From the AGA Journals

In a head-to-head comparison, two commercially available computer-aided diagnosis systems appeared clinically equivalent for the optical diagnosis of small colorectal polyps, according to a research letter published in Gastroenterology.

For the optical diagnosis of diminutive colorectal polyps, the comparable performances of both CAD EYE (Fujifilm Co.) and GI Genius (Medtronic) met cutoff guidelines to implement the cost-saving leave-in-situ and resect-and-discard strategies, wrote Cesare Hassan, MD, PhD, associate professor of gastroenterology at Humanitas University and member of the endoscopy unit at Humanitas Clinical Research Hospital in Milan, and colleagues.

“Screening colonoscopy is effective in reducing colorectal cancer risk but also represents a substantial financial burden,” the authors wrote. “Novel strategies based on artificial intelligence may enable targeted removal only of polyps deemed to be neoplastic, thus reducing patient burden for unnecessary removal of nonneoplastic polyps and reducing costs for histopathology.”

Several computer-aided diagnosis (CADx) systems are commercially available for optical diagnosis of colorectal polyps, the authors wrote. However, each artificial intelligence (AI) system has been trained and validated with different polyp datasets, which may contribute to variability and affect the clinical outcome of optical diagnosis-based strategies.

Dr. Hassan and colleagues conducted a prospective comparison trial at a single center to look at the real-life performances of two CADx systems on optical diagnosis of polyps smaller than 5 mm.

At colonoscopy, the same polyp was visualized by the same endoscopist on two different monitors simultaneously with the respective output from each of the two CADx systems. Pre- and post-CADx human diagnoses were also collected.

Between January 2022 and March 2022, 176 consecutive patients age 40 and older underwent colonoscopy for colorectal cancer screening, polypectomy surveillance, or gastrointestinal symptoms. About 60.8% of participants were men, and the average age was 60.

Among 543 polyps detected and removed, 169 (31.3%) were adenomas, and 373 (68.7%) were nonadenomas. Of those, 325 (59.9%) were rectosigmoid polyps of 5 mm or less in diameter and eligible for analyses in the study. This included 44 adenomas (13.5%) and 281 nonadenomas (86.5%).

The two CADx systems were grouped as CADx-A for CAD EYE and CADx-B for GI Genius. CADx-A provided prediction output for all 325 rectosigmoid polyps of 5 mm or less, whereas CADx-B wasn’t able to provide output for six of the nonadenomas, which were excluded from the analysis.

The negative predictive value (NPV) for rectosigmoid polyps of 5 mm or less was 97% for CADx-A and 97.7% for CADx-B, the authors wrote. The American Society for Gastrointestinal Endoscopy recommends a threshold for optical diagnosis of at least 90%.

In addition, the sensitivity for adenomas was 81.8% for CADx-A and 86.4% for CADx-B. The accuracy of CADx-A was slightly higher, at 93.2%, as compared with 91.5% for CADx-B.

Based on AI prediction alone, 269 of 319 polyps (84.3%) with CADx-A and 260 of 319 polyps (81.5%) with CADx-B would have been classified as nonneoplastic and avoided removal. This corresponded to a specificity of 94.9% for CADx-A and 92.4% for CADx-B, which wasn’t significantly different, the authors wrote. Concordance in histology prediction between the two systems was 94.7%.

Based on the 2020 U.S. Multi-Society Task Force on Colorectal Cancer (USMSTF) guidelines, the agreement with histopathology in surveillance interval assignment was 84.7% for CADx-A and 89.2% for CADx-B. Based on the 2020 European Society of Gastrointestinal Endoscopy (ESGE) guidelines, the agreement was 98.3% for both systems.

For rectosigmoid polyps of 5 mm or less, the NPV of unassisted optical diagnosis was 97.8% for a high-confidence diagnosis, but it wasn’t significantly different from the NPV of CADx-A (96.9%) or CADx-B (97.6%). The NPV of a CADx-assisted optical diagnosis at high confidence was 97.7%, without statistically significant differences as compared with unassisted interpretation.

Based on the 2020 USMSTF and ESGE guidelines, the agreement between unassisted interpretation and histopathology in surveillance interval assignment was 92.6% and 98.9%, respectively. There was total agreement between unassisted interpretation and CADx-assisted interpretation in surveillance interval assignment based on both guidelines.

As in previous findings, unassisted endoscopic diagnosis was on par with CADx-assisted, both in technical accuracy and clinical outcomes. The study authors attributed the lack of additional benefit from CADx to a high performance of unassisted-endoscopist diagnosis, with the 97.8% NPV for rectosigmoid polyps and 90% or greater concordance in postpolypectomy surveillance intervals with histology. In addition, a human endoscopist was the only one to achieve 90% or greater agreement in postpolypectomy surveillance intervals under the U.S. guidelines, mainly due to a very high specificity.

“This confirms the complexity of the human-machine interaction that should not be marginalized in the stand-alone performance of the machine,” the authors wrote.

However, the high accuracy of unassisted endoscopists in the academic center in Italy is unlikely to mirror the real performance in community settings, they added. Future studies should focus on nontertiary centers to show the additional benefit, if any, that CADx provides for leave-in-situ colorectal polyps.

“A high degree of concordance in clinical outcomes was shown when directly comparing in vivo two different systems of CADx,” the authors concluded. “This reassured our confidence in the standardization of performance that may be achieved with the incorporation of AI in clinical practice, irrespective of the availability of multiple systems.”

The study authors declared no funding source for this study. Several authors reported consulting relationships with numerous companies, including Fuji and Medtronic, which make the CAD EYE and GI Genius systems, respectively.

In a head-to-head comparison, two commercially available computer-aided diagnosis systems appeared clinically equivalent for the optical diagnosis of small colorectal polyps, according to a research letter published in Gastroenterology.

For the optical diagnosis of diminutive colorectal polyps, the comparable performances of both CAD EYE (Fujifilm Co.) and GI Genius (Medtronic) met cutoff guidelines to implement the cost-saving leave-in-situ and resect-and-discard strategies, wrote Cesare Hassan, MD, PhD, associate professor of gastroenterology at Humanitas University and member of the endoscopy unit at Humanitas Clinical Research Hospital in Milan, and colleagues.

“Screening colonoscopy is effective in reducing colorectal cancer risk but also represents a substantial financial burden,” the authors wrote. “Novel strategies based on artificial intelligence may enable targeted removal only of polyps deemed to be neoplastic, thus reducing patient burden for unnecessary removal of nonneoplastic polyps and reducing costs for histopathology.”

Several computer-aided diagnosis (CADx) systems are commercially available for optical diagnosis of colorectal polyps, the authors wrote. However, each artificial intelligence (AI) system has been trained and validated with different polyp datasets, which may contribute to variability and affect the clinical outcome of optical diagnosis-based strategies.

Dr. Hassan and colleagues conducted a prospective comparison trial at a single center to look at the real-life performances of two CADx systems on optical diagnosis of polyps smaller than 5 mm.

At colonoscopy, the same polyp was visualized by the same endoscopist on two different monitors simultaneously with the respective output from each of the two CADx systems. Pre- and post-CADx human diagnoses were also collected.

Between January 2022 and March 2022, 176 consecutive patients age 40 and older underwent colonoscopy for colorectal cancer screening, polypectomy surveillance, or gastrointestinal symptoms. About 60.8% of participants were men, and the average age was 60.

Among 543 polyps detected and removed, 169 (31.3%) were adenomas, and 373 (68.7%) were nonadenomas. Of those, 325 (59.9%) were rectosigmoid polyps of 5 mm or less in diameter and eligible for analyses in the study. This included 44 adenomas (13.5%) and 281 nonadenomas (86.5%).

The two CADx systems were grouped as CADx-A for CAD EYE and CADx-B for GI Genius. CADx-A provided prediction output for all 325 rectosigmoid polyps of 5 mm or less, whereas CADx-B wasn’t able to provide output for six of the nonadenomas, which were excluded from the analysis.

The negative predictive value (NPV) for rectosigmoid polyps of 5 mm or less was 97% for CADx-A and 97.7% for CADx-B, the authors wrote. The American Society for Gastrointestinal Endoscopy recommends a threshold for optical diagnosis of at least 90%.

In addition, the sensitivity for adenomas was 81.8% for CADx-A and 86.4% for CADx-B. The accuracy of CADx-A was slightly higher, at 93.2%, as compared with 91.5% for CADx-B.

Based on AI prediction alone, 269 of 319 polyps (84.3%) with CADx-A and 260 of 319 polyps (81.5%) with CADx-B would have been classified as nonneoplastic and avoided removal. This corresponded to a specificity of 94.9% for CADx-A and 92.4% for CADx-B, which wasn’t significantly different, the authors wrote. Concordance in histology prediction between the two systems was 94.7%.

Based on the 2020 U.S. Multi-Society Task Force on Colorectal Cancer (USMSTF) guidelines, the agreement with histopathology in surveillance interval assignment was 84.7% for CADx-A and 89.2% for CADx-B. Based on the 2020 European Society of Gastrointestinal Endoscopy (ESGE) guidelines, the agreement was 98.3% for both systems.

For rectosigmoid polyps of 5 mm or less, the NPV of unassisted optical diagnosis was 97.8% for a high-confidence diagnosis, but it wasn’t significantly different from the NPV of CADx-A (96.9%) or CADx-B (97.6%). The NPV of a CADx-assisted optical diagnosis at high confidence was 97.7%, without statistically significant differences as compared with unassisted interpretation.

Based on the 2020 USMSTF and ESGE guidelines, the agreement between unassisted interpretation and histopathology in surveillance interval assignment was 92.6% and 98.9%, respectively. There was total agreement between unassisted interpretation and CADx-assisted interpretation in surveillance interval assignment based on both guidelines.

As in previous findings, unassisted endoscopic diagnosis was on par with CADx-assisted, both in technical accuracy and clinical outcomes. The study authors attributed the lack of additional benefit from CADx to a high performance of unassisted-endoscopist diagnosis, with the 97.8% NPV for rectosigmoid polyps and 90% or greater concordance in postpolypectomy surveillance intervals with histology. In addition, a human endoscopist was the only one to achieve 90% or greater agreement in postpolypectomy surveillance intervals under the U.S. guidelines, mainly due to a very high specificity.

“This confirms the complexity of the human-machine interaction that should not be marginalized in the stand-alone performance of the machine,” the authors wrote.

However, the high accuracy of unassisted endoscopists in the academic center in Italy is unlikely to mirror the real performance in community settings, they added. Future studies should focus on nontertiary centers to show the additional benefit, if any, that CADx provides for leave-in-situ colorectal polyps.

“A high degree of concordance in clinical outcomes was shown when directly comparing in vivo two different systems of CADx,” the authors concluded. “This reassured our confidence in the standardization of performance that may be achieved with the incorporation of AI in clinical practice, irrespective of the availability of multiple systems.”

The study authors declared no funding source for this study. Several authors reported consulting relationships with numerous companies, including Fuji and Medtronic, which make the CAD EYE and GI Genius systems, respectively.

In a head-to-head comparison, two commercially available computer-aided diagnosis systems appeared clinically equivalent for the optical diagnosis of small colorectal polyps, according to a research letter published in Gastroenterology.

For the optical diagnosis of diminutive colorectal polyps, the comparable performances of both CAD EYE (Fujifilm Co.) and GI Genius (Medtronic) met cutoff guidelines to implement the cost-saving leave-in-situ and resect-and-discard strategies, wrote Cesare Hassan, MD, PhD, associate professor of gastroenterology at Humanitas University and member of the endoscopy unit at Humanitas Clinical Research Hospital in Milan, and colleagues.

“Screening colonoscopy is effective in reducing colorectal cancer risk but also represents a substantial financial burden,” the authors wrote. “Novel strategies based on artificial intelligence may enable targeted removal only of polyps deemed to be neoplastic, thus reducing patient burden for unnecessary removal of nonneoplastic polyps and reducing costs for histopathology.”

Several computer-aided diagnosis (CADx) systems are commercially available for optical diagnosis of colorectal polyps, the authors wrote. However, each artificial intelligence (AI) system has been trained and validated with different polyp datasets, which may contribute to variability and affect the clinical outcome of optical diagnosis-based strategies.

Dr. Hassan and colleagues conducted a prospective comparison trial at a single center to look at the real-life performances of two CADx systems on optical diagnosis of polyps smaller than 5 mm.

At colonoscopy, the same polyp was visualized by the same endoscopist on two different monitors simultaneously with the respective output from each of the two CADx systems. Pre- and post-CADx human diagnoses were also collected.

Between January 2022 and March 2022, 176 consecutive patients age 40 and older underwent colonoscopy for colorectal cancer screening, polypectomy surveillance, or gastrointestinal symptoms. About 60.8% of participants were men, and the average age was 60.

Among 543 polyps detected and removed, 169 (31.3%) were adenomas, and 373 (68.7%) were nonadenomas. Of those, 325 (59.9%) were rectosigmoid polyps of 5 mm or less in diameter and eligible for analyses in the study. This included 44 adenomas (13.5%) and 281 nonadenomas (86.5%).

The two CADx systems were grouped as CADx-A for CAD EYE and CADx-B for GI Genius. CADx-A provided prediction output for all 325 rectosigmoid polyps of 5 mm or less, whereas CADx-B wasn’t able to provide output for six of the nonadenomas, which were excluded from the analysis.

The negative predictive value (NPV) for rectosigmoid polyps of 5 mm or less was 97% for CADx-A and 97.7% for CADx-B, the authors wrote. The American Society for Gastrointestinal Endoscopy recommends a threshold for optical diagnosis of at least 90%.

In addition, the sensitivity for adenomas was 81.8% for CADx-A and 86.4% for CADx-B. The accuracy of CADx-A was slightly higher, at 93.2%, as compared with 91.5% for CADx-B.

Based on AI prediction alone, 269 of 319 polyps (84.3%) with CADx-A and 260 of 319 polyps (81.5%) with CADx-B would have been classified as nonneoplastic and avoided removal. This corresponded to a specificity of 94.9% for CADx-A and 92.4% for CADx-B, which wasn’t significantly different, the authors wrote. Concordance in histology prediction between the two systems was 94.7%.

Based on the 2020 U.S. Multi-Society Task Force on Colorectal Cancer (USMSTF) guidelines, the agreement with histopathology in surveillance interval assignment was 84.7% for CADx-A and 89.2% for CADx-B. Based on the 2020 European Society of Gastrointestinal Endoscopy (ESGE) guidelines, the agreement was 98.3% for both systems.

For rectosigmoid polyps of 5 mm or less, the NPV of unassisted optical diagnosis was 97.8% for a high-confidence diagnosis, but it wasn’t significantly different from the NPV of CADx-A (96.9%) or CADx-B (97.6%). The NPV of a CADx-assisted optical diagnosis at high confidence was 97.7%, without statistically significant differences as compared with unassisted interpretation.

Based on the 2020 USMSTF and ESGE guidelines, the agreement between unassisted interpretation and histopathology in surveillance interval assignment was 92.6% and 98.9%, respectively. There was total agreement between unassisted interpretation and CADx-assisted interpretation in surveillance interval assignment based on both guidelines.

As in previous findings, unassisted endoscopic diagnosis was on par with CADx-assisted, both in technical accuracy and clinical outcomes. The study authors attributed the lack of additional benefit from CADx to a high performance of unassisted-endoscopist diagnosis, with the 97.8% NPV for rectosigmoid polyps and 90% or greater concordance in postpolypectomy surveillance intervals with histology. In addition, a human endoscopist was the only one to achieve 90% or greater agreement in postpolypectomy surveillance intervals under the U.S. guidelines, mainly due to a very high specificity.

“This confirms the complexity of the human-machine interaction that should not be marginalized in the stand-alone performance of the machine,” the authors wrote.

However, the high accuracy of unassisted endoscopists in the academic center in Italy is unlikely to mirror the real performance in community settings, they added. Future studies should focus on nontertiary centers to show the additional benefit, if any, that CADx provides for leave-in-situ colorectal polyps.

“A high degree of concordance in clinical outcomes was shown when directly comparing in vivo two different systems of CADx,” the authors concluded. “This reassured our confidence in the standardization of performance that may be achieved with the incorporation of AI in clinical practice, irrespective of the availability of multiple systems.”

The study authors declared no funding source for this study. Several authors reported consulting relationships with numerous companies, including Fuji and Medtronic, which make the CAD EYE and GI Genius systems, respectively.

A noninvasive test for liver disease may be a useful, low-cost screening tool to select asymptomatic candidates for a detailed examination of heart failure with preserved ejection fraction (HFpEF), say authors of a report published in Gastro Hep Advances.

The fibrosis-4 (FIB-4) index was a significant predictor of high HFpEF risk, wrote Chisato Okamoto, MD, of the department of medical biochemistry at Osaka University Graduate School of Medicine and the National Cerebral and Cardiovascular Center in Japan, and colleagues.

“Recognition of heart failure with preserved ejection fraction at an early stage in mass screening is desirable, but difficult to achieve,” the authors wrote. “The FIB-4 index is calculated using only four parameters that are routinely evaluated in general health check-up programs.”

HFpEF is an emerging disease in recent years with a poor prognosis, they wrote. Early diagnosis can be challenging for several reasons, particularly because HFpEF patients are often asymptomatic until late in the disease process and have normal left ventricular filling pressures at rest. By using a tool to select probable cases from subclinical participants in a health check-up program, clinicians can refer patients for a diastolic stress test, which is considered the gold standard for diagnosing HFpEF.

Previous studies have found that the FIB-4 index, a noninvasive tool to estimate liver stiffness and fibrosis, is associated with a higher risk of major adverse cardiovascular events (MACE) in patients with HFpEF. In addition, patients with nonalcoholic fatty liver disease (NAFLD) have a twofold higher prevalence of HFpEF than the general population.

Dr. Okamoto and colleagues examined the association between the FIB-4 index and HFpEF risk based on the Heart Failure Association’s diagnostic algorithm for HFpEF in patients with breathlessness (HFA-PEFF). The researchers looked at the prognostic impact of the FIB-4 index in 710 patients who participated in a health check-up program in the rural community of Arita-cho, Japan, between 2006 and 2007. They excluded participants with a history of cardiovascular disease or reduced left ventricular systolic function (LVEF < 50%). Researchers calculated the FIB-4 index and HFA-PEFF score for all participants.

First, using the HFA-PEFF scores, the researchers sorted participants into five groups by HFpEF risk: 215 (30%) with zero points, 100 (14%) with 1 point, 171 (24%) with 2 points, 163 (23%) with 3 points, and 61 (9%) with 4-6 points. Participants in the high-risk group (scores 4-6) were older, mostly men, and had higher blood pressure, alcohol intake, hypertension, dyslipidemia, and liver disease. The higher the HFpEF risk group, the higher the rates of all-cause mortality, hospitalization for heart failure, and MACE.

Overall, the FIB-4 index was correlated with the HFpEF risk groups and showed a stepwise increase across the groups, with .94 for the low-risk group, 1.45 for the intermediate-risk group, and 1.99 for the high-risk group, the authors wrote. The FIB-4 index also correlated with markers associated with components of the HFA-PEFF scoring system.

Using multivariate logistic regression analysis, the FIB-4 index was associated with a high HFpEF risk, and an increase in FIB-4 was associated with increased odds of high HFpEF risk. The association remained significant across four separate models that accounted for risk factors associated with lifestyle-related diseases, blood parameters associated with liver disease, and chronic conditions such as hypertension, dyslipidemia, diabetes mellitus, and liver disease.

In additional area under the curve (AUC) analyses, the FIB-4 index was a significant predictor of high HFpEF risk. At cutoff values typically used for advanced liver fibrosis in NAFLD, a FIB-4 cutoff of 1.3 or less had a sensitivity of 85.2%, while a FIB-4 cutoff of 2.67 or higher had a specificity of 94.8%. At alternate cutoff values typically used for patients with HIV/hepatitis C virus infection, a FIB-4 cutoff of less than 1.45 had a sensitivity of 75.4%, while a FIB-4 cutoff of greater than 3.25 had a specificity of 98%.

Using cutoffs of 1.3 and 2.67, a higher FIB-4 was associated with higher rates of clinical events and MACE, as well as a higher HFpEF risk. Using the alternate cutoffs of 1.45 and 3.25, prognostic stratification of clinical events and MACE was also possible.

When all variables were included in the multivariate model, the FIB-4 index remained a significant prognostic predictor. The FIB-4 index stratified clinical prognosis was also an independent predictor of all-cause mortality and hospitalization for heart failure.

Although additional studies are needed to reveal the interaction between liver and heart function, the study authors wrote, the findings provide valuable insights that can help discover the cardiohepatic interaction to reduce the development of HFpEF.

“Since it can be easily, quickly, and inexpensively measured, routine or repeated measurements of the FIB-4 index could help in selecting preferred candidates for detailed examination of HFpEF risk, which may improve clinical outcomes by diagnosing HFpEF at an early stage,” they wrote.

The study was supported by grants from the Osaka Medical Research Foundation for Intractable Disease, the Japan Arteriosclerosis Prevention Fund, the Japan Society for the Promotion of Science, and the Japan Heart Foundation. The authors disclosed no conflicts.

A noninvasive test for liver disease may be a useful, low-cost screening tool to select asymptomatic candidates for a detailed examination of heart failure with preserved ejection fraction (HFpEF), say authors of a report published in Gastro Hep Advances.

The fibrosis-4 (FIB-4) index was a significant predictor of high HFpEF risk, wrote Chisato Okamoto, MD, of the department of medical biochemistry at Osaka University Graduate School of Medicine and the National Cerebral and Cardiovascular Center in Japan, and colleagues.

“Recognition of heart failure with preserved ejection fraction at an early stage in mass screening is desirable, but difficult to achieve,” the authors wrote. “The FIB-4 index is calculated using only four parameters that are routinely evaluated in general health check-up programs.”

HFpEF is an emerging disease in recent years with a poor prognosis, they wrote. Early diagnosis can be challenging for several reasons, particularly because HFpEF patients are often asymptomatic until late in the disease process and have normal left ventricular filling pressures at rest. By using a tool to select probable cases from subclinical participants in a health check-up program, clinicians can refer patients for a diastolic stress test, which is considered the gold standard for diagnosing HFpEF.

Previous studies have found that the FIB-4 index, a noninvasive tool to estimate liver stiffness and fibrosis, is associated with a higher risk of major adverse cardiovascular events (MACE) in patients with HFpEF. In addition, patients with nonalcoholic fatty liver disease (NAFLD) have a twofold higher prevalence of HFpEF than the general population.

Dr. Okamoto and colleagues examined the association between the FIB-4 index and HFpEF risk based on the Heart Failure Association’s diagnostic algorithm for HFpEF in patients with breathlessness (HFA-PEFF). The researchers looked at the prognostic impact of the FIB-4 index in 710 patients who participated in a health check-up program in the rural community of Arita-cho, Japan, between 2006 and 2007. They excluded participants with a history of cardiovascular disease or reduced left ventricular systolic function (LVEF < 50%). Researchers calculated the FIB-4 index and HFA-PEFF score for all participants.

First, using the HFA-PEFF scores, the researchers sorted participants into five groups by HFpEF risk: 215 (30%) with zero points, 100 (14%) with 1 point, 171 (24%) with 2 points, 163 (23%) with 3 points, and 61 (9%) with 4-6 points. Participants in the high-risk group (scores 4-6) were older, mostly men, and had higher blood pressure, alcohol intake, hypertension, dyslipidemia, and liver disease. The higher the HFpEF risk group, the higher the rates of all-cause mortality, hospitalization for heart failure, and MACE.

Overall, the FIB-4 index was correlated with the HFpEF risk groups and showed a stepwise increase across the groups, with .94 for the low-risk group, 1.45 for the intermediate-risk group, and 1.99 for the high-risk group, the authors wrote. The FIB-4 index also correlated with markers associated with components of the HFA-PEFF scoring system.

Using multivariate logistic regression analysis, the FIB-4 index was associated with a high HFpEF risk, and an increase in FIB-4 was associated with increased odds of high HFpEF risk. The association remained significant across four separate models that accounted for risk factors associated with lifestyle-related diseases, blood parameters associated with liver disease, and chronic conditions such as hypertension, dyslipidemia, diabetes mellitus, and liver disease.

In additional area under the curve (AUC) analyses, the FIB-4 index was a significant predictor of high HFpEF risk. At cutoff values typically used for advanced liver fibrosis in NAFLD, a FIB-4 cutoff of 1.3 or less had a sensitivity of 85.2%, while a FIB-4 cutoff of 2.67 or higher had a specificity of 94.8%. At alternate cutoff values typically used for patients with HIV/hepatitis C virus infection, a FIB-4 cutoff of less than 1.45 had a sensitivity of 75.4%, while a FIB-4 cutoff of greater than 3.25 had a specificity of 98%.

Using cutoffs of 1.3 and 2.67, a higher FIB-4 was associated with higher rates of clinical events and MACE, as well as a higher HFpEF risk. Using the alternate cutoffs of 1.45 and 3.25, prognostic stratification of clinical events and MACE was also possible.

When all variables were included in the multivariate model, the FIB-4 index remained a significant prognostic predictor. The FIB-4 index stratified clinical prognosis was also an independent predictor of all-cause mortality and hospitalization for heart failure.

Although additional studies are needed to reveal the interaction between liver and heart function, the study authors wrote, the findings provide valuable insights that can help discover the cardiohepatic interaction to reduce the development of HFpEF.

“Since it can be easily, quickly, and inexpensively measured, routine or repeated measurements of the FIB-4 index could help in selecting preferred candidates for detailed examination of HFpEF risk, which may improve clinical outcomes by diagnosing HFpEF at an early stage,” they wrote.

The study was supported by grants from the Osaka Medical Research Foundation for Intractable Disease, the Japan Arteriosclerosis Prevention Fund, the Japan Society for the Promotion of Science, and the Japan Heart Foundation. The authors disclosed no conflicts.

A noninvasive test for liver disease may be a useful, low-cost screening tool to select asymptomatic candidates for a detailed examination of heart failure with preserved ejection fraction (HFpEF), say authors of a report published in Gastro Hep Advances.

The fibrosis-4 (FIB-4) index was a significant predictor of high HFpEF risk, wrote Chisato Okamoto, MD, of the department of medical biochemistry at Osaka University Graduate School of Medicine and the National Cerebral and Cardiovascular Center in Japan, and colleagues.

“Recognition of heart failure with preserved ejection fraction at an early stage in mass screening is desirable, but difficult to achieve,” the authors wrote. “The FIB-4 index is calculated using only four parameters that are routinely evaluated in general health check-up programs.”

HFpEF is an emerging disease in recent years with a poor prognosis, they wrote. Early diagnosis can be challenging for several reasons, particularly because HFpEF patients are often asymptomatic until late in the disease process and have normal left ventricular filling pressures at rest. By using a tool to select probable cases from subclinical participants in a health check-up program, clinicians can refer patients for a diastolic stress test, which is considered the gold standard for diagnosing HFpEF.

Previous studies have found that the FIB-4 index, a noninvasive tool to estimate liver stiffness and fibrosis, is associated with a higher risk of major adverse cardiovascular events (MACE) in patients with HFpEF. In addition, patients with nonalcoholic fatty liver disease (NAFLD) have a twofold higher prevalence of HFpEF than the general population.

Dr. Okamoto and colleagues examined the association between the FIB-4 index and HFpEF risk based on the Heart Failure Association’s diagnostic algorithm for HFpEF in patients with breathlessness (HFA-PEFF). The researchers looked at the prognostic impact of the FIB-4 index in 710 patients who participated in a health check-up program in the rural community of Arita-cho, Japan, between 2006 and 2007. They excluded participants with a history of cardiovascular disease or reduced left ventricular systolic function (LVEF < 50%). Researchers calculated the FIB-4 index and HFA-PEFF score for all participants.

First, using the HFA-PEFF scores, the researchers sorted participants into five groups by HFpEF risk: 215 (30%) with zero points, 100 (14%) with 1 point, 171 (24%) with 2 points, 163 (23%) with 3 points, and 61 (9%) with 4-6 points. Participants in the high-risk group (scores 4-6) were older, mostly men, and had higher blood pressure, alcohol intake, hypertension, dyslipidemia, and liver disease. The higher the HFpEF risk group, the higher the rates of all-cause mortality, hospitalization for heart failure, and MACE.

Overall, the FIB-4 index was correlated with the HFpEF risk groups and showed a stepwise increase across the groups, with .94 for the low-risk group, 1.45 for the intermediate-risk group, and 1.99 for the high-risk group, the authors wrote. The FIB-4 index also correlated with markers associated with components of the HFA-PEFF scoring system.

Using multivariate logistic regression analysis, the FIB-4 index was associated with a high HFpEF risk, and an increase in FIB-4 was associated with increased odds of high HFpEF risk. The association remained significant across four separate models that accounted for risk factors associated with lifestyle-related diseases, blood parameters associated with liver disease, and chronic conditions such as hypertension, dyslipidemia, diabetes mellitus, and liver disease.

In additional area under the curve (AUC) analyses, the FIB-4 index was a significant predictor of high HFpEF risk. At cutoff values typically used for advanced liver fibrosis in NAFLD, a FIB-4 cutoff of 1.3 or less had a sensitivity of 85.2%, while a FIB-4 cutoff of 2.67 or higher had a specificity of 94.8%. At alternate cutoff values typically used for patients with HIV/hepatitis C virus infection, a FIB-4 cutoff of less than 1.45 had a sensitivity of 75.4%, while a FIB-4 cutoff of greater than 3.25 had a specificity of 98%.

Using cutoffs of 1.3 and 2.67, a higher FIB-4 was associated with higher rates of clinical events and MACE, as well as a higher HFpEF risk. Using the alternate cutoffs of 1.45 and 3.25, prognostic stratification of clinical events and MACE was also possible.

When all variables were included in the multivariate model, the FIB-4 index remained a significant prognostic predictor. The FIB-4 index stratified clinical prognosis was also an independent predictor of all-cause mortality and hospitalization for heart failure.

Although additional studies are needed to reveal the interaction between liver and heart function, the study authors wrote, the findings provide valuable insights that can help discover the cardiohepatic interaction to reduce the development of HFpEF.

“Since it can be easily, quickly, and inexpensively measured, routine or repeated measurements of the FIB-4 index could help in selecting preferred candidates for detailed examination of HFpEF risk, which may improve clinical outcomes by diagnosing HFpEF at an early stage,” they wrote.

The study was supported by grants from the Osaka Medical Research Foundation for Intractable Disease, the Japan Arteriosclerosis Prevention Fund, the Japan Society for the Promotion of Science, and the Japan Heart Foundation. The authors disclosed no conflicts.

Although rare, acute hepatic porphyrias (AHPs) may be more common than previously thought, particularly among women between ages 15 and 50, according to a new clinical practice update from the American Gastroenterological Association.

For acute attacks, treatment should include intravenous hemin, and for patients with recurrent attacks, a newly-approved therapy called givosiran should be considered, wrote the authors of the update, which was published Jan. 13 in Gastroenterology.

“Diagnoses of AHPs are often missed, with a delay of more than 15 years from initial presentation. The key to early diagnosis is to consider the diagnosis, especially in patients with recurring severe abdominal pain not ascribable to other causes,” wrote the authors, who were led by Bruce Wang, MD, a hepatologist with the University of California, San Francisco.

AHPs are inherited disorders of heme-metabolism, which include acute intermittent porphyria, hereditary coproporphyria, variegate porphyria, and porphyria due to severe deficiency of 5-aminolevulinic acid dehydratase.

Acute intermittent porphyria (AIP) is the most common type, with an estimated prevalence of symptomatic AHP of 1 in 100,000 patients. However, population-level genetic studies show that the prevalence of pathogenic variants for AIP is between 1 in 1,300 and 1 in 1,785.

The major clinical presentation includes attacks of severe abdominal pain, nausea, vomiting, constipation, muscle weakness, neuropathy, tachycardia, and hypertension, yet without peritoneal signs or abnormalities on cross-sectional imaging.

Recent advances in treatment have improved the outlook for patients with AHP. To provide timely guidance, the authors developed 12 clinical practice advice statements on the diagnosis and management of AHPs based on a review of the published literature and expert opinion.

First, AHP screening should be considered in the evaluation of all patients, particularly among women in their childbearing years between ages 15 and 50 with unexplained, recurrent severe abdominal pain that doesn’t have a clear etiology. About 90% of patients with symptomatic AHP are women, and more than 90% of them experience only one or a few acute attacks in their lifetime, which are often precipitated by factors that increase the activity of the enzyme ALAS1 in the liver.

For initial AHP diagnosis, biochemical testing should measure porphobilinogen (PBG) and delta-aminolevulinic acid (ALA) corrected to creatine on a random urine sample. All patients with significantly elevated urinary PBG or ALA should initially be presumed to have AHP, and during acute attacks, both will be elevated at least five-fold of the upper limit of normal. Because ALA and PBG are porphyrin precursors, urine porphyrin testing should not be used alone for AHP screening.

After that, genetic testing should be used to confirm the AHP diagnosis, as well as the specific type of AHP. Sequencing of the four genes ALAD, HMBS, CPOX, and PPOX leads to aminolevulinic acid dehydrase deficiency, acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria, respectively. When whole-gene sequencing is performed, about 95%-99% of cases can be identified. First-degree family members should be screened with genetic testing, and those who are mutation carriers should be counseled.

For acute attacks of AHP that are severe enough to require hospitalization, the currently approved treatment is intravenous hemin infusion, usually given once daily at a dose of 3-4 mg/kg body weight for 3-5 days. Due to potential thrombophlebitis, it’s best to administer hemin in a high-flow central vein via a peripherally inserted central catheter or central port.

In addition, treatment for acute attacks should include analgesics, antiemetics, and management of systemic arterial hypertension, tachycardia, hyponatremia, and hypomagnesemia. The primary goal of treatment during an acute attack is to decrease ALA production. Patients should be counseled to avoid identifiable triggers, such as porphyrinogenic medications, excess alcohol intake, tobacco use, and caloric deprivation.

Although recent advances have improved treatment for acute attacks, management for patients with frequent attacks remains challenging, the study authors wrote. About 3%-5% of patients with symptomatic AHP experience recurrent attacks, which is defined as four or more attacks per year. These attacks aren’t typically associated with identifiable triggers, although some that occur during the luteal phase of a patient’s menstrual cycle are believed to be triggered by progesterone. However, treatment with hormonal suppression therapy, such as GnRH agonists, has had limited success.

Off-label use of prophylactic intravenous heme therapy is common, although the effectiveness in preventing recurrent attacks isn’t well-established. In addition, chronic hemin use is associated with several complications, including infections, iron overload, and the need for indwelling central venous catheters.

Recently, the Food and Drug Administration approved givosiran, a small interfering RNA-based therapy that targets delta-aminolevulinate synthase 1, for treatment in adults with AHP. Monthly subcutaneous therapy appears to significantly lower rates of acute attacks among patients who experience recurrent attacks.

“We suggest prescribing givosiran only for those patients with recurrent acute attacks that are both biochemically and genetically confirmed,” the authors wrote. “Due to limited safety data, givosiran should not be used in women who are pregnant or planning a pregnancy.”

In the most severe cases, liver transplantation should be limited to patients with intractable symptoms and a significantly decreased quality of life who are refractory to pharmacotherapy. If living donor transplantation is considered, genetic testing should be used to screen related living donors since HMBS pathogenic variants in asymptomatic donors could results in poor posttransplantation outcomes.

In the long-term, patients with AHP should be monitored annually for liver disease and chronic kidney disease with serum creatinine and estimated glomerular filtration rate monitored. Patients also face an increased risk of hepatocellular carcinoma and should start screening at age 50, with a liver ultrasound every 6 months.

“Fortunately, most people with genetic defects never experience severe acute attacks or may experience only one or a few attacks throughout their lives,” the authors wrote.

The authors (Bruce Wang, MD, Herbert L. Bonkovsky, MD, AGAF, and Manisha Balwani, MD, MS) reported that they are part of the Porphyrias Consortium. The Porphyrias Consortium is part of the Rare Diseases Clinical Research Network, an initiative of the Division of Rare Diseases Research Innovation at the National Center for Advancing Translational Sciences. The consortium is funded through a collaboration between the center and the National Institute of Diabetes and Digestive and Kidney Diseases. Several authors disclosed funding support and honoraria for advisory board roles with various pharmaceutical companies, including Alnylam, which makes givosiran.

This article was updated 2/3/23.

Although rare, acute hepatic porphyrias (AHPs) may be more common than previously thought, particularly among women between ages 15 and 50, according to a new clinical practice update from the American Gastroenterological Association.

For acute attacks, treatment should include intravenous hemin, and for patients with recurrent attacks, a newly-approved therapy called givosiran should be considered, wrote the authors of the update, which was published Jan. 13 in Gastroenterology.

“Diagnoses of AHPs are often missed, with a delay of more than 15 years from initial presentation. The key to early diagnosis is to consider the diagnosis, especially in patients with recurring severe abdominal pain not ascribable to other causes,” wrote the authors, who were led by Bruce Wang, MD, a hepatologist with the University of California, San Francisco.

AHPs are inherited disorders of heme-metabolism, which include acute intermittent porphyria, hereditary coproporphyria, variegate porphyria, and porphyria due to severe deficiency of 5-aminolevulinic acid dehydratase.

Acute intermittent porphyria (AIP) is the most common type, with an estimated prevalence of symptomatic AHP of 1 in 100,000 patients. However, population-level genetic studies show that the prevalence of pathogenic variants for AIP is between 1 in 1,300 and 1 in 1,785.

The major clinical presentation includes attacks of severe abdominal pain, nausea, vomiting, constipation, muscle weakness, neuropathy, tachycardia, and hypertension, yet without peritoneal signs or abnormalities on cross-sectional imaging.

Recent advances in treatment have improved the outlook for patients with AHP. To provide timely guidance, the authors developed 12 clinical practice advice statements on the diagnosis and management of AHPs based on a review of the published literature and expert opinion.

First, AHP screening should be considered in the evaluation of all patients, particularly among women in their childbearing years between ages 15 and 50 with unexplained, recurrent severe abdominal pain that doesn’t have a clear etiology. About 90% of patients with symptomatic AHP are women, and more than 90% of them experience only one or a few acute attacks in their lifetime, which are often precipitated by factors that increase the activity of the enzyme ALAS1 in the liver.

For initial AHP diagnosis, biochemical testing should measure porphobilinogen (PBG) and delta-aminolevulinic acid (ALA) corrected to creatine on a random urine sample. All patients with significantly elevated urinary PBG or ALA should initially be presumed to have AHP, and during acute attacks, both will be elevated at least five-fold of the upper limit of normal. Because ALA and PBG are porphyrin precursors, urine porphyrin testing should not be used alone for AHP screening.

After that, genetic testing should be used to confirm the AHP diagnosis, as well as the specific type of AHP. Sequencing of the four genes ALAD, HMBS, CPOX, and PPOX leads to aminolevulinic acid dehydrase deficiency, acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria, respectively. When whole-gene sequencing is performed, about 95%-99% of cases can be identified. First-degree family members should be screened with genetic testing, and those who are mutation carriers should be counseled.

For acute attacks of AHP that are severe enough to require hospitalization, the currently approved treatment is intravenous hemin infusion, usually given once daily at a dose of 3-4 mg/kg body weight for 3-5 days. Due to potential thrombophlebitis, it’s best to administer hemin in a high-flow central vein via a peripherally inserted central catheter or central port.

In addition, treatment for acute attacks should include analgesics, antiemetics, and management of systemic arterial hypertension, tachycardia, hyponatremia, and hypomagnesemia. The primary goal of treatment during an acute attack is to decrease ALA production. Patients should be counseled to avoid identifiable triggers, such as porphyrinogenic medications, excess alcohol intake, tobacco use, and caloric deprivation.

Although recent advances have improved treatment for acute attacks, management for patients with frequent attacks remains challenging, the study authors wrote. About 3%-5% of patients with symptomatic AHP experience recurrent attacks, which is defined as four or more attacks per year. These attacks aren’t typically associated with identifiable triggers, although some that occur during the luteal phase of a patient’s menstrual cycle are believed to be triggered by progesterone. However, treatment with hormonal suppression therapy, such as GnRH agonists, has had limited success.

Off-label use of prophylactic intravenous heme therapy is common, although the effectiveness in preventing recurrent attacks isn’t well-established. In addition, chronic hemin use is associated with several complications, including infections, iron overload, and the need for indwelling central venous catheters.

Recently, the Food and Drug Administration approved givosiran, a small interfering RNA-based therapy that targets delta-aminolevulinate synthase 1, for treatment in adults with AHP. Monthly subcutaneous therapy appears to significantly lower rates of acute attacks among patients who experience recurrent attacks.

“We suggest prescribing givosiran only for those patients with recurrent acute attacks that are both biochemically and genetically confirmed,” the authors wrote. “Due to limited safety data, givosiran should not be used in women who are pregnant or planning a pregnancy.”

In the most severe cases, liver transplantation should be limited to patients with intractable symptoms and a significantly decreased quality of life who are refractory to pharmacotherapy. If living donor transplantation is considered, genetic testing should be used to screen related living donors since HMBS pathogenic variants in asymptomatic donors could results in poor posttransplantation outcomes.

In the long-term, patients with AHP should be monitored annually for liver disease and chronic kidney disease with serum creatinine and estimated glomerular filtration rate monitored. Patients also face an increased risk of hepatocellular carcinoma and should start screening at age 50, with a liver ultrasound every 6 months.

“Fortunately, most people with genetic defects never experience severe acute attacks or may experience only one or a few attacks throughout their lives,” the authors wrote.

The authors (Bruce Wang, MD, Herbert L. Bonkovsky, MD, AGAF, and Manisha Balwani, MD, MS) reported that they are part of the Porphyrias Consortium. The Porphyrias Consortium is part of the Rare Diseases Clinical Research Network, an initiative of the Division of Rare Diseases Research Innovation at the National Center for Advancing Translational Sciences. The consortium is funded through a collaboration between the center and the National Institute of Diabetes and Digestive and Kidney Diseases. Several authors disclosed funding support and honoraria for advisory board roles with various pharmaceutical companies, including Alnylam, which makes givosiran.

This article was updated 2/3/23.

Although rare, acute hepatic porphyrias (AHPs) may be more common than previously thought, particularly among women between ages 15 and 50, according to a new clinical practice update from the American Gastroenterological Association.

For acute attacks, treatment should include intravenous hemin, and for patients with recurrent attacks, a newly-approved therapy called givosiran should be considered, wrote the authors of the update, which was published Jan. 13 in Gastroenterology.

“Diagnoses of AHPs are often missed, with a delay of more than 15 years from initial presentation. The key to early diagnosis is to consider the diagnosis, especially in patients with recurring severe abdominal pain not ascribable to other causes,” wrote the authors, who were led by Bruce Wang, MD, a hepatologist with the University of California, San Francisco.

AHPs are inherited disorders of heme-metabolism, which include acute intermittent porphyria, hereditary coproporphyria, variegate porphyria, and porphyria due to severe deficiency of 5-aminolevulinic acid dehydratase.

Acute intermittent porphyria (AIP) is the most common type, with an estimated prevalence of symptomatic AHP of 1 in 100,000 patients. However, population-level genetic studies show that the prevalence of pathogenic variants for AIP is between 1 in 1,300 and 1 in 1,785.

The major clinical presentation includes attacks of severe abdominal pain, nausea, vomiting, constipation, muscle weakness, neuropathy, tachycardia, and hypertension, yet without peritoneal signs or abnormalities on cross-sectional imaging.

Recent advances in treatment have improved the outlook for patients with AHP. To provide timely guidance, the authors developed 12 clinical practice advice statements on the diagnosis and management of AHPs based on a review of the published literature and expert opinion.

First, AHP screening should be considered in the evaluation of all patients, particularly among women in their childbearing years between ages 15 and 50 with unexplained, recurrent severe abdominal pain that doesn’t have a clear etiology. About 90% of patients with symptomatic AHP are women, and more than 90% of them experience only one or a few acute attacks in their lifetime, which are often precipitated by factors that increase the activity of the enzyme ALAS1 in the liver.

For initial AHP diagnosis, biochemical testing should measure porphobilinogen (PBG) and delta-aminolevulinic acid (ALA) corrected to creatine on a random urine sample. All patients with significantly elevated urinary PBG or ALA should initially be presumed to have AHP, and during acute attacks, both will be elevated at least five-fold of the upper limit of normal. Because ALA and PBG are porphyrin precursors, urine porphyrin testing should not be used alone for AHP screening.

After that, genetic testing should be used to confirm the AHP diagnosis, as well as the specific type of AHP. Sequencing of the four genes ALAD, HMBS, CPOX, and PPOX leads to aminolevulinic acid dehydrase deficiency, acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria, respectively. When whole-gene sequencing is performed, about 95%-99% of cases can be identified. First-degree family members should be screened with genetic testing, and those who are mutation carriers should be counseled.

For acute attacks of AHP that are severe enough to require hospitalization, the currently approved treatment is intravenous hemin infusion, usually given once daily at a dose of 3-4 mg/kg body weight for 3-5 days. Due to potential thrombophlebitis, it’s best to administer hemin in a high-flow central vein via a peripherally inserted central catheter or central port.

In addition, treatment for acute attacks should include analgesics, antiemetics, and management of systemic arterial hypertension, tachycardia, hyponatremia, and hypomagnesemia. The primary goal of treatment during an acute attack is to decrease ALA production. Patients should be counseled to avoid identifiable triggers, such as porphyrinogenic medications, excess alcohol intake, tobacco use, and caloric deprivation.

Although recent advances have improved treatment for acute attacks, management for patients with frequent attacks remains challenging, the study authors wrote. About 3%-5% of patients with symptomatic AHP experience recurrent attacks, which is defined as four or more attacks per year. These attacks aren’t typically associated with identifiable triggers, although some that occur during the luteal phase of a patient’s menstrual cycle are believed to be triggered by progesterone. However, treatment with hormonal suppression therapy, such as GnRH agonists, has had limited success.

Off-label use of prophylactic intravenous heme therapy is common, although the effectiveness in preventing recurrent attacks isn’t well-established. In addition, chronic hemin use is associated with several complications, including infections, iron overload, and the need for indwelling central venous catheters.

Recently, the Food and Drug Administration approved givosiran, a small interfering RNA-based therapy that targets delta-aminolevulinate synthase 1, for treatment in adults with AHP. Monthly subcutaneous therapy appears to significantly lower rates of acute attacks among patients who experience recurrent attacks.

“We suggest prescribing givosiran only for those patients with recurrent acute attacks that are both biochemically and genetically confirmed,” the authors wrote. “Due to limited safety data, givosiran should not be used in women who are pregnant or planning a pregnancy.”

In the most severe cases, liver transplantation should be limited to patients with intractable symptoms and a significantly decreased quality of life who are refractory to pharmacotherapy. If living donor transplantation is considered, genetic testing should be used to screen related living donors since HMBS pathogenic variants in asymptomatic donors could results in poor posttransplantation outcomes.

In the long-term, patients with AHP should be monitored annually for liver disease and chronic kidney disease with serum creatinine and estimated glomerular filtration rate monitored. Patients also face an increased risk of hepatocellular carcinoma and should start screening at age 50, with a liver ultrasound every 6 months.

“Fortunately, most people with genetic defects never experience severe acute attacks or may experience only one or a few attacks throughout their lives,” the authors wrote.

The authors (Bruce Wang, MD, Herbert L. Bonkovsky, MD, AGAF, and Manisha Balwani, MD, MS) reported that they are part of the Porphyrias Consortium. The Porphyrias Consortium is part of the Rare Diseases Clinical Research Network, an initiative of the Division of Rare Diseases Research Innovation at the National Center for Advancing Translational Sciences. The consortium is funded through a collaboration between the center and the National Institute of Diabetes and Digestive and Kidney Diseases. Several authors disclosed funding support and honoraria for advisory board roles with various pharmaceutical companies, including Alnylam, which makes givosiran.

This article was updated 2/3/23.

An international group of physicians has issued consensus recommendations for the diagnosis and management of patients with early-onset colorectal cancer (eoCRC).

Led by Giulia Martina Cavestro, MD, PhD, a gastroenterologist with the University Vita Salute San Raffaele Hospital, Milan, the Delphi Initiative for Early-Onset Colorectal Cancer group penned 31 recommendations for treating patients 50 years and younger, several of which were highlighted as “strong.” The recommendations are based on a review of 145 studies.

“There was strong consensus that all individuals younger than 50 should undergo CRC risk stratification and prompt symptom assessment. All newly diagnosed eoCRC patients should receive germline genetic testing, ideally before surgery,” the authors wrote.

Colorectal cancer in men and women under age 50 years has been increasing since the 1990s in both low and high-income countries even as cases decline among individuals over 50 years old because of changes in lifestyle and screening programs.

Published in Clinical Gastroenterology and Hepatology, it represents the first consensus statement for eoCRC. Current knowledge gaps include determination of the need for surgical, adjuvant, neoadjuvant, and supportive treatment.

The recommendations include 31 statements spread over seven broad categories: Diagnosis, risk factors, genetics, patho-oncology, therapy, endoscopy, and supportive care.

In regards to diagnosis, any individual with alarming symptoms under the age of 50 should be assessed for CRC. Alarming symptoms include, but are not limited to, hematochezia, unexplained iron-deficiency anemia, or unexplained weight loss. A colonoscopy should be scheduled ideally within 30 days of seeing a physician. The preferred method is high-quality, high-definition white-light endoscopy.

Also, a risk assessment should be included. Any family history of CRC and/or a personal history of risk factors and comorbidities could identify high-risk individuals. About 28% of patients with early onset disease have a family history of colorectal cancer, which is similar to the frequency seen in late onset CRC.

After diagnosis, all patients should undergo germline genetic testing, ideally before surgery because it may influence treatment decisions. All tumors should be evaluated for mismatch repair phenotype (with either immunohistochemistry staining for MMR proteins or microsatellite instability testing) preferably before treatment. Age alone, the authors emphasized, shouldn’t drive decisions on endoscopic, surgical, and oncologic treatment.

Germline genetic testing should include APC, BMPR1A, EPCAM, MLH1, MSH2, MSH6, MUTYH, POLD1, POLE, PMS2, PTEN, SMAD4, STK11, and TP53. Other testing candidates, when not cost prohibitive, include genes that are somewhat common and can influence clinical management: BRCA1, BRCA2, ATM, CHEK2, and PALB2. Testing could also include genes that are less prevalent but that can also influence clinical management: BRIP1, BARD1, CDKN2A, CDH1, RAD51C and RAD51D. When not cost prohibitive, genetic testing can also include genes associated with CRC or polyposis, which include AXIN2, GREM1, MLH3, MSH3, MBD4, NTHL1, RNF43, and RPS20.

In terms of treatment, there is no evidence that neoadjuvant, adjuvant, or systemic therapies should differ between eoCRC and late-onset patients. Endoscopic, surgical, and oncologic treatment should be similar to older patients, but treatment options should be individualized based on factors that could include greater risk of metachronous CRC, germline and somatic testing results, concerns about fertility, concomitant indications for gynecologic cancer, and heightened risk of chemotherapy-induced nausea and vomiting.

After treatment, patients should receive standard surveillance at 1 and 3 years, and colonoscopies should be performed at least every 5 years. Those with hereditary CRC should receive surveillance based on their specific variant and phenotype.

All eoCRC patients should be counseled regarding fertility preservation and the potential impacts of treatments on fertility, and they should also receive psychosocial support. Patients who are at high risk of gynecologic cancers resulting from pathogenic or syndromic probable pathogenic variants can undergo prophylactic hysterectomy with or without bilateral oophorectomy. Fertility preservation options can be considered based on the estimated risk of gonadotoxicity, known risks of the treatment plan, and disease stage and severity.

Supportive care for eoCRC should be similar to the general population, though they may be at greater risk of chemotherapy-induced nausea and vomiting than late-onset patients, especially females with low body mass index. Other supportive interventions can include early personalized physical activity and nutritional support to maintain and recover muscle mass, as well as psychosocial or psychosexual counseling regarding the impact of treatments and the illness on sexual health.

The authors call for more research, specifically in the areas of risks and benefits of screening young populations who are at average or increased risk for CRC; identifying risk factors for eoCRC; outcomes research on neoadjuvant, adjuvant, and systemic therapies in eoCRC populations; comparison of long-term outcomes following surgical and endoscopic resections; and optimal follow-up and surveillance strategies following curative resection.

The recommendations were endorsed by the Associazione Italiana Familiarità, Ereditarietà Tumori, the Collaborative Group of the Americas on Inherited Gastrointestinal Cancers, the European Hereditary Tumor Group, and the International Society for Gastrointestinal Hereditary Tumours.

An international group of physicians has issued consensus recommendations for the diagnosis and management of patients with early-onset colorectal cancer (eoCRC).

Led by Giulia Martina Cavestro, MD, PhD, a gastroenterologist with the University Vita Salute San Raffaele Hospital, Milan, the Delphi Initiative for Early-Onset Colorectal Cancer group penned 31 recommendations for treating patients 50 years and younger, several of which were highlighted as “strong.” The recommendations are based on a review of 145 studies.

“There was strong consensus that all individuals younger than 50 should undergo CRC risk stratification and prompt symptom assessment. All newly diagnosed eoCRC patients should receive germline genetic testing, ideally before surgery,” the authors wrote.

Colorectal cancer in men and women under age 50 years has been increasing since the 1990s in both low and high-income countries even as cases decline among individuals over 50 years old because of changes in lifestyle and screening programs.

Published in Clinical Gastroenterology and Hepatology, it represents the first consensus statement for eoCRC. Current knowledge gaps include determination of the need for surgical, adjuvant, neoadjuvant, and supportive treatment.

The recommendations include 31 statements spread over seven broad categories: Diagnosis, risk factors, genetics, patho-oncology, therapy, endoscopy, and supportive care.

In regards to diagnosis, any individual with alarming symptoms under the age of 50 should be assessed for CRC. Alarming symptoms include, but are not limited to, hematochezia, unexplained iron-deficiency anemia, or unexplained weight loss. A colonoscopy should be scheduled ideally within 30 days of seeing a physician. The preferred method is high-quality, high-definition white-light endoscopy.

Also, a risk assessment should be included. Any family history of CRC and/or a personal history of risk factors and comorbidities could identify high-risk individuals. About 28% of patients with early onset disease have a family history of colorectal cancer, which is similar to the frequency seen in late onset CRC.

After diagnosis, all patients should undergo germline genetic testing, ideally before surgery because it may influence treatment decisions. All tumors should be evaluated for mismatch repair phenotype (with either immunohistochemistry staining for MMR proteins or microsatellite instability testing) preferably before treatment. Age alone, the authors emphasized, shouldn’t drive decisions on endoscopic, surgical, and oncologic treatment.

Germline genetic testing should include APC, BMPR1A, EPCAM, MLH1, MSH2, MSH6, MUTYH, POLD1, POLE, PMS2, PTEN, SMAD4, STK11, and TP53. Other testing candidates, when not cost prohibitive, include genes that are somewhat common and can influence clinical management: BRCA1, BRCA2, ATM, CHEK2, and PALB2. Testing could also include genes that are less prevalent but that can also influence clinical management: BRIP1, BARD1, CDKN2A, CDH1, RAD51C and RAD51D. When not cost prohibitive, genetic testing can also include genes associated with CRC or polyposis, which include AXIN2, GREM1, MLH3, MSH3, MBD4, NTHL1, RNF43, and RPS20.

In terms of treatment, there is no evidence that neoadjuvant, adjuvant, or systemic therapies should differ between eoCRC and late-onset patients. Endoscopic, surgical, and oncologic treatment should be similar to older patients, but treatment options should be individualized based on factors that could include greater risk of metachronous CRC, germline and somatic testing results, concerns about fertility, concomitant indications for gynecologic cancer, and heightened risk of chemotherapy-induced nausea and vomiting.

After treatment, patients should receive standard surveillance at 1 and 3 years, and colonoscopies should be performed at least every 5 years. Those with hereditary CRC should receive surveillance based on their specific variant and phenotype.

All eoCRC patients should be counseled regarding fertility preservation and the potential impacts of treatments on fertility, and they should also receive psychosocial support. Patients who are at high risk of gynecologic cancers resulting from pathogenic or syndromic probable pathogenic variants can undergo prophylactic hysterectomy with or without bilateral oophorectomy. Fertility preservation options can be considered based on the estimated risk of gonadotoxicity, known risks of the treatment plan, and disease stage and severity.

Supportive care for eoCRC should be similar to the general population, though they may be at greater risk of chemotherapy-induced nausea and vomiting than late-onset patients, especially females with low body mass index. Other supportive interventions can include early personalized physical activity and nutritional support to maintain and recover muscle mass, as well as psychosocial or psychosexual counseling regarding the impact of treatments and the illness on sexual health.

The authors call for more research, specifically in the areas of risks and benefits of screening young populations who are at average or increased risk for CRC; identifying risk factors for eoCRC; outcomes research on neoadjuvant, adjuvant, and systemic therapies in eoCRC populations; comparison of long-term outcomes following surgical and endoscopic resections; and optimal follow-up and surveillance strategies following curative resection.

The recommendations were endorsed by the Associazione Italiana Familiarità, Ereditarietà Tumori, the Collaborative Group of the Americas on Inherited Gastrointestinal Cancers, the European Hereditary Tumor Group, and the International Society for Gastrointestinal Hereditary Tumours.

An international group of physicians has issued consensus recommendations for the diagnosis and management of patients with early-onset colorectal cancer (eoCRC).

Led by Giulia Martina Cavestro, MD, PhD, a gastroenterologist with the University Vita Salute San Raffaele Hospital, Milan, the Delphi Initiative for Early-Onset Colorectal Cancer group penned 31 recommendations for treating patients 50 years and younger, several of which were highlighted as “strong.” The recommendations are based on a review of 145 studies.

“There was strong consensus that all individuals younger than 50 should undergo CRC risk stratification and prompt symptom assessment. All newly diagnosed eoCRC patients should receive germline genetic testing, ideally before surgery,” the authors wrote.

Colorectal cancer in men and women under age 50 years has been increasing since the 1990s in both low and high-income countries even as cases decline among individuals over 50 years old because of changes in lifestyle and screening programs.

Published in Clinical Gastroenterology and Hepatology, it represents the first consensus statement for eoCRC. Current knowledge gaps include determination of the need for surgical, adjuvant, neoadjuvant, and supportive treatment.

The recommendations include 31 statements spread over seven broad categories: Diagnosis, risk factors, genetics, patho-oncology, therapy, endoscopy, and supportive care.

In regards to diagnosis, any individual with alarming symptoms under the age of 50 should be assessed for CRC. Alarming symptoms include, but are not limited to, hematochezia, unexplained iron-deficiency anemia, or unexplained weight loss. A colonoscopy should be scheduled ideally within 30 days of seeing a physician. The preferred method is high-quality, high-definition white-light endoscopy.

Also, a risk assessment should be included. Any family history of CRC and/or a personal history of risk factors and comorbidities could identify high-risk individuals. About 28% of patients with early onset disease have a family history of colorectal cancer, which is similar to the frequency seen in late onset CRC.

After diagnosis, all patients should undergo germline genetic testing, ideally before surgery because it may influence treatment decisions. All tumors should be evaluated for mismatch repair phenotype (with either immunohistochemistry staining for MMR proteins or microsatellite instability testing) preferably before treatment. Age alone, the authors emphasized, shouldn’t drive decisions on endoscopic, surgical, and oncologic treatment.

Germline genetic testing should include APC, BMPR1A, EPCAM, MLH1, MSH2, MSH6, MUTYH, POLD1, POLE, PMS2, PTEN, SMAD4, STK11, and TP53. Other testing candidates, when not cost prohibitive, include genes that are somewhat common and can influence clinical management: BRCA1, BRCA2, ATM, CHEK2, and PALB2. Testing could also include genes that are less prevalent but that can also influence clinical management: BRIP1, BARD1, CDKN2A, CDH1, RAD51C and RAD51D. When not cost prohibitive, genetic testing can also include genes associated with CRC or polyposis, which include AXIN2, GREM1, MLH3, MSH3, MBD4, NTHL1, RNF43, and RPS20.

In terms of treatment, there is no evidence that neoadjuvant, adjuvant, or systemic therapies should differ between eoCRC and late-onset patients. Endoscopic, surgical, and oncologic treatment should be similar to older patients, but treatment options should be individualized based on factors that could include greater risk of metachronous CRC, germline and somatic testing results, concerns about fertility, concomitant indications for gynecologic cancer, and heightened risk of chemotherapy-induced nausea and vomiting.

After treatment, patients should receive standard surveillance at 1 and 3 years, and colonoscopies should be performed at least every 5 years. Those with hereditary CRC should receive surveillance based on their specific variant and phenotype.

All eoCRC patients should be counseled regarding fertility preservation and the potential impacts of treatments on fertility, and they should also receive psychosocial support. Patients who are at high risk of gynecologic cancers resulting from pathogenic or syndromic probable pathogenic variants can undergo prophylactic hysterectomy with or without bilateral oophorectomy. Fertility preservation options can be considered based on the estimated risk of gonadotoxicity, known risks of the treatment plan, and disease stage and severity.

Supportive care for eoCRC should be similar to the general population, though they may be at greater risk of chemotherapy-induced nausea and vomiting than late-onset patients, especially females with low body mass index. Other supportive interventions can include early personalized physical activity and nutritional support to maintain and recover muscle mass, as well as psychosocial or psychosexual counseling regarding the impact of treatments and the illness on sexual health.

The authors call for more research, specifically in the areas of risks and benefits of screening young populations who are at average or increased risk for CRC; identifying risk factors for eoCRC; outcomes research on neoadjuvant, adjuvant, and systemic therapies in eoCRC populations; comparison of long-term outcomes following surgical and endoscopic resections; and optimal follow-up and surveillance strategies following curative resection.

The recommendations were endorsed by the Associazione Italiana Familiarità, Ereditarietà Tumori, the Collaborative Group of the Americas on Inherited Gastrointestinal Cancers, the European Hereditary Tumor Group, and the International Society for Gastrointestinal Hereditary Tumours.

In a new retrospective analysis of patients with above-average risk of colorectal cancer, multiple negative fecal immunohistochemical tests (FITs) were associated with a lower risk of advanced neoplasia. The findings suggest that multiple negative FITs could potentially identify individuals in high-risk surveillance who aren’t truly high risk, which could in turn ease the logjam of colonoscopies and free resources for truly high-risk individuals.

The study, conducted in Australia, was published online in Clinical Gastroenterology and Hepatology. It included patients who completed at least two FIT exams between surveillance colonoscopies and had no neoplasia or nonadvanced adenoma at prior colonoscopy. Above-average risk was defined as a family history or by findings at surveillance colonoscopy.

The study has some limitations. It is a retrospective analysis between the years 2008 and 2019, and colonoscopy guidelines in the United States have since changed, with a recommendation of surveillance colonoscopy at 7-10 years following 1-2 adenomas discovered at surveillance colonoscopy, and the current study includes follow-up colonoscopy at 5 years. “These data are informative for patients up to 5 years, but they’re not really informative afterwards. They just don’t have those data yet,” said Reed Ness, MD, who was asked to comment on the study.

The authors also don’t describe what they mean by a family history of colorectal cancer risk. “My take was that it’s an interesting result which would seem to support the possibility of returning some patients with a family history or adenoma history to a noncolonoscopy screening regimen after a negative surveillance colonoscopy. We’ll need to see where the data lead us in the future,” said Dr. Ness, who is an associate professor of medicine at Vanderbilt University Medical Center, Nashville, Tenn.

“We’re letting people go 10 years now, and some people are uncomfortable with allowing patients to go 10 years. So you could think of a scenario where you use FIT to try to find people that might have higher-risk lesions that need to come back for colonoscopy within that 10 years,” said Dr. Ness. That issue is particularly relevant given the wide range of adenoma detection rates among gastroenterologists, because FIT could detect a polyp that was missed during a colonoscopy.

The study included two groups with increased risk – those with a family history of colon cancer, and those with previously detected adenomas. The family history cohort may be useful for clinical practice, according to Priyanka Kanth, MD, who was also asked to comment on the study. “Some people may not need [a colonoscopy] at 5 years if they have no polyps found and negative FIT,” said Dr. Kanth, who is an associate professor of gastroenterology at Georgetown University, Washington.

She feels less certain about the group with previously detected adenomas, given the change in U.S. guidelines. “We have already changed that, so I don’t think we need to really do FIT intervals for that cohort,” said Dr. Kanth. “I think this is a good study that has a lot of information and also reassures us that we don’t need such frequent colonoscopy surveillance,” she added.

Steve Serrao, MD, PhD, who was also asked for comment, emphasized the importance of high-quality colonoscopies that reach the cecum 95% of the time, and achieving high adenoma-detection rates. The system can get overwhelmed conducting colonoscopies on patients with good insurance coverage who have already undergone high-quality colonoscopies. “That pushes out patients that haven’t necessarily had a colonoscopy or a FIT. People who don’t have access are kind of crowded out by these false-positive tests. The best modality is actually to do a high-quality colonoscopy and then to have a really well-directed strategy following that colonoscopy,” said Dr. Serrao, who is division chief of gastroenterology and hepatology at Riverside University Health System, Moreno Valley, Calif.

The researchers analyzed data from 4,021 surveillance intervals and 3,369 participants. A total of 1,436 had no neoplasia at the prior colonoscopy, 1,704 had nonadvanced adenoma, and 880 had advanced adenoma. Participants completed no or one to four FIT tests between colonoscopies, with the final colonoscopy performed within 2 years of FIT tests. The median age was 63.9 years; 53.6% were female; 71.1% had a prior adenoma; and 28.9% had a family history of colorectal cancer. A total of 29.4% of participants had one negative FIT; 6.9% had four negative FITs during the interval period; and 31.0% did not complete any FIT tests.

Of follow-up colonoscopies, 9.9% revealed advanced adenomas. Among the patients with no prior neoplasia, those with one negative FIT had a cumulative index function for advanced neoplasia at 5 years of 8.5% (95% confidence interval, 4.9%-13.3%). This was higher than for those with three negative FITs (4.5%; 95% CI, 2.0%-8.6%) or four negative FITs (1.9%; 95% CI, 0.5%-5.0%). The association held for individuals with prior nonadvanced adenoma but not those with advanced adenoma.

Over the 5-year interval, three or more negative FIT tests were associated with a 50%-70% reduction in advanced neoplasia risk at follow-up colonoscopy (P < .001). There was no significant association over a 3-year interval. Dr. Kanth, Dr. Serrao, and Dr. Ness have no relevant financial disclosures.
 

In a new retrospective analysis of patients with above-average risk of colorectal cancer, multiple negative fecal immunohistochemical tests (FITs) were associated with a lower risk of advanced neoplasia. The findings suggest that multiple negative FITs could potentially identify individuals in high-risk surveillance who aren’t truly high risk, which could in turn ease the logjam of colonoscopies and free resources for truly high-risk individuals.

The study, conducted in Australia, was published online in Clinical Gastroenterology and Hepatology. It included patients who completed at least two FIT exams between surveillance colonoscopies and had no neoplasia or nonadvanced adenoma at prior colonoscopy. Above-average risk was defined as a family history or by findings at surveillance colonoscopy.

The study has some limitations. It is a retrospective analysis between the years 2008 and 2019, and colonoscopy guidelines in the United States have since changed, with a recommendation of surveillance colonoscopy at 7-10 years following 1-2 adenomas discovered at surveillance colonoscopy, and the current study includes follow-up colonoscopy at 5 years. “These data are informative for patients up to 5 years, but they’re not really informative afterwards. They just don’t have those data yet,” said Reed Ness, MD, who was asked to comment on the study.

The authors also don’t describe what they mean by a family history of colorectal cancer risk. “My take was that it’s an interesting result which would seem to support the possibility of returning some patients with a family history or adenoma history to a noncolonoscopy screening regimen after a negative surveillance colonoscopy. We’ll need to see where the data lead us in the future,” said Dr. Ness, who is an associate professor of medicine at Vanderbilt University Medical Center, Nashville, Tenn.

“We’re letting people go 10 years now, and some people are uncomfortable with allowing patients to go 10 years. So you could think of a scenario where you use FIT to try to find people that might have higher-risk lesions that need to come back for colonoscopy within that 10 years,” said Dr. Ness. That issue is particularly relevant given the wide range of adenoma detection rates among gastroenterologists, because FIT could detect a polyp that was missed during a colonoscopy.

The study included two groups with increased risk – those with a family history of colon cancer, and those with previously detected adenomas. The family history cohort may be useful for clinical practice, according to Priyanka Kanth, MD, who was also asked to comment on the study. “Some people may not need [a colonoscopy] at 5 years if they have no polyps found and negative FIT,” said Dr. Kanth, who is an associate professor of gastroenterology at Georgetown University, Washington.

She feels less certain about the group with previously detected adenomas, given the change in U.S. guidelines. “We have already changed that, so I don’t think we need to really do FIT intervals for that cohort,” said Dr. Kanth. “I think this is a good study that has a lot of information and also reassures us that we don’t need such frequent colonoscopy surveillance,” she added.

Steve Serrao, MD, PhD, who was also asked for comment, emphasized the importance of high-quality colonoscopies that reach the cecum 95% of the time, and achieving high adenoma-detection rates. The system can get overwhelmed conducting colonoscopies on patients with good insurance coverage who have already undergone high-quality colonoscopies. “That pushes out patients that haven’t necessarily had a colonoscopy or a FIT. People who don’t have access are kind of crowded out by these false-positive tests. The best modality is actually to do a high-quality colonoscopy and then to have a really well-directed strategy following that colonoscopy,” said Dr. Serrao, who is division chief of gastroenterology and hepatology at Riverside University Health System, Moreno Valley, Calif.

The researchers analyzed data from 4,021 surveillance intervals and 3,369 participants. A total of 1,436 had no neoplasia at the prior colonoscopy, 1,704 had nonadvanced adenoma, and 880 had advanced adenoma. Participants completed no or one to four FIT tests between colonoscopies, with the final colonoscopy performed within 2 years of FIT tests. The median age was 63.9 years; 53.6% were female; 71.1% had a prior adenoma; and 28.9% had a family history of colorectal cancer. A total of 29.4% of participants had one negative FIT; 6.9% had four negative FITs during the interval period; and 31.0% did not complete any FIT tests.

Of follow-up colonoscopies, 9.9% revealed advanced adenomas. Among the patients with no prior neoplasia, those with one negative FIT had a cumulative index function for advanced neoplasia at 5 years of 8.5% (95% confidence interval, 4.9%-13.3%). This was higher than for those with three negative FITs (4.5%; 95% CI, 2.0%-8.6%) or four negative FITs (1.9%; 95% CI, 0.5%-5.0%). The association held for individuals with prior nonadvanced adenoma but not those with advanced adenoma.

Over the 5-year interval, three or more negative FIT tests were associated with a 50%-70% reduction in advanced neoplasia risk at follow-up colonoscopy (P < .001). There was no significant association over a 3-year interval. Dr. Kanth, Dr. Serrao, and Dr. Ness have no relevant financial disclosures.
 

In a new retrospective analysis of patients with above-average risk of colorectal cancer, multiple negative fecal immunohistochemical tests (FITs) were associated with a lower risk of advanced neoplasia. The findings suggest that multiple negative FITs could potentially identify individuals in high-risk surveillance who aren’t truly high risk, which could in turn ease the logjam of colonoscopies and free resources for truly high-risk individuals.

The study, conducted in Australia, was published online in Clinical Gastroenterology and Hepatology. It included patients who completed at least two FIT exams between surveillance colonoscopies and had no neoplasia or nonadvanced adenoma at prior colonoscopy. Above-average risk was defined as a family history or by findings at surveillance colonoscopy.

The study has some limitations. It is a retrospective analysis between the years 2008 and 2019, and colonoscopy guidelines in the United States have since changed, with a recommendation of surveillance colonoscopy at 7-10 years following 1-2 adenomas discovered at surveillance colonoscopy, and the current study includes follow-up colonoscopy at 5 years. “These data are informative for patients up to 5 years, but they’re not really informative afterwards. They just don’t have those data yet,” said Reed Ness, MD, who was asked to comment on the study.

The authors also don’t describe what they mean by a family history of colorectal cancer risk. “My take was that it’s an interesting result which would seem to support the possibility of returning some patients with a family history or adenoma history to a noncolonoscopy screening regimen after a negative surveillance colonoscopy. We’ll need to see where the data lead us in the future,” said Dr. Ness, who is an associate professor of medicine at Vanderbilt University Medical Center, Nashville, Tenn.

“We’re letting people go 10 years now, and some people are uncomfortable with allowing patients to go 10 years. So you could think of a scenario where you use FIT to try to find people that might have higher-risk lesions that need to come back for colonoscopy within that 10 years,” said Dr. Ness. That issue is particularly relevant given the wide range of adenoma detection rates among gastroenterologists, because FIT could detect a polyp that was missed during a colonoscopy.

The study included two groups with increased risk – those with a family history of colon cancer, and those with previously detected adenomas. The family history cohort may be useful for clinical practice, according to Priyanka Kanth, MD, who was also asked to comment on the study. “Some people may not need [a colonoscopy] at 5 years if they have no polyps found and negative FIT,” said Dr. Kanth, who is an associate professor of gastroenterology at Georgetown University, Washington.

She feels less certain about the group with previously detected adenomas, given the change in U.S. guidelines. “We have already changed that, so I don’t think we need to really do FIT intervals for that cohort,” said Dr. Kanth. “I think this is a good study that has a lot of information and also reassures us that we don’t need such frequent colonoscopy surveillance,” she added.

Steve Serrao, MD, PhD, who was also asked for comment, emphasized the importance of high-quality colonoscopies that reach the cecum 95% of the time, and achieving high adenoma-detection rates. The system can get overwhelmed conducting colonoscopies on patients with good insurance coverage who have already undergone high-quality colonoscopies. “That pushes out patients that haven’t necessarily had a colonoscopy or a FIT. People who don’t have access are kind of crowded out by these false-positive tests. The best modality is actually to do a high-quality colonoscopy and then to have a really well-directed strategy following that colonoscopy,” said Dr. Serrao, who is division chief of gastroenterology and hepatology at Riverside University Health System, Moreno Valley, Calif.

The researchers analyzed data from 4,021 surveillance intervals and 3,369 participants. A total of 1,436 had no neoplasia at the prior colonoscopy, 1,704 had nonadvanced adenoma, and 880 had advanced adenoma. Participants completed no or one to four FIT tests between colonoscopies, with the final colonoscopy performed within 2 years of FIT tests. The median age was 63.9 years; 53.6% were female; 71.1% had a prior adenoma; and 28.9% had a family history of colorectal cancer. A total of 29.4% of participants had one negative FIT; 6.9% had four negative FITs during the interval period; and 31.0% did not complete any FIT tests.

Of follow-up colonoscopies, 9.9% revealed advanced adenomas. Among the patients with no prior neoplasia, those with one negative FIT had a cumulative index function for advanced neoplasia at 5 years of 8.5% (95% confidence interval, 4.9%-13.3%). This was higher than for those with three negative FITs (4.5%; 95% CI, 2.0%-8.6%) or four negative FITs (1.9%; 95% CI, 0.5%-5.0%). The association held for individuals with prior nonadvanced adenoma but not those with advanced adenoma.

Over the 5-year interval, three or more negative FIT tests were associated with a 50%-70% reduction in advanced neoplasia risk at follow-up colonoscopy (P < .001). There was no significant association over a 3-year interval. Dr. Kanth, Dr. Serrao, and Dr. Ness have no relevant financial disclosures.
 

Patients with moderate to severe active ulcerative colitis (UC) who received induction therapy with either ritlecitinib or brepocitinib showed significant improvement across multiple outcome metrics in a phase 2b “umbrella” study of the two investigational agents.

The study by William J. Sandborn, MD, division of gastroenterology, University of California, San Diego, and colleagues was published online in Clinical Gastroenterology and Hepatology.

Ritlecitinib is a dual inhibitor that selectively inhibits Janus kinase 3 (JAK3) and the TEC family of tyrosine kinases, while brepocitinib is a dual tyrosine kinase 2 (TYK2) and JAK1 inhibitor.

Both agents have demonstrated efficacy and acceptable safety in the treatment of alopecia areata and rheumatoid arthritis and are being evaluated for treating vitiligo, Crohn’s disease, and UC.

The different JAK selectivity profiles of ritlecitinib (JAK3/TEC) and brepocitinib (TYK2/JAK1), compared with other JAK inhibitors, could further the understanding of the role these pathways play in UC, the investigators note.
 

The VIBRATO study

As part of the phase 2b VIBRATO study, 317 patients with moderate to severe active UC (total Mayo Score ≥ 6) were randomly assigned to an 8-week induction course of once-daily oral ritlecitinib (20, 70, or 200 mg), brepocitinib (10, 30, or 60 mg), or matching placebo.

At week 8, compared with placebo, treatment with ritlecitinib or brepocitinib was associated with significantly lower mean total Mayo Scores (the primary endpoint) and higher rates of clinical remission, endoscopic and histologic improvement, and mucosal healing.

For both drugs, improvement on most metrics was dose dependent, with greater benefit at the highest dose.

For example, the placebo-adjusted mean total Mayo Score at week 8 was −4.6 for ritlecitinib 200 mg (P < .001) and −3.2 for brepocitinib 60 mg (P < .001). Both agents showed a “rapid” onset of action, with significant effects on the partial Mayo Score seen after just 2 weeks of treatment, the authors report.

Modified clinical remission at week 8 (a key secondary endpoint) was achieved in 36% of patients taking ritlecitinib 200 mg and 25.5% of those taking brepocitinib 60 mg (vs. 0% for patients taking placebo).

Endoscopic and histologic improvement, clinical response, mucosal healing, and the patient-reported outcome on the Inflammatory Bowel Disease Questionnaire followed a similar pattern, with a dose-dependent increase in treatment effect observed in most parameters at week 8, compared with placebo.
 

Longer-term data needed

Both agents were well tolerated with “acceptable short-term safety profiles,” the authors say.

There were no clinically significant findings for any laboratory parameters evaluated. Adverse events were mostly mild.

Infections were observed in 8.7% of patients taking ritlecitinib and 16.9% of those taking brepocitinib, compared with 4% of patients taking placebo. No serious cases of herpes zoster occurred.

One patient taking ritlecitinib suffered myocardial infarction and died, and one patient taking brepocitinib had peripheral artery thrombosis (left tibial artery). Both cases were considered unrelated to the study drug.

“As JAK inhibitors are associated with increased risk of major cardiovascular events and venous thromboembolisms, larger studies are needed for ritlecitinib and brepocitinib to fully understand their safety profiles,” the investigators say.

Limitations of the study include the small sample size and short 8-week treatment period. Longer-term safety and efficacy of both agents are being investigated.

The study was sponsored by Pfizer, which is developing both drugs. Dr. Sandborn and several coauthors have disclosed financial relationships with the company.

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

Patients with moderate to severe active ulcerative colitis (UC) who received induction therapy with either ritlecitinib or brepocitinib showed significant improvement across multiple outcome metrics in a phase 2b “umbrella” study of the two investigational agents.

The study by William J. Sandborn, MD, division of gastroenterology, University of California, San Diego, and colleagues was published online in Clinical Gastroenterology and Hepatology.

Ritlecitinib is a dual inhibitor that selectively inhibits Janus kinase 3 (JAK3) and the TEC family of tyrosine kinases, while brepocitinib is a dual tyrosine kinase 2 (TYK2) and JAK1 inhibitor.

Both agents have demonstrated efficacy and acceptable safety in the treatment of alopecia areata and rheumatoid arthritis and are being evaluated for treating vitiligo, Crohn’s disease, and UC.

The different JAK selectivity profiles of ritlecitinib (JAK3/TEC) and brepocitinib (TYK2/JAK1), compared with other JAK inhibitors, could further the understanding of the role these pathways play in UC, the investigators note.
 

The VIBRATO study

As part of the phase 2b VIBRATO study, 317 patients with moderate to severe active UC (total Mayo Score ≥ 6) were randomly assigned to an 8-week induction course of once-daily oral ritlecitinib (20, 70, or 200 mg), brepocitinib (10, 30, or 60 mg), or matching placebo.

At week 8, compared with placebo, treatment with ritlecitinib or brepocitinib was associated with significantly lower mean total Mayo Scores (the primary endpoint) and higher rates of clinical remission, endoscopic and histologic improvement, and mucosal healing.

For both drugs, improvement on most metrics was dose dependent, with greater benefit at the highest dose.

For example, the placebo-adjusted mean total Mayo Score at week 8 was −4.6 for ritlecitinib 200 mg (P < .001) and −3.2 for brepocitinib 60 mg (P < .001). Both agents showed a “rapid” onset of action, with significant effects on the partial Mayo Score seen after just 2 weeks of treatment, the authors report.

Modified clinical remission at week 8 (a key secondary endpoint) was achieved in 36% of patients taking ritlecitinib 200 mg and 25.5% of those taking brepocitinib 60 mg (vs. 0% for patients taking placebo).

Endoscopic and histologic improvement, clinical response, mucosal healing, and the patient-reported outcome on the Inflammatory Bowel Disease Questionnaire followed a similar pattern, with a dose-dependent increase in treatment effect observed in most parameters at week 8, compared with placebo.
 

Longer-term data needed

Both agents were well tolerated with “acceptable short-term safety profiles,” the authors say.

There were no clinically significant findings for any laboratory parameters evaluated. Adverse events were mostly mild.

Infections were observed in 8.7% of patients taking ritlecitinib and 16.9% of those taking brepocitinib, compared with 4% of patients taking placebo. No serious cases of herpes zoster occurred.

One patient taking ritlecitinib suffered myocardial infarction and died, and one patient taking brepocitinib had peripheral artery thrombosis (left tibial artery). Both cases were considered unrelated to the study drug.

“As JAK inhibitors are associated with increased risk of major cardiovascular events and venous thromboembolisms, larger studies are needed for ritlecitinib and brepocitinib to fully understand their safety profiles,” the investigators say.

Limitations of the study include the small sample size and short 8-week treatment period. Longer-term safety and efficacy of both agents are being investigated.

The study was sponsored by Pfizer, which is developing both drugs. Dr. Sandborn and several coauthors have disclosed financial relationships with the company.

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

Patients with moderate to severe active ulcerative colitis (UC) who received induction therapy with either ritlecitinib or brepocitinib showed significant improvement across multiple outcome metrics in a phase 2b “umbrella” study of the two investigational agents.

The study by William J. Sandborn, MD, division of gastroenterology, University of California, San Diego, and colleagues was published online in Clinical Gastroenterology and Hepatology.

Ritlecitinib is a dual inhibitor that selectively inhibits Janus kinase 3 (JAK3) and the TEC family of tyrosine kinases, while brepocitinib is a dual tyrosine kinase 2 (TYK2) and JAK1 inhibitor.

Both agents have demonstrated efficacy and acceptable safety in the treatment of alopecia areata and rheumatoid arthritis and are being evaluated for treating vitiligo, Crohn’s disease, and UC.

The different JAK selectivity profiles of ritlecitinib (JAK3/TEC) and brepocitinib (TYK2/JAK1), compared with other JAK inhibitors, could further the understanding of the role these pathways play in UC, the investigators note.
 

The VIBRATO study

As part of the phase 2b VIBRATO study, 317 patients with moderate to severe active UC (total Mayo Score ≥ 6) were randomly assigned to an 8-week induction course of once-daily oral ritlecitinib (20, 70, or 200 mg), brepocitinib (10, 30, or 60 mg), or matching placebo.

At week 8, compared with placebo, treatment with ritlecitinib or brepocitinib was associated with significantly lower mean total Mayo Scores (the primary endpoint) and higher rates of clinical remission, endoscopic and histologic improvement, and mucosal healing.

For both drugs, improvement on most metrics was dose dependent, with greater benefit at the highest dose.

For example, the placebo-adjusted mean total Mayo Score at week 8 was −4.6 for ritlecitinib 200 mg (P < .001) and −3.2 for brepocitinib 60 mg (P < .001). Both agents showed a “rapid” onset of action, with significant effects on the partial Mayo Score seen after just 2 weeks of treatment, the authors report.

Modified clinical remission at week 8 (a key secondary endpoint) was achieved in 36% of patients taking ritlecitinib 200 mg and 25.5% of those taking brepocitinib 60 mg (vs. 0% for patients taking placebo).

Endoscopic and histologic improvement, clinical response, mucosal healing, and the patient-reported outcome on the Inflammatory Bowel Disease Questionnaire followed a similar pattern, with a dose-dependent increase in treatment effect observed in most parameters at week 8, compared with placebo.
 

Longer-term data needed

Both agents were well tolerated with “acceptable short-term safety profiles,” the authors say.

There were no clinically significant findings for any laboratory parameters evaluated. Adverse events were mostly mild.

Infections were observed in 8.7% of patients taking ritlecitinib and 16.9% of those taking brepocitinib, compared with 4% of patients taking placebo. No serious cases of herpes zoster occurred.

One patient taking ritlecitinib suffered myocardial infarction and died, and one patient taking brepocitinib had peripheral artery thrombosis (left tibial artery). Both cases were considered unrelated to the study drug.

“As JAK inhibitors are associated with increased risk of major cardiovascular events and venous thromboembolisms, larger studies are needed for ritlecitinib and brepocitinib to fully understand their safety profiles,” the investigators say.

Limitations of the study include the small sample size and short 8-week treatment period. Longer-term safety and efficacy of both agents are being investigated.

The study was sponsored by Pfizer, which is developing both drugs. Dr. Sandborn and several coauthors have disclosed financial relationships with the company.

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

Two classes of drugs may be more effective than others for the treatment of gastroparesis, though the overall quality of evidence remains low to moderate and additional data are needed, according to a new report.

Oral dopamine antagonists and tachykinin-1 antagonists appear superior to placebo, finds the study. In addition, some drugs rank higher for addressing individual symptoms.

“Gastroparesis has a substantial impact on quality of life and societal functioning for patients, and the costs to the health service are high,” Alexander Ford, MBChB, MD, a professor of gastroenterology and honorary consultant gastroenterologist at the Leeds (England) Institute of Medical Research at St. James’s, University of Leeds, said in an interview.

“There are very few licensed therapies, but some novel drugs are in the pipeline, some existing drugs that are licensed for other conditions could be repurposed if efficacious, and some older drugs that have safety concerns may be beneficial,” he said. “Given the impact on patients and their symptoms, they may be willing to accept these safety risks in return for symptom improvement.”

Only one drug, the dopamine antagonist metoclopramide, has Food and Drug Administration approval for the treatment of gastroparesis, noted Dr. Ford and colleagues. The lack of other recommended drugs or new medications has resulted in off-label use of drugs in other classes.

The study was published online in Gastroenterology.
 

Investigating treatments

To address the lack of evidence supporting the efficacy and safety of licensed and unlicensed drugs for the condition, the researchers conducted a systematic review and network meta-analysis of randomized controlled trials of drugs for gastroparesis dating from 1947 to September 2022. The trials involved more than dozen drugs in several classes.

They determined drug efficacy on the basis of global symptoms of gastroparesis and individual symptoms such as nausea, vomiting, abdominal pain, bloating, or fullness. They judged safety on the basis of total adverse events and adverse events leading to withdrawal.

The research team extracted data as intention-to-treat analyses, assuming dropouts to be treatment failures. They reported efficacy as a pooled relative risk of symptoms not improving and ranked the drugs according to P-score.

The analysis included 29 randomized controlled trials with 3,772 patients. Only four trials were at low risk of bias.

Overall, only two drug classes were considered efficacious: oral dopamine antagonists (RR, 0.58; P-score, 0.96) and tachykinin-1 antagonists (RR, 0.69; P-score, 0.83).

On the basis of 25 trials that reported on global symptoms, clebopride ranked first for efficacy (RR, 0.30; P-score, 0.99), followed by domperidone (RR, 0.69; P-score, 0.76). None of the other drugs were superior to the placebo. After direct and indirect comparisons, clebopride was superior to all other drugs except aprepitant.

After excluding three trials with a placebo run-in and a trial where only responders to single-blind domperidone were randomized, the researchers analyzed 21 trials with 2,233 patients. In this analysis, domperidone ranked first (RR, 0.48; P-score, 0.93), followed by oral metoclopramide (RR, 0.54; P-score, 0.87). None of the other drugs were superior to placebo.

Among 16 trials, including 1,381 patients, that confirmed delayed gastric emptying among all participants, only clebopride and metoclopramide were more efficacious than placebo. Clebopride ranked first (RR, 0.30; P-score, 0.95) and metoclopramide ranked third (RR, 0.48).

Among 13 trials with 785 patients with diabetic gastroparesis, none of the active drugs were superior to placebo. Among 12 trials recruiting patients with idiopathic or mixed etiology gastroparesis, clebopride ranked first (RR, 0.30; P-score, 0.93).

On the basis of trials that assessed individual symptoms, oral metoclopramide ranked first for nausea (RR, 0.46; P-score, 0.95), fullness (RR, 0.67; P-score, 0.86), and bloating (RR, 0.53; P-score, 0.97). However, the data came from one small trial. Tradipitant and TZP-102, a ghrelin agonist, were efficacious for nausea, and TZP-102 ranked second for fullness. No drugs were more efficacious than the placebo for abdominal pain or vomiting.

Among 20 trials that reported on the total number of adverse events, camicinal was the least likely to be associated with adverse events (RR, 0.77; P-score, 0.93) and prucalopride was the most likely to be associated with adverse events (RR, 2.96; P-score, 0.10). Prucalopride, oral metoclopramide, and aprepitant also were more likely than placebo to be associated with adverse events.

In 23 trials that reported on withdrawals caused by adverse events, camicinal was the least likely to be associated with withdrawals (RR, 0.20; P-score, 0.87). Nortriptyline was the most likely to be associated with withdrawals (RR, 3.33; P-score, 0.16). However, there were no significant differences between any individual drug and placebo.
 

Urgent need remains

More trials of drugs to treat gastroparesis are needed, Ford said.

“We need to consider the reintroduction of dopamine antagonists, if patients are willing to accept the safety concerns,” he added. “The other important point is most drugs were not of benefit. There is an urgent need to find efficacious therapies, and these should be fast-tracked for licensing approval if efficacy is proven.”

The study is “helpful for practicing clinicians since it provides a comprehensive review of clinical trials in gastroparesis,” Anthony Lembo, MD, a gastroenterologist at the Cleveland Clinic, said in an interview.

Dr. Lembo, who wasn’t involved with this study, has researched several drugs for gastroparesis, including relamorelin and TZP-102. He agreed that additional research is needed.

“There is a paucity of novel treatments currently in development,” he said. “However, there is interest in developing a product similar to domperidone without cardiac side effects, as well as performing larger studies with botulinum toxin injection.”

The authors did not disclose a funding source for the study. One author disclosed research funding from the National Institutes of Health and consulting roles with various pharmaceutical companies. Ford and the other authors reported no disclosures. Dr. Lembo reported no relevant disclosures.

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

Two classes of drugs may be more effective than others for the treatment of gastroparesis, though the overall quality of evidence remains low to moderate and additional data are needed, according to a new report.

Oral dopamine antagonists and tachykinin-1 antagonists appear superior to placebo, finds the study. In addition, some drugs rank higher for addressing individual symptoms.

“Gastroparesis has a substantial impact on quality of life and societal functioning for patients, and the costs to the health service are high,” Alexander Ford, MBChB, MD, a professor of gastroenterology and honorary consultant gastroenterologist at the Leeds (England) Institute of Medical Research at St. James’s, University of Leeds, said in an interview.

“There are very few licensed therapies, but some novel drugs are in the pipeline, some existing drugs that are licensed for other conditions could be repurposed if efficacious, and some older drugs that have safety concerns may be beneficial,” he said. “Given the impact on patients and their symptoms, they may be willing to accept these safety risks in return for symptom improvement.”

Only one drug, the dopamine antagonist metoclopramide, has Food and Drug Administration approval for the treatment of gastroparesis, noted Dr. Ford and colleagues. The lack of other recommended drugs or new medications has resulted in off-label use of drugs in other classes.

The study was published online in Gastroenterology.
 

Investigating treatments

To address the lack of evidence supporting the efficacy and safety of licensed and unlicensed drugs for the condition, the researchers conducted a systematic review and network meta-analysis of randomized controlled trials of drugs for gastroparesis dating from 1947 to September 2022. The trials involved more than dozen drugs in several classes.

They determined drug efficacy on the basis of global symptoms of gastroparesis and individual symptoms such as nausea, vomiting, abdominal pain, bloating, or fullness. They judged safety on the basis of total adverse events and adverse events leading to withdrawal.

The research team extracted data as intention-to-treat analyses, assuming dropouts to be treatment failures. They reported efficacy as a pooled relative risk of symptoms not improving and ranked the drugs according to P-score.

The analysis included 29 randomized controlled trials with 3,772 patients. Only four trials were at low risk of bias.

Overall, only two drug classes were considered efficacious: oral dopamine antagonists (RR, 0.58; P-score, 0.96) and tachykinin-1 antagonists (RR, 0.69; P-score, 0.83).

On the basis of 25 trials that reported on global symptoms, clebopride ranked first for efficacy (RR, 0.30; P-score, 0.99), followed by domperidone (RR, 0.69; P-score, 0.76). None of the other drugs were superior to the placebo. After direct and indirect comparisons, clebopride was superior to all other drugs except aprepitant.

After excluding three trials with a placebo run-in and a trial where only responders to single-blind domperidone were randomized, the researchers analyzed 21 trials with 2,233 patients. In this analysis, domperidone ranked first (RR, 0.48; P-score, 0.93), followed by oral metoclopramide (RR, 0.54; P-score, 0.87). None of the other drugs were superior to placebo.

Among 16 trials, including 1,381 patients, that confirmed delayed gastric emptying among all participants, only clebopride and metoclopramide were more efficacious than placebo. Clebopride ranked first (RR, 0.30; P-score, 0.95) and metoclopramide ranked third (RR, 0.48).

Among 13 trials with 785 patients with diabetic gastroparesis, none of the active drugs were superior to placebo. Among 12 trials recruiting patients with idiopathic or mixed etiology gastroparesis, clebopride ranked first (RR, 0.30; P-score, 0.93).

On the basis of trials that assessed individual symptoms, oral metoclopramide ranked first for nausea (RR, 0.46; P-score, 0.95), fullness (RR, 0.67; P-score, 0.86), and bloating (RR, 0.53; P-score, 0.97). However, the data came from one small trial. Tradipitant and TZP-102, a ghrelin agonist, were efficacious for nausea, and TZP-102 ranked second for fullness. No drugs were more efficacious than the placebo for abdominal pain or vomiting.

Among 20 trials that reported on the total number of adverse events, camicinal was the least likely to be associated with adverse events (RR, 0.77; P-score, 0.93) and prucalopride was the most likely to be associated with adverse events (RR, 2.96; P-score, 0.10). Prucalopride, oral metoclopramide, and aprepitant also were more likely than placebo to be associated with adverse events.

In 23 trials that reported on withdrawals caused by adverse events, camicinal was the least likely to be associated with withdrawals (RR, 0.20; P-score, 0.87). Nortriptyline was the most likely to be associated with withdrawals (RR, 3.33; P-score, 0.16). However, there were no significant differences between any individual drug and placebo.
 

Urgent need remains

More trials of drugs to treat gastroparesis are needed, Ford said.

“We need to consider the reintroduction of dopamine antagonists, if patients are willing to accept the safety concerns,” he added. “The other important point is most drugs were not of benefit. There is an urgent need to find efficacious therapies, and these should be fast-tracked for licensing approval if efficacy is proven.”

The study is “helpful for practicing clinicians since it provides a comprehensive review of clinical trials in gastroparesis,” Anthony Lembo, MD, a gastroenterologist at the Cleveland Clinic, said in an interview.

Dr. Lembo, who wasn’t involved with this study, has researched several drugs for gastroparesis, including relamorelin and TZP-102. He agreed that additional research is needed.

“There is a paucity of novel treatments currently in development,” he said. “However, there is interest in developing a product similar to domperidone without cardiac side effects, as well as performing larger studies with botulinum toxin injection.”

The authors did not disclose a funding source for the study. One author disclosed research funding from the National Institutes of Health and consulting roles with various pharmaceutical companies. Ford and the other authors reported no disclosures. Dr. Lembo reported no relevant disclosures.

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

Two classes of drugs may be more effective than others for the treatment of gastroparesis, though the overall quality of evidence remains low to moderate and additional data are needed, according to a new report.

Oral dopamine antagonists and tachykinin-1 antagonists appear superior to placebo, finds the study. In addition, some drugs rank higher for addressing individual symptoms.

“Gastroparesis has a substantial impact on quality of life and societal functioning for patients, and the costs to the health service are high,” Alexander Ford, MBChB, MD, a professor of gastroenterology and honorary consultant gastroenterologist at the Leeds (England) Institute of Medical Research at St. James’s, University of Leeds, said in an interview.

“There are very few licensed therapies, but some novel drugs are in the pipeline, some existing drugs that are licensed for other conditions could be repurposed if efficacious, and some older drugs that have safety concerns may be beneficial,” he said. “Given the impact on patients and their symptoms, they may be willing to accept these safety risks in return for symptom improvement.”

Only one drug, the dopamine antagonist metoclopramide, has Food and Drug Administration approval for the treatment of gastroparesis, noted Dr. Ford and colleagues. The lack of other recommended drugs or new medications has resulted in off-label use of drugs in other classes.

The study was published online in Gastroenterology.
 

Investigating treatments

To address the lack of evidence supporting the efficacy and safety of licensed and unlicensed drugs for the condition, the researchers conducted a systematic review and network meta-analysis of randomized controlled trials of drugs for gastroparesis dating from 1947 to September 2022. The trials involved more than dozen drugs in several classes.

They determined drug efficacy on the basis of global symptoms of gastroparesis and individual symptoms such as nausea, vomiting, abdominal pain, bloating, or fullness. They judged safety on the basis of total adverse events and adverse events leading to withdrawal.

The research team extracted data as intention-to-treat analyses, assuming dropouts to be treatment failures. They reported efficacy as a pooled relative risk of symptoms not improving and ranked the drugs according to P-score.

The analysis included 29 randomized controlled trials with 3,772 patients. Only four trials were at low risk of bias.

Overall, only two drug classes were considered efficacious: oral dopamine antagonists (RR, 0.58; P-score, 0.96) and tachykinin-1 antagonists (RR, 0.69; P-score, 0.83).

On the basis of 25 trials that reported on global symptoms, clebopride ranked first for efficacy (RR, 0.30; P-score, 0.99), followed by domperidone (RR, 0.69; P-score, 0.76). None of the other drugs were superior to the placebo. After direct and indirect comparisons, clebopride was superior to all other drugs except aprepitant.

After excluding three trials with a placebo run-in and a trial where only responders to single-blind domperidone were randomized, the researchers analyzed 21 trials with 2,233 patients. In this analysis, domperidone ranked first (RR, 0.48; P-score, 0.93), followed by oral metoclopramide (RR, 0.54; P-score, 0.87). None of the other drugs were superior to placebo.

Among 16 trials, including 1,381 patients, that confirmed delayed gastric emptying among all participants, only clebopride and metoclopramide were more efficacious than placebo. Clebopride ranked first (RR, 0.30; P-score, 0.95) and metoclopramide ranked third (RR, 0.48).

Among 13 trials with 785 patients with diabetic gastroparesis, none of the active drugs were superior to placebo. Among 12 trials recruiting patients with idiopathic or mixed etiology gastroparesis, clebopride ranked first (RR, 0.30; P-score, 0.93).

On the basis of trials that assessed individual symptoms, oral metoclopramide ranked first for nausea (RR, 0.46; P-score, 0.95), fullness (RR, 0.67; P-score, 0.86), and bloating (RR, 0.53; P-score, 0.97). However, the data came from one small trial. Tradipitant and TZP-102, a ghrelin agonist, were efficacious for nausea, and TZP-102 ranked second for fullness. No drugs were more efficacious than the placebo for abdominal pain or vomiting.

Among 20 trials that reported on the total number of adverse events, camicinal was the least likely to be associated with adverse events (RR, 0.77; P-score, 0.93) and prucalopride was the most likely to be associated with adverse events (RR, 2.96; P-score, 0.10). Prucalopride, oral metoclopramide, and aprepitant also were more likely than placebo to be associated with adverse events.

In 23 trials that reported on withdrawals caused by adverse events, camicinal was the least likely to be associated with withdrawals (RR, 0.20; P-score, 0.87). Nortriptyline was the most likely to be associated with withdrawals (RR, 3.33; P-score, 0.16). However, there were no significant differences between any individual drug and placebo.
 

Urgent need remains

More trials of drugs to treat gastroparesis are needed, Ford said.

“We need to consider the reintroduction of dopamine antagonists, if patients are willing to accept the safety concerns,” he added. “The other important point is most drugs were not of benefit. There is an urgent need to find efficacious therapies, and these should be fast-tracked for licensing approval if efficacy is proven.”

The study is “helpful for practicing clinicians since it provides a comprehensive review of clinical trials in gastroparesis,” Anthony Lembo, MD, a gastroenterologist at the Cleveland Clinic, said in an interview.

Dr. Lembo, who wasn’t involved with this study, has researched several drugs for gastroparesis, including relamorelin and TZP-102. He agreed that additional research is needed.

“There is a paucity of novel treatments currently in development,” he said. “However, there is interest in developing a product similar to domperidone without cardiac side effects, as well as performing larger studies with botulinum toxin injection.”

The authors did not disclose a funding source for the study. One author disclosed research funding from the National Institutes of Health and consulting roles with various pharmaceutical companies. Ford and the other authors reported no disclosures. Dr. Lembo reported no relevant disclosures.

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

Clinicians should conduct regular, structured follow-up on treatments for eosinophilic esophagitis (EoE), according to an expert panel.

“Follow-up should comprise symptom assessment and periodic or repeated endoscopy with histological assessment in specific EoE settings,” wrote Ulrike von Arnim, MD, from University Hospital Magdeburg (Germany), and an international team of colleagues in Clinical Gastroenterology and Hepatology.

Although medicine and diet can control EoE, there is presently no cure, and long-term management is needed to prevent recurrence and long-term effects such as esophageal remodeling, fibrosis, and stricture, the researchers said. Yet they could find no evidence-based recommendations for clinical monitoring of the condition.

With the participation of The International Gastrointestinal Eosinophil Researchers (TIGER) and the European Consortium for Eosinophilic Diseases of the GI Tract (EUREOS), they assembled a team of 18 gastroenterologists, pathologists, and allergists from the United States and Western Europe with expertise in the condition.

Almost all panelists had more than 10 years of subspecialty EoE care and more than five relevant research publications. All were members of TIGER or EUREOS. The panel met by video conferencing and responded to surveys to develop a consensus about why, by what means, and when to monitor patients with EoE.

The group reached 75% or greater agreement on 11 statements on these subjects.

Regular follow-ups are needed because they enable clinicians to detect whether treatments have stopped working, improve therapy adherence, and introduce patients to any new treatments that become available, while preventing gaps in care that can worsen outcomes, the group wrote.

Symptoms don’t give a precise indication of esophageal healing and shouldn’t be the sole measure for disease activity, the experts wrote. They recommended other approaches to monitoring, including biopsies. They also endorse the Endoscopic Reference Score as an outcome measure.

The panel recommended noninvasive tissue sampling, mentioning the esophageal string test and the Cytosponge as examples, but called for more research on these two techniques.

Blood markers, oral swabs, breath condensates, and stool and urine samples are not recommended as approaches for monitoring EoE, they wrote.

The optimal interval to measure the efficacy of a therapy is more difficult to decide, the panel noted.

“The clinician’s decision should take into account the clinical severity of the disease, estimated risk of imminent subsequent food impaction, presence of stenosis, as well as mode of action and reported outcome of the chosen medical, dietary, or mechanical treatment,” they wrote. Intervals from 6 to 24 weeks may be appropriate.

For diets and topical corticosteroids, they agreed on an interval of 8-12 weeks to confirm remission but say a longer time might be preferred for slower-acting therapies, such as monoclonal antibodies.

The panel had the most trouble reaching a consensus on how often to follow up on patients whose disease is in remission or is stable. They settled on 12 to 24 months after the last endoscopy. Any longer than 2 years risks missing increased disease activity, they wrote.

This follow-up should include assessment of symptoms and a gastrointestinal endoscopy in cases of relapse or suspected stricture, as well as when treatment modification is being considered or when assessment of histological activity is desired, the panel recommended.

Almost all the panelists disclosed financial relationships with pharmaceutical or medical device companies.

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

Clinicians should conduct regular, structured follow-up on treatments for eosinophilic esophagitis (EoE), according to an expert panel.

“Follow-up should comprise symptom assessment and periodic or repeated endoscopy with histological assessment in specific EoE settings,” wrote Ulrike von Arnim, MD, from University Hospital Magdeburg (Germany), and an international team of colleagues in Clinical Gastroenterology and Hepatology.

Although medicine and diet can control EoE, there is presently no cure, and long-term management is needed to prevent recurrence and long-term effects such as esophageal remodeling, fibrosis, and stricture, the researchers said. Yet they could find no evidence-based recommendations for clinical monitoring of the condition.

With the participation of The International Gastrointestinal Eosinophil Researchers (TIGER) and the European Consortium for Eosinophilic Diseases of the GI Tract (EUREOS), they assembled a team of 18 gastroenterologists, pathologists, and allergists from the United States and Western Europe with expertise in the condition.

Almost all panelists had more than 10 years of subspecialty EoE care and more than five relevant research publications. All were members of TIGER or EUREOS. The panel met by video conferencing and responded to surveys to develop a consensus about why, by what means, and when to monitor patients with EoE.

The group reached 75% or greater agreement on 11 statements on these subjects.

Regular follow-ups are needed because they enable clinicians to detect whether treatments have stopped working, improve therapy adherence, and introduce patients to any new treatments that become available, while preventing gaps in care that can worsen outcomes, the group wrote.

Symptoms don’t give a precise indication of esophageal healing and shouldn’t be the sole measure for disease activity, the experts wrote. They recommended other approaches to monitoring, including biopsies. They also endorse the Endoscopic Reference Score as an outcome measure.

The panel recommended noninvasive tissue sampling, mentioning the esophageal string test and the Cytosponge as examples, but called for more research on these two techniques.

Blood markers, oral swabs, breath condensates, and stool and urine samples are not recommended as approaches for monitoring EoE, they wrote.

The optimal interval to measure the efficacy of a therapy is more difficult to decide, the panel noted.

“The clinician’s decision should take into account the clinical severity of the disease, estimated risk of imminent subsequent food impaction, presence of stenosis, as well as mode of action and reported outcome of the chosen medical, dietary, or mechanical treatment,” they wrote. Intervals from 6 to 24 weeks may be appropriate.

For diets and topical corticosteroids, they agreed on an interval of 8-12 weeks to confirm remission but say a longer time might be preferred for slower-acting therapies, such as monoclonal antibodies.

The panel had the most trouble reaching a consensus on how often to follow up on patients whose disease is in remission or is stable. They settled on 12 to 24 months after the last endoscopy. Any longer than 2 years risks missing increased disease activity, they wrote.

This follow-up should include assessment of symptoms and a gastrointestinal endoscopy in cases of relapse or suspected stricture, as well as when treatment modification is being considered or when assessment of histological activity is desired, the panel recommended.

Almost all the panelists disclosed financial relationships with pharmaceutical or medical device companies.

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

Clinicians should conduct regular, structured follow-up on treatments for eosinophilic esophagitis (EoE), according to an expert panel.

“Follow-up should comprise symptom assessment and periodic or repeated endoscopy with histological assessment in specific EoE settings,” wrote Ulrike von Arnim, MD, from University Hospital Magdeburg (Germany), and an international team of colleagues in Clinical Gastroenterology and Hepatology.

Although medicine and diet can control EoE, there is presently no cure, and long-term management is needed to prevent recurrence and long-term effects such as esophageal remodeling, fibrosis, and stricture, the researchers said. Yet they could find no evidence-based recommendations for clinical monitoring of the condition.

With the participation of The International Gastrointestinal Eosinophil Researchers (TIGER) and the European Consortium for Eosinophilic Diseases of the GI Tract (EUREOS), they assembled a team of 18 gastroenterologists, pathologists, and allergists from the United States and Western Europe with expertise in the condition.

Almost all panelists had more than 10 years of subspecialty EoE care and more than five relevant research publications. All were members of TIGER or EUREOS. The panel met by video conferencing and responded to surveys to develop a consensus about why, by what means, and when to monitor patients with EoE.

The group reached 75% or greater agreement on 11 statements on these subjects.

Regular follow-ups are needed because they enable clinicians to detect whether treatments have stopped working, improve therapy adherence, and introduce patients to any new treatments that become available, while preventing gaps in care that can worsen outcomes, the group wrote.

Symptoms don’t give a precise indication of esophageal healing and shouldn’t be the sole measure for disease activity, the experts wrote. They recommended other approaches to monitoring, including biopsies. They also endorse the Endoscopic Reference Score as an outcome measure.

The panel recommended noninvasive tissue sampling, mentioning the esophageal string test and the Cytosponge as examples, but called for more research on these two techniques.

Blood markers, oral swabs, breath condensates, and stool and urine samples are not recommended as approaches for monitoring EoE, they wrote.

The optimal interval to measure the efficacy of a therapy is more difficult to decide, the panel noted.

“The clinician’s decision should take into account the clinical severity of the disease, estimated risk of imminent subsequent food impaction, presence of stenosis, as well as mode of action and reported outcome of the chosen medical, dietary, or mechanical treatment,” they wrote. Intervals from 6 to 24 weeks may be appropriate.

For diets and topical corticosteroids, they agreed on an interval of 8-12 weeks to confirm remission but say a longer time might be preferred for slower-acting therapies, such as monoclonal antibodies.

The panel had the most trouble reaching a consensus on how often to follow up on patients whose disease is in remission or is stable. They settled on 12 to 24 months after the last endoscopy. Any longer than 2 years risks missing increased disease activity, they wrote.

This follow-up should include assessment of symptoms and a gastrointestinal endoscopy in cases of relapse or suspected stricture, as well as when treatment modification is being considered or when assessment of histological activity is desired, the panel recommended.

Almost all the panelists disclosed financial relationships with pharmaceutical or medical device companies.

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

Starting colorectal cancer screening earlier than age 50 appears to be cost-effective for both men and women across all body mass index (BMI) measures, according to a study published in Clinical Gastroenterology and Hepatology.

In particular, colonoscopy is cost-effective at age 45 for all BMI strata and at age 40 in obese men. In addition, fecal immunochemical testing (FIT) is highly cost-effective at ages 40 or 45 for all BMI values, wrote Aaron Yeoh, MD, a gastroenterologist at the Stanford (Calif.) University, and colleagues.

Increased body fatness, defined as a high BMI, has increased sharply in recent decades and has been associated with a higher risk of colorectal cancer (CRC). Given the rising incidence of CRC in younger people, the American Cancer Society and U.S. Preventive Services Task Force now endorse screening at age 45. In previous analyses, Dr. Yeoh and colleagues suggested that the policy is likely to be cost-effective, but they didn’t explore the potential differences by BMI.

“Our results suggest that 45 years of age is a reasonable screening initiation age for women and men with BMI ranging from normal through all classes of obesity,” the authors wrote. “Before changing screening policy, supportive data from clinical studies would be needed. Our approach can be applied to future efforts aiming to risk-stratify CRC screening based on multiple clinical factors or biomarkers.”

The research team examined the potential effectiveness and cost-effectiveness of screening tailored to BMI starting as early as age 40 and ending at age 75 in 10 separate cohorts of men and women of normal weight (18.5 to <25 kg/m²), overweight (25 to <30 kg/m²), and three strata of obesity – obese I (30 to <35 kg/m²), obese II (35 to <40 kg/m²), and obese III (>40 kg/m²).

For each cohort, the researchers estimated incremental costs per quality-adjusted life year (QALY) gained by initiating screening at age 40 versus age 45 versus age 50, or by shortening colonoscopy intervals. They modeled screening colonoscopy every 10 years (Colo10) or every 5 years (Colo5), or annual FIT, offered from ages 40, 45, or 50 through age 75 with 100% adherence, with postpolypectomy surveillance through age 80.

For model inputs, the research team favored high-quality data from meta-analyses or large prospective trials. Screening, treatment, and complication costs were set at 2018 Centers for Medicare & Medicaid Services rates for ages 65 and older and modified to reflect commercial costs at ages 65 and younger. The authors assumed use of moderate sedation, and sensitivity analyses addressed possible increased costs and complications of colonoscopy under propofol.

Overall, without screening, sex-specific total CRC deaths were similar for people with overweight or obesity I-III and slightly higher than for people with normal BMI. For both men and women across all BMI strata, Colo10 or FIT starting at age 50 substantially decreased CRC incidence and mortality versus no screening, and the magnitude of the clinical impact was comparable across BMI.

For both sexes across BMI, Colo10 or FIT starting at age 50 was highly cost-effective. The cost per QALY gained for Colo10 compared with no screening became more favorable as BMI increased from normal to obesity III. FIT was cost-saving compared with no screening for all cohorts and was cost-saving or highly cost-effective compared with Colo10 within each cohort.

Initiating Colo10 at age 45 showed incremental decreases in CRC incidence and mortality, which were modest compared with the gains of Colo10 at age 50 versus no screening. However, the incremental gains were achieved at acceptable incremental costs ranging from $64,500 to $85,900 per QALY gained in women and from $33,400 to $64,200 per QALY gained in men.

Initiating Colo10 at age 40 in women and men in the lowest three BMI strata was associated with high incremental costs per QALY gained. In contrast, Colo10 initiation at age 40 cost $80,400 per QALY gained in men with obesity III and $93,300 per QALY gained in men with obesity II.

FIT starting at ages 40 or 45 yielded progressively greater decreases in CRC incidence and mortality for both men and women across BMI strata, and it was highly cost-effective versus starting at later ages. Compared with Colo10, at every screening initiation age, FIT was cost-saving or preferred based on very high incremental costs per QALY, and FIT required substantially fewer colonoscopies per person.

Intensifying screening by shortening the colonoscopy interval to Colo5 was never preferred over shifting Colo10 to earlier screening initiation ages. In all cohorts, Colo5 was either less effective and more costly than Colo10 at a younger age, or when it was more effective, the cost per QALY gained was substantially higher than $100,000 per QALY gained.

Additional studies are needed to understand obesity-specific colonoscopy risks and costs, the authors wrote. In addition, obesity is only one of several factors that should be considered when tailoring CRC screening to the level of CRC risk, they wrote.

“As the search for a multifactor prediction tool that is ready for clinical application continues, we face the question of how to approach single CRC risk factors such as obesity,” they wrote. “While screening guidelines based on BMI can be envisioned if supportive clinical data accumulate, clinical implementation must overcome operational challenges.”

The study funding was not disclosed. One author reported advisory and consultant roles for several medical companies, and the remaining authors disclosed no conflicts.

Starting colorectal cancer screening earlier than age 50 appears to be cost-effective for both men and women across all body mass index (BMI) measures, according to a study published in Clinical Gastroenterology and Hepatology.

In particular, colonoscopy is cost-effective at age 45 for all BMI strata and at age 40 in obese men. In addition, fecal immunochemical testing (FIT) is highly cost-effective at ages 40 or 45 for all BMI values, wrote Aaron Yeoh, MD, a gastroenterologist at the Stanford (Calif.) University, and colleagues.

Increased body fatness, defined as a high BMI, has increased sharply in recent decades and has been associated with a higher risk of colorectal cancer (CRC). Given the rising incidence of CRC in younger people, the American Cancer Society and U.S. Preventive Services Task Force now endorse screening at age 45. In previous analyses, Dr. Yeoh and colleagues suggested that the policy is likely to be cost-effective, but they didn’t explore the potential differences by BMI.

“Our results suggest that 45 years of age is a reasonable screening initiation age for women and men with BMI ranging from normal through all classes of obesity,” the authors wrote. “Before changing screening policy, supportive data from clinical studies would be needed. Our approach can be applied to future efforts aiming to risk-stratify CRC screening based on multiple clinical factors or biomarkers.”

The research team examined the potential effectiveness and cost-effectiveness of screening tailored to BMI starting as early as age 40 and ending at age 75 in 10 separate cohorts of men and women of normal weight (18.5 to <25 kg/m²), overweight (25 to <30 kg/m²), and three strata of obesity – obese I (30 to <35 kg/m²), obese II (35 to <40 kg/m²), and obese III (>40 kg/m²).

For each cohort, the researchers estimated incremental costs per quality-adjusted life year (QALY) gained by initiating screening at age 40 versus age 45 versus age 50, or by shortening colonoscopy intervals. They modeled screening colonoscopy every 10 years (Colo10) or every 5 years (Colo5), or annual FIT, offered from ages 40, 45, or 50 through age 75 with 100% adherence, with postpolypectomy surveillance through age 80.

For model inputs, the research team favored high-quality data from meta-analyses or large prospective trials. Screening, treatment, and complication costs were set at 2018 Centers for Medicare & Medicaid Services rates for ages 65 and older and modified to reflect commercial costs at ages 65 and younger. The authors assumed use of moderate sedation, and sensitivity analyses addressed possible increased costs and complications of colonoscopy under propofol.

Overall, without screening, sex-specific total CRC deaths were similar for people with overweight or obesity I-III and slightly higher than for people with normal BMI. For both men and women across all BMI strata, Colo10 or FIT starting at age 50 substantially decreased CRC incidence and mortality versus no screening, and the magnitude of the clinical impact was comparable across BMI.

For both sexes across BMI, Colo10 or FIT starting at age 50 was highly cost-effective. The cost per QALY gained for Colo10 compared with no screening became more favorable as BMI increased from normal to obesity III. FIT was cost-saving compared with no screening for all cohorts and was cost-saving or highly cost-effective compared with Colo10 within each cohort.

Initiating Colo10 at age 45 showed incremental decreases in CRC incidence and mortality, which were modest compared with the gains of Colo10 at age 50 versus no screening. However, the incremental gains were achieved at acceptable incremental costs ranging from $64,500 to $85,900 per QALY gained in women and from $33,400 to $64,200 per QALY gained in men.

Initiating Colo10 at age 40 in women and men in the lowest three BMI strata was associated with high incremental costs per QALY gained. In contrast, Colo10 initiation at age 40 cost $80,400 per QALY gained in men with obesity III and $93,300 per QALY gained in men with obesity II.

FIT starting at ages 40 or 45 yielded progressively greater decreases in CRC incidence and mortality for both men and women across BMI strata, and it was highly cost-effective versus starting at later ages. Compared with Colo10, at every screening initiation age, FIT was cost-saving or preferred based on very high incremental costs per QALY, and FIT required substantially fewer colonoscopies per person.

Intensifying screening by shortening the colonoscopy interval to Colo5 was never preferred over shifting Colo10 to earlier screening initiation ages. In all cohorts, Colo5 was either less effective and more costly than Colo10 at a younger age, or when it was more effective, the cost per QALY gained was substantially higher than $100,000 per QALY gained.

Additional studies are needed to understand obesity-specific colonoscopy risks and costs, the authors wrote. In addition, obesity is only one of several factors that should be considered when tailoring CRC screening to the level of CRC risk, they wrote.

“As the search for a multifactor prediction tool that is ready for clinical application continues, we face the question of how to approach single CRC risk factors such as obesity,” they wrote. “While screening guidelines based on BMI can be envisioned if supportive clinical data accumulate, clinical implementation must overcome operational challenges.”

The study funding was not disclosed. One author reported advisory and consultant roles for several medical companies, and the remaining authors disclosed no conflicts.

Starting colorectal cancer screening earlier than age 50 appears to be cost-effective for both men and women across all body mass index (BMI) measures, according to a study published in Clinical Gastroenterology and Hepatology.

In particular, colonoscopy is cost-effective at age 45 for all BMI strata and at age 40 in obese men. In addition, fecal immunochemical testing (FIT) is highly cost-effective at ages 40 or 45 for all BMI values, wrote Aaron Yeoh, MD, a gastroenterologist at the Stanford (Calif.) University, and colleagues.

Increased body fatness, defined as a high BMI, has increased sharply in recent decades and has been associated with a higher risk of colorectal cancer (CRC). Given the rising incidence of CRC in younger people, the American Cancer Society and U.S. Preventive Services Task Force now endorse screening at age 45. In previous analyses, Dr. Yeoh and colleagues suggested that the policy is likely to be cost-effective, but they didn’t explore the potential differences by BMI.

“Our results suggest that 45 years of age is a reasonable screening initiation age for women and men with BMI ranging from normal through all classes of obesity,” the authors wrote. “Before changing screening policy, supportive data from clinical studies would be needed. Our approach can be applied to future efforts aiming to risk-stratify CRC screening based on multiple clinical factors or biomarkers.”

The research team examined the potential effectiveness and cost-effectiveness of screening tailored to BMI starting as early as age 40 and ending at age 75 in 10 separate cohorts of men and women of normal weight (18.5 to <25 kg/m²), overweight (25 to <30 kg/m²), and three strata of obesity – obese I (30 to <35 kg/m²), obese II (35 to <40 kg/m²), and obese III (>40 kg/m²).

For each cohort, the researchers estimated incremental costs per quality-adjusted life year (QALY) gained by initiating screening at age 40 versus age 45 versus age 50, or by shortening colonoscopy intervals. They modeled screening colonoscopy every 10 years (Colo10) or every 5 years (Colo5), or annual FIT, offered from ages 40, 45, or 50 through age 75 with 100% adherence, with postpolypectomy surveillance through age 80.

For model inputs, the research team favored high-quality data from meta-analyses or large prospective trials. Screening, treatment, and complication costs were set at 2018 Centers for Medicare & Medicaid Services rates for ages 65 and older and modified to reflect commercial costs at ages 65 and younger. The authors assumed use of moderate sedation, and sensitivity analyses addressed possible increased costs and complications of colonoscopy under propofol.

Overall, without screening, sex-specific total CRC deaths were similar for people with overweight or obesity I-III and slightly higher than for people with normal BMI. For both men and women across all BMI strata, Colo10 or FIT starting at age 50 substantially decreased CRC incidence and mortality versus no screening, and the magnitude of the clinical impact was comparable across BMI.

For both sexes across BMI, Colo10 or FIT starting at age 50 was highly cost-effective. The cost per QALY gained for Colo10 compared with no screening became more favorable as BMI increased from normal to obesity III. FIT was cost-saving compared with no screening for all cohorts and was cost-saving or highly cost-effective compared with Colo10 within each cohort.

Initiating Colo10 at age 45 showed incremental decreases in CRC incidence and mortality, which were modest compared with the gains of Colo10 at age 50 versus no screening. However, the incremental gains were achieved at acceptable incremental costs ranging from $64,500 to $85,900 per QALY gained in women and from $33,400 to $64,200 per QALY gained in men.

Initiating Colo10 at age 40 in women and men in the lowest three BMI strata was associated with high incremental costs per QALY gained. In contrast, Colo10 initiation at age 40 cost $80,400 per QALY gained in men with obesity III and $93,300 per QALY gained in men with obesity II.

FIT starting at ages 40 or 45 yielded progressively greater decreases in CRC incidence and mortality for both men and women across BMI strata, and it was highly cost-effective versus starting at later ages. Compared with Colo10, at every screening initiation age, FIT was cost-saving or preferred based on very high incremental costs per QALY, and FIT required substantially fewer colonoscopies per person.

Intensifying screening by shortening the colonoscopy interval to Colo5 was never preferred over shifting Colo10 to earlier screening initiation ages. In all cohorts, Colo5 was either less effective and more costly than Colo10 at a younger age, or when it was more effective, the cost per QALY gained was substantially higher than $100,000 per QALY gained.

Additional studies are needed to understand obesity-specific colonoscopy risks and costs, the authors wrote. In addition, obesity is only one of several factors that should be considered when tailoring CRC screening to the level of CRC risk, they wrote.

“As the search for a multifactor prediction tool that is ready for clinical application continues, we face the question of how to approach single CRC risk factors such as obesity,” they wrote. “While screening guidelines based on BMI can be envisioned if supportive clinical data accumulate, clinical implementation must overcome operational challenges.”

The study funding was not disclosed. One author reported advisory and consultant roles for several medical companies, and the remaining authors disclosed no conflicts.

For people with inflammatory bowel disease (IBD) taking immunosuppressive medication, a third dose of a COVID-19 mRNA vaccine significantly increases neutralizing antibodies against the original SARS-CoV-2 strain, but the picture is more complicated for protection against the Omicron variant, according to a research letter published in Gastroenterology.

Though IBD patients do mount a response against Omicron, the response is substantially lower for those taking tofacitinib or infliximab, particularly infliximab monotherapy.

“As further mutations in the viral genome accumulate over time, with the attendant risk of immune evasion, it remains important to continue to reappraise vaccination strategy, including the implementation of personalized approaches for some patients, such as those treated with anti-TNF drugs and JAK inhibitors,” wrote Zhigang Liu, PhD, a research associate in the department of metabolism, digestion, and reproduction at Imperial College London, and his colleagues. “Preferential use of bivalent vaccines may be especially valuable in IBD patients taking anti-TNF agents or JAK inhibitors,” they wrote. Their study did not assess neutralizing antibodies resulting from use of the bivalent vaccine, however.

The researchers tracked 268 participants, including 49 healthy participants serving as controls, from May 2021 through March 2022. The other participants had IBD and included 51 patients taking thiopurines, 36 patients taking infliximab, 39 taking both infliximab and thiopurines, 39 taking ustekinumab, 38 taking vedolizumab, and 16 taking tofacitinib. The IBD patients were all enrolled in the SARS-CoV-2 Vaccination Immunogenicity in Immunosuppressed Inflammatory Bowel Disease Patients (VIP) cohort.

None of the participants had evidence of a SARS-CoV-2 infection at baseline. All had received two doses of an mRNA COVID-19 vaccine (all received Pfizer, except two controls who received Moderna) or two doses of the AstraZeneca vaccine as their primary vaccination. All received an mRNA vaccine for their third dose. Among the IBD patients, 137 received the AstraZeneca in their primary two-dose series, and 82 received Pfizer.

First the researchers assessed the participants’ humoral response to the vaccine against the original SARS-CoV-2 strain and against the Omicron BA.1 variant. Neutralizing antibody titers rose significantly against both strains after the third vaccine dose for all participants.

“However, 50% neutralization titer (NT50) values were significantly lower against Omicron than against the ancestral strain in all study groups, irrespective of the immunosuppressive treatment regimen,” the authors reported. NT50 values are a measure that reflect a vaccine-induced humoral immunity against SARS-CoV-2 after vaccination.

Compared to the healthy controls, individuals receiving infliximab, tofacitinib, or infliximab/thiopurine combination therapy showed significantly lower responses after the second and third vaccine doses. Thirteen patients did not generate NT50 against Omicron after the second vaccine dose, and 7 of them were on infliximab monotherapy. They represented nearly 20% of all infliximab monotherapy participants.

Next the researchers assessed the risk of a breakthrough infection according to neutralizing titer thresholds. Individuals with an NT50 less than 500 had 1.6 times greater odds of a breakthrough infection than those with an NT50 above 500, they noted. After two vaccine doses, 46% of participants with IBD had an NT50 above 500 for the ancestral strain, which rose to 85% of those with IBD after a third dose.

In the healthy control group, 35% had an NT50 under 500 after two doses, and 14% of them had a breakthrough infection, all of which were mild and none of which required hospitalization. The NT50 in healthy controls, however, was not significantly associated with risk of breakthrough infection.

“In this study, neutralizing titers elicited against the omicron variant were generally poor for all individuals and were substantially lower in recipients of infliximab, infliximab/thiopurine combination, or tofacitinib therapy,” the authors concluded. “This raises concerns about whether currently available vaccines will be sufficient to protect against continually evolving SARS-CoV-2 variants, especially in patients established on certain immunosuppressive drugs.”

The small population sizes for each subgroup based on medication was one of the study’s limitations. Another was the fact that it was underpowered to conclusively determine whether an increased risk of breakthrough infection exists in IBD patients who have lower titers of neutralizing antibodies. A limitation for generalization to U.S. patients is that just 64% of the IBD patients received the AstraZeneca vaccine, which is not offered in the United States, for their first two doses before receiving the third mRNA (Pfizer) dose.

The study was funded by Pfizer in an independent research grant and by the NIHR Biomedical Research Centres in Imperial College London and Imperial College Healthcare NHS Trust and Cambridge, and the NIHR Clinical Research Facility Cambridge.

Dr. Liu and one other author had no disclosures. The other 18 authors have a range of disclosures related to various pharmaceutical companies, including Pfizer.

For people with inflammatory bowel disease (IBD) taking immunosuppressive medication, a third dose of a COVID-19 mRNA vaccine significantly increases neutralizing antibodies against the original SARS-CoV-2 strain, but the picture is more complicated for protection against the Omicron variant, according to a research letter published in Gastroenterology.

Though IBD patients do mount a response against Omicron, the response is substantially lower for those taking tofacitinib or infliximab, particularly infliximab monotherapy.

“As further mutations in the viral genome accumulate over time, with the attendant risk of immune evasion, it remains important to continue to reappraise vaccination strategy, including the implementation of personalized approaches for some patients, such as those treated with anti-TNF drugs and JAK inhibitors,” wrote Zhigang Liu, PhD, a research associate in the department of metabolism, digestion, and reproduction at Imperial College London, and his colleagues. “Preferential use of bivalent vaccines may be especially valuable in IBD patients taking anti-TNF agents or JAK inhibitors,” they wrote. Their study did not assess neutralizing antibodies resulting from use of the bivalent vaccine, however.

The researchers tracked 268 participants, including 49 healthy participants serving as controls, from May 2021 through March 2022. The other participants had IBD and included 51 patients taking thiopurines, 36 patients taking infliximab, 39 taking both infliximab and thiopurines, 39 taking ustekinumab, 38 taking vedolizumab, and 16 taking tofacitinib. The IBD patients were all enrolled in the SARS-CoV-2 Vaccination Immunogenicity in Immunosuppressed Inflammatory Bowel Disease Patients (VIP) cohort.

None of the participants had evidence of a SARS-CoV-2 infection at baseline. All had received two doses of an mRNA COVID-19 vaccine (all received Pfizer, except two controls who received Moderna) or two doses of the AstraZeneca vaccine as their primary vaccination. All received an mRNA vaccine for their third dose. Among the IBD patients, 137 received the AstraZeneca in their primary two-dose series, and 82 received Pfizer.

First the researchers assessed the participants’ humoral response to the vaccine against the original SARS-CoV-2 strain and against the Omicron BA.1 variant. Neutralizing antibody titers rose significantly against both strains after the third vaccine dose for all participants.

“However, 50% neutralization titer (NT50) values were significantly lower against Omicron than against the ancestral strain in all study groups, irrespective of the immunosuppressive treatment regimen,” the authors reported. NT50 values are a measure that reflect a vaccine-induced humoral immunity against SARS-CoV-2 after vaccination.

Compared to the healthy controls, individuals receiving infliximab, tofacitinib, or infliximab/thiopurine combination therapy showed significantly lower responses after the second and third vaccine doses. Thirteen patients did not generate NT50 against Omicron after the second vaccine dose, and 7 of them were on infliximab monotherapy. They represented nearly 20% of all infliximab monotherapy participants.

Next the researchers assessed the risk of a breakthrough infection according to neutralizing titer thresholds. Individuals with an NT50 less than 500 had 1.6 times greater odds of a breakthrough infection than those with an NT50 above 500, they noted. After two vaccine doses, 46% of participants with IBD had an NT50 above 500 for the ancestral strain, which rose to 85% of those with IBD after a third dose.

In the healthy control group, 35% had an NT50 under 500 after two doses, and 14% of them had a breakthrough infection, all of which were mild and none of which required hospitalization. The NT50 in healthy controls, however, was not significantly associated with risk of breakthrough infection.

“In this study, neutralizing titers elicited against the omicron variant were generally poor for all individuals and were substantially lower in recipients of infliximab, infliximab/thiopurine combination, or tofacitinib therapy,” the authors concluded. “This raises concerns about whether currently available vaccines will be sufficient to protect against continually evolving SARS-CoV-2 variants, especially in patients established on certain immunosuppressive drugs.”

The small population sizes for each subgroup based on medication was one of the study’s limitations. Another was the fact that it was underpowered to conclusively determine whether an increased risk of breakthrough infection exists in IBD patients who have lower titers of neutralizing antibodies. A limitation for generalization to U.S. patients is that just 64% of the IBD patients received the AstraZeneca vaccine, which is not offered in the United States, for their first two doses before receiving the third mRNA (Pfizer) dose.

The study was funded by Pfizer in an independent research grant and by the NIHR Biomedical Research Centres in Imperial College London and Imperial College Healthcare NHS Trust and Cambridge, and the NIHR Clinical Research Facility Cambridge.

Dr. Liu and one other author had no disclosures. The other 18 authors have a range of disclosures related to various pharmaceutical companies, including Pfizer.

For people with inflammatory bowel disease (IBD) taking immunosuppressive medication, a third dose of a COVID-19 mRNA vaccine significantly increases neutralizing antibodies against the original SARS-CoV-2 strain, but the picture is more complicated for protection against the Omicron variant, according to a research letter published in Gastroenterology.

Though IBD patients do mount a response against Omicron, the response is substantially lower for those taking tofacitinib or infliximab, particularly infliximab monotherapy.

“As further mutations in the viral genome accumulate over time, with the attendant risk of immune evasion, it remains important to continue to reappraise vaccination strategy, including the implementation of personalized approaches for some patients, such as those treated with anti-TNF drugs and JAK inhibitors,” wrote Zhigang Liu, PhD, a research associate in the department of metabolism, digestion, and reproduction at Imperial College London, and his colleagues. “Preferential use of bivalent vaccines may be especially valuable in IBD patients taking anti-TNF agents or JAK inhibitors,” they wrote. Their study did not assess neutralizing antibodies resulting from use of the bivalent vaccine, however.

The researchers tracked 268 participants, including 49 healthy participants serving as controls, from May 2021 through March 2022. The other participants had IBD and included 51 patients taking thiopurines, 36 patients taking infliximab, 39 taking both infliximab and thiopurines, 39 taking ustekinumab, 38 taking vedolizumab, and 16 taking tofacitinib. The IBD patients were all enrolled in the SARS-CoV-2 Vaccination Immunogenicity in Immunosuppressed Inflammatory Bowel Disease Patients (VIP) cohort.

None of the participants had evidence of a SARS-CoV-2 infection at baseline. All had received two doses of an mRNA COVID-19 vaccine (all received Pfizer, except two controls who received Moderna) or two doses of the AstraZeneca vaccine as their primary vaccination. All received an mRNA vaccine for their third dose. Among the IBD patients, 137 received the AstraZeneca in their primary two-dose series, and 82 received Pfizer.

First the researchers assessed the participants’ humoral response to the vaccine against the original SARS-CoV-2 strain and against the Omicron BA.1 variant. Neutralizing antibody titers rose significantly against both strains after the third vaccine dose for all participants.

“However, 50% neutralization titer (NT50) values were significantly lower against Omicron than against the ancestral strain in all study groups, irrespective of the immunosuppressive treatment regimen,” the authors reported. NT50 values are a measure that reflect a vaccine-induced humoral immunity against SARS-CoV-2 after vaccination.

Compared to the healthy controls, individuals receiving infliximab, tofacitinib, or infliximab/thiopurine combination therapy showed significantly lower responses after the second and third vaccine doses. Thirteen patients did not generate NT50 against Omicron after the second vaccine dose, and 7 of them were on infliximab monotherapy. They represented nearly 20% of all infliximab monotherapy participants.

Next the researchers assessed the risk of a breakthrough infection according to neutralizing titer thresholds. Individuals with an NT50 less than 500 had 1.6 times greater odds of a breakthrough infection than those with an NT50 above 500, they noted. After two vaccine doses, 46% of participants with IBD had an NT50 above 500 for the ancestral strain, which rose to 85% of those with IBD after a third dose.

In the healthy control group, 35% had an NT50 under 500 after two doses, and 14% of them had a breakthrough infection, all of which were mild and none of which required hospitalization. The NT50 in healthy controls, however, was not significantly associated with risk of breakthrough infection.

“In this study, neutralizing titers elicited against the omicron variant were generally poor for all individuals and were substantially lower in recipients of infliximab, infliximab/thiopurine combination, or tofacitinib therapy,” the authors concluded. “This raises concerns about whether currently available vaccines will be sufficient to protect against continually evolving SARS-CoV-2 variants, especially in patients established on certain immunosuppressive drugs.”

The small population sizes for each subgroup based on medication was one of the study’s limitations. Another was the fact that it was underpowered to conclusively determine whether an increased risk of breakthrough infection exists in IBD patients who have lower titers of neutralizing antibodies. A limitation for generalization to U.S. patients is that just 64% of the IBD patients received the AstraZeneca vaccine, which is not offered in the United States, for their first two doses before receiving the third mRNA (Pfizer) dose.

The study was funded by Pfizer in an independent research grant and by the NIHR Biomedical Research Centres in Imperial College London and Imperial College Healthcare NHS Trust and Cambridge, and the NIHR Clinical Research Facility Cambridge.

Dr. Liu and one other author had no disclosures. The other 18 authors have a range of disclosures related to various pharmaceutical companies, including Pfizer.