TBD Meeting (3042-23)

CHICAGO – It has been a busy year for hepatology with major developments in the detection, management, and prevention of chronic liver disease. Two landmark phase 2 trials of the glucagon-like peptide 1 (GLP-1) receptor agonist, semaglutide, Food and Drug Administration–approved for type 2 diabetes or obesity, demonstrated improvements in nonalcoholic steatohepatitis (NASH) activity and resolution in stage 2 or 3 fibrosis (F2/F3), but not F4 fibrosis.^1,2 The first randomized trial to compare the efficacy and safety of bariatric surgery with lifestyle intervention plus best medical care for histologically confirmed NASH demonstrated the superiority of bariatric surgery.³

There has been a paradigm shift in risk stratification of cirrhosis and targets for prevention and treatment of decompensation. A newer term, advanced chronic liver disease (ACLD), represents a shift away from needing a histologic or radiologic diagnosis of cirrhosis while reduction in portal pressure is a therapeutic goal. Evidence supports noninvasive liver stiffness measurement (LSM) using transient elastography to identify those with clinically significant portal hypertension (CSPH) (e.g., hepatic venous pressure gradient ≥ 10 mm Hg) who may benefit from therapy to lower portal pressure. Accordingly, based on landmark studies, the American Association for the Study of Liver Diseases (AASLD) recommends early utilization of nonselective beta-blocker therapy, with carvedilol as a preferred agent, in CSPH to decrease the risk of decompensation and mortality.⁴

University of Miami

Surveillance and treatment approaches for hepatocellular carcinoma (HCC) continue to evolve as reflected in new AASLD guidance in June 2023. Screening among high-risk patients should include ultrasound and serum alpha-fetoprotein every 6 months and novel screening approaches including imaging and blood-based biomarkers are on the horizon. There also have been significant advances in systemic therapies for HCC. First-line therapy for advanced HCC with CTP A cirrhosis now includes either atezolizumab/bevacizumab or durvalumab/tremelimumab. There is an evolving role for systemic therapy in the adjuvant setting as well, with emerging data supporting checkpoint inhibitors after resection or ablation among patients at high risk of recurrence.

Allocation policies continue to evolve for liver transplantation as waitlist prioritization transitions to MELD 3.0. The new score improves predictive accuracy for short-term mortality and addresses sex disparity in waitlist outcomes by lowering the prioritization of creatinine (and its threshold) and adding albumin to the current MELD-Na formula. MELD 3.0 will be adopted by the United Network for Organ Sharing in July 2023.

It has been a whirlwind 2023 for the liver community and we are excited and hopeful for new breakthroughs to come.

Dr. VanWagner is with the division of digestive and liver diseases, University of Texas Southwestern Medical Center; Dr. Serper is with the division of gastroenterology and hepatology, University of Pennsylvania; Dr. Goldberg is with the division of digestive health and liver diseases, University of Miami; and Dr. Verna is with the division of digestive and liver diseases, Columbia University. Dr. VanWagner is an adviser for Numares and Novo Nordisk and received a research grant from W.L. Gore & Associates. Dr. Serper disclosed research funding from Grifols. Dr. Verna disclosed research support from Salix. Dr. Goldberg had no disclosures. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2023. DDW is sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and The Society for Surgery of the Alimentary Tract (SSAT).

References

1. Loomba R et al. Semaglutide 2.4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: A randomised, placebo-controlled phase 2 trial. Lancet Gastroenterol Hepatol. 2023;8:511-22.

2. Newsome PN et al. A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis. N Engl J Med. 2021;384:1113-24.

3. Verrastro O et al. Bariatric-metabolic surgery versus lifestyle intervention plus best medical care in non-alcoholic steatohepatitis (BRAVES): A multicentre, open-label, randomised trial. Lancet 2023;401:1786-97.

4. Rowe IA et al. Quantifying the benefit of nonselective beta-blockers in the prevention of hepatic decompensation: A Bayesian reanalysis of the PREDESCI trial. Hepatology 2023 Mar 13. doi: 10.1097/HEP.0000000000000342.

5. Nadim MK and Garcia-Tsao G. Acute kidney injury in patients with cirrhosis. N Engl J Med. 2023;388:733-45.

6. Bureau C et al. The use of rifaximin in the prevention of overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunt: A randomized controlled trial. Ann Intern Med. 2021;174:633-40.

CHICAGO – It has been a busy year for hepatology with major developments in the detection, management, and prevention of chronic liver disease. Two landmark phase 2 trials of the glucagon-like peptide 1 (GLP-1) receptor agonist, semaglutide, Food and Drug Administration–approved for type 2 diabetes or obesity, demonstrated improvements in nonalcoholic steatohepatitis (NASH) activity and resolution in stage 2 or 3 fibrosis (F2/F3), but not F4 fibrosis.^1,2 The first randomized trial to compare the efficacy and safety of bariatric surgery with lifestyle intervention plus best medical care for histologically confirmed NASH demonstrated the superiority of bariatric surgery.³

There has been a paradigm shift in risk stratification of cirrhosis and targets for prevention and treatment of decompensation. A newer term, advanced chronic liver disease (ACLD), represents a shift away from needing a histologic or radiologic diagnosis of cirrhosis while reduction in portal pressure is a therapeutic goal. Evidence supports noninvasive liver stiffness measurement (LSM) using transient elastography to identify those with clinically significant portal hypertension (CSPH) (e.g., hepatic venous pressure gradient ≥ 10 mm Hg) who may benefit from therapy to lower portal pressure. Accordingly, based on landmark studies, the American Association for the Study of Liver Diseases (AASLD) recommends early utilization of nonselective beta-blocker therapy, with carvedilol as a preferred agent, in CSPH to decrease the risk of decompensation and mortality.⁴

University of Miami

Surveillance and treatment approaches for hepatocellular carcinoma (HCC) continue to evolve as reflected in new AASLD guidance in June 2023. Screening among high-risk patients should include ultrasound and serum alpha-fetoprotein every 6 months and novel screening approaches including imaging and blood-based biomarkers are on the horizon. There also have been significant advances in systemic therapies for HCC. First-line therapy for advanced HCC with CTP A cirrhosis now includes either atezolizumab/bevacizumab or durvalumab/tremelimumab. There is an evolving role for systemic therapy in the adjuvant setting as well, with emerging data supporting checkpoint inhibitors after resection or ablation among patients at high risk of recurrence.

Allocation policies continue to evolve for liver transplantation as waitlist prioritization transitions to MELD 3.0. The new score improves predictive accuracy for short-term mortality and addresses sex disparity in waitlist outcomes by lowering the prioritization of creatinine (and its threshold) and adding albumin to the current MELD-Na formula. MELD 3.0 will be adopted by the United Network for Organ Sharing in July 2023.

It has been a whirlwind 2023 for the liver community and we are excited and hopeful for new breakthroughs to come.

Dr. VanWagner is with the division of digestive and liver diseases, University of Texas Southwestern Medical Center; Dr. Serper is with the division of gastroenterology and hepatology, University of Pennsylvania; Dr. Goldberg is with the division of digestive health and liver diseases, University of Miami; and Dr. Verna is with the division of digestive and liver diseases, Columbia University. Dr. VanWagner is an adviser for Numares and Novo Nordisk and received a research grant from W.L. Gore & Associates. Dr. Serper disclosed research funding from Grifols. Dr. Verna disclosed research support from Salix. Dr. Goldberg had no disclosures. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2023. DDW is sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and The Society for Surgery of the Alimentary Tract (SSAT).

References

1. Loomba R et al. Semaglutide 2.4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: A randomised, placebo-controlled phase 2 trial. Lancet Gastroenterol Hepatol. 2023;8:511-22.

2. Newsome PN et al. A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis. N Engl J Med. 2021;384:1113-24.

3. Verrastro O et al. Bariatric-metabolic surgery versus lifestyle intervention plus best medical care in non-alcoholic steatohepatitis (BRAVES): A multicentre, open-label, randomised trial. Lancet 2023;401:1786-97.

4. Rowe IA et al. Quantifying the benefit of nonselective beta-blockers in the prevention of hepatic decompensation: A Bayesian reanalysis of the PREDESCI trial. Hepatology 2023 Mar 13. doi: 10.1097/HEP.0000000000000342.

5. Nadim MK and Garcia-Tsao G. Acute kidney injury in patients with cirrhosis. N Engl J Med. 2023;388:733-45.

6. Bureau C et al. The use of rifaximin in the prevention of overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunt: A randomized controlled trial. Ann Intern Med. 2021;174:633-40.

CHICAGO – It has been a busy year for hepatology with major developments in the detection, management, and prevention of chronic liver disease. Two landmark phase 2 trials of the glucagon-like peptide 1 (GLP-1) receptor agonist, semaglutide, Food and Drug Administration–approved for type 2 diabetes or obesity, demonstrated improvements in nonalcoholic steatohepatitis (NASH) activity and resolution in stage 2 or 3 fibrosis (F2/F3), but not F4 fibrosis.^1,2 The first randomized trial to compare the efficacy and safety of bariatric surgery with lifestyle intervention plus best medical care for histologically confirmed NASH demonstrated the superiority of bariatric surgery.³

There has been a paradigm shift in risk stratification of cirrhosis and targets for prevention and treatment of decompensation. A newer term, advanced chronic liver disease (ACLD), represents a shift away from needing a histologic or radiologic diagnosis of cirrhosis while reduction in portal pressure is a therapeutic goal. Evidence supports noninvasive liver stiffness measurement (LSM) using transient elastography to identify those with clinically significant portal hypertension (CSPH) (e.g., hepatic venous pressure gradient ≥ 10 mm Hg) who may benefit from therapy to lower portal pressure. Accordingly, based on landmark studies, the American Association for the Study of Liver Diseases (AASLD) recommends early utilization of nonselective beta-blocker therapy, with carvedilol as a preferred agent, in CSPH to decrease the risk of decompensation and mortality.⁴

University of Miami

Surveillance and treatment approaches for hepatocellular carcinoma (HCC) continue to evolve as reflected in new AASLD guidance in June 2023. Screening among high-risk patients should include ultrasound and serum alpha-fetoprotein every 6 months and novel screening approaches including imaging and blood-based biomarkers are on the horizon. There also have been significant advances in systemic therapies for HCC. First-line therapy for advanced HCC with CTP A cirrhosis now includes either atezolizumab/bevacizumab or durvalumab/tremelimumab. There is an evolving role for systemic therapy in the adjuvant setting as well, with emerging data supporting checkpoint inhibitors after resection or ablation among patients at high risk of recurrence.

Allocation policies continue to evolve for liver transplantation as waitlist prioritization transitions to MELD 3.0. The new score improves predictive accuracy for short-term mortality and addresses sex disparity in waitlist outcomes by lowering the prioritization of creatinine (and its threshold) and adding albumin to the current MELD-Na formula. MELD 3.0 will be adopted by the United Network for Organ Sharing in July 2023.

It has been a whirlwind 2023 for the liver community and we are excited and hopeful for new breakthroughs to come.

Dr. VanWagner is with the division of digestive and liver diseases, University of Texas Southwestern Medical Center; Dr. Serper is with the division of gastroenterology and hepatology, University of Pennsylvania; Dr. Goldberg is with the division of digestive health and liver diseases, University of Miami; and Dr. Verna is with the division of digestive and liver diseases, Columbia University. Dr. VanWagner is an adviser for Numares and Novo Nordisk and received a research grant from W.L. Gore & Associates. Dr. Serper disclosed research funding from Grifols. Dr. Verna disclosed research support from Salix. Dr. Goldberg had no disclosures. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2023. DDW is sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and The Society for Surgery of the Alimentary Tract (SSAT).

References

1. Loomba R et al. Semaglutide 2.4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: A randomised, placebo-controlled phase 2 trial. Lancet Gastroenterol Hepatol. 2023;8:511-22.

2. Newsome PN et al. A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis. N Engl J Med. 2021;384:1113-24.

3. Verrastro O et al. Bariatric-metabolic surgery versus lifestyle intervention plus best medical care in non-alcoholic steatohepatitis (BRAVES): A multicentre, open-label, randomised trial. Lancet 2023;401:1786-97.

4. Rowe IA et al. Quantifying the benefit of nonselective beta-blockers in the prevention of hepatic decompensation: A Bayesian reanalysis of the PREDESCI trial. Hepatology 2023 Mar 13. doi: 10.1097/HEP.0000000000000342.

5. Nadim MK and Garcia-Tsao G. Acute kidney injury in patients with cirrhosis. N Engl J Med. 2023;388:733-45.

6. Bureau C et al. The use of rifaximin in the prevention of overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunt: A randomized controlled trial. Ann Intern Med. 2021;174:633-40.

Findings from a landmark clinical trial in pediatric Crohn’s disease show a clear benefit of adding methotrexate to treatment with the tumor necrosis factor inhibitor (TNFi) adalimumab (Humira), but not to infliximab therapy.

Children initiating treatment with adalimumab plus a low dose of methotrexate experienced a twofold reduction in treatment failure, note the authors of the largest, double-blind, randomized trial to date in pediatric Crohn’s disease. However, children initiating infliximab, another TNFi, had similar outcomes with or without methotrexate.

“We believe these results are practice changing,” said principal investigator Michael Kappelman, MD, MPH, professor of pediatrics at University of North Carolina.

All patients with pediatric Crohn’s disease starting on adalimumab, and their parents, should be informed that combining the drug with low-dose oral methotrexate improves treatment effectiveness, he said.

“Those without contraindications should be offered combination therapy, and shared decision-making should be incorporated into final treatment decisions. In contrast, most patients starting infliximab are not likely to experience added benefits from low-dose oral methotrexate,” Dr. Kappelman added.

The study was published online in Gastroenterology and was presented in May in Chicago at the annual Digestive Disease Week® (DDW).

Impactful study

“This is an important study, published in a very high-ranking journal, that will have a huge impact on how we practice,” Jacob Kurowski, MD, department of pediatric gastroenterology, hepatology and nutrition, Cleveland Clinic Children’s, who wasn’t involved in the study, said.

Treatment with a TNFi, including infliximab and adalimumab, is a mainstay of pediatric Crohn’s disease therapy. However, not all patients achieve remission, and many lose response over time.

The current trial compared the effectiveness and safety of adding a low-dose of oral methotrexate to adalimumab or infliximab vs. TNFi therapy alone in 297 children with Crohn’s disease. The mean age was 13.9 years, and about two-thirds were boys. None had a prior history of TNFi therapy.

Participants initiating infliximab or adalimumab were randomly allocated (1:1) to oral methotrexate or placebo. Of them, 110 infliximab initiators and 46 adalimumab initiators received methotrexate, while 102 infliximab initiators and 39 adalimumab initiators were given placebo. Methotrexate was administered as a weekly dose of 15 mg for children weighing 40 kg or more, 12.5 mg for children 30 kg to less than 40 kg, and 10 mg for children 20 kg to less than 30 kg. All participants received pretreatment with ondansetron 4 mg (or placebo) to prevent nausea and folic acid (1 mg per day). Participants were followed for 12-36 months.

The primary outcome was a failure to achieve or maintain steroid-free remission defined by occurrence of any of the following:

• Short Pediatric Crohn’s Disease Activity Index (SPCDAI) score of less than 15 by week 26.
• Failure to complete a steroid taper by week 16.
• SPCDAI score of 15 or higher as a result of active Crohn’s disease at two or more consecutive visits beyond week 26.
• Hospitalization or surgery for Crohn’s disease beyond week 26.
• Use of corticosteroids for Crohn’s disease for 10 or more weeks cumulatively beyond week 16.
• Discontinuation of anti-TNF and/or study drug for lack of effectiveness or toxicity.

Overall, 88 of 297 children (30%) experienced treatment failure, including 57 of 212 (27%) on infliximab and 31 of 85 (36%) on adalimumab. Overall, 40 of 156 children (26%) on combination therapy and 48 of 141 (34%) on monotherapy experienced treatment failure.

Kaplan Meier analysis of the overall population showed a nonsignificant trend toward lower event rates with combination therapy (hazard ratio, 0.69; 95% confidence interval, 0.45-1.05; P = .08).

After stratification by TNFi, there was no difference in time to treatment failure among infliximab initiators between combination and monotherapy (HR, 0.93; 95% CI, 0.55-1.56; P = .78). In contrast, among adalimumab initiators, combination therapy was significantly associated with a longer time to treatment failure (HR, 0.40; 95% CI 0.19-0.81; P = .01).

There was a nonsignificant trend toward lower development of antidrug antibodies with combination therapy (risk ratio 0.72 with infliximab and 0.71 with adalimumab). This trend is in line with adult studies and adds substantially to the pediatric literature on this topic, the researchers note.

No differences in patient-reported outcomes were observed. There were slightly more adverse events with combination therapy, as expected, but fewer serious adverse events.
 

Shared decision-making

Dr. Kappelman noted that the study was not designed to answer the question of which is better – adalimumab plus methotrexate or infliximab alone.

“This is an area for future research. At this point, we believe it is an individualized decision, and appropriate counseling is needed to support shared decision-making,” he said.

The trial was not designed to evaluate the role of proactive therapeutic drug monitoring. However, proactive TDM is endorsed in the ImproveCareNow Model IBD Care guidelines and was considered standard of care at the 35 study sites.

The findings “suggest strong consideration of using combination therapy for pediatric Crohn’s disease patients initiating adalimumab, but not infliximab,” Dr. Kappelman and colleagues say.

“Dissemination and implementation of these findings should lead to improved outcomes in this patient population, including consideration of deimplementation of combination therapy in infliximab-treated patients,” they add.

The decision about which approach to use is still very dependent on patients and their providers, Dr. Kurowski said.

“The study shows that you can safely use infliximab as monotherapy, with low risk of antibody formation, while utilizing proactive therapeutic drug monitoring and dose optimization,” he said. “The study also shows that adalimumab in combination with low-dose methotrexate can be strongly considered when needed.”

The researchers’ standardization of methotrexate doses by weight “is another significant contribution and provides a guide for clinicians,” Dr. Kurowski added.

The study was funded by grants from the Patient-Centered Outcomes Research Institute, the Helmsley Charitable Trust, and National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Kappelman has consulted for AbbVie, Janssen, Pfizer, Takeda, and Lilly; holds shares in Johnson & Johnson; and has received research support from Pfizer, Takeda, Janssen, AbbVie, Lilly, Genentech, Boehringer Ingelheim, Bristol-Myers Squibb, Celtrion, and Arena Pharmaceuticals. Dr. Kurowski reports no relevant financial relationships.

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

Findings from a landmark clinical trial in pediatric Crohn’s disease show a clear benefit of adding methotrexate to treatment with the tumor necrosis factor inhibitor (TNFi) adalimumab (Humira), but not to infliximab therapy.

Children initiating treatment with adalimumab plus a low dose of methotrexate experienced a twofold reduction in treatment failure, note the authors of the largest, double-blind, randomized trial to date in pediatric Crohn’s disease. However, children initiating infliximab, another TNFi, had similar outcomes with or without methotrexate.

“We believe these results are practice changing,” said principal investigator Michael Kappelman, MD, MPH, professor of pediatrics at University of North Carolina.

All patients with pediatric Crohn’s disease starting on adalimumab, and their parents, should be informed that combining the drug with low-dose oral methotrexate improves treatment effectiveness, he said.

“Those without contraindications should be offered combination therapy, and shared decision-making should be incorporated into final treatment decisions. In contrast, most patients starting infliximab are not likely to experience added benefits from low-dose oral methotrexate,” Dr. Kappelman added.

The study was published online in Gastroenterology and was presented in May in Chicago at the annual Digestive Disease Week® (DDW).

Impactful study

“This is an important study, published in a very high-ranking journal, that will have a huge impact on how we practice,” Jacob Kurowski, MD, department of pediatric gastroenterology, hepatology and nutrition, Cleveland Clinic Children’s, who wasn’t involved in the study, said.

Treatment with a TNFi, including infliximab and adalimumab, is a mainstay of pediatric Crohn’s disease therapy. However, not all patients achieve remission, and many lose response over time.

The current trial compared the effectiveness and safety of adding a low-dose of oral methotrexate to adalimumab or infliximab vs. TNFi therapy alone in 297 children with Crohn’s disease. The mean age was 13.9 years, and about two-thirds were boys. None had a prior history of TNFi therapy.

Participants initiating infliximab or adalimumab were randomly allocated (1:1) to oral methotrexate or placebo. Of them, 110 infliximab initiators and 46 adalimumab initiators received methotrexate, while 102 infliximab initiators and 39 adalimumab initiators were given placebo. Methotrexate was administered as a weekly dose of 15 mg for children weighing 40 kg or more, 12.5 mg for children 30 kg to less than 40 kg, and 10 mg for children 20 kg to less than 30 kg. All participants received pretreatment with ondansetron 4 mg (or placebo) to prevent nausea and folic acid (1 mg per day). Participants were followed for 12-36 months.

The primary outcome was a failure to achieve or maintain steroid-free remission defined by occurrence of any of the following:

• Short Pediatric Crohn’s Disease Activity Index (SPCDAI) score of less than 15 by week 26.
• Failure to complete a steroid taper by week 16.
• SPCDAI score of 15 or higher as a result of active Crohn’s disease at two or more consecutive visits beyond week 26.
• Hospitalization or surgery for Crohn’s disease beyond week 26.
• Use of corticosteroids for Crohn’s disease for 10 or more weeks cumulatively beyond week 16.
• Discontinuation of anti-TNF and/or study drug for lack of effectiveness or toxicity.

Overall, 88 of 297 children (30%) experienced treatment failure, including 57 of 212 (27%) on infliximab and 31 of 85 (36%) on adalimumab. Overall, 40 of 156 children (26%) on combination therapy and 48 of 141 (34%) on monotherapy experienced treatment failure.

Kaplan Meier analysis of the overall population showed a nonsignificant trend toward lower event rates with combination therapy (hazard ratio, 0.69; 95% confidence interval, 0.45-1.05; P = .08).

After stratification by TNFi, there was no difference in time to treatment failure among infliximab initiators between combination and monotherapy (HR, 0.93; 95% CI, 0.55-1.56; P = .78). In contrast, among adalimumab initiators, combination therapy was significantly associated with a longer time to treatment failure (HR, 0.40; 95% CI 0.19-0.81; P = .01).

There was a nonsignificant trend toward lower development of antidrug antibodies with combination therapy (risk ratio 0.72 with infliximab and 0.71 with adalimumab). This trend is in line with adult studies and adds substantially to the pediatric literature on this topic, the researchers note.

No differences in patient-reported outcomes were observed. There were slightly more adverse events with combination therapy, as expected, but fewer serious adverse events.
 

Shared decision-making

Dr. Kappelman noted that the study was not designed to answer the question of which is better – adalimumab plus methotrexate or infliximab alone.

“This is an area for future research. At this point, we believe it is an individualized decision, and appropriate counseling is needed to support shared decision-making,” he said.

The trial was not designed to evaluate the role of proactive therapeutic drug monitoring. However, proactive TDM is endorsed in the ImproveCareNow Model IBD Care guidelines and was considered standard of care at the 35 study sites.

The findings “suggest strong consideration of using combination therapy for pediatric Crohn’s disease patients initiating adalimumab, but not infliximab,” Dr. Kappelman and colleagues say.

“Dissemination and implementation of these findings should lead to improved outcomes in this patient population, including consideration of deimplementation of combination therapy in infliximab-treated patients,” they add.

The decision about which approach to use is still very dependent on patients and their providers, Dr. Kurowski said.

“The study shows that you can safely use infliximab as monotherapy, with low risk of antibody formation, while utilizing proactive therapeutic drug monitoring and dose optimization,” he said. “The study also shows that adalimumab in combination with low-dose methotrexate can be strongly considered when needed.”

The researchers’ standardization of methotrexate doses by weight “is another significant contribution and provides a guide for clinicians,” Dr. Kurowski added.

The study was funded by grants from the Patient-Centered Outcomes Research Institute, the Helmsley Charitable Trust, and National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Kappelman has consulted for AbbVie, Janssen, Pfizer, Takeda, and Lilly; holds shares in Johnson & Johnson; and has received research support from Pfizer, Takeda, Janssen, AbbVie, Lilly, Genentech, Boehringer Ingelheim, Bristol-Myers Squibb, Celtrion, and Arena Pharmaceuticals. Dr. Kurowski reports no relevant financial relationships.

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

Findings from a landmark clinical trial in pediatric Crohn’s disease show a clear benefit of adding methotrexate to treatment with the tumor necrosis factor inhibitor (TNFi) adalimumab (Humira), but not to infliximab therapy.

Children initiating treatment with adalimumab plus a low dose of methotrexate experienced a twofold reduction in treatment failure, note the authors of the largest, double-blind, randomized trial to date in pediatric Crohn’s disease. However, children initiating infliximab, another TNFi, had similar outcomes with or without methotrexate.

“We believe these results are practice changing,” said principal investigator Michael Kappelman, MD, MPH, professor of pediatrics at University of North Carolina.

All patients with pediatric Crohn’s disease starting on adalimumab, and their parents, should be informed that combining the drug with low-dose oral methotrexate improves treatment effectiveness, he said.

“Those without contraindications should be offered combination therapy, and shared decision-making should be incorporated into final treatment decisions. In contrast, most patients starting infliximab are not likely to experience added benefits from low-dose oral methotrexate,” Dr. Kappelman added.

The study was published online in Gastroenterology and was presented in May in Chicago at the annual Digestive Disease Week® (DDW).

Impactful study

“This is an important study, published in a very high-ranking journal, that will have a huge impact on how we practice,” Jacob Kurowski, MD, department of pediatric gastroenterology, hepatology and nutrition, Cleveland Clinic Children’s, who wasn’t involved in the study, said.

Treatment with a TNFi, including infliximab and adalimumab, is a mainstay of pediatric Crohn’s disease therapy. However, not all patients achieve remission, and many lose response over time.

The current trial compared the effectiveness and safety of adding a low-dose of oral methotrexate to adalimumab or infliximab vs. TNFi therapy alone in 297 children with Crohn’s disease. The mean age was 13.9 years, and about two-thirds were boys. None had a prior history of TNFi therapy.

Participants initiating infliximab or adalimumab were randomly allocated (1:1) to oral methotrexate or placebo. Of them, 110 infliximab initiators and 46 adalimumab initiators received methotrexate, while 102 infliximab initiators and 39 adalimumab initiators were given placebo. Methotrexate was administered as a weekly dose of 15 mg for children weighing 40 kg or more, 12.5 mg for children 30 kg to less than 40 kg, and 10 mg for children 20 kg to less than 30 kg. All participants received pretreatment with ondansetron 4 mg (or placebo) to prevent nausea and folic acid (1 mg per day). Participants were followed for 12-36 months.

The primary outcome was a failure to achieve or maintain steroid-free remission defined by occurrence of any of the following:

• Short Pediatric Crohn’s Disease Activity Index (SPCDAI) score of less than 15 by week 26.
• Failure to complete a steroid taper by week 16.
• SPCDAI score of 15 or higher as a result of active Crohn’s disease at two or more consecutive visits beyond week 26.
• Hospitalization or surgery for Crohn’s disease beyond week 26.
• Use of corticosteroids for Crohn’s disease for 10 or more weeks cumulatively beyond week 16.
• Discontinuation of anti-TNF and/or study drug for lack of effectiveness or toxicity.

Overall, 88 of 297 children (30%) experienced treatment failure, including 57 of 212 (27%) on infliximab and 31 of 85 (36%) on adalimumab. Overall, 40 of 156 children (26%) on combination therapy and 48 of 141 (34%) on monotherapy experienced treatment failure.

Kaplan Meier analysis of the overall population showed a nonsignificant trend toward lower event rates with combination therapy (hazard ratio, 0.69; 95% confidence interval, 0.45-1.05; P = .08).

After stratification by TNFi, there was no difference in time to treatment failure among infliximab initiators between combination and monotherapy (HR, 0.93; 95% CI, 0.55-1.56; P = .78). In contrast, among adalimumab initiators, combination therapy was significantly associated with a longer time to treatment failure (HR, 0.40; 95% CI 0.19-0.81; P = .01).

There was a nonsignificant trend toward lower development of antidrug antibodies with combination therapy (risk ratio 0.72 with infliximab and 0.71 with adalimumab). This trend is in line with adult studies and adds substantially to the pediatric literature on this topic, the researchers note.

No differences in patient-reported outcomes were observed. There were slightly more adverse events with combination therapy, as expected, but fewer serious adverse events.
 

Shared decision-making

Dr. Kappelman noted that the study was not designed to answer the question of which is better – adalimumab plus methotrexate or infliximab alone.

“This is an area for future research. At this point, we believe it is an individualized decision, and appropriate counseling is needed to support shared decision-making,” he said.

The trial was not designed to evaluate the role of proactive therapeutic drug monitoring. However, proactive TDM is endorsed in the ImproveCareNow Model IBD Care guidelines and was considered standard of care at the 35 study sites.

The findings “suggest strong consideration of using combination therapy for pediatric Crohn’s disease patients initiating adalimumab, but not infliximab,” Dr. Kappelman and colleagues say.

“Dissemination and implementation of these findings should lead to improved outcomes in this patient population, including consideration of deimplementation of combination therapy in infliximab-treated patients,” they add.

The decision about which approach to use is still very dependent on patients and their providers, Dr. Kurowski said.

“The study shows that you can safely use infliximab as monotherapy, with low risk of antibody formation, while utilizing proactive therapeutic drug monitoring and dose optimization,” he said. “The study also shows that adalimumab in combination with low-dose methotrexate can be strongly considered when needed.”

The researchers’ standardization of methotrexate doses by weight “is another significant contribution and provides a guide for clinicians,” Dr. Kurowski added.

The study was funded by grants from the Patient-Centered Outcomes Research Institute, the Helmsley Charitable Trust, and National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Kappelman has consulted for AbbVie, Janssen, Pfizer, Takeda, and Lilly; holds shares in Johnson & Johnson; and has received research support from Pfizer, Takeda, Janssen, AbbVie, Lilly, Genentech, Boehringer Ingelheim, Bristol-Myers Squibb, Celtrion, and Arena Pharmaceuticals. Dr. Kurowski reports no relevant financial relationships.

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

CHICAGO – In celiac disease, one of the most promising areas of research includes the development of treatments that target HLA-DQ2 gene variants associated with the condition.

There are a number of clinical trials underway, including one for the investigational drug TPM502, which carries three gluten-specific antigenic peptides with overlapping T-cell epitopes for the HLA-DQ2.5 gene. And, research is underway for the novel KAN-101, which aims to restore the immune tolerance of gluten by targeting receptors on the liver. It received Fast Track designation by the Food and Drug Administration in 2022.

During the annual Digestive Disease Week® (DDW), researchers shared the results from a new proof-of-concept study for DONQ52, a bispecific antibody that targets HLA-DQ2.5. DONQ52 was found to be highly effective in blocking gluten-specific T cells, said investigator Jason A. Tye-Din, PhD, a researcher with The Walter and Eliza Hall Institute of Medical Research, Melbourne, and an investigator with Chugai Pharmaceutical, which is funding the DONQ52 research which has since advanced to a phase 1 study of 56 patients.

There are no existing drug therapies for celiac disease, which leaves patients with a lifelong, and strict, gluten-free diet as treatment. This strategy, however, often fails to induce mucosal healing or symptom control, and has stimulated a search for novel therapies, said Melinda Y. Hardy, PhD, a postdoctoral researcher with the University of Melbourne, and the first author of the DONQ52 study. While targeting the gluten-specific immune response is highly attractive, it presents safety and pharmacokinetic challenges, so a better alternative would be to develop antibodies that selectively bind to HLA-DQ2.5, which is found in 80%-90% of celiac disease patients, she said. DONQ52 blocks at least 25 gluten peptides, and binds specifically to complexes of HLA-DQ2.5 and a range of immunogenic gluten peptides.

The study included 20 patients who consumed wheat bread for 3 days. Blood samples were taken 1 day before the start of the trial and 6 days after it concluded. Twenty patients were found to be wheat challenged, 10 were barley challenged, and 14 were rye challenged.

All were tested for gluten-specific T-cell responses in the presence or absence of DONQ52, which was designed to reduce the wheat-specific T-cell response because 90% of gluten intake is from wheat. “If you have celiac disease, you have a reservoir of these gluten-specific T cells. When you eat gluten, they’ll be activated and switched on and that’s what we want to block,” Dr. Tye-Din said.

The main assessment – a day 6 wheat challenge among 15 responders – revealed a more than 80% reduction in T-cell responses to a peptide cocktail. DONQ52 also reduced barley and rye T cell responses in a day 6 challenge, although to a lesser degree (40%/80%).

“DONQ52 is designed to target individual peptides that trigger the disease, and we showed that it did it very well to the wheat peptides, well over 80%. That’s a very impressive reduction in responses,” he said. A further test among 20 samples showed that DONQ52 did not activate T-cells nonspecifically. “You don’t want to trigger an unnecessary response,” Dr. Tye-Din added.

“DONQ52 effectively reduces activation of wheat gluten-specific T cells. It also has broad reactivity extending to barley and rye T-cell epitopes,” said Dr. Hardy.

The study was funded by Chugai Pharmaceutical. Dr. Hardy is a coinventor on a provisional patent describing oats peptides in celiac disease therapeutics and diagnostics. Dr. Tye-Din disclosed associations with Chugai, Genentech, Janssen, and Takeda, among others.

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.

CHICAGO – In celiac disease, one of the most promising areas of research includes the development of treatments that target HLA-DQ2 gene variants associated with the condition.

There are a number of clinical trials underway, including one for the investigational drug TPM502, which carries three gluten-specific antigenic peptides with overlapping T-cell epitopes for the HLA-DQ2.5 gene. And, research is underway for the novel KAN-101, which aims to restore the immune tolerance of gluten by targeting receptors on the liver. It received Fast Track designation by the Food and Drug Administration in 2022.

During the annual Digestive Disease Week® (DDW), researchers shared the results from a new proof-of-concept study for DONQ52, a bispecific antibody that targets HLA-DQ2.5. DONQ52 was found to be highly effective in blocking gluten-specific T cells, said investigator Jason A. Tye-Din, PhD, a researcher with The Walter and Eliza Hall Institute of Medical Research, Melbourne, and an investigator with Chugai Pharmaceutical, which is funding the DONQ52 research which has since advanced to a phase 1 study of 56 patients.

There are no existing drug therapies for celiac disease, which leaves patients with a lifelong, and strict, gluten-free diet as treatment. This strategy, however, often fails to induce mucosal healing or symptom control, and has stimulated a search for novel therapies, said Melinda Y. Hardy, PhD, a postdoctoral researcher with the University of Melbourne, and the first author of the DONQ52 study. While targeting the gluten-specific immune response is highly attractive, it presents safety and pharmacokinetic challenges, so a better alternative would be to develop antibodies that selectively bind to HLA-DQ2.5, which is found in 80%-90% of celiac disease patients, she said. DONQ52 blocks at least 25 gluten peptides, and binds specifically to complexes of HLA-DQ2.5 and a range of immunogenic gluten peptides.

The study included 20 patients who consumed wheat bread for 3 days. Blood samples were taken 1 day before the start of the trial and 6 days after it concluded. Twenty patients were found to be wheat challenged, 10 were barley challenged, and 14 were rye challenged.

All were tested for gluten-specific T-cell responses in the presence or absence of DONQ52, which was designed to reduce the wheat-specific T-cell response because 90% of gluten intake is from wheat. “If you have celiac disease, you have a reservoir of these gluten-specific T cells. When you eat gluten, they’ll be activated and switched on and that’s what we want to block,” Dr. Tye-Din said.

The main assessment – a day 6 wheat challenge among 15 responders – revealed a more than 80% reduction in T-cell responses to a peptide cocktail. DONQ52 also reduced barley and rye T cell responses in a day 6 challenge, although to a lesser degree (40%/80%).

“DONQ52 is designed to target individual peptides that trigger the disease, and we showed that it did it very well to the wheat peptides, well over 80%. That’s a very impressive reduction in responses,” he said. A further test among 20 samples showed that DONQ52 did not activate T-cells nonspecifically. “You don’t want to trigger an unnecessary response,” Dr. Tye-Din added.

“DONQ52 effectively reduces activation of wheat gluten-specific T cells. It also has broad reactivity extending to barley and rye T-cell epitopes,” said Dr. Hardy.

The study was funded by Chugai Pharmaceutical. Dr. Hardy is a coinventor on a provisional patent describing oats peptides in celiac disease therapeutics and diagnostics. Dr. Tye-Din disclosed associations with Chugai, Genentech, Janssen, and Takeda, among others.

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.

CHICAGO – In celiac disease, one of the most promising areas of research includes the development of treatments that target HLA-DQ2 gene variants associated with the condition.

There are a number of clinical trials underway, including one for the investigational drug TPM502, which carries three gluten-specific antigenic peptides with overlapping T-cell epitopes for the HLA-DQ2.5 gene. And, research is underway for the novel KAN-101, which aims to restore the immune tolerance of gluten by targeting receptors on the liver. It received Fast Track designation by the Food and Drug Administration in 2022.

During the annual Digestive Disease Week® (DDW), researchers shared the results from a new proof-of-concept study for DONQ52, a bispecific antibody that targets HLA-DQ2.5. DONQ52 was found to be highly effective in blocking gluten-specific T cells, said investigator Jason A. Tye-Din, PhD, a researcher with The Walter and Eliza Hall Institute of Medical Research, Melbourne, and an investigator with Chugai Pharmaceutical, which is funding the DONQ52 research which has since advanced to a phase 1 study of 56 patients.

There are no existing drug therapies for celiac disease, which leaves patients with a lifelong, and strict, gluten-free diet as treatment. This strategy, however, often fails to induce mucosal healing or symptom control, and has stimulated a search for novel therapies, said Melinda Y. Hardy, PhD, a postdoctoral researcher with the University of Melbourne, and the first author of the DONQ52 study. While targeting the gluten-specific immune response is highly attractive, it presents safety and pharmacokinetic challenges, so a better alternative would be to develop antibodies that selectively bind to HLA-DQ2.5, which is found in 80%-90% of celiac disease patients, she said. DONQ52 blocks at least 25 gluten peptides, and binds specifically to complexes of HLA-DQ2.5 and a range of immunogenic gluten peptides.

The study included 20 patients who consumed wheat bread for 3 days. Blood samples were taken 1 day before the start of the trial and 6 days after it concluded. Twenty patients were found to be wheat challenged, 10 were barley challenged, and 14 were rye challenged.

All were tested for gluten-specific T-cell responses in the presence or absence of DONQ52, which was designed to reduce the wheat-specific T-cell response because 90% of gluten intake is from wheat. “If you have celiac disease, you have a reservoir of these gluten-specific T cells. When you eat gluten, they’ll be activated and switched on and that’s what we want to block,” Dr. Tye-Din said.

The main assessment – a day 6 wheat challenge among 15 responders – revealed a more than 80% reduction in T-cell responses to a peptide cocktail. DONQ52 also reduced barley and rye T cell responses in a day 6 challenge, although to a lesser degree (40%/80%).

“DONQ52 is designed to target individual peptides that trigger the disease, and we showed that it did it very well to the wheat peptides, well over 80%. That’s a very impressive reduction in responses,” he said. A further test among 20 samples showed that DONQ52 did not activate T-cells nonspecifically. “You don’t want to trigger an unnecessary response,” Dr. Tye-Din added.

“DONQ52 effectively reduces activation of wheat gluten-specific T cells. It also has broad reactivity extending to barley and rye T-cell epitopes,” said Dr. Hardy.

The study was funded by Chugai Pharmaceutical. Dr. Hardy is a coinventor on a provisional patent describing oats peptides in celiac disease therapeutics and diagnostics. Dr. Tye-Din disclosed associations with Chugai, Genentech, Janssen, and Takeda, among others.

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.

CHICAGO – Irrespective of the number of infliximab switches, multiple, successive switches from infliximab originator to biosimilars are effective and safe in patients with inflammatory bowel disease (IBD), according to analysis of a real world IBD cohort presented at the annual Digestive Disease Week® (DDW).

“These findings are of major socioeconomic importance, especially in low- and middle-income countries where the access to health care may be limited,” said study author Beatriz Gros, MD, an advanced clinical fellow in gastroenterology at Western General Hospital of Edinburgh.

While switching from originator infliximab to biosimilar infliximab is known observationally to be safe and effective, data on single and double switches are scarce, and are lacking on triple switches. Infliximab, the first monoclonal antibody biologic inhibiting anti–tumor necrosis factor was approved by the Food and Drug Administration and by the European Medicines Agency in 1998 and 1999, respectively. Economic pressures led to the development of biosimilars, with the first EMA approval in 2013 and FDA approval in 2016. Uptake in Europe has been broad and expanding following evidence that early therapy is associated with better outcomes. In the United States, a recent RAND Corporation study estimated savings to be $38.4 billion or 5.9% of projected total spending on biologics from 2021 to 2025, Dr. Gros reported.

The Edinburgh IBD unit has undertaken three switch programs starting with originator to CT-P13 in 2016, CT-P13 to SB2 in 2020, and SB2 to CT-P13 in 2021. Their prospective, observational cohort study assessing safety and efficacy after switching from SB2 to CT-P13 has, as a primary endpoint, CT-P13 persistence following the switch from SB2. Stratification of persistence according to the number of switches, effectiveness, immunogenicity, and safety were secondary outcomes.

During routine virtual biologic clinic care, researchers collected clinical disease activity scores (Harvey-Bradshaw Index; partial Mayo score), laboratory parameters (including C-reactive protein [CRP], IFX trough, and antibody levels), and fecal calprotectin on 297 IBD patients (median age, 37 years; 61.6% male). Among them, 67 had three switches, 138 had two switches, and 92 had one switch. Median disease duration was longer (11.4 years) for those with three switches than for two switches (6.3 years) or one switch (2.3 years) (P < .0001)

Infliximab persistence

Out of 297 patients, 269 (90.6%) remained on infliximab at week 24. Reasons for discontinuing treatment were immunogenicity (15/297; 5.1%), secondary loss of response (7/297, 2.4%), adverse events (3/297, 1%), patient’s choice (2/297, 0.7%), and primary nonresponse (1/297, 0.3%).

While infliximab persistence was 82.6%, 92.8% and 97% in patients with one, two and three infliximab switches, respectively (P = .003), after confounder adjustment, the number of switches was not independently associated with infliximab persistence, Dr. Gros said.

What factors actually did predict infliximab persistence? Multivariable analysis identified absence of biochemical remission (CRP > 5 mg/L [hazard ratio, 3.21; 95% confidence interval, 1.43-7.24]); a diagnosis of ulcerative colitis/ inflammatory bowel disease unclassified (HR, 2.69; 95% CI, 1.19-6.06), detectable antibodies against infliximab at switch (HR, 5.81; 95% CI, 2.27-12.84) and time on infliximab (HR, 0.77; 95% CI, 0.62-0.95) as independent predictors for infliximab persistence rather than number of infliximab switches.

Clinical (P = .77), biochemical (P = .75), and fecal biomarker (P = .63) remission rates, Dr. Gros reported, were comparable at baseline, week 12 and week 24, with baseline rates for clinical, biochemical and fecal biomarker remission at 79.4%, 85.2%, and 85.3%, respectively, and at 81%, 86.5%, and 84.4% at week 24.

“Immunogenicity has been a major concern regarding multiple switches, although both our study and previous literature demonstrated that this seemed to be not happening more often to patients who had multiple switches compared to those who had fewer or none. Our study found that, of the 14 (7.1%) patients who developed de novo antibodies, none of them underwent three switches,” she said.

Dr. Gros disclosed relationships with Pfizer, AbbVie, and Jansen.

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.

CHICAGO – Irrespective of the number of infliximab switches, multiple, successive switches from infliximab originator to biosimilars are effective and safe in patients with inflammatory bowel disease (IBD), according to analysis of a real world IBD cohort presented at the annual Digestive Disease Week® (DDW).

“These findings are of major socioeconomic importance, especially in low- and middle-income countries where the access to health care may be limited,” said study author Beatriz Gros, MD, an advanced clinical fellow in gastroenterology at Western General Hospital of Edinburgh.

While switching from originator infliximab to biosimilar infliximab is known observationally to be safe and effective, data on single and double switches are scarce, and are lacking on triple switches. Infliximab, the first monoclonal antibody biologic inhibiting anti–tumor necrosis factor was approved by the Food and Drug Administration and by the European Medicines Agency in 1998 and 1999, respectively. Economic pressures led to the development of biosimilars, with the first EMA approval in 2013 and FDA approval in 2016. Uptake in Europe has been broad and expanding following evidence that early therapy is associated with better outcomes. In the United States, a recent RAND Corporation study estimated savings to be $38.4 billion or 5.9% of projected total spending on biologics from 2021 to 2025, Dr. Gros reported.

The Edinburgh IBD unit has undertaken three switch programs starting with originator to CT-P13 in 2016, CT-P13 to SB2 in 2020, and SB2 to CT-P13 in 2021. Their prospective, observational cohort study assessing safety and efficacy after switching from SB2 to CT-P13 has, as a primary endpoint, CT-P13 persistence following the switch from SB2. Stratification of persistence according to the number of switches, effectiveness, immunogenicity, and safety were secondary outcomes.

During routine virtual biologic clinic care, researchers collected clinical disease activity scores (Harvey-Bradshaw Index; partial Mayo score), laboratory parameters (including C-reactive protein [CRP], IFX trough, and antibody levels), and fecal calprotectin on 297 IBD patients (median age, 37 years; 61.6% male). Among them, 67 had three switches, 138 had two switches, and 92 had one switch. Median disease duration was longer (11.4 years) for those with three switches than for two switches (6.3 years) or one switch (2.3 years) (P < .0001)

Infliximab persistence

Out of 297 patients, 269 (90.6%) remained on infliximab at week 24. Reasons for discontinuing treatment were immunogenicity (15/297; 5.1%), secondary loss of response (7/297, 2.4%), adverse events (3/297, 1%), patient’s choice (2/297, 0.7%), and primary nonresponse (1/297, 0.3%).

While infliximab persistence was 82.6%, 92.8% and 97% in patients with one, two and three infliximab switches, respectively (P = .003), after confounder adjustment, the number of switches was not independently associated with infliximab persistence, Dr. Gros said.

What factors actually did predict infliximab persistence? Multivariable analysis identified absence of biochemical remission (CRP > 5 mg/L [hazard ratio, 3.21; 95% confidence interval, 1.43-7.24]); a diagnosis of ulcerative colitis/ inflammatory bowel disease unclassified (HR, 2.69; 95% CI, 1.19-6.06), detectable antibodies against infliximab at switch (HR, 5.81; 95% CI, 2.27-12.84) and time on infliximab (HR, 0.77; 95% CI, 0.62-0.95) as independent predictors for infliximab persistence rather than number of infliximab switches.

Clinical (P = .77), biochemical (P = .75), and fecal biomarker (P = .63) remission rates, Dr. Gros reported, were comparable at baseline, week 12 and week 24, with baseline rates for clinical, biochemical and fecal biomarker remission at 79.4%, 85.2%, and 85.3%, respectively, and at 81%, 86.5%, and 84.4% at week 24.

“Immunogenicity has been a major concern regarding multiple switches, although both our study and previous literature demonstrated that this seemed to be not happening more often to patients who had multiple switches compared to those who had fewer or none. Our study found that, of the 14 (7.1%) patients who developed de novo antibodies, none of them underwent three switches,” she said.

Dr. Gros disclosed relationships with Pfizer, AbbVie, and Jansen.

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.

CHICAGO – Irrespective of the number of infliximab switches, multiple, successive switches from infliximab originator to biosimilars are effective and safe in patients with inflammatory bowel disease (IBD), according to analysis of a real world IBD cohort presented at the annual Digestive Disease Week® (DDW).

“These findings are of major socioeconomic importance, especially in low- and middle-income countries where the access to health care may be limited,” said study author Beatriz Gros, MD, an advanced clinical fellow in gastroenterology at Western General Hospital of Edinburgh.

While switching from originator infliximab to biosimilar infliximab is known observationally to be safe and effective, data on single and double switches are scarce, and are lacking on triple switches. Infliximab, the first monoclonal antibody biologic inhibiting anti–tumor necrosis factor was approved by the Food and Drug Administration and by the European Medicines Agency in 1998 and 1999, respectively. Economic pressures led to the development of biosimilars, with the first EMA approval in 2013 and FDA approval in 2016. Uptake in Europe has been broad and expanding following evidence that early therapy is associated with better outcomes. In the United States, a recent RAND Corporation study estimated savings to be $38.4 billion or 5.9% of projected total spending on biologics from 2021 to 2025, Dr. Gros reported.

The Edinburgh IBD unit has undertaken three switch programs starting with originator to CT-P13 in 2016, CT-P13 to SB2 in 2020, and SB2 to CT-P13 in 2021. Their prospective, observational cohort study assessing safety and efficacy after switching from SB2 to CT-P13 has, as a primary endpoint, CT-P13 persistence following the switch from SB2. Stratification of persistence according to the number of switches, effectiveness, immunogenicity, and safety were secondary outcomes.

During routine virtual biologic clinic care, researchers collected clinical disease activity scores (Harvey-Bradshaw Index; partial Mayo score), laboratory parameters (including C-reactive protein [CRP], IFX trough, and antibody levels), and fecal calprotectin on 297 IBD patients (median age, 37 years; 61.6% male). Among them, 67 had three switches, 138 had two switches, and 92 had one switch. Median disease duration was longer (11.4 years) for those with three switches than for two switches (6.3 years) or one switch (2.3 years) (P < .0001)

Infliximab persistence

Out of 297 patients, 269 (90.6%) remained on infliximab at week 24. Reasons for discontinuing treatment were immunogenicity (15/297; 5.1%), secondary loss of response (7/297, 2.4%), adverse events (3/297, 1%), patient’s choice (2/297, 0.7%), and primary nonresponse (1/297, 0.3%).

While infliximab persistence was 82.6%, 92.8% and 97% in patients with one, two and three infliximab switches, respectively (P = .003), after confounder adjustment, the number of switches was not independently associated with infliximab persistence, Dr. Gros said.

What factors actually did predict infliximab persistence? Multivariable analysis identified absence of biochemical remission (CRP > 5 mg/L [hazard ratio, 3.21; 95% confidence interval, 1.43-7.24]); a diagnosis of ulcerative colitis/ inflammatory bowel disease unclassified (HR, 2.69; 95% CI, 1.19-6.06), detectable antibodies against infliximab at switch (HR, 5.81; 95% CI, 2.27-12.84) and time on infliximab (HR, 0.77; 95% CI, 0.62-0.95) as independent predictors for infliximab persistence rather than number of infliximab switches.

Clinical (P = .77), biochemical (P = .75), and fecal biomarker (P = .63) remission rates, Dr. Gros reported, were comparable at baseline, week 12 and week 24, with baseline rates for clinical, biochemical and fecal biomarker remission at 79.4%, 85.2%, and 85.3%, respectively, and at 81%, 86.5%, and 84.4% at week 24.

“Immunogenicity has been a major concern regarding multiple switches, although both our study and previous literature demonstrated that this seemed to be not happening more often to patients who had multiple switches compared to those who had fewer or none. Our study found that, of the 14 (7.1%) patients who developed de novo antibodies, none of them underwent three switches,” she said.

Dr. Gros disclosed relationships with Pfizer, AbbVie, and Jansen.

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.

CHICAGO – Only 1%-3% of patients who have had bariatric surgery take Food and Drug Administration–approved antiobesity medications even though 25% of patients experience significant weight regain within a few years of surgery, according to a study presented at the annual Digestive Disease Week® meeting.

Obesity is a chronic, relapsing condition that must be treated as such, said the study’s author Stephen A. Firkins, MD, a fellow of gastroenterology and hepatology at the Cleveland Clinic. “Barriers to antiobesity medications must be identified.”

“If a quarter of all patients experience weight regain and another quarter experience insufficient weight loss – but only 5% are being prescribed an FDA-approved AOM – that means there’s underutilization,” Dr. Firkins said.

Data from the National Health and Nutrition Examination Survey show that 30.7% of all men and women in the United States are overweight and of these, 42.4% are obese. For the severely obese, bariatric surgery, including sleeve gastrectomy, Roux-en-Y gastric bypass, and one anastomosis gastric bypass, are viable options with differing degrees of long-term success.

And while antiobesity medications such as orlistat (Xenical, Alli), phentermine/topiramate (Qsymia), naltrexone/bupropion (Contrave), liraglutide (Saxenda), semaglutide (Wegovy), and setmelanotide (Imcivree), may be considered before bariatric surgery, there are questions about the need for its use after surgery.

“While these are often employed or considered presurgically, there is a paucity of literature describing their utilization postsurgically, particularly in regards to newer antiobesity medications such as the [glucagonlike peptide–1] receptor agonists,” Dr. Firkins said.

The aim of Dr. Firkins’ analysis of the large, publicly available IBM Explorys Electronic Health Record, which included 59,160 adult post–bariatric surgery patients, was to identify postoperative weight control medication use and trends among different populations.

He found rates of postsurgical weight control medication use at 8% for topiramate (off label), 2.9% for liraglutide, 1.03% for phentermine/topiramate, 0.95% for naltrexone/bupropion, 0.52% for semaglutide and 0.1% for orlistat. Rates of topiramate use were higher for patients in the 35- 39-year range, and for orlistat and liraglutide in the 65- to 69-year range.

The differences, Dr. Firkins said, were likely related to side-effect profiles and accumulations of comorbidities with advancing age. Black patients were more likely to be prescribed the medications. Also, further analysis showed a significantly higher use of these medications among individuals with hypertension, diabetes, and hyperlipidemia.

The analyses raised several questions for future study, Dr. Firkins said: “What is the optimal timing of antiobesity medication initiation? Is it at the plateau of peak weight loss typically seen at 1-3 years post surgery? Or, after weight is regained? What is the phenotype of patients who are going to be good responders versus poor responders to a particular medication category?”

“Upon recognition of insufficient weight loss/weight regain, a multidisciplinary strategy towards management is warranted, including behavioral and dietary counseling, and consideration of AOM early use, as well as endoscopic or surgical revision,” he said.

Dr. Firkins had no disclosures.

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.

CHICAGO – Only 1%-3% of patients who have had bariatric surgery take Food and Drug Administration–approved antiobesity medications even though 25% of patients experience significant weight regain within a few years of surgery, according to a study presented at the annual Digestive Disease Week® meeting.

Obesity is a chronic, relapsing condition that must be treated as such, said the study’s author Stephen A. Firkins, MD, a fellow of gastroenterology and hepatology at the Cleveland Clinic. “Barriers to antiobesity medications must be identified.”

“If a quarter of all patients experience weight regain and another quarter experience insufficient weight loss – but only 5% are being prescribed an FDA-approved AOM – that means there’s underutilization,” Dr. Firkins said.

Data from the National Health and Nutrition Examination Survey show that 30.7% of all men and women in the United States are overweight and of these, 42.4% are obese. For the severely obese, bariatric surgery, including sleeve gastrectomy, Roux-en-Y gastric bypass, and one anastomosis gastric bypass, are viable options with differing degrees of long-term success.

And while antiobesity medications such as orlistat (Xenical, Alli), phentermine/topiramate (Qsymia), naltrexone/bupropion (Contrave), liraglutide (Saxenda), semaglutide (Wegovy), and setmelanotide (Imcivree), may be considered before bariatric surgery, there are questions about the need for its use after surgery.

“While these are often employed or considered presurgically, there is a paucity of literature describing their utilization postsurgically, particularly in regards to newer antiobesity medications such as the [glucagonlike peptide–1] receptor agonists,” Dr. Firkins said.

The aim of Dr. Firkins’ analysis of the large, publicly available IBM Explorys Electronic Health Record, which included 59,160 adult post–bariatric surgery patients, was to identify postoperative weight control medication use and trends among different populations.

He found rates of postsurgical weight control medication use at 8% for topiramate (off label), 2.9% for liraglutide, 1.03% for phentermine/topiramate, 0.95% for naltrexone/bupropion, 0.52% for semaglutide and 0.1% for orlistat. Rates of topiramate use were higher for patients in the 35- 39-year range, and for orlistat and liraglutide in the 65- to 69-year range.

The differences, Dr. Firkins said, were likely related to side-effect profiles and accumulations of comorbidities with advancing age. Black patients were more likely to be prescribed the medications. Also, further analysis showed a significantly higher use of these medications among individuals with hypertension, diabetes, and hyperlipidemia.

The analyses raised several questions for future study, Dr. Firkins said: “What is the optimal timing of antiobesity medication initiation? Is it at the plateau of peak weight loss typically seen at 1-3 years post surgery? Or, after weight is regained? What is the phenotype of patients who are going to be good responders versus poor responders to a particular medication category?”

“Upon recognition of insufficient weight loss/weight regain, a multidisciplinary strategy towards management is warranted, including behavioral and dietary counseling, and consideration of AOM early use, as well as endoscopic or surgical revision,” he said.

Dr. Firkins had no disclosures.

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.

CHICAGO – Only 1%-3% of patients who have had bariatric surgery take Food and Drug Administration–approved antiobesity medications even though 25% of patients experience significant weight regain within a few years of surgery, according to a study presented at the annual Digestive Disease Week® meeting.

Obesity is a chronic, relapsing condition that must be treated as such, said the study’s author Stephen A. Firkins, MD, a fellow of gastroenterology and hepatology at the Cleveland Clinic. “Barriers to antiobesity medications must be identified.”

“If a quarter of all patients experience weight regain and another quarter experience insufficient weight loss – but only 5% are being prescribed an FDA-approved AOM – that means there’s underutilization,” Dr. Firkins said.

Data from the National Health and Nutrition Examination Survey show that 30.7% of all men and women in the United States are overweight and of these, 42.4% are obese. For the severely obese, bariatric surgery, including sleeve gastrectomy, Roux-en-Y gastric bypass, and one anastomosis gastric bypass, are viable options with differing degrees of long-term success.

And while antiobesity medications such as orlistat (Xenical, Alli), phentermine/topiramate (Qsymia), naltrexone/bupropion (Contrave), liraglutide (Saxenda), semaglutide (Wegovy), and setmelanotide (Imcivree), may be considered before bariatric surgery, there are questions about the need for its use after surgery.

“While these are often employed or considered presurgically, there is a paucity of literature describing their utilization postsurgically, particularly in regards to newer antiobesity medications such as the [glucagonlike peptide–1] receptor agonists,” Dr. Firkins said.

The aim of Dr. Firkins’ analysis of the large, publicly available IBM Explorys Electronic Health Record, which included 59,160 adult post–bariatric surgery patients, was to identify postoperative weight control medication use and trends among different populations.

He found rates of postsurgical weight control medication use at 8% for topiramate (off label), 2.9% for liraglutide, 1.03% for phentermine/topiramate, 0.95% for naltrexone/bupropion, 0.52% for semaglutide and 0.1% for orlistat. Rates of topiramate use were higher for patients in the 35- 39-year range, and for orlistat and liraglutide in the 65- to 69-year range.

The differences, Dr. Firkins said, were likely related to side-effect profiles and accumulations of comorbidities with advancing age. Black patients were more likely to be prescribed the medications. Also, further analysis showed a significantly higher use of these medications among individuals with hypertension, diabetes, and hyperlipidemia.

The analyses raised several questions for future study, Dr. Firkins said: “What is the optimal timing of antiobesity medication initiation? Is it at the plateau of peak weight loss typically seen at 1-3 years post surgery? Or, after weight is regained? What is the phenotype of patients who are going to be good responders versus poor responders to a particular medication category?”

“Upon recognition of insufficient weight loss/weight regain, a multidisciplinary strategy towards management is warranted, including behavioral and dietary counseling, and consideration of AOM early use, as well as endoscopic or surgical revision,” he said.

Dr. Firkins had no disclosures.

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.

CHICAGO – The regular use of aspirin or other nonsteroidal anti-inflammatory drugs was found to be associated with a lower risk of early-onset conventional and advanced adenomas. The authors say that aspirin could prove to be an effective strategy in preventing early-onset colorectal cancer cases.

“What we have here is a 15% reduction for all adenomas and 33% for those with advanced histology, which to us is quite substantial. We have not seen that much [33%] in previous studies so I would think it definitely needs more study,” said Cassandra D. Fritz, MD, MPHS, a gastroenterologist with Washington University, St. Louis, in an oral presentation given at the annual Digestive Disease Week^®.

“This finding is important given the alarming rise in the incidence and mortality of early-onset colorectal cancer (age < 50 years), and our limited understanding of the underlying drivers to direct prevention efforts,” Dr. Fritz said. Early-onset colorectal cancer cases have doubled since 1995, she said.

The study confirms evidence from 30 years of research that suggests regular aspirin use reduces cancer risk. In patients with Lynch syndrome, the CAPP2 study showed that aspirin has a protective effect against colorectal cancer at 20 years follow-up.

While emerging data have suggested that aspirin use may reduce later-onset colorectal cancer, it was not known if regular aspirin and NSAID use are associated with diminished risk of early-onset conventional adenomas, and especially the high-risk adenomas conferring greater malignant potential known to be the major precursor of early-onset colorectal cancer. An unpublished analysis of molecular markers by the study’s senior author, Yin Cao, ScD, MPH, also of Washington University, found that at least 57% of early-onset colorectal cancers developed from the conventional adenoma-carcinoma pathway.

The objective of the new study was to assess the association between regular aspirin or NSAID use at least twice weekly, with the risk of developing early-onset adenoma. The analysis is based on an evaluation of data from the Nurses’ Health Study II of 32,058 women who had at least one colonoscopy before age 50 (1991-2015). High-risk adenomas included those that were at least 1 cm with tubulovillous/villous histology or high-grade dysplasia, or the presence of at least three adenomas.

There were 1,247 early-onset adenomas, among which 290 were considered high risk. The risk of adenomas among patients who took aspirin or NSAIDs regularly for cardiovascular protection or for inflammatory conditions, was lower than in those who did not take aspirin and/or NSAIDs regularly. While the association was similar for high-risk vs. low-risk adenomas, the benefit was more pronounced for adenomas of tubulovillous/villous histology or with high-grade dysplasia (odds ratio, 0.67; 95% confidence interval, 0.51-0.89), a 33% reduction, compared with tubular adenomas (OR, 0.90; 95% CI, 0.79-1.0; P for heterogeneity = .02).

With later-onset adenomas, risk reduction was confined primarily to large (OR, 0.76; 95% CI, 0.62-0.93) or multiple adenomas (OR, 0.57; 95% CI, 0.40-0.83), but not adenomas of advanced histology (OR, 0.92; 95% CI, 0.73-1.17).

“With colorectal cancer rates increasing, we still don’t have any preventative strategies beyond screening. With this 15% reduction with aspirin/NSAIDS in early-onset adenoma – and particularly for the quite substantial 33% benefit in advanced adenoma with advanced histology, we need to think about a precision-based chemoprevention strategy for early-onset precursors of colorectal cancer,” Dr. Cao said.

The U.S. Preventive Services Task Force issued a new recommendation in 2021 stating that colorectal cancer screening for people with average risk should start 5 years sooner at age 45. “As we know,” Dr. Yin said, “many younger adults are not screened. That’s why we’re looking into potential early-onset colorectal cancer chemopreventative agents.”

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

Dr. Fritz had no disclosures and Dr. Cao listed consulting for Geneoscopy.

CHICAGO – The regular use of aspirin or other nonsteroidal anti-inflammatory drugs was found to be associated with a lower risk of early-onset conventional and advanced adenomas. The authors say that aspirin could prove to be an effective strategy in preventing early-onset colorectal cancer cases.

“What we have here is a 15% reduction for all adenomas and 33% for those with advanced histology, which to us is quite substantial. We have not seen that much [33%] in previous studies so I would think it definitely needs more study,” said Cassandra D. Fritz, MD, MPHS, a gastroenterologist with Washington University, St. Louis, in an oral presentation given at the annual Digestive Disease Week^®.

“This finding is important given the alarming rise in the incidence and mortality of early-onset colorectal cancer (age < 50 years), and our limited understanding of the underlying drivers to direct prevention efforts,” Dr. Fritz said. Early-onset colorectal cancer cases have doubled since 1995, she said.

The study confirms evidence from 30 years of research that suggests regular aspirin use reduces cancer risk. In patients with Lynch syndrome, the CAPP2 study showed that aspirin has a protective effect against colorectal cancer at 20 years follow-up.

While emerging data have suggested that aspirin use may reduce later-onset colorectal cancer, it was not known if regular aspirin and NSAID use are associated with diminished risk of early-onset conventional adenomas, and especially the high-risk adenomas conferring greater malignant potential known to be the major precursor of early-onset colorectal cancer. An unpublished analysis of molecular markers by the study’s senior author, Yin Cao, ScD, MPH, also of Washington University, found that at least 57% of early-onset colorectal cancers developed from the conventional adenoma-carcinoma pathway.

The objective of the new study was to assess the association between regular aspirin or NSAID use at least twice weekly, with the risk of developing early-onset adenoma. The analysis is based on an evaluation of data from the Nurses’ Health Study II of 32,058 women who had at least one colonoscopy before age 50 (1991-2015). High-risk adenomas included those that were at least 1 cm with tubulovillous/villous histology or high-grade dysplasia, or the presence of at least three adenomas.

There were 1,247 early-onset adenomas, among which 290 were considered high risk. The risk of adenomas among patients who took aspirin or NSAIDs regularly for cardiovascular protection or for inflammatory conditions, was lower than in those who did not take aspirin and/or NSAIDs regularly. While the association was similar for high-risk vs. low-risk adenomas, the benefit was more pronounced for adenomas of tubulovillous/villous histology or with high-grade dysplasia (odds ratio, 0.67; 95% confidence interval, 0.51-0.89), a 33% reduction, compared with tubular adenomas (OR, 0.90; 95% CI, 0.79-1.0; P for heterogeneity = .02).

With later-onset adenomas, risk reduction was confined primarily to large (OR, 0.76; 95% CI, 0.62-0.93) or multiple adenomas (OR, 0.57; 95% CI, 0.40-0.83), but not adenomas of advanced histology (OR, 0.92; 95% CI, 0.73-1.17).

“With colorectal cancer rates increasing, we still don’t have any preventative strategies beyond screening. With this 15% reduction with aspirin/NSAIDS in early-onset adenoma – and particularly for the quite substantial 33% benefit in advanced adenoma with advanced histology, we need to think about a precision-based chemoprevention strategy for early-onset precursors of colorectal cancer,” Dr. Cao said.

The U.S. Preventive Services Task Force issued a new recommendation in 2021 stating that colorectal cancer screening for people with average risk should start 5 years sooner at age 45. “As we know,” Dr. Yin said, “many younger adults are not screened. That’s why we’re looking into potential early-onset colorectal cancer chemopreventative agents.”

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

Dr. Fritz had no disclosures and Dr. Cao listed consulting for Geneoscopy.

CHICAGO – The regular use of aspirin or other nonsteroidal anti-inflammatory drugs was found to be associated with a lower risk of early-onset conventional and advanced adenomas. The authors say that aspirin could prove to be an effective strategy in preventing early-onset colorectal cancer cases.

“What we have here is a 15% reduction for all adenomas and 33% for those with advanced histology, which to us is quite substantial. We have not seen that much [33%] in previous studies so I would think it definitely needs more study,” said Cassandra D. Fritz, MD, MPHS, a gastroenterologist with Washington University, St. Louis, in an oral presentation given at the annual Digestive Disease Week^®.

“This finding is important given the alarming rise in the incidence and mortality of early-onset colorectal cancer (age < 50 years), and our limited understanding of the underlying drivers to direct prevention efforts,” Dr. Fritz said. Early-onset colorectal cancer cases have doubled since 1995, she said.

The study confirms evidence from 30 years of research that suggests regular aspirin use reduces cancer risk. In patients with Lynch syndrome, the CAPP2 study showed that aspirin has a protective effect against colorectal cancer at 20 years follow-up.

While emerging data have suggested that aspirin use may reduce later-onset colorectal cancer, it was not known if regular aspirin and NSAID use are associated with diminished risk of early-onset conventional adenomas, and especially the high-risk adenomas conferring greater malignant potential known to be the major precursor of early-onset colorectal cancer. An unpublished analysis of molecular markers by the study’s senior author, Yin Cao, ScD, MPH, also of Washington University, found that at least 57% of early-onset colorectal cancers developed from the conventional adenoma-carcinoma pathway.

The objective of the new study was to assess the association between regular aspirin or NSAID use at least twice weekly, with the risk of developing early-onset adenoma. The analysis is based on an evaluation of data from the Nurses’ Health Study II of 32,058 women who had at least one colonoscopy before age 50 (1991-2015). High-risk adenomas included those that were at least 1 cm with tubulovillous/villous histology or high-grade dysplasia, or the presence of at least three adenomas.

There were 1,247 early-onset adenomas, among which 290 were considered high risk. The risk of adenomas among patients who took aspirin or NSAIDs regularly for cardiovascular protection or for inflammatory conditions, was lower than in those who did not take aspirin and/or NSAIDs regularly. While the association was similar for high-risk vs. low-risk adenomas, the benefit was more pronounced for adenomas of tubulovillous/villous histology or with high-grade dysplasia (odds ratio, 0.67; 95% confidence interval, 0.51-0.89), a 33% reduction, compared with tubular adenomas (OR, 0.90; 95% CI, 0.79-1.0; P for heterogeneity = .02).

With later-onset adenomas, risk reduction was confined primarily to large (OR, 0.76; 95% CI, 0.62-0.93) or multiple adenomas (OR, 0.57; 95% CI, 0.40-0.83), but not adenomas of advanced histology (OR, 0.92; 95% CI, 0.73-1.17).

“With colorectal cancer rates increasing, we still don’t have any preventative strategies beyond screening. With this 15% reduction with aspirin/NSAIDS in early-onset adenoma – and particularly for the quite substantial 33% benefit in advanced adenoma with advanced histology, we need to think about a precision-based chemoprevention strategy for early-onset precursors of colorectal cancer,” Dr. Cao said.

The U.S. Preventive Services Task Force issued a new recommendation in 2021 stating that colorectal cancer screening for people with average risk should start 5 years sooner at age 45. “As we know,” Dr. Yin said, “many younger adults are not screened. That’s why we’re looking into potential early-onset colorectal cancer chemopreventative agents.”

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

Dr. Fritz had no disclosures and Dr. Cao listed consulting for Geneoscopy.

Efficacy and long-term safety data of novel drugs, thiopurine withdrawal, and the effect of high-dose opioid use on outcomes are among the key takeaways in ulcerative colitis from Digestive Disease Week (DDW) 2023, as reported by Dr Joseph Feuerstein, from Harvard Medical School,  in Boston, Massachusetts. 

Dr Feuerstein starts with the QUASAR study of the IL-13 inhibitor guselkumab, which showed that the drug was associated with significantly improved clinical remission over placebo.  

Next, an open-label extension of the True North study demonstrated that the oral S1P receptor modulator ozanimod proved to be safe over a 3-year follow-up period. Another trial examining safety found that withdrawal from thiopurine and vedolizumab combination therapy may not be a viable strategy. 

Dr Feuerstein then turns to a retrospective analysis of older patients who underwent segmental colectomy in which the procedure was associated with low rates of complications and postoperative flares. 

Finally, another retrospective study suggested that, contrary to expectations, high-dose opioid use does not appear to worsen clinical outcomes in acute severe ulcerative colitis. 

--

Joseph D. Feuerstein, MD, Associate Professor of Medicine, Department of Gastroenterology, Harvard Medical School; Attending in Gastroenterology, Center for Inflammatory Bowel Disease, Beth Israel Deaconess Medical Center, Boston, Massachusetts 

Joseph D. Feuerstein, MD, has disclosed no relevant financial relationships. 

Digestive Disease Week® was sponsored by the American Gastroenterological Association, the American Association for the Study of Liver Diseases, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

Efficacy and long-term safety data of novel drugs, thiopurine withdrawal, and the effect of high-dose opioid use on outcomes are among the key takeaways in ulcerative colitis from Digestive Disease Week (DDW) 2023, as reported by Dr Joseph Feuerstein, from Harvard Medical School,  in Boston, Massachusetts. 

Dr Feuerstein starts with the QUASAR study of the IL-13 inhibitor guselkumab, which showed that the drug was associated with significantly improved clinical remission over placebo.  

Next, an open-label extension of the True North study demonstrated that the oral S1P receptor modulator ozanimod proved to be safe over a 3-year follow-up period. Another trial examining safety found that withdrawal from thiopurine and vedolizumab combination therapy may not be a viable strategy. 

Dr Feuerstein then turns to a retrospective analysis of older patients who underwent segmental colectomy in which the procedure was associated with low rates of complications and postoperative flares. 

Finally, another retrospective study suggested that, contrary to expectations, high-dose opioid use does not appear to worsen clinical outcomes in acute severe ulcerative colitis. 

--

Joseph D. Feuerstein, MD, Associate Professor of Medicine, Department of Gastroenterology, Harvard Medical School; Attending in Gastroenterology, Center for Inflammatory Bowel Disease, Beth Israel Deaconess Medical Center, Boston, Massachusetts 

Joseph D. Feuerstein, MD, has disclosed no relevant financial relationships. 

Digestive Disease Week® was sponsored by the American Gastroenterological Association, the American Association for the Study of Liver Diseases, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

Efficacy and long-term safety data of novel drugs, thiopurine withdrawal, and the effect of high-dose opioid use on outcomes are among the key takeaways in ulcerative colitis from Digestive Disease Week (DDW) 2023, as reported by Dr Joseph Feuerstein, from Harvard Medical School,  in Boston, Massachusetts. 

Dr Feuerstein starts with the QUASAR study of the IL-13 inhibitor guselkumab, which showed that the drug was associated with significantly improved clinical remission over placebo.  

Next, an open-label extension of the True North study demonstrated that the oral S1P receptor modulator ozanimod proved to be safe over a 3-year follow-up period. Another trial examining safety found that withdrawal from thiopurine and vedolizumab combination therapy may not be a viable strategy. 

Dr Feuerstein then turns to a retrospective analysis of older patients who underwent segmental colectomy in which the procedure was associated with low rates of complications and postoperative flares. 

Finally, another retrospective study suggested that, contrary to expectations, high-dose opioid use does not appear to worsen clinical outcomes in acute severe ulcerative colitis. 

--

Joseph D. Feuerstein, MD, Associate Professor of Medicine, Department of Gastroenterology, Harvard Medical School; Attending in Gastroenterology, Center for Inflammatory Bowel Disease, Beth Israel Deaconess Medical Center, Boston, Massachusetts 

Joseph D. Feuerstein, MD, has disclosed no relevant financial relationships. 

Digestive Disease Week® was sponsored by the American Gastroenterological Association, the American Association for the Study of Liver Diseases, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

CHICAGO – An analysis of posts on TikTok about cirrhosis finds that approximately 40% of these posts include misinformation, according to a study presented at the annual Digestive Disease Week® (DDW).

TikTok’s short video format is increasingly becoming a major source for news and information, especially for adolescents and young adults. In 2022 the technology news website The Verge reported that about 10% of all U.S. adults regularly get news from TikTok, including an estimated 26% of adults under 30.

“Our study highlights the alarming prevalence of misinformation related to liver disease and cirrhosis on the TikTok platform. This misinformation can potentially lead to harm and poor health outcomes for individuals seeking accurate information about their conditions,” wrote the study authors in their abstract.

The study, which was led by Macklin Loveland, MD, an internal medicine resident at the University of Arizona, Tucson, found that, among 2,223 TikTok posts related to liver disease or cirrhosis as of November 2022, 60.3% were found to have accurate medical information, but the remaining 39.7% contained misinformation.

Some of the misinformation offered highly dubious and potentially dangerous advice, such as “Reishi mushrooms can reverse liver damage,” when in fact there is evidence to suggest that reishi mushrooms, especially in powder form, may be toxic to the liver and may even cause fatal fulminant hepatitis.

In an interview, Dr. Loveland said that much of the good information about liver disease on TikTok seems to come from patients with cirrhosis or other liver diseases who post videos chronicling their experiences, whereas bad information seems to come from people who are trying to pitch a product such as “natural” or “alternative” medicine.

“People who have real-life, firsthand experiences with cirrhosis have a really nice platform to talk about their disease process and share information with other people with similar disease processes, and the majority of them are accurate,” he said. “Where the inaccuracies come in are when people are trying to profit off a product or sell a dietary supplement, and then things go by the wayside.”

It’s important for TikTok users to understand the intentions of other users, he said, and expressed the hope that content mediators within TikTok would help to keep misinformation at bay.

Skyler B. Johnson, MD, assistant professor of radiation oncology at the University of Utah Huntsman Cancer Institute, Salt Lake City, has studied misinformation about cancer on social media, and as he and colleagues reported in the Journal of the National Cancer Institute, of 200 articles on cancer posted on social media sites, 32.5% contained misinformation and 30.5% contained harmful information.

In an interview, Dr. Johnson, who was not involved in the study by Dr. Loveland and colleagues, offered advice for colleagues about countering misinformation.

“What we’re trying to do, as part of our research group, is encourage physicians to take an active role in addressing misinformation with their patients and also in their social networking interactions,” he said. “When I see a new patient with a new diagnosis of cancer, I warn them that they’re going to encounter things online that may or may not be true.”

He noted that, often when physicians instruct patients not to go online to research their disease, the first thing the vast majority of patients do after leaving the office is to jump online.

Instead, Dr. Johnson recommended inoculating patients against misinformation – not to discourage them from going online, but to inform them about the myriad good and bad information sources, and steer them toward trustworthy sites such as government agencies (the National Institutes of Health, Centers for Disease Control and Prevention, etc), academic medical center sites, or select nonprofit organizations, foundations, and medical associations.

“But at the end of the day, even those you have to be somewhat vigilant about, because there are some unscrupulous providers who exploit even those sites,” he added.
 

Study details

Dr. Loveland and colleagues used the TikTok search engine to look for posts containing the terms “cirrhosis” and “liver disease,” and watched all such videos that turned up in the search from beginning to end. They classified each post as either educational in intent or whether it depicted a firsthand experience with liver disease.

They determined whether each post was accurate or erroneous according to guidelines from the American Association for the Study of Liver Disease, American College of Gastroenterology, and American Gastroenterological Association. They also recorded the number of likes, comments, and the number of times that each video was shared.

Accurate posts were viewed and liked significantly more often than inaccurate ones, and accurate posts had significantly more comments that faulty posts.

However, both accurate and inaccurate posts were shared a similar number of times, suggesting that bad-quality information can metastasize just as easily as good information can be disseminated.

Dr. Loveland and colleagues echoed the recommendations of Dr. Johnson, stating that “health care provides should be aware of the potential for misinformation on social media and should strive to provide their patients with accurate and evidence-based information to inform their health care decisions.”

The study was internally funded. Dr. Loveland and Dr. Johnson reported having no conflicts of interest to disclose.

DDW is sponsored by the American Association for the Study of Liver Diseases, the AGA, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.

CHICAGO – An analysis of posts on TikTok about cirrhosis finds that approximately 40% of these posts include misinformation, according to a study presented at the annual Digestive Disease Week® (DDW).

TikTok’s short video format is increasingly becoming a major source for news and information, especially for adolescents and young adults. In 2022 the technology news website The Verge reported that about 10% of all U.S. adults regularly get news from TikTok, including an estimated 26% of adults under 30.

“Our study highlights the alarming prevalence of misinformation related to liver disease and cirrhosis on the TikTok platform. This misinformation can potentially lead to harm and poor health outcomes for individuals seeking accurate information about their conditions,” wrote the study authors in their abstract.

The study, which was led by Macklin Loveland, MD, an internal medicine resident at the University of Arizona, Tucson, found that, among 2,223 TikTok posts related to liver disease or cirrhosis as of November 2022, 60.3% were found to have accurate medical information, but the remaining 39.7% contained misinformation.

Some of the misinformation offered highly dubious and potentially dangerous advice, such as “Reishi mushrooms can reverse liver damage,” when in fact there is evidence to suggest that reishi mushrooms, especially in powder form, may be toxic to the liver and may even cause fatal fulminant hepatitis.

In an interview, Dr. Loveland said that much of the good information about liver disease on TikTok seems to come from patients with cirrhosis or other liver diseases who post videos chronicling their experiences, whereas bad information seems to come from people who are trying to pitch a product such as “natural” or “alternative” medicine.

“People who have real-life, firsthand experiences with cirrhosis have a really nice platform to talk about their disease process and share information with other people with similar disease processes, and the majority of them are accurate,” he said. “Where the inaccuracies come in are when people are trying to profit off a product or sell a dietary supplement, and then things go by the wayside.”

It’s important for TikTok users to understand the intentions of other users, he said, and expressed the hope that content mediators within TikTok would help to keep misinformation at bay.

Skyler B. Johnson, MD, assistant professor of radiation oncology at the University of Utah Huntsman Cancer Institute, Salt Lake City, has studied misinformation about cancer on social media, and as he and colleagues reported in the Journal of the National Cancer Institute, of 200 articles on cancer posted on social media sites, 32.5% contained misinformation and 30.5% contained harmful information.

In an interview, Dr. Johnson, who was not involved in the study by Dr. Loveland and colleagues, offered advice for colleagues about countering misinformation.

“What we’re trying to do, as part of our research group, is encourage physicians to take an active role in addressing misinformation with their patients and also in their social networking interactions,” he said. “When I see a new patient with a new diagnosis of cancer, I warn them that they’re going to encounter things online that may or may not be true.”

He noted that, often when physicians instruct patients not to go online to research their disease, the first thing the vast majority of patients do after leaving the office is to jump online.

Instead, Dr. Johnson recommended inoculating patients against misinformation – not to discourage them from going online, but to inform them about the myriad good and bad information sources, and steer them toward trustworthy sites such as government agencies (the National Institutes of Health, Centers for Disease Control and Prevention, etc), academic medical center sites, or select nonprofit organizations, foundations, and medical associations.

“But at the end of the day, even those you have to be somewhat vigilant about, because there are some unscrupulous providers who exploit even those sites,” he added.
 

Study details

Dr. Loveland and colleagues used the TikTok search engine to look for posts containing the terms “cirrhosis” and “liver disease,” and watched all such videos that turned up in the search from beginning to end. They classified each post as either educational in intent or whether it depicted a firsthand experience with liver disease.

They determined whether each post was accurate or erroneous according to guidelines from the American Association for the Study of Liver Disease, American College of Gastroenterology, and American Gastroenterological Association. They also recorded the number of likes, comments, and the number of times that each video was shared.

Accurate posts were viewed and liked significantly more often than inaccurate ones, and accurate posts had significantly more comments that faulty posts.

However, both accurate and inaccurate posts were shared a similar number of times, suggesting that bad-quality information can metastasize just as easily as good information can be disseminated.

Dr. Loveland and colleagues echoed the recommendations of Dr. Johnson, stating that “health care provides should be aware of the potential for misinformation on social media and should strive to provide their patients with accurate and evidence-based information to inform their health care decisions.”

The study was internally funded. Dr. Loveland and Dr. Johnson reported having no conflicts of interest to disclose.

DDW is sponsored by the American Association for the Study of Liver Diseases, the AGA, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.

CHICAGO – An analysis of posts on TikTok about cirrhosis finds that approximately 40% of these posts include misinformation, according to a study presented at the annual Digestive Disease Week® (DDW).

TikTok’s short video format is increasingly becoming a major source for news and information, especially for adolescents and young adults. In 2022 the technology news website The Verge reported that about 10% of all U.S. adults regularly get news from TikTok, including an estimated 26% of adults under 30.

“Our study highlights the alarming prevalence of misinformation related to liver disease and cirrhosis on the TikTok platform. This misinformation can potentially lead to harm and poor health outcomes for individuals seeking accurate information about their conditions,” wrote the study authors in their abstract.

The study, which was led by Macklin Loveland, MD, an internal medicine resident at the University of Arizona, Tucson, found that, among 2,223 TikTok posts related to liver disease or cirrhosis as of November 2022, 60.3% were found to have accurate medical information, but the remaining 39.7% contained misinformation.

Some of the misinformation offered highly dubious and potentially dangerous advice, such as “Reishi mushrooms can reverse liver damage,” when in fact there is evidence to suggest that reishi mushrooms, especially in powder form, may be toxic to the liver and may even cause fatal fulminant hepatitis.

In an interview, Dr. Loveland said that much of the good information about liver disease on TikTok seems to come from patients with cirrhosis or other liver diseases who post videos chronicling their experiences, whereas bad information seems to come from people who are trying to pitch a product such as “natural” or “alternative” medicine.

“People who have real-life, firsthand experiences with cirrhosis have a really nice platform to talk about their disease process and share information with other people with similar disease processes, and the majority of them are accurate,” he said. “Where the inaccuracies come in are when people are trying to profit off a product or sell a dietary supplement, and then things go by the wayside.”

It’s important for TikTok users to understand the intentions of other users, he said, and expressed the hope that content mediators within TikTok would help to keep misinformation at bay.

Skyler B. Johnson, MD, assistant professor of radiation oncology at the University of Utah Huntsman Cancer Institute, Salt Lake City, has studied misinformation about cancer on social media, and as he and colleagues reported in the Journal of the National Cancer Institute, of 200 articles on cancer posted on social media sites, 32.5% contained misinformation and 30.5% contained harmful information.

In an interview, Dr. Johnson, who was not involved in the study by Dr. Loveland and colleagues, offered advice for colleagues about countering misinformation.

“What we’re trying to do, as part of our research group, is encourage physicians to take an active role in addressing misinformation with their patients and also in their social networking interactions,” he said. “When I see a new patient with a new diagnosis of cancer, I warn them that they’re going to encounter things online that may or may not be true.”

He noted that, often when physicians instruct patients not to go online to research their disease, the first thing the vast majority of patients do after leaving the office is to jump online.

Instead, Dr. Johnson recommended inoculating patients against misinformation – not to discourage them from going online, but to inform them about the myriad good and bad information sources, and steer them toward trustworthy sites such as government agencies (the National Institutes of Health, Centers for Disease Control and Prevention, etc), academic medical center sites, or select nonprofit organizations, foundations, and medical associations.

“But at the end of the day, even those you have to be somewhat vigilant about, because there are some unscrupulous providers who exploit even those sites,” he added.
 

Study details

Dr. Loveland and colleagues used the TikTok search engine to look for posts containing the terms “cirrhosis” and “liver disease,” and watched all such videos that turned up in the search from beginning to end. They classified each post as either educational in intent or whether it depicted a firsthand experience with liver disease.

They determined whether each post was accurate or erroneous according to guidelines from the American Association for the Study of Liver Disease, American College of Gastroenterology, and American Gastroenterological Association. They also recorded the number of likes, comments, and the number of times that each video was shared.

Accurate posts were viewed and liked significantly more often than inaccurate ones, and accurate posts had significantly more comments that faulty posts.

However, both accurate and inaccurate posts were shared a similar number of times, suggesting that bad-quality information can metastasize just as easily as good information can be disseminated.

Dr. Loveland and colleagues echoed the recommendations of Dr. Johnson, stating that “health care provides should be aware of the potential for misinformation on social media and should strive to provide their patients with accurate and evidence-based information to inform their health care decisions.”

The study was internally funded. Dr. Loveland and Dr. Johnson reported having no conflicts of interest to disclose.

DDW is sponsored by the American Association for the Study of Liver Diseases, the AGA, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.

CHICAGO – Preoperative clinical diagnoses of pancreatic cystic neoplasms (PCNs) are frequently found to be in error when patients go to surgery as recommended under international guidelines, data from a retrospective study show.

An analysis of all pancreatic resections performed for presumed PCN at the Verona Pancreas Institute, Italy, from 2011 through 2020 showed a high degree of discrepancy between the preoperative clinical diagnosis and the final postoperative pathology, with some lesions being misdiagnosed in nearly two-thirds of cases, reported Anna Burelli, MD, of the department of general and pancreatic surgery at the University of Verona.

“Diagnostic errors are still common for resected PCNs. Morphological and clinical information alone still poorly frame actual targets for surgery, and hopefully the development of new reliable biomarkers will represent the next evolution in pancreatic cystic neoplasm management,” she said in an oral abstract session at the annual Digestive Disease Week^® (DDW).

Diagnostic errors are significant issues in care of patients with PCN, because clinicians must balance the need for prompt, definitive treatment when necessary with the need for avoiding the significant morbidity of pancreatic resection for patients with lesions that turn out to be nonmalignant.

The investigators define “misdiagnosis” as a discrepancy between the preoperative clinical diagnosis and the postoperative pathology, and “mismatch” as a discrepancy between the preoperative suspicion of malignant or benign disease and the final pathology.
 

Checkered history

In previous cases series from Massachusetts General Hospital in Boston (2010) and the Verona Pancreas Institute (2012) – both experienced, high-volume centers – PCN misdiagnosis rates were 30% and 21%, respectively, and results from the current study show that things haven’t changed much since then, Dr. Burelli said.

PCNs are divided into neoplastic and nonneoplastic categories, with mucin-producing subtypes considered to be precancerous lesions that require accurate diagnosis and close monitoring.

Examples of neoplastic PCNs are intraductal papillary mucinous neoplasms (IPMNs) of the main pancreatic duct or side branch and mucinous cystadenomas. In contrast, serous cystadenomas, considered nonneoplastic, are mostly benign lesions discovered incidentally during abdominal imaging for another indication. It is very difficult, however, to distinguish between the two PCN subtypes clinically.

For example, Dr. Burelli showed images from a patient who received a preoperative diagnosis of mixed IPMN that was in fact found to be chronic pancreatitis on postoperative pathology.

Dr. Burelli noted that AGA and joint European guidelines for management of PCNs have been updated over the past decade, with the latest AGA iteration in 2015.

A 2017 study evaluating the 2015 AGA guidelines for management of asymptomatic PCNs found that following the guidelines in a large multicenter cohort “would have resulted in 60 % fewer patients being referred for surgical resection, and accurately recommended surveillance in 95% of patients with asymptomatic PCNs.”

Misdiagnosis and mismatch common

In the current study, Dr. Burelli and colleagues reviewed all pancreatic resections performed for PCNs at their center from 2011 through 2020.

Of 601 patients included in the retrospective study, 301 underwent endoscopic ultrasound (EUS).

The investigators identified misdiagnosis in 19% of cases and mismatch in 34%, and there was no significant improvement in diagnostic accuracy among the 50% of patients who underwent EUS.

The most frequently misdiagnosed lesions were cystic neuroendocrine tumors, in 61% of cases. The least misdiagnosed lesions were pseudopapillary tumors, in 6% of cases.

Many of the diagnostic errors were clinically important. For example, seven cases presumed to be serous cystic neoplasms (an almost always benign lesion) were found on final pathology to have a different, malignant histology.

Mismatch examples included 50 IPMNs with high-risk stigmata that were presumed to be malignant before surgery but were nonmalignant on final pathology, and 38 IPMNs without high-risk stigmata which were thought on clinical examination to be benign but turned out to be malignant on final pathology.

“Our results are in line with the current literature,” Dr. Burelli said, citing a recent meta-analysis showing that among 3,292 patients who underwent resection for mucinous cystic neoplasms (MCNs), the pooled rate of malignancy was 16.1%, yet the 2012 International Association of Pancreatology guidelines recommend surgery for all fit patients with MCNs, and joint European evidence-based guidelines from 2018 recommend surgery for MCNs 40 mm or larger, those with mural nodules, and for patients who are symptomatic.

The 16.1% pooled malignancy rate suggests “that there is space for surveillance in most cases of MCNs,” she said.

In addition, morphologic and clinical evaluation for IPMN with high-risk stigmata have been shown to have low specificity and low sensitivity, “so should guideline recommendations be revised?” Dr. Burelli said.

She pointed to a recent multi-institutional study in Gastroenterology showing that real-time next-generation sequencing of pancreatic cyst fluid “is sensitive and specific for various pancreatic cyst types and advanced neoplasia arising from mucinous cysts, but also reveals the diversity of genomic alterations seen in pancreatic cysts and their clinical significance.”

“This is not the future; this is the present,” she concluded.

Invited discussant R. Matthew Walsh, MD, a surgeon specializing in pancreatic and cancer surgery at the Cleveland Clinic, complimented the contributions of her group.

“The patient that you showed with chronic pancreatitis could have very well benefited from the operation regardless of the diagnosis if they were symptomatic,” he said, addressing Dr. Burelli. “So what is the group that is the regrettable surgical patients, and where are you aiming your studies? Is it really the 24% with high-risk features in IPMN that have low-grade dysplasia, or is it the 58% who we’re not sure why they were operated on because they didn’t have high-grade features who had low-grade dysplasia?”

She replied that “the goal here is to avoid surgery for benign entities, and we know that the only true benign entities are serous cystic neoplasms, and all the others have a malignant potential, but we think at Verona Pancreas Institute there is no reason to operate on low-grade dysplasia free patients. This is what we really would like to avoid.”

Dr. Walsh also asked, given their finding that EUS did not appear to offer a benefit to patients or change decision making, which patients should still get EUS.

“I think that only patients in which the diagnosis is uncertain or in which there are some worrisome features or high-risk stigmata should undergo EUS before surgery, and also to continue follow-up,” Dr. Burelli said. “I don’t think that the conclusion is that EUS is not useful, but it’s not useful in all.”

For example, large, microcystic lesions can be readily identified radiographically, but other, more complex cases may still require EUS to help nail down or refine a diagnosis, she said.

The study was internally funded. Dr. Burelli and Dr. Walsh reported having no conflicts of interest.

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

CHICAGO – Preoperative clinical diagnoses of pancreatic cystic neoplasms (PCNs) are frequently found to be in error when patients go to surgery as recommended under international guidelines, data from a retrospective study show.

An analysis of all pancreatic resections performed for presumed PCN at the Verona Pancreas Institute, Italy, from 2011 through 2020 showed a high degree of discrepancy between the preoperative clinical diagnosis and the final postoperative pathology, with some lesions being misdiagnosed in nearly two-thirds of cases, reported Anna Burelli, MD, of the department of general and pancreatic surgery at the University of Verona.

“Diagnostic errors are still common for resected PCNs. Morphological and clinical information alone still poorly frame actual targets for surgery, and hopefully the development of new reliable biomarkers will represent the next evolution in pancreatic cystic neoplasm management,” she said in an oral abstract session at the annual Digestive Disease Week^® (DDW).

Diagnostic errors are significant issues in care of patients with PCN, because clinicians must balance the need for prompt, definitive treatment when necessary with the need for avoiding the significant morbidity of pancreatic resection for patients with lesions that turn out to be nonmalignant.

The investigators define “misdiagnosis” as a discrepancy between the preoperative clinical diagnosis and the postoperative pathology, and “mismatch” as a discrepancy between the preoperative suspicion of malignant or benign disease and the final pathology.
 

Checkered history

In previous cases series from Massachusetts General Hospital in Boston (2010) and the Verona Pancreas Institute (2012) – both experienced, high-volume centers – PCN misdiagnosis rates were 30% and 21%, respectively, and results from the current study show that things haven’t changed much since then, Dr. Burelli said.

PCNs are divided into neoplastic and nonneoplastic categories, with mucin-producing subtypes considered to be precancerous lesions that require accurate diagnosis and close monitoring.

Examples of neoplastic PCNs are intraductal papillary mucinous neoplasms (IPMNs) of the main pancreatic duct or side branch and mucinous cystadenomas. In contrast, serous cystadenomas, considered nonneoplastic, are mostly benign lesions discovered incidentally during abdominal imaging for another indication. It is very difficult, however, to distinguish between the two PCN subtypes clinically.

For example, Dr. Burelli showed images from a patient who received a preoperative diagnosis of mixed IPMN that was in fact found to be chronic pancreatitis on postoperative pathology.

Dr. Burelli noted that AGA and joint European guidelines for management of PCNs have been updated over the past decade, with the latest AGA iteration in 2015.

A 2017 study evaluating the 2015 AGA guidelines for management of asymptomatic PCNs found that following the guidelines in a large multicenter cohort “would have resulted in 60 % fewer patients being referred for surgical resection, and accurately recommended surveillance in 95% of patients with asymptomatic PCNs.”

Misdiagnosis and mismatch common

In the current study, Dr. Burelli and colleagues reviewed all pancreatic resections performed for PCNs at their center from 2011 through 2020.

Of 601 patients included in the retrospective study, 301 underwent endoscopic ultrasound (EUS).

The investigators identified misdiagnosis in 19% of cases and mismatch in 34%, and there was no significant improvement in diagnostic accuracy among the 50% of patients who underwent EUS.

The most frequently misdiagnosed lesions were cystic neuroendocrine tumors, in 61% of cases. The least misdiagnosed lesions were pseudopapillary tumors, in 6% of cases.

Many of the diagnostic errors were clinically important. For example, seven cases presumed to be serous cystic neoplasms (an almost always benign lesion) were found on final pathology to have a different, malignant histology.

Mismatch examples included 50 IPMNs with high-risk stigmata that were presumed to be malignant before surgery but were nonmalignant on final pathology, and 38 IPMNs without high-risk stigmata which were thought on clinical examination to be benign but turned out to be malignant on final pathology.

“Our results are in line with the current literature,” Dr. Burelli said, citing a recent meta-analysis showing that among 3,292 patients who underwent resection for mucinous cystic neoplasms (MCNs), the pooled rate of malignancy was 16.1%, yet the 2012 International Association of Pancreatology guidelines recommend surgery for all fit patients with MCNs, and joint European evidence-based guidelines from 2018 recommend surgery for MCNs 40 mm or larger, those with mural nodules, and for patients who are symptomatic.

The 16.1% pooled malignancy rate suggests “that there is space for surveillance in most cases of MCNs,” she said.

In addition, morphologic and clinical evaluation for IPMN with high-risk stigmata have been shown to have low specificity and low sensitivity, “so should guideline recommendations be revised?” Dr. Burelli said.

She pointed to a recent multi-institutional study in Gastroenterology showing that real-time next-generation sequencing of pancreatic cyst fluid “is sensitive and specific for various pancreatic cyst types and advanced neoplasia arising from mucinous cysts, but also reveals the diversity of genomic alterations seen in pancreatic cysts and their clinical significance.”

“This is not the future; this is the present,” she concluded.

Invited discussant R. Matthew Walsh, MD, a surgeon specializing in pancreatic and cancer surgery at the Cleveland Clinic, complimented the contributions of her group.

“The patient that you showed with chronic pancreatitis could have very well benefited from the operation regardless of the diagnosis if they were symptomatic,” he said, addressing Dr. Burelli. “So what is the group that is the regrettable surgical patients, and where are you aiming your studies? Is it really the 24% with high-risk features in IPMN that have low-grade dysplasia, or is it the 58% who we’re not sure why they were operated on because they didn’t have high-grade features who had low-grade dysplasia?”

She replied that “the goal here is to avoid surgery for benign entities, and we know that the only true benign entities are serous cystic neoplasms, and all the others have a malignant potential, but we think at Verona Pancreas Institute there is no reason to operate on low-grade dysplasia free patients. This is what we really would like to avoid.”

Dr. Walsh also asked, given their finding that EUS did not appear to offer a benefit to patients or change decision making, which patients should still get EUS.

“I think that only patients in which the diagnosis is uncertain or in which there are some worrisome features or high-risk stigmata should undergo EUS before surgery, and also to continue follow-up,” Dr. Burelli said. “I don’t think that the conclusion is that EUS is not useful, but it’s not useful in all.”

For example, large, microcystic lesions can be readily identified radiographically, but other, more complex cases may still require EUS to help nail down or refine a diagnosis, she said.

The study was internally funded. Dr. Burelli and Dr. Walsh reported having no conflicts of interest.

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

CHICAGO – Preoperative clinical diagnoses of pancreatic cystic neoplasms (PCNs) are frequently found to be in error when patients go to surgery as recommended under international guidelines, data from a retrospective study show.

An analysis of all pancreatic resections performed for presumed PCN at the Verona Pancreas Institute, Italy, from 2011 through 2020 showed a high degree of discrepancy between the preoperative clinical diagnosis and the final postoperative pathology, with some lesions being misdiagnosed in nearly two-thirds of cases, reported Anna Burelli, MD, of the department of general and pancreatic surgery at the University of Verona.

“Diagnostic errors are still common for resected PCNs. Morphological and clinical information alone still poorly frame actual targets for surgery, and hopefully the development of new reliable biomarkers will represent the next evolution in pancreatic cystic neoplasm management,” she said in an oral abstract session at the annual Digestive Disease Week^® (DDW).

Diagnostic errors are significant issues in care of patients with PCN, because clinicians must balance the need for prompt, definitive treatment when necessary with the need for avoiding the significant morbidity of pancreatic resection for patients with lesions that turn out to be nonmalignant.

The investigators define “misdiagnosis” as a discrepancy between the preoperative clinical diagnosis and the postoperative pathology, and “mismatch” as a discrepancy between the preoperative suspicion of malignant or benign disease and the final pathology.
 

Checkered history

In previous cases series from Massachusetts General Hospital in Boston (2010) and the Verona Pancreas Institute (2012) – both experienced, high-volume centers – PCN misdiagnosis rates were 30% and 21%, respectively, and results from the current study show that things haven’t changed much since then, Dr. Burelli said.

PCNs are divided into neoplastic and nonneoplastic categories, with mucin-producing subtypes considered to be precancerous lesions that require accurate diagnosis and close monitoring.

Examples of neoplastic PCNs are intraductal papillary mucinous neoplasms (IPMNs) of the main pancreatic duct or side branch and mucinous cystadenomas. In contrast, serous cystadenomas, considered nonneoplastic, are mostly benign lesions discovered incidentally during abdominal imaging for another indication. It is very difficult, however, to distinguish between the two PCN subtypes clinically.

For example, Dr. Burelli showed images from a patient who received a preoperative diagnosis of mixed IPMN that was in fact found to be chronic pancreatitis on postoperative pathology.

Dr. Burelli noted that AGA and joint European guidelines for management of PCNs have been updated over the past decade, with the latest AGA iteration in 2015.

A 2017 study evaluating the 2015 AGA guidelines for management of asymptomatic PCNs found that following the guidelines in a large multicenter cohort “would have resulted in 60 % fewer patients being referred for surgical resection, and accurately recommended surveillance in 95% of patients with asymptomatic PCNs.”

Misdiagnosis and mismatch common

In the current study, Dr. Burelli and colleagues reviewed all pancreatic resections performed for PCNs at their center from 2011 through 2020.

Of 601 patients included in the retrospective study, 301 underwent endoscopic ultrasound (EUS).

The investigators identified misdiagnosis in 19% of cases and mismatch in 34%, and there was no significant improvement in diagnostic accuracy among the 50% of patients who underwent EUS.

The most frequently misdiagnosed lesions were cystic neuroendocrine tumors, in 61% of cases. The least misdiagnosed lesions were pseudopapillary tumors, in 6% of cases.

Many of the diagnostic errors were clinically important. For example, seven cases presumed to be serous cystic neoplasms (an almost always benign lesion) were found on final pathology to have a different, malignant histology.

Mismatch examples included 50 IPMNs with high-risk stigmata that were presumed to be malignant before surgery but were nonmalignant on final pathology, and 38 IPMNs without high-risk stigmata which were thought on clinical examination to be benign but turned out to be malignant on final pathology.

“Our results are in line with the current literature,” Dr. Burelli said, citing a recent meta-analysis showing that among 3,292 patients who underwent resection for mucinous cystic neoplasms (MCNs), the pooled rate of malignancy was 16.1%, yet the 2012 International Association of Pancreatology guidelines recommend surgery for all fit patients with MCNs, and joint European evidence-based guidelines from 2018 recommend surgery for MCNs 40 mm or larger, those with mural nodules, and for patients who are symptomatic.

The 16.1% pooled malignancy rate suggests “that there is space for surveillance in most cases of MCNs,” she said.

In addition, morphologic and clinical evaluation for IPMN with high-risk stigmata have been shown to have low specificity and low sensitivity, “so should guideline recommendations be revised?” Dr. Burelli said.

She pointed to a recent multi-institutional study in Gastroenterology showing that real-time next-generation sequencing of pancreatic cyst fluid “is sensitive and specific for various pancreatic cyst types and advanced neoplasia arising from mucinous cysts, but also reveals the diversity of genomic alterations seen in pancreatic cysts and their clinical significance.”

“This is not the future; this is the present,” she concluded.

Invited discussant R. Matthew Walsh, MD, a surgeon specializing in pancreatic and cancer surgery at the Cleveland Clinic, complimented the contributions of her group.

“The patient that you showed with chronic pancreatitis could have very well benefited from the operation regardless of the diagnosis if they were symptomatic,” he said, addressing Dr. Burelli. “So what is the group that is the regrettable surgical patients, and where are you aiming your studies? Is it really the 24% with high-risk features in IPMN that have low-grade dysplasia, or is it the 58% who we’re not sure why they were operated on because they didn’t have high-grade features who had low-grade dysplasia?”

She replied that “the goal here is to avoid surgery for benign entities, and we know that the only true benign entities are serous cystic neoplasms, and all the others have a malignant potential, but we think at Verona Pancreas Institute there is no reason to operate on low-grade dysplasia free patients. This is what we really would like to avoid.”

Dr. Walsh also asked, given their finding that EUS did not appear to offer a benefit to patients or change decision making, which patients should still get EUS.

“I think that only patients in which the diagnosis is uncertain or in which there are some worrisome features or high-risk stigmata should undergo EUS before surgery, and also to continue follow-up,” Dr. Burelli said. “I don’t think that the conclusion is that EUS is not useful, but it’s not useful in all.”

For example, large, microcystic lesions can be readily identified radiographically, but other, more complex cases may still require EUS to help nail down or refine a diagnosis, she said.

The study was internally funded. Dr. Burelli and Dr. Walsh reported having no conflicts of interest.

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

CHICAGO – New data from an ongoing study shows that regular meat consumption is associated with inflammatory bowel disease (IBD) flares, specifically for patients with ulcerative colitis.

The data, which was presented on May 7 in Chicago at the annual Digestive Disease Week® meeting, is based on an analysis of data from the PREdiCCt study (Prognostic Effect of Environmental Factors in Crohn’s and Colitis) in which diets of patients with IBD were tracked over 2-3 months with 2-year follow-ups. While the study itself includes nearly 3,000 patients from the United Kingdom who are in clinical remission, this analysis included 497 patients with Crohn’s disease and 520 with ulcerative colitis.

The highest level of patient-reported meat consumption was associated with doubled risk for hard flares – defined as an increase in symptoms plus elevation in c-reactive protein (CRP) and fecal calprotection (FCAL) plus a change in IBD therapy – in patients with ulcerative colitis, said study author Charlie W Lees, PhD, FRCP(Ed), Western General Hospital and University of Edinburgh.

Investigators also evaluated the occurrence of soft flares, which was defined as a negative response to the question, “Do you think your disease has been well controlled in the past month or since you last logged on to the portal?”

After a median follow-up of 1,481.5 days, hard flares occurred at a rate of 5.6% per year, but it did not differ by IBD subtype. However, soft flares accumulated rapidly. Hard flares with baseline FCAL levels in the 50-250 mcg/g range, as well as FCAL levels above 250 mcg, were associated with flares.

The mean baseline total protein intake was 91.9 g per day of which 35.8 g came from animal sources. The hazard ratio for the highest vs. lowest quartile of meat intake in the ulcerative colitis group was 2.08. They found no associations between hard flares with intake of total dietary fiber, N-6 polyunsaturated acids, or ultraprocessed foods, which Dr. Lees found surprising.

“Perhaps most intriguingly, when we look at ultraprocessed food intake, no difference in Crohn’s disease, and no difference in ulcerative colitis,” Dr. Lees said.

The finding is in contradiction to a study reported at the Crohn’s & Colitis Congress this year that found additives in ultraprocessed foods appear to have deleterious effects on intestinal microbiota, while others may exert their influence through mechanisms, such as endoplasmic stress.

However, the new data are consistent with a previously reported association between meat consumption and ulcerative colitis development, and suggests that reducing meat consumption could help to reduce the risk of flare in patients with ulcerative colitis.

PREdiCCt is designed to examine dietary, environmental, genetic, and microbiotic factors that are associated with disease flares in patients with Crohn’s disease and ulcerative colitis. Investigators are evaluating potential contributions to disease flares from total animal protein intake, dietary fiber, N-6 polyunsaturated fatty acids, dietary emulsifiers, and ultraprocessed foods, and total bacterial gene count in stool samples. They aim to examine data from 2,500 microbiome samples currently being sequenced at the Wellcome Sanger Institute in Hinxton, England, to determine whether the association between meat and ulcerative colitis flares could be related, as they hypothesize, to diet-induced alterations in the gut microbiome.

The research is preliminary with many unanswered questions, said Russell D. Cohen, MD, director of the inflammatory bowel disease center at the University of Chicago.

“I think he still has to evaluate a lot of the data that he has already collected because, are you talking about meat? Are you talking about poultry? Are you talking about fish? It is interesting, but it still needs to be evaluated further before we make any conclusive decisions,” he said. Dr. Cohen was not involved in the research.

He said the presumed effect of meat consumption on disease exacerbation appeared to take years, “which is a little surprising. If you really thought that IBD was due to something in diet, you would see the response right away, so it doesn’t follow timewise. Why does it takes 5 years? It should be within 5 weeks or 5 days.”

Dr. Lees disclosed relationships with Abbvie, Takeda, Pfizer, Galapagos, and BDD Pharma, among others.

DDW is sponsored by the American Gastroenterological Association, the American Association for the Study of Liver Diseases, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

CHICAGO – New data from an ongoing study shows that regular meat consumption is associated with inflammatory bowel disease (IBD) flares, specifically for patients with ulcerative colitis.

The data, which was presented on May 7 in Chicago at the annual Digestive Disease Week® meeting, is based on an analysis of data from the PREdiCCt study (Prognostic Effect of Environmental Factors in Crohn’s and Colitis) in which diets of patients with IBD were tracked over 2-3 months with 2-year follow-ups. While the study itself includes nearly 3,000 patients from the United Kingdom who are in clinical remission, this analysis included 497 patients with Crohn’s disease and 520 with ulcerative colitis.

The highest level of patient-reported meat consumption was associated with doubled risk for hard flares – defined as an increase in symptoms plus elevation in c-reactive protein (CRP) and fecal calprotection (FCAL) plus a change in IBD therapy – in patients with ulcerative colitis, said study author Charlie W Lees, PhD, FRCP(Ed), Western General Hospital and University of Edinburgh.

Investigators also evaluated the occurrence of soft flares, which was defined as a negative response to the question, “Do you think your disease has been well controlled in the past month or since you last logged on to the portal?”

After a median follow-up of 1,481.5 days, hard flares occurred at a rate of 5.6% per year, but it did not differ by IBD subtype. However, soft flares accumulated rapidly. Hard flares with baseline FCAL levels in the 50-250 mcg/g range, as well as FCAL levels above 250 mcg, were associated with flares.

The mean baseline total protein intake was 91.9 g per day of which 35.8 g came from animal sources. The hazard ratio for the highest vs. lowest quartile of meat intake in the ulcerative colitis group was 2.08. They found no associations between hard flares with intake of total dietary fiber, N-6 polyunsaturated acids, or ultraprocessed foods, which Dr. Lees found surprising.

“Perhaps most intriguingly, when we look at ultraprocessed food intake, no difference in Crohn’s disease, and no difference in ulcerative colitis,” Dr. Lees said.

The finding is in contradiction to a study reported at the Crohn’s & Colitis Congress this year that found additives in ultraprocessed foods appear to have deleterious effects on intestinal microbiota, while others may exert their influence through mechanisms, such as endoplasmic stress.

However, the new data are consistent with a previously reported association between meat consumption and ulcerative colitis development, and suggests that reducing meat consumption could help to reduce the risk of flare in patients with ulcerative colitis.

PREdiCCt is designed to examine dietary, environmental, genetic, and microbiotic factors that are associated with disease flares in patients with Crohn’s disease and ulcerative colitis. Investigators are evaluating potential contributions to disease flares from total animal protein intake, dietary fiber, N-6 polyunsaturated fatty acids, dietary emulsifiers, and ultraprocessed foods, and total bacterial gene count in stool samples. They aim to examine data from 2,500 microbiome samples currently being sequenced at the Wellcome Sanger Institute in Hinxton, England, to determine whether the association between meat and ulcerative colitis flares could be related, as they hypothesize, to diet-induced alterations in the gut microbiome.

The research is preliminary with many unanswered questions, said Russell D. Cohen, MD, director of the inflammatory bowel disease center at the University of Chicago.

“I think he still has to evaluate a lot of the data that he has already collected because, are you talking about meat? Are you talking about poultry? Are you talking about fish? It is interesting, but it still needs to be evaluated further before we make any conclusive decisions,” he said. Dr. Cohen was not involved in the research.

He said the presumed effect of meat consumption on disease exacerbation appeared to take years, “which is a little surprising. If you really thought that IBD was due to something in diet, you would see the response right away, so it doesn’t follow timewise. Why does it takes 5 years? It should be within 5 weeks or 5 days.”

Dr. Lees disclosed relationships with Abbvie, Takeda, Pfizer, Galapagos, and BDD Pharma, among others.

DDW is sponsored by the American Gastroenterological Association, the American Association for the Study of Liver Diseases, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

CHICAGO – New data from an ongoing study shows that regular meat consumption is associated with inflammatory bowel disease (IBD) flares, specifically for patients with ulcerative colitis.

The data, which was presented on May 7 in Chicago at the annual Digestive Disease Week® meeting, is based on an analysis of data from the PREdiCCt study (Prognostic Effect of Environmental Factors in Crohn’s and Colitis) in which diets of patients with IBD were tracked over 2-3 months with 2-year follow-ups. While the study itself includes nearly 3,000 patients from the United Kingdom who are in clinical remission, this analysis included 497 patients with Crohn’s disease and 520 with ulcerative colitis.

The highest level of patient-reported meat consumption was associated with doubled risk for hard flares – defined as an increase in symptoms plus elevation in c-reactive protein (CRP) and fecal calprotection (FCAL) plus a change in IBD therapy – in patients with ulcerative colitis, said study author Charlie W Lees, PhD, FRCP(Ed), Western General Hospital and University of Edinburgh.

Investigators also evaluated the occurrence of soft flares, which was defined as a negative response to the question, “Do you think your disease has been well controlled in the past month or since you last logged on to the portal?”

After a median follow-up of 1,481.5 days, hard flares occurred at a rate of 5.6% per year, but it did not differ by IBD subtype. However, soft flares accumulated rapidly. Hard flares with baseline FCAL levels in the 50-250 mcg/g range, as well as FCAL levels above 250 mcg, were associated with flares.

The mean baseline total protein intake was 91.9 g per day of which 35.8 g came from animal sources. The hazard ratio for the highest vs. lowest quartile of meat intake in the ulcerative colitis group was 2.08. They found no associations between hard flares with intake of total dietary fiber, N-6 polyunsaturated acids, or ultraprocessed foods, which Dr. Lees found surprising.

“Perhaps most intriguingly, when we look at ultraprocessed food intake, no difference in Crohn’s disease, and no difference in ulcerative colitis,” Dr. Lees said.

The finding is in contradiction to a study reported at the Crohn’s & Colitis Congress this year that found additives in ultraprocessed foods appear to have deleterious effects on intestinal microbiota, while others may exert their influence through mechanisms, such as endoplasmic stress.

However, the new data are consistent with a previously reported association between meat consumption and ulcerative colitis development, and suggests that reducing meat consumption could help to reduce the risk of flare in patients with ulcerative colitis.

PREdiCCt is designed to examine dietary, environmental, genetic, and microbiotic factors that are associated with disease flares in patients with Crohn’s disease and ulcerative colitis. Investigators are evaluating potential contributions to disease flares from total animal protein intake, dietary fiber, N-6 polyunsaturated fatty acids, dietary emulsifiers, and ultraprocessed foods, and total bacterial gene count in stool samples. They aim to examine data from 2,500 microbiome samples currently being sequenced at the Wellcome Sanger Institute in Hinxton, England, to determine whether the association between meat and ulcerative colitis flares could be related, as they hypothesize, to diet-induced alterations in the gut microbiome.

The research is preliminary with many unanswered questions, said Russell D. Cohen, MD, director of the inflammatory bowel disease center at the University of Chicago.

“I think he still has to evaluate a lot of the data that he has already collected because, are you talking about meat? Are you talking about poultry? Are you talking about fish? It is interesting, but it still needs to be evaluated further before we make any conclusive decisions,” he said. Dr. Cohen was not involved in the research.

He said the presumed effect of meat consumption on disease exacerbation appeared to take years, “which is a little surprising. If you really thought that IBD was due to something in diet, you would see the response right away, so it doesn’t follow timewise. Why does it takes 5 years? It should be within 5 weeks or 5 days.”

Dr. Lees disclosed relationships with Abbvie, Takeda, Pfizer, Galapagos, and BDD Pharma, among others.

DDW is sponsored by the American Gastroenterological Association, the American Association for the Study of Liver Diseases, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.