IBD & Intestinal Disorders

The human gut microbiota is a complex consortium of microbes that includes bacteria, viruses, archaea, and fungi. There are enormous numbers of bacteria in the gut with a collective genome estimated at 150-fold greater than the size of our own genome. Thus, the gut microbiota can produce small molecules, some determined by dietary substrates that are unique and cannot be produced by mammalian cells. Growing evidence suggests that these small molecules may play a role in the pathogenesis of certain diseases, a number of which are associated with "dysbiosis" – alteration in the composition of the microbiota.

One strategy to maintain health and/or treat disease might involve altering the dysbiotic gut microbiota through dietary intervention. Although the interaction between diet and the gut microbiota is complex, investigators have shown consistently that decreases in gut microbiome "richness" (numbers of various bacteria and their genes) is associated with both disease states and the consumption of a Westernized diet. Using this knowledge, investigators are very interested in determining whether or not dietary interventions, such as defined formula and/or elemental diets, successfully treat Crohn’s disease via a gut microbiome–dependent mechanism. The ultimate goal of such research is to develop a "healthier" diet for patients suffering from inflammatory bowel disease.

Diet not only alters the composition of the gut microbiota but it also serves as a substrate by which it can produce a large number of small molecules that, after first pass metabolism through the liver, can circulate systemically and have important effects on host physiology. For example, the conversion of dietary fats from choline into trimethyl amine (TMA) by the microbiota and its subsequent oxidation by the liver, leads to the production of TMAO, a small molecule that accelerates coronary vascular disease in mice and is a biomarker for patients at risk for atherosclerotic heart disease in humans. The enzyme in bacteria that leads to the production of TMA from choline has been described, thus opening up opportunities for the development of gut microbiota–based biomarkers that could be used to stratify the risk of coronary vascular disease in humans. Conceptually, strategies targeting TMA-producing bacteria and/or novel dietary modifications might also be developed to reduce the risk of heart disease.

Similar strategies could be used to develop gut microbiota–based therapies targeting immune-mediated disease, such as IBD and asthma, with a focus on the consumption of fermentable carbohydrates, the production of short-chain fatty acids, the activation of G-protein coupled receptors, and the restoration of immune tolerance through T regulatory cells. Ultimately, there may be significant opportunities to enhance current dietary interventions that target the gut microbiota, such as prebiotics, probiotics, and synbiotics, to develop more potent and effective interventions by applying the vast amount of new knowledge gained over the past decade from the study of the interaction between diet and the gut microbiome.

Dr. Wu is the Ferdinand G. Weisbrod Professor of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia. His comments were made during the ASGE and AGA joint Presidential Plenary at the annual Digestive Disease Week.

The human gut microbiota is a complex consortium of microbes that includes bacteria, viruses, archaea, and fungi. There are enormous numbers of bacteria in the gut with a collective genome estimated at 150-fold greater than the size of our own genome. Thus, the gut microbiota can produce small molecules, some determined by dietary substrates that are unique and cannot be produced by mammalian cells. Growing evidence suggests that these small molecules may play a role in the pathogenesis of certain diseases, a number of which are associated with "dysbiosis" – alteration in the composition of the microbiota.

One strategy to maintain health and/or treat disease might involve altering the dysbiotic gut microbiota through dietary intervention. Although the interaction between diet and the gut microbiota is complex, investigators have shown consistently that decreases in gut microbiome "richness" (numbers of various bacteria and their genes) is associated with both disease states and the consumption of a Westernized diet. Using this knowledge, investigators are very interested in determining whether or not dietary interventions, such as defined formula and/or elemental diets, successfully treat Crohn’s disease via a gut microbiome–dependent mechanism. The ultimate goal of such research is to develop a "healthier" diet for patients suffering from inflammatory bowel disease.

Diet not only alters the composition of the gut microbiota but it also serves as a substrate by which it can produce a large number of small molecules that, after first pass metabolism through the liver, can circulate systemically and have important effects on host physiology. For example, the conversion of dietary fats from choline into trimethyl amine (TMA) by the microbiota and its subsequent oxidation by the liver, leads to the production of TMAO, a small molecule that accelerates coronary vascular disease in mice and is a biomarker for patients at risk for atherosclerotic heart disease in humans. The enzyme in bacteria that leads to the production of TMA from choline has been described, thus opening up opportunities for the development of gut microbiota–based biomarkers that could be used to stratify the risk of coronary vascular disease in humans. Conceptually, strategies targeting TMA-producing bacteria and/or novel dietary modifications might also be developed to reduce the risk of heart disease.

Similar strategies could be used to develop gut microbiota–based therapies targeting immune-mediated disease, such as IBD and asthma, with a focus on the consumption of fermentable carbohydrates, the production of short-chain fatty acids, the activation of G-protein coupled receptors, and the restoration of immune tolerance through T regulatory cells. Ultimately, there may be significant opportunities to enhance current dietary interventions that target the gut microbiota, such as prebiotics, probiotics, and synbiotics, to develop more potent and effective interventions by applying the vast amount of new knowledge gained over the past decade from the study of the interaction between diet and the gut microbiome.

Dr. Wu is the Ferdinand G. Weisbrod Professor of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia. His comments were made during the ASGE and AGA joint Presidential Plenary at the annual Digestive Disease Week.

The human gut microbiota is a complex consortium of microbes that includes bacteria, viruses, archaea, and fungi. There are enormous numbers of bacteria in the gut with a collective genome estimated at 150-fold greater than the size of our own genome. Thus, the gut microbiota can produce small molecules, some determined by dietary substrates that are unique and cannot be produced by mammalian cells. Growing evidence suggests that these small molecules may play a role in the pathogenesis of certain diseases, a number of which are associated with "dysbiosis" – alteration in the composition of the microbiota.

One strategy to maintain health and/or treat disease might involve altering the dysbiotic gut microbiota through dietary intervention. Although the interaction between diet and the gut microbiota is complex, investigators have shown consistently that decreases in gut microbiome "richness" (numbers of various bacteria and their genes) is associated with both disease states and the consumption of a Westernized diet. Using this knowledge, investigators are very interested in determining whether or not dietary interventions, such as defined formula and/or elemental diets, successfully treat Crohn’s disease via a gut microbiome–dependent mechanism. The ultimate goal of such research is to develop a "healthier" diet for patients suffering from inflammatory bowel disease.

Diet not only alters the composition of the gut microbiota but it also serves as a substrate by which it can produce a large number of small molecules that, after first pass metabolism through the liver, can circulate systemically and have important effects on host physiology. For example, the conversion of dietary fats from choline into trimethyl amine (TMA) by the microbiota and its subsequent oxidation by the liver, leads to the production of TMAO, a small molecule that accelerates coronary vascular disease in mice and is a biomarker for patients at risk for atherosclerotic heart disease in humans. The enzyme in bacteria that leads to the production of TMA from choline has been described, thus opening up opportunities for the development of gut microbiota–based biomarkers that could be used to stratify the risk of coronary vascular disease in humans. Conceptually, strategies targeting TMA-producing bacteria and/or novel dietary modifications might also be developed to reduce the risk of heart disease.

Similar strategies could be used to develop gut microbiota–based therapies targeting immune-mediated disease, such as IBD and asthma, with a focus on the consumption of fermentable carbohydrates, the production of short-chain fatty acids, the activation of G-protein coupled receptors, and the restoration of immune tolerance through T regulatory cells. Ultimately, there may be significant opportunities to enhance current dietary interventions that target the gut microbiota, such as prebiotics, probiotics, and synbiotics, to develop more potent and effective interventions by applying the vast amount of new knowledge gained over the past decade from the study of the interaction between diet and the gut microbiome.

Dr. Wu is the Ferdinand G. Weisbrod Professor of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia. His comments were made during the ASGE and AGA joint Presidential Plenary at the annual Digestive Disease Week.

The human gut microbiota is a complex consortium of microbes that includes bacteria, viruses, archaea, and fungi. There are enormous numbers of bacteria in the gut with a collective genome estimated at 150-fold greater than the size of our own genome. Thus, the gut microbiota can produce small molecules, some determined by dietary substrates that are unique and cannot be produced by mammalian cells. Growing evidence suggests that these small molecules may play a role in the pathogenesis of certain diseases, a number of which are associated with "dysbiosis" – alteration in the composition of the microbiota.

One strategy to maintain health and/or treat disease might involve altering the dysbiotic gut microbiota through dietary intervention. Although the interaction between diet and the gut microbiota is complex, investigators have shown consistently that decreases in gut microbiome "richness" (numbers of various bacteria and their genes) is associated with both disease states and the consumption of a Westernized diet. Using this knowledge, investigators are very interested in determining whether or not dietary interventions, such as defined formula and/or elemental diets, successfully treat Crohn’s disease via a gut microbiome–dependent mechanism. The ultimate goal of such research is to develop a "healthier" diet for patients suffering from inflammatory bowel disease.

Diet not only alters the composition of the gut microbiota but it also serves as a substrate by which it can produce a large number of small molecules that, after first pass metabolism through the liver, can circulate systemically and have important effects on host physiology. For example, the conversion of dietary fats from choline into trimethyl amine (TMA) by the microbiota and its subsequent oxidation by the liver, leads to the production of TMAO, a small molecule that accelerates coronary vascular disease in mice and is a biomarker for patients at risk for atherosclerotic heart disease in humans. The enzyme in bacteria that leads to the production of TMA from choline has been described, thus opening up opportunities for the development of gut microbiota–based biomarkers that could be used to stratify the risk of coronary vascular disease in humans. Conceptually, strategies targeting TMA-producing bacteria and/or novel dietary modifications might also be developed to reduce the risk of heart disease.

Similar strategies could be used to develop gut microbiota–based therapies targeting immune-mediated disease, such as IBD and asthma, with a focus on the consumption of fermentable carbohydrates, the production of short-chain fatty acids, the activation of G-protein coupled receptors, and the restoration of immune tolerance through T regulatory cells. Ultimately, there may be significant opportunities to enhance current dietary interventions that target the gut microbiota, such as prebiotics, probiotics, and synbiotics, to develop more potent and effective interventions by applying the vast amount of new knowledge gained over the past decade from the study of the interaction between diet and the gut microbiome.

Dr. Wu is the Ferdinand G. Weisbrod Professor of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia. His comments were made during the ASGE and AGA joint Presidential Plenary at the annual Digestive Disease Week.

The human gut microbiota is a complex consortium of microbes that includes bacteria, viruses, archaea, and fungi. There are enormous numbers of bacteria in the gut with a collective genome estimated at 150-fold greater than the size of our own genome. Thus, the gut microbiota can produce small molecules, some determined by dietary substrates that are unique and cannot be produced by mammalian cells. Growing evidence suggests that these small molecules may play a role in the pathogenesis of certain diseases, a number of which are associated with "dysbiosis" – alteration in the composition of the microbiota.

One strategy to maintain health and/or treat disease might involve altering the dysbiotic gut microbiota through dietary intervention. Although the interaction between diet and the gut microbiota is complex, investigators have shown consistently that decreases in gut microbiome "richness" (numbers of various bacteria and their genes) is associated with both disease states and the consumption of a Westernized diet. Using this knowledge, investigators are very interested in determining whether or not dietary interventions, such as defined formula and/or elemental diets, successfully treat Crohn’s disease via a gut microbiome–dependent mechanism. The ultimate goal of such research is to develop a "healthier" diet for patients suffering from inflammatory bowel disease.

Diet not only alters the composition of the gut microbiota but it also serves as a substrate by which it can produce a large number of small molecules that, after first pass metabolism through the liver, can circulate systemically and have important effects on host physiology. For example, the conversion of dietary fats from choline into trimethyl amine (TMA) by the microbiota and its subsequent oxidation by the liver, leads to the production of TMAO, a small molecule that accelerates coronary vascular disease in mice and is a biomarker for patients at risk for atherosclerotic heart disease in humans. The enzyme in bacteria that leads to the production of TMA from choline has been described, thus opening up opportunities for the development of gut microbiota–based biomarkers that could be used to stratify the risk of coronary vascular disease in humans. Conceptually, strategies targeting TMA-producing bacteria and/or novel dietary modifications might also be developed to reduce the risk of heart disease.

Similar strategies could be used to develop gut microbiota–based therapies targeting immune-mediated disease, such as IBD and asthma, with a focus on the consumption of fermentable carbohydrates, the production of short-chain fatty acids, the activation of G-protein coupled receptors, and the restoration of immune tolerance through T regulatory cells. Ultimately, there may be significant opportunities to enhance current dietary interventions that target the gut microbiota, such as prebiotics, probiotics, and synbiotics, to develop more potent and effective interventions by applying the vast amount of new knowledge gained over the past decade from the study of the interaction between diet and the gut microbiome.

Dr. Wu is the Ferdinand G. Weisbrod Professor of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia. His comments were made during the ASGE and AGA joint Presidential Plenary at the annual Digestive Disease Week.

The human gut microbiota is a complex consortium of microbes that includes bacteria, viruses, archaea, and fungi. There are enormous numbers of bacteria in the gut with a collective genome estimated at 150-fold greater than the size of our own genome. Thus, the gut microbiota can produce small molecules, some determined by dietary substrates that are unique and cannot be produced by mammalian cells. Growing evidence suggests that these small molecules may play a role in the pathogenesis of certain diseases, a number of which are associated with "dysbiosis" – alteration in the composition of the microbiota.

One strategy to maintain health and/or treat disease might involve altering the dysbiotic gut microbiota through dietary intervention. Although the interaction between diet and the gut microbiota is complex, investigators have shown consistently that decreases in gut microbiome "richness" (numbers of various bacteria and their genes) is associated with both disease states and the consumption of a Westernized diet. Using this knowledge, investigators are very interested in determining whether or not dietary interventions, such as defined formula and/or elemental diets, successfully treat Crohn’s disease via a gut microbiome–dependent mechanism. The ultimate goal of such research is to develop a "healthier" diet for patients suffering from inflammatory bowel disease.

Diet not only alters the composition of the gut microbiota but it also serves as a substrate by which it can produce a large number of small molecules that, after first pass metabolism through the liver, can circulate systemically and have important effects on host physiology. For example, the conversion of dietary fats from choline into trimethyl amine (TMA) by the microbiota and its subsequent oxidation by the liver, leads to the production of TMAO, a small molecule that accelerates coronary vascular disease in mice and is a biomarker for patients at risk for atherosclerotic heart disease in humans. The enzyme in bacteria that leads to the production of TMA from choline has been described, thus opening up opportunities for the development of gut microbiota–based biomarkers that could be used to stratify the risk of coronary vascular disease in humans. Conceptually, strategies targeting TMA-producing bacteria and/or novel dietary modifications might also be developed to reduce the risk of heart disease.

Similar strategies could be used to develop gut microbiota–based therapies targeting immune-mediated disease, such as IBD and asthma, with a focus on the consumption of fermentable carbohydrates, the production of short-chain fatty acids, the activation of G-protein coupled receptors, and the restoration of immune tolerance through T regulatory cells. Ultimately, there may be significant opportunities to enhance current dietary interventions that target the gut microbiota, such as prebiotics, probiotics, and synbiotics, to develop more potent and effective interventions by applying the vast amount of new knowledge gained over the past decade from the study of the interaction between diet and the gut microbiome.

Dr. Wu is the Ferdinand G. Weisbrod Professor of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia. His comments were made during the ASGE and AGA joint Presidential Plenary at the annual Digestive Disease Week.

Pregnant mothers with celiac disease have little to fear when it comes to birth defects, despite previous underpowered reports to the contrary, wrote Daniela Zugna, Ph.D., and her colleagues in the July issue of Clinical Gastroenterology and Hepatology (doi.org/10.1016/j.cgh.2013.10.012).

Dr. Zugna of University of Turin, in Italy, looked at a total of 5,774 mothers with celiac disease (CD) and 3,039 fathers with CD, cross-referenced with the Swedish Medical Birth Register, the Patient Register, the Register of Congenital Malformations and the Multigeneration Register.

From 1973 through 2009, the mothers gave birth to 11,382 children, and 6,002 children were born to fathers with CD.

These were compared with nearly 41,000 and 20,000 children of healthy mothers and fathers born over the same time period, respectively.

The authors found that 672 babies of mothers with CD (5.9%) and 2,098 control offspring (5.1%) were born with congenital malformations; these included heart defects, neural tube defects, limb deficiencies, and orofacial clefts, among others.

That amounted to an adjusted prevalence odds ratio of having a child with birth defects of 1.15 for mothers with CD (95% confidence interval, 1.05-1.26).

For fathers, the figures were 352 children with birth defects born to CD patients (5.9%) and 1,009 to healthy controls (5.1%), for a similar odds ratio of 1.14 (95% CI, 1.00-1.29).

However, when the data were restricted to births between 2000 and 2009, the significance of these differences vanished: in this most modern era, mothers with CD carried a nonsignificant OR of 1.11 (95% CI, 0.79-1.56).

By the same token, fathers of babies born between 2000 and 2009 had an OR of 1.01 for having a child with birth defects (95% CI, 0.81-1.26).

In postulating reasons for the slightly increased number of birth defects seen over the span of the study, the authors wrote: "While folic acid deficiency is common in newly diagnosed CD, it is sometimes seen after diagnosis, perhaps because of a lack of folic acid in the gluten-free diet."

And regarding the possible connection between fathers with CD and their children, "If spouses to men with CD are also primarily on a gluten-free diet, this may actually explain the excess risk for congenital malformation in paternal offspring."

Alternatively, "Low sperm quality in men with CD could potentially influence the risk of malformations."

The authors conceded several important weaknesses in this study. For one, they did not have data on diet adherence in CD, nor on the periconceptional or perinatal use of folic acid supplementation.

Moreover, a substantial proportion of pregnancies with neural tube defects discovered during prenatal screening were likely to have been terminated, potentially resulting in artificially low rates of this malformation: indeed, the authors pointed to data showing that between 1999 and 2009, between 51% and 93% of all NTD pregnancies were terminated, depending on the specific defect.

Finally, "Over time, symptoms have changed in CD," they wrote.

"It is possible that, with increased use of celiac serology, milder cases of CD are now diagnosed in which there is no association with congenital malformation."

The authors disclosed no conflicts of interest; individual authors disclosed several grants from nonprofit and research agencies in Europe, including the Italian Association for Cancer Research, the Stockholm County Council, the Danish Medical Research Council, and the Karolinska Institutet, among others.

Pregnant mothers with celiac disease have little to fear when it comes to birth defects, despite previous underpowered reports to the contrary, wrote Daniela Zugna, Ph.D., and her colleagues in the July issue of Clinical Gastroenterology and Hepatology (doi.org/10.1016/j.cgh.2013.10.012).

Dr. Zugna of University of Turin, in Italy, looked at a total of 5,774 mothers with celiac disease (CD) and 3,039 fathers with CD, cross-referenced with the Swedish Medical Birth Register, the Patient Register, the Register of Congenital Malformations and the Multigeneration Register.

From 1973 through 2009, the mothers gave birth to 11,382 children, and 6,002 children were born to fathers with CD.

These were compared with nearly 41,000 and 20,000 children of healthy mothers and fathers born over the same time period, respectively.

The authors found that 672 babies of mothers with CD (5.9%) and 2,098 control offspring (5.1%) were born with congenital malformations; these included heart defects, neural tube defects, limb deficiencies, and orofacial clefts, among others.

That amounted to an adjusted prevalence odds ratio of having a child with birth defects of 1.15 for mothers with CD (95% confidence interval, 1.05-1.26).

For fathers, the figures were 352 children with birth defects born to CD patients (5.9%) and 1,009 to healthy controls (5.1%), for a similar odds ratio of 1.14 (95% CI, 1.00-1.29).

However, when the data were restricted to births between 2000 and 2009, the significance of these differences vanished: in this most modern era, mothers with CD carried a nonsignificant OR of 1.11 (95% CI, 0.79-1.56).

By the same token, fathers of babies born between 2000 and 2009 had an OR of 1.01 for having a child with birth defects (95% CI, 0.81-1.26).

In postulating reasons for the slightly increased number of birth defects seen over the span of the study, the authors wrote: "While folic acid deficiency is common in newly diagnosed CD, it is sometimes seen after diagnosis, perhaps because of a lack of folic acid in the gluten-free diet."

And regarding the possible connection between fathers with CD and their children, "If spouses to men with CD are also primarily on a gluten-free diet, this may actually explain the excess risk for congenital malformation in paternal offspring."

Alternatively, "Low sperm quality in men with CD could potentially influence the risk of malformations."

The authors conceded several important weaknesses in this study. For one, they did not have data on diet adherence in CD, nor on the periconceptional or perinatal use of folic acid supplementation.

Moreover, a substantial proportion of pregnancies with neural tube defects discovered during prenatal screening were likely to have been terminated, potentially resulting in artificially low rates of this malformation: indeed, the authors pointed to data showing that between 1999 and 2009, between 51% and 93% of all NTD pregnancies were terminated, depending on the specific defect.

Finally, "Over time, symptoms have changed in CD," they wrote.

"It is possible that, with increased use of celiac serology, milder cases of CD are now diagnosed in which there is no association with congenital malformation."

The authors disclosed no conflicts of interest; individual authors disclosed several grants from nonprofit and research agencies in Europe, including the Italian Association for Cancer Research, the Stockholm County Council, the Danish Medical Research Council, and the Karolinska Institutet, among others.

Pregnant mothers with celiac disease have little to fear when it comes to birth defects, despite previous underpowered reports to the contrary, wrote Daniela Zugna, Ph.D., and her colleagues in the July issue of Clinical Gastroenterology and Hepatology (doi.org/10.1016/j.cgh.2013.10.012).

Dr. Zugna of University of Turin, in Italy, looked at a total of 5,774 mothers with celiac disease (CD) and 3,039 fathers with CD, cross-referenced with the Swedish Medical Birth Register, the Patient Register, the Register of Congenital Malformations and the Multigeneration Register.

From 1973 through 2009, the mothers gave birth to 11,382 children, and 6,002 children were born to fathers with CD.

These were compared with nearly 41,000 and 20,000 children of healthy mothers and fathers born over the same time period, respectively.

The authors found that 672 babies of mothers with CD (5.9%) and 2,098 control offspring (5.1%) were born with congenital malformations; these included heart defects, neural tube defects, limb deficiencies, and orofacial clefts, among others.

That amounted to an adjusted prevalence odds ratio of having a child with birth defects of 1.15 for mothers with CD (95% confidence interval, 1.05-1.26).

For fathers, the figures were 352 children with birth defects born to CD patients (5.9%) and 1,009 to healthy controls (5.1%), for a similar odds ratio of 1.14 (95% CI, 1.00-1.29).

However, when the data were restricted to births between 2000 and 2009, the significance of these differences vanished: in this most modern era, mothers with CD carried a nonsignificant OR of 1.11 (95% CI, 0.79-1.56).

By the same token, fathers of babies born between 2000 and 2009 had an OR of 1.01 for having a child with birth defects (95% CI, 0.81-1.26).

In postulating reasons for the slightly increased number of birth defects seen over the span of the study, the authors wrote: "While folic acid deficiency is common in newly diagnosed CD, it is sometimes seen after diagnosis, perhaps because of a lack of folic acid in the gluten-free diet."

And regarding the possible connection between fathers with CD and their children, "If spouses to men with CD are also primarily on a gluten-free diet, this may actually explain the excess risk for congenital malformation in paternal offspring."

Alternatively, "Low sperm quality in men with CD could potentially influence the risk of malformations."

The authors conceded several important weaknesses in this study. For one, they did not have data on diet adherence in CD, nor on the periconceptional or perinatal use of folic acid supplementation.

Moreover, a substantial proportion of pregnancies with neural tube defects discovered during prenatal screening were likely to have been terminated, potentially resulting in artificially low rates of this malformation: indeed, the authors pointed to data showing that between 1999 and 2009, between 51% and 93% of all NTD pregnancies were terminated, depending on the specific defect.

Finally, "Over time, symptoms have changed in CD," they wrote.

"It is possible that, with increased use of celiac serology, milder cases of CD are now diagnosed in which there is no association with congenital malformation."

The authors disclosed no conflicts of interest; individual authors disclosed several grants from nonprofit and research agencies in Europe, including the Italian Association for Cancer Research, the Stockholm County Council, the Danish Medical Research Council, and the Karolinska Institutet, among others.

CHICAGO – The antihypertensive agent olmesartan is associated with increased risk of a severe sprue-like enteropathy, as highlighted in a nationwide French cohort study.

This olmesartan-related illness is characterized by villous atrophy, severe chronic diarrhea, and weight loss, with negative serology for celiac disease.

The hospitalization rate for this disorder is time dependent. The risk doesn’t increase significantly until after the first year on therapy but climbs steeply thereafter, Dr. Myriam Mezzarobba reported at the annual Digestive Disease Week.

Importantly, angiotensin receptor blockers other than olmesartan (Benicar) were not associated with an increased risk of severe intestinal malabsorption in the French study. Neither were ACE inhibitors, added Dr. Mezzarobba of the French National Health Insurance Fund, Paris.

A few prior reports based on relatively limited patient numbers and/or short follow-up have indicated conflicting results regarding a possible association between olmesartan and severe intestinal malabsorption. This controversy provided the impetus for Dr. Mezzarobba and coinvestigators to conduct a cohort study harnessing the database of SNIIRAM, the French national health insurance plan covering 50 million residents, with linkage to the country’s centralized hospitalization database.

The investigators zeroed in on 4.5 million patients who started on an angiotensin receptor blocker or ACE inhibitor during 2007-2012. During more than 9 million person-years of follow-up, 218 of these individuals were hospitalized with a discharge diagnosis of intestinal malabsorption.

The incidence rate for this outcome among patients on olmesartan was 2.6 cases per 100,000 person-years during their first year on the medication, rising to 6.7 per 100,000 person-years during the second year and 8.9 per 100,000 person-years after 2 years on the drug.

In contrast, the rates among patients on other angiotensin receptor blockers were 2.1, 2.0, and 1.5 per 100,000 person-years, respectively, during the same treatment duration periods. And in patients on an ACE inhibitor, the rates were 3.7, 2.0, and 0.9 cases per 100,000 person-years during the first, second, and beyond the second year on therapy.

In a regression analysis controlled for age and sex, the adjusted rate ratio for hospitalization for intestinal malabsorption in patients on olmesartan compared with those on an ACE inhibitor was 0.7 for those on medication for less than a year, 3.3 during years 1-2, and 10.3 for those on olmesartan for longer than 2 years.

The typical pattern of this disorder is clinical and histologic remission following olmesartan discontinuation, Dr. Mezzarobba noted.

Session discussant Dr. Benjamin Lebwohl stressed that the French study holds a key lesson for gastroenterologists everywhere.

"Lest we become very aggressive in our case finding for celiac disease – and many of us are now looking more closely for this disease – we need to remember that villous atrophy is not always due to celiac disease," said Dr. Lebwohl, a gastroenterologist at Columbia University, New York.

He characterized the association between olmesartan and severe intestinal malabsorption found in the French national study as "robust," adding: "Importantly, this risk was not an acute risk. It increased over time. This is not an acute drug reaction, this is something that can develop at any point, even years after starting olmesartan."

Dr. Mezzarobba and Dr. Lebwohl reported having no financial conflicts.

bjancin@frontlinemedcom.com

CHICAGO – The antihypertensive agent olmesartan is associated with increased risk of a severe sprue-like enteropathy, as highlighted in a nationwide French cohort study.

This olmesartan-related illness is characterized by villous atrophy, severe chronic diarrhea, and weight loss, with negative serology for celiac disease.

The hospitalization rate for this disorder is time dependent. The risk doesn’t increase significantly until after the first year on therapy but climbs steeply thereafter, Dr. Myriam Mezzarobba reported at the annual Digestive Disease Week.

Importantly, angiotensin receptor blockers other than olmesartan (Benicar) were not associated with an increased risk of severe intestinal malabsorption in the French study. Neither were ACE inhibitors, added Dr. Mezzarobba of the French National Health Insurance Fund, Paris.

A few prior reports based on relatively limited patient numbers and/or short follow-up have indicated conflicting results regarding a possible association between olmesartan and severe intestinal malabsorption. This controversy provided the impetus for Dr. Mezzarobba and coinvestigators to conduct a cohort study harnessing the database of SNIIRAM, the French national health insurance plan covering 50 million residents, with linkage to the country’s centralized hospitalization database.

The investigators zeroed in on 4.5 million patients who started on an angiotensin receptor blocker or ACE inhibitor during 2007-2012. During more than 9 million person-years of follow-up, 218 of these individuals were hospitalized with a discharge diagnosis of intestinal malabsorption.

The incidence rate for this outcome among patients on olmesartan was 2.6 cases per 100,000 person-years during their first year on the medication, rising to 6.7 per 100,000 person-years during the second year and 8.9 per 100,000 person-years after 2 years on the drug.

In contrast, the rates among patients on other angiotensin receptor blockers were 2.1, 2.0, and 1.5 per 100,000 person-years, respectively, during the same treatment duration periods. And in patients on an ACE inhibitor, the rates were 3.7, 2.0, and 0.9 cases per 100,000 person-years during the first, second, and beyond the second year on therapy.

In a regression analysis controlled for age and sex, the adjusted rate ratio for hospitalization for intestinal malabsorption in patients on olmesartan compared with those on an ACE inhibitor was 0.7 for those on medication for less than a year, 3.3 during years 1-2, and 10.3 for those on olmesartan for longer than 2 years.

The typical pattern of this disorder is clinical and histologic remission following olmesartan discontinuation, Dr. Mezzarobba noted.

Session discussant Dr. Benjamin Lebwohl stressed that the French study holds a key lesson for gastroenterologists everywhere.

"Lest we become very aggressive in our case finding for celiac disease – and many of us are now looking more closely for this disease – we need to remember that villous atrophy is not always due to celiac disease," said Dr. Lebwohl, a gastroenterologist at Columbia University, New York.

He characterized the association between olmesartan and severe intestinal malabsorption found in the French national study as "robust," adding: "Importantly, this risk was not an acute risk. It increased over time. This is not an acute drug reaction, this is something that can develop at any point, even years after starting olmesartan."

Dr. Mezzarobba and Dr. Lebwohl reported having no financial conflicts.

bjancin@frontlinemedcom.com

CHICAGO – The antihypertensive agent olmesartan is associated with increased risk of a severe sprue-like enteropathy, as highlighted in a nationwide French cohort study.

This olmesartan-related illness is characterized by villous atrophy, severe chronic diarrhea, and weight loss, with negative serology for celiac disease.

The hospitalization rate for this disorder is time dependent. The risk doesn’t increase significantly until after the first year on therapy but climbs steeply thereafter, Dr. Myriam Mezzarobba reported at the annual Digestive Disease Week.

Importantly, angiotensin receptor blockers other than olmesartan (Benicar) were not associated with an increased risk of severe intestinal malabsorption in the French study. Neither were ACE inhibitors, added Dr. Mezzarobba of the French National Health Insurance Fund, Paris.

A few prior reports based on relatively limited patient numbers and/or short follow-up have indicated conflicting results regarding a possible association between olmesartan and severe intestinal malabsorption. This controversy provided the impetus for Dr. Mezzarobba and coinvestigators to conduct a cohort study harnessing the database of SNIIRAM, the French national health insurance plan covering 50 million residents, with linkage to the country’s centralized hospitalization database.

The investigators zeroed in on 4.5 million patients who started on an angiotensin receptor blocker or ACE inhibitor during 2007-2012. During more than 9 million person-years of follow-up, 218 of these individuals were hospitalized with a discharge diagnosis of intestinal malabsorption.

The incidence rate for this outcome among patients on olmesartan was 2.6 cases per 100,000 person-years during their first year on the medication, rising to 6.7 per 100,000 person-years during the second year and 8.9 per 100,000 person-years after 2 years on the drug.

In contrast, the rates among patients on other angiotensin receptor blockers were 2.1, 2.0, and 1.5 per 100,000 person-years, respectively, during the same treatment duration periods. And in patients on an ACE inhibitor, the rates were 3.7, 2.0, and 0.9 cases per 100,000 person-years during the first, second, and beyond the second year on therapy.

In a regression analysis controlled for age and sex, the adjusted rate ratio for hospitalization for intestinal malabsorption in patients on olmesartan compared with those on an ACE inhibitor was 0.7 for those on medication for less than a year, 3.3 during years 1-2, and 10.3 for those on olmesartan for longer than 2 years.

The typical pattern of this disorder is clinical and histologic remission following olmesartan discontinuation, Dr. Mezzarobba noted.

Session discussant Dr. Benjamin Lebwohl stressed that the French study holds a key lesson for gastroenterologists everywhere.

"Lest we become very aggressive in our case finding for celiac disease – and many of us are now looking more closely for this disease – we need to remember that villous atrophy is not always due to celiac disease," said Dr. Lebwohl, a gastroenterologist at Columbia University, New York.

He characterized the association between olmesartan and severe intestinal malabsorption found in the French national study as "robust," adding: "Importantly, this risk was not an acute risk. It increased over time. This is not an acute drug reaction, this is something that can develop at any point, even years after starting olmesartan."

Dr. Mezzarobba and Dr. Lebwohl reported having no financial conflicts.

bjancin@frontlinemedcom.com

CHICAGO – An 8-week course in mindfulness-based stress reduction reduced the severity of irritable bowel syndrome symptoms 6 and 12 months later, compared with 8 weeks of participation in a control group, follow-up on 68 women found.

Scores for overall irritable bowel syndrome (IBS) severity on the IBS Severity Scale (IBS-SS) were similar between groups at baseline (284 in the intervention group and 288 in the control group) but had improved significantly more in the mindfulness training group at 6 months (scores decreased 151 and 108 points, respectively) and at 12 months (scores decreased 115 vs. 26 points, respectively) compared with baseline.

The investigators originally reported significant benefits from the mindfulness course, compared with the control group immediately after the group sessions and at 3 months of follow-up in the prospective, randomized, controlled trial involving 75 patients (Am. J. Gastroenterol. 2011;106:1678-88). The current follow-up to 6 and 12 months shows lasting symptomatic improvements from mindfulness training, Olafur S. Palsson, Psy.D., and his associates reported at the annual Digestive Disease Week.

Among the 68 patients who completed 1 year of follow-up in the current analysis, the 33 who got mindfulness training also showed significantly greater improvements in secondary outcomes, compared with the 35 patients in the support group, said Dr. Palsson, a professor of medicine at the University of North Carolina, Chapel Hill.

Scores on the IBS Quality of Life Instrument were similar between groups at baseline (65 in the mindfulness group and 67 in the control group) but improved significantly more in the mindfulness group by 12 months (by 15 vs. 3, respectively).

Scores for gut-focused anxiety on the Visceral Sensitivity Index – which were not significantly different between groups at baseline or immediately after the group sessions – improved significantly more in the mindfulness group than in the control group by 3 months and the gains remained significantly greater at 6 months (by 12 vs. 2, respectively) and at 12 months (by 9 vs. –1, respectively).

"To our knowledge, these follow-up findings demonstrate some of the longest-duration therapeutic effects of mindfulness training ever reported in a clinical trial," he said.

Both interventions consisted of eight weekly sessions and a half-day retreat. The control group attended a conventional support group. The mindfulness course was based on the Mindfulness-Based Stress Reduction Program of Jon Kabat-Zinn, Ph.D., and Saki F. Santorelli, Ed.D., both of the University of Massachusetts, Worcester.

The longitudinal study controlled for the effects of race and income (less than or at least $40,000/year). The results suggest that the impact of mindfulness training on bowel symptom severity and gut-focused anxiety are well maintained and that improvements in health-related quality of life develop gradually over many months after the training, Dr. Palsson said. General psychological well-being did not change significantly based on the training, he added.

Scores for mindfulness on the Five-Facet Mindfulness Questionnaire were higher at every follow-up in the mindfulness group, compared with the control group, but the differences were not statistically significant. Mindfulness scores peaked in the mindfulness group at around 6 months and were attenuated at 12 months.

Patients ranged in age from 19 to 71 years, with a mean age of 43 years. Most patients were white, and women who were minorities or had lower incomes were more likely to drop out of the trial over time.

The National Center for Complementary and Alternative Medicine funded the study. Dr. Palsson and his coinvestigators reported financial associations with Takeda Pharmaceuticals, Ono Pharmaceuticals, Ironwood Pharmaceuticals, Entera Health, and/or the Rome Foundation.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

CHICAGO – An 8-week course in mindfulness-based stress reduction reduced the severity of irritable bowel syndrome symptoms 6 and 12 months later, compared with 8 weeks of participation in a control group, follow-up on 68 women found.

Scores for overall irritable bowel syndrome (IBS) severity on the IBS Severity Scale (IBS-SS) were similar between groups at baseline (284 in the intervention group and 288 in the control group) but had improved significantly more in the mindfulness training group at 6 months (scores decreased 151 and 108 points, respectively) and at 12 months (scores decreased 115 vs. 26 points, respectively) compared with baseline.

The investigators originally reported significant benefits from the mindfulness course, compared with the control group immediately after the group sessions and at 3 months of follow-up in the prospective, randomized, controlled trial involving 75 patients (Am. J. Gastroenterol. 2011;106:1678-88). The current follow-up to 6 and 12 months shows lasting symptomatic improvements from mindfulness training, Olafur S. Palsson, Psy.D., and his associates reported at the annual Digestive Disease Week.

Among the 68 patients who completed 1 year of follow-up in the current analysis, the 33 who got mindfulness training also showed significantly greater improvements in secondary outcomes, compared with the 35 patients in the support group, said Dr. Palsson, a professor of medicine at the University of North Carolina, Chapel Hill.

Scores on the IBS Quality of Life Instrument were similar between groups at baseline (65 in the mindfulness group and 67 in the control group) but improved significantly more in the mindfulness group by 12 months (by 15 vs. 3, respectively).

Scores for gut-focused anxiety on the Visceral Sensitivity Index – which were not significantly different between groups at baseline or immediately after the group sessions – improved significantly more in the mindfulness group than in the control group by 3 months and the gains remained significantly greater at 6 months (by 12 vs. 2, respectively) and at 12 months (by 9 vs. –1, respectively).

"To our knowledge, these follow-up findings demonstrate some of the longest-duration therapeutic effects of mindfulness training ever reported in a clinical trial," he said.

Both interventions consisted of eight weekly sessions and a half-day retreat. The control group attended a conventional support group. The mindfulness course was based on the Mindfulness-Based Stress Reduction Program of Jon Kabat-Zinn, Ph.D., and Saki F. Santorelli, Ed.D., both of the University of Massachusetts, Worcester.

The longitudinal study controlled for the effects of race and income (less than or at least $40,000/year). The results suggest that the impact of mindfulness training on bowel symptom severity and gut-focused anxiety are well maintained and that improvements in health-related quality of life develop gradually over many months after the training, Dr. Palsson said. General psychological well-being did not change significantly based on the training, he added.

Scores for mindfulness on the Five-Facet Mindfulness Questionnaire were higher at every follow-up in the mindfulness group, compared with the control group, but the differences were not statistically significant. Mindfulness scores peaked in the mindfulness group at around 6 months and were attenuated at 12 months.

Patients ranged in age from 19 to 71 years, with a mean age of 43 years. Most patients were white, and women who were minorities or had lower incomes were more likely to drop out of the trial over time.

The National Center for Complementary and Alternative Medicine funded the study. Dr. Palsson and his coinvestigators reported financial associations with Takeda Pharmaceuticals, Ono Pharmaceuticals, Ironwood Pharmaceuticals, Entera Health, and/or the Rome Foundation.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

CHICAGO – An 8-week course in mindfulness-based stress reduction reduced the severity of irritable bowel syndrome symptoms 6 and 12 months later, compared with 8 weeks of participation in a control group, follow-up on 68 women found.

Scores for overall irritable bowel syndrome (IBS) severity on the IBS Severity Scale (IBS-SS) were similar between groups at baseline (284 in the intervention group and 288 in the control group) but had improved significantly more in the mindfulness training group at 6 months (scores decreased 151 and 108 points, respectively) and at 12 months (scores decreased 115 vs. 26 points, respectively) compared with baseline.

The investigators originally reported significant benefits from the mindfulness course, compared with the control group immediately after the group sessions and at 3 months of follow-up in the prospective, randomized, controlled trial involving 75 patients (Am. J. Gastroenterol. 2011;106:1678-88). The current follow-up to 6 and 12 months shows lasting symptomatic improvements from mindfulness training, Olafur S. Palsson, Psy.D., and his associates reported at the annual Digestive Disease Week.

Among the 68 patients who completed 1 year of follow-up in the current analysis, the 33 who got mindfulness training also showed significantly greater improvements in secondary outcomes, compared with the 35 patients in the support group, said Dr. Palsson, a professor of medicine at the University of North Carolina, Chapel Hill.

Scores on the IBS Quality of Life Instrument were similar between groups at baseline (65 in the mindfulness group and 67 in the control group) but improved significantly more in the mindfulness group by 12 months (by 15 vs. 3, respectively).

Scores for gut-focused anxiety on the Visceral Sensitivity Index – which were not significantly different between groups at baseline or immediately after the group sessions – improved significantly more in the mindfulness group than in the control group by 3 months and the gains remained significantly greater at 6 months (by 12 vs. 2, respectively) and at 12 months (by 9 vs. –1, respectively).

"To our knowledge, these follow-up findings demonstrate some of the longest-duration therapeutic effects of mindfulness training ever reported in a clinical trial," he said.

Both interventions consisted of eight weekly sessions and a half-day retreat. The control group attended a conventional support group. The mindfulness course was based on the Mindfulness-Based Stress Reduction Program of Jon Kabat-Zinn, Ph.D., and Saki F. Santorelli, Ed.D., both of the University of Massachusetts, Worcester.

The longitudinal study controlled for the effects of race and income (less than or at least $40,000/year). The results suggest that the impact of mindfulness training on bowel symptom severity and gut-focused anxiety are well maintained and that improvements in health-related quality of life develop gradually over many months after the training, Dr. Palsson said. General psychological well-being did not change significantly based on the training, he added.

Scores for mindfulness on the Five-Facet Mindfulness Questionnaire were higher at every follow-up in the mindfulness group, compared with the control group, but the differences were not statistically significant. Mindfulness scores peaked in the mindfulness group at around 6 months and were attenuated at 12 months.

Patients ranged in age from 19 to 71 years, with a mean age of 43 years. Most patients were white, and women who were minorities or had lower incomes were more likely to drop out of the trial over time.

The National Center for Complementary and Alternative Medicine funded the study. Dr. Palsson and his coinvestigators reported financial associations with Takeda Pharmaceuticals, Ono Pharmaceuticals, Ironwood Pharmaceuticals, Entera Health, and/or the Rome Foundation.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

CHICAGO – New data shine a light on the trade-offs involved in resuming low-dose aspirin therapy for secondary cardiovascular prevention following a lower gastrointestinal bleeding event.

Going back onto daily low-dose aspirin was associated with a 2.7-fold greater risk of recurrent lower GI bleeding than no use of aspirin during 5 years of follow-up. However, the risk of a major cardiovascular event – nonfatal myocardial infarction or stroke or death due to a vascular cause – was reduced by 38%. Moreover, the rate of death due to nonvascular causes was 3.2-fold lower among the aspirin-using group, Dr. Francis K.L. Chan reported at the annual Digestive Disease Week.

He presented a single-center retrospective cohort study involving 295 patients who developed endoscopically confirmed lower GI bleeding while on low-dose aspirin for secondary cardiovascular prevention. A total of 174 subjects in this observational study resumed aspirin and 121 did not.

The two groups were similar in terms of their cardiovascular risk profiles based upon conventional risk factors. However, the aspirin nonusers, with a mean age of 76 years, were on average 3 years older than those who resumed aspirin. The nonusers were also more likely to have had a severe index lower GI bleed requiring transfusion of more than 2 units of blood products, by a margin of 55%-40%. An upper GI bleeding source was excluded by endoscopy in all participants, noted Dr. Chan of the Chinese University of Hong Kong.

The 5-year cumulative incidence of recurrent lower GI bleeding was 18.9% among the aspirin users, compared with 6.9% in the nonusers. The incidence of a major cardiovascular event was 22.8% in the aspirin group versus 36.5% among aspirin nonusers. And the 5-year incidence of death due to nonvascular causes was 8.2% in the aspirin users, compared with 26.7% in nonusers.

The nature of the Hong Kong health care system is such that all outcomes of interest were reliably captured. Eighty-four percent of patients in the aspirin user group received prescriptions for aspirin during at least 75% of the follow-up period, while 87% of the nonuser group received aspirin during 10% or less of the study period.

Audience members praised Dr. Chan for providing "clear-cut" and "very significant" findings addressing the previously unanswered but clinically important question of the risks and benefits of aspirin resumption versus nonuse following a lower GI bleed occurring while on therapy.

The study was carried out with institutional funds. Dr. Chan is on speakers bureaus for AstraZeneca, Pfizer, Takeda, and Eisai.

bjancin@frontlinemedcom.com

CHICAGO – New data shine a light on the trade-offs involved in resuming low-dose aspirin therapy for secondary cardiovascular prevention following a lower gastrointestinal bleeding event.

Going back onto daily low-dose aspirin was associated with a 2.7-fold greater risk of recurrent lower GI bleeding than no use of aspirin during 5 years of follow-up. However, the risk of a major cardiovascular event – nonfatal myocardial infarction or stroke or death due to a vascular cause – was reduced by 38%. Moreover, the rate of death due to nonvascular causes was 3.2-fold lower among the aspirin-using group, Dr. Francis K.L. Chan reported at the annual Digestive Disease Week.

He presented a single-center retrospective cohort study involving 295 patients who developed endoscopically confirmed lower GI bleeding while on low-dose aspirin for secondary cardiovascular prevention. A total of 174 subjects in this observational study resumed aspirin and 121 did not.

The two groups were similar in terms of their cardiovascular risk profiles based upon conventional risk factors. However, the aspirin nonusers, with a mean age of 76 years, were on average 3 years older than those who resumed aspirin. The nonusers were also more likely to have had a severe index lower GI bleed requiring transfusion of more than 2 units of blood products, by a margin of 55%-40%. An upper GI bleeding source was excluded by endoscopy in all participants, noted Dr. Chan of the Chinese University of Hong Kong.

The 5-year cumulative incidence of recurrent lower GI bleeding was 18.9% among the aspirin users, compared with 6.9% in the nonusers. The incidence of a major cardiovascular event was 22.8% in the aspirin group versus 36.5% among aspirin nonusers. And the 5-year incidence of death due to nonvascular causes was 8.2% in the aspirin users, compared with 26.7% in nonusers.

The nature of the Hong Kong health care system is such that all outcomes of interest were reliably captured. Eighty-four percent of patients in the aspirin user group received prescriptions for aspirin during at least 75% of the follow-up period, while 87% of the nonuser group received aspirin during 10% or less of the study period.

Audience members praised Dr. Chan for providing "clear-cut" and "very significant" findings addressing the previously unanswered but clinically important question of the risks and benefits of aspirin resumption versus nonuse following a lower GI bleed occurring while on therapy.

The study was carried out with institutional funds. Dr. Chan is on speakers bureaus for AstraZeneca, Pfizer, Takeda, and Eisai.

bjancin@frontlinemedcom.com

CHICAGO – New data shine a light on the trade-offs involved in resuming low-dose aspirin therapy for secondary cardiovascular prevention following a lower gastrointestinal bleeding event.

Going back onto daily low-dose aspirin was associated with a 2.7-fold greater risk of recurrent lower GI bleeding than no use of aspirin during 5 years of follow-up. However, the risk of a major cardiovascular event – nonfatal myocardial infarction or stroke or death due to a vascular cause – was reduced by 38%. Moreover, the rate of death due to nonvascular causes was 3.2-fold lower among the aspirin-using group, Dr. Francis K.L. Chan reported at the annual Digestive Disease Week.

He presented a single-center retrospective cohort study involving 295 patients who developed endoscopically confirmed lower GI bleeding while on low-dose aspirin for secondary cardiovascular prevention. A total of 174 subjects in this observational study resumed aspirin and 121 did not.

The two groups were similar in terms of their cardiovascular risk profiles based upon conventional risk factors. However, the aspirin nonusers, with a mean age of 76 years, were on average 3 years older than those who resumed aspirin. The nonusers were also more likely to have had a severe index lower GI bleed requiring transfusion of more than 2 units of blood products, by a margin of 55%-40%. An upper GI bleeding source was excluded by endoscopy in all participants, noted Dr. Chan of the Chinese University of Hong Kong.

The 5-year cumulative incidence of recurrent lower GI bleeding was 18.9% among the aspirin users, compared with 6.9% in the nonusers. The incidence of a major cardiovascular event was 22.8% in the aspirin group versus 36.5% among aspirin nonusers. And the 5-year incidence of death due to nonvascular causes was 8.2% in the aspirin users, compared with 26.7% in nonusers.

The nature of the Hong Kong health care system is such that all outcomes of interest were reliably captured. Eighty-four percent of patients in the aspirin user group received prescriptions for aspirin during at least 75% of the follow-up period, while 87% of the nonuser group received aspirin during 10% or less of the study period.

Audience members praised Dr. Chan for providing "clear-cut" and "very significant" findings addressing the previously unanswered but clinically important question of the risks and benefits of aspirin resumption versus nonuse following a lower GI bleed occurring while on therapy.

The study was carried out with institutional funds. Dr. Chan is on speakers bureaus for AstraZeneca, Pfizer, Takeda, and Eisai.

bjancin@frontlinemedcom.com

The tumor necrosis factor–alpha antagonists infliximab, adalimumab, and certolizumab did not raise the risk of cancer in a nationwide Danish cohort study of patients with inflammatory bowel disease who were followed for approximately 10 years, according to a report published online June 17 in JAMA.

At present, the effectiveness of these agents in inflammatory bowel disease (IBD) must be weighed against their potential adverse effects, which include immunosuppression that is suspected to increase the risk of cancer. But few studies have examined this risk, and those that have done so have had short (less than 1 year) exposure and follow-up times, said Dr. Nynne Nyboe Andersen of the department of epidemiology research, Statens Serum Institut, Copenhagen, and her associates.

They assessed the risks of any cancer and of 11 individual cancers in 56,146 IBD patients aged 15 and older living in Denmark in 1999-2012, of whom 4,553 took TNF-alpha antagonists. Median follow-up was 9.3 years, and median duration of therapy with TNF-alpha antagonists was 3.7 years. The two study groups were propensity matched for year of birth, sex, socioeconomic status, comorbidities, use of other medications, subtype of IBD, and history of gastrointestinal or anal fistula, abscess, fissure, or surgery.

A total of 6.7% of the patients who never took TNF-alpha antagonists developed cancer during follow-up, compared with 1.8% of patients who took the drugs, indicating no increase in cancer risk associated with TNF-alpha antagonists. Further analyses of the data found no association between use of these agents and the risk of overall cancer, regardless of the patient’s sex, age, the duration of therapy, or the cumulative dose, and sensitivity analyses confirmed these results, the investigators said (JAMA 2014 June 17 [doi:10.1001/jama.2014.5613]).

There also was no association between use of TNF-alpha antagonists and any individual cancer. "However, it should be noted that because of the relatively small sample size and the small number of cancer cases in our study, statistical power was limited in subgroup analyses of site-specific cancers," Dr. Andersen and her associates said.

"Stratifying for cancer risk according to years since first exposure, no specific time-dependent pattern was observed in our study. However, considering the often protracted progression of cancer, an increased risk in the long term cannot be excluded, and future studies with longer follow-up are needed," they added.

The Lundbeck Foundation, Danish Cancer Society, Crohn’s and Colitis Association of Denmark, and Danish Council of Independent Research supported the study. Dr. Andersen reported receiving funding from Merck Sharp & Dohme; her associates reported ties to Merck Sharp & Dohme, Tillotts, Calpro, Ferring, and AbbVie.

The tumor necrosis factor–alpha antagonists infliximab, adalimumab, and certolizumab did not raise the risk of cancer in a nationwide Danish cohort study of patients with inflammatory bowel disease who were followed for approximately 10 years, according to a report published online June 17 in JAMA.

At present, the effectiveness of these agents in inflammatory bowel disease (IBD) must be weighed against their potential adverse effects, which include immunosuppression that is suspected to increase the risk of cancer. But few studies have examined this risk, and those that have done so have had short (less than 1 year) exposure and follow-up times, said Dr. Nynne Nyboe Andersen of the department of epidemiology research, Statens Serum Institut, Copenhagen, and her associates.

They assessed the risks of any cancer and of 11 individual cancers in 56,146 IBD patients aged 15 and older living in Denmark in 1999-2012, of whom 4,553 took TNF-alpha antagonists. Median follow-up was 9.3 years, and median duration of therapy with TNF-alpha antagonists was 3.7 years. The two study groups were propensity matched for year of birth, sex, socioeconomic status, comorbidities, use of other medications, subtype of IBD, and history of gastrointestinal or anal fistula, abscess, fissure, or surgery.

A total of 6.7% of the patients who never took TNF-alpha antagonists developed cancer during follow-up, compared with 1.8% of patients who took the drugs, indicating no increase in cancer risk associated with TNF-alpha antagonists. Further analyses of the data found no association between use of these agents and the risk of overall cancer, regardless of the patient’s sex, age, the duration of therapy, or the cumulative dose, and sensitivity analyses confirmed these results, the investigators said (JAMA 2014 June 17 [doi:10.1001/jama.2014.5613]).

There also was no association between use of TNF-alpha antagonists and any individual cancer. "However, it should be noted that because of the relatively small sample size and the small number of cancer cases in our study, statistical power was limited in subgroup analyses of site-specific cancers," Dr. Andersen and her associates said.

"Stratifying for cancer risk according to years since first exposure, no specific time-dependent pattern was observed in our study. However, considering the often protracted progression of cancer, an increased risk in the long term cannot be excluded, and future studies with longer follow-up are needed," they added.

The Lundbeck Foundation, Danish Cancer Society, Crohn’s and Colitis Association of Denmark, and Danish Council of Independent Research supported the study. Dr. Andersen reported receiving funding from Merck Sharp & Dohme; her associates reported ties to Merck Sharp & Dohme, Tillotts, Calpro, Ferring, and AbbVie.

The tumor necrosis factor–alpha antagonists infliximab, adalimumab, and certolizumab did not raise the risk of cancer in a nationwide Danish cohort study of patients with inflammatory bowel disease who were followed for approximately 10 years, according to a report published online June 17 in JAMA.

At present, the effectiveness of these agents in inflammatory bowel disease (IBD) must be weighed against their potential adverse effects, which include immunosuppression that is suspected to increase the risk of cancer. But few studies have examined this risk, and those that have done so have had short (less than 1 year) exposure and follow-up times, said Dr. Nynne Nyboe Andersen of the department of epidemiology research, Statens Serum Institut, Copenhagen, and her associates.

They assessed the risks of any cancer and of 11 individual cancers in 56,146 IBD patients aged 15 and older living in Denmark in 1999-2012, of whom 4,553 took TNF-alpha antagonists. Median follow-up was 9.3 years, and median duration of therapy with TNF-alpha antagonists was 3.7 years. The two study groups were propensity matched for year of birth, sex, socioeconomic status, comorbidities, use of other medications, subtype of IBD, and history of gastrointestinal or anal fistula, abscess, fissure, or surgery.

A total of 6.7% of the patients who never took TNF-alpha antagonists developed cancer during follow-up, compared with 1.8% of patients who took the drugs, indicating no increase in cancer risk associated with TNF-alpha antagonists. Further analyses of the data found no association between use of these agents and the risk of overall cancer, regardless of the patient’s sex, age, the duration of therapy, or the cumulative dose, and sensitivity analyses confirmed these results, the investigators said (JAMA 2014 June 17 [doi:10.1001/jama.2014.5613]).

There also was no association between use of TNF-alpha antagonists and any individual cancer. "However, it should be noted that because of the relatively small sample size and the small number of cancer cases in our study, statistical power was limited in subgroup analyses of site-specific cancers," Dr. Andersen and her associates said.

"Stratifying for cancer risk according to years since first exposure, no specific time-dependent pattern was observed in our study. However, considering the often protracted progression of cancer, an increased risk in the long term cannot be excluded, and future studies with longer follow-up are needed," they added.

The Lundbeck Foundation, Danish Cancer Society, Crohn’s and Colitis Association of Denmark, and Danish Council of Independent Research supported the study. Dr. Andersen reported receiving funding from Merck Sharp & Dohme; her associates reported ties to Merck Sharp & Dohme, Tillotts, Calpro, Ferring, and AbbVie.

CHICAGO – Women with inflammatory bowel disease can safely continue monotherapy with azathioprine/6-mercaptopurine or antitumor necrosis–alpha agents during pregnancy to maintain remission, according to an analysis of 1,289 women and 1,039 live births.

Infants exposed to azathioprine/6 MP and anti-TNF-alpha agents achieve developmental milestone scores at rates similar to unexposed infants and do not have higher rates of congenital anomalies, lead author Dr. Uma Mahadevan said at the annual Digestive Disease Week.

Overall, there were 55 congenital anomalies, with 21 diagnosed at birth. Events were similar among infants with in utero exposure to azathioprine, anti-TNF agents, combination therapy, and those with no drug exposure (12 vs. 17 vs. 7 vs. 19 events).

Exposure was defined as any use of azathioprine/6 MP or the anti-TNF-alpha agents infliximab (Remicade), adalimumab (Humira), or certolizumab pegol (Cimzia) at any time from 3 months prior to conception to the end of the pregnancy. Nine women had exposure to the recombinant monoclonal antibody natalizumab (Tysabri) and were included in the anti-TNF agents group.

The analysis was based on the PIANO registry, a prospective cohort of pregnant women with IBD who were followed by telephone or in-person questionnaire at every trimester, at delivery, at 4, 9, and 12 months after delivery, and annually for the first 4 years of their child’s life. Seven women received their diagnosis of IBD during pregnancy, 59.4% had Crohn’s disease, 38.3% ulcerative colitis, and 2.3% were indeterminate.

Two-thirds of women reported breastfeeding, with unexposed women significantly more likely to breastfeed than women with exposure to azathioprine, anti-TNF agents, or combination therapy (85% vs. 65% vs. 71% vs. 61%; P less than .0001).

After controlling for drug exposure, breastfeeding was not associated with an increased risk of infant infection or reduced height or weight, reported Dr. Mahadevan, with the University of California San Francisco.

Infants exposed to combination therapy, however, had higher rates of preterm birth, after adjustment for none/mild vs. moderate/severe IBD activity (odds ratio, 2.6; P less than .05).

Infants exposed to combination therapy who were born to mothers with ulcerative colitis also had increased rates of preterm birth (odds ratio, 4.9), low birth weight (OR, 6.1), and NICU stay (OR, 3.9).

One possible reason for this signal is that women with ulcerative colitis in the PIANO registry, as well as two other studies, have more disease activity during pregnancy, Dr. Mahadevan suggested. Another possibility is that mothers with ulcerative colitis may have low levels of untreated inflammation.

With just 161 women available for analysis, the PIANO investigators previously reported a significant increase in infant infections at 12 months of age in those exposed to combination infliximab or adalimumab plus azathioprine. Most anti-TNF agents cross the placenta in the second and third trimester, which has raised concerns about immune system development and risk of subsequent infections.

In the current analysis, there was no increase in infant infections when the investigators looked at all anti-TNF drugs. "But when we removed certolizumab from the analysis, it was significant just as it was 2 years ago," Dr. Mahadevan said in an interview. "Certolizumab is not actively transported across the placenta. Fortunately, the majority of the infections were minor, including otitis media and upper respiratory infections."

Developmental milestones

Overall, infants exposed to azathioprine or anti-TNF agents were found to achieve developmental milestones at rates similar to unexposed infants of mothers with IBD based on Denver Childhood Developmental Test and Ages and Stages Questionnaire scores, she said.

After controlling for preterm birth, the mean developmental milestone score at 4 months was 0.92 for infants with no drug exposure, with a nonsignificant mean delta difference of 0.01, 0.01, 0.00 points for infants exposed to azathioprine, anti-TNF agents, and combination therapy, respectively.

In a surprising twist, infants exposed to anti-TNF agents alone actually had significantly better scores at 12 months than unexposed infants, bettering the average score of 0.81 in the unexposed group by a mean delta of 0.02 points (P = .01), Dr. Mahadevan said.

"I wouldn’t interpret this data [as indicating] that biologics make your baby smarter. I think the key thing is that it doesn’t make it worse," she remarked. "When you see the deltas, they are pretty small."

On the Ages and Stages Questionnaire, the biologic group had significantly better mean scores than the unexposed group for gross motor skills at 36 months (55.94 vs. 47.53; P = .01), gross motor skills at 48 months (60 vs. 51.20; P = .02), fine motor skills at 48 months (53.50 vs. 42.11; P = .01), and personal/social interaction at 48 months (58 vs. 51.93; P = .04).

The azathioprine-exposed group always had better scores than the unexposed group, Dr. Mahadevan said. Where it was statistically significant was for personal/social interaction at 24 months (50.75 vs. 47.34; P = .04), problem solving at 36 months (mean 52.04 vs. 48.66; P = .05), and problem solving at 48 months (mean 59.92 vs. 57.66; P = .02).

Dr. Mahadevan observed that the data may change because not all infants have reached each time point and may not reflect outcomes in lower socioeconomic groups since more than 90% of women were of similar socioeconomic and educational status.

Still, the findings are reassuring in the absence of any randomized controlled trials. A recent report found children born to mothers with IBD had higher rates of attention-deficit hyperactivity disorder and gross motor abnormalities (J. Crohns Colitis 2013;7:542-50), while a case series reported normal neuropsychological development in 25 consecutive children exposed in utero to TNF-alpha inhibitors (Inflamm. Bowel Dis. 2014;20:495-501), she noted.

A recent systematic review of 58 articles or abstracts also found no association between TNF-alpha inhibitor use during pregnancy with IBD and adverse pregnancy outcomes, congenital abnormalities, or infections in the first year of life (BMC Medicine 2013;11:174).

The study was supported by the Crohn’s and Colitis Foundation of America. Dr. Mahadevan reported serving as an advisor for Janssen-Cilag, AbbVie, Takeda, and UCB Pharma, and receiving research grants from Prometheus Laboratories and GlaxoSmithKline.

pwendling@frontlinemedcom.com

CHICAGO – Women with inflammatory bowel disease can safely continue monotherapy with azathioprine/6-mercaptopurine or antitumor necrosis–alpha agents during pregnancy to maintain remission, according to an analysis of 1,289 women and 1,039 live births.

Infants exposed to azathioprine/6 MP and anti-TNF-alpha agents achieve developmental milestone scores at rates similar to unexposed infants and do not have higher rates of congenital anomalies, lead author Dr. Uma Mahadevan said at the annual Digestive Disease Week.

Overall, there were 55 congenital anomalies, with 21 diagnosed at birth. Events were similar among infants with in utero exposure to azathioprine, anti-TNF agents, combination therapy, and those with no drug exposure (12 vs. 17 vs. 7 vs. 19 events).

Exposure was defined as any use of azathioprine/6 MP or the anti-TNF-alpha agents infliximab (Remicade), adalimumab (Humira), or certolizumab pegol (Cimzia) at any time from 3 months prior to conception to the end of the pregnancy. Nine women had exposure to the recombinant monoclonal antibody natalizumab (Tysabri) and were included in the anti-TNF agents group.

The analysis was based on the PIANO registry, a prospective cohort of pregnant women with IBD who were followed by telephone or in-person questionnaire at every trimester, at delivery, at 4, 9, and 12 months after delivery, and annually for the first 4 years of their child’s life. Seven women received their diagnosis of IBD during pregnancy, 59.4% had Crohn’s disease, 38.3% ulcerative colitis, and 2.3% were indeterminate.

Two-thirds of women reported breastfeeding, with unexposed women significantly more likely to breastfeed than women with exposure to azathioprine, anti-TNF agents, or combination therapy (85% vs. 65% vs. 71% vs. 61%; P less than .0001).

After controlling for drug exposure, breastfeeding was not associated with an increased risk of infant infection or reduced height or weight, reported Dr. Mahadevan, with the University of California San Francisco.

Infants exposed to combination therapy, however, had higher rates of preterm birth, after adjustment for none/mild vs. moderate/severe IBD activity (odds ratio, 2.6; P less than .05).

Infants exposed to combination therapy who were born to mothers with ulcerative colitis also had increased rates of preterm birth (odds ratio, 4.9), low birth weight (OR, 6.1), and NICU stay (OR, 3.9).

One possible reason for this signal is that women with ulcerative colitis in the PIANO registry, as well as two other studies, have more disease activity during pregnancy, Dr. Mahadevan suggested. Another possibility is that mothers with ulcerative colitis may have low levels of untreated inflammation.

With just 161 women available for analysis, the PIANO investigators previously reported a significant increase in infant infections at 12 months of age in those exposed to combination infliximab or adalimumab plus azathioprine. Most anti-TNF agents cross the placenta in the second and third trimester, which has raised concerns about immune system development and risk of subsequent infections.

In the current analysis, there was no increase in infant infections when the investigators looked at all anti-TNF drugs. "But when we removed certolizumab from the analysis, it was significant just as it was 2 years ago," Dr. Mahadevan said in an interview. "Certolizumab is not actively transported across the placenta. Fortunately, the majority of the infections were minor, including otitis media and upper respiratory infections."

Developmental milestones

Overall, infants exposed to azathioprine or anti-TNF agents were found to achieve developmental milestones at rates similar to unexposed infants of mothers with IBD based on Denver Childhood Developmental Test and Ages and Stages Questionnaire scores, she said.

After controlling for preterm birth, the mean developmental milestone score at 4 months was 0.92 for infants with no drug exposure, with a nonsignificant mean delta difference of 0.01, 0.01, 0.00 points for infants exposed to azathioprine, anti-TNF agents, and combination therapy, respectively.

In a surprising twist, infants exposed to anti-TNF agents alone actually had significantly better scores at 12 months than unexposed infants, bettering the average score of 0.81 in the unexposed group by a mean delta of 0.02 points (P = .01), Dr. Mahadevan said.

"I wouldn’t interpret this data [as indicating] that biologics make your baby smarter. I think the key thing is that it doesn’t make it worse," she remarked. "When you see the deltas, they are pretty small."

On the Ages and Stages Questionnaire, the biologic group had significantly better mean scores than the unexposed group for gross motor skills at 36 months (55.94 vs. 47.53; P = .01), gross motor skills at 48 months (60 vs. 51.20; P = .02), fine motor skills at 48 months (53.50 vs. 42.11; P = .01), and personal/social interaction at 48 months (58 vs. 51.93; P = .04).

The azathioprine-exposed group always had better scores than the unexposed group, Dr. Mahadevan said. Where it was statistically significant was for personal/social interaction at 24 months (50.75 vs. 47.34; P = .04), problem solving at 36 months (mean 52.04 vs. 48.66; P = .05), and problem solving at 48 months (mean 59.92 vs. 57.66; P = .02).

Dr. Mahadevan observed that the data may change because not all infants have reached each time point and may not reflect outcomes in lower socioeconomic groups since more than 90% of women were of similar socioeconomic and educational status.

Still, the findings are reassuring in the absence of any randomized controlled trials. A recent report found children born to mothers with IBD had higher rates of attention-deficit hyperactivity disorder and gross motor abnormalities (J. Crohns Colitis 2013;7:542-50), while a case series reported normal neuropsychological development in 25 consecutive children exposed in utero to TNF-alpha inhibitors (Inflamm. Bowel Dis. 2014;20:495-501), she noted.

A recent systematic review of 58 articles or abstracts also found no association between TNF-alpha inhibitor use during pregnancy with IBD and adverse pregnancy outcomes, congenital abnormalities, or infections in the first year of life (BMC Medicine 2013;11:174).

The study was supported by the Crohn’s and Colitis Foundation of America. Dr. Mahadevan reported serving as an advisor for Janssen-Cilag, AbbVie, Takeda, and UCB Pharma, and receiving research grants from Prometheus Laboratories and GlaxoSmithKline.

pwendling@frontlinemedcom.com

CHICAGO – Women with inflammatory bowel disease can safely continue monotherapy with azathioprine/6-mercaptopurine or antitumor necrosis–alpha agents during pregnancy to maintain remission, according to an analysis of 1,289 women and 1,039 live births.

Infants exposed to azathioprine/6 MP and anti-TNF-alpha agents achieve developmental milestone scores at rates similar to unexposed infants and do not have higher rates of congenital anomalies, lead author Dr. Uma Mahadevan said at the annual Digestive Disease Week.

Overall, there were 55 congenital anomalies, with 21 diagnosed at birth. Events were similar among infants with in utero exposure to azathioprine, anti-TNF agents, combination therapy, and those with no drug exposure (12 vs. 17 vs. 7 vs. 19 events).

Exposure was defined as any use of azathioprine/6 MP or the anti-TNF-alpha agents infliximab (Remicade), adalimumab (Humira), or certolizumab pegol (Cimzia) at any time from 3 months prior to conception to the end of the pregnancy. Nine women had exposure to the recombinant monoclonal antibody natalizumab (Tysabri) and were included in the anti-TNF agents group.

The analysis was based on the PIANO registry, a prospective cohort of pregnant women with IBD who were followed by telephone or in-person questionnaire at every trimester, at delivery, at 4, 9, and 12 months after delivery, and annually for the first 4 years of their child’s life. Seven women received their diagnosis of IBD during pregnancy, 59.4% had Crohn’s disease, 38.3% ulcerative colitis, and 2.3% were indeterminate.

Two-thirds of women reported breastfeeding, with unexposed women significantly more likely to breastfeed than women with exposure to azathioprine, anti-TNF agents, or combination therapy (85% vs. 65% vs. 71% vs. 61%; P less than .0001).

After controlling for drug exposure, breastfeeding was not associated with an increased risk of infant infection or reduced height or weight, reported Dr. Mahadevan, with the University of California San Francisco.

Infants exposed to combination therapy, however, had higher rates of preterm birth, after adjustment for none/mild vs. moderate/severe IBD activity (odds ratio, 2.6; P less than .05).

Infants exposed to combination therapy who were born to mothers with ulcerative colitis also had increased rates of preterm birth (odds ratio, 4.9), low birth weight (OR, 6.1), and NICU stay (OR, 3.9).

One possible reason for this signal is that women with ulcerative colitis in the PIANO registry, as well as two other studies, have more disease activity during pregnancy, Dr. Mahadevan suggested. Another possibility is that mothers with ulcerative colitis may have low levels of untreated inflammation.

With just 161 women available for analysis, the PIANO investigators previously reported a significant increase in infant infections at 12 months of age in those exposed to combination infliximab or adalimumab plus azathioprine. Most anti-TNF agents cross the placenta in the second and third trimester, which has raised concerns about immune system development and risk of subsequent infections.

In the current analysis, there was no increase in infant infections when the investigators looked at all anti-TNF drugs. "But when we removed certolizumab from the analysis, it was significant just as it was 2 years ago," Dr. Mahadevan said in an interview. "Certolizumab is not actively transported across the placenta. Fortunately, the majority of the infections were minor, including otitis media and upper respiratory infections."

Developmental milestones

Overall, infants exposed to azathioprine or anti-TNF agents were found to achieve developmental milestones at rates similar to unexposed infants of mothers with IBD based on Denver Childhood Developmental Test and Ages and Stages Questionnaire scores, she said.

After controlling for preterm birth, the mean developmental milestone score at 4 months was 0.92 for infants with no drug exposure, with a nonsignificant mean delta difference of 0.01, 0.01, 0.00 points for infants exposed to azathioprine, anti-TNF agents, and combination therapy, respectively.

In a surprising twist, infants exposed to anti-TNF agents alone actually had significantly better scores at 12 months than unexposed infants, bettering the average score of 0.81 in the unexposed group by a mean delta of 0.02 points (P = .01), Dr. Mahadevan said.

"I wouldn’t interpret this data [as indicating] that biologics make your baby smarter. I think the key thing is that it doesn’t make it worse," she remarked. "When you see the deltas, they are pretty small."

On the Ages and Stages Questionnaire, the biologic group had significantly better mean scores than the unexposed group for gross motor skills at 36 months (55.94 vs. 47.53; P = .01), gross motor skills at 48 months (60 vs. 51.20; P = .02), fine motor skills at 48 months (53.50 vs. 42.11; P = .01), and personal/social interaction at 48 months (58 vs. 51.93; P = .04).

The azathioprine-exposed group always had better scores than the unexposed group, Dr. Mahadevan said. Where it was statistically significant was for personal/social interaction at 24 months (50.75 vs. 47.34; P = .04), problem solving at 36 months (mean 52.04 vs. 48.66; P = .05), and problem solving at 48 months (mean 59.92 vs. 57.66; P = .02).

Dr. Mahadevan observed that the data may change because not all infants have reached each time point and may not reflect outcomes in lower socioeconomic groups since more than 90% of women were of similar socioeconomic and educational status.

Still, the findings are reassuring in the absence of any randomized controlled trials. A recent report found children born to mothers with IBD had higher rates of attention-deficit hyperactivity disorder and gross motor abnormalities (J. Crohns Colitis 2013;7:542-50), while a case series reported normal neuropsychological development in 25 consecutive children exposed in utero to TNF-alpha inhibitors (Inflamm. Bowel Dis. 2014;20:495-501), she noted.

A recent systematic review of 58 articles or abstracts also found no association between TNF-alpha inhibitor use during pregnancy with IBD and adverse pregnancy outcomes, congenital abnormalities, or infections in the first year of life (BMC Medicine 2013;11:174).

The study was supported by the Crohn’s and Colitis Foundation of America. Dr. Mahadevan reported serving as an advisor for Janssen-Cilag, AbbVie, Takeda, and UCB Pharma, and receiving research grants from Prometheus Laboratories and GlaxoSmithKline.

pwendling@frontlinemedcom.com

CHICAGO – Norfloxacin therapy relieved symptoms of irritable bowel syndrome better than placebo did in a prospective study of 80 patients, especially in patients with small intestinal bacterial overgrowth.*

The double-blind study randomized 15 patients with small intestinal bacterial overgrowth and 65 patients without overgrowth to treatment with either norfloxacin 400 mg b.i.d. or placebo for 10 days. Small intestinal bacterial overgrowth was diagnosed by a quantitative upper gut aspirate culture showing a total bacterial count of at least 10⁵/mL colony-forming units (CFU) of upper gut aspirate, or a glucose hydrogen breath test showing a rise in breath hydrogen of at least 12 ppm after glucose ingestion.

One month later, irritable bowel syndrome (IBS) symptoms resolved in 15 of 40 patients who received the fluoroquinolone antibiotic (38%) and in none of the 40 patients who got placebo, Dr. Uday C. Ghoshal and his associates reported at the annual Digestive Disease Week. Symptoms were assessed using the Rome III criteria.

Among the 15 patients with small intestinal bacterial overgrowth, symptoms resolved in 7 of 8 who received norfloxacin (88%) and in 0 of 7 who got placebo, reported Dr. Ghoshal of the Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.

Among the 65 patients who tested negative for small intestinal bacterial overgrowth, symptoms resolved in 8 of 32 who got norfloxacin (25%) and in none of 33 patients on placebo. There was a trend for greater effectiveness with norfloxacin in the 19 patients with moderate colony counts (lower than 10⁵ CFO but at least 10³ CFU/mL), with symptoms resolving in 5 of 11 who got norfloxacin (46%) and in none of 8 patients on placebo, but the difference between treatment groups was not statistically significant. Among the 46 patients with the lowest colony counts (below 10³ CFU/mL), symptoms resolved in 3 of 21 who got norfloxacin (14%) and in none of 25 on placebo, which was statistically significant.

Mean symptoms scores before treatment in the norfloxacin group were 6 in those with small intestinal bacterial overgrowth, 10 in those without the overgrowth but with moderate colonization, and 8 in those with the least colonization, and decreased significantly in each subgroup 1 month after treatment to 2, 5, and 5, respectively. Among patients on placebo, mean symptom scores before treatment were 10 in those with small intestinal bacterial overgrowth, 6 in those with moderate colonization, and 9 in those with the least colonization and did not change significantly by 1 month after treatment, increasing to 11 in the overgrowth group and remaining at 6 and 9 in the other subgroups.

Repeat cultures and/or glucose hydrogen breath tests 1 month after treatment in 15 patients who consented to retesting suggested that norfloxacin was more effective than placebo was in eradicating small bacterial intestinal bacterial overgrowth, with eradication in 4 of 8 patients on the drug and none of 7 patients on placebo, Dr. Ghoshal said.

Patients were excluded from the study if they had taken antibiotics or probiotics within 8 weeks of the trial or if they had diabetes, thyroid disease, or previous abdominal surgery.

Dr. Ghoshal reported having no financial disclosures.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

Correction, 6/6/14: An earlier version of this article made multiple incorrect references to inflammatory bowel syndrome instead of irritable bowel syndrome.

CHICAGO – Norfloxacin therapy relieved symptoms of irritable bowel syndrome better than placebo did in a prospective study of 80 patients, especially in patients with small intestinal bacterial overgrowth.*

The double-blind study randomized 15 patients with small intestinal bacterial overgrowth and 65 patients without overgrowth to treatment with either norfloxacin 400 mg b.i.d. or placebo for 10 days. Small intestinal bacterial overgrowth was diagnosed by a quantitative upper gut aspirate culture showing a total bacterial count of at least 10⁵/mL colony-forming units (CFU) of upper gut aspirate, or a glucose hydrogen breath test showing a rise in breath hydrogen of at least 12 ppm after glucose ingestion.

One month later, irritable bowel syndrome (IBS) symptoms resolved in 15 of 40 patients who received the fluoroquinolone antibiotic (38%) and in none of the 40 patients who got placebo, Dr. Uday C. Ghoshal and his associates reported at the annual Digestive Disease Week. Symptoms were assessed using the Rome III criteria.

Among the 15 patients with small intestinal bacterial overgrowth, symptoms resolved in 7 of 8 who received norfloxacin (88%) and in 0 of 7 who got placebo, reported Dr. Ghoshal of the Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.

Among the 65 patients who tested negative for small intestinal bacterial overgrowth, symptoms resolved in 8 of 32 who got norfloxacin (25%) and in none of 33 patients on placebo. There was a trend for greater effectiveness with norfloxacin in the 19 patients with moderate colony counts (lower than 10⁵ CFO but at least 10³ CFU/mL), with symptoms resolving in 5 of 11 who got norfloxacin (46%) and in none of 8 patients on placebo, but the difference between treatment groups was not statistically significant. Among the 46 patients with the lowest colony counts (below 10³ CFU/mL), symptoms resolved in 3 of 21 who got norfloxacin (14%) and in none of 25 on placebo, which was statistically significant.

Mean symptoms scores before treatment in the norfloxacin group were 6 in those with small intestinal bacterial overgrowth, 10 in those without the overgrowth but with moderate colonization, and 8 in those with the least colonization, and decreased significantly in each subgroup 1 month after treatment to 2, 5, and 5, respectively. Among patients on placebo, mean symptom scores before treatment were 10 in those with small intestinal bacterial overgrowth, 6 in those with moderate colonization, and 9 in those with the least colonization and did not change significantly by 1 month after treatment, increasing to 11 in the overgrowth group and remaining at 6 and 9 in the other subgroups.

Repeat cultures and/or glucose hydrogen breath tests 1 month after treatment in 15 patients who consented to retesting suggested that norfloxacin was more effective than placebo was in eradicating small bacterial intestinal bacterial overgrowth, with eradication in 4 of 8 patients on the drug and none of 7 patients on placebo, Dr. Ghoshal said.

Patients were excluded from the study if they had taken antibiotics or probiotics within 8 weeks of the trial or if they had diabetes, thyroid disease, or previous abdominal surgery.

Dr. Ghoshal reported having no financial disclosures.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

Correction, 6/6/14: An earlier version of this article made multiple incorrect references to inflammatory bowel syndrome instead of irritable bowel syndrome.

CHICAGO – Norfloxacin therapy relieved symptoms of irritable bowel syndrome better than placebo did in a prospective study of 80 patients, especially in patients with small intestinal bacterial overgrowth.*

The double-blind study randomized 15 patients with small intestinal bacterial overgrowth and 65 patients without overgrowth to treatment with either norfloxacin 400 mg b.i.d. or placebo for 10 days. Small intestinal bacterial overgrowth was diagnosed by a quantitative upper gut aspirate culture showing a total bacterial count of at least 10⁵/mL colony-forming units (CFU) of upper gut aspirate, or a glucose hydrogen breath test showing a rise in breath hydrogen of at least 12 ppm after glucose ingestion.

One month later, irritable bowel syndrome (IBS) symptoms resolved in 15 of 40 patients who received the fluoroquinolone antibiotic (38%) and in none of the 40 patients who got placebo, Dr. Uday C. Ghoshal and his associates reported at the annual Digestive Disease Week. Symptoms were assessed using the Rome III criteria.

Among the 15 patients with small intestinal bacterial overgrowth, symptoms resolved in 7 of 8 who received norfloxacin (88%) and in 0 of 7 who got placebo, reported Dr. Ghoshal of the Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.

Among the 65 patients who tested negative for small intestinal bacterial overgrowth, symptoms resolved in 8 of 32 who got norfloxacin (25%) and in none of 33 patients on placebo. There was a trend for greater effectiveness with norfloxacin in the 19 patients with moderate colony counts (lower than 10⁵ CFO but at least 10³ CFU/mL), with symptoms resolving in 5 of 11 who got norfloxacin (46%) and in none of 8 patients on placebo, but the difference between treatment groups was not statistically significant. Among the 46 patients with the lowest colony counts (below 10³ CFU/mL), symptoms resolved in 3 of 21 who got norfloxacin (14%) and in none of 25 on placebo, which was statistically significant.

Mean symptoms scores before treatment in the norfloxacin group were 6 in those with small intestinal bacterial overgrowth, 10 in those without the overgrowth but with moderate colonization, and 8 in those with the least colonization, and decreased significantly in each subgroup 1 month after treatment to 2, 5, and 5, respectively. Among patients on placebo, mean symptom scores before treatment were 10 in those with small intestinal bacterial overgrowth, 6 in those with moderate colonization, and 9 in those with the least colonization and did not change significantly by 1 month after treatment, increasing to 11 in the overgrowth group and remaining at 6 and 9 in the other subgroups.

Repeat cultures and/or glucose hydrogen breath tests 1 month after treatment in 15 patients who consented to retesting suggested that norfloxacin was more effective than placebo was in eradicating small bacterial intestinal bacterial overgrowth, with eradication in 4 of 8 patients on the drug and none of 7 patients on placebo, Dr. Ghoshal said.

Patients were excluded from the study if they had taken antibiotics or probiotics within 8 weeks of the trial or if they had diabetes, thyroid disease, or previous abdominal surgery.

Dr. Ghoshal reported having no financial disclosures.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

Correction, 6/6/14: An earlier version of this article made multiple incorrect references to inflammatory bowel syndrome instead of irritable bowel syndrome.

Once-daily ramosetron improved stool consistency in male patients with diarrhea-predominant irritable bowel syndrome, Dr. Shin Fukudo and colleagues reported in the June issue of Clinical Gastroenterology and Hepatology 2014 [doi:10.1016/j.cgh.2013.11.024].

Indeed, compared with other 5-hydroxytryptamine₃ (5-HT3) agonists in its class, the "high selectivity, clear efficacy, and lower incidence of serious adverse events suggest that ramosetron is the most promising therapeutic agent for IBS-D [irritable bowel syndrome–diarrhea subtype]," Dr. Fukudo and associates wrote.

In the current study, which was funded by the drug’s maker, Astellas Pharma, Dr. Fukudo of Tohoku University Graduate School of Medicine, in Sendai, Japan, looked at male patients aged 20-64 years diagnosed with IBS-D according to Rome III criteria.

To begin, subjects were monitored for 1 week to gather baseline assessments of severity of abdominal pain/discomfort, using a five-point ordinate scale, as well as stool consistency – the primary endpoint of the study – using the Bristol Stool Form Scale (BSFS).

For inclusion in the analysis, patients had to demonstrate mean abdominal pain/discomfort scores of at least 0.7 during the baseline period, have no type 1 or 2 stool form, and have an overall mean score of greater than 5 on the BSFS.

Patients were then randomized to a 12-week regimen of either ramosetron 5 mcg daily before breakfast or placebo and began recording their IBS symptoms daily on paper diary cards as well as in a voice-activated electronic database system.

Overall, 148 placebo patients and 147 ramosetron-treated patients were included in the analysis.

Looking at the primary endpoint, Dr. Fukudo found that in the first month, 50.3% of patients in the ramosetron group reported improvement in stool consistency (95% confidence interval, 42.0%-58.7%) versus 19.6% among placebo patients (95% CI, 13.5%-26.9%) (P less than 0.001).

That trend held for the remainder of the study, with a significantly greater portion of ramosetron patients consistently logging gains in stool consistency from month to month.

Similarly, the ramosetron group also recorded changes in the severity of abdominal pain/discomfort week from baseline, with a decrease in severity of 0.78, compared with mean weekly reductions of 0.60 among placebo patients.

The difference between groups, however, was only significant at week 5, with a mean 0.70 decrease in symptoms over the previous week, compared with 0.48 for placebo (P = .012).

Safety profiles, meanwhile, were similar for both drugs: adverse events occurred in 46.9% and 51.7% of ramosetron and placebo patients, respectively, with constipation occurring in 3.4% of treatment patients versus 0.7% of placebo patients, a nonsignificant difference.

Moreover, "All episodes of constipation and hard stools in the ramosetron group, assumed to be caused by the pharmacologic actions of ramosetron, were classified as mild and resolved early without using rescue drugs."

According to the researchers, the efficacy of ramosetron likely stems from the "crucial role" that 5-hydroxytryptamine plays in IBS-D pathophysiology.

"IBS-D patients have exaggerated colonic motility in response to colorectal distention," they wrote.

Since the distention-induced peristaltic reflex is mediated by 5-HT, and since abnormal neurotransmission of 5-HT via the 5-HT3 receptor has been reported in IBS-diarrhea patients, "Use of a 5-HT3 antagonist for IBS-D patients is a logical consequence."

In addition to the disclosure that the study was funded by Astellas Pharma, Dr. Fukudo also disclosed working as a contracted consultant to the company, along with a coinvestigator; the three remaining authors are Astellas employees.

Once-daily ramosetron improved stool consistency in male patients with diarrhea-predominant irritable bowel syndrome, Dr. Shin Fukudo and colleagues reported in the June issue of Clinical Gastroenterology and Hepatology 2014 [doi:10.1016/j.cgh.2013.11.024].

Indeed, compared with other 5-hydroxytryptamine₃ (5-HT3) agonists in its class, the "high selectivity, clear efficacy, and lower incidence of serious adverse events suggest that ramosetron is the most promising therapeutic agent for IBS-D [irritable bowel syndrome–diarrhea subtype]," Dr. Fukudo and associates wrote.

In the current study, which was funded by the drug’s maker, Astellas Pharma, Dr. Fukudo of Tohoku University Graduate School of Medicine, in Sendai, Japan, looked at male patients aged 20-64 years diagnosed with IBS-D according to Rome III criteria.

To begin, subjects were monitored for 1 week to gather baseline assessments of severity of abdominal pain/discomfort, using a five-point ordinate scale, as well as stool consistency – the primary endpoint of the study – using the Bristol Stool Form Scale (BSFS).

For inclusion in the analysis, patients had to demonstrate mean abdominal pain/discomfort scores of at least 0.7 during the baseline period, have no type 1 or 2 stool form, and have an overall mean score of greater than 5 on the BSFS.

Patients were then randomized to a 12-week regimen of either ramosetron 5 mcg daily before breakfast or placebo and began recording their IBS symptoms daily on paper diary cards as well as in a voice-activated electronic database system.

Overall, 148 placebo patients and 147 ramosetron-treated patients were included in the analysis.

Looking at the primary endpoint, Dr. Fukudo found that in the first month, 50.3% of patients in the ramosetron group reported improvement in stool consistency (95% confidence interval, 42.0%-58.7%) versus 19.6% among placebo patients (95% CI, 13.5%-26.9%) (P less than 0.001).

That trend held for the remainder of the study, with a significantly greater portion of ramosetron patients consistently logging gains in stool consistency from month to month.

Similarly, the ramosetron group also recorded changes in the severity of abdominal pain/discomfort week from baseline, with a decrease in severity of 0.78, compared with mean weekly reductions of 0.60 among placebo patients.

The difference between groups, however, was only significant at week 5, with a mean 0.70 decrease in symptoms over the previous week, compared with 0.48 for placebo (P = .012).

Safety profiles, meanwhile, were similar for both drugs: adverse events occurred in 46.9% and 51.7% of ramosetron and placebo patients, respectively, with constipation occurring in 3.4% of treatment patients versus 0.7% of placebo patients, a nonsignificant difference.

Moreover, "All episodes of constipation and hard stools in the ramosetron group, assumed to be caused by the pharmacologic actions of ramosetron, were classified as mild and resolved early without using rescue drugs."

According to the researchers, the efficacy of ramosetron likely stems from the "crucial role" that 5-hydroxytryptamine plays in IBS-D pathophysiology.

"IBS-D patients have exaggerated colonic motility in response to colorectal distention," they wrote.

Since the distention-induced peristaltic reflex is mediated by 5-HT, and since abnormal neurotransmission of 5-HT via the 5-HT3 receptor has been reported in IBS-diarrhea patients, "Use of a 5-HT3 antagonist for IBS-D patients is a logical consequence."

In addition to the disclosure that the study was funded by Astellas Pharma, Dr. Fukudo also disclosed working as a contracted consultant to the company, along with a coinvestigator; the three remaining authors are Astellas employees.

Once-daily ramosetron improved stool consistency in male patients with diarrhea-predominant irritable bowel syndrome, Dr. Shin Fukudo and colleagues reported in the June issue of Clinical Gastroenterology and Hepatology 2014 [doi:10.1016/j.cgh.2013.11.024].

Indeed, compared with other 5-hydroxytryptamine₃ (5-HT3) agonists in its class, the "high selectivity, clear efficacy, and lower incidence of serious adverse events suggest that ramosetron is the most promising therapeutic agent for IBS-D [irritable bowel syndrome–diarrhea subtype]," Dr. Fukudo and associates wrote.

In the current study, which was funded by the drug’s maker, Astellas Pharma, Dr. Fukudo of Tohoku University Graduate School of Medicine, in Sendai, Japan, looked at male patients aged 20-64 years diagnosed with IBS-D according to Rome III criteria.

To begin, subjects were monitored for 1 week to gather baseline assessments of severity of abdominal pain/discomfort, using a five-point ordinate scale, as well as stool consistency – the primary endpoint of the study – using the Bristol Stool Form Scale (BSFS).

For inclusion in the analysis, patients had to demonstrate mean abdominal pain/discomfort scores of at least 0.7 during the baseline period, have no type 1 or 2 stool form, and have an overall mean score of greater than 5 on the BSFS.

Patients were then randomized to a 12-week regimen of either ramosetron 5 mcg daily before breakfast or placebo and began recording their IBS symptoms daily on paper diary cards as well as in a voice-activated electronic database system.

Overall, 148 placebo patients and 147 ramosetron-treated patients were included in the analysis.

Looking at the primary endpoint, Dr. Fukudo found that in the first month, 50.3% of patients in the ramosetron group reported improvement in stool consistency (95% confidence interval, 42.0%-58.7%) versus 19.6% among placebo patients (95% CI, 13.5%-26.9%) (P less than 0.001).

That trend held for the remainder of the study, with a significantly greater portion of ramosetron patients consistently logging gains in stool consistency from month to month.

Similarly, the ramosetron group also recorded changes in the severity of abdominal pain/discomfort week from baseline, with a decrease in severity of 0.78, compared with mean weekly reductions of 0.60 among placebo patients.

The difference between groups, however, was only significant at week 5, with a mean 0.70 decrease in symptoms over the previous week, compared with 0.48 for placebo (P = .012).

Safety profiles, meanwhile, were similar for both drugs: adverse events occurred in 46.9% and 51.7% of ramosetron and placebo patients, respectively, with constipation occurring in 3.4% of treatment patients versus 0.7% of placebo patients, a nonsignificant difference.

Moreover, "All episodes of constipation and hard stools in the ramosetron group, assumed to be caused by the pharmacologic actions of ramosetron, were classified as mild and resolved early without using rescue drugs."

According to the researchers, the efficacy of ramosetron likely stems from the "crucial role" that 5-hydroxytryptamine plays in IBS-D pathophysiology.

"IBS-D patients have exaggerated colonic motility in response to colorectal distention," they wrote.

Since the distention-induced peristaltic reflex is mediated by 5-HT, and since abnormal neurotransmission of 5-HT via the 5-HT3 receptor has been reported in IBS-diarrhea patients, "Use of a 5-HT3 antagonist for IBS-D patients is a logical consequence."

In addition to the disclosure that the study was funded by Astellas Pharma, Dr. Fukudo also disclosed working as a contracted consultant to the company, along with a coinvestigator; the three remaining authors are Astellas employees.