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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
Automated ERCP Report Card Offers High Accuracy, Minimal Work
offering a real-time gauge of both individual- and institutional-level quality indicators, according to the developers.
The tool boasts an accuracy level exceeding 96%, integrates with multiple electronic health records, and requires minimal additional work time, reported Anmol Singh, MD, of TriStar Centennial Medical Center, Nashville, Tennessee, and colleagues.
“Implementation of quality indicator tracking remains difficult due to the complexity of ERCP as compared with other endoscopic procedures, resulting in significant limitations in the extraction and synthesis of these data,” the investigators wrote in Techniques and Innovations in Gastrointestinal Endoscopy. “Manual extraction methods such as self-assessment forms and chart reviews are both time intensive and error prone, and current automated extraction methods, such as natural language processing, can require substantial resources to implement and undesirably complicate the endoscopy work flow.”
To overcome these challenges, Dr. Singh and colleagues designed an analytics tool that automatically collects ERCP quality indicators from endoscopy reports with “minimal input” from the endoscopist, and is compatible with “any electronic reporting system.”
Development relied upon endoscopy records from 2,146 ERCPs performed by 12 endoscopists at four facilities. The most common reason for ERCP was choledocholithiasis, followed by malignant and benign biliary stricture. Most common procedures were stent placement and sphincterotomy.
Data were aggregated in a Health Level–7 (HL-7) interface, an international standard system that enables compatibility between different types of electronic health records. Some inputs were entered by the performing endoscopist via drop-down menus.
Next, data were shifted into an analytics suite, which evaluated quality indicators, including cannulation difficulty and success rate, and administration of post-ERCP pancreatitis prophylaxis.
Manual review showed that this approach yielded an accuracy of 96.5%-100%.
Beyond this high level of accuracy, Dr. Singh and colleagues described several reasons why their tool may be superior to previous attempts at an automated ERCP report card.
“Our HL-7–based tool offers several advantages, including versatility via compatibility with multiple types of commercial reporting software and flexibility in customizing the type and aesthetic of the data displayed,” they wrote. “These features improve the user interface, keep costs down, and allow for integration into smaller or nonacademic practice settings.”
They also highlighted how the tool measures quality in relation to procedure indication and difficulty at the provider level.
“Unlike in colonoscopy, where metrics such as adenoma detection rate can be ubiquitously applied to all screening procedures, the difficulty and risk profile of ERCP is inextricably dependent on patient and procedural factors such as indication of the procedure, history of interventions, or history of altered anatomy,” Dr. Singh and colleagues wrote. “Prior studies have shown that both the cost-effectiveness and complication rates of procedures are influenced by procedural indication and complexity. As such, benchmarking an individual provider’s performance necessarily requires the correct procedural context.”
With further optimization, this tool can be integrated into various types of existing endoscopy reporting software at a reasonable cost, and with minimal impact on routine work flow, the investigators concluded.
The investigators disclosed relationships with AbbVie, Boston Scientific, Organon, and others.
offering a real-time gauge of both individual- and institutional-level quality indicators, according to the developers.
The tool boasts an accuracy level exceeding 96%, integrates with multiple electronic health records, and requires minimal additional work time, reported Anmol Singh, MD, of TriStar Centennial Medical Center, Nashville, Tennessee, and colleagues.
“Implementation of quality indicator tracking remains difficult due to the complexity of ERCP as compared with other endoscopic procedures, resulting in significant limitations in the extraction and synthesis of these data,” the investigators wrote in Techniques and Innovations in Gastrointestinal Endoscopy. “Manual extraction methods such as self-assessment forms and chart reviews are both time intensive and error prone, and current automated extraction methods, such as natural language processing, can require substantial resources to implement and undesirably complicate the endoscopy work flow.”
To overcome these challenges, Dr. Singh and colleagues designed an analytics tool that automatically collects ERCP quality indicators from endoscopy reports with “minimal input” from the endoscopist, and is compatible with “any electronic reporting system.”
Development relied upon endoscopy records from 2,146 ERCPs performed by 12 endoscopists at four facilities. The most common reason for ERCP was choledocholithiasis, followed by malignant and benign biliary stricture. Most common procedures were stent placement and sphincterotomy.
Data were aggregated in a Health Level–7 (HL-7) interface, an international standard system that enables compatibility between different types of electronic health records. Some inputs were entered by the performing endoscopist via drop-down menus.
Next, data were shifted into an analytics suite, which evaluated quality indicators, including cannulation difficulty and success rate, and administration of post-ERCP pancreatitis prophylaxis.
Manual review showed that this approach yielded an accuracy of 96.5%-100%.
Beyond this high level of accuracy, Dr. Singh and colleagues described several reasons why their tool may be superior to previous attempts at an automated ERCP report card.
“Our HL-7–based tool offers several advantages, including versatility via compatibility with multiple types of commercial reporting software and flexibility in customizing the type and aesthetic of the data displayed,” they wrote. “These features improve the user interface, keep costs down, and allow for integration into smaller or nonacademic practice settings.”
They also highlighted how the tool measures quality in relation to procedure indication and difficulty at the provider level.
“Unlike in colonoscopy, where metrics such as adenoma detection rate can be ubiquitously applied to all screening procedures, the difficulty and risk profile of ERCP is inextricably dependent on patient and procedural factors such as indication of the procedure, history of interventions, or history of altered anatomy,” Dr. Singh and colleagues wrote. “Prior studies have shown that both the cost-effectiveness and complication rates of procedures are influenced by procedural indication and complexity. As such, benchmarking an individual provider’s performance necessarily requires the correct procedural context.”
With further optimization, this tool can be integrated into various types of existing endoscopy reporting software at a reasonable cost, and with minimal impact on routine work flow, the investigators concluded.
The investigators disclosed relationships with AbbVie, Boston Scientific, Organon, and others.
offering a real-time gauge of both individual- and institutional-level quality indicators, according to the developers.
The tool boasts an accuracy level exceeding 96%, integrates with multiple electronic health records, and requires minimal additional work time, reported Anmol Singh, MD, of TriStar Centennial Medical Center, Nashville, Tennessee, and colleagues.
“Implementation of quality indicator tracking remains difficult due to the complexity of ERCP as compared with other endoscopic procedures, resulting in significant limitations in the extraction and synthesis of these data,” the investigators wrote in Techniques and Innovations in Gastrointestinal Endoscopy. “Manual extraction methods such as self-assessment forms and chart reviews are both time intensive and error prone, and current automated extraction methods, such as natural language processing, can require substantial resources to implement and undesirably complicate the endoscopy work flow.”
To overcome these challenges, Dr. Singh and colleagues designed an analytics tool that automatically collects ERCP quality indicators from endoscopy reports with “minimal input” from the endoscopist, and is compatible with “any electronic reporting system.”
Development relied upon endoscopy records from 2,146 ERCPs performed by 12 endoscopists at four facilities. The most common reason for ERCP was choledocholithiasis, followed by malignant and benign biliary stricture. Most common procedures were stent placement and sphincterotomy.
Data were aggregated in a Health Level–7 (HL-7) interface, an international standard system that enables compatibility between different types of electronic health records. Some inputs were entered by the performing endoscopist via drop-down menus.
Next, data were shifted into an analytics suite, which evaluated quality indicators, including cannulation difficulty and success rate, and administration of post-ERCP pancreatitis prophylaxis.
Manual review showed that this approach yielded an accuracy of 96.5%-100%.
Beyond this high level of accuracy, Dr. Singh and colleagues described several reasons why their tool may be superior to previous attempts at an automated ERCP report card.
“Our HL-7–based tool offers several advantages, including versatility via compatibility with multiple types of commercial reporting software and flexibility in customizing the type and aesthetic of the data displayed,” they wrote. “These features improve the user interface, keep costs down, and allow for integration into smaller or nonacademic practice settings.”
They also highlighted how the tool measures quality in relation to procedure indication and difficulty at the provider level.
“Unlike in colonoscopy, where metrics such as adenoma detection rate can be ubiquitously applied to all screening procedures, the difficulty and risk profile of ERCP is inextricably dependent on patient and procedural factors such as indication of the procedure, history of interventions, or history of altered anatomy,” Dr. Singh and colleagues wrote. “Prior studies have shown that both the cost-effectiveness and complication rates of procedures are influenced by procedural indication and complexity. As such, benchmarking an individual provider’s performance necessarily requires the correct procedural context.”
With further optimization, this tool can be integrated into various types of existing endoscopy reporting software at a reasonable cost, and with minimal impact on routine work flow, the investigators concluded.
The investigators disclosed relationships with AbbVie, Boston Scientific, Organon, and others.
FROM TECHNIQUES AND INNOVATIONS IN GASTROINTESTINAL ENDOSCOPY
Family Size, Dog Ownership Linked With Reduced Risk of Crohn’s
, according to investigators.
Those who live with a pet bird may be more likely to develop CD, although few participants in the study lived with birds, requiring a cautious interpretation of this latter finding, lead author Mingyue Xue, PhD, of Mount Sinai Hospital, Toronto, Ontario, Canada, and colleagues reported.
“Environmental factors, such as smoking, large families, urban environments, and exposure to pets, have been shown to be associated with the risk of CD development,” the investigators wrote in Clinical Gastroenterology and Hepatology. “However, most of these studies were based on a retrospective study design, which makes it challenging to understand when and how environmental factors trigger the biological changes that lead to disease.”
The present study prospectively followed 4289 asymptomatic first-degree relatives (FDRs) of patients with CD. Environmental factors were identified via regression models that also considered biological factors, including gut inflammation via fecal calprotectin (FCP) levels, altered intestinal permeability measured by urinary fractional excretion of lactulose to mannitol ratio (LMR), and fecal microbiome composition through 16S rRNA sequencing.
After a median follow-up period of 5.62 years, 86 FDRs (1.9%) developed CD.
Living in a household of at least three people in the first year of life was associated with a 57% reduced risk of CD development (hazard ratio [HR], 0.43; P = .019). Similarly, living with a pet dog between the ages of 5 and 15 also demonstrated a protective effect, dropping risk of CD by 39% (HR, 0.61; P = .025).
“Our analysis revealed a protective trend of living with dogs that transcends the age of exposure, suggesting that dog ownership could confer health benefits in reducing the risk of CD,” the investigators wrote. “Our study also found that living in a large family during the first year of life is significantly associated with the future onset of CD, aligning with prior research that indicates that a larger family size in the first year of life can reduce the risk of developing IBD.”
In contrast, the study identified bird ownership at time of recruitment as a risk factor for CD, increasing risk almost three-fold (HR, 2.84; P = .005). The investigators urged a careful interpretation of this latter finding, however, as relatively few FDRs lived with birds.
“[A]lthough our sample size can be considered large, some environmental variables were uncommon, such as the participants having birds as pets, and would greatly benefit from replication of our findings in other cohorts,” Dr. Xue and colleagues noted.
They suggested several possible ways in which the above environmental factors may impact CD risk, including effects on subclinical inflammation, microbiome composition, and gut permeability.
“Understanding the relationship between CD-related environmental factors and these predisease biomarkers may shed light on the underlying mechanisms by which environmental factors impact host health and ultimately lead to CD onset,” the investigators concluded.
The study was supported by Crohn’s and Colitis Canada, Canadian Institutes of Health Research, the Helmsley Charitable Trust, and others. The investigators disclosed no conflicts of interest.
, according to investigators.
Those who live with a pet bird may be more likely to develop CD, although few participants in the study lived with birds, requiring a cautious interpretation of this latter finding, lead author Mingyue Xue, PhD, of Mount Sinai Hospital, Toronto, Ontario, Canada, and colleagues reported.
“Environmental factors, such as smoking, large families, urban environments, and exposure to pets, have been shown to be associated with the risk of CD development,” the investigators wrote in Clinical Gastroenterology and Hepatology. “However, most of these studies were based on a retrospective study design, which makes it challenging to understand when and how environmental factors trigger the biological changes that lead to disease.”
The present study prospectively followed 4289 asymptomatic first-degree relatives (FDRs) of patients with CD. Environmental factors were identified via regression models that also considered biological factors, including gut inflammation via fecal calprotectin (FCP) levels, altered intestinal permeability measured by urinary fractional excretion of lactulose to mannitol ratio (LMR), and fecal microbiome composition through 16S rRNA sequencing.
After a median follow-up period of 5.62 years, 86 FDRs (1.9%) developed CD.
Living in a household of at least three people in the first year of life was associated with a 57% reduced risk of CD development (hazard ratio [HR], 0.43; P = .019). Similarly, living with a pet dog between the ages of 5 and 15 also demonstrated a protective effect, dropping risk of CD by 39% (HR, 0.61; P = .025).
“Our analysis revealed a protective trend of living with dogs that transcends the age of exposure, suggesting that dog ownership could confer health benefits in reducing the risk of CD,” the investigators wrote. “Our study also found that living in a large family during the first year of life is significantly associated with the future onset of CD, aligning with prior research that indicates that a larger family size in the first year of life can reduce the risk of developing IBD.”
In contrast, the study identified bird ownership at time of recruitment as a risk factor for CD, increasing risk almost three-fold (HR, 2.84; P = .005). The investigators urged a careful interpretation of this latter finding, however, as relatively few FDRs lived with birds.
“[A]lthough our sample size can be considered large, some environmental variables were uncommon, such as the participants having birds as pets, and would greatly benefit from replication of our findings in other cohorts,” Dr. Xue and colleagues noted.
They suggested several possible ways in which the above environmental factors may impact CD risk, including effects on subclinical inflammation, microbiome composition, and gut permeability.
“Understanding the relationship between CD-related environmental factors and these predisease biomarkers may shed light on the underlying mechanisms by which environmental factors impact host health and ultimately lead to CD onset,” the investigators concluded.
The study was supported by Crohn’s and Colitis Canada, Canadian Institutes of Health Research, the Helmsley Charitable Trust, and others. The investigators disclosed no conflicts of interest.
, according to investigators.
Those who live with a pet bird may be more likely to develop CD, although few participants in the study lived with birds, requiring a cautious interpretation of this latter finding, lead author Mingyue Xue, PhD, of Mount Sinai Hospital, Toronto, Ontario, Canada, and colleagues reported.
“Environmental factors, such as smoking, large families, urban environments, and exposure to pets, have been shown to be associated with the risk of CD development,” the investigators wrote in Clinical Gastroenterology and Hepatology. “However, most of these studies were based on a retrospective study design, which makes it challenging to understand when and how environmental factors trigger the biological changes that lead to disease.”
The present study prospectively followed 4289 asymptomatic first-degree relatives (FDRs) of patients with CD. Environmental factors were identified via regression models that also considered biological factors, including gut inflammation via fecal calprotectin (FCP) levels, altered intestinal permeability measured by urinary fractional excretion of lactulose to mannitol ratio (LMR), and fecal microbiome composition through 16S rRNA sequencing.
After a median follow-up period of 5.62 years, 86 FDRs (1.9%) developed CD.
Living in a household of at least three people in the first year of life was associated with a 57% reduced risk of CD development (hazard ratio [HR], 0.43; P = .019). Similarly, living with a pet dog between the ages of 5 and 15 also demonstrated a protective effect, dropping risk of CD by 39% (HR, 0.61; P = .025).
“Our analysis revealed a protective trend of living with dogs that transcends the age of exposure, suggesting that dog ownership could confer health benefits in reducing the risk of CD,” the investigators wrote. “Our study also found that living in a large family during the first year of life is significantly associated with the future onset of CD, aligning with prior research that indicates that a larger family size in the first year of life can reduce the risk of developing IBD.”
In contrast, the study identified bird ownership at time of recruitment as a risk factor for CD, increasing risk almost three-fold (HR, 2.84; P = .005). The investigators urged a careful interpretation of this latter finding, however, as relatively few FDRs lived with birds.
“[A]lthough our sample size can be considered large, some environmental variables were uncommon, such as the participants having birds as pets, and would greatly benefit from replication of our findings in other cohorts,” Dr. Xue and colleagues noted.
They suggested several possible ways in which the above environmental factors may impact CD risk, including effects on subclinical inflammation, microbiome composition, and gut permeability.
“Understanding the relationship between CD-related environmental factors and these predisease biomarkers may shed light on the underlying mechanisms by which environmental factors impact host health and ultimately lead to CD onset,” the investigators concluded.
The study was supported by Crohn’s and Colitis Canada, Canadian Institutes of Health Research, the Helmsley Charitable Trust, and others. The investigators disclosed no conflicts of interest.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Stool-Based Methylation Test May Improve CRC Screening
based on a prospective, real-world study.
These findings suggest that the mSDC2 assay could improve the efficacy and resource utilization of existing screening programs, reported co–lead authors Shengbing Zhao, MD and Zixuan He, MD, of Naval Medical University, Shanghai, China, and colleagues.
“Conventional risk-stratification strategies, such as fecal immunochemical test (FIT) and life risk factors, are still criticized for being inferior at identifying early-stage CRC and ACN, and their real-world performance is probably further weakened by the low annual participation rate and compliance of subsequent colonoscopy,” the investigators wrote in Gastroenterology. Recent case studies have reported “high diagnostic performance” using stool-based testing for mSDC2, which is “the most accurate single-targeted gene” for colorectal neoplasia, according to the investigators; however, real-world outcomes have yet to be demonstrated, prompting the present study. The prospective, multicenter, community-based trial compared the diagnostic performance of the mSDC2 test against FIT and Asia-Pacific Colorectal Screening (APCS) scores.
The primary outcome was detection of ACN. Secondary outcomes included detection of CRC, early-stage CRC, ACN, colorectal neoplasia (CN), and clinically relevant serrated polyp (CRSP). Screening strategies were also compared in terms of cost-effectiveness and impact on colonoscopy workload.The final dataset included 10,360 participants aged 45-75 years who underwent screening between 2020 and 2022.
After determining APCS scores, stool samples were analyzed for mSDC2 and FIT markers. Based on risk stratification results, participants were invited to undergo colonoscopy. A total of 3,381 participants completed colonoscopy, with 1914 from the increased-risk population and 1467 from the average-risk population. Participants who tested positive for mSDC2 had significantly higher detection rates for all measured outcomes than those who tested negative (all, P < .05). For example, the detection rate for ACN was 26.6% in mSDC2-positive participants, compared with 9.3% in mSDC2-negative participants, with a relative risk of 2.87 (95% CI, 2.39-3.44). For CRC, the detection rate was 4.2% in mSDC2-positive participants vs 0.1% in mSDC2-negative participants, yielding a relative risk of 29.73 (95% CI, 10.29-85.91). Performance held steady across subgroups.The mSDC2 test demonstrated cost-effectiveness by significantly reducing the number of colonoscopies needed to detect one case of ACN or CRC. Specifically, the number of colonoscopies needed to screen for ACN and CRC was reduced by 56.2% and 81.5%, respectively. Parallel combinations of mSDC2 with APCS or FIT enhanced both diagnostic performance and cost-effectiveness.
“This study further illustrates that the mSDC2 test consistently improves predictive abilities for CN, CRSP, ACN, and CRC, which is not influenced by subgroups of lesion location or risk factors, even under the risk stratification by FIT or APCS,” the investigators wrote. “The excellent diagnostic ability of mSDC2 in premalignant lesions, early-stage CRC, and early-onset CRC indicates a promising value in early detection and prevention of CRC ... the mSDC2 test or a parallel combination of multiple screening methods might be promising to improve real-world CRC screening performance and reduce colonoscopy workload in community practice.”The study was supported by the National Key Research and Development Program of China, Deep Blue Project of Naval Medical University, the Creative Biosciences, and others. The investigators reported no conflicts of interest.
based on a prospective, real-world study.
These findings suggest that the mSDC2 assay could improve the efficacy and resource utilization of existing screening programs, reported co–lead authors Shengbing Zhao, MD and Zixuan He, MD, of Naval Medical University, Shanghai, China, and colleagues.
“Conventional risk-stratification strategies, such as fecal immunochemical test (FIT) and life risk factors, are still criticized for being inferior at identifying early-stage CRC and ACN, and their real-world performance is probably further weakened by the low annual participation rate and compliance of subsequent colonoscopy,” the investigators wrote in Gastroenterology. Recent case studies have reported “high diagnostic performance” using stool-based testing for mSDC2, which is “the most accurate single-targeted gene” for colorectal neoplasia, according to the investigators; however, real-world outcomes have yet to be demonstrated, prompting the present study. The prospective, multicenter, community-based trial compared the diagnostic performance of the mSDC2 test against FIT and Asia-Pacific Colorectal Screening (APCS) scores.
The primary outcome was detection of ACN. Secondary outcomes included detection of CRC, early-stage CRC, ACN, colorectal neoplasia (CN), and clinically relevant serrated polyp (CRSP). Screening strategies were also compared in terms of cost-effectiveness and impact on colonoscopy workload.The final dataset included 10,360 participants aged 45-75 years who underwent screening between 2020 and 2022.
After determining APCS scores, stool samples were analyzed for mSDC2 and FIT markers. Based on risk stratification results, participants were invited to undergo colonoscopy. A total of 3,381 participants completed colonoscopy, with 1914 from the increased-risk population and 1467 from the average-risk population. Participants who tested positive for mSDC2 had significantly higher detection rates for all measured outcomes than those who tested negative (all, P < .05). For example, the detection rate for ACN was 26.6% in mSDC2-positive participants, compared with 9.3% in mSDC2-negative participants, with a relative risk of 2.87 (95% CI, 2.39-3.44). For CRC, the detection rate was 4.2% in mSDC2-positive participants vs 0.1% in mSDC2-negative participants, yielding a relative risk of 29.73 (95% CI, 10.29-85.91). Performance held steady across subgroups.The mSDC2 test demonstrated cost-effectiveness by significantly reducing the number of colonoscopies needed to detect one case of ACN or CRC. Specifically, the number of colonoscopies needed to screen for ACN and CRC was reduced by 56.2% and 81.5%, respectively. Parallel combinations of mSDC2 with APCS or FIT enhanced both diagnostic performance and cost-effectiveness.
“This study further illustrates that the mSDC2 test consistently improves predictive abilities for CN, CRSP, ACN, and CRC, which is not influenced by subgroups of lesion location or risk factors, even under the risk stratification by FIT or APCS,” the investigators wrote. “The excellent diagnostic ability of mSDC2 in premalignant lesions, early-stage CRC, and early-onset CRC indicates a promising value in early detection and prevention of CRC ... the mSDC2 test or a parallel combination of multiple screening methods might be promising to improve real-world CRC screening performance and reduce colonoscopy workload in community practice.”The study was supported by the National Key Research and Development Program of China, Deep Blue Project of Naval Medical University, the Creative Biosciences, and others. The investigators reported no conflicts of interest.
based on a prospective, real-world study.
These findings suggest that the mSDC2 assay could improve the efficacy and resource utilization of existing screening programs, reported co–lead authors Shengbing Zhao, MD and Zixuan He, MD, of Naval Medical University, Shanghai, China, and colleagues.
“Conventional risk-stratification strategies, such as fecal immunochemical test (FIT) and life risk factors, are still criticized for being inferior at identifying early-stage CRC and ACN, and their real-world performance is probably further weakened by the low annual participation rate and compliance of subsequent colonoscopy,” the investigators wrote in Gastroenterology. Recent case studies have reported “high diagnostic performance” using stool-based testing for mSDC2, which is “the most accurate single-targeted gene” for colorectal neoplasia, according to the investigators; however, real-world outcomes have yet to be demonstrated, prompting the present study. The prospective, multicenter, community-based trial compared the diagnostic performance of the mSDC2 test against FIT and Asia-Pacific Colorectal Screening (APCS) scores.
The primary outcome was detection of ACN. Secondary outcomes included detection of CRC, early-stage CRC, ACN, colorectal neoplasia (CN), and clinically relevant serrated polyp (CRSP). Screening strategies were also compared in terms of cost-effectiveness and impact on colonoscopy workload.The final dataset included 10,360 participants aged 45-75 years who underwent screening between 2020 and 2022.
After determining APCS scores, stool samples were analyzed for mSDC2 and FIT markers. Based on risk stratification results, participants were invited to undergo colonoscopy. A total of 3,381 participants completed colonoscopy, with 1914 from the increased-risk population and 1467 from the average-risk population. Participants who tested positive for mSDC2 had significantly higher detection rates for all measured outcomes than those who tested negative (all, P < .05). For example, the detection rate for ACN was 26.6% in mSDC2-positive participants, compared with 9.3% in mSDC2-negative participants, with a relative risk of 2.87 (95% CI, 2.39-3.44). For CRC, the detection rate was 4.2% in mSDC2-positive participants vs 0.1% in mSDC2-negative participants, yielding a relative risk of 29.73 (95% CI, 10.29-85.91). Performance held steady across subgroups.The mSDC2 test demonstrated cost-effectiveness by significantly reducing the number of colonoscopies needed to detect one case of ACN or CRC. Specifically, the number of colonoscopies needed to screen for ACN and CRC was reduced by 56.2% and 81.5%, respectively. Parallel combinations of mSDC2 with APCS or FIT enhanced both diagnostic performance and cost-effectiveness.
“This study further illustrates that the mSDC2 test consistently improves predictive abilities for CN, CRSP, ACN, and CRC, which is not influenced by subgroups of lesion location or risk factors, even under the risk stratification by FIT or APCS,” the investigators wrote. “The excellent diagnostic ability of mSDC2 in premalignant lesions, early-stage CRC, and early-onset CRC indicates a promising value in early detection and prevention of CRC ... the mSDC2 test or a parallel combination of multiple screening methods might be promising to improve real-world CRC screening performance and reduce colonoscopy workload in community practice.”The study was supported by the National Key Research and Development Program of China, Deep Blue Project of Naval Medical University, the Creative Biosciences, and others. The investigators reported no conflicts of interest.
FROM GASTROENTEROLOGY
Snare Tip Soft Coagulation Leaves Clean Margins After Resection
according to a recent study.
Since STSC was faster to apply than APC and results in lower cost and plastic waste (because of APC requiring an additional catheter), STSC was the preferred option.
“The reduction in recurrence rate with thermal margin treatment is arguably the most important development in endoscopic mucosal resection in the past 2 decades,” said lead author Douglas Rex, MD, AGAF, a distinguished professor emeritus at the Indiana University School of Medicine and director of endoscopy at Indiana University Hospitals, both in Indianapolis.
“Margin thermal therapy with STSC should now be standard treatment after piecemeal EMR in the colorectum,” he said. “Before applying STSC, the endoscopist must ensure that the entire lesion is resected down to the submucosa. Then STSC should be aggressively applied to 100% of the margin.”
The study was published in Clinical Gastroenterology and Hepatology .
Comparing Treatments
Dr. Rex and colleagues performed a randomized three-arm trial in nine U.S. centers, comparing STSC with APC and no margin treatment in patients undergoing colorectal EMR of nonpedunculated lesions of 15 mm or greater.
All lesions underwent conventional injection and snare resection EMR using electrocautery, but the endoscopist chose the injection fluid and snare type and size. Areas with residual polyp that weren’t removable by snare resection because of flat shape or fibrosis were removed by hot or cold avulsion. After that, patients were randomized to one of the three arms.
Patients were scheduled for a follow-up appointment six months after the initial EMR. Any visible recurrence was resected using methods at the discretion of the endoscopist, and if no visible recurrence was present, EMR site biopsies were recommended.
Among 384 patients with 414 lesions, 308 patients with 328 lesions completed at least one follow-up appointment. The median interval to the first follow-up was 6.4 months, ranging from 2 to 37 months. The primary endpoint was the presence of recurrent or residual polyp at first follow-up.
The median polyp size was 25 mm, and 65 of the 414 polyps (15.7%) were 15-19 mm in size. Overall, 14.8% of lesions were resected en bloc, with no difference between the study arms.
The proportion of lesions with residual polyp at first follow-up was 4.6% with STSC, 9.3% with APC, and 21.4% among control subjects with no margin treatment.
The odds of having a residual polyp at first follow-up were lower for STSC and APC when compared with control subjects (odds ratio [OR] of 0.182 and 0.341, or P = .001 and P = .01, respectively). There wasn’t a significant difference in the odds of recurrence between STSC and APC (OR, 1.874).
In 259 lesions in 248 patients that were 20 mm or greater, the recurrence rates at first follow-up were 5.9% for STSC, 10.1% for APC, and 25.9% for the control group. In these lesions, STSC and APC remained associated with a lower risk of recurrence versus the control (OR, 0.18 and 0.323, respectively). The difference in recurrence rates between STSC and APC wasn’t significant.
Even still, STSC took less time to apply than APC, with a median time of 3.35 minutes vs 4.08 minutes.
The rates of adverse events were low, with no difference between the three arms. There were no immediate or delayed perforations in any arm, and the overall occurrence of delayed bleeding was low at 3.6%.
“I think STSC won the trial because it was numerically (though not statistically) superior to APC, was faster to apply, and using STSC results in lower cost and less plastic compared to APC,” Dr. Rex said.
Additional Considerations
Based on charges at the nine U.S. centers and a survey of two manufacturers, APC catheters typically cost $175-$275 each, the study authors wrote, noting that APC results in increased cost, plastic waste because of the catheter, and carbon emissions associated with its manufacture.
“What we’re seeing — now over several trials — is STSC appears to be the most effective method of treating the edges, and it’s inexpensive because it uses the same device used for snare resection, so there’s no incremental cost for the device,” said Michael Wallace, MD, professor of medicine and director of the digestive diseases research program at Mayo Clinic, Jacksonville, Florida.
Dr. Wallace, who wasn’t involved with this study, has researched thermal ablation after EMR, including both the margins and the base.
“The single most important message now is that patients shouldn’t be getting surgical resections for endoscopically treatable polyps,” he said. “We see many patients who are told they need to get surgery, but overwhelmingly, the data shows we can remove polyps without surgery.”
Dr. Rex and several authors declared fees and grants from numerous companies outside of this study. Dr. Wallace reported no relevant disclosures.
according to a recent study.
Since STSC was faster to apply than APC and results in lower cost and plastic waste (because of APC requiring an additional catheter), STSC was the preferred option.
“The reduction in recurrence rate with thermal margin treatment is arguably the most important development in endoscopic mucosal resection in the past 2 decades,” said lead author Douglas Rex, MD, AGAF, a distinguished professor emeritus at the Indiana University School of Medicine and director of endoscopy at Indiana University Hospitals, both in Indianapolis.
“Margin thermal therapy with STSC should now be standard treatment after piecemeal EMR in the colorectum,” he said. “Before applying STSC, the endoscopist must ensure that the entire lesion is resected down to the submucosa. Then STSC should be aggressively applied to 100% of the margin.”
The study was published in Clinical Gastroenterology and Hepatology .
Comparing Treatments
Dr. Rex and colleagues performed a randomized three-arm trial in nine U.S. centers, comparing STSC with APC and no margin treatment in patients undergoing colorectal EMR of nonpedunculated lesions of 15 mm or greater.
All lesions underwent conventional injection and snare resection EMR using electrocautery, but the endoscopist chose the injection fluid and snare type and size. Areas with residual polyp that weren’t removable by snare resection because of flat shape or fibrosis were removed by hot or cold avulsion. After that, patients were randomized to one of the three arms.
Patients were scheduled for a follow-up appointment six months after the initial EMR. Any visible recurrence was resected using methods at the discretion of the endoscopist, and if no visible recurrence was present, EMR site biopsies were recommended.
Among 384 patients with 414 lesions, 308 patients with 328 lesions completed at least one follow-up appointment. The median interval to the first follow-up was 6.4 months, ranging from 2 to 37 months. The primary endpoint was the presence of recurrent or residual polyp at first follow-up.
The median polyp size was 25 mm, and 65 of the 414 polyps (15.7%) were 15-19 mm in size. Overall, 14.8% of lesions were resected en bloc, with no difference between the study arms.
The proportion of lesions with residual polyp at first follow-up was 4.6% with STSC, 9.3% with APC, and 21.4% among control subjects with no margin treatment.
The odds of having a residual polyp at first follow-up were lower for STSC and APC when compared with control subjects (odds ratio [OR] of 0.182 and 0.341, or P = .001 and P = .01, respectively). There wasn’t a significant difference in the odds of recurrence between STSC and APC (OR, 1.874).
In 259 lesions in 248 patients that were 20 mm or greater, the recurrence rates at first follow-up were 5.9% for STSC, 10.1% for APC, and 25.9% for the control group. In these lesions, STSC and APC remained associated with a lower risk of recurrence versus the control (OR, 0.18 and 0.323, respectively). The difference in recurrence rates between STSC and APC wasn’t significant.
Even still, STSC took less time to apply than APC, with a median time of 3.35 minutes vs 4.08 minutes.
The rates of adverse events were low, with no difference between the three arms. There were no immediate or delayed perforations in any arm, and the overall occurrence of delayed bleeding was low at 3.6%.
“I think STSC won the trial because it was numerically (though not statistically) superior to APC, was faster to apply, and using STSC results in lower cost and less plastic compared to APC,” Dr. Rex said.
Additional Considerations
Based on charges at the nine U.S. centers and a survey of two manufacturers, APC catheters typically cost $175-$275 each, the study authors wrote, noting that APC results in increased cost, plastic waste because of the catheter, and carbon emissions associated with its manufacture.
“What we’re seeing — now over several trials — is STSC appears to be the most effective method of treating the edges, and it’s inexpensive because it uses the same device used for snare resection, so there’s no incremental cost for the device,” said Michael Wallace, MD, professor of medicine and director of the digestive diseases research program at Mayo Clinic, Jacksonville, Florida.
Dr. Wallace, who wasn’t involved with this study, has researched thermal ablation after EMR, including both the margins and the base.
“The single most important message now is that patients shouldn’t be getting surgical resections for endoscopically treatable polyps,” he said. “We see many patients who are told they need to get surgery, but overwhelmingly, the data shows we can remove polyps without surgery.”
Dr. Rex and several authors declared fees and grants from numerous companies outside of this study. Dr. Wallace reported no relevant disclosures.
according to a recent study.
Since STSC was faster to apply than APC and results in lower cost and plastic waste (because of APC requiring an additional catheter), STSC was the preferred option.
“The reduction in recurrence rate with thermal margin treatment is arguably the most important development in endoscopic mucosal resection in the past 2 decades,” said lead author Douglas Rex, MD, AGAF, a distinguished professor emeritus at the Indiana University School of Medicine and director of endoscopy at Indiana University Hospitals, both in Indianapolis.
“Margin thermal therapy with STSC should now be standard treatment after piecemeal EMR in the colorectum,” he said. “Before applying STSC, the endoscopist must ensure that the entire lesion is resected down to the submucosa. Then STSC should be aggressively applied to 100% of the margin.”
The study was published in Clinical Gastroenterology and Hepatology .
Comparing Treatments
Dr. Rex and colleagues performed a randomized three-arm trial in nine U.S. centers, comparing STSC with APC and no margin treatment in patients undergoing colorectal EMR of nonpedunculated lesions of 15 mm or greater.
All lesions underwent conventional injection and snare resection EMR using electrocautery, but the endoscopist chose the injection fluid and snare type and size. Areas with residual polyp that weren’t removable by snare resection because of flat shape or fibrosis were removed by hot or cold avulsion. After that, patients were randomized to one of the three arms.
Patients were scheduled for a follow-up appointment six months after the initial EMR. Any visible recurrence was resected using methods at the discretion of the endoscopist, and if no visible recurrence was present, EMR site biopsies were recommended.
Among 384 patients with 414 lesions, 308 patients with 328 lesions completed at least one follow-up appointment. The median interval to the first follow-up was 6.4 months, ranging from 2 to 37 months. The primary endpoint was the presence of recurrent or residual polyp at first follow-up.
The median polyp size was 25 mm, and 65 of the 414 polyps (15.7%) were 15-19 mm in size. Overall, 14.8% of lesions were resected en bloc, with no difference between the study arms.
The proportion of lesions with residual polyp at first follow-up was 4.6% with STSC, 9.3% with APC, and 21.4% among control subjects with no margin treatment.
The odds of having a residual polyp at first follow-up were lower for STSC and APC when compared with control subjects (odds ratio [OR] of 0.182 and 0.341, or P = .001 and P = .01, respectively). There wasn’t a significant difference in the odds of recurrence between STSC and APC (OR, 1.874).
In 259 lesions in 248 patients that were 20 mm or greater, the recurrence rates at first follow-up were 5.9% for STSC, 10.1% for APC, and 25.9% for the control group. In these lesions, STSC and APC remained associated with a lower risk of recurrence versus the control (OR, 0.18 and 0.323, respectively). The difference in recurrence rates between STSC and APC wasn’t significant.
Even still, STSC took less time to apply than APC, with a median time of 3.35 minutes vs 4.08 minutes.
The rates of adverse events were low, with no difference between the three arms. There were no immediate or delayed perforations in any arm, and the overall occurrence of delayed bleeding was low at 3.6%.
“I think STSC won the trial because it was numerically (though not statistically) superior to APC, was faster to apply, and using STSC results in lower cost and less plastic compared to APC,” Dr. Rex said.
Additional Considerations
Based on charges at the nine U.S. centers and a survey of two manufacturers, APC catheters typically cost $175-$275 each, the study authors wrote, noting that APC results in increased cost, plastic waste because of the catheter, and carbon emissions associated with its manufacture.
“What we’re seeing — now over several trials — is STSC appears to be the most effective method of treating the edges, and it’s inexpensive because it uses the same device used for snare resection, so there’s no incremental cost for the device,” said Michael Wallace, MD, professor of medicine and director of the digestive diseases research program at Mayo Clinic, Jacksonville, Florida.
Dr. Wallace, who wasn’t involved with this study, has researched thermal ablation after EMR, including both the margins and the base.
“The single most important message now is that patients shouldn’t be getting surgical resections for endoscopically treatable polyps,” he said. “We see many patients who are told they need to get surgery, but overwhelmingly, the data shows we can remove polyps without surgery.”
Dr. Rex and several authors declared fees and grants from numerous companies outside of this study. Dr. Wallace reported no relevant disclosures.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY