Gastroenterology

The National Comprehensive Cancer Network (NCCN) has expanded two cancer genetic risk assessment guidelines to meet the growing understanding of hereditary cancer risk and use of genetic tests in cancer prevention, screening, and treatment. 

Additional cancer types were included in the title and content for both guidelines. Prostate cancer was added to Genetic/Familial High-Risk Assessment: Breast, Ovarian, Pancreatic, and Prostate, and endometrial and gastric cancer were added to Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric.

For these cancers, the expanded guidelines include information on when genetic testing is recommended and what type of testing may be best. These guidelines also detail the hereditary conditions and genetic mutations associated with elevated cancer risk and include appropriate “next steps” for individuals who have them, which may involve increased screening or prevention surgeries.

“These updates include the spectrum of genes associated with genetic syndromes, the range of risk associated with each pathogenic variant, the improvements in screening and prevention strategies, the role of genetic data to inform cancer treatment, and the expansion of the role of genetic counseling as this field moves forward,” Mary B. Daly, MD, PhD, with Fox Chase Cancer Center, Philadelphia, Pennsylvania, said in a news release. Daly chaired the panel that updated the breast, ovarian, pancreatic, and prostate cancer guidelines.

Oncologists should, for instance, ask patients about their family and personal history of cancer and known germline variants at time of initial diagnosis. With prostate cancer, if patients meet criteria for germline testing, multigene testing should include a host of variants, including BRCA1, BRCA2, ATM, PALB2, CHEK2, HOXB13, MLH1, MSH2, MSH6, and PMS2.

The updated guidelines on genetic risk assessment of colorectal, endometrial, and gastric cancer include new recommendations to consider for hereditary cancer screening in patients with newly diagnosed endometrial cancer, for evaluating and managing CDH1-associated gastric cancer risk, and for managing gastric cancer risk in patients with APC pathogenic variants. 

For CDH1-associated gastric cancer, for instance, the guidelines recommend carriers be referred to institutions with expertise in managing risks for cancer associated with CDH1, “given the still limited understanding and rarity of this syndrome.” 

“These expanded guidelines reflect the recommendations from leading experts on genetic testing based on the latest scientific research across the cancer spectrum, consolidated into two convenient resources,” said NCCN CEO Crystal S. Denlinger, MD, with Fox Chase Cancer Center, in a news release. 

“This information is critical for guiding shared decision-making between health care providers and their patients, enhancing screening practices as appropriate, and potentially choosing options for prevention and targeted treatment choices. Genetic testing guidelines enable us to better care for people with cancer and their family members,” Denlinger added.

A version of this article first appeared on Medscape.com.

The National Comprehensive Cancer Network (NCCN) has expanded two cancer genetic risk assessment guidelines to meet the growing understanding of hereditary cancer risk and use of genetic tests in cancer prevention, screening, and treatment. 

Additional cancer types were included in the title and content for both guidelines. Prostate cancer was added to Genetic/Familial High-Risk Assessment: Breast, Ovarian, Pancreatic, and Prostate, and endometrial and gastric cancer were added to Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric.

For these cancers, the expanded guidelines include information on when genetic testing is recommended and what type of testing may be best. These guidelines also detail the hereditary conditions and genetic mutations associated with elevated cancer risk and include appropriate “next steps” for individuals who have them, which may involve increased screening or prevention surgeries.

“These updates include the spectrum of genes associated with genetic syndromes, the range of risk associated with each pathogenic variant, the improvements in screening and prevention strategies, the role of genetic data to inform cancer treatment, and the expansion of the role of genetic counseling as this field moves forward,” Mary B. Daly, MD, PhD, with Fox Chase Cancer Center, Philadelphia, Pennsylvania, said in a news release. Daly chaired the panel that updated the breast, ovarian, pancreatic, and prostate cancer guidelines.

Oncologists should, for instance, ask patients about their family and personal history of cancer and known germline variants at time of initial diagnosis. With prostate cancer, if patients meet criteria for germline testing, multigene testing should include a host of variants, including BRCA1, BRCA2, ATM, PALB2, CHEK2, HOXB13, MLH1, MSH2, MSH6, and PMS2.

The updated guidelines on genetic risk assessment of colorectal, endometrial, and gastric cancer include new recommendations to consider for hereditary cancer screening in patients with newly diagnosed endometrial cancer, for evaluating and managing CDH1-associated gastric cancer risk, and for managing gastric cancer risk in patients with APC pathogenic variants. 

For CDH1-associated gastric cancer, for instance, the guidelines recommend carriers be referred to institutions with expertise in managing risks for cancer associated with CDH1, “given the still limited understanding and rarity of this syndrome.” 

“These expanded guidelines reflect the recommendations from leading experts on genetic testing based on the latest scientific research across the cancer spectrum, consolidated into two convenient resources,” said NCCN CEO Crystal S. Denlinger, MD, with Fox Chase Cancer Center, in a news release. 

“This information is critical for guiding shared decision-making between health care providers and their patients, enhancing screening practices as appropriate, and potentially choosing options for prevention and targeted treatment choices. Genetic testing guidelines enable us to better care for people with cancer and their family members,” Denlinger added.

A version of this article first appeared on Medscape.com.

The National Comprehensive Cancer Network (NCCN) has expanded two cancer genetic risk assessment guidelines to meet the growing understanding of hereditary cancer risk and use of genetic tests in cancer prevention, screening, and treatment. 

Additional cancer types were included in the title and content for both guidelines. Prostate cancer was added to Genetic/Familial High-Risk Assessment: Breast, Ovarian, Pancreatic, and Prostate, and endometrial and gastric cancer were added to Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric.

For these cancers, the expanded guidelines include information on when genetic testing is recommended and what type of testing may be best. These guidelines also detail the hereditary conditions and genetic mutations associated with elevated cancer risk and include appropriate “next steps” for individuals who have them, which may involve increased screening or prevention surgeries.

“These updates include the spectrum of genes associated with genetic syndromes, the range of risk associated with each pathogenic variant, the improvements in screening and prevention strategies, the role of genetic data to inform cancer treatment, and the expansion of the role of genetic counseling as this field moves forward,” Mary B. Daly, MD, PhD, with Fox Chase Cancer Center, Philadelphia, Pennsylvania, said in a news release. Daly chaired the panel that updated the breast, ovarian, pancreatic, and prostate cancer guidelines.

Oncologists should, for instance, ask patients about their family and personal history of cancer and known germline variants at time of initial diagnosis. With prostate cancer, if patients meet criteria for germline testing, multigene testing should include a host of variants, including BRCA1, BRCA2, ATM, PALB2, CHEK2, HOXB13, MLH1, MSH2, MSH6, and PMS2.

The updated guidelines on genetic risk assessment of colorectal, endometrial, and gastric cancer include new recommendations to consider for hereditary cancer screening in patients with newly diagnosed endometrial cancer, for evaluating and managing CDH1-associated gastric cancer risk, and for managing gastric cancer risk in patients with APC pathogenic variants. 

For CDH1-associated gastric cancer, for instance, the guidelines recommend carriers be referred to institutions with expertise in managing risks for cancer associated with CDH1, “given the still limited understanding and rarity of this syndrome.” 

“These expanded guidelines reflect the recommendations from leading experts on genetic testing based on the latest scientific research across the cancer spectrum, consolidated into two convenient resources,” said NCCN CEO Crystal S. Denlinger, MD, with Fox Chase Cancer Center, in a news release. 

“This information is critical for guiding shared decision-making between health care providers and their patients, enhancing screening practices as appropriate, and potentially choosing options for prevention and targeted treatment choices. Genetic testing guidelines enable us to better care for people with cancer and their family members,” Denlinger added.

A version of this article first appeared on Medscape.com.

TOPLINE:

Patients with stages I-III screen-detected colorectal cancer (CRC) have better disease-free survival rates than those with non-screen–detected CRC, an effect that was independent of patient, tumor, and treatment characteristics.

METHODOLOGY:

• Patients with screen-detected CRC have better stage-specific overall survival rates than those with non-screen–detected CRC, but the impact of screening on recurrence rates is unknown.
• A retrospective study analyzed patients with CRC (age, 55-75 years) from the Netherlands Cancer Registry diagnosed by screening or not.
• Screen-detected CRC were identified in patients who underwent colonoscopy after a positive fecal immunochemical test (FIT), whereas non-screen–detected CRC were those that were detected in symptomatic patients.

TAKEAWAY:

• Researchers included 3725 patients with CRC (39.6% women), of which 1652 (44.3%) and 2073 (55.7%) patients had screen-detected and non-screen–detected CRC, respectively; CRC was distributed approximately evenly across stages I-III (35.3%, 27.1%, and 37.6%, respectively).
• Screen-detected CRC had significantly higher 3-year rates of disease-free survival compared with non-screen–detected CRC (87.8% vs 77.2%; P < .001).
• The improvement in disease-free survival rates for screen-detected CRC was particularly notable in stage III cases, with rates of 77.9% vs 66.7% for non-screen–detected CRC (P < .001).
• Screen-detected CRC was more often detected at an earlier stage than non-screen–detected CRC (stage I or II: 72.4% vs 54.4%; P < .001).
• Across all stages, detection of CRC by screening was associated with a 33% lower risk for recurrence (P < .001) independent of patient age, gender, tumor location, stage, and treatment.
• Recurrence was the strongest predictor of overall survival across the study population (hazard ratio, 15.90; P < .001).

IN PRACTICE:

“Apart from CRC stage, mode of detection could be used to assess an individual’s risk for recurrence and survival, which may contribute to a more personalized treatment,” the authors wrote.

SOURCE:

The study, led by Sanne J.K.F. Pluimers, Department of Gastroenterology and Hepatology, Erasmus University Medical Center/Erasmus MC Cancer Institute, Rotterdam, the Netherlands, was published online in Clinical Gastroenterology and Hepatology.

LIMITATIONS:

The follow-up time was relatively short, restricting the ability to evaluate the long-term effects of screening on CRC recurrence. This study focused on recurrence solely within the FIT-based screening program, and the results were not generalizable to other screening methods. Due to Dutch privacy law, data on CRC-specific causes of death were unavailable, which may have affected the specificity of survival outcomes.

DISCLOSURES:

There was no funding source for this study. The authors declared no conflicts of interest.

 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Patients with stages I-III screen-detected colorectal cancer (CRC) have better disease-free survival rates than those with non-screen–detected CRC, an effect that was independent of patient, tumor, and treatment characteristics.

METHODOLOGY:

• Patients with screen-detected CRC have better stage-specific overall survival rates than those with non-screen–detected CRC, but the impact of screening on recurrence rates is unknown.
• A retrospective study analyzed patients with CRC (age, 55-75 years) from the Netherlands Cancer Registry diagnosed by screening or not.
• Screen-detected CRC were identified in patients who underwent colonoscopy after a positive fecal immunochemical test (FIT), whereas non-screen–detected CRC were those that were detected in symptomatic patients.

TAKEAWAY:

• Researchers included 3725 patients with CRC (39.6% women), of which 1652 (44.3%) and 2073 (55.7%) patients had screen-detected and non-screen–detected CRC, respectively; CRC was distributed approximately evenly across stages I-III (35.3%, 27.1%, and 37.6%, respectively).
• Screen-detected CRC had significantly higher 3-year rates of disease-free survival compared with non-screen–detected CRC (87.8% vs 77.2%; P < .001).
• The improvement in disease-free survival rates for screen-detected CRC was particularly notable in stage III cases, with rates of 77.9% vs 66.7% for non-screen–detected CRC (P < .001).
• Screen-detected CRC was more often detected at an earlier stage than non-screen–detected CRC (stage I or II: 72.4% vs 54.4%; P < .001).
• Across all stages, detection of CRC by screening was associated with a 33% lower risk for recurrence (P < .001) independent of patient age, gender, tumor location, stage, and treatment.
• Recurrence was the strongest predictor of overall survival across the study population (hazard ratio, 15.90; P < .001).

IN PRACTICE:

“Apart from CRC stage, mode of detection could be used to assess an individual’s risk for recurrence and survival, which may contribute to a more personalized treatment,” the authors wrote.

SOURCE:

The study, led by Sanne J.K.F. Pluimers, Department of Gastroenterology and Hepatology, Erasmus University Medical Center/Erasmus MC Cancer Institute, Rotterdam, the Netherlands, was published online in Clinical Gastroenterology and Hepatology.

LIMITATIONS:

The follow-up time was relatively short, restricting the ability to evaluate the long-term effects of screening on CRC recurrence. This study focused on recurrence solely within the FIT-based screening program, and the results were not generalizable to other screening methods. Due to Dutch privacy law, data on CRC-specific causes of death were unavailable, which may have affected the specificity of survival outcomes.

DISCLOSURES:

There was no funding source for this study. The authors declared no conflicts of interest.

 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Patients with stages I-III screen-detected colorectal cancer (CRC) have better disease-free survival rates than those with non-screen–detected CRC, an effect that was independent of patient, tumor, and treatment characteristics.

METHODOLOGY:

• Patients with screen-detected CRC have better stage-specific overall survival rates than those with non-screen–detected CRC, but the impact of screening on recurrence rates is unknown.
• A retrospective study analyzed patients with CRC (age, 55-75 years) from the Netherlands Cancer Registry diagnosed by screening or not.
• Screen-detected CRC were identified in patients who underwent colonoscopy after a positive fecal immunochemical test (FIT), whereas non-screen–detected CRC were those that were detected in symptomatic patients.

TAKEAWAY:

• Researchers included 3725 patients with CRC (39.6% women), of which 1652 (44.3%) and 2073 (55.7%) patients had screen-detected and non-screen–detected CRC, respectively; CRC was distributed approximately evenly across stages I-III (35.3%, 27.1%, and 37.6%, respectively).
• Screen-detected CRC had significantly higher 3-year rates of disease-free survival compared with non-screen–detected CRC (87.8% vs 77.2%; P < .001).
• The improvement in disease-free survival rates for screen-detected CRC was particularly notable in stage III cases, with rates of 77.9% vs 66.7% for non-screen–detected CRC (P < .001).
• Screen-detected CRC was more often detected at an earlier stage than non-screen–detected CRC (stage I or II: 72.4% vs 54.4%; P < .001).
• Across all stages, detection of CRC by screening was associated with a 33% lower risk for recurrence (P < .001) independent of patient age, gender, tumor location, stage, and treatment.
• Recurrence was the strongest predictor of overall survival across the study population (hazard ratio, 15.90; P < .001).

IN PRACTICE:

“Apart from CRC stage, mode of detection could be used to assess an individual’s risk for recurrence and survival, which may contribute to a more personalized treatment,” the authors wrote.

SOURCE:

The study, led by Sanne J.K.F. Pluimers, Department of Gastroenterology and Hepatology, Erasmus University Medical Center/Erasmus MC Cancer Institute, Rotterdam, the Netherlands, was published online in Clinical Gastroenterology and Hepatology.

LIMITATIONS:

The follow-up time was relatively short, restricting the ability to evaluate the long-term effects of screening on CRC recurrence. This study focused on recurrence solely within the FIT-based screening program, and the results were not generalizable to other screening methods. Due to Dutch privacy law, data on CRC-specific causes of death were unavailable, which may have affected the specificity of survival outcomes.

DISCLOSURES:

There was no funding source for this study. The authors declared no conflicts of interest.

 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

The increase in incidence of pancreatic cancer among young Americans is largely caused by improved detection of early-stage endocrine cancer, not an increase in pancreatic adenocarcinoma. Given the stable mortality rates in this population, the increase in incidence likely reflects previously undetected cases instead of a true rise in new cases, researchers say.

METHODOLOGY:

• Data from several registries have indicated that the incidence of pancreatic cancer among younger individuals, particularly women, is on the rise in the United States and worldwide.
• In a new analysis, researchers wanted to see if the observed increase in pancreatic cancer incidence among young Americans represented a true rise in cancer occurrence or indicated greater diagnostic scrutiny. If pancreatic cancer incidence is really increasing, “incidence and mortality would be expected to increase concurrently, as would early- and late-stage diagnoses,” the researchers explained.
• The researchers collected data on pancreatic cancer incidence, histology, and stage distribution for individuals aged 15-39 years from US Cancer Statistics, a database covering almost the entire US population from 2001 to 2020. Pancreatic cancer mortality data from the same timeframe came from the National Vital Statistics System.
• The researchers looked at four histologic categories: Adenocarcinoma, the dominant pancreatic cancer histology, as well as more rare subtypes — endocrine and solid pseudopapillary — and “other” category. Researchers also categorized stage-specific incidence as early stage (in situ or localized) or late stage (regional or distant).

TAKEAWAY:

• The incidence of pancreatic cancer increased 2.1-fold in young women (incidence, 3.3-6.9 per million) and 1.6-fold in young men (incidence, 3.9-6.2 per million) between 2001 and 2019. However, mortality rates remained stable for women (1.5 deaths per million; annual percent change [AAPC], −0.5%; 95% CI, –1.4% to 0.5%) and men (2.5 deaths per million; AAPC, –0.1%; 95% CI, –0.8% to 0.6%) over this period.
• Looking at cancer subtypes, the increase in incidence was largely caused by early-stage endocrine cancer and solid pseudopapillary neoplasms in women, not adenocarcinoma (which remained stable over the study period).
• Looking at cancer stage, most of the increase in incidence came from detection of smaller tumors (< 2 cm) and early-stage cancer, which rose from 0.6 to 3.7 per million in women and from 0.4 to 2.2 per million in men. The authors also found no statistically significant change in the incidence of late-stage cancer in women or men.
• Rates of surgical treatment for pancreatic cancer increased, more than tripling among women (from 1.5 to 4.7 per million) and more than doubling among men (from 1.1 to 2.3 per million).

IN PRACTICE:

“Pancreatic cancer now can be another cancer subject to overdiagnosis: The detection of disease not destined to cause symptoms or death,” the authors concluded. “Although the observed changes in incidence are small, overdiagnosis is especially concerning for pancreatic cancer, as pancreatic surgery has substantial risk for morbidity (in particular, pancreatic fistulas) and mortality.”

SOURCE:

The study, with first author Vishal R. Patel, MD, MPH, and corresponding author H. Gilbert Welch, MD, MPH, from Brigham and Women’s Hospital, Boston, was published online on November 19 in Annals of Internal Medicine.

LIMITATIONS:

The study was limited by the lack of data on the method of cancer detection, which may have affected the interpretation of the findings.

DISCLOSURES:

Disclosure forms are available with the article online.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

The increase in incidence of pancreatic cancer among young Americans is largely caused by improved detection of early-stage endocrine cancer, not an increase in pancreatic adenocarcinoma. Given the stable mortality rates in this population, the increase in incidence likely reflects previously undetected cases instead of a true rise in new cases, researchers say.

METHODOLOGY:

• Data from several registries have indicated that the incidence of pancreatic cancer among younger individuals, particularly women, is on the rise in the United States and worldwide.
• In a new analysis, researchers wanted to see if the observed increase in pancreatic cancer incidence among young Americans represented a true rise in cancer occurrence or indicated greater diagnostic scrutiny. If pancreatic cancer incidence is really increasing, “incidence and mortality would be expected to increase concurrently, as would early- and late-stage diagnoses,” the researchers explained.
• The researchers collected data on pancreatic cancer incidence, histology, and stage distribution for individuals aged 15-39 years from US Cancer Statistics, a database covering almost the entire US population from 2001 to 2020. Pancreatic cancer mortality data from the same timeframe came from the National Vital Statistics System.
• The researchers looked at four histologic categories: Adenocarcinoma, the dominant pancreatic cancer histology, as well as more rare subtypes — endocrine and solid pseudopapillary — and “other” category. Researchers also categorized stage-specific incidence as early stage (in situ or localized) or late stage (regional or distant).

TAKEAWAY:

• The incidence of pancreatic cancer increased 2.1-fold in young women (incidence, 3.3-6.9 per million) and 1.6-fold in young men (incidence, 3.9-6.2 per million) between 2001 and 2019. However, mortality rates remained stable for women (1.5 deaths per million; annual percent change [AAPC], −0.5%; 95% CI, –1.4% to 0.5%) and men (2.5 deaths per million; AAPC, –0.1%; 95% CI, –0.8% to 0.6%) over this period.
• Looking at cancer subtypes, the increase in incidence was largely caused by early-stage endocrine cancer and solid pseudopapillary neoplasms in women, not adenocarcinoma (which remained stable over the study period).
• Looking at cancer stage, most of the increase in incidence came from detection of smaller tumors (< 2 cm) and early-stage cancer, which rose from 0.6 to 3.7 per million in women and from 0.4 to 2.2 per million in men. The authors also found no statistically significant change in the incidence of late-stage cancer in women or men.
• Rates of surgical treatment for pancreatic cancer increased, more than tripling among women (from 1.5 to 4.7 per million) and more than doubling among men (from 1.1 to 2.3 per million).

IN PRACTICE:

“Pancreatic cancer now can be another cancer subject to overdiagnosis: The detection of disease not destined to cause symptoms or death,” the authors concluded. “Although the observed changes in incidence are small, overdiagnosis is especially concerning for pancreatic cancer, as pancreatic surgery has substantial risk for morbidity (in particular, pancreatic fistulas) and mortality.”

SOURCE:

The study, with first author Vishal R. Patel, MD, MPH, and corresponding author H. Gilbert Welch, MD, MPH, from Brigham and Women’s Hospital, Boston, was published online on November 19 in Annals of Internal Medicine.

LIMITATIONS:

The study was limited by the lack of data on the method of cancer detection, which may have affected the interpretation of the findings.

DISCLOSURES:

Disclosure forms are available with the article online.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

The increase in incidence of pancreatic cancer among young Americans is largely caused by improved detection of early-stage endocrine cancer, not an increase in pancreatic adenocarcinoma. Given the stable mortality rates in this population, the increase in incidence likely reflects previously undetected cases instead of a true rise in new cases, researchers say.

METHODOLOGY:

• Data from several registries have indicated that the incidence of pancreatic cancer among younger individuals, particularly women, is on the rise in the United States and worldwide.
• In a new analysis, researchers wanted to see if the observed increase in pancreatic cancer incidence among young Americans represented a true rise in cancer occurrence or indicated greater diagnostic scrutiny. If pancreatic cancer incidence is really increasing, “incidence and mortality would be expected to increase concurrently, as would early- and late-stage diagnoses,” the researchers explained.
• The researchers collected data on pancreatic cancer incidence, histology, and stage distribution for individuals aged 15-39 years from US Cancer Statistics, a database covering almost the entire US population from 2001 to 2020. Pancreatic cancer mortality data from the same timeframe came from the National Vital Statistics System.
• The researchers looked at four histologic categories: Adenocarcinoma, the dominant pancreatic cancer histology, as well as more rare subtypes — endocrine and solid pseudopapillary — and “other” category. Researchers also categorized stage-specific incidence as early stage (in situ or localized) or late stage (regional or distant).

TAKEAWAY:

• The incidence of pancreatic cancer increased 2.1-fold in young women (incidence, 3.3-6.9 per million) and 1.6-fold in young men (incidence, 3.9-6.2 per million) between 2001 and 2019. However, mortality rates remained stable for women (1.5 deaths per million; annual percent change [AAPC], −0.5%; 95% CI, –1.4% to 0.5%) and men (2.5 deaths per million; AAPC, –0.1%; 95% CI, –0.8% to 0.6%) over this period.
• Looking at cancer subtypes, the increase in incidence was largely caused by early-stage endocrine cancer and solid pseudopapillary neoplasms in women, not adenocarcinoma (which remained stable over the study period).
• Looking at cancer stage, most of the increase in incidence came from detection of smaller tumors (< 2 cm) and early-stage cancer, which rose from 0.6 to 3.7 per million in women and from 0.4 to 2.2 per million in men. The authors also found no statistically significant change in the incidence of late-stage cancer in women or men.
• Rates of surgical treatment for pancreatic cancer increased, more than tripling among women (from 1.5 to 4.7 per million) and more than doubling among men (from 1.1 to 2.3 per million).

IN PRACTICE:

“Pancreatic cancer now can be another cancer subject to overdiagnosis: The detection of disease not destined to cause symptoms or death,” the authors concluded. “Although the observed changes in incidence are small, overdiagnosis is especially concerning for pancreatic cancer, as pancreatic surgery has substantial risk for morbidity (in particular, pancreatic fistulas) and mortality.”

SOURCE:

The study, with first author Vishal R. Patel, MD, MPH, and corresponding author H. Gilbert Welch, MD, MPH, from Brigham and Women’s Hospital, Boston, was published online on November 19 in Annals of Internal Medicine.

LIMITATIONS:

The study was limited by the lack of data on the method of cancer detection, which may have affected the interpretation of the findings.

DISCLOSURES:

Disclosure forms are available with the article online.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

WASHINGTON — Immune checkpoint inhibitor (ICI) therapy does not increase mortality in people with preexisting autoimmune diseases, new research has found. 

Results from a large database analysis of patients with and without autoimmune diseases suggest it is safe to treat them with ICI if they develop a cancer for which it is indicated, Greg Challener, MD, a postdoctoral fellow at the Rheumatology and Allergy Clinical Epidemiology Research Center, Massachusetts General Hospital, Boston, said at the American College of Rheumatology 2024 Annual Meeting.

“One message is that, when rheumatologists are asked by oncologists about patients with rheumatoid arthritis or vasculitis or other autoimmune diseases and whether it’s safe to treat them with immune checkpoint inhibitors, this result provides some evidence that it probably is safe…. Checkpoint inhibitors are really incredible drugs, and they’ve improved mortality for a lot of cancers, particularly melanoma, and so I think there should be a pretty high threshold for us to say a patient shouldn’t receive them because of an autoimmune condition,” he told this news organization.

Another implication, Challener said, is that people with autoimmune diseases shouldn’t routinely be excluded from clinical trials of ICIs. Currently they are excluded because of concerns about exacerbation of underlying autoimmunity, possible interference between the ICI and the immunosuppressive drugs used to treat the autoimmune condition, and a theoretical risk for serious adverse events. 

“Clinical trials are continuing to exclude these patients, and they paint with a very broad brush anyone with underlying autoimmunity ... I’m hoping that that changes. I don’t think there’s a great evidence base to support that practice, and it’s unfortunate that patients with underlying autoimmune diseases are excluded from important studies,” Challener said.

Asked to comment, session moderator Matlock Jeffries, MD, director of the Arthritis Research Unit at the Oklahoma Medical Research Foundation, Oklahoma City, told this news organization that he agrees the data are generally reassuring. “If one of our patients gets cancer and their oncologist wants to use a checkpoint inhibitor, we’d obviously still monitor them for complications, but we wouldn’t automatically assume the combination of a checkpoint inhibitor and autoimmune disease would increase their mortality.” 

 

No Difference in Mortality for Those With and Without Autoimmune Disease

Challener and colleagues used administrative health data from the TriNetX Diamond network of 92 US healthcare sites with 212 million patients. All patients included in the study were receiving anti-programmed death protein 1/programmed death ligand 1 to treat malignancies involving the skin, lung/bronchus, digestive organs, or urinary tract. The study population also had at least one rheumatologic, gastrointestinal, neurologic, dermatologic, or endocrine autoimmune disease.

Propensity score matching between those with and without autoimmune disease was performed for about 100 covariates. Prior to the matching, the autoimmune disease group had significantly higher rates of cardiovascular and other comorbidities. The matching yielded 23,714 individuals with autoimmune disease and the same number without who had similar demographics and comorbidity rates, as well as malignancy type, alcohol/tobacco use, and medication use. 

At a median follow-up of 250 days, the risk for mortality prior to propensity matching was 40.0% in the autoimmune disease group and 38.1% for those without, a significant difference with hazard ratio 1.07 (95% CI, 1.05-1.10). But after the matching, the difference was no longer significant: 39.8% vs 40.2%, respectively (0.97, 0.94-1.00). 

The Kaplan-Meier curves for survival probability for those with or without autoimmune disease were nearly superimposed, showing no difference up to 1600 days. An analysis of just the patients with rheumatic diseases yielded similar results, Challener said. 

 

Some Caveats About the Data

Jeffries, who is also an associate professor of medicine at the University of Oklahoma Health Sciences Center, Oklahoma City, and the Oklahoma VA, said he would like to see additional data on outcomes, both for the autoimmune conditions and the cancers. Challener said there are plans to look at other hard endpoints such as myocardial infarction and end-stage renal disease, but that the database is limited. 

Both Challener and Jeffries also cautioned that the reassurance may not apply to patients with active disease. 

“One thing this research doesn’t address is whether active autoimmune disease might have a different outcome compared to more kind of quiet disease…. If you have a patient who has extremely active rheumatoid arthritis or extremely active giant cell arthritis, for instance, I think that could be more challenging. I would be frightened to put a patient with really active GCA on pembrolizumab or say that it’s safe without their disease being controlled. But for someone who has well-controlled disease or minimally active disease, this is very reassuring,” Challener told this news organization.

“I think this may also be important in that it’s a good argument to tell the drug companies to include autoimmune patients in these trials so we can get better data,” Jeffries said.

Challener and Jeffries had no relevant disclosures. 
 

A version of this article appeared on Medscape.com.

WASHINGTON — Immune checkpoint inhibitor (ICI) therapy does not increase mortality in people with preexisting autoimmune diseases, new research has found. 

Results from a large database analysis of patients with and without autoimmune diseases suggest it is safe to treat them with ICI if they develop a cancer for which it is indicated, Greg Challener, MD, a postdoctoral fellow at the Rheumatology and Allergy Clinical Epidemiology Research Center, Massachusetts General Hospital, Boston, said at the American College of Rheumatology 2024 Annual Meeting.

“One message is that, when rheumatologists are asked by oncologists about patients with rheumatoid arthritis or vasculitis or other autoimmune diseases and whether it’s safe to treat them with immune checkpoint inhibitors, this result provides some evidence that it probably is safe…. Checkpoint inhibitors are really incredible drugs, and they’ve improved mortality for a lot of cancers, particularly melanoma, and so I think there should be a pretty high threshold for us to say a patient shouldn’t receive them because of an autoimmune condition,” he told this news organization.

Another implication, Challener said, is that people with autoimmune diseases shouldn’t routinely be excluded from clinical trials of ICIs. Currently they are excluded because of concerns about exacerbation of underlying autoimmunity, possible interference between the ICI and the immunosuppressive drugs used to treat the autoimmune condition, and a theoretical risk for serious adverse events. 

“Clinical trials are continuing to exclude these patients, and they paint with a very broad brush anyone with underlying autoimmunity ... I’m hoping that that changes. I don’t think there’s a great evidence base to support that practice, and it’s unfortunate that patients with underlying autoimmune diseases are excluded from important studies,” Challener said.

Asked to comment, session moderator Matlock Jeffries, MD, director of the Arthritis Research Unit at the Oklahoma Medical Research Foundation, Oklahoma City, told this news organization that he agrees the data are generally reassuring. “If one of our patients gets cancer and their oncologist wants to use a checkpoint inhibitor, we’d obviously still monitor them for complications, but we wouldn’t automatically assume the combination of a checkpoint inhibitor and autoimmune disease would increase their mortality.” 

 

No Difference in Mortality for Those With and Without Autoimmune Disease

Challener and colleagues used administrative health data from the TriNetX Diamond network of 92 US healthcare sites with 212 million patients. All patients included in the study were receiving anti-programmed death protein 1/programmed death ligand 1 to treat malignancies involving the skin, lung/bronchus, digestive organs, or urinary tract. The study population also had at least one rheumatologic, gastrointestinal, neurologic, dermatologic, or endocrine autoimmune disease.

Propensity score matching between those with and without autoimmune disease was performed for about 100 covariates. Prior to the matching, the autoimmune disease group had significantly higher rates of cardiovascular and other comorbidities. The matching yielded 23,714 individuals with autoimmune disease and the same number without who had similar demographics and comorbidity rates, as well as malignancy type, alcohol/tobacco use, and medication use. 

At a median follow-up of 250 days, the risk for mortality prior to propensity matching was 40.0% in the autoimmune disease group and 38.1% for those without, a significant difference with hazard ratio 1.07 (95% CI, 1.05-1.10). But after the matching, the difference was no longer significant: 39.8% vs 40.2%, respectively (0.97, 0.94-1.00). 

The Kaplan-Meier curves for survival probability for those with or without autoimmune disease were nearly superimposed, showing no difference up to 1600 days. An analysis of just the patients with rheumatic diseases yielded similar results, Challener said. 

 

Some Caveats About the Data

Jeffries, who is also an associate professor of medicine at the University of Oklahoma Health Sciences Center, Oklahoma City, and the Oklahoma VA, said he would like to see additional data on outcomes, both for the autoimmune conditions and the cancers. Challener said there are plans to look at other hard endpoints such as myocardial infarction and end-stage renal disease, but that the database is limited. 

Both Challener and Jeffries also cautioned that the reassurance may not apply to patients with active disease. 

“One thing this research doesn’t address is whether active autoimmune disease might have a different outcome compared to more kind of quiet disease…. If you have a patient who has extremely active rheumatoid arthritis or extremely active giant cell arthritis, for instance, I think that could be more challenging. I would be frightened to put a patient with really active GCA on pembrolizumab or say that it’s safe without their disease being controlled. But for someone who has well-controlled disease or minimally active disease, this is very reassuring,” Challener told this news organization.

“I think this may also be important in that it’s a good argument to tell the drug companies to include autoimmune patients in these trials so we can get better data,” Jeffries said.

Challener and Jeffries had no relevant disclosures. 
 

A version of this article appeared on Medscape.com.

WASHINGTON — Immune checkpoint inhibitor (ICI) therapy does not increase mortality in people with preexisting autoimmune diseases, new research has found. 

Results from a large database analysis of patients with and without autoimmune diseases suggest it is safe to treat them with ICI if they develop a cancer for which it is indicated, Greg Challener, MD, a postdoctoral fellow at the Rheumatology and Allergy Clinical Epidemiology Research Center, Massachusetts General Hospital, Boston, said at the American College of Rheumatology 2024 Annual Meeting.

“One message is that, when rheumatologists are asked by oncologists about patients with rheumatoid arthritis or vasculitis or other autoimmune diseases and whether it’s safe to treat them with immune checkpoint inhibitors, this result provides some evidence that it probably is safe…. Checkpoint inhibitors are really incredible drugs, and they’ve improved mortality for a lot of cancers, particularly melanoma, and so I think there should be a pretty high threshold for us to say a patient shouldn’t receive them because of an autoimmune condition,” he told this news organization.

Another implication, Challener said, is that people with autoimmune diseases shouldn’t routinely be excluded from clinical trials of ICIs. Currently they are excluded because of concerns about exacerbation of underlying autoimmunity, possible interference between the ICI and the immunosuppressive drugs used to treat the autoimmune condition, and a theoretical risk for serious adverse events. 

“Clinical trials are continuing to exclude these patients, and they paint with a very broad brush anyone with underlying autoimmunity ... I’m hoping that that changes. I don’t think there’s a great evidence base to support that practice, and it’s unfortunate that patients with underlying autoimmune diseases are excluded from important studies,” Challener said.

Asked to comment, session moderator Matlock Jeffries, MD, director of the Arthritis Research Unit at the Oklahoma Medical Research Foundation, Oklahoma City, told this news organization that he agrees the data are generally reassuring. “If one of our patients gets cancer and their oncologist wants to use a checkpoint inhibitor, we’d obviously still monitor them for complications, but we wouldn’t automatically assume the combination of a checkpoint inhibitor and autoimmune disease would increase their mortality.” 

 

No Difference in Mortality for Those With and Without Autoimmune Disease

Challener and colleagues used administrative health data from the TriNetX Diamond network of 92 US healthcare sites with 212 million patients. All patients included in the study were receiving anti-programmed death protein 1/programmed death ligand 1 to treat malignancies involving the skin, lung/bronchus, digestive organs, or urinary tract. The study population also had at least one rheumatologic, gastrointestinal, neurologic, dermatologic, or endocrine autoimmune disease.

Propensity score matching between those with and without autoimmune disease was performed for about 100 covariates. Prior to the matching, the autoimmune disease group had significantly higher rates of cardiovascular and other comorbidities. The matching yielded 23,714 individuals with autoimmune disease and the same number without who had similar demographics and comorbidity rates, as well as malignancy type, alcohol/tobacco use, and medication use. 

At a median follow-up of 250 days, the risk for mortality prior to propensity matching was 40.0% in the autoimmune disease group and 38.1% for those without, a significant difference with hazard ratio 1.07 (95% CI, 1.05-1.10). But after the matching, the difference was no longer significant: 39.8% vs 40.2%, respectively (0.97, 0.94-1.00). 

The Kaplan-Meier curves for survival probability for those with or without autoimmune disease were nearly superimposed, showing no difference up to 1600 days. An analysis of just the patients with rheumatic diseases yielded similar results, Challener said. 

 

Some Caveats About the Data

Jeffries, who is also an associate professor of medicine at the University of Oklahoma Health Sciences Center, Oklahoma City, and the Oklahoma VA, said he would like to see additional data on outcomes, both for the autoimmune conditions and the cancers. Challener said there are plans to look at other hard endpoints such as myocardial infarction and end-stage renal disease, but that the database is limited. 

Both Challener and Jeffries also cautioned that the reassurance may not apply to patients with active disease. 

“One thing this research doesn’t address is whether active autoimmune disease might have a different outcome compared to more kind of quiet disease…. If you have a patient who has extremely active rheumatoid arthritis or extremely active giant cell arthritis, for instance, I think that could be more challenging. I would be frightened to put a patient with really active GCA on pembrolizumab or say that it’s safe without their disease being controlled. But for someone who has well-controlled disease or minimally active disease, this is very reassuring,” Challener told this news organization.

“I think this may also be important in that it’s a good argument to tell the drug companies to include autoimmune patients in these trials so we can get better data,” Jeffries said.

Challener and Jeffries had no relevant disclosures. 
 

A version of this article appeared on Medscape.com.

SAN DIEGO — The prevalence of and number of deaths from alcohol-associated liver disease (ALD) and alcohol use disorder (AUD) are growing among people age 70 and older in the United States, according to the results of a new study.

Even as mortality rates decline globally, AUD deaths rose in the United States, increasing 1.63% per year between 2010 and 2019. Deaths from cirrhosis increased by 0.56% each year, and deaths from primary liver cancer associated with alcohol increased by 3.09% per year.

Several factors, such as an aging US population and increasing alcohol consumption, play a major role in the uptick in mortality, said lead author Pojsakorn Danpanichkul, MD, an internal medicine resident at Texas Tech University Health Sciences Center, Lubbock, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).

“Healthcare providers should increase screening for alcohol use among older adults and consider the added risks of alcohol consumption. Public health strategies should target alcohol prevention and treatment programs tailored to older adults,” he said.

“Older adults are more vulnerable to the harmful effects of alcohol due to natural declines in liver function and metabolism, leading to a higher risk of liver disease and complications,” he explained. However, “little research has focused on this issue.”

 

Trends in US Not Seen Globally

Danpanichkul and colleagues analyzed data from the Global Burden of Disease Study for 2010-2019, calculating the annual percent change for the burden of AUD, ALD, and liver cancer from alcohol in patients age 70 and older. The research team then compared data in the United States to global estimates for these same diseases.

In 2019, there were 556,340 cases of AUD, 112,560 cases of ALD, and 3720 cases of liver cancer from alcohol in older adults in the United States. In addition, there were 1750 deaths attributed to AUD, 4860 deaths from ALD, and 3010 deaths caused by primary liver cancer from alcohol.

The age-standardized prevalence rates (ASPRs) per 100,000 people were 1547 cases of AUD, 313 cases of ALD, and 10 cases of primary liver cancer caused by alcohol.

The age-standardized death rates (ASDRs) per 100,000 people were 4.88 for AUD, 13.52 for ALD, and 8.38 for primary liver cancer.

During the time period studied, upward trends occurred in the United States, with annual ASPRs increasing by 2.52% for AUD, 1.78% for ALD, and 3.31% for primary liver cancer due to alcohol. Globally, the trends were lower, with annual increases of 0.2% for AUD, 0.38% for ALD, and 0.67% for primary liver cancer from alcohol.

During the same time, ASDRs also increased in all three categories in the United States, while global trends showed a 0.91% decline in AUD deaths and 0.6% decline in ALD deaths. Liver cancer deaths, however, increased by 0.3% worldwide.

Targeted strategies are essential to reduce this growing health burden, especially in an aging population, Danpanichkul said. “These interventions should focus on early detection, intervention, and management for individuals at risk or already affected by ALD and AUD.”

Future studies should investigate alcohol consumption and mortality trends in other age groups, including by sex, location (such as state or territory), and race and ethnicity, he said. Data for more recent years would be compelling as well.

 

Increased Alcohol Use During and After Pandemic

Numerous studies have indicated that alcohol use increased in 2020 during the COVID-19 pandemic and has remained elevated since then. 

In a study published in the Annals of Internal Medicine, for instance, alcohol use per 100 people increased 2.69% in 2020 and 2.96% in 2022, as compared with 2018. Increases occurred across all subgroups, including age, sex, race, ethnicity, and US region.

“During the COVID-19 pandemic, many people stayed at home, watched the television, and increased their alcohol intake” — in the United States and also in Japan — said Hisanori Muto, MD, senior assistant professor of gastroenterology at Fujita Health University in Nagoya, Japan, who wasn’t involved with this study.

“Although the global numbers may appear lower, we’re also seeing an increase in AUD and ALD in Japan, similar to the United States,” he said. “It’s very important to watch these trends and address these diseases.”

Danpanichkul and Muto reported no relevant disclosures.

A version of this article appeared on Medscape.com.

SAN DIEGO — The prevalence of and number of deaths from alcohol-associated liver disease (ALD) and alcohol use disorder (AUD) are growing among people age 70 and older in the United States, according to the results of a new study.

Even as mortality rates decline globally, AUD deaths rose in the United States, increasing 1.63% per year between 2010 and 2019. Deaths from cirrhosis increased by 0.56% each year, and deaths from primary liver cancer associated with alcohol increased by 3.09% per year.

Several factors, such as an aging US population and increasing alcohol consumption, play a major role in the uptick in mortality, said lead author Pojsakorn Danpanichkul, MD, an internal medicine resident at Texas Tech University Health Sciences Center, Lubbock, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).

“Healthcare providers should increase screening for alcohol use among older adults and consider the added risks of alcohol consumption. Public health strategies should target alcohol prevention and treatment programs tailored to older adults,” he said.

“Older adults are more vulnerable to the harmful effects of alcohol due to natural declines in liver function and metabolism, leading to a higher risk of liver disease and complications,” he explained. However, “little research has focused on this issue.”

 

Trends in US Not Seen Globally

Danpanichkul and colleagues analyzed data from the Global Burden of Disease Study for 2010-2019, calculating the annual percent change for the burden of AUD, ALD, and liver cancer from alcohol in patients age 70 and older. The research team then compared data in the United States to global estimates for these same diseases.

In 2019, there were 556,340 cases of AUD, 112,560 cases of ALD, and 3720 cases of liver cancer from alcohol in older adults in the United States. In addition, there were 1750 deaths attributed to AUD, 4860 deaths from ALD, and 3010 deaths caused by primary liver cancer from alcohol.

The age-standardized prevalence rates (ASPRs) per 100,000 people were 1547 cases of AUD, 313 cases of ALD, and 10 cases of primary liver cancer caused by alcohol.

The age-standardized death rates (ASDRs) per 100,000 people were 4.88 for AUD, 13.52 for ALD, and 8.38 for primary liver cancer.

During the time period studied, upward trends occurred in the United States, with annual ASPRs increasing by 2.52% for AUD, 1.78% for ALD, and 3.31% for primary liver cancer due to alcohol. Globally, the trends were lower, with annual increases of 0.2% for AUD, 0.38% for ALD, and 0.67% for primary liver cancer from alcohol.

During the same time, ASDRs also increased in all three categories in the United States, while global trends showed a 0.91% decline in AUD deaths and 0.6% decline in ALD deaths. Liver cancer deaths, however, increased by 0.3% worldwide.

Targeted strategies are essential to reduce this growing health burden, especially in an aging population, Danpanichkul said. “These interventions should focus on early detection, intervention, and management for individuals at risk or already affected by ALD and AUD.”

Future studies should investigate alcohol consumption and mortality trends in other age groups, including by sex, location (such as state or territory), and race and ethnicity, he said. Data for more recent years would be compelling as well.

 

Increased Alcohol Use During and After Pandemic

Numerous studies have indicated that alcohol use increased in 2020 during the COVID-19 pandemic and has remained elevated since then. 

In a study published in the Annals of Internal Medicine, for instance, alcohol use per 100 people increased 2.69% in 2020 and 2.96% in 2022, as compared with 2018. Increases occurred across all subgroups, including age, sex, race, ethnicity, and US region.

“During the COVID-19 pandemic, many people stayed at home, watched the television, and increased their alcohol intake” — in the United States and also in Japan — said Hisanori Muto, MD, senior assistant professor of gastroenterology at Fujita Health University in Nagoya, Japan, who wasn’t involved with this study.

“Although the global numbers may appear lower, we’re also seeing an increase in AUD and ALD in Japan, similar to the United States,” he said. “It’s very important to watch these trends and address these diseases.”

Danpanichkul and Muto reported no relevant disclosures.

A version of this article appeared on Medscape.com.

SAN DIEGO — The prevalence of and number of deaths from alcohol-associated liver disease (ALD) and alcohol use disorder (AUD) are growing among people age 70 and older in the United States, according to the results of a new study.

Even as mortality rates decline globally, AUD deaths rose in the United States, increasing 1.63% per year between 2010 and 2019. Deaths from cirrhosis increased by 0.56% each year, and deaths from primary liver cancer associated with alcohol increased by 3.09% per year.

Several factors, such as an aging US population and increasing alcohol consumption, play a major role in the uptick in mortality, said lead author Pojsakorn Danpanichkul, MD, an internal medicine resident at Texas Tech University Health Sciences Center, Lubbock, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).

“Healthcare providers should increase screening for alcohol use among older adults and consider the added risks of alcohol consumption. Public health strategies should target alcohol prevention and treatment programs tailored to older adults,” he said.

“Older adults are more vulnerable to the harmful effects of alcohol due to natural declines in liver function and metabolism, leading to a higher risk of liver disease and complications,” he explained. However, “little research has focused on this issue.”

 

Trends in US Not Seen Globally

Danpanichkul and colleagues analyzed data from the Global Burden of Disease Study for 2010-2019, calculating the annual percent change for the burden of AUD, ALD, and liver cancer from alcohol in patients age 70 and older. The research team then compared data in the United States to global estimates for these same diseases.

In 2019, there were 556,340 cases of AUD, 112,560 cases of ALD, and 3720 cases of liver cancer from alcohol in older adults in the United States. In addition, there were 1750 deaths attributed to AUD, 4860 deaths from ALD, and 3010 deaths caused by primary liver cancer from alcohol.

The age-standardized prevalence rates (ASPRs) per 100,000 people were 1547 cases of AUD, 313 cases of ALD, and 10 cases of primary liver cancer caused by alcohol.

The age-standardized death rates (ASDRs) per 100,000 people were 4.88 for AUD, 13.52 for ALD, and 8.38 for primary liver cancer.

During the time period studied, upward trends occurred in the United States, with annual ASPRs increasing by 2.52% for AUD, 1.78% for ALD, and 3.31% for primary liver cancer due to alcohol. Globally, the trends were lower, with annual increases of 0.2% for AUD, 0.38% for ALD, and 0.67% for primary liver cancer from alcohol.

During the same time, ASDRs also increased in all three categories in the United States, while global trends showed a 0.91% decline in AUD deaths and 0.6% decline in ALD deaths. Liver cancer deaths, however, increased by 0.3% worldwide.

Targeted strategies are essential to reduce this growing health burden, especially in an aging population, Danpanichkul said. “These interventions should focus on early detection, intervention, and management for individuals at risk or already affected by ALD and AUD.”

Future studies should investigate alcohol consumption and mortality trends in other age groups, including by sex, location (such as state or territory), and race and ethnicity, he said. Data for more recent years would be compelling as well.

 

Increased Alcohol Use During and After Pandemic

Numerous studies have indicated that alcohol use increased in 2020 during the COVID-19 pandemic and has remained elevated since then. 

In a study published in the Annals of Internal Medicine, for instance, alcohol use per 100 people increased 2.69% in 2020 and 2.96% in 2022, as compared with 2018. Increases occurred across all subgroups, including age, sex, race, ethnicity, and US region.

“During the COVID-19 pandemic, many people stayed at home, watched the television, and increased their alcohol intake” — in the United States and also in Japan — said Hisanori Muto, MD, senior assistant professor of gastroenterology at Fujita Health University in Nagoya, Japan, who wasn’t involved with this study.

“Although the global numbers may appear lower, we’re also seeing an increase in AUD and ALD in Japan, similar to the United States,” he said. “It’s very important to watch these trends and address these diseases.”

Danpanichkul and Muto reported no relevant disclosures.

A version of this article appeared on Medscape.com.

PHILADELPHIA — Patients with inflammatory bowel disease (IBD) don’t appear to face an increased risk of major adverse cardiovascular events (MACE) or venous thromboembolism (VTE) when taking Janus kinase inhibitors (JAKi), compared with anti–tumor necrosis factor (TNF) agents, according to a study presented at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.

In particular, 1.76% of patients taking JAKi and 1.94% of patients taking anti-TNF developed MACE. There also weren’t significant differences when comparing ulcerative colitis with Crohn’s disease, upadacitinib with tofacitinib, or JAKi with infliximab.

“IBD is associated with an increased risk of cardiovascular diseases, and with the emergence of JAK inhibitors and anti-TNF therapies, there is a concern about the increased risk of MACE,” said lead author Saqr Alsakarneh, MD, an internal medicine resident at the University of Missouri–Kansas City School of Medicine.

Previous randomized controlled trials have indicated increased risks of MACE with JAKi and anti-TNF agents, compared with placebo, but researchers haven’t conducted a head-to-head comparison, he said.

“A potential explanation for previous associations could be linked to immune modulation and inflammation that can increase coagulation risk, as well as fluctuation in disease severity while patients are on the medications, which can impact cardiovascular risk factors,” he added.

Alsakarneh and colleagues conducted a retrospective cohort study using the TriNetX database to identify adult patients with IBD who were treated with JAKi or anti-TNF therapy after diagnosis. After matching patients in the JAKi cohort with patients in the anti-TNF cohort, the research team looked for MACE and VTE within a year of medication initiation, as well as associations by age, sex, and IBD type.

Overall, 3740 patients in the JAKi cohort had a mean age of 43.1 and were 48.9% women and 75.3% White individuals, while 3,740 patients in the anti-TNF cohort had a mean age of 43 and were 48.9% women and 75.3% White individuals.

After excluding those with a history of a prior cardiovascular event, 57 patients (1.76%) in the JAKi cohort developed MACE, compared with 63 patients (1.94%) in the anti-TNF cohort. There weren’t significant differences between the groups in MACE (adjusted hazard ratio [aHR], 0.99) or VTE (aHR, 0.9).

Among patients aged ≥ 65, 25 patients (5.3%) in the JAKi cohort developed MACE, as compared with 30 patients (6.4%) in the anti-TNF cohort. There weren’t significant differences between the groups in MACE (aHR, 0.83) or VTE (aHR, 0.77).

In addition, there were no differences when comparing Crohn’s disease with ulcerative colitis for MACE (aHR, 1.69) or VTE (aHR, 0.85); upadacitinib with tofacitinib for MACE (aHR, 1.1) or VTE (aHR, 1.13); or JAKi medications with infliximab for MACE (aHR, 0.85) or VTE (aHR, 0.8).

Patients in the JAKi group were more likely to undergo intestinal resection surgery (aHR, 1.32), but there wasn’t a statistically significant difference in systematic corticosteroid use (aHR, 0.99).

The study limitations included the inability to assess for disease severity, dose-dependent risk for MACE or VTE, or long-term outcomes among the two cohorts, Alsakarneh said. Prospective controlled trials are needed to confirm findings.

 

“This is a wonderful study and nice to see. We presented the same thing at Digestive Disease Week that’s being confirmed in this data,” said Miguel Regueiro, MD, AGAF, chief of Cleveland Clinic’s Digestive Disease Institute in Ohio. Regueiro, who wasn’t involved with the study, attended the conference session.

“Looking ahead, all of us are wondering if the regulatory guidance by the FDA [Food and Drug Administration] is going to change the label so we don’t need to step through a TNF,” he said. “I think we’re seeing study after study showing safety or at least not an increased risk with JAK.”

The study was awarded an ACG Noteworthy Abstract. Alsakarneh and Regueiro reported no relevant disclosures.

A version of this article appeared on Medscape.com.

PHILADELPHIA — Patients with inflammatory bowel disease (IBD) don’t appear to face an increased risk of major adverse cardiovascular events (MACE) or venous thromboembolism (VTE) when taking Janus kinase inhibitors (JAKi), compared with anti–tumor necrosis factor (TNF) agents, according to a study presented at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.

In particular, 1.76% of patients taking JAKi and 1.94% of patients taking anti-TNF developed MACE. There also weren’t significant differences when comparing ulcerative colitis with Crohn’s disease, upadacitinib with tofacitinib, or JAKi with infliximab.

“IBD is associated with an increased risk of cardiovascular diseases, and with the emergence of JAK inhibitors and anti-TNF therapies, there is a concern about the increased risk of MACE,” said lead author Saqr Alsakarneh, MD, an internal medicine resident at the University of Missouri–Kansas City School of Medicine.

Previous randomized controlled trials have indicated increased risks of MACE with JAKi and anti-TNF agents, compared with placebo, but researchers haven’t conducted a head-to-head comparison, he said.

“A potential explanation for previous associations could be linked to immune modulation and inflammation that can increase coagulation risk, as well as fluctuation in disease severity while patients are on the medications, which can impact cardiovascular risk factors,” he added.

Alsakarneh and colleagues conducted a retrospective cohort study using the TriNetX database to identify adult patients with IBD who were treated with JAKi or anti-TNF therapy after diagnosis. After matching patients in the JAKi cohort with patients in the anti-TNF cohort, the research team looked for MACE and VTE within a year of medication initiation, as well as associations by age, sex, and IBD type.

Overall, 3740 patients in the JAKi cohort had a mean age of 43.1 and were 48.9% women and 75.3% White individuals, while 3,740 patients in the anti-TNF cohort had a mean age of 43 and were 48.9% women and 75.3% White individuals.

After excluding those with a history of a prior cardiovascular event, 57 patients (1.76%) in the JAKi cohort developed MACE, compared with 63 patients (1.94%) in the anti-TNF cohort. There weren’t significant differences between the groups in MACE (adjusted hazard ratio [aHR], 0.99) or VTE (aHR, 0.9).

Among patients aged ≥ 65, 25 patients (5.3%) in the JAKi cohort developed MACE, as compared with 30 patients (6.4%) in the anti-TNF cohort. There weren’t significant differences between the groups in MACE (aHR, 0.83) or VTE (aHR, 0.77).

In addition, there were no differences when comparing Crohn’s disease with ulcerative colitis for MACE (aHR, 1.69) or VTE (aHR, 0.85); upadacitinib with tofacitinib for MACE (aHR, 1.1) or VTE (aHR, 1.13); or JAKi medications with infliximab for MACE (aHR, 0.85) or VTE (aHR, 0.8).

Patients in the JAKi group were more likely to undergo intestinal resection surgery (aHR, 1.32), but there wasn’t a statistically significant difference in systematic corticosteroid use (aHR, 0.99).

The study limitations included the inability to assess for disease severity, dose-dependent risk for MACE or VTE, or long-term outcomes among the two cohorts, Alsakarneh said. Prospective controlled trials are needed to confirm findings.

 

“This is a wonderful study and nice to see. We presented the same thing at Digestive Disease Week that’s being confirmed in this data,” said Miguel Regueiro, MD, AGAF, chief of Cleveland Clinic’s Digestive Disease Institute in Ohio. Regueiro, who wasn’t involved with the study, attended the conference session.

“Looking ahead, all of us are wondering if the regulatory guidance by the FDA [Food and Drug Administration] is going to change the label so we don’t need to step through a TNF,” he said. “I think we’re seeing study after study showing safety or at least not an increased risk with JAK.”

The study was awarded an ACG Noteworthy Abstract. Alsakarneh and Regueiro reported no relevant disclosures.

A version of this article appeared on Medscape.com.

PHILADELPHIA — Patients with inflammatory bowel disease (IBD) don’t appear to face an increased risk of major adverse cardiovascular events (MACE) or venous thromboembolism (VTE) when taking Janus kinase inhibitors (JAKi), compared with anti–tumor necrosis factor (TNF) agents, according to a study presented at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.

In particular, 1.76% of patients taking JAKi and 1.94% of patients taking anti-TNF developed MACE. There also weren’t significant differences when comparing ulcerative colitis with Crohn’s disease, upadacitinib with tofacitinib, or JAKi with infliximab.

“IBD is associated with an increased risk of cardiovascular diseases, and with the emergence of JAK inhibitors and anti-TNF therapies, there is a concern about the increased risk of MACE,” said lead author Saqr Alsakarneh, MD, an internal medicine resident at the University of Missouri–Kansas City School of Medicine.

Previous randomized controlled trials have indicated increased risks of MACE with JAKi and anti-TNF agents, compared with placebo, but researchers haven’t conducted a head-to-head comparison, he said.

“A potential explanation for previous associations could be linked to immune modulation and inflammation that can increase coagulation risk, as well as fluctuation in disease severity while patients are on the medications, which can impact cardiovascular risk factors,” he added.

Alsakarneh and colleagues conducted a retrospective cohort study using the TriNetX database to identify adult patients with IBD who were treated with JAKi or anti-TNF therapy after diagnosis. After matching patients in the JAKi cohort with patients in the anti-TNF cohort, the research team looked for MACE and VTE within a year of medication initiation, as well as associations by age, sex, and IBD type.

Overall, 3740 patients in the JAKi cohort had a mean age of 43.1 and were 48.9% women and 75.3% White individuals, while 3,740 patients in the anti-TNF cohort had a mean age of 43 and were 48.9% women and 75.3% White individuals.

After excluding those with a history of a prior cardiovascular event, 57 patients (1.76%) in the JAKi cohort developed MACE, compared with 63 patients (1.94%) in the anti-TNF cohort. There weren’t significant differences between the groups in MACE (adjusted hazard ratio [aHR], 0.99) or VTE (aHR, 0.9).

Among patients aged ≥ 65, 25 patients (5.3%) in the JAKi cohort developed MACE, as compared with 30 patients (6.4%) in the anti-TNF cohort. There weren’t significant differences between the groups in MACE (aHR, 0.83) or VTE (aHR, 0.77).

In addition, there were no differences when comparing Crohn’s disease with ulcerative colitis for MACE (aHR, 1.69) or VTE (aHR, 0.85); upadacitinib with tofacitinib for MACE (aHR, 1.1) or VTE (aHR, 1.13); or JAKi medications with infliximab for MACE (aHR, 0.85) or VTE (aHR, 0.8).

Patients in the JAKi group were more likely to undergo intestinal resection surgery (aHR, 1.32), but there wasn’t a statistically significant difference in systematic corticosteroid use (aHR, 0.99).

The study limitations included the inability to assess for disease severity, dose-dependent risk for MACE or VTE, or long-term outcomes among the two cohorts, Alsakarneh said. Prospective controlled trials are needed to confirm findings.

 

“This is a wonderful study and nice to see. We presented the same thing at Digestive Disease Week that’s being confirmed in this data,” said Miguel Regueiro, MD, AGAF, chief of Cleveland Clinic’s Digestive Disease Institute in Ohio. Regueiro, who wasn’t involved with the study, attended the conference session.

“Looking ahead, all of us are wondering if the regulatory guidance by the FDA [Food and Drug Administration] is going to change the label so we don’t need to step through a TNF,” he said. “I think we’re seeing study after study showing safety or at least not an increased risk with JAK.”

The study was awarded an ACG Noteworthy Abstract. Alsakarneh and Regueiro reported no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Replacing animal-based protein sources with plant-based alternatives in older adults reduced both the quality and quantity of protein intake only when all animal-based foods were eliminated for a vegan scenario, finds a simulation study that suggests a switch to 60% plant-based protein seems to be safe.

METHODOLOGY:

• For environmental and health reasons, the Dutch Health Council advises a switch to an animal-based to plant-based protein ratio of 40:60, but older adults also need adequate protein intake to prevent muscle loss and maintain health, and it’s uncertain if they can meet their protein requirements through a more sustainable diet.
• This simulation study evaluated the impact of more sustainable eating patterns on protein quantity and quality by using data of 607 community-dwelling older adults aged 65-79 years from the Dutch National Food Consumption Survey 2019-2021.
• Data on food consumption were collected via two 24-hour dietary recalls per participant on nonconsecutive days and calculated as three main meals and four in-between moments each day.
• In the simulation, certain food products in the original diet were replaced from a list of similar plant-based alternatives, using a random number generator, to create scenarios for two flexitarian diets (40% and 80% meat and fish were replaced), one pescetarian diet (meat was replaced, but not fish and other animal-based products), one vegetarian diet (meat and fish were replaced, but not other animal-based products), and one vegan diet (fish, meat, and animal-based products were replaced).
• Protein intake was calculated in three ways for each meal moment, including by total protein intake (quantity) and by the proportion of indispensable amino acids that must be eaten together within a limited timeframe (quality).

TAKEAWAY:

• In the reference diet, the total daily plant-based protein intake was 39.0% in men and 37.7% in women, while in the vegetarian scenario, it was 59.1% in men and 54.2% in women.
• In the flexitarian, pescetarian, and vegetarian scenarios, the usable protein intake was comparable; in the vegan scenario, both total protein intake and usable protein intake were lower, leading to nearly 50% less usable protein than in the original diet.
• In the original diet, 7.5% of men and 11.1% of women did not meet the estimated average requirements (EARs) for utilizable protein; in the vegan scenario, 83.3% of both sexes had a protein intake below the EAR.
• The loss in protein intake (quantity) in all scenarios was mainly observed at dinner; the loss in protein quality was greatest at breakfast and lunch, especially in lysine (found in beans or soy milk).

IN PRACTICE:

“Changing protein intake to 60% plant-based protein seems to be safe for older adults in terms of protein intake. In contrast, a vegan pattern was associated with a substantial decline in protein availability, leading to a majority of older adults not reaching the recommended protein levels,” the authors wrote.

SOURCE:

The study was led by Jos W. Borkent, HAN University of Applied Sciences, Nijmegen, the Netherlands. It was published online in The Journal of Nutrition, Health and Aging.

LIMITATIONS:

Study limitations included the use of a simulation model, which may not fully reflect real-life dietary practices. The strict timeframe for assessing protein quality (optimal combinations of indispensible amino acids) within one meal moment may have led to an underestimation of protein availability, especially in the vegan scenario. Additionally, the choice of processed meat replacements in the vegan scenario may not have represented protein sources of the highest quality available. Higher protein quality per meal in the vegan scenario is possible when smart combinations are made in multiple meal components.

DISCLOSURES:

The study was partly funded by a grant from the Taskforce for Applied Research SIA, which is part of the Netherlands Organisation for Scientific Research and financed by the Dutch Ministry of Education, Culture and Science and by a fund of the Dutch Dairy Association. The authors declared that they had no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Replacing animal-based protein sources with plant-based alternatives in older adults reduced both the quality and quantity of protein intake only when all animal-based foods were eliminated for a vegan scenario, finds a simulation study that suggests a switch to 60% plant-based protein seems to be safe.

METHODOLOGY:

• For environmental and health reasons, the Dutch Health Council advises a switch to an animal-based to plant-based protein ratio of 40:60, but older adults also need adequate protein intake to prevent muscle loss and maintain health, and it’s uncertain if they can meet their protein requirements through a more sustainable diet.
• This simulation study evaluated the impact of more sustainable eating patterns on protein quantity and quality by using data of 607 community-dwelling older adults aged 65-79 years from the Dutch National Food Consumption Survey 2019-2021.
• Data on food consumption were collected via two 24-hour dietary recalls per participant on nonconsecutive days and calculated as three main meals and four in-between moments each day.
• In the simulation, certain food products in the original diet were replaced from a list of similar plant-based alternatives, using a random number generator, to create scenarios for two flexitarian diets (40% and 80% meat and fish were replaced), one pescetarian diet (meat was replaced, but not fish and other animal-based products), one vegetarian diet (meat and fish were replaced, but not other animal-based products), and one vegan diet (fish, meat, and animal-based products were replaced).
• Protein intake was calculated in three ways for each meal moment, including by total protein intake (quantity) and by the proportion of indispensable amino acids that must be eaten together within a limited timeframe (quality).

TAKEAWAY:

• In the reference diet, the total daily plant-based protein intake was 39.0% in men and 37.7% in women, while in the vegetarian scenario, it was 59.1% in men and 54.2% in women.
• In the flexitarian, pescetarian, and vegetarian scenarios, the usable protein intake was comparable; in the vegan scenario, both total protein intake and usable protein intake were lower, leading to nearly 50% less usable protein than in the original diet.
• In the original diet, 7.5% of men and 11.1% of women did not meet the estimated average requirements (EARs) for utilizable protein; in the vegan scenario, 83.3% of both sexes had a protein intake below the EAR.
• The loss in protein intake (quantity) in all scenarios was mainly observed at dinner; the loss in protein quality was greatest at breakfast and lunch, especially in lysine (found in beans or soy milk).

IN PRACTICE:

“Changing protein intake to 60% plant-based protein seems to be safe for older adults in terms of protein intake. In contrast, a vegan pattern was associated with a substantial decline in protein availability, leading to a majority of older adults not reaching the recommended protein levels,” the authors wrote.

SOURCE:

The study was led by Jos W. Borkent, HAN University of Applied Sciences, Nijmegen, the Netherlands. It was published online in The Journal of Nutrition, Health and Aging.

LIMITATIONS:

Study limitations included the use of a simulation model, which may not fully reflect real-life dietary practices. The strict timeframe for assessing protein quality (optimal combinations of indispensible amino acids) within one meal moment may have led to an underestimation of protein availability, especially in the vegan scenario. Additionally, the choice of processed meat replacements in the vegan scenario may not have represented protein sources of the highest quality available. Higher protein quality per meal in the vegan scenario is possible when smart combinations are made in multiple meal components.

DISCLOSURES:

The study was partly funded by a grant from the Taskforce for Applied Research SIA, which is part of the Netherlands Organisation for Scientific Research and financed by the Dutch Ministry of Education, Culture and Science and by a fund of the Dutch Dairy Association. The authors declared that they had no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Replacing animal-based protein sources with plant-based alternatives in older adults reduced both the quality and quantity of protein intake only when all animal-based foods were eliminated for a vegan scenario, finds a simulation study that suggests a switch to 60% plant-based protein seems to be safe.

METHODOLOGY:

• For environmental and health reasons, the Dutch Health Council advises a switch to an animal-based to plant-based protein ratio of 40:60, but older adults also need adequate protein intake to prevent muscle loss and maintain health, and it’s uncertain if they can meet their protein requirements through a more sustainable diet.
• This simulation study evaluated the impact of more sustainable eating patterns on protein quantity and quality by using data of 607 community-dwelling older adults aged 65-79 years from the Dutch National Food Consumption Survey 2019-2021.
• Data on food consumption were collected via two 24-hour dietary recalls per participant on nonconsecutive days and calculated as three main meals and four in-between moments each day.
• In the simulation, certain food products in the original diet were replaced from a list of similar plant-based alternatives, using a random number generator, to create scenarios for two flexitarian diets (40% and 80% meat and fish were replaced), one pescetarian diet (meat was replaced, but not fish and other animal-based products), one vegetarian diet (meat and fish were replaced, but not other animal-based products), and one vegan diet (fish, meat, and animal-based products were replaced).
• Protein intake was calculated in three ways for each meal moment, including by total protein intake (quantity) and by the proportion of indispensable amino acids that must be eaten together within a limited timeframe (quality).

TAKEAWAY:

• In the reference diet, the total daily plant-based protein intake was 39.0% in men and 37.7% in women, while in the vegetarian scenario, it was 59.1% in men and 54.2% in women.
• In the flexitarian, pescetarian, and vegetarian scenarios, the usable protein intake was comparable; in the vegan scenario, both total protein intake and usable protein intake were lower, leading to nearly 50% less usable protein than in the original diet.
• In the original diet, 7.5% of men and 11.1% of women did not meet the estimated average requirements (EARs) for utilizable protein; in the vegan scenario, 83.3% of both sexes had a protein intake below the EAR.
• The loss in protein intake (quantity) in all scenarios was mainly observed at dinner; the loss in protein quality was greatest at breakfast and lunch, especially in lysine (found in beans or soy milk).

IN PRACTICE:

“Changing protein intake to 60% plant-based protein seems to be safe for older adults in terms of protein intake. In contrast, a vegan pattern was associated with a substantial decline in protein availability, leading to a majority of older adults not reaching the recommended protein levels,” the authors wrote.

SOURCE:

The study was led by Jos W. Borkent, HAN University of Applied Sciences, Nijmegen, the Netherlands. It was published online in The Journal of Nutrition, Health and Aging.

LIMITATIONS:

Study limitations included the use of a simulation model, which may not fully reflect real-life dietary practices. The strict timeframe for assessing protein quality (optimal combinations of indispensible amino acids) within one meal moment may have led to an underestimation of protein availability, especially in the vegan scenario. Additionally, the choice of processed meat replacements in the vegan scenario may not have represented protein sources of the highest quality available. Higher protein quality per meal in the vegan scenario is possible when smart combinations are made in multiple meal components.

DISCLOSURES:

The study was partly funded by a grant from the Taskforce for Applied Research SIA, which is part of the Netherlands Organisation for Scientific Research and financed by the Dutch Ministry of Education, Culture and Science and by a fund of the Dutch Dairy Association. The authors declared that they had no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

I’m just back from the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting in Philadelphia, Pennsylvania. 

In part 2 of this series, I’m offering my highlights from this year’s meeting. (Part 1 is available here.) They are not presented in any particular order, but instead I am sharing what I found to be the most exciting among the thousands of abstracts and presentations. 

 

Performing Capsule Endoscopy in Patients Taking GLP-1s 

We’ve heard a lot about glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and the possibility that they might contribute to an increased risk for retained gastric contents and aspiration during endoscopy.

In the first study I’d like to highlight, researchers from the Mayo Clinic in Jacksonville, Florida, investigated video capsule endoscopy in patients with diabetes who were taking GLP-1 RAs vs a control group with diabetes not taking GLP-1 Ras. Patients in this retrospective matched cohort study were well balanced for demographics and diabetes-related characteristics.

Researchers found that in 7% of the 68 patients in the GLP-1 RA cohort, the video capsule endoscopy actually failed to pass through the stomach, whereas it passed successfully in all 68 patients in the control group (P =.06). The GLP-1 RA cohort had a longer transit time by a factor of almost four times (P <.001).

Multivariate analysis also showed that gastric transit time was approximately 80 minutes longer in the GLP-1 RA cohort (P <.001). Interestingly, 23.5% (16 of 68 patients) in the GLP-1 RA group experienced incomplete passage of the video capsule endoscopy through the small intestine, which was significantly higher than the proportion observed in the control group (4.4%; P <.01). 

We need to look at potential strategies to mitigate these effects. Be aware of these results as you perform capsule endoscopy in patients taking GLP-1 RAs. 

 

Barrett Esophagus On the Rise in the Young 

The second study that caught my eye revealed the increasing incidence of young-onset Barrett esophagus (BE).

This population-based study used data obtained from TriNetX, a multi-institutional national database that offers a composite of health records from 88 healthcare organizations. Eligible patients had to have a negative upper esophagogastroduodenoscopy for BE prior to subsequently developing BE. Researchers stratified patients as to whether they were younger (< 50 years) or older (≥ 50 years), with further age ranges analyzed within those groups. 

Young-onset BE accounted for 20% of all incident cases. The majority (94%) had nondysplastic BE. The incidence rate was not significantly different depending on whether patients were in the 45- to 49-year or 50- to 54-year age group. 

Regression analysis revealed that there was a significantly increased trend for young-onset BE with hiatal hernia (odds ratio [OR], 2.6), smoking (OR, 2.3), White race (OR, 2.3), obstructive sleep apnea (OR, 2.2), male gender (OR, 2.0), and — at relatively lower risk levels — gastroesophageal reflux disease symptoms (OR, 1.2) and body mass index (OR, 1.1). The researchers did not analyze patients based on the presence of obesity, which is one of the risk factors for BE mentioned in national guidelines.

Results also showed that 6% of those with young-onset BE had BE-related neoplasia. 

ACG guidelines recommend screening for BE beginning at age 50 in those with some of the risk factors noted in this study, including the presence of chronic gastroesophageal reflux disease symptoms. However, doing so may not capture the growing number of patients with young-onset BE. 

We’ve seen a similar rise in rates of young-onset colorectal cancer, which has caused us to reevaluate our screening methods. Maybe we should do this for BE as well, specifically for patients presenting with these risk factors. 

There’s a caveat to be aware of, which comes from my personal experience. I was biopsied for short-segment BE, and because it came up on my health record, it increased my life insurance premiums. This was because I was identified as having the risk profile of, essentially, an otherwise healthy smoker. 

Dr Nicholas J. Shaheen and colleagues published a study several years ago showing that many insurance companies would not certify young, otherwise healthy people once diagnosed with BE. This is something to be aware of when you start to screen for BE, especially among younger patients.

 

A Novel Biologic for Eosinophilic Esophagitis 

The next study presented results from a randomized, placebo-controlled, phase 3 study of cendakimab, a biologic agent in development for the treatment of eosinophilic esophagitis (EoE).

Dupilumab, which is an anti–interleukin (IL)-4 antibody, is the first treatment approved by the US Food and Drug Administration (FDA) for the treatment of EoE. Cendakimab, in turn, is a monoclonal antibody that neutralizes IL-13, a cytokine that plays a key role in EoE. 

The study was led by Dr Evan Dellon from the University of North Carolina at Chapel Hill. Dellon and colleagues analyzed two different dosing regimens of cendakimab — 360 mg once weekly for 48 weeks, or 360 mg once weekly for 24 weeks followed by 360 mg every other week for 24 weeks — vs placebo for 48 weeks. 

There was a significant effect for both cendakimab regimens in terms of symptom improvement and histologic response. There wasn’t much difference between participants that maintained once-weekly dosing and those who switched over to receive cendakimab every other week at 24 weeks. Only a minimal number of serious adverse events leading to discontinuation were noted in the study, with no notable difference between the treatment groups. 

I think we’ll probably see this drug become available to us soon after it goes through the FDA review process, at which point it will add to our ability to use formative biologics in patients with EoE.

 

No Clear Benefit to Adding Bezlotoxumab to Fecal Microbiota Transplantation 

Next was a very interesting study, and I think a clinically relevant one, about using fecal microbiota transplantation (FMT) alone or in combination with bezlotoxumab in patients with inflammatory bowel disease (IBD) with recurrent Clostridioides difficile infection.

Bezlotoxumab is a fully human monoclonal antibody that binds to C difficile toxin B. This drug has been studied and is approved for use, but it’s also extremely expensive, at a cost of approximately $4000 per dose. 

Patients with IBD were eligible for inclusion if they had had two or more episodes of C difficile infection. They were then randomized in a 1:1 ration to receive either a single infusion of bezlotoxumab or placebo prior to FMT. The primary endpoint was C difficile infection recurrence within 8 weeks, which was defined as diarrhea plus a positive enzyme immunoassay toxin test. The secondary outcome was C difficile decolonization following treatment. 

Researchers observed no statistically significant difference between the two cohorts. Steroid use prior to FMT significantly increased the risk for ongoing C difficile colonization (P =.03). 

In summary, this is a case where it doesn’t seem that more is better. Bezlotoxumab didn’t add much, which calls into question the justification for its combined use with FMT. 

 

Additional Positive Data for Seladelpar in Primary Biliary Cholangitis and Cirrhosis 

Reassuring findings were presented on seladelpar, which was granted accelerated approval by the FDA in August. 

Seladelpar is a selective peroxisome proliferator–activated receptor delta agonist that works in biliary cholangitis by regulating the genes involved in blocking biliary bile acid synthesis and controlling inflammation and fibrosis. 

Results from the phase 3 RESPONSE trial were published in The New England Journal of Medicine in February reporting on the use of seladelpar in primary biliary cholangitis.

Whereas the RESPONSE trial removed decompensated patients, the ongoing phase 3 ASSURE trial results presented at this year’s meeting included patients with compensated cirrhosis. Approximately 94% of the patients in this study had Child-Pugh class A and 6% had class B cirrhosis. Eligibility required that patients had an inadequate response or were intolerant to ursodeoxycholic acid. Patients were administered open-label seladelpar 10 mg orally daily and followed for up to 1 year.

The good news is that there were no safety signals, which is reassuring news for our patients with compensated cirrhosis. 

 

Advantages to Respiratory Syncytial Virus Vaccination in IBD 

Another study that offered results certainly worthy of attention dealt with vaccination recommendations in patients with IBD. 

Vaccination for respiratory syncytial virus (RSV) is now available in the United States. Its use was recommended for patients with IBD as early as 2021 per the Canadian Association of Gastroenterology’s clinical practice guideline, which discusses both live and nonlive vaccines. We should be aggressive in recommending this vaccine to our patients with IBD, but we haven’t really had one until recently. 

Researchers behind this retrospective cohort study used the TriNetX database, which includes over 100 million unique patient charts. They identified patients with IBD, who were then divided into two groups according to whether they received the RSV vaccine or not. 

Although this analysis was conducted in patients > 60 years of age, the US Centers for Disease Control and Prevention recommends RSV vaccination for all those over the age of 75 years, as well as for those 60-74 years old based on severity of risk. 

For the primary endpoint of risk for RSV pneumonia, the OR was dramatically better in those who were vaccinated, with an approximately 80% risk reduction. Additionally, vaccinated patients experienced risk reductions of approximately 60% for acute respiratory failure, 50% for hospital inpatient admission, and 70% for requiring intensive care unit services. 

This is a strong study showing not only that RSV vaccine did not exacerbate IBD but also that it improved outcomes in these patients. There’s a live-attenuated RSV vaccination that’s administered intranasally, which wouldn’t be used in your biologic or immunosuppressed patients with IBD, but the intramuscularly administered RSV vaccine doesn’t have any risk.

I think we can immediately begin recommending the RSV vaccine for our patients with IBD, particularly in those 60 years of age or older.

 

The Impact of Palliative Care Consultations in Decompensated Cirrhosis 

The next study I’d like to highlight offers important data on the impact of palliative care consultation on 30- and 90-day readmission in patients with decompensated cirrhosis, which is a major cause of morbidity and mortality.

Researchers queried the National Readmissions Database over a 10-year period (2010-2019) to determine whether patients received a palliative care consult during index admission. They drew on a population of over 1.6 million patients admitted with decompensated cirrhosis. 

Of this group, only 7.4% received a palliative care consultation at the index admission. But if they had this consultation, it was associated with a dramatic effect on readmission at 30 and 90 days. There was statistically significant risk reduction of approximately 70% for both 30- and 90-day readmission compared with those who didn’t receive the palliative consult (P <.001).

The take-home message here is to get a palliative care consult with these patients when they come in. Your hospital will unquestionably experience value in this reduction in readmission, especially considering that readmission within 30 days may not even be covered. Look at these results and start to take advantage of this valuable consultation.

 

Auxora: A Novel Treatment for Acute Pancreatitis 

The last study for discussion offered very interesting data related to a drug called Auxora, a calcium release–activated calcium-channel inhibitor.

There is growing data that overactive calcium release–activated calcium channels aggravate acute pancreatitis and accelerate systemic inflammatory response syndrome (SIRS).

Acute pancreatitis with necrosis encompasses both local and systemic inflammation and is associated with significant mortality and morbidity. It is estimated that among patients with acute pancreatitis, 20%-30% have pancreatic necrosis, 30% develop infection, and 25% develop organ failure. 

The presence of SIRS seems to herald the activation of these complex inflammatory pathways, which then leads to organ failure and necrosis, which can potentially be stemmed through this calcium channel inhibitor. Phase 2 studies of Auxora found that its use was associated with significant reduction in the risk for progression.

This subsequent phase 3 study looked at patients with acute pancreatitis and accompanying grade ≥ 2 SIRS criteria. They were randomized to receive placebo or Auxora at doses of 2 mg/kg, 1 mg/kg, or 0.5 mg/kg, which was administered intravenously over 4 hours for 3 consecutive days. 

The primary endpoint was time to solid food tolerance, which was defined as eating ≥ 50% of a ≥ 500-calorie low-fat solid meal without increased abdominal pain or emesis, which is an important target because we always aim for enteral nutrition in patients with acute pancreatitis. The key secondary endpoint was severe respiratory failure, which was defined as invasive mechanical ventilation or ≥ 48 hours of either high-flow nasal cannula or noninvasive mechanical ventilation. 

The primary endpoint was dramatically improved among those receiving Auxora, who achieved early onset of refeed. It appears that the high-dose 2 mg/kg may be the most beneficial in achieving improvement. 

There were no patients with suspected or unexpected adverse events in the study population. Additionally, no patients receiving Auxora at any dose level went on to develop respiratory failure. 

The present results show that Auxora decreases the time for solid food tolerance, as well as the rates of respiratory failure and necrotizing pancreatitis in patients presenting with two or more SIRS criteria. We’ll certainly look forward to more data, but it provides hope for a new treatment for acute pancreatitis.

There were lots of intriguing data presented at ACG 2024. Obviously, we’d like to see them evolve in subsequent journal manuscripts. 

Some of the take-home messages I presented are actionable now, whereas for others, we’ll have to wait and see what the final data show as well as the results of ongoing FDA approval before applying them. 

 

Dr Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. He reported serving in an advisory position with ISOTHRIVE. This transcript has been edited for clarity.

A version of this article first appeared on Medscape.com.

I’m just back from the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting in Philadelphia, Pennsylvania. 

In part 2 of this series, I’m offering my highlights from this year’s meeting. (Part 1 is available here.) They are not presented in any particular order, but instead I am sharing what I found to be the most exciting among the thousands of abstracts and presentations. 

 

Performing Capsule Endoscopy in Patients Taking GLP-1s 

We’ve heard a lot about glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and the possibility that they might contribute to an increased risk for retained gastric contents and aspiration during endoscopy.

In the first study I’d like to highlight, researchers from the Mayo Clinic in Jacksonville, Florida, investigated video capsule endoscopy in patients with diabetes who were taking GLP-1 RAs vs a control group with diabetes not taking GLP-1 Ras. Patients in this retrospective matched cohort study were well balanced for demographics and diabetes-related characteristics.

Researchers found that in 7% of the 68 patients in the GLP-1 RA cohort, the video capsule endoscopy actually failed to pass through the stomach, whereas it passed successfully in all 68 patients in the control group (P =.06). The GLP-1 RA cohort had a longer transit time by a factor of almost four times (P <.001).

Multivariate analysis also showed that gastric transit time was approximately 80 minutes longer in the GLP-1 RA cohort (P <.001). Interestingly, 23.5% (16 of 68 patients) in the GLP-1 RA group experienced incomplete passage of the video capsule endoscopy through the small intestine, which was significantly higher than the proportion observed in the control group (4.4%; P <.01). 

We need to look at potential strategies to mitigate these effects. Be aware of these results as you perform capsule endoscopy in patients taking GLP-1 RAs. 

 

Barrett Esophagus On the Rise in the Young 

The second study that caught my eye revealed the increasing incidence of young-onset Barrett esophagus (BE).

This population-based study used data obtained from TriNetX, a multi-institutional national database that offers a composite of health records from 88 healthcare organizations. Eligible patients had to have a negative upper esophagogastroduodenoscopy for BE prior to subsequently developing BE. Researchers stratified patients as to whether they were younger (< 50 years) or older (≥ 50 years), with further age ranges analyzed within those groups. 

Young-onset BE accounted for 20% of all incident cases. The majority (94%) had nondysplastic BE. The incidence rate was not significantly different depending on whether patients were in the 45- to 49-year or 50- to 54-year age group. 

Regression analysis revealed that there was a significantly increased trend for young-onset BE with hiatal hernia (odds ratio [OR], 2.6), smoking (OR, 2.3), White race (OR, 2.3), obstructive sleep apnea (OR, 2.2), male gender (OR, 2.0), and — at relatively lower risk levels — gastroesophageal reflux disease symptoms (OR, 1.2) and body mass index (OR, 1.1). The researchers did not analyze patients based on the presence of obesity, which is one of the risk factors for BE mentioned in national guidelines.

Results also showed that 6% of those with young-onset BE had BE-related neoplasia. 

ACG guidelines recommend screening for BE beginning at age 50 in those with some of the risk factors noted in this study, including the presence of chronic gastroesophageal reflux disease symptoms. However, doing so may not capture the growing number of patients with young-onset BE. 

We’ve seen a similar rise in rates of young-onset colorectal cancer, which has caused us to reevaluate our screening methods. Maybe we should do this for BE as well, specifically for patients presenting with these risk factors. 

There’s a caveat to be aware of, which comes from my personal experience. I was biopsied for short-segment BE, and because it came up on my health record, it increased my life insurance premiums. This was because I was identified as having the risk profile of, essentially, an otherwise healthy smoker. 

Dr Nicholas J. Shaheen and colleagues published a study several years ago showing that many insurance companies would not certify young, otherwise healthy people once diagnosed with BE. This is something to be aware of when you start to screen for BE, especially among younger patients.

 

A Novel Biologic for Eosinophilic Esophagitis 

The next study presented results from a randomized, placebo-controlled, phase 3 study of cendakimab, a biologic agent in development for the treatment of eosinophilic esophagitis (EoE).

Dupilumab, which is an anti–interleukin (IL)-4 antibody, is the first treatment approved by the US Food and Drug Administration (FDA) for the treatment of EoE. Cendakimab, in turn, is a monoclonal antibody that neutralizes IL-13, a cytokine that plays a key role in EoE. 

The study was led by Dr Evan Dellon from the University of North Carolina at Chapel Hill. Dellon and colleagues analyzed two different dosing regimens of cendakimab — 360 mg once weekly for 48 weeks, or 360 mg once weekly for 24 weeks followed by 360 mg every other week for 24 weeks — vs placebo for 48 weeks. 

There was a significant effect for both cendakimab regimens in terms of symptom improvement and histologic response. There wasn’t much difference between participants that maintained once-weekly dosing and those who switched over to receive cendakimab every other week at 24 weeks. Only a minimal number of serious adverse events leading to discontinuation were noted in the study, with no notable difference between the treatment groups. 

I think we’ll probably see this drug become available to us soon after it goes through the FDA review process, at which point it will add to our ability to use formative biologics in patients with EoE.

 

No Clear Benefit to Adding Bezlotoxumab to Fecal Microbiota Transplantation 

Next was a very interesting study, and I think a clinically relevant one, about using fecal microbiota transplantation (FMT) alone or in combination with bezlotoxumab in patients with inflammatory bowel disease (IBD) with recurrent Clostridioides difficile infection.

Bezlotoxumab is a fully human monoclonal antibody that binds to C difficile toxin B. This drug has been studied and is approved for use, but it’s also extremely expensive, at a cost of approximately $4000 per dose. 

Patients with IBD were eligible for inclusion if they had had two or more episodes of C difficile infection. They were then randomized in a 1:1 ration to receive either a single infusion of bezlotoxumab or placebo prior to FMT. The primary endpoint was C difficile infection recurrence within 8 weeks, which was defined as diarrhea plus a positive enzyme immunoassay toxin test. The secondary outcome was C difficile decolonization following treatment. 

Researchers observed no statistically significant difference between the two cohorts. Steroid use prior to FMT significantly increased the risk for ongoing C difficile colonization (P =.03). 

In summary, this is a case where it doesn’t seem that more is better. Bezlotoxumab didn’t add much, which calls into question the justification for its combined use with FMT. 

 

Additional Positive Data for Seladelpar in Primary Biliary Cholangitis and Cirrhosis 

Reassuring findings were presented on seladelpar, which was granted accelerated approval by the FDA in August. 

Seladelpar is a selective peroxisome proliferator–activated receptor delta agonist that works in biliary cholangitis by regulating the genes involved in blocking biliary bile acid synthesis and controlling inflammation and fibrosis. 

Results from the phase 3 RESPONSE trial were published in The New England Journal of Medicine in February reporting on the use of seladelpar in primary biliary cholangitis.

Whereas the RESPONSE trial removed decompensated patients, the ongoing phase 3 ASSURE trial results presented at this year’s meeting included patients with compensated cirrhosis. Approximately 94% of the patients in this study had Child-Pugh class A and 6% had class B cirrhosis. Eligibility required that patients had an inadequate response or were intolerant to ursodeoxycholic acid. Patients were administered open-label seladelpar 10 mg orally daily and followed for up to 1 year.

The good news is that there were no safety signals, which is reassuring news for our patients with compensated cirrhosis. 

 

Advantages to Respiratory Syncytial Virus Vaccination in IBD 

Another study that offered results certainly worthy of attention dealt with vaccination recommendations in patients with IBD. 

Vaccination for respiratory syncytial virus (RSV) is now available in the United States. Its use was recommended for patients with IBD as early as 2021 per the Canadian Association of Gastroenterology’s clinical practice guideline, which discusses both live and nonlive vaccines. We should be aggressive in recommending this vaccine to our patients with IBD, but we haven’t really had one until recently. 

Researchers behind this retrospective cohort study used the TriNetX database, which includes over 100 million unique patient charts. They identified patients with IBD, who were then divided into two groups according to whether they received the RSV vaccine or not. 

Although this analysis was conducted in patients > 60 years of age, the US Centers for Disease Control and Prevention recommends RSV vaccination for all those over the age of 75 years, as well as for those 60-74 years old based on severity of risk. 

For the primary endpoint of risk for RSV pneumonia, the OR was dramatically better in those who were vaccinated, with an approximately 80% risk reduction. Additionally, vaccinated patients experienced risk reductions of approximately 60% for acute respiratory failure, 50% for hospital inpatient admission, and 70% for requiring intensive care unit services. 

This is a strong study showing not only that RSV vaccine did not exacerbate IBD but also that it improved outcomes in these patients. There’s a live-attenuated RSV vaccination that’s administered intranasally, which wouldn’t be used in your biologic or immunosuppressed patients with IBD, but the intramuscularly administered RSV vaccine doesn’t have any risk.

I think we can immediately begin recommending the RSV vaccine for our patients with IBD, particularly in those 60 years of age or older.

 

The Impact of Palliative Care Consultations in Decompensated Cirrhosis 

The next study I’d like to highlight offers important data on the impact of palliative care consultation on 30- and 90-day readmission in patients with decompensated cirrhosis, which is a major cause of morbidity and mortality.

Researchers queried the National Readmissions Database over a 10-year period (2010-2019) to determine whether patients received a palliative care consult during index admission. They drew on a population of over 1.6 million patients admitted with decompensated cirrhosis. 

Of this group, only 7.4% received a palliative care consultation at the index admission. But if they had this consultation, it was associated with a dramatic effect on readmission at 30 and 90 days. There was statistically significant risk reduction of approximately 70% for both 30- and 90-day readmission compared with those who didn’t receive the palliative consult (P <.001).

The take-home message here is to get a palliative care consult with these patients when they come in. Your hospital will unquestionably experience value in this reduction in readmission, especially considering that readmission within 30 days may not even be covered. Look at these results and start to take advantage of this valuable consultation.

 

Auxora: A Novel Treatment for Acute Pancreatitis 

The last study for discussion offered very interesting data related to a drug called Auxora, a calcium release–activated calcium-channel inhibitor.

There is growing data that overactive calcium release–activated calcium channels aggravate acute pancreatitis and accelerate systemic inflammatory response syndrome (SIRS).

Acute pancreatitis with necrosis encompasses both local and systemic inflammation and is associated with significant mortality and morbidity. It is estimated that among patients with acute pancreatitis, 20%-30% have pancreatic necrosis, 30% develop infection, and 25% develop organ failure. 

The presence of SIRS seems to herald the activation of these complex inflammatory pathways, which then leads to organ failure and necrosis, which can potentially be stemmed through this calcium channel inhibitor. Phase 2 studies of Auxora found that its use was associated with significant reduction in the risk for progression.

This subsequent phase 3 study looked at patients with acute pancreatitis and accompanying grade ≥ 2 SIRS criteria. They were randomized to receive placebo or Auxora at doses of 2 mg/kg, 1 mg/kg, or 0.5 mg/kg, which was administered intravenously over 4 hours for 3 consecutive days. 

The primary endpoint was time to solid food tolerance, which was defined as eating ≥ 50% of a ≥ 500-calorie low-fat solid meal without increased abdominal pain or emesis, which is an important target because we always aim for enteral nutrition in patients with acute pancreatitis. The key secondary endpoint was severe respiratory failure, which was defined as invasive mechanical ventilation or ≥ 48 hours of either high-flow nasal cannula or noninvasive mechanical ventilation. 

The primary endpoint was dramatically improved among those receiving Auxora, who achieved early onset of refeed. It appears that the high-dose 2 mg/kg may be the most beneficial in achieving improvement. 

There were no patients with suspected or unexpected adverse events in the study population. Additionally, no patients receiving Auxora at any dose level went on to develop respiratory failure. 

The present results show that Auxora decreases the time for solid food tolerance, as well as the rates of respiratory failure and necrotizing pancreatitis in patients presenting with two or more SIRS criteria. We’ll certainly look forward to more data, but it provides hope for a new treatment for acute pancreatitis.

There were lots of intriguing data presented at ACG 2024. Obviously, we’d like to see them evolve in subsequent journal manuscripts. 

Some of the take-home messages I presented are actionable now, whereas for others, we’ll have to wait and see what the final data show as well as the results of ongoing FDA approval before applying them. 

 

Dr Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. He reported serving in an advisory position with ISOTHRIVE. This transcript has been edited for clarity.

A version of this article first appeared on Medscape.com.

I’m just back from the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting in Philadelphia, Pennsylvania. 

In part 2 of this series, I’m offering my highlights from this year’s meeting. (Part 1 is available here.) They are not presented in any particular order, but instead I am sharing what I found to be the most exciting among the thousands of abstracts and presentations. 

 

Performing Capsule Endoscopy in Patients Taking GLP-1s 

We’ve heard a lot about glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and the possibility that they might contribute to an increased risk for retained gastric contents and aspiration during endoscopy.

In the first study I’d like to highlight, researchers from the Mayo Clinic in Jacksonville, Florida, investigated video capsule endoscopy in patients with diabetes who were taking GLP-1 RAs vs a control group with diabetes not taking GLP-1 Ras. Patients in this retrospective matched cohort study were well balanced for demographics and diabetes-related characteristics.

Researchers found that in 7% of the 68 patients in the GLP-1 RA cohort, the video capsule endoscopy actually failed to pass through the stomach, whereas it passed successfully in all 68 patients in the control group (P =.06). The GLP-1 RA cohort had a longer transit time by a factor of almost four times (P <.001).

Multivariate analysis also showed that gastric transit time was approximately 80 minutes longer in the GLP-1 RA cohort (P <.001). Interestingly, 23.5% (16 of 68 patients) in the GLP-1 RA group experienced incomplete passage of the video capsule endoscopy through the small intestine, which was significantly higher than the proportion observed in the control group (4.4%; P <.01). 

We need to look at potential strategies to mitigate these effects. Be aware of these results as you perform capsule endoscopy in patients taking GLP-1 RAs. 

 

Barrett Esophagus On the Rise in the Young 

The second study that caught my eye revealed the increasing incidence of young-onset Barrett esophagus (BE).

This population-based study used data obtained from TriNetX, a multi-institutional national database that offers a composite of health records from 88 healthcare organizations. Eligible patients had to have a negative upper esophagogastroduodenoscopy for BE prior to subsequently developing BE. Researchers stratified patients as to whether they were younger (< 50 years) or older (≥ 50 years), with further age ranges analyzed within those groups. 

Young-onset BE accounted for 20% of all incident cases. The majority (94%) had nondysplastic BE. The incidence rate was not significantly different depending on whether patients were in the 45- to 49-year or 50- to 54-year age group. 

Regression analysis revealed that there was a significantly increased trend for young-onset BE with hiatal hernia (odds ratio [OR], 2.6), smoking (OR, 2.3), White race (OR, 2.3), obstructive sleep apnea (OR, 2.2), male gender (OR, 2.0), and — at relatively lower risk levels — gastroesophageal reflux disease symptoms (OR, 1.2) and body mass index (OR, 1.1). The researchers did not analyze patients based on the presence of obesity, which is one of the risk factors for BE mentioned in national guidelines.

Results also showed that 6% of those with young-onset BE had BE-related neoplasia. 

ACG guidelines recommend screening for BE beginning at age 50 in those with some of the risk factors noted in this study, including the presence of chronic gastroesophageal reflux disease symptoms. However, doing so may not capture the growing number of patients with young-onset BE. 

We’ve seen a similar rise in rates of young-onset colorectal cancer, which has caused us to reevaluate our screening methods. Maybe we should do this for BE as well, specifically for patients presenting with these risk factors. 

There’s a caveat to be aware of, which comes from my personal experience. I was biopsied for short-segment BE, and because it came up on my health record, it increased my life insurance premiums. This was because I was identified as having the risk profile of, essentially, an otherwise healthy smoker. 

Dr Nicholas J. Shaheen and colleagues published a study several years ago showing that many insurance companies would not certify young, otherwise healthy people once diagnosed with BE. This is something to be aware of when you start to screen for BE, especially among younger patients.

 

A Novel Biologic for Eosinophilic Esophagitis 

The next study presented results from a randomized, placebo-controlled, phase 3 study of cendakimab, a biologic agent in development for the treatment of eosinophilic esophagitis (EoE).

Dupilumab, which is an anti–interleukin (IL)-4 antibody, is the first treatment approved by the US Food and Drug Administration (FDA) for the treatment of EoE. Cendakimab, in turn, is a monoclonal antibody that neutralizes IL-13, a cytokine that plays a key role in EoE. 

The study was led by Dr Evan Dellon from the University of North Carolina at Chapel Hill. Dellon and colleagues analyzed two different dosing regimens of cendakimab — 360 mg once weekly for 48 weeks, or 360 mg once weekly for 24 weeks followed by 360 mg every other week for 24 weeks — vs placebo for 48 weeks. 

There was a significant effect for both cendakimab regimens in terms of symptom improvement and histologic response. There wasn’t much difference between participants that maintained once-weekly dosing and those who switched over to receive cendakimab every other week at 24 weeks. Only a minimal number of serious adverse events leading to discontinuation were noted in the study, with no notable difference between the treatment groups. 

I think we’ll probably see this drug become available to us soon after it goes through the FDA review process, at which point it will add to our ability to use formative biologics in patients with EoE.

 

No Clear Benefit to Adding Bezlotoxumab to Fecal Microbiota Transplantation 

Next was a very interesting study, and I think a clinically relevant one, about using fecal microbiota transplantation (FMT) alone or in combination with bezlotoxumab in patients with inflammatory bowel disease (IBD) with recurrent Clostridioides difficile infection.

Bezlotoxumab is a fully human monoclonal antibody that binds to C difficile toxin B. This drug has been studied and is approved for use, but it’s also extremely expensive, at a cost of approximately $4000 per dose. 

Patients with IBD were eligible for inclusion if they had had two or more episodes of C difficile infection. They were then randomized in a 1:1 ration to receive either a single infusion of bezlotoxumab or placebo prior to FMT. The primary endpoint was C difficile infection recurrence within 8 weeks, which was defined as diarrhea plus a positive enzyme immunoassay toxin test. The secondary outcome was C difficile decolonization following treatment. 

Researchers observed no statistically significant difference between the two cohorts. Steroid use prior to FMT significantly increased the risk for ongoing C difficile colonization (P =.03). 

In summary, this is a case where it doesn’t seem that more is better. Bezlotoxumab didn’t add much, which calls into question the justification for its combined use with FMT. 

 

Additional Positive Data for Seladelpar in Primary Biliary Cholangitis and Cirrhosis 

Reassuring findings were presented on seladelpar, which was granted accelerated approval by the FDA in August. 

Seladelpar is a selective peroxisome proliferator–activated receptor delta agonist that works in biliary cholangitis by regulating the genes involved in blocking biliary bile acid synthesis and controlling inflammation and fibrosis. 

Results from the phase 3 RESPONSE trial were published in The New England Journal of Medicine in February reporting on the use of seladelpar in primary biliary cholangitis.

Whereas the RESPONSE trial removed decompensated patients, the ongoing phase 3 ASSURE trial results presented at this year’s meeting included patients with compensated cirrhosis. Approximately 94% of the patients in this study had Child-Pugh class A and 6% had class B cirrhosis. Eligibility required that patients had an inadequate response or were intolerant to ursodeoxycholic acid. Patients were administered open-label seladelpar 10 mg orally daily and followed for up to 1 year.

The good news is that there were no safety signals, which is reassuring news for our patients with compensated cirrhosis. 

 

Advantages to Respiratory Syncytial Virus Vaccination in IBD 

Another study that offered results certainly worthy of attention dealt with vaccination recommendations in patients with IBD. 

Vaccination for respiratory syncytial virus (RSV) is now available in the United States. Its use was recommended for patients with IBD as early as 2021 per the Canadian Association of Gastroenterology’s clinical practice guideline, which discusses both live and nonlive vaccines. We should be aggressive in recommending this vaccine to our patients with IBD, but we haven’t really had one until recently. 

Researchers behind this retrospective cohort study used the TriNetX database, which includes over 100 million unique patient charts. They identified patients with IBD, who were then divided into two groups according to whether they received the RSV vaccine or not. 

Although this analysis was conducted in patients > 60 years of age, the US Centers for Disease Control and Prevention recommends RSV vaccination for all those over the age of 75 years, as well as for those 60-74 years old based on severity of risk. 

For the primary endpoint of risk for RSV pneumonia, the OR was dramatically better in those who were vaccinated, with an approximately 80% risk reduction. Additionally, vaccinated patients experienced risk reductions of approximately 60% for acute respiratory failure, 50% for hospital inpatient admission, and 70% for requiring intensive care unit services. 

This is a strong study showing not only that RSV vaccine did not exacerbate IBD but also that it improved outcomes in these patients. There’s a live-attenuated RSV vaccination that’s administered intranasally, which wouldn’t be used in your biologic or immunosuppressed patients with IBD, but the intramuscularly administered RSV vaccine doesn’t have any risk.

I think we can immediately begin recommending the RSV vaccine for our patients with IBD, particularly in those 60 years of age or older.

 

The Impact of Palliative Care Consultations in Decompensated Cirrhosis 

The next study I’d like to highlight offers important data on the impact of palliative care consultation on 30- and 90-day readmission in patients with decompensated cirrhosis, which is a major cause of morbidity and mortality.

Researchers queried the National Readmissions Database over a 10-year period (2010-2019) to determine whether patients received a palliative care consult during index admission. They drew on a population of over 1.6 million patients admitted with decompensated cirrhosis. 

Of this group, only 7.4% received a palliative care consultation at the index admission. But if they had this consultation, it was associated with a dramatic effect on readmission at 30 and 90 days. There was statistically significant risk reduction of approximately 70% for both 30- and 90-day readmission compared with those who didn’t receive the palliative consult (P <.001).

The take-home message here is to get a palliative care consult with these patients when they come in. Your hospital will unquestionably experience value in this reduction in readmission, especially considering that readmission within 30 days may not even be covered. Look at these results and start to take advantage of this valuable consultation.

 

Auxora: A Novel Treatment for Acute Pancreatitis 

The last study for discussion offered very interesting data related to a drug called Auxora, a calcium release–activated calcium-channel inhibitor.

There is growing data that overactive calcium release–activated calcium channels aggravate acute pancreatitis and accelerate systemic inflammatory response syndrome (SIRS).

Acute pancreatitis with necrosis encompasses both local and systemic inflammation and is associated with significant mortality and morbidity. It is estimated that among patients with acute pancreatitis, 20%-30% have pancreatic necrosis, 30% develop infection, and 25% develop organ failure. 

The presence of SIRS seems to herald the activation of these complex inflammatory pathways, which then leads to organ failure and necrosis, which can potentially be stemmed through this calcium channel inhibitor. Phase 2 studies of Auxora found that its use was associated with significant reduction in the risk for progression.

This subsequent phase 3 study looked at patients with acute pancreatitis and accompanying grade ≥ 2 SIRS criteria. They were randomized to receive placebo or Auxora at doses of 2 mg/kg, 1 mg/kg, or 0.5 mg/kg, which was administered intravenously over 4 hours for 3 consecutive days. 

The primary endpoint was time to solid food tolerance, which was defined as eating ≥ 50% of a ≥ 500-calorie low-fat solid meal without increased abdominal pain or emesis, which is an important target because we always aim for enteral nutrition in patients with acute pancreatitis. The key secondary endpoint was severe respiratory failure, which was defined as invasive mechanical ventilation or ≥ 48 hours of either high-flow nasal cannula or noninvasive mechanical ventilation. 

The primary endpoint was dramatically improved among those receiving Auxora, who achieved early onset of refeed. It appears that the high-dose 2 mg/kg may be the most beneficial in achieving improvement. 

There were no patients with suspected or unexpected adverse events in the study population. Additionally, no patients receiving Auxora at any dose level went on to develop respiratory failure. 

The present results show that Auxora decreases the time for solid food tolerance, as well as the rates of respiratory failure and necrotizing pancreatitis in patients presenting with two or more SIRS criteria. We’ll certainly look forward to more data, but it provides hope for a new treatment for acute pancreatitis.

There were lots of intriguing data presented at ACG 2024. Obviously, we’d like to see them evolve in subsequent journal manuscripts. 

Some of the take-home messages I presented are actionable now, whereas for others, we’ll have to wait and see what the final data show as well as the results of ongoing FDA approval before applying them. 

 

Dr Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. He reported serving in an advisory position with ISOTHRIVE. This transcript has been edited for clarity.

A version of this article first appeared on Medscape.com.

WASHINGTON — The B cell–depleting agent inebilizumab (Uplizna) dramatically reduced the risk of flares and increased year-long remission of IgG4-related disease (RD), new research has found.

In a phase 3, multicenter, double-blind, randomized, placebo-controlled trial of 135 adults with active IgG4-RD, treatment with inebilizumab resulted in a significant 87% reduction in flare risk and nearly fivefold greater likelihood of flare-free remission at 1 year. The results were published online November 14 in The New England Journal of Medicine and were presented at the annual meeting of the American College of Rheumatology (ACR).

The drug’s manufacturer, Amgen, released top-line results of the trial, called MITIGATE, in June 2024.

 

Until now, the mainstay of management for the chronic multiorgan disease IgG4-RD has been glucocorticoids, which can cause numerous adverse effects. “It is hoped that inebilizumab can be used as an important steroid-sparing medication in this disease to reduce steroid toxicity,” lead author John H. Stone, MD, professor of medicine at Harvard Medical School, Boston, Massachusetts, said in an interview, noting that it may not entirely eliminate the need for steroid treatment, but for many, it appears to work after the remission induction period as a monotherapy without steroids. 

Asked to comment, Leonard H. Calabrese, DO, head of the Section of Clinical Immunology and manager of the Clinical Immunology Clinic at the Cleveland Clinic, Ohio, said: “There has been anecdotal or observational evidence for some effect with other immunosuppressive agents, including rituximab, but no robust clinical trial until this study. This clearly has demonstrated efficacy by reducing the risk of flares. And most importantly, putting people into remission means no active disease in any given organ. ... This gives us another tool in the toolbox to attack B cell–directed diseases, and I think it really makes a lot of sense.”

Calabrese cautioned, though, that “this is a disease that extends over many years. This is just a 1-year study. Label extensions will be important.”

 

And several questions remain, Calabrese noted: “How long do patients need to remain on drug? What will happen when the drug is stopped? Can they be retreated? These are the natural questions that arise in any sentinel study like this. But this is extremely encouraging. And I think it’s great for patients. I also think it’s a clarion call to increase awareness about this disease since there’s now strong evidence of effective treatment.” 

 

Underrecognized, Often Misdiagnosed as Cancer

Indeed, IgG4-RD, a chronic, relapsing, autoimmune, fibro-inflammatory multiorgan disease, was only first described in Japan in 2003. Since then, it has been reported all over the world yet remains vastly underrecognized. It is often misdiagnosed as cancer because it produces lesions in multiple organs. It received an ICD-10 code only about a year ago. A previous study estimated a prevalence of about 5.3 persons per 100,000 but that is likely to be a three- to fourfold underestimate, said Stone, who is also executive chairman of the IgG4ward! Foundation. 

“Nobody had heard of the disease until about 20 years ago. ... And there are many people in the world who have still not heard of it despite the fact that it is a multiorgan autoimmune disease and is probably as common, or more common, than many other diseases that rheumatologists spend a lot of time thinking about, such as scleroderma.”

While knowledge about the disease is increasing in rheumatology circles, it’s less well-recognized among many of the specialties where patients present, depending on the location of their lesions. These include gastroenterology, ophthalmology, pulmonary medicine, neurology, and nephrology. “All would be likely to see this disease,” Stone said. 

The disease can be mistaken for tumors in many of those locations and even as metastatic cancer, he noted, adding that “any time a patient has a mass lesion in a typical organ, the pancreas, the major salivary glands, the lungs, or the kidneys, this should be on the differential diagnosis.” 

The diagnosis of IgG4-RD is a clinical one, involving “quadrangulation between clinical features, serological findings, IgG4 levels in the blood, radiology studies, and then pathology biopsies when those are available,” Stone said. 

Calabrese characterized the current situation as “we’re all blind men on the elephant. To the neurologist or the neurosurgeon, it’s a mass in the brain. It could present to the ophthalmologist as an [eye] tumor. It can be thyroid gland failure, pulmonary disease, retroperitoneal fibrosis, hepatobiliary disease, and beyond. So, whoever sees that patient, there’s often a long lag time in recognizing it.”

And interestingly, Stone noted that unlike other autoimmune diseases, IgG4-RD primarily affects middle-aged men rather than younger-to-middle-aged women. And when IgG4-RD is diagnosed, glucocorticoid treatment can be particularly toxic when the pancreas is involved, heightening the risk for hyperglycemia and potentially causing diabetes. 

 

Dramatic Improvement in Flares, Remission Achievement

MITIGATE is a phase 3, multicenter, double-blind, randomized, placebo-controlled trial in which 135 adults (mean age 58.2 years, 88 men) with active IgG4-RD were randomized 1:1 to receive 300-mg intravenous infusions of inebilizumab or placebo on days 1 and 15, and again at week 26. At baseline, 62 (45.9%) participants had newly diagnosed IgG4-RD and 73 (54.1%) had recurrent disease. 

Both groups received identical glucocorticoid tapers. Overall, 127 (94.1%) completed the 52 weeks of treatment. 

By 52 weeks, only seven patients in the inebilizumab group (10%) had experienced disease flares vs 40 (60%) in the placebo group, a significant difference with a hazard ratio of 0.13 (P < .001). 

The percentage of participants achieving flare-free, treatment-free complete remission was 59 with inebilizumab (57%), compared with just 15 (22%) in the placebo group (odds ratio [OR], 4.68; P < .001). And for flare-free, glucocorticoid-free complete remission, those proportions were 40 (59%) vs 15 (22%), respectively (OR, 4.96; P < .001). 

Excluding the 8-week glucocorticoid taper period, mean total glucocorticoid use was 1264.2 mg less in the inebilizumab than the placebo group, a significant reduction. Overall, 61 participants (90%) were able to entirely discontinue glucocorticoids during the trial, compared with just 25 (37%) in the placebo group. 

Adverse events of grade 3 or higher occurred in 12 participants (18%) in the inebilizumab group and 8 (12%) in the placebo group; serious adverse events occurred in 12 (18%) and 6 (9%), respectively. However, no serious adverse event occurred in more than one participant, and there were no deaths. Adverse events led to withdrawal from the trial in six patients (9%) in the inebilizumab group and three patients (4%) in the placebo group. 

Adverse events that occurred in more than 10% of participants in the inebilizumab group were COVID-19 in 16 participants (24%), lymphopenia in 11 (16%), and urinary tract infection in 8 (12%). 

Importantly, Stone noted, B-cell depletion can reduce responses to vaccines, so patients should receive all recommended vaccinations, including COVID-19, influenza, respiratory syncytial virus, and others, prior to initiating therapy. 

Uplizna (inebilizumab-cdon) was approved by the Food and Drug Administration (FDA) for the treatment of neuromyelitis optica spectrum disorder in 2020. In October 2024, the FDA granted Amgen breakthrough therapy designation for use in IgG4-RD. The company is also developing the drug for use in myasthenia gravis.

The study was funded by Amgen. Stone has reported being a consultant for Amgen, Zenas, Argenx, Bristol Myers Squibb, Novartis, Sanofi, and Horizon Pharma. Calabrese has reported being a consultant and/or speaker for Amgen, AstraZeneca, Jansen, Sanofi, and UCB.

A version of this article first appeared on Medscape.com.

WASHINGTON — The B cell–depleting agent inebilizumab (Uplizna) dramatically reduced the risk of flares and increased year-long remission of IgG4-related disease (RD), new research has found.

In a phase 3, multicenter, double-blind, randomized, placebo-controlled trial of 135 adults with active IgG4-RD, treatment with inebilizumab resulted in a significant 87% reduction in flare risk and nearly fivefold greater likelihood of flare-free remission at 1 year. The results were published online November 14 in The New England Journal of Medicine and were presented at the annual meeting of the American College of Rheumatology (ACR).

The drug’s manufacturer, Amgen, released top-line results of the trial, called MITIGATE, in June 2024.

 

Until now, the mainstay of management for the chronic multiorgan disease IgG4-RD has been glucocorticoids, which can cause numerous adverse effects. “It is hoped that inebilizumab can be used as an important steroid-sparing medication in this disease to reduce steroid toxicity,” lead author John H. Stone, MD, professor of medicine at Harvard Medical School, Boston, Massachusetts, said in an interview, noting that it may not entirely eliminate the need for steroid treatment, but for many, it appears to work after the remission induction period as a monotherapy without steroids. 

Asked to comment, Leonard H. Calabrese, DO, head of the Section of Clinical Immunology and manager of the Clinical Immunology Clinic at the Cleveland Clinic, Ohio, said: “There has been anecdotal or observational evidence for some effect with other immunosuppressive agents, including rituximab, but no robust clinical trial until this study. This clearly has demonstrated efficacy by reducing the risk of flares. And most importantly, putting people into remission means no active disease in any given organ. ... This gives us another tool in the toolbox to attack B cell–directed diseases, and I think it really makes a lot of sense.”

Calabrese cautioned, though, that “this is a disease that extends over many years. This is just a 1-year study. Label extensions will be important.”

 

And several questions remain, Calabrese noted: “How long do patients need to remain on drug? What will happen when the drug is stopped? Can they be retreated? These are the natural questions that arise in any sentinel study like this. But this is extremely encouraging. And I think it’s great for patients. I also think it’s a clarion call to increase awareness about this disease since there’s now strong evidence of effective treatment.” 

 

Underrecognized, Often Misdiagnosed as Cancer

Indeed, IgG4-RD, a chronic, relapsing, autoimmune, fibro-inflammatory multiorgan disease, was only first described in Japan in 2003. Since then, it has been reported all over the world yet remains vastly underrecognized. It is often misdiagnosed as cancer because it produces lesions in multiple organs. It received an ICD-10 code only about a year ago. A previous study estimated a prevalence of about 5.3 persons per 100,000 but that is likely to be a three- to fourfold underestimate, said Stone, who is also executive chairman of the IgG4ward! Foundation. 

“Nobody had heard of the disease until about 20 years ago. ... And there are many people in the world who have still not heard of it despite the fact that it is a multiorgan autoimmune disease and is probably as common, or more common, than many other diseases that rheumatologists spend a lot of time thinking about, such as scleroderma.”

While knowledge about the disease is increasing in rheumatology circles, it’s less well-recognized among many of the specialties where patients present, depending on the location of their lesions. These include gastroenterology, ophthalmology, pulmonary medicine, neurology, and nephrology. “All would be likely to see this disease,” Stone said. 

The disease can be mistaken for tumors in many of those locations and even as metastatic cancer, he noted, adding that “any time a patient has a mass lesion in a typical organ, the pancreas, the major salivary glands, the lungs, or the kidneys, this should be on the differential diagnosis.” 

The diagnosis of IgG4-RD is a clinical one, involving “quadrangulation between clinical features, serological findings, IgG4 levels in the blood, radiology studies, and then pathology biopsies when those are available,” Stone said. 

Calabrese characterized the current situation as “we’re all blind men on the elephant. To the neurologist or the neurosurgeon, it’s a mass in the brain. It could present to the ophthalmologist as an [eye] tumor. It can be thyroid gland failure, pulmonary disease, retroperitoneal fibrosis, hepatobiliary disease, and beyond. So, whoever sees that patient, there’s often a long lag time in recognizing it.”

And interestingly, Stone noted that unlike other autoimmune diseases, IgG4-RD primarily affects middle-aged men rather than younger-to-middle-aged women. And when IgG4-RD is diagnosed, glucocorticoid treatment can be particularly toxic when the pancreas is involved, heightening the risk for hyperglycemia and potentially causing diabetes. 

 

Dramatic Improvement in Flares, Remission Achievement

MITIGATE is a phase 3, multicenter, double-blind, randomized, placebo-controlled trial in which 135 adults (mean age 58.2 years, 88 men) with active IgG4-RD were randomized 1:1 to receive 300-mg intravenous infusions of inebilizumab or placebo on days 1 and 15, and again at week 26. At baseline, 62 (45.9%) participants had newly diagnosed IgG4-RD and 73 (54.1%) had recurrent disease. 

Both groups received identical glucocorticoid tapers. Overall, 127 (94.1%) completed the 52 weeks of treatment. 

By 52 weeks, only seven patients in the inebilizumab group (10%) had experienced disease flares vs 40 (60%) in the placebo group, a significant difference with a hazard ratio of 0.13 (P < .001). 

The percentage of participants achieving flare-free, treatment-free complete remission was 59 with inebilizumab (57%), compared with just 15 (22%) in the placebo group (odds ratio [OR], 4.68; P < .001). And for flare-free, glucocorticoid-free complete remission, those proportions were 40 (59%) vs 15 (22%), respectively (OR, 4.96; P < .001). 

Excluding the 8-week glucocorticoid taper period, mean total glucocorticoid use was 1264.2 mg less in the inebilizumab than the placebo group, a significant reduction. Overall, 61 participants (90%) were able to entirely discontinue glucocorticoids during the trial, compared with just 25 (37%) in the placebo group. 

Adverse events of grade 3 or higher occurred in 12 participants (18%) in the inebilizumab group and 8 (12%) in the placebo group; serious adverse events occurred in 12 (18%) and 6 (9%), respectively. However, no serious adverse event occurred in more than one participant, and there were no deaths. Adverse events led to withdrawal from the trial in six patients (9%) in the inebilizumab group and three patients (4%) in the placebo group. 

Adverse events that occurred in more than 10% of participants in the inebilizumab group were COVID-19 in 16 participants (24%), lymphopenia in 11 (16%), and urinary tract infection in 8 (12%). 

Importantly, Stone noted, B-cell depletion can reduce responses to vaccines, so patients should receive all recommended vaccinations, including COVID-19, influenza, respiratory syncytial virus, and others, prior to initiating therapy. 

Uplizna (inebilizumab-cdon) was approved by the Food and Drug Administration (FDA) for the treatment of neuromyelitis optica spectrum disorder in 2020. In October 2024, the FDA granted Amgen breakthrough therapy designation for use in IgG4-RD. The company is also developing the drug for use in myasthenia gravis.

The study was funded by Amgen. Stone has reported being a consultant for Amgen, Zenas, Argenx, Bristol Myers Squibb, Novartis, Sanofi, and Horizon Pharma. Calabrese has reported being a consultant and/or speaker for Amgen, AstraZeneca, Jansen, Sanofi, and UCB.

A version of this article first appeared on Medscape.com.

WASHINGTON — The B cell–depleting agent inebilizumab (Uplizna) dramatically reduced the risk of flares and increased year-long remission of IgG4-related disease (RD), new research has found.

In a phase 3, multicenter, double-blind, randomized, placebo-controlled trial of 135 adults with active IgG4-RD, treatment with inebilizumab resulted in a significant 87% reduction in flare risk and nearly fivefold greater likelihood of flare-free remission at 1 year. The results were published online November 14 in The New England Journal of Medicine and were presented at the annual meeting of the American College of Rheumatology (ACR).

The drug’s manufacturer, Amgen, released top-line results of the trial, called MITIGATE, in June 2024.

 

Until now, the mainstay of management for the chronic multiorgan disease IgG4-RD has been glucocorticoids, which can cause numerous adverse effects. “It is hoped that inebilizumab can be used as an important steroid-sparing medication in this disease to reduce steroid toxicity,” lead author John H. Stone, MD, professor of medicine at Harvard Medical School, Boston, Massachusetts, said in an interview, noting that it may not entirely eliminate the need for steroid treatment, but for many, it appears to work after the remission induction period as a monotherapy without steroids. 

Asked to comment, Leonard H. Calabrese, DO, head of the Section of Clinical Immunology and manager of the Clinical Immunology Clinic at the Cleveland Clinic, Ohio, said: “There has been anecdotal or observational evidence for some effect with other immunosuppressive agents, including rituximab, but no robust clinical trial until this study. This clearly has demonstrated efficacy by reducing the risk of flares. And most importantly, putting people into remission means no active disease in any given organ. ... This gives us another tool in the toolbox to attack B cell–directed diseases, and I think it really makes a lot of sense.”

Calabrese cautioned, though, that “this is a disease that extends over many years. This is just a 1-year study. Label extensions will be important.”

 

And several questions remain, Calabrese noted: “How long do patients need to remain on drug? What will happen when the drug is stopped? Can they be retreated? These are the natural questions that arise in any sentinel study like this. But this is extremely encouraging. And I think it’s great for patients. I also think it’s a clarion call to increase awareness about this disease since there’s now strong evidence of effective treatment.” 

 

Underrecognized, Often Misdiagnosed as Cancer

Indeed, IgG4-RD, a chronic, relapsing, autoimmune, fibro-inflammatory multiorgan disease, was only first described in Japan in 2003. Since then, it has been reported all over the world yet remains vastly underrecognized. It is often misdiagnosed as cancer because it produces lesions in multiple organs. It received an ICD-10 code only about a year ago. A previous study estimated a prevalence of about 5.3 persons per 100,000 but that is likely to be a three- to fourfold underestimate, said Stone, who is also executive chairman of the IgG4ward! Foundation. 

“Nobody had heard of the disease until about 20 years ago. ... And there are many people in the world who have still not heard of it despite the fact that it is a multiorgan autoimmune disease and is probably as common, or more common, than many other diseases that rheumatologists spend a lot of time thinking about, such as scleroderma.”

While knowledge about the disease is increasing in rheumatology circles, it’s less well-recognized among many of the specialties where patients present, depending on the location of their lesions. These include gastroenterology, ophthalmology, pulmonary medicine, neurology, and nephrology. “All would be likely to see this disease,” Stone said. 

The disease can be mistaken for tumors in many of those locations and even as metastatic cancer, he noted, adding that “any time a patient has a mass lesion in a typical organ, the pancreas, the major salivary glands, the lungs, or the kidneys, this should be on the differential diagnosis.” 

The diagnosis of IgG4-RD is a clinical one, involving “quadrangulation between clinical features, serological findings, IgG4 levels in the blood, radiology studies, and then pathology biopsies when those are available,” Stone said. 

Calabrese characterized the current situation as “we’re all blind men on the elephant. To the neurologist or the neurosurgeon, it’s a mass in the brain. It could present to the ophthalmologist as an [eye] tumor. It can be thyroid gland failure, pulmonary disease, retroperitoneal fibrosis, hepatobiliary disease, and beyond. So, whoever sees that patient, there’s often a long lag time in recognizing it.”

And interestingly, Stone noted that unlike other autoimmune diseases, IgG4-RD primarily affects middle-aged men rather than younger-to-middle-aged women. And when IgG4-RD is diagnosed, glucocorticoid treatment can be particularly toxic when the pancreas is involved, heightening the risk for hyperglycemia and potentially causing diabetes. 

 

Dramatic Improvement in Flares, Remission Achievement

MITIGATE is a phase 3, multicenter, double-blind, randomized, placebo-controlled trial in which 135 adults (mean age 58.2 years, 88 men) with active IgG4-RD were randomized 1:1 to receive 300-mg intravenous infusions of inebilizumab or placebo on days 1 and 15, and again at week 26. At baseline, 62 (45.9%) participants had newly diagnosed IgG4-RD and 73 (54.1%) had recurrent disease. 

Both groups received identical glucocorticoid tapers. Overall, 127 (94.1%) completed the 52 weeks of treatment. 

By 52 weeks, only seven patients in the inebilizumab group (10%) had experienced disease flares vs 40 (60%) in the placebo group, a significant difference with a hazard ratio of 0.13 (P < .001). 

The percentage of participants achieving flare-free, treatment-free complete remission was 59 with inebilizumab (57%), compared with just 15 (22%) in the placebo group (odds ratio [OR], 4.68; P < .001). And for flare-free, glucocorticoid-free complete remission, those proportions were 40 (59%) vs 15 (22%), respectively (OR, 4.96; P < .001). 

Excluding the 8-week glucocorticoid taper period, mean total glucocorticoid use was 1264.2 mg less in the inebilizumab than the placebo group, a significant reduction. Overall, 61 participants (90%) were able to entirely discontinue glucocorticoids during the trial, compared with just 25 (37%) in the placebo group. 

Adverse events of grade 3 or higher occurred in 12 participants (18%) in the inebilizumab group and 8 (12%) in the placebo group; serious adverse events occurred in 12 (18%) and 6 (9%), respectively. However, no serious adverse event occurred in more than one participant, and there were no deaths. Adverse events led to withdrawal from the trial in six patients (9%) in the inebilizumab group and three patients (4%) in the placebo group. 

Adverse events that occurred in more than 10% of participants in the inebilizumab group were COVID-19 in 16 participants (24%), lymphopenia in 11 (16%), and urinary tract infection in 8 (12%). 

Importantly, Stone noted, B-cell depletion can reduce responses to vaccines, so patients should receive all recommended vaccinations, including COVID-19, influenza, respiratory syncytial virus, and others, prior to initiating therapy. 

Uplizna (inebilizumab-cdon) was approved by the Food and Drug Administration (FDA) for the treatment of neuromyelitis optica spectrum disorder in 2020. In October 2024, the FDA granted Amgen breakthrough therapy designation for use in IgG4-RD. The company is also developing the drug for use in myasthenia gravis.

The study was funded by Amgen. Stone has reported being a consultant for Amgen, Zenas, Argenx, Bristol Myers Squibb, Novartis, Sanofi, and Horizon Pharma. Calabrese has reported being a consultant and/or speaker for Amgen, AstraZeneca, Jansen, Sanofi, and UCB.

A version of this article first appeared on Medscape.com.

TOPLINE:

Novel first-generation cell-free DNA blood (cf-bDNA) tests for colorectal cancer (CRC) cost more and are less effective than colonoscopy or stool tests, a new analysis suggests.

METHODOLOGY:

• Researchers estimated the clinical and economic impacts of emerging blood- and stool-based CRC screening tests with established alternatives in average-risk adults aged 45 years and older.
• The established screening tools were colonoscopy, a fecal immunochemical test (FIT), and a multitarget stool DNA test (MT-sDNA, Exact Sciences Cologuard).
• The four emerging screening methods were two cf-bDNA tests (Guardant Shield and Freenome); an enhanced, a next-generation multitarget stool test (ngMT-sDNA), and a novel FIT-RNA test (Geneoscopy ColoSense).

TAKEAWAY:

• Assuming 100% participation in all screening steps, colonoscopy and FIT yielded reductions of more than 70% in CRC incidence and 75% in mortality vs no screening.
• The MT-sDNA test reduced CRC incidence by 68% and mortality by 73%, with similar rates for the ngMT-sDNA and FIT-RNA tests vs no screening. The cf-bDNA tests yielded CRC incidence and mortality reductions of only 42% and 56%.
• Colonoscopy and FIT were more effective and less costly than the cf-bDNA and MT-sDNA tests, and the MT-sDNA test was more effective and less costly than the cf-bDNA test.
• Population benefits from blood tests were seen only in those who declined colonoscopy and stool tests. Substituting a blood test for those already using colonoscopy or stool tests led to worse population-level outcomes.

IN PRACTICE:

“First-generation novel cf-bDNA tests have the potential to decrease meaningfully the incidence and mortality of CRC compared with no screening but substantially less profoundly than screening colonoscopy or stool tests. Net population benefit or harm can follow incorporation of first-generation cf-bDNA CRC screening tests into practice, depending on the balance between bringing unscreened persons into screening (addition) vs shifting persons away from the more effective strategies of colonoscopy or stool testing (substitution),” the authors concluded.

SOURCE:

The study, with first author Uri Ladabaum, MD, MS, Stanford University School of Medicine, California, was published online in Annals of Internal Medicine.

LIMITATIONS:

Limitations included test-specific participation patterns being unknown over time. 

DISCLOSURES:

Disclosure forms for the authors are available with the article online. Funding was provided by the Gorrindo Family Fund.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Novel first-generation cell-free DNA blood (cf-bDNA) tests for colorectal cancer (CRC) cost more and are less effective than colonoscopy or stool tests, a new analysis suggests.

METHODOLOGY:

• Researchers estimated the clinical and economic impacts of emerging blood- and stool-based CRC screening tests with established alternatives in average-risk adults aged 45 years and older.
• The established screening tools were colonoscopy, a fecal immunochemical test (FIT), and a multitarget stool DNA test (MT-sDNA, Exact Sciences Cologuard).
• The four emerging screening methods were two cf-bDNA tests (Guardant Shield and Freenome); an enhanced, a next-generation multitarget stool test (ngMT-sDNA), and a novel FIT-RNA test (Geneoscopy ColoSense).

TAKEAWAY:

• Assuming 100% participation in all screening steps, colonoscopy and FIT yielded reductions of more than 70% in CRC incidence and 75% in mortality vs no screening.
• The MT-sDNA test reduced CRC incidence by 68% and mortality by 73%, with similar rates for the ngMT-sDNA and FIT-RNA tests vs no screening. The cf-bDNA tests yielded CRC incidence and mortality reductions of only 42% and 56%.
• Colonoscopy and FIT were more effective and less costly than the cf-bDNA and MT-sDNA tests, and the MT-sDNA test was more effective and less costly than the cf-bDNA test.
• Population benefits from blood tests were seen only in those who declined colonoscopy and stool tests. Substituting a blood test for those already using colonoscopy or stool tests led to worse population-level outcomes.

IN PRACTICE:

“First-generation novel cf-bDNA tests have the potential to decrease meaningfully the incidence and mortality of CRC compared with no screening but substantially less profoundly than screening colonoscopy or stool tests. Net population benefit or harm can follow incorporation of first-generation cf-bDNA CRC screening tests into practice, depending on the balance between bringing unscreened persons into screening (addition) vs shifting persons away from the more effective strategies of colonoscopy or stool testing (substitution),” the authors concluded.

SOURCE:

The study, with first author Uri Ladabaum, MD, MS, Stanford University School of Medicine, California, was published online in Annals of Internal Medicine.

LIMITATIONS:

Limitations included test-specific participation patterns being unknown over time. 

DISCLOSURES:

Disclosure forms for the authors are available with the article online. Funding was provided by the Gorrindo Family Fund.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Novel first-generation cell-free DNA blood (cf-bDNA) tests for colorectal cancer (CRC) cost more and are less effective than colonoscopy or stool tests, a new analysis suggests.

METHODOLOGY:

• Researchers estimated the clinical and economic impacts of emerging blood- and stool-based CRC screening tests with established alternatives in average-risk adults aged 45 years and older.
• The established screening tools were colonoscopy, a fecal immunochemical test (FIT), and a multitarget stool DNA test (MT-sDNA, Exact Sciences Cologuard).
• The four emerging screening methods were two cf-bDNA tests (Guardant Shield and Freenome); an enhanced, a next-generation multitarget stool test (ngMT-sDNA), and a novel FIT-RNA test (Geneoscopy ColoSense).

TAKEAWAY:

• Assuming 100% participation in all screening steps, colonoscopy and FIT yielded reductions of more than 70% in CRC incidence and 75% in mortality vs no screening.
• The MT-sDNA test reduced CRC incidence by 68% and mortality by 73%, with similar rates for the ngMT-sDNA and FIT-RNA tests vs no screening. The cf-bDNA tests yielded CRC incidence and mortality reductions of only 42% and 56%.
• Colonoscopy and FIT were more effective and less costly than the cf-bDNA and MT-sDNA tests, and the MT-sDNA test was more effective and less costly than the cf-bDNA test.
• Population benefits from blood tests were seen only in those who declined colonoscopy and stool tests. Substituting a blood test for those already using colonoscopy or stool tests led to worse population-level outcomes.

IN PRACTICE:

“First-generation novel cf-bDNA tests have the potential to decrease meaningfully the incidence and mortality of CRC compared with no screening but substantially less profoundly than screening colonoscopy or stool tests. Net population benefit or harm can follow incorporation of first-generation cf-bDNA CRC screening tests into practice, depending on the balance between bringing unscreened persons into screening (addition) vs shifting persons away from the more effective strategies of colonoscopy or stool testing (substitution),” the authors concluded.

SOURCE:

The study, with first author Uri Ladabaum, MD, MS, Stanford University School of Medicine, California, was published online in Annals of Internal Medicine.

LIMITATIONS:

Limitations included test-specific participation patterns being unknown over time. 

DISCLOSURES:

Disclosure forms for the authors are available with the article online. Funding was provided by the Gorrindo Family Fund.
 

A version of this article appeared on Medscape.com.