eradication as the preferred treatment for patients with confirmed dysplasia of any grade. He also noted that the removal of nodular lesions by endoscopic mucosal resection or endoscopic submucosal dissection is a crucial part of endoscopic eradication therapy.
In a lecture titled “The truth about PPIs,” Byron Cryer, MD, reviewed a number of potential adverse effects of PPIs, including Clostridium difficile–associated diarrhea, bone fractures, kidney disease, dementia, myocardial infarction, and interactions with clopidogrel. He pointed out that most of these putative adverse effects have been identified as modest increases in risks noted in observational studies, and the quality of this evidence is considered low or very low. In contrast, the benefits of PPIs for patients with complicated GERD and for patients at risk for NSAID complications have been established in high-quality, randomized controlled trials. Dr. Cryer concluded that, when PPIs are prescribed appropriately, their benefits likely outweigh their risks. However, he also noted that PPIs frequently are prescribed inappropriately, in which case they have no benefit and their potential for risk assumes greater importance.
Sheila Crowe, MD, AGAF, delivered the last lecture of the session, discussing celiac disease and gluten sensitivity. She reviewed recent data suggesting a role for infection with reovirus in triggering the development of celiac disease, and she noted that tissue transglutaminase IgA remains the best test to screen for the condition. She discussed the controversial topic of nonceliac gluten sensitivity, in which patients report symptoms or health alterations that they perceive to be the result of gluten ingestion. She pointed out difficulties in establishing an unequivocal diagnosis of nonceliac gluten sensitivity and, for patients without celiac disease, she highlighted a number of potential drawbacks of a gluten-free diet, including its expense, higher fat and sugar content, and increased levels of toxic metals such as arsenic and mercury.
Dr. Spechler is chief of the division of gastroenterology and co-director of the Center for Esophageal Diseases, Baylor University Medical Center at Dallas; he is an investigator/professor and co-director of the Center for Esophageal Research, Baylor Scott and White Research Institute, Dallas. This is a summary provided by the moderator of one of the AGA Postgraduate Courses held at DDW 2017.
Prakash Gyawali, MD, led off the session with a lecture on functional heartburn, which he defined as burning retrosternal discomfort not relieved by antisecretory therapy, in a patient for whom endoscopy, esophageal pH monitoring, and manometry have revealed no evidence of gastroesophageal reflux disease (GERD), eosinophilic esophagitis (EoE), or major esophageal motility disorders. When performing pH monitoring to assess for functional heartburn, Dr. Gyawali advised that the test be done with patients off of proton pump inhibitors (PPIs). Despite similarity to the heartburn sensation of GERD, Dr. Gyawali pointed out how functional heartburn has features resembling irritable bowel syndrome, such as its association with anxiety and depression, and its response to neuromodulators (e.g., antidepressants). He discussed how new impedance-based esophageal metrics such as the postswallow-induced peristaltic wave index and measurement of mean nocturnal baseline impedance might be used to confirm a diagnosis of functional heartburn. Although neuromodulators remain the mainstay of management for functional heartburn, Dr. Gyawali discussed encouraging preliminary results of studies on psychotherapy, hypnotherapy, and alternative therapies such as acupuncture.
Rhonda Souza, MD, AGAF, discussed EoE, focusing especially on the controversial condition of PPI-responsive esophageal eosinophilia (PPI-REE) in which patients have typical EoE symptoms and histology, with no evidence of GERD by endoscopy or esophageal pH monitoring, yet they respond to PPI therapy. She discussed two possible explanations for PPI-REE: 1) the patients have subclinical GERD that responds to PPI antisecretory effects, or 2) the patients have EoE that responds to PPI anti-inflammatory effects. Dr. Souza reviewed data from her laboratory showing that omeprazole can block the secretion of eotaxin-3, a potent eosinophil chemoattractant in esophageal epithelial cells stimulated with allergic (Th2) cytokines in vitro. This potential anti-inflammatory PPI effect is entirely independent of any effect on gastric acid inhibition. After reviewing recent clinical and esophageal transcriptome data, Dr. Souza concluded that PPI-REE is probably just a subset of EoE, not an independent disorder.
John Inadomi, MD, AGAF, discussed Barrett’s esophagus and esophageal adenocarcinoma. He pointed out the inadequacy of current screening programs, noting studies showing that less than 10% of patients found to have esophageal adenocarcinoma had a prior diagnosis of Barrett’s esophagus. He estimated the annual incidence of adenocarcinoma at 0.12%-0.5% for patients with nondysplastic Barrett’s metaplasia. He discussed how current American College of Gastroenterology guidelines call for screening men who have chronic GERD symptoms with at least two other Barrett’s cancer risk factors (age greater than 50 years, white race, central obesity, cigarette smoking, family history of Barrett’s esophagus), and noted how the very low risk of esophageal adenocarcinoma in women (similar to the risk of breast cancer in men) supports the ACG recommendation not to screen women routinely for Barrett’s esophagus. Dr. Inadomi recommended endoscopic eradication as the preferred treatment for patients with confirmed dysplasia of any grade. He also noted that the removal of nodular lesions by endoscopic mucosal resection or endoscopic submucosal dissection is a crucial part of endoscopic eradication therapy.
In a lecture titled “The truth about PPIs,” Byron Cryer, MD, reviewed a number of potential adverse effects of PPIs, including Clostridium difficile–associated diarrhea, bone fractures, kidney disease, dementia, myocardial infarction, and interactions with clopidogrel. He pointed out that most of these putative adverse effects have been identified as modest increases in risks noted in observational studies, and the quality of this evidence is considered low or very low. In contrast, the benefits of PPIs for patients with complicated GERD and for patients at risk for NSAID complications have been established in high-quality, randomized controlled trials. Dr. Cryer concluded that, when PPIs are prescribed appropriately, their benefits likely outweigh their risks. However, he also noted that PPIs frequently are prescribed inappropriately, in which case they have no benefit and their potential for risk assumes greater importance.
Sheila Crowe, MD, AGAF, delivered the last lecture of the session, discussing celiac disease and gluten sensitivity. She reviewed recent data suggesting a role for infection with reovirus in triggering the development of celiac disease, and she noted that tissue transglutaminase IgA remains the best test to screen for the condition. She discussed the controversial topic of nonceliac gluten sensitivity, in which patients report symptoms or health alterations that they perceive to be the result of gluten ingestion. She pointed out difficulties in establishing an unequivocal diagnosis of nonceliac gluten sensitivity and, for patients without celiac disease, she highlighted a number of potential drawbacks of a gluten-free diet, including its expense, higher fat and sugar content, and increased levels of toxic metals such as arsenic and mercury.
Dr. Spechler is chief of the division of gastroenterology and co-director of the Center for Esophageal Diseases, Baylor University Medical Center at Dallas; he is an investigator/professor and co-director of the Center for Esophageal Research, Baylor Scott and White Research Institute, Dallas. This is a summary provided by the moderator of one of the AGA Postgraduate Courses held at DDW 2017.
Antimicrobial development model links financial incentives with public health needs
A new model promoting the development and sustainable use of antimicrobials has been proposed by the Duke University Margolis Center for Health Policy.
Dubbed the “Priority Antimicrobial Value and Entry (PAVE) Award,” the model “provides developers quick access to a significant reward upon market entry of an effective antimicrobial, and provides strong incentives to shift reimbursement from insurance plans to population- and value-based contracts, not payments based on volume of sales,” according to a white paper detailing the proposal.
“This model builds on and reinforces the shift to quality and value in U.S. health care, with payments more directly linked to public health benefits and total costs,” Gregory Daniel, PhD, deputy director of the Margolis Center and lead author of the report, said in a viewpoint published online in JAMA (2017 Aug 3. doi: 10.1001/jama.2017.10164). “Along with strong push mechanisms that remove some of the financial risk associated with initial development of drug candidates, these measures could make a major contribution to the global effort to create and sustain a robust pipeline of antimicrobials that address current and growing public health needs – and would do so through an approach well suited to the reforming U.S. health care system.”
The proposal combines incentives provided from both the public and private sectors.
Payments from public funds would be largest in year 1 and would decrease over the next 5-6 years, with each payment “contingent upon developers demonstrating an increasing share of their revenue from population-based [alternative payment models] linked to value to society through availability, support for sustainable use, and continued data collection,” the report notes, describing a method that emphasizes value and delinks revenues from volume.
Delinking revenues from volume has been a part of two prominent proposals in Europe. One proposed by Chatham House, a London-based public policy institute, also proposed a number of financial incentives, such as public funding and tax credits, to help finance development in addition to MERs. A second being developed in the European Union, expected to be finalized later this year, would provide grants for early stage research, establishment of a nonprofit developer to manage and finance discovery through commercialization, a MER to developers that meet certain criteria, an annual licensing fee to developers for access to their product, and a dual-pricing model that allows for higher prices to be charged for appropriate use.
The Duke paper identifies a number of contracting models, such as a manufacturer contracting with a health plan on a per-member per-month basis to provide the drug as needed, or episode-based payments as needed, for all hospitalized patients identified with specific diagnosis-related groups.
“Successful implementation of the PAVE Award will require cooperation between developers, payers, and providers,” the Duke policy researchers stated. “The contract should encourage short- and long-term savings from reduced inappropriate use, as well as reduced infection-related costs, such as extended hospital stays, treatment complications, and additional infections.”
For infectious diseases physicians, there are a few specific roles in addition to any that are played beyond being a part of the medical research.
“For example, as the clinicians on the front lines seeing the patients, they are able to really identify what are the emerging threats on the horizon and where do we need to be targeting R&D. I think that is useful for helping to inform which antibiotics should be eligible to receive market entry rewards,” Amanda Jezek, senior vice president of public policy and government relations at the Infectious Diseases Society of America, said in an interview. She also noted that physicians will be instrumental in “helping to create the political will to advance proposals like this because they are the ones who can really speak to what the need for patients is on the ground, in communities, and in hospitals.”
Physicians also will play a vital role in ensuring that any new antimicrobial drugs are not overused.
“Once these antibiotics are approved, infectious diseases physicians lead stewardship programs that are essential for ensuring that these drugs are used appropriately, and that is critical because if you start overusing the new antibiotics, resistance to them will develop quickly and you are back to where you started,” said Ms. Jezek, who was part of the advisory group that helped to inform the report.
A new model promoting the development and sustainable use of antimicrobials has been proposed by the Duke University Margolis Center for Health Policy.
Dubbed the “Priority Antimicrobial Value and Entry (PAVE) Award,” the model “provides developers quick access to a significant reward upon market entry of an effective antimicrobial, and provides strong incentives to shift reimbursement from insurance plans to population- and value-based contracts, not payments based on volume of sales,” according to a white paper detailing the proposal.
“This model builds on and reinforces the shift to quality and value in U.S. health care, with payments more directly linked to public health benefits and total costs,” Gregory Daniel, PhD, deputy director of the Margolis Center and lead author of the report, said in a viewpoint published online in JAMA (2017 Aug 3. doi: 10.1001/jama.2017.10164). “Along with strong push mechanisms that remove some of the financial risk associated with initial development of drug candidates, these measures could make a major contribution to the global effort to create and sustain a robust pipeline of antimicrobials that address current and growing public health needs – and would do so through an approach well suited to the reforming U.S. health care system.”
The proposal combines incentives provided from both the public and private sectors.
Payments from public funds would be largest in year 1 and would decrease over the next 5-6 years, with each payment “contingent upon developers demonstrating an increasing share of their revenue from population-based [alternative payment models] linked to value to society through availability, support for sustainable use, and continued data collection,” the report notes, describing a method that emphasizes value and delinks revenues from volume.
Delinking revenues from volume has been a part of two prominent proposals in Europe. One proposed by Chatham House, a London-based public policy institute, also proposed a number of financial incentives, such as public funding and tax credits, to help finance development in addition to MERs. A second being developed in the European Union, expected to be finalized later this year, would provide grants for early stage research, establishment of a nonprofit developer to manage and finance discovery through commercialization, a MER to developers that meet certain criteria, an annual licensing fee to developers for access to their product, and a dual-pricing model that allows for higher prices to be charged for appropriate use.
The Duke paper identifies a number of contracting models, such as a manufacturer contracting with a health plan on a per-member per-month basis to provide the drug as needed, or episode-based payments as needed, for all hospitalized patients identified with specific diagnosis-related groups.
“Successful implementation of the PAVE Award will require cooperation between developers, payers, and providers,” the Duke policy researchers stated. “The contract should encourage short- and long-term savings from reduced inappropriate use, as well as reduced infection-related costs, such as extended hospital stays, treatment complications, and additional infections.”
For infectious diseases physicians, there are a few specific roles in addition to any that are played beyond being a part of the medical research.
“For example, as the clinicians on the front lines seeing the patients, they are able to really identify what are the emerging threats on the horizon and where do we need to be targeting R&D. I think that is useful for helping to inform which antibiotics should be eligible to receive market entry rewards,” Amanda Jezek, senior vice president of public policy and government relations at the Infectious Diseases Society of America, said in an interview. She also noted that physicians will be instrumental in “helping to create the political will to advance proposals like this because they are the ones who can really speak to what the need for patients is on the ground, in communities, and in hospitals.”
Physicians also will play a vital role in ensuring that any new antimicrobial drugs are not overused.
“Once these antibiotics are approved, infectious diseases physicians lead stewardship programs that are essential for ensuring that these drugs are used appropriately, and that is critical because if you start overusing the new antibiotics, resistance to them will develop quickly and you are back to where you started,” said Ms. Jezek, who was part of the advisory group that helped to inform the report.
A new model promoting the development and sustainable use of antimicrobials has been proposed by the Duke University Margolis Center for Health Policy.
Dubbed the “Priority Antimicrobial Value and Entry (PAVE) Award,” the model “provides developers quick access to a significant reward upon market entry of an effective antimicrobial, and provides strong incentives to shift reimbursement from insurance plans to population- and value-based contracts, not payments based on volume of sales,” according to a white paper detailing the proposal.
“This model builds on and reinforces the shift to quality and value in U.S. health care, with payments more directly linked to public health benefits and total costs,” Gregory Daniel, PhD, deputy director of the Margolis Center and lead author of the report, said in a viewpoint published online in JAMA (2017 Aug 3. doi: 10.1001/jama.2017.10164). “Along with strong push mechanisms that remove some of the financial risk associated with initial development of drug candidates, these measures could make a major contribution to the global effort to create and sustain a robust pipeline of antimicrobials that address current and growing public health needs – and would do so through an approach well suited to the reforming U.S. health care system.”
The proposal combines incentives provided from both the public and private sectors.
Payments from public funds would be largest in year 1 and would decrease over the next 5-6 years, with each payment “contingent upon developers demonstrating an increasing share of their revenue from population-based [alternative payment models] linked to value to society through availability, support for sustainable use, and continued data collection,” the report notes, describing a method that emphasizes value and delinks revenues from volume.
Delinking revenues from volume has been a part of two prominent proposals in Europe. One proposed by Chatham House, a London-based public policy institute, also proposed a number of financial incentives, such as public funding and tax credits, to help finance development in addition to MERs. A second being developed in the European Union, expected to be finalized later this year, would provide grants for early stage research, establishment of a nonprofit developer to manage and finance discovery through commercialization, a MER to developers that meet certain criteria, an annual licensing fee to developers for access to their product, and a dual-pricing model that allows for higher prices to be charged for appropriate use.
The Duke paper identifies a number of contracting models, such as a manufacturer contracting with a health plan on a per-member per-month basis to provide the drug as needed, or episode-based payments as needed, for all hospitalized patients identified with specific diagnosis-related groups.
“Successful implementation of the PAVE Award will require cooperation between developers, payers, and providers,” the Duke policy researchers stated. “The contract should encourage short- and long-term savings from reduced inappropriate use, as well as reduced infection-related costs, such as extended hospital stays, treatment complications, and additional infections.”
For infectious diseases physicians, there are a few specific roles in addition to any that are played beyond being a part of the medical research.
“For example, as the clinicians on the front lines seeing the patients, they are able to really identify what are the emerging threats on the horizon and where do we need to be targeting R&D. I think that is useful for helping to inform which antibiotics should be eligible to receive market entry rewards,” Amanda Jezek, senior vice president of public policy and government relations at the Infectious Diseases Society of America, said in an interview. She also noted that physicians will be instrumental in “helping to create the political will to advance proposals like this because they are the ones who can really speak to what the need for patients is on the ground, in communities, and in hospitals.”
Physicians also will play a vital role in ensuring that any new antimicrobial drugs are not overused.
“Once these antibiotics are approved, infectious diseases physicians lead stewardship programs that are essential for ensuring that these drugs are used appropriately, and that is critical because if you start overusing the new antibiotics, resistance to them will develop quickly and you are back to where you started,” said Ms. Jezek, who was part of the advisory group that helped to inform the report.