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MASLD Healthcare Costs Climbing Fast in Canada
according to a new study.
The expected surge reflects the growing prevalence of MASLD and its associated conditions, emphasizing the necessity for a comprehensive approach to address this escalating public health issue, reported lead author K. Ally Memedovich, BHSc, of the University of Calgary in Alberta, Canada, and colleagues.
“The costs associated with the management of MASLD in Canada remain unknown but have been estimated as being very high,” the investigators wrote in Gastro Hep Advances. “Specifically, in one study from the United States, the healthcare costs and utilization of those with MASLD was nearly double that of patients without MASLD but with similar health status. This difference was largely due to increases in imaging, hospitalization, liver fibrosis assessment, laboratory tests, and outpatient visits.”
Although projections are available to estimate the future prevalence of MASLD in Canada, no models are available to predict the growing national economic burden, prompting the present study.
Memedovich and colleagues analyzed healthcare usage data from 6,358 patients diagnosed with MASLD disease in Calgary from 2018 to 2020. Using provincial administrative data, they calculated both liver-specific and total healthcare costs associated with different stages of liver fibrosis, ranging from F0/F1 (minimal fibrosis) to F4 (advanced fibrosis or cirrhosis).
The patients’ liver fibrosis stages were determined using liver stiffness measurements obtained through shear wave elastography. Average annual cost per patient was then calculated for each fibrosis stage by analyzing hospitalizations, ambulatory care, and physician claims data.
The annual average liver-specific cost per patient increased with severity of liver fibrosis; costs for patients with fibrosis stages F0/F1, F2, F3, and F4 were C$7.02, C$35.30, C$60.46, and C$72.55, respectively. By 2050, liver-specific healthcare costs are projected to increase by C$51 million, reaching C$136 million Canada-wide.
Total healthcare costs were markedly higher; annual costs for patients with fibrosis stages F0/F1, F2, F3, and F4 were C$397.90, C$781.53, C$2,881.84, and C$1,598.82, respectively. As a result, total healthcare costs are expected to rise by nearly C$2 billion, contributing to a Canadian healthcare burden of C$5.81 billion annually by 2050.
The study revealed that over 90% of the healthcare costs for MASLD patients were attributed not to liver disease itself but to the management of associated comorbidities such as diabetes, hypertension, mental illness, and obesity. For instance, diabetes was the most common reason for physician visits among MASLD patients, accounting for 65.2% of cases. One study limitation was exclusion of decompensated cirrhosis, liver cancer, or a liver transplant recipient because of low prevalence in this cohort, potentially contributing to low liver specific healthcare costs.
Memedovich and colleagues noted that chronic diseases account for approximately C$68 billion annually in direct healthcare costs in Canada, representing around 58% of total healthcare expenditures. Estimates suggest that 1% annual reduction in chronic disease prevalence could save C$107 billion over the course of 20 years.
“Therefore, an approach that focuses on preventing and managing chronic diseases overall is needed to reduce the burden of MASLD on the healthcare system,” they wrote. This study was funded by LiveRx via an Alberta Innovates grant. The investigators disclosed relationships with Gilead, Abbott, GSK, and others.
Metabolic dysfunction–associated steatotic liver disease (MASLD) is the most common chronic liver disease, and its clinical burden is expected to mirror the rising rates of obesity and diabetes over the next couple decades. The cost analysis by Memdovich and colleagues provides a timely report on the healthcare burden of MASLD in Canada. Their results are, nevertheless, generalizable to other healthcare systems.
The authors found that nearly 98% of total healthcare costs of patients with MASLD were not specifically related to liver treatment, but rather linked to the management of patients’ cardiometabolic comorbidities. Projection estimates based on this cohort suggests a steep rise in the total healthcare costs over the coming decades reflecting increasing rates of comorbidities, with largest changes expected in the advanced fibrosis patient group. These findings highlight the need for early recognition of MASLD followed by a collaborative effort in management of MASLD in conjunction with its associated cardiometabolic comorbidities.
As rates for obesity, diabetes, and MASLD continue to rise, there is an urgency to create a global strategy for MASLD management that focuses on both prevention and treatment. Public health strategies are needed to increase awareness and focus on the treatment and prevention cardiometabolic risk factors that appear to be the main drivers of healthcare costs among patients with MASLD. A concerted effort is needed from providers, both primary care and specialists, for early recognition and treatment of MASLD. Such a public health response combined with recent advent in pharmacotherapy for weight loss and metabolic dysfunction–associated steatohepatitis may alter the projected costs and hopefully decrease the disease burden associated advanced MASLD.
Akshay Shetty, MD, is assistant professor of medicine and surgery at the David Geffen School of Medicine, University of California, San Francisco. He has no conflicts of interest to declare. Sammy Saab, MD, MPH, AGAF, is professor of medicine and surgery at the David Geffen School of Medicine at UCLA. He is on the speakers bureau for AbbVie, Gilead, Eisai, Intercept, Ipsen, Salix, Mallinckrodt, and Takeda, and has been a consultant for Gilead, Ipsen, Mallinckrodt, Madrigal, and Orphalan.
Metabolic dysfunction–associated steatotic liver disease (MASLD) is the most common chronic liver disease, and its clinical burden is expected to mirror the rising rates of obesity and diabetes over the next couple decades. The cost analysis by Memdovich and colleagues provides a timely report on the healthcare burden of MASLD in Canada. Their results are, nevertheless, generalizable to other healthcare systems.
The authors found that nearly 98% of total healthcare costs of patients with MASLD were not specifically related to liver treatment, but rather linked to the management of patients’ cardiometabolic comorbidities. Projection estimates based on this cohort suggests a steep rise in the total healthcare costs over the coming decades reflecting increasing rates of comorbidities, with largest changes expected in the advanced fibrosis patient group. These findings highlight the need for early recognition of MASLD followed by a collaborative effort in management of MASLD in conjunction with its associated cardiometabolic comorbidities.
As rates for obesity, diabetes, and MASLD continue to rise, there is an urgency to create a global strategy for MASLD management that focuses on both prevention and treatment. Public health strategies are needed to increase awareness and focus on the treatment and prevention cardiometabolic risk factors that appear to be the main drivers of healthcare costs among patients with MASLD. A concerted effort is needed from providers, both primary care and specialists, for early recognition and treatment of MASLD. Such a public health response combined with recent advent in pharmacotherapy for weight loss and metabolic dysfunction–associated steatohepatitis may alter the projected costs and hopefully decrease the disease burden associated advanced MASLD.
Akshay Shetty, MD, is assistant professor of medicine and surgery at the David Geffen School of Medicine, University of California, San Francisco. He has no conflicts of interest to declare. Sammy Saab, MD, MPH, AGAF, is professor of medicine and surgery at the David Geffen School of Medicine at UCLA. He is on the speakers bureau for AbbVie, Gilead, Eisai, Intercept, Ipsen, Salix, Mallinckrodt, and Takeda, and has been a consultant for Gilead, Ipsen, Mallinckrodt, Madrigal, and Orphalan.
Metabolic dysfunction–associated steatotic liver disease (MASLD) is the most common chronic liver disease, and its clinical burden is expected to mirror the rising rates of obesity and diabetes over the next couple decades. The cost analysis by Memdovich and colleagues provides a timely report on the healthcare burden of MASLD in Canada. Their results are, nevertheless, generalizable to other healthcare systems.
The authors found that nearly 98% of total healthcare costs of patients with MASLD were not specifically related to liver treatment, but rather linked to the management of patients’ cardiometabolic comorbidities. Projection estimates based on this cohort suggests a steep rise in the total healthcare costs over the coming decades reflecting increasing rates of comorbidities, with largest changes expected in the advanced fibrosis patient group. These findings highlight the need for early recognition of MASLD followed by a collaborative effort in management of MASLD in conjunction with its associated cardiometabolic comorbidities.
As rates for obesity, diabetes, and MASLD continue to rise, there is an urgency to create a global strategy for MASLD management that focuses on both prevention and treatment. Public health strategies are needed to increase awareness and focus on the treatment and prevention cardiometabolic risk factors that appear to be the main drivers of healthcare costs among patients with MASLD. A concerted effort is needed from providers, both primary care and specialists, for early recognition and treatment of MASLD. Such a public health response combined with recent advent in pharmacotherapy for weight loss and metabolic dysfunction–associated steatohepatitis may alter the projected costs and hopefully decrease the disease burden associated advanced MASLD.
Akshay Shetty, MD, is assistant professor of medicine and surgery at the David Geffen School of Medicine, University of California, San Francisco. He has no conflicts of interest to declare. Sammy Saab, MD, MPH, AGAF, is professor of medicine and surgery at the David Geffen School of Medicine at UCLA. He is on the speakers bureau for AbbVie, Gilead, Eisai, Intercept, Ipsen, Salix, Mallinckrodt, and Takeda, and has been a consultant for Gilead, Ipsen, Mallinckrodt, Madrigal, and Orphalan.
according to a new study.
The expected surge reflects the growing prevalence of MASLD and its associated conditions, emphasizing the necessity for a comprehensive approach to address this escalating public health issue, reported lead author K. Ally Memedovich, BHSc, of the University of Calgary in Alberta, Canada, and colleagues.
“The costs associated with the management of MASLD in Canada remain unknown but have been estimated as being very high,” the investigators wrote in Gastro Hep Advances. “Specifically, in one study from the United States, the healthcare costs and utilization of those with MASLD was nearly double that of patients without MASLD but with similar health status. This difference was largely due to increases in imaging, hospitalization, liver fibrosis assessment, laboratory tests, and outpatient visits.”
Although projections are available to estimate the future prevalence of MASLD in Canada, no models are available to predict the growing national economic burden, prompting the present study.
Memedovich and colleagues analyzed healthcare usage data from 6,358 patients diagnosed with MASLD disease in Calgary from 2018 to 2020. Using provincial administrative data, they calculated both liver-specific and total healthcare costs associated with different stages of liver fibrosis, ranging from F0/F1 (minimal fibrosis) to F4 (advanced fibrosis or cirrhosis).
The patients’ liver fibrosis stages were determined using liver stiffness measurements obtained through shear wave elastography. Average annual cost per patient was then calculated for each fibrosis stage by analyzing hospitalizations, ambulatory care, and physician claims data.
The annual average liver-specific cost per patient increased with severity of liver fibrosis; costs for patients with fibrosis stages F0/F1, F2, F3, and F4 were C$7.02, C$35.30, C$60.46, and C$72.55, respectively. By 2050, liver-specific healthcare costs are projected to increase by C$51 million, reaching C$136 million Canada-wide.
Total healthcare costs were markedly higher; annual costs for patients with fibrosis stages F0/F1, F2, F3, and F4 were C$397.90, C$781.53, C$2,881.84, and C$1,598.82, respectively. As a result, total healthcare costs are expected to rise by nearly C$2 billion, contributing to a Canadian healthcare burden of C$5.81 billion annually by 2050.
The study revealed that over 90% of the healthcare costs for MASLD patients were attributed not to liver disease itself but to the management of associated comorbidities such as diabetes, hypertension, mental illness, and obesity. For instance, diabetes was the most common reason for physician visits among MASLD patients, accounting for 65.2% of cases. One study limitation was exclusion of decompensated cirrhosis, liver cancer, or a liver transplant recipient because of low prevalence in this cohort, potentially contributing to low liver specific healthcare costs.
Memedovich and colleagues noted that chronic diseases account for approximately C$68 billion annually in direct healthcare costs in Canada, representing around 58% of total healthcare expenditures. Estimates suggest that 1% annual reduction in chronic disease prevalence could save C$107 billion over the course of 20 years.
“Therefore, an approach that focuses on preventing and managing chronic diseases overall is needed to reduce the burden of MASLD on the healthcare system,” they wrote. This study was funded by LiveRx via an Alberta Innovates grant. The investigators disclosed relationships with Gilead, Abbott, GSK, and others.
according to a new study.
The expected surge reflects the growing prevalence of MASLD and its associated conditions, emphasizing the necessity for a comprehensive approach to address this escalating public health issue, reported lead author K. Ally Memedovich, BHSc, of the University of Calgary in Alberta, Canada, and colleagues.
“The costs associated with the management of MASLD in Canada remain unknown but have been estimated as being very high,” the investigators wrote in Gastro Hep Advances. “Specifically, in one study from the United States, the healthcare costs and utilization of those with MASLD was nearly double that of patients without MASLD but with similar health status. This difference was largely due to increases in imaging, hospitalization, liver fibrosis assessment, laboratory tests, and outpatient visits.”
Although projections are available to estimate the future prevalence of MASLD in Canada, no models are available to predict the growing national economic burden, prompting the present study.
Memedovich and colleagues analyzed healthcare usage data from 6,358 patients diagnosed with MASLD disease in Calgary from 2018 to 2020. Using provincial administrative data, they calculated both liver-specific and total healthcare costs associated with different stages of liver fibrosis, ranging from F0/F1 (minimal fibrosis) to F4 (advanced fibrosis or cirrhosis).
The patients’ liver fibrosis stages were determined using liver stiffness measurements obtained through shear wave elastography. Average annual cost per patient was then calculated for each fibrosis stage by analyzing hospitalizations, ambulatory care, and physician claims data.
The annual average liver-specific cost per patient increased with severity of liver fibrosis; costs for patients with fibrosis stages F0/F1, F2, F3, and F4 were C$7.02, C$35.30, C$60.46, and C$72.55, respectively. By 2050, liver-specific healthcare costs are projected to increase by C$51 million, reaching C$136 million Canada-wide.
Total healthcare costs were markedly higher; annual costs for patients with fibrosis stages F0/F1, F2, F3, and F4 were C$397.90, C$781.53, C$2,881.84, and C$1,598.82, respectively. As a result, total healthcare costs are expected to rise by nearly C$2 billion, contributing to a Canadian healthcare burden of C$5.81 billion annually by 2050.
The study revealed that over 90% of the healthcare costs for MASLD patients were attributed not to liver disease itself but to the management of associated comorbidities such as diabetes, hypertension, mental illness, and obesity. For instance, diabetes was the most common reason for physician visits among MASLD patients, accounting for 65.2% of cases. One study limitation was exclusion of decompensated cirrhosis, liver cancer, or a liver transplant recipient because of low prevalence in this cohort, potentially contributing to low liver specific healthcare costs.
Memedovich and colleagues noted that chronic diseases account for approximately C$68 billion annually in direct healthcare costs in Canada, representing around 58% of total healthcare expenditures. Estimates suggest that 1% annual reduction in chronic disease prevalence could save C$107 billion over the course of 20 years.
“Therefore, an approach that focuses on preventing and managing chronic diseases overall is needed to reduce the burden of MASLD on the healthcare system,” they wrote. This study was funded by LiveRx via an Alberta Innovates grant. The investigators disclosed relationships with Gilead, Abbott, GSK, and others.
FROM GASTRO HEP ADVANCES
Live Rotavirus Vaccine Safe for Newborns of Biologic-Treated Moms With IBD
No adverse events or impairment of the immune system emerged in babies at 7 days, 1 month, and 9 months post vaccination, in findings from a small Canadian study published in Clinical Gastroenterology and Hepatology.
The study found normal extended immune function testing in infants despite third-trimester maternal biologic therapy and regardless of circulating drug levels. The data provide reassurance about live rotavirus vaccination in this population and may also offer insights into the safety of other live vaccines in biologic-exposed individuals, wrote investigators led by gastroenterologist Cynthia H. Seow, MD, a professor in the Cumming School of Medicine at the University of Calgary in Alberta, Canada.
“Despite the well-established safety and effectiveness of non–live vaccination in individuals with IBD, including those on immunomodulators and biologic therapy, vaccine uptake in pregnant women with IBD and their infants remains suboptimal,” Seow said in an interview. This largely arises from maternal and physician concerns regarding transplacental transfer of IBD therapies and their impact on the safety of vaccination.
“These concerns were heightened after reports emerged of five fatal outcomes following the administration of the live Bacille Calmette-Guérin [BCG] vaccine in biologic-exposed infants. However, it had already been reported that inadvertent administration of the live oral rotavirus vaccine, a very different vaccine in terms of target and mechanism of action, in biologic-exposed individuals had not been associated with significant adverse effects,” she said.
They undertook their analysis with the hypothesis that vaccination would carry low risk, although the live oral vaccine is not currently recommended in biologic-exposed infants. “Yet rotavirus is a leading cause of severe, dehydrating diarrhea in children under the age of 5 years globally, and vaccination has led to significant reductions in hospitalizations and mortality,” Seow added.
Provision of the vaccine to anti–tumor necrosis factor (TNF)–exposed infants has been incorporated into the Canadian Public Health and Immunization guidelines, as the majority of the biologic-exposed infants were exposed to anti-TNF agents. “And with collection of further data, we expect that this will be extended to other biologic agent exposure. These data are important to pregnant women with IBD as they help to normalize their care. Pregnancy is difficult enough without having to remember exceptions to care,” Seow said.
“Before some of the studies came out, broad guidelines recommended that live vaccines should not be used in biologic-exposed infants, but this had been thought to be overly zealous and too conservative, and the risk was thought to be low,” said Elizabeth Spencer, MD, an assistant professor of pediatrics in the Division of Pediatric Gastroenterology at the Icahn School of Medicine at Mount Sinai in New York City, in an interview. Spencer was not involved in the Canadian study.
“At our center, we had some moms on biologics during pregnancy who forgot and had their babies vaccinated for rotavirus, and the babies were all fine,” she said.
The safety of this vaccine has been confirmed by several small studies and recently the PIANO Helmsley Global Consensus on Pregnancy and Inflammatory Bowel Disease, which was presented at Digestive Disease Week 2024. The consensus encompasses preconception counseling and the safety of IBD medications during pregnancy and lactation.
“Another concern, however, was that giving a live GI bug like rotavirus to babies might overstimulate their immune systems and provoke IBD,” Spencer added. “While a number of population-based studies in the US and Europe showed that was not the case, at least in the general population, there was a suggestion that, down the road, vaccination might be mildly protective against IBD in some cases.”
She added the caveat that these studies were not done in mothers and their babies with IBD, who might be inherently at greater risk for IBD. “So, a question for future research would be, ‘Is immune stimulation of the gut in IBD moms and their babies a good or a bad thing for their gut?’ ”
Spencer conceded that “the data present a bit of a blurry picture, but I think it’s always better just to vaccinate according to the regular schedule. The current data say there is no added risk, but it would be nice to look specifically at risk in moms with IBD and their children.”
The Study
The prospective cohort study is a substudy of a larger 2023 one that included biologic use in a range of maternal illnesses, not just IBD.
For the current study, Seow and colleagues identified 57 infants born to 52 mothers with IBD attending a pregnancy clinic at the University of Calgary in the period 2019-2023. Almost 81% of the mothers had Crohn’s disease, and the median duration of IBD was 10 years. The median gestational age at delivery was 39 weeks, and almost 60% of deliveries were vaginal. The infants had been exposed in utero to infliximab (n = 21), adalimumab (n = 19), vedolizumab (n = 10), and ustekinumab (n = 7) in the third trimester.
The 57 biologic-exposed infants underwent standardized clinical assessments, drug concentration, and immune function testing. The live oral rotavirus vaccine series was provided to 50 infants, with the first dose at a median of 13 weeks of age. Immunologic assessments validated for age were normal in all infants despite median infliximab concentrations of 6.1 μg/mL (range, 0.4-28.8 μg/mL), adalimumab concentrations of 1.7 μg/mL (range, 0.7-7.9 μg/mL), ustekinumab concentrations of 0.6 μg/mL (range, 0-1.1), and undetectable for vedolizumab at 10.7 weeks of age.
As anticipated, infant immune function was normal regardless of circulating drug levels.
The overall message, said Seow, is “healthy mum equals healthy baby. Be more concerned regarding active inflammation than active medications. In almost all circumstances, treat to target in pregnancy as you would in the nonpregnant state.” She added, however, that further studies are needed to determine the safety and optimal timing of other live vaccines, such as the BCG, in the presence of biologic therapy.
This study was funded by the Alberta Children’s Hospital Research Institute. Seow reported advisory/speaker’s fees for Janssen, AbbVie, Takeda, Pfizer, Fresenius Kabi, Bristol-Myers Squibb, Pharmascience, and Lilly, as well as funding from Alberta Children’s Hospital Research Institute, Crohn’s and Colitis Canada, the Canadian Institutes of Health Research, and Calgary Health Trust, and data safety monitoring from New South Wales Government Health, Australia. Multiple coauthors disclosed similar consulting or speaker relationships with private industry. Spencer had no competing interests with regard to her comments.
A version of this article first appeared on Medscape.com.
No adverse events or impairment of the immune system emerged in babies at 7 days, 1 month, and 9 months post vaccination, in findings from a small Canadian study published in Clinical Gastroenterology and Hepatology.
The study found normal extended immune function testing in infants despite third-trimester maternal biologic therapy and regardless of circulating drug levels. The data provide reassurance about live rotavirus vaccination in this population and may also offer insights into the safety of other live vaccines in biologic-exposed individuals, wrote investigators led by gastroenterologist Cynthia H. Seow, MD, a professor in the Cumming School of Medicine at the University of Calgary in Alberta, Canada.
“Despite the well-established safety and effectiveness of non–live vaccination in individuals with IBD, including those on immunomodulators and biologic therapy, vaccine uptake in pregnant women with IBD and their infants remains suboptimal,” Seow said in an interview. This largely arises from maternal and physician concerns regarding transplacental transfer of IBD therapies and their impact on the safety of vaccination.
“These concerns were heightened after reports emerged of five fatal outcomes following the administration of the live Bacille Calmette-Guérin [BCG] vaccine in biologic-exposed infants. However, it had already been reported that inadvertent administration of the live oral rotavirus vaccine, a very different vaccine in terms of target and mechanism of action, in biologic-exposed individuals had not been associated with significant adverse effects,” she said.
They undertook their analysis with the hypothesis that vaccination would carry low risk, although the live oral vaccine is not currently recommended in biologic-exposed infants. “Yet rotavirus is a leading cause of severe, dehydrating diarrhea in children under the age of 5 years globally, and vaccination has led to significant reductions in hospitalizations and mortality,” Seow added.
Provision of the vaccine to anti–tumor necrosis factor (TNF)–exposed infants has been incorporated into the Canadian Public Health and Immunization guidelines, as the majority of the biologic-exposed infants were exposed to anti-TNF agents. “And with collection of further data, we expect that this will be extended to other biologic agent exposure. These data are important to pregnant women with IBD as they help to normalize their care. Pregnancy is difficult enough without having to remember exceptions to care,” Seow said.
“Before some of the studies came out, broad guidelines recommended that live vaccines should not be used in biologic-exposed infants, but this had been thought to be overly zealous and too conservative, and the risk was thought to be low,” said Elizabeth Spencer, MD, an assistant professor of pediatrics in the Division of Pediatric Gastroenterology at the Icahn School of Medicine at Mount Sinai in New York City, in an interview. Spencer was not involved in the Canadian study.
“At our center, we had some moms on biologics during pregnancy who forgot and had their babies vaccinated for rotavirus, and the babies were all fine,” she said.
The safety of this vaccine has been confirmed by several small studies and recently the PIANO Helmsley Global Consensus on Pregnancy and Inflammatory Bowel Disease, which was presented at Digestive Disease Week 2024. The consensus encompasses preconception counseling and the safety of IBD medications during pregnancy and lactation.
“Another concern, however, was that giving a live GI bug like rotavirus to babies might overstimulate their immune systems and provoke IBD,” Spencer added. “While a number of population-based studies in the US and Europe showed that was not the case, at least in the general population, there was a suggestion that, down the road, vaccination might be mildly protective against IBD in some cases.”
She added the caveat that these studies were not done in mothers and their babies with IBD, who might be inherently at greater risk for IBD. “So, a question for future research would be, ‘Is immune stimulation of the gut in IBD moms and their babies a good or a bad thing for their gut?’ ”
Spencer conceded that “the data present a bit of a blurry picture, but I think it’s always better just to vaccinate according to the regular schedule. The current data say there is no added risk, but it would be nice to look specifically at risk in moms with IBD and their children.”
The Study
The prospective cohort study is a substudy of a larger 2023 one that included biologic use in a range of maternal illnesses, not just IBD.
For the current study, Seow and colleagues identified 57 infants born to 52 mothers with IBD attending a pregnancy clinic at the University of Calgary in the period 2019-2023. Almost 81% of the mothers had Crohn’s disease, and the median duration of IBD was 10 years. The median gestational age at delivery was 39 weeks, and almost 60% of deliveries were vaginal. The infants had been exposed in utero to infliximab (n = 21), adalimumab (n = 19), vedolizumab (n = 10), and ustekinumab (n = 7) in the third trimester.
The 57 biologic-exposed infants underwent standardized clinical assessments, drug concentration, and immune function testing. The live oral rotavirus vaccine series was provided to 50 infants, with the first dose at a median of 13 weeks of age. Immunologic assessments validated for age were normal in all infants despite median infliximab concentrations of 6.1 μg/mL (range, 0.4-28.8 μg/mL), adalimumab concentrations of 1.7 μg/mL (range, 0.7-7.9 μg/mL), ustekinumab concentrations of 0.6 μg/mL (range, 0-1.1), and undetectable for vedolizumab at 10.7 weeks of age.
As anticipated, infant immune function was normal regardless of circulating drug levels.
The overall message, said Seow, is “healthy mum equals healthy baby. Be more concerned regarding active inflammation than active medications. In almost all circumstances, treat to target in pregnancy as you would in the nonpregnant state.” She added, however, that further studies are needed to determine the safety and optimal timing of other live vaccines, such as the BCG, in the presence of biologic therapy.
This study was funded by the Alberta Children’s Hospital Research Institute. Seow reported advisory/speaker’s fees for Janssen, AbbVie, Takeda, Pfizer, Fresenius Kabi, Bristol-Myers Squibb, Pharmascience, and Lilly, as well as funding from Alberta Children’s Hospital Research Institute, Crohn’s and Colitis Canada, the Canadian Institutes of Health Research, and Calgary Health Trust, and data safety monitoring from New South Wales Government Health, Australia. Multiple coauthors disclosed similar consulting or speaker relationships with private industry. Spencer had no competing interests with regard to her comments.
A version of this article first appeared on Medscape.com.
No adverse events or impairment of the immune system emerged in babies at 7 days, 1 month, and 9 months post vaccination, in findings from a small Canadian study published in Clinical Gastroenterology and Hepatology.
The study found normal extended immune function testing in infants despite third-trimester maternal biologic therapy and regardless of circulating drug levels. The data provide reassurance about live rotavirus vaccination in this population and may also offer insights into the safety of other live vaccines in biologic-exposed individuals, wrote investigators led by gastroenterologist Cynthia H. Seow, MD, a professor in the Cumming School of Medicine at the University of Calgary in Alberta, Canada.
“Despite the well-established safety and effectiveness of non–live vaccination in individuals with IBD, including those on immunomodulators and biologic therapy, vaccine uptake in pregnant women with IBD and their infants remains suboptimal,” Seow said in an interview. This largely arises from maternal and physician concerns regarding transplacental transfer of IBD therapies and their impact on the safety of vaccination.
“These concerns were heightened after reports emerged of five fatal outcomes following the administration of the live Bacille Calmette-Guérin [BCG] vaccine in biologic-exposed infants. However, it had already been reported that inadvertent administration of the live oral rotavirus vaccine, a very different vaccine in terms of target and mechanism of action, in biologic-exposed individuals had not been associated with significant adverse effects,” she said.
They undertook their analysis with the hypothesis that vaccination would carry low risk, although the live oral vaccine is not currently recommended in biologic-exposed infants. “Yet rotavirus is a leading cause of severe, dehydrating diarrhea in children under the age of 5 years globally, and vaccination has led to significant reductions in hospitalizations and mortality,” Seow added.
Provision of the vaccine to anti–tumor necrosis factor (TNF)–exposed infants has been incorporated into the Canadian Public Health and Immunization guidelines, as the majority of the biologic-exposed infants were exposed to anti-TNF agents. “And with collection of further data, we expect that this will be extended to other biologic agent exposure. These data are important to pregnant women with IBD as they help to normalize their care. Pregnancy is difficult enough without having to remember exceptions to care,” Seow said.
“Before some of the studies came out, broad guidelines recommended that live vaccines should not be used in biologic-exposed infants, but this had been thought to be overly zealous and too conservative, and the risk was thought to be low,” said Elizabeth Spencer, MD, an assistant professor of pediatrics in the Division of Pediatric Gastroenterology at the Icahn School of Medicine at Mount Sinai in New York City, in an interview. Spencer was not involved in the Canadian study.
“At our center, we had some moms on biologics during pregnancy who forgot and had their babies vaccinated for rotavirus, and the babies were all fine,” she said.
The safety of this vaccine has been confirmed by several small studies and recently the PIANO Helmsley Global Consensus on Pregnancy and Inflammatory Bowel Disease, which was presented at Digestive Disease Week 2024. The consensus encompasses preconception counseling and the safety of IBD medications during pregnancy and lactation.
“Another concern, however, was that giving a live GI bug like rotavirus to babies might overstimulate their immune systems and provoke IBD,” Spencer added. “While a number of population-based studies in the US and Europe showed that was not the case, at least in the general population, there was a suggestion that, down the road, vaccination might be mildly protective against IBD in some cases.”
She added the caveat that these studies were not done in mothers and their babies with IBD, who might be inherently at greater risk for IBD. “So, a question for future research would be, ‘Is immune stimulation of the gut in IBD moms and their babies a good or a bad thing for their gut?’ ”
Spencer conceded that “the data present a bit of a blurry picture, but I think it’s always better just to vaccinate according to the regular schedule. The current data say there is no added risk, but it would be nice to look specifically at risk in moms with IBD and their children.”
The Study
The prospective cohort study is a substudy of a larger 2023 one that included biologic use in a range of maternal illnesses, not just IBD.
For the current study, Seow and colleagues identified 57 infants born to 52 mothers with IBD attending a pregnancy clinic at the University of Calgary in the period 2019-2023. Almost 81% of the mothers had Crohn’s disease, and the median duration of IBD was 10 years. The median gestational age at delivery was 39 weeks, and almost 60% of deliveries were vaginal. The infants had been exposed in utero to infliximab (n = 21), adalimumab (n = 19), vedolizumab (n = 10), and ustekinumab (n = 7) in the third trimester.
The 57 biologic-exposed infants underwent standardized clinical assessments, drug concentration, and immune function testing. The live oral rotavirus vaccine series was provided to 50 infants, with the first dose at a median of 13 weeks of age. Immunologic assessments validated for age were normal in all infants despite median infliximab concentrations of 6.1 μg/mL (range, 0.4-28.8 μg/mL), adalimumab concentrations of 1.7 μg/mL (range, 0.7-7.9 μg/mL), ustekinumab concentrations of 0.6 μg/mL (range, 0-1.1), and undetectable for vedolizumab at 10.7 weeks of age.
As anticipated, infant immune function was normal regardless of circulating drug levels.
The overall message, said Seow, is “healthy mum equals healthy baby. Be more concerned regarding active inflammation than active medications. In almost all circumstances, treat to target in pregnancy as you would in the nonpregnant state.” She added, however, that further studies are needed to determine the safety and optimal timing of other live vaccines, such as the BCG, in the presence of biologic therapy.
This study was funded by the Alberta Children’s Hospital Research Institute. Seow reported advisory/speaker’s fees for Janssen, AbbVie, Takeda, Pfizer, Fresenius Kabi, Bristol-Myers Squibb, Pharmascience, and Lilly, as well as funding from Alberta Children’s Hospital Research Institute, Crohn’s and Colitis Canada, the Canadian Institutes of Health Research, and Calgary Health Trust, and data safety monitoring from New South Wales Government Health, Australia. Multiple coauthors disclosed similar consulting or speaker relationships with private industry. Spencer had no competing interests with regard to her comments.
A version of this article first appeared on Medscape.com.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Vonoprazan Offers PPI Alternative for Heartburn with Non-Erosive Reflux
according to investigators.
Benefits of vonoprazan were seen as soon as the first day of treatment and persisted through the 20-week extension period, lead author Loren Laine, MD, AGAF, of Yale School of Medicine, New Haven, Connecticut, and colleagues reported.
“A potential alternative to PPI therapy is a potassium-competitive acid blocker, a new class of antisecretory agents that provide more potent inhibition of gastric acid secretion than PPIs,” the investigators wrote in Clinical Gastroenterology and Hepatology.
While a small observational study found that 18 out of 26 patients (69%) with PPI-resistant NERD had improved symptoms with vonoprazan, subsequent randomized trials in Japan failed to meet their primary endpoints, Laine and colleagues noted. The present randomized trial was therefore conducted to determine how vonoprazan might help a US patient population.
The study involved 772 patients who reported heartburn at least 4 days per week during screening, but without erosive esophagitis on endoscopy. Participants were randomized into three groups: placebo, vonoprazan 10 mg, or vonoprazan 20 mg. These protocols were administered for 4 weeks, followed by a 20-week extension, in which placebo patients were rerandomized to receive one of the two vonoprazan dose levels.
The primary endpoint was the percentage of days without daytime or nighttime heartburn (24-hour heartburn-free days) during the initial 4-week treatment period. The secondary endpoint, assessed during the same timeframe, was percentage of days without need for a rescue antacid.
In the 4-week placebo-controlled period, patients treated with vonoprazan 10 mg and 20 mg showed a significant improvement in heartburn-free days, compared with placebo. The percentage of 24-hour heartburn-free days was 27.7% in the placebo group vs 44.8% in the 10-mg vonoprazan group (least squares mean difference 17.1%; P < .0001) and 44.4% in the 20 mg vonoprazan group (least squares mean difference 16.7%; P < .0001).
Benefits of vonoprazan were seen as early as the first day of treatment, with 8.3% and 11.6% more patients in the 10-mg and 20-mg groups, respectively, experiencing a heartburn-free day, compared with placebo. By day 2, these differences increased to 18.1% and 23.2%, respectively.
The percentage of days without rescue antacid use was also significantly higher in both vonoprazan groups. Patients in the 10 mg and 20 mg groups had 63.3% and 61.2% of days without antacid use, respectively, compared with 47.6% in the placebo group (P < .0001 for both comparisons).
These benefits persisted throughout the 20-week extension period, with similar percentages of heartburn-free days across all groups. Mean percentages of 24-hour heartburn-free days ranged from 61% to 63% in the extension phase, while median percentages spanned 76%-79%.
Adverse events were infrequent and comparable across all groups. The most common adverse event was nausea, occurring slightly more frequently in the vonoprazan groups (2.3% in the 10-mg group and 3.1% in the 20-mg group) vs placebo (0.4%). Serious adverse events were rare and were deemed unrelated to treatment. No new safety signals were identified during the 20-week extension period. Increases in serum gastrin levels, a marker of acid suppression, returned to near baseline after discontinuation of vonoprazan.
“In conclusion, the potassium-competitive acid blocker vonoprazan was efficacious in reducing heartburn symptoms in patients with NERD, with the benefit appearing to begin as early as the first day of therapy,” Laine and colleagues wrote.
In July 2024, the Food and Drug Administration approved vonoprazan for treating heartburn in patients with nonerosive gastroesophageal reflux disease.This study was funded by Phathom Pharmaceuticals. The investigators disclosed additional relationships with Takeda, Medtronic, Carnot, and others.
Proton pump inhibitors (PPIs) have revolutionized the treatment of gastroesophageal reflux disease (GERD). One might ask what the reason would be to challenge this giant of the pharmacopeia with another medication for GERD.
In this important study by Laine et al, vonoprazan is expectedly efficacious in treating nonerosive GERD (NERD) but notably less so when compared with the authors’ trial for erosive GERD. This is not surprising owing to the multiple and common acid independent etiologies of NERD, such as esophageal hypersensitivity. The high placebo response supports this. Two notable results, however, merit emphasis in potential advantages over PPIs.
First, vonoprazan is effective at day 1 of therapy by eliminating the need for loading. Second, nocturnal reflux, a purer form of GERD, is better controlled with a morning dose of vonopazan mitigating against nocturnal acid breakthrough and the need for twice-daily dosing with PPIs and/or addition of an H2 antagonist. These results by no means advocate for replacement of PPIs with PCABs, but at least suggest specific populations of GERD patients who may specifically benefit from PCAB use. The study also indirectly emphasizes that careful selection of NERD patients whose GERD symptoms are predominantly caused by increased esophageal acid exposure are the most appropriate candidates. The ultimate answer as to where vonoprazan will be used in our practice is evolving.
David Katzka, MD, is based in the Division of Digestive and Liver Diseases, Columbia University Medical Center, New York City. He has received research support from Takeda, Sanofi, and Regeneron. He is also an associate editor for GI & Hepatology News.
Proton pump inhibitors (PPIs) have revolutionized the treatment of gastroesophageal reflux disease (GERD). One might ask what the reason would be to challenge this giant of the pharmacopeia with another medication for GERD.
In this important study by Laine et al, vonoprazan is expectedly efficacious in treating nonerosive GERD (NERD) but notably less so when compared with the authors’ trial for erosive GERD. This is not surprising owing to the multiple and common acid independent etiologies of NERD, such as esophageal hypersensitivity. The high placebo response supports this. Two notable results, however, merit emphasis in potential advantages over PPIs.
First, vonoprazan is effective at day 1 of therapy by eliminating the need for loading. Second, nocturnal reflux, a purer form of GERD, is better controlled with a morning dose of vonopazan mitigating against nocturnal acid breakthrough and the need for twice-daily dosing with PPIs and/or addition of an H2 antagonist. These results by no means advocate for replacement of PPIs with PCABs, but at least suggest specific populations of GERD patients who may specifically benefit from PCAB use. The study also indirectly emphasizes that careful selection of NERD patients whose GERD symptoms are predominantly caused by increased esophageal acid exposure are the most appropriate candidates. The ultimate answer as to where vonoprazan will be used in our practice is evolving.
David Katzka, MD, is based in the Division of Digestive and Liver Diseases, Columbia University Medical Center, New York City. He has received research support from Takeda, Sanofi, and Regeneron. He is also an associate editor for GI & Hepatology News.
Proton pump inhibitors (PPIs) have revolutionized the treatment of gastroesophageal reflux disease (GERD). One might ask what the reason would be to challenge this giant of the pharmacopeia with another medication for GERD.
In this important study by Laine et al, vonoprazan is expectedly efficacious in treating nonerosive GERD (NERD) but notably less so when compared with the authors’ trial for erosive GERD. This is not surprising owing to the multiple and common acid independent etiologies of NERD, such as esophageal hypersensitivity. The high placebo response supports this. Two notable results, however, merit emphasis in potential advantages over PPIs.
First, vonoprazan is effective at day 1 of therapy by eliminating the need for loading. Second, nocturnal reflux, a purer form of GERD, is better controlled with a morning dose of vonopazan mitigating against nocturnal acid breakthrough and the need for twice-daily dosing with PPIs and/or addition of an H2 antagonist. These results by no means advocate for replacement of PPIs with PCABs, but at least suggest specific populations of GERD patients who may specifically benefit from PCAB use. The study also indirectly emphasizes that careful selection of NERD patients whose GERD symptoms are predominantly caused by increased esophageal acid exposure are the most appropriate candidates. The ultimate answer as to where vonoprazan will be used in our practice is evolving.
David Katzka, MD, is based in the Division of Digestive and Liver Diseases, Columbia University Medical Center, New York City. He has received research support from Takeda, Sanofi, and Regeneron. He is also an associate editor for GI & Hepatology News.
according to investigators.
Benefits of vonoprazan were seen as soon as the first day of treatment and persisted through the 20-week extension period, lead author Loren Laine, MD, AGAF, of Yale School of Medicine, New Haven, Connecticut, and colleagues reported.
“A potential alternative to PPI therapy is a potassium-competitive acid blocker, a new class of antisecretory agents that provide more potent inhibition of gastric acid secretion than PPIs,” the investigators wrote in Clinical Gastroenterology and Hepatology.
While a small observational study found that 18 out of 26 patients (69%) with PPI-resistant NERD had improved symptoms with vonoprazan, subsequent randomized trials in Japan failed to meet their primary endpoints, Laine and colleagues noted. The present randomized trial was therefore conducted to determine how vonoprazan might help a US patient population.
The study involved 772 patients who reported heartburn at least 4 days per week during screening, but without erosive esophagitis on endoscopy. Participants were randomized into three groups: placebo, vonoprazan 10 mg, or vonoprazan 20 mg. These protocols were administered for 4 weeks, followed by a 20-week extension, in which placebo patients were rerandomized to receive one of the two vonoprazan dose levels.
The primary endpoint was the percentage of days without daytime or nighttime heartburn (24-hour heartburn-free days) during the initial 4-week treatment period. The secondary endpoint, assessed during the same timeframe, was percentage of days without need for a rescue antacid.
In the 4-week placebo-controlled period, patients treated with vonoprazan 10 mg and 20 mg showed a significant improvement in heartburn-free days, compared with placebo. The percentage of 24-hour heartburn-free days was 27.7% in the placebo group vs 44.8% in the 10-mg vonoprazan group (least squares mean difference 17.1%; P < .0001) and 44.4% in the 20 mg vonoprazan group (least squares mean difference 16.7%; P < .0001).
Benefits of vonoprazan were seen as early as the first day of treatment, with 8.3% and 11.6% more patients in the 10-mg and 20-mg groups, respectively, experiencing a heartburn-free day, compared with placebo. By day 2, these differences increased to 18.1% and 23.2%, respectively.
The percentage of days without rescue antacid use was also significantly higher in both vonoprazan groups. Patients in the 10 mg and 20 mg groups had 63.3% and 61.2% of days without antacid use, respectively, compared with 47.6% in the placebo group (P < .0001 for both comparisons).
These benefits persisted throughout the 20-week extension period, with similar percentages of heartburn-free days across all groups. Mean percentages of 24-hour heartburn-free days ranged from 61% to 63% in the extension phase, while median percentages spanned 76%-79%.
Adverse events were infrequent and comparable across all groups. The most common adverse event was nausea, occurring slightly more frequently in the vonoprazan groups (2.3% in the 10-mg group and 3.1% in the 20-mg group) vs placebo (0.4%). Serious adverse events were rare and were deemed unrelated to treatment. No new safety signals were identified during the 20-week extension period. Increases in serum gastrin levels, a marker of acid suppression, returned to near baseline after discontinuation of vonoprazan.
“In conclusion, the potassium-competitive acid blocker vonoprazan was efficacious in reducing heartburn symptoms in patients with NERD, with the benefit appearing to begin as early as the first day of therapy,” Laine and colleagues wrote.
In July 2024, the Food and Drug Administration approved vonoprazan for treating heartburn in patients with nonerosive gastroesophageal reflux disease.This study was funded by Phathom Pharmaceuticals. The investigators disclosed additional relationships with Takeda, Medtronic, Carnot, and others.
according to investigators.
Benefits of vonoprazan were seen as soon as the first day of treatment and persisted through the 20-week extension period, lead author Loren Laine, MD, AGAF, of Yale School of Medicine, New Haven, Connecticut, and colleagues reported.
“A potential alternative to PPI therapy is a potassium-competitive acid blocker, a new class of antisecretory agents that provide more potent inhibition of gastric acid secretion than PPIs,” the investigators wrote in Clinical Gastroenterology and Hepatology.
While a small observational study found that 18 out of 26 patients (69%) with PPI-resistant NERD had improved symptoms with vonoprazan, subsequent randomized trials in Japan failed to meet their primary endpoints, Laine and colleagues noted. The present randomized trial was therefore conducted to determine how vonoprazan might help a US patient population.
The study involved 772 patients who reported heartburn at least 4 days per week during screening, but without erosive esophagitis on endoscopy. Participants were randomized into three groups: placebo, vonoprazan 10 mg, or vonoprazan 20 mg. These protocols were administered for 4 weeks, followed by a 20-week extension, in which placebo patients were rerandomized to receive one of the two vonoprazan dose levels.
The primary endpoint was the percentage of days without daytime or nighttime heartburn (24-hour heartburn-free days) during the initial 4-week treatment period. The secondary endpoint, assessed during the same timeframe, was percentage of days without need for a rescue antacid.
In the 4-week placebo-controlled period, patients treated with vonoprazan 10 mg and 20 mg showed a significant improvement in heartburn-free days, compared with placebo. The percentage of 24-hour heartburn-free days was 27.7% in the placebo group vs 44.8% in the 10-mg vonoprazan group (least squares mean difference 17.1%; P < .0001) and 44.4% in the 20 mg vonoprazan group (least squares mean difference 16.7%; P < .0001).
Benefits of vonoprazan were seen as early as the first day of treatment, with 8.3% and 11.6% more patients in the 10-mg and 20-mg groups, respectively, experiencing a heartburn-free day, compared with placebo. By day 2, these differences increased to 18.1% and 23.2%, respectively.
The percentage of days without rescue antacid use was also significantly higher in both vonoprazan groups. Patients in the 10 mg and 20 mg groups had 63.3% and 61.2% of days without antacid use, respectively, compared with 47.6% in the placebo group (P < .0001 for both comparisons).
These benefits persisted throughout the 20-week extension period, with similar percentages of heartburn-free days across all groups. Mean percentages of 24-hour heartburn-free days ranged from 61% to 63% in the extension phase, while median percentages spanned 76%-79%.
Adverse events were infrequent and comparable across all groups. The most common adverse event was nausea, occurring slightly more frequently in the vonoprazan groups (2.3% in the 10-mg group and 3.1% in the 20-mg group) vs placebo (0.4%). Serious adverse events were rare and were deemed unrelated to treatment. No new safety signals were identified during the 20-week extension period. Increases in serum gastrin levels, a marker of acid suppression, returned to near baseline after discontinuation of vonoprazan.
“In conclusion, the potassium-competitive acid blocker vonoprazan was efficacious in reducing heartburn symptoms in patients with NERD, with the benefit appearing to begin as early as the first day of therapy,” Laine and colleagues wrote.
In July 2024, the Food and Drug Administration approved vonoprazan for treating heartburn in patients with nonerosive gastroesophageal reflux disease.This study was funded by Phathom Pharmaceuticals. The investigators disclosed additional relationships with Takeda, Medtronic, Carnot, and others.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Celiac Screening in Kids Appears Cost-Effective
If these screening strategies are deemed feasible by clinicians and patients, then implementation in routine care is needed, lead author Jan Heijdra Suasnabar, MSc, of Leiden University Medical Centre in the Netherlands, and colleagues reported.
“Cohort studies have shown that CD likely develops early in life and can be easily diagnosed by detection of CD-specific antibodies against the enzyme tissue transglutaminase type 2 (IgA-TG2),” the investigators wrote in Gastroenterology.
Despite the ease of diagnosis, as few as one in five cases of CD are detected using current clinical strategies, meaning many cases are diagnosed years after symptom onset.
“Such high rates of missed/delayed diagnoses have been attributed to CD’s varied and nonspecific symptoms, lack of awareness, and the resource-intensive process necessary to establish the diagnosis,” Heijdra Suasnabar and colleagues wrote. “From an economic perspective, the burden of CD translates into substantial excess healthcare and societal costs.”
These practice gaps prompted the present study, which explored the long-term cost effectiveness of mass CD screening and active case finding among pediatric patients.
The investigators employed a model-based cost-effectiveness analysis with a hypothetical cohort representing all children with CD in the Netherlands. Iterations of this model evaluated long-term costs as these children moved through the healthcare system along various CD detection strategies.
The first strategy was based on the current Dutch approach, which is the same as that in the United States: Patients are only evaluated for CD if they present with symptoms that prompt suspicion of disease. Based on data from population-based studies, the model assumed that approximately one in three cases would be detected using this strategy.
The second strategy involved mass screening using IgA-TG2 point-of-care testing (sensitivity, 0.94; specificity, 0.944) via youth health care clinics, regardless of symptoms.
The third strategy, called “active case finding,” represented something of an intermediate approach, in which children with at least 1 CD-related symptom underwent point-of-care antibody testing.
For both mass screening and active case finding strategies, a positive antibody test was followed with confirmatory diagnostic testing.
Compared with current clinical approach, mass screening added 7.46 more quality-adjusted life-years (QALYs) per CD patient with an increased cost of €28,635 per CD patient. Active case finding gained 4.33 QALYs per CD patient while incurring an additional cost of €15,585 per CD patient.
Based on a willingness-to-pay threshold of €20,000 per QALY, the investigators deemed both strategies “highly cost effective,” compared with current standard of care. Some of these costs were offset by “substantial” reductions in productivity losses, they noted, including CD-related absences from work and school.
“Our results illustrate how an earlier detection of CD through screening or case finding, although more costly, leads to improved health outcomes and a reduction in disease burden, compared with current care,” Heijdra Suasnabar and colleagues wrote.
Their concluding remarks highlighted the conservative scenarios built into their model, and suggested that their findings offer solid evidence for implementing new CD-testing strategies.
“If found to be feasible and acceptable by clinicians and patients, these strategies should be implemented in the Netherlands,” they wrote.This study was supported by the Netherlands Organization for Health Research and Development. The investigators disclosed no conflicts of interest.
Celiac disease (CD) is common, affecting about 1% of the population, but it remains underdiagnosed because of its heterogeneous presentation and limited provider awareness. Most cases are detected only after patients develop gastrointestinal symptoms or laboratory abnormalities.
In this cost-effectiveness analysis, Suasnabar and colleagues demonstrate that screening children for celiac disease would be highly cost-effective relative to the current practice of clinical detection. They modeled point-of-care-testing using tissue transglutaminase IgA in all 3-year-old children in the Netherlands. While both mass screening and case-finding (via a standardized questionnaire) would increase healthcare costs relative to current care, both strategies would improve quality of life (QoL), reduce long-term complications (such as osteoporosis and non-Hodgkin lymphoma), and minimize productivity losses in individuals with CD. In sensitivity analyses accounting for uncertainty in QoL inputs and in the utility of diagnosing and treating asymptomatic CD, each screening strategy remained well below accepted willingness-to-pay thresholds.
John B. Doyle, MD, is a gastroenterology fellow in the Division of Digestive and Liver Diseases at Columbia University Medical Center, New York City. Benjamin Lebwohl, MD, MS, AGAF, is professor of medicine and epidemiology at Columbia University Medical Center and director of clinical research at The Celiac Disease Center at Columbia. They have no conflicts of interest to declare.
Celiac disease (CD) is common, affecting about 1% of the population, but it remains underdiagnosed because of its heterogeneous presentation and limited provider awareness. Most cases are detected only after patients develop gastrointestinal symptoms or laboratory abnormalities.
In this cost-effectiveness analysis, Suasnabar and colleagues demonstrate that screening children for celiac disease would be highly cost-effective relative to the current practice of clinical detection. They modeled point-of-care-testing using tissue transglutaminase IgA in all 3-year-old children in the Netherlands. While both mass screening and case-finding (via a standardized questionnaire) would increase healthcare costs relative to current care, both strategies would improve quality of life (QoL), reduce long-term complications (such as osteoporosis and non-Hodgkin lymphoma), and minimize productivity losses in individuals with CD. In sensitivity analyses accounting for uncertainty in QoL inputs and in the utility of diagnosing and treating asymptomatic CD, each screening strategy remained well below accepted willingness-to-pay thresholds.
John B. Doyle, MD, is a gastroenterology fellow in the Division of Digestive and Liver Diseases at Columbia University Medical Center, New York City. Benjamin Lebwohl, MD, MS, AGAF, is professor of medicine and epidemiology at Columbia University Medical Center and director of clinical research at The Celiac Disease Center at Columbia. They have no conflicts of interest to declare.
Celiac disease (CD) is common, affecting about 1% of the population, but it remains underdiagnosed because of its heterogeneous presentation and limited provider awareness. Most cases are detected only after patients develop gastrointestinal symptoms or laboratory abnormalities.
In this cost-effectiveness analysis, Suasnabar and colleagues demonstrate that screening children for celiac disease would be highly cost-effective relative to the current practice of clinical detection. They modeled point-of-care-testing using tissue transglutaminase IgA in all 3-year-old children in the Netherlands. While both mass screening and case-finding (via a standardized questionnaire) would increase healthcare costs relative to current care, both strategies would improve quality of life (QoL), reduce long-term complications (such as osteoporosis and non-Hodgkin lymphoma), and minimize productivity losses in individuals with CD. In sensitivity analyses accounting for uncertainty in QoL inputs and in the utility of diagnosing and treating asymptomatic CD, each screening strategy remained well below accepted willingness-to-pay thresholds.
John B. Doyle, MD, is a gastroenterology fellow in the Division of Digestive and Liver Diseases at Columbia University Medical Center, New York City. Benjamin Lebwohl, MD, MS, AGAF, is professor of medicine and epidemiology at Columbia University Medical Center and director of clinical research at The Celiac Disease Center at Columbia. They have no conflicts of interest to declare.
If these screening strategies are deemed feasible by clinicians and patients, then implementation in routine care is needed, lead author Jan Heijdra Suasnabar, MSc, of Leiden University Medical Centre in the Netherlands, and colleagues reported.
“Cohort studies have shown that CD likely develops early in life and can be easily diagnosed by detection of CD-specific antibodies against the enzyme tissue transglutaminase type 2 (IgA-TG2),” the investigators wrote in Gastroenterology.
Despite the ease of diagnosis, as few as one in five cases of CD are detected using current clinical strategies, meaning many cases are diagnosed years after symptom onset.
“Such high rates of missed/delayed diagnoses have been attributed to CD’s varied and nonspecific symptoms, lack of awareness, and the resource-intensive process necessary to establish the diagnosis,” Heijdra Suasnabar and colleagues wrote. “From an economic perspective, the burden of CD translates into substantial excess healthcare and societal costs.”
These practice gaps prompted the present study, which explored the long-term cost effectiveness of mass CD screening and active case finding among pediatric patients.
The investigators employed a model-based cost-effectiveness analysis with a hypothetical cohort representing all children with CD in the Netherlands. Iterations of this model evaluated long-term costs as these children moved through the healthcare system along various CD detection strategies.
The first strategy was based on the current Dutch approach, which is the same as that in the United States: Patients are only evaluated for CD if they present with symptoms that prompt suspicion of disease. Based on data from population-based studies, the model assumed that approximately one in three cases would be detected using this strategy.
The second strategy involved mass screening using IgA-TG2 point-of-care testing (sensitivity, 0.94; specificity, 0.944) via youth health care clinics, regardless of symptoms.
The third strategy, called “active case finding,” represented something of an intermediate approach, in which children with at least 1 CD-related symptom underwent point-of-care antibody testing.
For both mass screening and active case finding strategies, a positive antibody test was followed with confirmatory diagnostic testing.
Compared with current clinical approach, mass screening added 7.46 more quality-adjusted life-years (QALYs) per CD patient with an increased cost of €28,635 per CD patient. Active case finding gained 4.33 QALYs per CD patient while incurring an additional cost of €15,585 per CD patient.
Based on a willingness-to-pay threshold of €20,000 per QALY, the investigators deemed both strategies “highly cost effective,” compared with current standard of care. Some of these costs were offset by “substantial” reductions in productivity losses, they noted, including CD-related absences from work and school.
“Our results illustrate how an earlier detection of CD through screening or case finding, although more costly, leads to improved health outcomes and a reduction in disease burden, compared with current care,” Heijdra Suasnabar and colleagues wrote.
Their concluding remarks highlighted the conservative scenarios built into their model, and suggested that their findings offer solid evidence for implementing new CD-testing strategies.
“If found to be feasible and acceptable by clinicians and patients, these strategies should be implemented in the Netherlands,” they wrote.This study was supported by the Netherlands Organization for Health Research and Development. The investigators disclosed no conflicts of interest.
If these screening strategies are deemed feasible by clinicians and patients, then implementation in routine care is needed, lead author Jan Heijdra Suasnabar, MSc, of Leiden University Medical Centre in the Netherlands, and colleagues reported.
“Cohort studies have shown that CD likely develops early in life and can be easily diagnosed by detection of CD-specific antibodies against the enzyme tissue transglutaminase type 2 (IgA-TG2),” the investigators wrote in Gastroenterology.
Despite the ease of diagnosis, as few as one in five cases of CD are detected using current clinical strategies, meaning many cases are diagnosed years after symptom onset.
“Such high rates of missed/delayed diagnoses have been attributed to CD’s varied and nonspecific symptoms, lack of awareness, and the resource-intensive process necessary to establish the diagnosis,” Heijdra Suasnabar and colleagues wrote. “From an economic perspective, the burden of CD translates into substantial excess healthcare and societal costs.”
These practice gaps prompted the present study, which explored the long-term cost effectiveness of mass CD screening and active case finding among pediatric patients.
The investigators employed a model-based cost-effectiveness analysis with a hypothetical cohort representing all children with CD in the Netherlands. Iterations of this model evaluated long-term costs as these children moved through the healthcare system along various CD detection strategies.
The first strategy was based on the current Dutch approach, which is the same as that in the United States: Patients are only evaluated for CD if they present with symptoms that prompt suspicion of disease. Based on data from population-based studies, the model assumed that approximately one in three cases would be detected using this strategy.
The second strategy involved mass screening using IgA-TG2 point-of-care testing (sensitivity, 0.94; specificity, 0.944) via youth health care clinics, regardless of symptoms.
The third strategy, called “active case finding,” represented something of an intermediate approach, in which children with at least 1 CD-related symptom underwent point-of-care antibody testing.
For both mass screening and active case finding strategies, a positive antibody test was followed with confirmatory diagnostic testing.
Compared with current clinical approach, mass screening added 7.46 more quality-adjusted life-years (QALYs) per CD patient with an increased cost of €28,635 per CD patient. Active case finding gained 4.33 QALYs per CD patient while incurring an additional cost of €15,585 per CD patient.
Based on a willingness-to-pay threshold of €20,000 per QALY, the investigators deemed both strategies “highly cost effective,” compared with current standard of care. Some of these costs were offset by “substantial” reductions in productivity losses, they noted, including CD-related absences from work and school.
“Our results illustrate how an earlier detection of CD through screening or case finding, although more costly, leads to improved health outcomes and a reduction in disease burden, compared with current care,” Heijdra Suasnabar and colleagues wrote.
Their concluding remarks highlighted the conservative scenarios built into their model, and suggested that their findings offer solid evidence for implementing new CD-testing strategies.
“If found to be feasible and acceptable by clinicians and patients, these strategies should be implemented in the Netherlands,” they wrote.This study was supported by the Netherlands Organization for Health Research and Development. The investigators disclosed no conflicts of interest.
FROM GASTROENTEROLOGY
Reducing Biologic Discontinuation Among Pediatric Crohn’s Patients
, according to investigators.
These findings, and others concerning a lack of high-dose therapy and poor follow-up, suggest that more work is needed to optimize biologic therapy in this patient population, reported lead author Sabina Ali, MD, of UCSF Benioff Children’s Hospital, Oakland, California, and colleagues.
“With few medications available for treating CD, limited therapeutic longevity places patients at risk of exhausting treatment options,” the investigators wrote in Clinical Gastroenterology and Hepatology. “This is especially problematic for children, for whom infliximab and adalimumab remain the only medications approved by the Food and Drug Administration (FDA), and who require effective long-term therapy to maintain remission and prevent morbidity and disability for decades to come.”
Despite these concerns, reasons behind biologic discontinuation in the pediatric CD population have been poorly characterized, prompting the present study.
Dr. Ali and colleagues analyzed prospectively collected data from 823 patients treated at seven pediatric inflammatory bowel disease centers. Median age was 13 years, with slightly more male than female patients (60% vs 40%).
Within this group, 86% started biologics, most often infliximab (78%), followed by adalimumab (21%), and distantly, others (less than 1%). Most patients (86%) underwent TDM at some point during the treatment process, while one quarter (26%) took concomitant immunomodulators for at least 1 year.
Slightly less than one third of patients (29%) discontinued their first biologic after a median of approximately 2 years. The most common reason for discontinuation was inefficacy (34%), followed by nonadherence (12%), anti-drug antibodies (8%), and adverse events (8%).
Among those who discontinued due to inefficacy, 85% underwent prediscontinuation evaluation. When TDM of adalimumab or infliximab was performed prior to discontinuation, almost 2 out of 3 patients (62%) had drug levels lower than 10 µg/mL.
“We cannot determine the reasons dose escalation was not attempted,” the investigators wrote. “However, trough levels greater than 10 mg/mL may be associated with improved efficacy.”
Most patients (91%) who stopped their first biologic started a second, and more than one third (36%) also discontinued that second option, usually after about 1 year. After 4 years, only 10% of patients remained on their second biologic therapy. By study end, almost 1 out of 12 patients were on their third or fourth biologic, and 17% of patients were on a biologic currently not approved by the FDA.
Beyond characterizing these usage and discontinuation rates, the investigators also assessed factors associated with discontinuation or therapeutic persistence.
Proactive TDM was the strongest factor driving therapeutic persistence, as it reduced risk of discontinuation by 63%. Concomitant immunomodulatory therapy also reduced discontinuation risk, by 30%. Conversely, usage of 5-aminoasalicylate in the first 90 days of diagnosis was associated with a 70% higher discontinuation rate.
“The reason for this [latter finding about aminosalicylates] is not clear but may be an indicator of insurance-related or other barriers to care,” the investigators wrote.
Dr. Ali and colleagues concluded by noting how concerning, and commonplace, biologic discontinuation is in this patient population.
“This poses a serious problem for pediatric patients who will require treatment for decades to come,” they wrote. “Thoughtful strategies are needed to preserve treatment longevity and minimize the loss of treatment options.”
This work was supported by the Gary and Rachel Glick Charitable Fund. The investigators disclosed relationships with Janssen, Eli Lilly, AbbVie, and others.
As pediatric gastroenterologists, our practice has significantly changed over time, including the approach of using more effective medications sooner and adoption of therapeutic drug monitoring (TDM) as standard of care to optimize dosing. This study found the use of TDM during the induction phase of biologic therapy increased over the study duration from 2% to 70%, which is remarkable. Pediatric patients tend to have more extensive and severe disease, often necessitating higher dosing. With limited Food and Drug Administration–approved medications to treat children with IBD, it is imperative that we position these medications appropriately and be assertive with dose optimization to improve patient outcomes.
Alarmingly, one third of patients discontinued their biologic after 2.2 years. Concerningly, half discontinued their biologics without a trial of high-dose therapy and 14% without any evaluation. Trough levels >10 mg/mL may be associated with improved efficacy and low antibody levels can be overcome, however many of these patients had levels lower than this. This is likely a missed opportunity to capture response and increase durability with dose escalation. Biologic discontinuation was reduced by 60% with the use of proactive TDM and 32% with concomitant immunomodulators (on >12 months, compared with monotherapy). Pediatric data supporting the use of concomitant immunomodulators has been mixed.
As pediatric IBD physicians, we need to increase our diligence to optimize biologic therapy early. Early dose optimization could negate the observed protective impact from concomitant immunomodulator use in many cases, thereby decreasing risk of potential side effects. This highlights the importance of a shared decision-making discussion with our patients and families.
Further research is needed to address strategies to increase drug durability including TDM and dose optimization, adherence, health literacy, engagement, and the role for patient education to enhance medication optimization and durability.
Jennifer L. Dotson, MD, MPH, is chief of pediatric gastroenterology, hepatology, and nutrition at Arkansas Children’s Hospital and professor of pediatrics at the University of Arkansas for Medical Sciences, both in Little Rock. She declares no conflicts of interest.
As pediatric gastroenterologists, our practice has significantly changed over time, including the approach of using more effective medications sooner and adoption of therapeutic drug monitoring (TDM) as standard of care to optimize dosing. This study found the use of TDM during the induction phase of biologic therapy increased over the study duration from 2% to 70%, which is remarkable. Pediatric patients tend to have more extensive and severe disease, often necessitating higher dosing. With limited Food and Drug Administration–approved medications to treat children with IBD, it is imperative that we position these medications appropriately and be assertive with dose optimization to improve patient outcomes.
Alarmingly, one third of patients discontinued their biologic after 2.2 years. Concerningly, half discontinued their biologics without a trial of high-dose therapy and 14% without any evaluation. Trough levels >10 mg/mL may be associated with improved efficacy and low antibody levels can be overcome, however many of these patients had levels lower than this. This is likely a missed opportunity to capture response and increase durability with dose escalation. Biologic discontinuation was reduced by 60% with the use of proactive TDM and 32% with concomitant immunomodulators (on >12 months, compared with monotherapy). Pediatric data supporting the use of concomitant immunomodulators has been mixed.
As pediatric IBD physicians, we need to increase our diligence to optimize biologic therapy early. Early dose optimization could negate the observed protective impact from concomitant immunomodulator use in many cases, thereby decreasing risk of potential side effects. This highlights the importance of a shared decision-making discussion with our patients and families.
Further research is needed to address strategies to increase drug durability including TDM and dose optimization, adherence, health literacy, engagement, and the role for patient education to enhance medication optimization and durability.
Jennifer L. Dotson, MD, MPH, is chief of pediatric gastroenterology, hepatology, and nutrition at Arkansas Children’s Hospital and professor of pediatrics at the University of Arkansas for Medical Sciences, both in Little Rock. She declares no conflicts of interest.
As pediatric gastroenterologists, our practice has significantly changed over time, including the approach of using more effective medications sooner and adoption of therapeutic drug monitoring (TDM) as standard of care to optimize dosing. This study found the use of TDM during the induction phase of biologic therapy increased over the study duration from 2% to 70%, which is remarkable. Pediatric patients tend to have more extensive and severe disease, often necessitating higher dosing. With limited Food and Drug Administration–approved medications to treat children with IBD, it is imperative that we position these medications appropriately and be assertive with dose optimization to improve patient outcomes.
Alarmingly, one third of patients discontinued their biologic after 2.2 years. Concerningly, half discontinued their biologics without a trial of high-dose therapy and 14% without any evaluation. Trough levels >10 mg/mL may be associated with improved efficacy and low antibody levels can be overcome, however many of these patients had levels lower than this. This is likely a missed opportunity to capture response and increase durability with dose escalation. Biologic discontinuation was reduced by 60% with the use of proactive TDM and 32% with concomitant immunomodulators (on >12 months, compared with monotherapy). Pediatric data supporting the use of concomitant immunomodulators has been mixed.
As pediatric IBD physicians, we need to increase our diligence to optimize biologic therapy early. Early dose optimization could negate the observed protective impact from concomitant immunomodulator use in many cases, thereby decreasing risk of potential side effects. This highlights the importance of a shared decision-making discussion with our patients and families.
Further research is needed to address strategies to increase drug durability including TDM and dose optimization, adherence, health literacy, engagement, and the role for patient education to enhance medication optimization and durability.
Jennifer L. Dotson, MD, MPH, is chief of pediatric gastroenterology, hepatology, and nutrition at Arkansas Children’s Hospital and professor of pediatrics at the University of Arkansas for Medical Sciences, both in Little Rock. She declares no conflicts of interest.
, according to investigators.
These findings, and others concerning a lack of high-dose therapy and poor follow-up, suggest that more work is needed to optimize biologic therapy in this patient population, reported lead author Sabina Ali, MD, of UCSF Benioff Children’s Hospital, Oakland, California, and colleagues.
“With few medications available for treating CD, limited therapeutic longevity places patients at risk of exhausting treatment options,” the investigators wrote in Clinical Gastroenterology and Hepatology. “This is especially problematic for children, for whom infliximab and adalimumab remain the only medications approved by the Food and Drug Administration (FDA), and who require effective long-term therapy to maintain remission and prevent morbidity and disability for decades to come.”
Despite these concerns, reasons behind biologic discontinuation in the pediatric CD population have been poorly characterized, prompting the present study.
Dr. Ali and colleagues analyzed prospectively collected data from 823 patients treated at seven pediatric inflammatory bowel disease centers. Median age was 13 years, with slightly more male than female patients (60% vs 40%).
Within this group, 86% started biologics, most often infliximab (78%), followed by adalimumab (21%), and distantly, others (less than 1%). Most patients (86%) underwent TDM at some point during the treatment process, while one quarter (26%) took concomitant immunomodulators for at least 1 year.
Slightly less than one third of patients (29%) discontinued their first biologic after a median of approximately 2 years. The most common reason for discontinuation was inefficacy (34%), followed by nonadherence (12%), anti-drug antibodies (8%), and adverse events (8%).
Among those who discontinued due to inefficacy, 85% underwent prediscontinuation evaluation. When TDM of adalimumab or infliximab was performed prior to discontinuation, almost 2 out of 3 patients (62%) had drug levels lower than 10 µg/mL.
“We cannot determine the reasons dose escalation was not attempted,” the investigators wrote. “However, trough levels greater than 10 mg/mL may be associated with improved efficacy.”
Most patients (91%) who stopped their first biologic started a second, and more than one third (36%) also discontinued that second option, usually after about 1 year. After 4 years, only 10% of patients remained on their second biologic therapy. By study end, almost 1 out of 12 patients were on their third or fourth biologic, and 17% of patients were on a biologic currently not approved by the FDA.
Beyond characterizing these usage and discontinuation rates, the investigators also assessed factors associated with discontinuation or therapeutic persistence.
Proactive TDM was the strongest factor driving therapeutic persistence, as it reduced risk of discontinuation by 63%. Concomitant immunomodulatory therapy also reduced discontinuation risk, by 30%. Conversely, usage of 5-aminoasalicylate in the first 90 days of diagnosis was associated with a 70% higher discontinuation rate.
“The reason for this [latter finding about aminosalicylates] is not clear but may be an indicator of insurance-related or other barriers to care,” the investigators wrote.
Dr. Ali and colleagues concluded by noting how concerning, and commonplace, biologic discontinuation is in this patient population.
“This poses a serious problem for pediatric patients who will require treatment for decades to come,” they wrote. “Thoughtful strategies are needed to preserve treatment longevity and minimize the loss of treatment options.”
This work was supported by the Gary and Rachel Glick Charitable Fund. The investigators disclosed relationships with Janssen, Eli Lilly, AbbVie, and others.
, according to investigators.
These findings, and others concerning a lack of high-dose therapy and poor follow-up, suggest that more work is needed to optimize biologic therapy in this patient population, reported lead author Sabina Ali, MD, of UCSF Benioff Children’s Hospital, Oakland, California, and colleagues.
“With few medications available for treating CD, limited therapeutic longevity places patients at risk of exhausting treatment options,” the investigators wrote in Clinical Gastroenterology and Hepatology. “This is especially problematic for children, for whom infliximab and adalimumab remain the only medications approved by the Food and Drug Administration (FDA), and who require effective long-term therapy to maintain remission and prevent morbidity and disability for decades to come.”
Despite these concerns, reasons behind biologic discontinuation in the pediatric CD population have been poorly characterized, prompting the present study.
Dr. Ali and colleagues analyzed prospectively collected data from 823 patients treated at seven pediatric inflammatory bowel disease centers. Median age was 13 years, with slightly more male than female patients (60% vs 40%).
Within this group, 86% started biologics, most often infliximab (78%), followed by adalimumab (21%), and distantly, others (less than 1%). Most patients (86%) underwent TDM at some point during the treatment process, while one quarter (26%) took concomitant immunomodulators for at least 1 year.
Slightly less than one third of patients (29%) discontinued their first biologic after a median of approximately 2 years. The most common reason for discontinuation was inefficacy (34%), followed by nonadherence (12%), anti-drug antibodies (8%), and adverse events (8%).
Among those who discontinued due to inefficacy, 85% underwent prediscontinuation evaluation. When TDM of adalimumab or infliximab was performed prior to discontinuation, almost 2 out of 3 patients (62%) had drug levels lower than 10 µg/mL.
“We cannot determine the reasons dose escalation was not attempted,” the investigators wrote. “However, trough levels greater than 10 mg/mL may be associated with improved efficacy.”
Most patients (91%) who stopped their first biologic started a second, and more than one third (36%) also discontinued that second option, usually after about 1 year. After 4 years, only 10% of patients remained on their second biologic therapy. By study end, almost 1 out of 12 patients were on their third or fourth biologic, and 17% of patients were on a biologic currently not approved by the FDA.
Beyond characterizing these usage and discontinuation rates, the investigators also assessed factors associated with discontinuation or therapeutic persistence.
Proactive TDM was the strongest factor driving therapeutic persistence, as it reduced risk of discontinuation by 63%. Concomitant immunomodulatory therapy also reduced discontinuation risk, by 30%. Conversely, usage of 5-aminoasalicylate in the first 90 days of diagnosis was associated with a 70% higher discontinuation rate.
“The reason for this [latter finding about aminosalicylates] is not clear but may be an indicator of insurance-related or other barriers to care,” the investigators wrote.
Dr. Ali and colleagues concluded by noting how concerning, and commonplace, biologic discontinuation is in this patient population.
“This poses a serious problem for pediatric patients who will require treatment for decades to come,” they wrote. “Thoughtful strategies are needed to preserve treatment longevity and minimize the loss of treatment options.”
This work was supported by the Gary and Rachel Glick Charitable Fund. The investigators disclosed relationships with Janssen, Eli Lilly, AbbVie, and others.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Baveno VI Criteria Appear Cost-Effective for Detecting Varices in Cirrhosis
Compared with endoscopy, , according to new research.
Although upper gastrointestinal endoscopy continues to be the gold standard for detecting varices, the Baveno VI criteria combine liver stiffness and platelet count values to rule out high-risk varices, which can save on endoscopy costs.
“The Baveno VI criteria can reduce the need for endoscopies in patients with cirrhosis, but it is important to ascertain if they are also cost-effective,” said senior author Emmanuel Tsochatzis, MD, professor of hepatology at the University College London Institute for Liver and Digestive Health and Royal Free Hospital in London.
“Our findings confirm that the application of these criteria is highly cost-effective, and given the fact that they are also safe, should be considered for widespread implementation,” he said.
The study was published online in Clinical Gastroenterology and Hepatology.
Baveno VI Criteria Analysis
On the basis of the Baveno VI Consensus, endoscopy screening can be avoided in patients with compensated advanced chronic liver disease and Child-Pugh A cirrhosis who have a platelet count > 150,000/mm3 and a liver stiffness measurement < 20 kPa.
In addition, expanded Baveno VI criteria have suggested optimized cut-off values to avoid even more endoscopies — at a platelet value of > 110,000/mm3 and a liver stiffness < 25 kPa.
Previous research indicates that the expanded criteria could avoid double the number of endoscopies, the authors wrote, with a risk of missing high-risk varices in 1.6% of patients with the criteria and 0.6% of overall study participants. Both criteria have been validated in large groups of patients with compensated cirrhosis of different etiologies, but the cost-effectiveness hasn’t been analyzed.
Dr. Tsochatzis and colleagues created an analytical decision model to estimate the costs and benefits of using the Baveno VI criteria as compared with endoscopy as the standard of care among a hypothetical cohort of 1000 patients with Child-Pugh A cirrhosis. The research team looked at costs and clinical outcomes based on the United Kingdom National Health Service perspective at 1 year from diagnosis and then estimated the expected costs and outcomes at 5 years and 20 years, including factors such as liver disease progression and variceal bleeding.
As part of the model, the Baveno VI criteria were implemented at annual screenings with targeted endoscopy for patients who met the criteria, as compared with endoscopy as a biannual screening using esophagogastroduodenoscopy for everyone.
In general, the Baveno VI criteria were cost-effective compared with endoscopy in all analyses, including all time points, as well as deterministic and probabilistic sensitivity analyses. The cost of using the criteria was £67 per patient, as compared with £411 per patient for esophagogastroduodenoscopy.
For the 1000 patients, the criteria produced 0.16 additional quality-adjusted life years (QALYs) per patient at an incremental cost of £326, or about $443, over 5 years. This resulted in an incremental cost-effectiveness ratio (ICER) of £2081, or $2830, per additional QALY gained.
In addition, the incremental net monetary benefit of the Baveno VI criteria was £2808, or $3819, over 5 years per patient.
The results were also consistent and cost-effective in Canada and Spain using relevant cost inputs from those countries. In Canada, the ICER per QALY estimates were €3535, or $3712, over 5 years and €4610, or $4841, over 20 years. In Spain, the ICER per QALY estimates were €1966, or $2064, over 5 years and €2225, or $2336, over 20 years.
Baveno VI Considerations
Despite the small risk of false negatives, the Baveno VI criteria could avoid unnecessary endoscopies and provide significant cost savings, the study authors wrote.
“It should be mentioned, however, that sparing endoscopies could result in missing the incidental detection of esophageal and gastric cancers, particularly in patients with higher risk, such as those who misuse alcohol,” Dr. Tsochatzis said.
Future studies could investigate ways to broaden the applicability of the Baveno VI criteria to other patient subgroups, identify optimal cut-off points, and incorporate patients with systemic therapies.
“Baveno VI criteria can be safely used to avoid endoscopy in a substantial proportion of patients with compensated cirrhosis,” said Wayne Bai, MBChB, a gastroenterologist at Waikato Hospital and the University of Auckland in New Zealand.
Dr. Bai, who wasn’t involved with this study, has researched the Baveno VI criteria and participated in Baveno VII criteria meetings. In an analysis of more than two dozen studies, he and colleagues found that the Baveno VI criteria had a pooled 99% negative predictive value for ruling out high-risk varices and weren’t affected by the cause of cirrhosis. However, expanding the criteria had suboptimal performance in some cases.
“The progressive change in approach to the management of compensated cirrhosis, progressively focusing on treating portal hypertension with beta-blockers independently of the presence of varices, might render these criteria less relevant,” he said.
The authors were supported by funds from the National Institute for Health and Care Research Applied Research Collaboration North Thames, the Instituto de Salud Carlos III, and the European Union’s European Regional Development Fund and European Social Fund. Dr Bai reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
Compared with endoscopy, , according to new research.
Although upper gastrointestinal endoscopy continues to be the gold standard for detecting varices, the Baveno VI criteria combine liver stiffness and platelet count values to rule out high-risk varices, which can save on endoscopy costs.
“The Baveno VI criteria can reduce the need for endoscopies in patients with cirrhosis, but it is important to ascertain if they are also cost-effective,” said senior author Emmanuel Tsochatzis, MD, professor of hepatology at the University College London Institute for Liver and Digestive Health and Royal Free Hospital in London.
“Our findings confirm that the application of these criteria is highly cost-effective, and given the fact that they are also safe, should be considered for widespread implementation,” he said.
The study was published online in Clinical Gastroenterology and Hepatology.
Baveno VI Criteria Analysis
On the basis of the Baveno VI Consensus, endoscopy screening can be avoided in patients with compensated advanced chronic liver disease and Child-Pugh A cirrhosis who have a platelet count > 150,000/mm3 and a liver stiffness measurement < 20 kPa.
In addition, expanded Baveno VI criteria have suggested optimized cut-off values to avoid even more endoscopies — at a platelet value of > 110,000/mm3 and a liver stiffness < 25 kPa.
Previous research indicates that the expanded criteria could avoid double the number of endoscopies, the authors wrote, with a risk of missing high-risk varices in 1.6% of patients with the criteria and 0.6% of overall study participants. Both criteria have been validated in large groups of patients with compensated cirrhosis of different etiologies, but the cost-effectiveness hasn’t been analyzed.
Dr. Tsochatzis and colleagues created an analytical decision model to estimate the costs and benefits of using the Baveno VI criteria as compared with endoscopy as the standard of care among a hypothetical cohort of 1000 patients with Child-Pugh A cirrhosis. The research team looked at costs and clinical outcomes based on the United Kingdom National Health Service perspective at 1 year from diagnosis and then estimated the expected costs and outcomes at 5 years and 20 years, including factors such as liver disease progression and variceal bleeding.
As part of the model, the Baveno VI criteria were implemented at annual screenings with targeted endoscopy for patients who met the criteria, as compared with endoscopy as a biannual screening using esophagogastroduodenoscopy for everyone.
In general, the Baveno VI criteria were cost-effective compared with endoscopy in all analyses, including all time points, as well as deterministic and probabilistic sensitivity analyses. The cost of using the criteria was £67 per patient, as compared with £411 per patient for esophagogastroduodenoscopy.
For the 1000 patients, the criteria produced 0.16 additional quality-adjusted life years (QALYs) per patient at an incremental cost of £326, or about $443, over 5 years. This resulted in an incremental cost-effectiveness ratio (ICER) of £2081, or $2830, per additional QALY gained.
In addition, the incremental net monetary benefit of the Baveno VI criteria was £2808, or $3819, over 5 years per patient.
The results were also consistent and cost-effective in Canada and Spain using relevant cost inputs from those countries. In Canada, the ICER per QALY estimates were €3535, or $3712, over 5 years and €4610, or $4841, over 20 years. In Spain, the ICER per QALY estimates were €1966, or $2064, over 5 years and €2225, or $2336, over 20 years.
Baveno VI Considerations
Despite the small risk of false negatives, the Baveno VI criteria could avoid unnecessary endoscopies and provide significant cost savings, the study authors wrote.
“It should be mentioned, however, that sparing endoscopies could result in missing the incidental detection of esophageal and gastric cancers, particularly in patients with higher risk, such as those who misuse alcohol,” Dr. Tsochatzis said.
Future studies could investigate ways to broaden the applicability of the Baveno VI criteria to other patient subgroups, identify optimal cut-off points, and incorporate patients with systemic therapies.
“Baveno VI criteria can be safely used to avoid endoscopy in a substantial proportion of patients with compensated cirrhosis,” said Wayne Bai, MBChB, a gastroenterologist at Waikato Hospital and the University of Auckland in New Zealand.
Dr. Bai, who wasn’t involved with this study, has researched the Baveno VI criteria and participated in Baveno VII criteria meetings. In an analysis of more than two dozen studies, he and colleagues found that the Baveno VI criteria had a pooled 99% negative predictive value for ruling out high-risk varices and weren’t affected by the cause of cirrhosis. However, expanding the criteria had suboptimal performance in some cases.
“The progressive change in approach to the management of compensated cirrhosis, progressively focusing on treating portal hypertension with beta-blockers independently of the presence of varices, might render these criteria less relevant,” he said.
The authors were supported by funds from the National Institute for Health and Care Research Applied Research Collaboration North Thames, the Instituto de Salud Carlos III, and the European Union’s European Regional Development Fund and European Social Fund. Dr Bai reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
Compared with endoscopy, , according to new research.
Although upper gastrointestinal endoscopy continues to be the gold standard for detecting varices, the Baveno VI criteria combine liver stiffness and platelet count values to rule out high-risk varices, which can save on endoscopy costs.
“The Baveno VI criteria can reduce the need for endoscopies in patients with cirrhosis, but it is important to ascertain if they are also cost-effective,” said senior author Emmanuel Tsochatzis, MD, professor of hepatology at the University College London Institute for Liver and Digestive Health and Royal Free Hospital in London.
“Our findings confirm that the application of these criteria is highly cost-effective, and given the fact that they are also safe, should be considered for widespread implementation,” he said.
The study was published online in Clinical Gastroenterology and Hepatology.
Baveno VI Criteria Analysis
On the basis of the Baveno VI Consensus, endoscopy screening can be avoided in patients with compensated advanced chronic liver disease and Child-Pugh A cirrhosis who have a platelet count > 150,000/mm3 and a liver stiffness measurement < 20 kPa.
In addition, expanded Baveno VI criteria have suggested optimized cut-off values to avoid even more endoscopies — at a platelet value of > 110,000/mm3 and a liver stiffness < 25 kPa.
Previous research indicates that the expanded criteria could avoid double the number of endoscopies, the authors wrote, with a risk of missing high-risk varices in 1.6% of patients with the criteria and 0.6% of overall study participants. Both criteria have been validated in large groups of patients with compensated cirrhosis of different etiologies, but the cost-effectiveness hasn’t been analyzed.
Dr. Tsochatzis and colleagues created an analytical decision model to estimate the costs and benefits of using the Baveno VI criteria as compared with endoscopy as the standard of care among a hypothetical cohort of 1000 patients with Child-Pugh A cirrhosis. The research team looked at costs and clinical outcomes based on the United Kingdom National Health Service perspective at 1 year from diagnosis and then estimated the expected costs and outcomes at 5 years and 20 years, including factors such as liver disease progression and variceal bleeding.
As part of the model, the Baveno VI criteria were implemented at annual screenings with targeted endoscopy for patients who met the criteria, as compared with endoscopy as a biannual screening using esophagogastroduodenoscopy for everyone.
In general, the Baveno VI criteria were cost-effective compared with endoscopy in all analyses, including all time points, as well as deterministic and probabilistic sensitivity analyses. The cost of using the criteria was £67 per patient, as compared with £411 per patient for esophagogastroduodenoscopy.
For the 1000 patients, the criteria produced 0.16 additional quality-adjusted life years (QALYs) per patient at an incremental cost of £326, or about $443, over 5 years. This resulted in an incremental cost-effectiveness ratio (ICER) of £2081, or $2830, per additional QALY gained.
In addition, the incremental net monetary benefit of the Baveno VI criteria was £2808, or $3819, over 5 years per patient.
The results were also consistent and cost-effective in Canada and Spain using relevant cost inputs from those countries. In Canada, the ICER per QALY estimates were €3535, or $3712, over 5 years and €4610, or $4841, over 20 years. In Spain, the ICER per QALY estimates were €1966, or $2064, over 5 years and €2225, or $2336, over 20 years.
Baveno VI Considerations
Despite the small risk of false negatives, the Baveno VI criteria could avoid unnecessary endoscopies and provide significant cost savings, the study authors wrote.
“It should be mentioned, however, that sparing endoscopies could result in missing the incidental detection of esophageal and gastric cancers, particularly in patients with higher risk, such as those who misuse alcohol,” Dr. Tsochatzis said.
Future studies could investigate ways to broaden the applicability of the Baveno VI criteria to other patient subgroups, identify optimal cut-off points, and incorporate patients with systemic therapies.
“Baveno VI criteria can be safely used to avoid endoscopy in a substantial proportion of patients with compensated cirrhosis,” said Wayne Bai, MBChB, a gastroenterologist at Waikato Hospital and the University of Auckland in New Zealand.
Dr. Bai, who wasn’t involved with this study, has researched the Baveno VI criteria and participated in Baveno VII criteria meetings. In an analysis of more than two dozen studies, he and colleagues found that the Baveno VI criteria had a pooled 99% negative predictive value for ruling out high-risk varices and weren’t affected by the cause of cirrhosis. However, expanding the criteria had suboptimal performance in some cases.
“The progressive change in approach to the management of compensated cirrhosis, progressively focusing on treating portal hypertension with beta-blockers independently of the presence of varices, might render these criteria less relevant,” he said.
The authors were supported by funds from the National Institute for Health and Care Research Applied Research Collaboration North Thames, the Instituto de Salud Carlos III, and the European Union’s European Regional Development Fund and European Social Fund. Dr Bai reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Study Questions Relationship Between Crohn’s Strictures and Cancer Risk
, according to investigators.
Although 8% of patients with strictures in a multicenter study were diagnosed with CRC, this diagnosis was made either simultaneously or within 1 year of stricture diagnosis, suggesting that cancer may have driven stricture development, and not the other way around, lead author Thomas Hunaut, MD, of Université de Champagne-Ardenne, Reims, France, and colleagues reported.
“The occurrence of colonic stricture in CD always raises concerns about the risk for dysplasia/cancer,” the investigators wrote in Gastro Hep Advances, noting that no consensus approach is currently available to guide stricture management. “Few studies with conflicting results have evaluated the frequency of CRC associated with colonic stricture in CD, and the natural history of colonic stricture in CD is poorly known.”The present retrospective study included 88 consecutive CD patients with 96 colorectal strictures who were managed at three French referral centers between 1993 and 2022.
Strictures were symptomatic in 62.5% of cases, not passable by scope in 61.4% of cases, and ulcerated in 70.5% of cases. Colonic resection was needed in 47.7% of patients, while endoscopic balloon dilation was performed in 13.6% of patients.
After a median follow-up of 21.5 months, seven patients (8%) were diagnosed with malignant stricture, including five cases of colonic adenocarcinoma, one case of neuroendocrine carcinoma, and one case of B-cell lymphoproliferative neoplasia.
Malignant strictures were more common among older patients with longer disease duration and frequent obstructive symptoms; however, these factors were not supported by multivariate analyses, likely due to sample size, according to the investigators.
Instead, Dr. Hunaut and colleagues highlighted the timing of the diagnoses. In four out of seven patients with malignant stricture, both stricture and cancer were diagnosed at the same time. In the remaining three patients, cancer was diagnosed at 3 months, 8 months, and 12 months after stricture diagnosis. No cases of cancer were diagnosed later than 1 year after the stricture diagnosis.
“We believe that this result is important for the management of colonic strictures complicating CD in clinical practice,” Dr. Hunaut and colleagues wrote.
The simultaneity or proximity of the diagnoses suggests that the “strictures observed are already a neoplastic complication of the colonic inflammatory disease,” they explained.
In other words, common concerns about strictures causing cancer at the same site could be unfounded.
This conclusion echoes a recent administrative database study that reported no independent association between colorectal stricture and CRC, the investigators noted.
“Given the recent evidence on the risk of cancer associated with colonic strictures in CD, systematic colectomy is probably no longer justified,” they wrote. “Factors such as a long disease duration, primary sclerosing cholangitis, a history of dysplasia, and nonpassable and/or symptomatic stricture despite endoscopic dilation tend to argue in favor of surgery — especially if limited resection is possible.”
In contrast, patients with strictures who have low risk of CRC may be better served by a conservative approach, including endoscopy and systematic biopsies, followed by close endoscopic surveillance, according to the investigators. If the stricture is impassable, they recommended endoscopic balloon dilation, followed by intensification of medical therapy if ulceration is observed.
The investigators disclosed relationships with MSD, Ferring, Biogen, and others.
, according to investigators.
Although 8% of patients with strictures in a multicenter study were diagnosed with CRC, this diagnosis was made either simultaneously or within 1 year of stricture diagnosis, suggesting that cancer may have driven stricture development, and not the other way around, lead author Thomas Hunaut, MD, of Université de Champagne-Ardenne, Reims, France, and colleagues reported.
“The occurrence of colonic stricture in CD always raises concerns about the risk for dysplasia/cancer,” the investigators wrote in Gastro Hep Advances, noting that no consensus approach is currently available to guide stricture management. “Few studies with conflicting results have evaluated the frequency of CRC associated with colonic stricture in CD, and the natural history of colonic stricture in CD is poorly known.”The present retrospective study included 88 consecutive CD patients with 96 colorectal strictures who were managed at three French referral centers between 1993 and 2022.
Strictures were symptomatic in 62.5% of cases, not passable by scope in 61.4% of cases, and ulcerated in 70.5% of cases. Colonic resection was needed in 47.7% of patients, while endoscopic balloon dilation was performed in 13.6% of patients.
After a median follow-up of 21.5 months, seven patients (8%) were diagnosed with malignant stricture, including five cases of colonic adenocarcinoma, one case of neuroendocrine carcinoma, and one case of B-cell lymphoproliferative neoplasia.
Malignant strictures were more common among older patients with longer disease duration and frequent obstructive symptoms; however, these factors were not supported by multivariate analyses, likely due to sample size, according to the investigators.
Instead, Dr. Hunaut and colleagues highlighted the timing of the diagnoses. In four out of seven patients with malignant stricture, both stricture and cancer were diagnosed at the same time. In the remaining three patients, cancer was diagnosed at 3 months, 8 months, and 12 months after stricture diagnosis. No cases of cancer were diagnosed later than 1 year after the stricture diagnosis.
“We believe that this result is important for the management of colonic strictures complicating CD in clinical practice,” Dr. Hunaut and colleagues wrote.
The simultaneity or proximity of the diagnoses suggests that the “strictures observed are already a neoplastic complication of the colonic inflammatory disease,” they explained.
In other words, common concerns about strictures causing cancer at the same site could be unfounded.
This conclusion echoes a recent administrative database study that reported no independent association between colorectal stricture and CRC, the investigators noted.
“Given the recent evidence on the risk of cancer associated with colonic strictures in CD, systematic colectomy is probably no longer justified,” they wrote. “Factors such as a long disease duration, primary sclerosing cholangitis, a history of dysplasia, and nonpassable and/or symptomatic stricture despite endoscopic dilation tend to argue in favor of surgery — especially if limited resection is possible.”
In contrast, patients with strictures who have low risk of CRC may be better served by a conservative approach, including endoscopy and systematic biopsies, followed by close endoscopic surveillance, according to the investigators. If the stricture is impassable, they recommended endoscopic balloon dilation, followed by intensification of medical therapy if ulceration is observed.
The investigators disclosed relationships with MSD, Ferring, Biogen, and others.
, according to investigators.
Although 8% of patients with strictures in a multicenter study were diagnosed with CRC, this diagnosis was made either simultaneously or within 1 year of stricture diagnosis, suggesting that cancer may have driven stricture development, and not the other way around, lead author Thomas Hunaut, MD, of Université de Champagne-Ardenne, Reims, France, and colleagues reported.
“The occurrence of colonic stricture in CD always raises concerns about the risk for dysplasia/cancer,” the investigators wrote in Gastro Hep Advances, noting that no consensus approach is currently available to guide stricture management. “Few studies with conflicting results have evaluated the frequency of CRC associated with colonic stricture in CD, and the natural history of colonic stricture in CD is poorly known.”The present retrospective study included 88 consecutive CD patients with 96 colorectal strictures who were managed at three French referral centers between 1993 and 2022.
Strictures were symptomatic in 62.5% of cases, not passable by scope in 61.4% of cases, and ulcerated in 70.5% of cases. Colonic resection was needed in 47.7% of patients, while endoscopic balloon dilation was performed in 13.6% of patients.
After a median follow-up of 21.5 months, seven patients (8%) were diagnosed with malignant stricture, including five cases of colonic adenocarcinoma, one case of neuroendocrine carcinoma, and one case of B-cell lymphoproliferative neoplasia.
Malignant strictures were more common among older patients with longer disease duration and frequent obstructive symptoms; however, these factors were not supported by multivariate analyses, likely due to sample size, according to the investigators.
Instead, Dr. Hunaut and colleagues highlighted the timing of the diagnoses. In four out of seven patients with malignant stricture, both stricture and cancer were diagnosed at the same time. In the remaining three patients, cancer was diagnosed at 3 months, 8 months, and 12 months after stricture diagnosis. No cases of cancer were diagnosed later than 1 year after the stricture diagnosis.
“We believe that this result is important for the management of colonic strictures complicating CD in clinical practice,” Dr. Hunaut and colleagues wrote.
The simultaneity or proximity of the diagnoses suggests that the “strictures observed are already a neoplastic complication of the colonic inflammatory disease,” they explained.
In other words, common concerns about strictures causing cancer at the same site could be unfounded.
This conclusion echoes a recent administrative database study that reported no independent association between colorectal stricture and CRC, the investigators noted.
“Given the recent evidence on the risk of cancer associated with colonic strictures in CD, systematic colectomy is probably no longer justified,” they wrote. “Factors such as a long disease duration, primary sclerosing cholangitis, a history of dysplasia, and nonpassable and/or symptomatic stricture despite endoscopic dilation tend to argue in favor of surgery — especially if limited resection is possible.”
In contrast, patients with strictures who have low risk of CRC may be better served by a conservative approach, including endoscopy and systematic biopsies, followed by close endoscopic surveillance, according to the investigators. If the stricture is impassable, they recommended endoscopic balloon dilation, followed by intensification of medical therapy if ulceration is observed.
The investigators disclosed relationships with MSD, Ferring, Biogen, and others.
FROM GASTRO HEP ADVANCES
Subcutaneous Infliximab Beats Placebo for IBD Maintenance Therapy
These two randomized trials should increase confidence in SC infliximab as a convenient alternative to intravenous delivery, reported co–lead authors Stephen B. Hanauer, MD, AGAF, of Northwestern Feinberg School of Medicine, Chicago, Illinois, and Bruce E. Sands, MD, AGAF, of Icahn School of Medicine at Mount Sinai, New York City, and colleagues.
Specifically, the trials evaluated CT-P13, an infliximab biosimilar, which was Food and Drug Administration approved for intravenous (IV) use in 2016. The SC formulation was approved in the United States in 2023 as a new drug, requiring phase 3 efficacy confirmatory trials.
“Physicians and patients may prefer SC to IV treatment for IBD, owing to the convenience and flexibility of at-home self-administration, a different exposure profile with high steady-state levels, reduced exposure to nosocomial infection, and health care system resource benefits,” the investigators wrote in Gastroenterology.
One trial included patients with Crohn’s disease (CD), while the other enrolled patients with ulcerative colitis (UC). Eligibility depended upon inadequate responses or intolerance to corticosteroids and immunomodulators.
All participants began by receiving open-label IV CT-P13, at a dosage of 5 mg/kg, at weeks 0, 2, and 6. At week 10, those who responded to the IV induction therapy were randomized in a 2:1 ratio to continue with either the SC formulation of CT-P13 (120 mg) or switch to placebo, administered every 2 weeks until week 54.
The CD study randomized 343 patients, while the UC study had a larger cohort, with 438 randomized. Median age of participants was in the mid-30s to late 30s, with a majority being White and male. Baseline disease severity, assessed by the Crohn’s Disease Activity Index (CDAI) for CD and the modified Mayo score for UC, was similar across treatment groups.
The primary efficacy endpoint was clinical remission at week 54, defined as a CDAI score of less than 150 for CD and a modified Mayo score of 0-1 for UC.
In the CD study, 62.3% of patients receiving CT-P13 SC achieved clinical remission, compared with 32.1% in the placebo group, with a treatment difference of 32.1% (95% CI, 20.9-42.1; P < .0001). In addition, 51.1% of CT-P13 SC-treated patients achieved endoscopic response, compared with 17.9% in the placebo group, yielding a treatment difference of 34.6% (95% CI, 24.1-43.5; P < .0001).
In the UC study, 43.2% of patients on CT-P13 SC achieved clinical remission at week 54, compared with 20.8% of those on placebo, with a treatment difference of 21.1% (95% CI, 11.8-29.3; P < .0001). Key secondary endpoints, including endoscopic-histologic mucosal improvement, also favored CT-P13 SC over placebo with statistically significant differences.
The safety profile of CT-P13 SC was comparable with that of IV infliximab, with no new safety concerns emerging during the trials.
“Our results demonstrate the superior efficacy of CT-P13 SC over placebo for maintenance therapy in patients with moderately to severely active CD or UC after induction with CT-P13 IV,” the investigators wrote. “Importantly, the findings confirm that CT-P13 SC is well tolerated in this population, with no clinically meaningful differences in safety profile, compared with placebo. Overall, the results support CT-P13 SC as a treatment option for maintenance therapy in patients with IBD.”
The LIBERTY studies were funded by Celltrion. The investigators disclosed relationships with Pfizer, Gilead, Takeda, and others.
Intravenous (IV) infliximab-dyyb, also called CT-P13 in clinical trials, is a biosimilar that was approved in the United States in 2016 under the brand name Inflectra. It received approval in Europe and elsewhere under the brand name Remsima.
The study from Hanauer and colleagues represents a milestone in biosimilar development as the authors studied an injectable form of the approved IV biosimilar, infliximab-dyyb. How might efficacy compare amongst the two formulations? The LIBERTY studies did not include an active IV infliximab comparator to answer this question. Based on a phase 1, open label trial, subcutaneous (SC) infliximab appears noninferior to IV infliximab.
It is remarkable that we have progressed from creating highly similar copies of older biologics whose patents have expired, to reimagining and modifying biosimilars to potentially improve on efficacy, dosing, tolerability, or as in the case of SC infliximab-dyyb, providing a new mode of delivery. For SC infliximab, whether the innovator designation will cause different patterns of use based on cost or other factors, compared with places where the injectable and intravenous formulations are both considered biosimilars, remains to be seen.
Fernando S. Velayos, MD, MPH, AGAF, is director of the Inflammatory Bowel Disease Program, The Permanente Group Northern California; adjunct investigator at the Kaiser Permanente Division of Research; and chief of Gastroenterology and Hepatology, Kaiser Permanente San Francisco Medical Center. He reported no conflicts of interest.
Intravenous (IV) infliximab-dyyb, also called CT-P13 in clinical trials, is a biosimilar that was approved in the United States in 2016 under the brand name Inflectra. It received approval in Europe and elsewhere under the brand name Remsima.
The study from Hanauer and colleagues represents a milestone in biosimilar development as the authors studied an injectable form of the approved IV biosimilar, infliximab-dyyb. How might efficacy compare amongst the two formulations? The LIBERTY studies did not include an active IV infliximab comparator to answer this question. Based on a phase 1, open label trial, subcutaneous (SC) infliximab appears noninferior to IV infliximab.
It is remarkable that we have progressed from creating highly similar copies of older biologics whose patents have expired, to reimagining and modifying biosimilars to potentially improve on efficacy, dosing, tolerability, or as in the case of SC infliximab-dyyb, providing a new mode of delivery. For SC infliximab, whether the innovator designation will cause different patterns of use based on cost or other factors, compared with places where the injectable and intravenous formulations are both considered biosimilars, remains to be seen.
Fernando S. Velayos, MD, MPH, AGAF, is director of the Inflammatory Bowel Disease Program, The Permanente Group Northern California; adjunct investigator at the Kaiser Permanente Division of Research; and chief of Gastroenterology and Hepatology, Kaiser Permanente San Francisco Medical Center. He reported no conflicts of interest.
Intravenous (IV) infliximab-dyyb, also called CT-P13 in clinical trials, is a biosimilar that was approved in the United States in 2016 under the brand name Inflectra. It received approval in Europe and elsewhere under the brand name Remsima.
The study from Hanauer and colleagues represents a milestone in biosimilar development as the authors studied an injectable form of the approved IV biosimilar, infliximab-dyyb. How might efficacy compare amongst the two formulations? The LIBERTY studies did not include an active IV infliximab comparator to answer this question. Based on a phase 1, open label trial, subcutaneous (SC) infliximab appears noninferior to IV infliximab.
It is remarkable that we have progressed from creating highly similar copies of older biologics whose patents have expired, to reimagining and modifying biosimilars to potentially improve on efficacy, dosing, tolerability, or as in the case of SC infliximab-dyyb, providing a new mode of delivery. For SC infliximab, whether the innovator designation will cause different patterns of use based on cost or other factors, compared with places where the injectable and intravenous formulations are both considered biosimilars, remains to be seen.
Fernando S. Velayos, MD, MPH, AGAF, is director of the Inflammatory Bowel Disease Program, The Permanente Group Northern California; adjunct investigator at the Kaiser Permanente Division of Research; and chief of Gastroenterology and Hepatology, Kaiser Permanente San Francisco Medical Center. He reported no conflicts of interest.
These two randomized trials should increase confidence in SC infliximab as a convenient alternative to intravenous delivery, reported co–lead authors Stephen B. Hanauer, MD, AGAF, of Northwestern Feinberg School of Medicine, Chicago, Illinois, and Bruce E. Sands, MD, AGAF, of Icahn School of Medicine at Mount Sinai, New York City, and colleagues.
Specifically, the trials evaluated CT-P13, an infliximab biosimilar, which was Food and Drug Administration approved for intravenous (IV) use in 2016. The SC formulation was approved in the United States in 2023 as a new drug, requiring phase 3 efficacy confirmatory trials.
“Physicians and patients may prefer SC to IV treatment for IBD, owing to the convenience and flexibility of at-home self-administration, a different exposure profile with high steady-state levels, reduced exposure to nosocomial infection, and health care system resource benefits,” the investigators wrote in Gastroenterology.
One trial included patients with Crohn’s disease (CD), while the other enrolled patients with ulcerative colitis (UC). Eligibility depended upon inadequate responses or intolerance to corticosteroids and immunomodulators.
All participants began by receiving open-label IV CT-P13, at a dosage of 5 mg/kg, at weeks 0, 2, and 6. At week 10, those who responded to the IV induction therapy were randomized in a 2:1 ratio to continue with either the SC formulation of CT-P13 (120 mg) or switch to placebo, administered every 2 weeks until week 54.
The CD study randomized 343 patients, while the UC study had a larger cohort, with 438 randomized. Median age of participants was in the mid-30s to late 30s, with a majority being White and male. Baseline disease severity, assessed by the Crohn’s Disease Activity Index (CDAI) for CD and the modified Mayo score for UC, was similar across treatment groups.
The primary efficacy endpoint was clinical remission at week 54, defined as a CDAI score of less than 150 for CD and a modified Mayo score of 0-1 for UC.
In the CD study, 62.3% of patients receiving CT-P13 SC achieved clinical remission, compared with 32.1% in the placebo group, with a treatment difference of 32.1% (95% CI, 20.9-42.1; P < .0001). In addition, 51.1% of CT-P13 SC-treated patients achieved endoscopic response, compared with 17.9% in the placebo group, yielding a treatment difference of 34.6% (95% CI, 24.1-43.5; P < .0001).
In the UC study, 43.2% of patients on CT-P13 SC achieved clinical remission at week 54, compared with 20.8% of those on placebo, with a treatment difference of 21.1% (95% CI, 11.8-29.3; P < .0001). Key secondary endpoints, including endoscopic-histologic mucosal improvement, also favored CT-P13 SC over placebo with statistically significant differences.
The safety profile of CT-P13 SC was comparable with that of IV infliximab, with no new safety concerns emerging during the trials.
“Our results demonstrate the superior efficacy of CT-P13 SC over placebo for maintenance therapy in patients with moderately to severely active CD or UC after induction with CT-P13 IV,” the investigators wrote. “Importantly, the findings confirm that CT-P13 SC is well tolerated in this population, with no clinically meaningful differences in safety profile, compared with placebo. Overall, the results support CT-P13 SC as a treatment option for maintenance therapy in patients with IBD.”
The LIBERTY studies were funded by Celltrion. The investigators disclosed relationships with Pfizer, Gilead, Takeda, and others.
These two randomized trials should increase confidence in SC infliximab as a convenient alternative to intravenous delivery, reported co–lead authors Stephen B. Hanauer, MD, AGAF, of Northwestern Feinberg School of Medicine, Chicago, Illinois, and Bruce E. Sands, MD, AGAF, of Icahn School of Medicine at Mount Sinai, New York City, and colleagues.
Specifically, the trials evaluated CT-P13, an infliximab biosimilar, which was Food and Drug Administration approved for intravenous (IV) use in 2016. The SC formulation was approved in the United States in 2023 as a new drug, requiring phase 3 efficacy confirmatory trials.
“Physicians and patients may prefer SC to IV treatment for IBD, owing to the convenience and flexibility of at-home self-administration, a different exposure profile with high steady-state levels, reduced exposure to nosocomial infection, and health care system resource benefits,” the investigators wrote in Gastroenterology.
One trial included patients with Crohn’s disease (CD), while the other enrolled patients with ulcerative colitis (UC). Eligibility depended upon inadequate responses or intolerance to corticosteroids and immunomodulators.
All participants began by receiving open-label IV CT-P13, at a dosage of 5 mg/kg, at weeks 0, 2, and 6. At week 10, those who responded to the IV induction therapy were randomized in a 2:1 ratio to continue with either the SC formulation of CT-P13 (120 mg) or switch to placebo, administered every 2 weeks until week 54.
The CD study randomized 343 patients, while the UC study had a larger cohort, with 438 randomized. Median age of participants was in the mid-30s to late 30s, with a majority being White and male. Baseline disease severity, assessed by the Crohn’s Disease Activity Index (CDAI) for CD and the modified Mayo score for UC, was similar across treatment groups.
The primary efficacy endpoint was clinical remission at week 54, defined as a CDAI score of less than 150 for CD and a modified Mayo score of 0-1 for UC.
In the CD study, 62.3% of patients receiving CT-P13 SC achieved clinical remission, compared with 32.1% in the placebo group, with a treatment difference of 32.1% (95% CI, 20.9-42.1; P < .0001). In addition, 51.1% of CT-P13 SC-treated patients achieved endoscopic response, compared with 17.9% in the placebo group, yielding a treatment difference of 34.6% (95% CI, 24.1-43.5; P < .0001).
In the UC study, 43.2% of patients on CT-P13 SC achieved clinical remission at week 54, compared with 20.8% of those on placebo, with a treatment difference of 21.1% (95% CI, 11.8-29.3; P < .0001). Key secondary endpoints, including endoscopic-histologic mucosal improvement, also favored CT-P13 SC over placebo with statistically significant differences.
The safety profile of CT-P13 SC was comparable with that of IV infliximab, with no new safety concerns emerging during the trials.
“Our results demonstrate the superior efficacy of CT-P13 SC over placebo for maintenance therapy in patients with moderately to severely active CD or UC after induction with CT-P13 IV,” the investigators wrote. “Importantly, the findings confirm that CT-P13 SC is well tolerated in this population, with no clinically meaningful differences in safety profile, compared with placebo. Overall, the results support CT-P13 SC as a treatment option for maintenance therapy in patients with IBD.”
The LIBERTY studies were funded by Celltrion. The investigators disclosed relationships with Pfizer, Gilead, Takeda, and others.
FROM GASTROENTEROLOGY
New Associations Identified Between IBD and Extraintestinal Manifestations
, according to a recent study.
For instance, antinuclear cytoplastic antibody is associated with primary sclerosing cholangitis (PSC) in Crohn’s disease, and CPEB4 genetic variation is associated with skin manifestations.
“Up to 40% of people with IBD suffer with symptoms from inflammation that occurs outside the gut, particularly affecting the liver, skin, and joints. These symptoms can often have a bigger impact on quality of life than the gut inflammation itself and can actually be life-threatening,” said senior author Dermot McGovern, MD, PhD, AGAF, director of translational medicine at the F. Widjaja Foundation Inflammatory Bowel Disease and Immunobiology Research Institute at Cedars-Sinai Medical Center, Los Angeles.
“With the advances in therapies for IBD, including availability of gut-selective agents, treatment choices often incorporate whether a patient has one of these manifestations or not,” he said. “We need to understand who is at increased risk of these and why.”
The study was published in Gastroenterology .
Analyzing Associations
Dr. McGovern and colleagues analyzed data for 12,083 unrelated European ancestry IBD cases with presence or absence of EIMs across four cohorts in the Cedars-Sinai Medical Center IBD Research Repository, National Institute for Diabetes and Digestive and Kidney Diseases IBD Genetics Consortium, Sinai Helmsley Alliance for Research Excellence Consortium, and Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn’s Disease.
In particular, the researchers looked at EIM phenotypes such as ankylosing spondylitis and sacroiliitis, PSC, peripheral arthritis, and skin and ocular manifestations. They analyzed clinical and serologic parameters through regression analyses using a mixed-effects model, as well as within-case logistic regression for genetic associations.
Overall, 14% of patients had at least one EIM. Contrary to previous reports, only 2% had multiple EIMs, and most co-occurrences were negatively correlated. Nearly all EIMs were more common in Crohn’s disease, except for PSC, which was more common in ulcerative colitis.
In general, EIMs occurred more often in women, particularly with Crohn’s disease and colonic disease location, and in patients who required surgery. Jewish ancestry was associated with psoriasis and overall skin manifestations.
Smoking increased the risk for multiple EIMs, except for PSC, where there appeared to be a “protective” effect. Older age at diagnosis and a family history of IBD were associated with increased risk for certain EIMs as well.
In addition, the research team noted multiple serologic associations, such as immunoglobulin (Ig) G and IgA, perinuclear antinuclear cytoplastic antibodies, and anti–Pseudomonas fluorescens–associated sequences with any EIM, as well as particular associations with PSC, such as anti-Saccharomyces cerevisiae antibodies and anti-flagellin.
There were also genome-wide significant associations within the major histocompatibility complex and CPEB4. Genetic associations implicated tumor necrosis factor, Janus kinase-signal transducer and activator of transcription, and interleukin 6 as potential targets for EIMs.
“We are working with colleagues across the world to increase the sample size, as we believe there is more to find,” Dr. McGovern said. “Importantly, this includes non-European ancestry subjects, as there is an urgent need to increase the diversity of populations we study so advances in clinical care are available to all communities.”
Considering Target Therapies
As medicine becomes more specialized, physicians should remember to consider the whole patient while choosing treatment strategies.
“Sometimes doctors wear blinders to the whole person, and it’s important to be aware of a holistic approach, where a gastroenterologist also asks about potential joint inflammation or a rheumatologist asks about bowel inflammation,” said David Rubin, MD, AGAF, chief of the Section of Gastroenterology, Hepatology and Nutrition at the University of Chicago Medicine, Chicago.
Dr. Rubin, who wasn’t involved with this study, has researched and published on EIMs in IBD. He and colleagues analyzed the prevalence, pathophysiology, and clinical presentation of EIMs to better understand possibilities for disease management.
“As we’ve gotten a better understanding of the immune system, we’ve learned that an EIM can sometimes provide a clue to the treatment we might use,” he said. “Given a similar amount of bowel inflammation, if one patient also has joint pain and another doesn’t, we might choose different treatments based on the immune pathway that might be involved.”
In future studies, researchers may consider whether these genetic or serologic markers could predict EIM manifestation before it occurs clinically, Dr. Rubin said. He and colleagues are also studying the links between IBD and mental health associations.
“So far, we don’t have a blood test or biopsy test that tells you which treatment is more or less likely to work, so we need to think carefully as clinicians and look to other organ systems for clues,” he said. “It’s not only more efficient to pick a single therapy to treat both the skin and bowel, but it may actually be more effective if both have a particular dominant pathway.”
The study was supported by internal funds from the F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute. Several authors reported consultant roles or other associations with pharmaceutical companies. Dr. Rubin reported no relevant disclosures.
A version of this article appeared on Medscape.com.
, according to a recent study.
For instance, antinuclear cytoplastic antibody is associated with primary sclerosing cholangitis (PSC) in Crohn’s disease, and CPEB4 genetic variation is associated with skin manifestations.
“Up to 40% of people with IBD suffer with symptoms from inflammation that occurs outside the gut, particularly affecting the liver, skin, and joints. These symptoms can often have a bigger impact on quality of life than the gut inflammation itself and can actually be life-threatening,” said senior author Dermot McGovern, MD, PhD, AGAF, director of translational medicine at the F. Widjaja Foundation Inflammatory Bowel Disease and Immunobiology Research Institute at Cedars-Sinai Medical Center, Los Angeles.
“With the advances in therapies for IBD, including availability of gut-selective agents, treatment choices often incorporate whether a patient has one of these manifestations or not,” he said. “We need to understand who is at increased risk of these and why.”
The study was published in Gastroenterology .
Analyzing Associations
Dr. McGovern and colleagues analyzed data for 12,083 unrelated European ancestry IBD cases with presence or absence of EIMs across four cohorts in the Cedars-Sinai Medical Center IBD Research Repository, National Institute for Diabetes and Digestive and Kidney Diseases IBD Genetics Consortium, Sinai Helmsley Alliance for Research Excellence Consortium, and Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn’s Disease.
In particular, the researchers looked at EIM phenotypes such as ankylosing spondylitis and sacroiliitis, PSC, peripheral arthritis, and skin and ocular manifestations. They analyzed clinical and serologic parameters through regression analyses using a mixed-effects model, as well as within-case logistic regression for genetic associations.
Overall, 14% of patients had at least one EIM. Contrary to previous reports, only 2% had multiple EIMs, and most co-occurrences were negatively correlated. Nearly all EIMs were more common in Crohn’s disease, except for PSC, which was more common in ulcerative colitis.
In general, EIMs occurred more often in women, particularly with Crohn’s disease and colonic disease location, and in patients who required surgery. Jewish ancestry was associated with psoriasis and overall skin manifestations.
Smoking increased the risk for multiple EIMs, except for PSC, where there appeared to be a “protective” effect. Older age at diagnosis and a family history of IBD were associated with increased risk for certain EIMs as well.
In addition, the research team noted multiple serologic associations, such as immunoglobulin (Ig) G and IgA, perinuclear antinuclear cytoplastic antibodies, and anti–Pseudomonas fluorescens–associated sequences with any EIM, as well as particular associations with PSC, such as anti-Saccharomyces cerevisiae antibodies and anti-flagellin.
There were also genome-wide significant associations within the major histocompatibility complex and CPEB4. Genetic associations implicated tumor necrosis factor, Janus kinase-signal transducer and activator of transcription, and interleukin 6 as potential targets for EIMs.
“We are working with colleagues across the world to increase the sample size, as we believe there is more to find,” Dr. McGovern said. “Importantly, this includes non-European ancestry subjects, as there is an urgent need to increase the diversity of populations we study so advances in clinical care are available to all communities.”
Considering Target Therapies
As medicine becomes more specialized, physicians should remember to consider the whole patient while choosing treatment strategies.
“Sometimes doctors wear blinders to the whole person, and it’s important to be aware of a holistic approach, where a gastroenterologist also asks about potential joint inflammation or a rheumatologist asks about bowel inflammation,” said David Rubin, MD, AGAF, chief of the Section of Gastroenterology, Hepatology and Nutrition at the University of Chicago Medicine, Chicago.
Dr. Rubin, who wasn’t involved with this study, has researched and published on EIMs in IBD. He and colleagues analyzed the prevalence, pathophysiology, and clinical presentation of EIMs to better understand possibilities for disease management.
“As we’ve gotten a better understanding of the immune system, we’ve learned that an EIM can sometimes provide a clue to the treatment we might use,” he said. “Given a similar amount of bowel inflammation, if one patient also has joint pain and another doesn’t, we might choose different treatments based on the immune pathway that might be involved.”
In future studies, researchers may consider whether these genetic or serologic markers could predict EIM manifestation before it occurs clinically, Dr. Rubin said. He and colleagues are also studying the links between IBD and mental health associations.
“So far, we don’t have a blood test or biopsy test that tells you which treatment is more or less likely to work, so we need to think carefully as clinicians and look to other organ systems for clues,” he said. “It’s not only more efficient to pick a single therapy to treat both the skin and bowel, but it may actually be more effective if both have a particular dominant pathway.”
The study was supported by internal funds from the F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute. Several authors reported consultant roles or other associations with pharmaceutical companies. Dr. Rubin reported no relevant disclosures.
A version of this article appeared on Medscape.com.
, according to a recent study.
For instance, antinuclear cytoplastic antibody is associated with primary sclerosing cholangitis (PSC) in Crohn’s disease, and CPEB4 genetic variation is associated with skin manifestations.
“Up to 40% of people with IBD suffer with symptoms from inflammation that occurs outside the gut, particularly affecting the liver, skin, and joints. These symptoms can often have a bigger impact on quality of life than the gut inflammation itself and can actually be life-threatening,” said senior author Dermot McGovern, MD, PhD, AGAF, director of translational medicine at the F. Widjaja Foundation Inflammatory Bowel Disease and Immunobiology Research Institute at Cedars-Sinai Medical Center, Los Angeles.
“With the advances in therapies for IBD, including availability of gut-selective agents, treatment choices often incorporate whether a patient has one of these manifestations or not,” he said. “We need to understand who is at increased risk of these and why.”
The study was published in Gastroenterology .
Analyzing Associations
Dr. McGovern and colleagues analyzed data for 12,083 unrelated European ancestry IBD cases with presence or absence of EIMs across four cohorts in the Cedars-Sinai Medical Center IBD Research Repository, National Institute for Diabetes and Digestive and Kidney Diseases IBD Genetics Consortium, Sinai Helmsley Alliance for Research Excellence Consortium, and Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn’s Disease.
In particular, the researchers looked at EIM phenotypes such as ankylosing spondylitis and sacroiliitis, PSC, peripheral arthritis, and skin and ocular manifestations. They analyzed clinical and serologic parameters through regression analyses using a mixed-effects model, as well as within-case logistic regression for genetic associations.
Overall, 14% of patients had at least one EIM. Contrary to previous reports, only 2% had multiple EIMs, and most co-occurrences were negatively correlated. Nearly all EIMs were more common in Crohn’s disease, except for PSC, which was more common in ulcerative colitis.
In general, EIMs occurred more often in women, particularly with Crohn’s disease and colonic disease location, and in patients who required surgery. Jewish ancestry was associated with psoriasis and overall skin manifestations.
Smoking increased the risk for multiple EIMs, except for PSC, where there appeared to be a “protective” effect. Older age at diagnosis and a family history of IBD were associated with increased risk for certain EIMs as well.
In addition, the research team noted multiple serologic associations, such as immunoglobulin (Ig) G and IgA, perinuclear antinuclear cytoplastic antibodies, and anti–Pseudomonas fluorescens–associated sequences with any EIM, as well as particular associations with PSC, such as anti-Saccharomyces cerevisiae antibodies and anti-flagellin.
There were also genome-wide significant associations within the major histocompatibility complex and CPEB4. Genetic associations implicated tumor necrosis factor, Janus kinase-signal transducer and activator of transcription, and interleukin 6 as potential targets for EIMs.
“We are working with colleagues across the world to increase the sample size, as we believe there is more to find,” Dr. McGovern said. “Importantly, this includes non-European ancestry subjects, as there is an urgent need to increase the diversity of populations we study so advances in clinical care are available to all communities.”
Considering Target Therapies
As medicine becomes more specialized, physicians should remember to consider the whole patient while choosing treatment strategies.
“Sometimes doctors wear blinders to the whole person, and it’s important to be aware of a holistic approach, where a gastroenterologist also asks about potential joint inflammation or a rheumatologist asks about bowel inflammation,” said David Rubin, MD, AGAF, chief of the Section of Gastroenterology, Hepatology and Nutrition at the University of Chicago Medicine, Chicago.
Dr. Rubin, who wasn’t involved with this study, has researched and published on EIMs in IBD. He and colleagues analyzed the prevalence, pathophysiology, and clinical presentation of EIMs to better understand possibilities for disease management.
“As we’ve gotten a better understanding of the immune system, we’ve learned that an EIM can sometimes provide a clue to the treatment we might use,” he said. “Given a similar amount of bowel inflammation, if one patient also has joint pain and another doesn’t, we might choose different treatments based on the immune pathway that might be involved.”
In future studies, researchers may consider whether these genetic or serologic markers could predict EIM manifestation before it occurs clinically, Dr. Rubin said. He and colleagues are also studying the links between IBD and mental health associations.
“So far, we don’t have a blood test or biopsy test that tells you which treatment is more or less likely to work, so we need to think carefully as clinicians and look to other organ systems for clues,” he said. “It’s not only more efficient to pick a single therapy to treat both the skin and bowel, but it may actually be more effective if both have a particular dominant pathway.”
The study was supported by internal funds from the F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute. Several authors reported consultant roles or other associations with pharmaceutical companies. Dr. Rubin reported no relevant disclosures.
A version of this article appeared on Medscape.com.
Cold Snare Resection Safe for Large Nonpedunculated Colorectal Polyps
In findings from Germany’s randomized controlled CHRONICLE trial, published in Gastroenterology , the cold technique almost eliminated major adverse events (AEs) — but at the cost of higher rates of recurrence and residual adenoma at first follow-up.
“The exact definition of the ideal lesions requires further research,” wrote investigators led by Ingo Steinbrück, MD, of the Department of Medicine and Gastroenterology at the Academic Teaching Hospital of the University of Freiburg, Freiburg im Breisgau, Germany. “Further studies have to confirm to what extent polyp size and histology can determine an individualized approach.”
The researchers noted that while hot snare resection is the gold standard for larger nonpedunculated polyps of ≥ 2 cm, previous research has found the cold technique, which resects without cutting and cauterizing current, to be superior for small polyps .
“Our study suggests that sessile serrated lesions larger than 2 cm should be resected with the cold snare. Selected cases of lateral spreading tumors may also be good candidates for cold snare resection when safety concerns are paramount,” Dr. Steinbrück said in an interview. “Cold snare resection is standard of care in our center in these cases, but our data show no superiority over hot snare in terms of resection speed.”
Despite recommendations for its use, the cold snare method appears to be underused in the United States.
The Study
From June 2021 to July 2023, the 19-center intention-to-treat analysis enrolled 363 patients (48.2% women) with a total of 396 polyps and randomly assigned those with polyps of ≥ 20 mm to cold (n = 193) or hot EMR (n = 203). The primary outcome was major AEs such as perforation or post-endoscopic bleeding.
Major AEs occurred in 1.0% of the cold group and in 7.9% of the hot group (P = .001, odds ratio [OR], 0.12; 95% CI, 0.03-0.54).
Rates for perforation and post-endoscopic bleeding were significantly lower in the cold group, with 0 vs 8 (0% vs 3.9%, P = .007) perforations in the two groups, respectively, as well as 1.0% vs 4.4% (P = .040) for postprocedural bleeding.
Somewhat surprisingly, intraprocedural bleeding was also less common in the cold EMR group at 14% vs 23%.
Residual adenoma, however, was found more frequently in the cold group at 23.7% vs 13.8% (OR, 1.94; 95% CI,1.12-3.38; P = .020).
Commenting on the study but not involved in it, Seth Crockett, MD, MPH, AGAF, a professor of medicine in the Division of Gastroenterology and Hepatology at Oregon Health & Science University in Portland, Oregon, called the CHRONICLE findings very important.
“Interestingly, near identical results were found in a recent report from a multicenter US trial presented at DDW earlier this year by Pohl et al., which adds credence to their findings,” he said. “While this study helps move the needle toward using cold EMR for large polyps, it also highlights an Achilles heel of this approach, a higher risk of residual polyps during follow-up.”
In other study findings, postpolypectomy syndrome occurred with similar frequency in both groups (3.1% vs 4.4%, P = .490).
As to the size factor, multivariable analysis revealed that a lesion diameter of at least 4 cm was an independent predictor of major AEs (OR, 3.37), residual adenoma (OR, 2.47), and high-grade dysplasia/cancer for residual adenoma (OR, 2.92).
In the case of suspected sessile serrated lesions, the rate of residual neoplasia was 8.3% (n = 4 of 48; 95% CI, 3.3-19.5) in the cold group and 4.8% (n = 2 of 42; 95% CI, 1.3-15.8) in the hot group (P = .681).
As for laterally spreading tumors (LSTs), Dr. Steinbrück said, “The higher recurrence rate after cold snare resection of LST nodular mixed types is unacceptable, and therefore, hot snare EMR with margin coagulation should be the treatment of choice.
“For LST granular type homogeneous and LST nongranular type without suspicion of malignancy, cold snare EMR with additional measures such as margin coagulation may be an option in selected cases — for example, when the risk of delayed bleeding is high,” he said.
Implications
This study has several implications, Dr. Crockett said. First, more research and innovation are needed to develop techniques to maximize complete resection during cold EMR and minimize residual polyp rates. “Ideally, this would involve other cold techniques so as not to offset the safety benefits of cold EMR,” he noted.
Second, patient selection is important, as cold EMR is likely more suitable for those with serrated lesions and for those in whom follow-up can be assured, he added. “For patients who have the largest polyps, particularly lesions of the laterally spreading tumor, nodular mixed type, and those who do not wish to participate in surveillance, hot EMR may be preferable, at least at this point.”
The authors agreed that new technical development that improves the outcomes and cost-effectiveness of cold snare polypectomy and combines its demonstrated safety with recurrence reduction is necessary, as are studies to identify optimal candidate lesions.
“The next step is to evaluate whether cold snare EMR with additional measures leads to a recurrence rate comparable to hot snare EMR with margin coagulation,” Dr. Steinbrück said. “If this is the case, cold snare resection may be the future treatment of choice for all large nonpedunculated polyps without suspected malignancy in the colorectum.”
This work was supported by the Gastroenterology Foundation, Küsnacht, Switzerland. Dr. Steinbrück reported lecture fees and travel grants from Olympus Medical, a polypectomy device maker, and Falk Pharma. Numerous coauthors disclosed financial relationships with pharmaceutical and medical device companies, including Olympus Medical. Dr. Crockett disclosed no competing interests relevant to his comments.
A version of this article appeared on Medscape.com.
In findings from Germany’s randomized controlled CHRONICLE trial, published in Gastroenterology , the cold technique almost eliminated major adverse events (AEs) — but at the cost of higher rates of recurrence and residual adenoma at first follow-up.
“The exact definition of the ideal lesions requires further research,” wrote investigators led by Ingo Steinbrück, MD, of the Department of Medicine and Gastroenterology at the Academic Teaching Hospital of the University of Freiburg, Freiburg im Breisgau, Germany. “Further studies have to confirm to what extent polyp size and histology can determine an individualized approach.”
The researchers noted that while hot snare resection is the gold standard for larger nonpedunculated polyps of ≥ 2 cm, previous research has found the cold technique, which resects without cutting and cauterizing current, to be superior for small polyps .
“Our study suggests that sessile serrated lesions larger than 2 cm should be resected with the cold snare. Selected cases of lateral spreading tumors may also be good candidates for cold snare resection when safety concerns are paramount,” Dr. Steinbrück said in an interview. “Cold snare resection is standard of care in our center in these cases, but our data show no superiority over hot snare in terms of resection speed.”
Despite recommendations for its use, the cold snare method appears to be underused in the United States.
The Study
From June 2021 to July 2023, the 19-center intention-to-treat analysis enrolled 363 patients (48.2% women) with a total of 396 polyps and randomly assigned those with polyps of ≥ 20 mm to cold (n = 193) or hot EMR (n = 203). The primary outcome was major AEs such as perforation or post-endoscopic bleeding.
Major AEs occurred in 1.0% of the cold group and in 7.9% of the hot group (P = .001, odds ratio [OR], 0.12; 95% CI, 0.03-0.54).
Rates for perforation and post-endoscopic bleeding were significantly lower in the cold group, with 0 vs 8 (0% vs 3.9%, P = .007) perforations in the two groups, respectively, as well as 1.0% vs 4.4% (P = .040) for postprocedural bleeding.
Somewhat surprisingly, intraprocedural bleeding was also less common in the cold EMR group at 14% vs 23%.
Residual adenoma, however, was found more frequently in the cold group at 23.7% vs 13.8% (OR, 1.94; 95% CI,1.12-3.38; P = .020).
Commenting on the study but not involved in it, Seth Crockett, MD, MPH, AGAF, a professor of medicine in the Division of Gastroenterology and Hepatology at Oregon Health & Science University in Portland, Oregon, called the CHRONICLE findings very important.
“Interestingly, near identical results were found in a recent report from a multicenter US trial presented at DDW earlier this year by Pohl et al., which adds credence to their findings,” he said. “While this study helps move the needle toward using cold EMR for large polyps, it also highlights an Achilles heel of this approach, a higher risk of residual polyps during follow-up.”
In other study findings, postpolypectomy syndrome occurred with similar frequency in both groups (3.1% vs 4.4%, P = .490).
As to the size factor, multivariable analysis revealed that a lesion diameter of at least 4 cm was an independent predictor of major AEs (OR, 3.37), residual adenoma (OR, 2.47), and high-grade dysplasia/cancer for residual adenoma (OR, 2.92).
In the case of suspected sessile serrated lesions, the rate of residual neoplasia was 8.3% (n = 4 of 48; 95% CI, 3.3-19.5) in the cold group and 4.8% (n = 2 of 42; 95% CI, 1.3-15.8) in the hot group (P = .681).
As for laterally spreading tumors (LSTs), Dr. Steinbrück said, “The higher recurrence rate after cold snare resection of LST nodular mixed types is unacceptable, and therefore, hot snare EMR with margin coagulation should be the treatment of choice.
“For LST granular type homogeneous and LST nongranular type without suspicion of malignancy, cold snare EMR with additional measures such as margin coagulation may be an option in selected cases — for example, when the risk of delayed bleeding is high,” he said.
Implications
This study has several implications, Dr. Crockett said. First, more research and innovation are needed to develop techniques to maximize complete resection during cold EMR and minimize residual polyp rates. “Ideally, this would involve other cold techniques so as not to offset the safety benefits of cold EMR,” he noted.
Second, patient selection is important, as cold EMR is likely more suitable for those with serrated lesions and for those in whom follow-up can be assured, he added. “For patients who have the largest polyps, particularly lesions of the laterally spreading tumor, nodular mixed type, and those who do not wish to participate in surveillance, hot EMR may be preferable, at least at this point.”
The authors agreed that new technical development that improves the outcomes and cost-effectiveness of cold snare polypectomy and combines its demonstrated safety with recurrence reduction is necessary, as are studies to identify optimal candidate lesions.
“The next step is to evaluate whether cold snare EMR with additional measures leads to a recurrence rate comparable to hot snare EMR with margin coagulation,” Dr. Steinbrück said. “If this is the case, cold snare resection may be the future treatment of choice for all large nonpedunculated polyps without suspected malignancy in the colorectum.”
This work was supported by the Gastroenterology Foundation, Küsnacht, Switzerland. Dr. Steinbrück reported lecture fees and travel grants from Olympus Medical, a polypectomy device maker, and Falk Pharma. Numerous coauthors disclosed financial relationships with pharmaceutical and medical device companies, including Olympus Medical. Dr. Crockett disclosed no competing interests relevant to his comments.
A version of this article appeared on Medscape.com.
In findings from Germany’s randomized controlled CHRONICLE trial, published in Gastroenterology , the cold technique almost eliminated major adverse events (AEs) — but at the cost of higher rates of recurrence and residual adenoma at first follow-up.
“The exact definition of the ideal lesions requires further research,” wrote investigators led by Ingo Steinbrück, MD, of the Department of Medicine and Gastroenterology at the Academic Teaching Hospital of the University of Freiburg, Freiburg im Breisgau, Germany. “Further studies have to confirm to what extent polyp size and histology can determine an individualized approach.”
The researchers noted that while hot snare resection is the gold standard for larger nonpedunculated polyps of ≥ 2 cm, previous research has found the cold technique, which resects without cutting and cauterizing current, to be superior for small polyps .
“Our study suggests that sessile serrated lesions larger than 2 cm should be resected with the cold snare. Selected cases of lateral spreading tumors may also be good candidates for cold snare resection when safety concerns are paramount,” Dr. Steinbrück said in an interview. “Cold snare resection is standard of care in our center in these cases, but our data show no superiority over hot snare in terms of resection speed.”
Despite recommendations for its use, the cold snare method appears to be underused in the United States.
The Study
From June 2021 to July 2023, the 19-center intention-to-treat analysis enrolled 363 patients (48.2% women) with a total of 396 polyps and randomly assigned those with polyps of ≥ 20 mm to cold (n = 193) or hot EMR (n = 203). The primary outcome was major AEs such as perforation or post-endoscopic bleeding.
Major AEs occurred in 1.0% of the cold group and in 7.9% of the hot group (P = .001, odds ratio [OR], 0.12; 95% CI, 0.03-0.54).
Rates for perforation and post-endoscopic bleeding were significantly lower in the cold group, with 0 vs 8 (0% vs 3.9%, P = .007) perforations in the two groups, respectively, as well as 1.0% vs 4.4% (P = .040) for postprocedural bleeding.
Somewhat surprisingly, intraprocedural bleeding was also less common in the cold EMR group at 14% vs 23%.
Residual adenoma, however, was found more frequently in the cold group at 23.7% vs 13.8% (OR, 1.94; 95% CI,1.12-3.38; P = .020).
Commenting on the study but not involved in it, Seth Crockett, MD, MPH, AGAF, a professor of medicine in the Division of Gastroenterology and Hepatology at Oregon Health & Science University in Portland, Oregon, called the CHRONICLE findings very important.
“Interestingly, near identical results were found in a recent report from a multicenter US trial presented at DDW earlier this year by Pohl et al., which adds credence to their findings,” he said. “While this study helps move the needle toward using cold EMR for large polyps, it also highlights an Achilles heel of this approach, a higher risk of residual polyps during follow-up.”
In other study findings, postpolypectomy syndrome occurred with similar frequency in both groups (3.1% vs 4.4%, P = .490).
As to the size factor, multivariable analysis revealed that a lesion diameter of at least 4 cm was an independent predictor of major AEs (OR, 3.37), residual adenoma (OR, 2.47), and high-grade dysplasia/cancer for residual adenoma (OR, 2.92).
In the case of suspected sessile serrated lesions, the rate of residual neoplasia was 8.3% (n = 4 of 48; 95% CI, 3.3-19.5) in the cold group and 4.8% (n = 2 of 42; 95% CI, 1.3-15.8) in the hot group (P = .681).
As for laterally spreading tumors (LSTs), Dr. Steinbrück said, “The higher recurrence rate after cold snare resection of LST nodular mixed types is unacceptable, and therefore, hot snare EMR with margin coagulation should be the treatment of choice.
“For LST granular type homogeneous and LST nongranular type without suspicion of malignancy, cold snare EMR with additional measures such as margin coagulation may be an option in selected cases — for example, when the risk of delayed bleeding is high,” he said.
Implications
This study has several implications, Dr. Crockett said. First, more research and innovation are needed to develop techniques to maximize complete resection during cold EMR and minimize residual polyp rates. “Ideally, this would involve other cold techniques so as not to offset the safety benefits of cold EMR,” he noted.
Second, patient selection is important, as cold EMR is likely more suitable for those with serrated lesions and for those in whom follow-up can be assured, he added. “For patients who have the largest polyps, particularly lesions of the laterally spreading tumor, nodular mixed type, and those who do not wish to participate in surveillance, hot EMR may be preferable, at least at this point.”
The authors agreed that new technical development that improves the outcomes and cost-effectiveness of cold snare polypectomy and combines its demonstrated safety with recurrence reduction is necessary, as are studies to identify optimal candidate lesions.
“The next step is to evaluate whether cold snare EMR with additional measures leads to a recurrence rate comparable to hot snare EMR with margin coagulation,” Dr. Steinbrück said. “If this is the case, cold snare resection may be the future treatment of choice for all large nonpedunculated polyps without suspected malignancy in the colorectum.”
This work was supported by the Gastroenterology Foundation, Küsnacht, Switzerland. Dr. Steinbrück reported lecture fees and travel grants from Olympus Medical, a polypectomy device maker, and Falk Pharma. Numerous coauthors disclosed financial relationships with pharmaceutical and medical device companies, including Olympus Medical. Dr. Crockett disclosed no competing interests relevant to his comments.
A version of this article appeared on Medscape.com.
FROM GASTROENTEROLOGY