From the AGA Journals

Among hospitalized patients with cirrhosis, a machine learning (ML) model enhanced mortality prediction compared with traditional methods and was consistent across country income levels in a large global study.

“This highly inclusive, representative, and globally derived model has been externally validated,” Jasmohan Bajaj, MD, AGAF, professor of medicine at Virginia Commonwealth University in Richmond, Virginia, told GI & Hepatology News. “This gives us a crystal ball. It helps hospital teams, transplant centers, gastroenterology and intensive care unit services triage and prioritize patients more effectively.”

The study supporting the model, which Bajaj said “could be used at this stage,” was published online in Gastroenterology. The model is available for downloading at https://silveys.shinyapps.io/app_cleared/.

 

CLEARED Cohort Analyzed

Wide variations across the world regarding available resources, outpatient services, reasons for admission, and etiologies of cirrhosis can influence patient outcomes, according to Bajaj and colleagues. Therefore, they sought to use ML approaches to improve prognostication for all countries.

They analyzed admission-day data from the prospective Chronic Liver Disease Evolution And Registry for Events and Decompensation (CLEARED) consortium, which includes inpatients with cirrhosis enrolled from six continents. The analysis compared ML approaches with logistical regression to predict inpatient mortality.

The researchers performed internal validation (75/25 split) and subdivision using World-Bank income status: low/low-middle (L-LMIC), upper middle (UMIC), and high (HIC). They determined that the ML model with the best area-under-the-curve (AUC) would be externally validated in a US-Veteran cirrhosis inpatient population.

The CLEARED cohort included 7239 cirrhosis inpatients (mean age, 56 years; 64% men; median MELD-Na, 25) from 115 centers globally; 22.5% of centers belonged to LMICs, 41% to UMICs, and 34% to HICs.

A total of 808 patients (11.1%) died in the hospital.

Random-Forest analysis showed the best AUC (0.815) with high calibration. This was significantly better than parametric logistic regression (AUC, 0.774) and LASSO (AUC, 0.787) models.

Random-Forest also was better than logistic regression regardless of country income-level: HIC (AUC,0.806), UMIC (AUC, 0.867), and L-LMICs (AUC, 0.768).

Of the top 15 important variables selected from Random-Forest, admission for acute kidney injury, hepatic encephalopathy, high MELD-Na/white blood count, and not being in high income country were variables most predictive of mortality.

In contrast, higher albumin, hemoglobin, diuretic use on admission, viral etiology, and being in a high-income country were most protective.

The Random-Forest model was validated in 28,670 veterans (mean age, 67 years; 96% men; median MELD-Na,15), with an inpatient mortality of 4% (1158 patients).

The final Random-Forest model, using 48 of the 67 original covariates, attained a strong AUC of 0.859. A refit version using only the top 15 variables achieved a comparable AUC of 0.851.

 

Clinical Relevance

“Cirrhosis and resultant organ failures remain a dynamic and multidisciplinary problem,” Bajaj noted. “Machine learning techniques are one part of multi-faceted management strategy that is required in this population.”

If patients fall into the high-risk category, he said, “careful consultation with patients, families, and clinical teams is needed before providing information, including where this model was derived from. The results of these discussions could be instructive regarding decisions for transfer, more aggressive monitoring/ICU transfer, palliative care or transplant assessments.”

Meena B. Bansal, MD, system chief, Division of Liver Diseases, Mount Sinai Health System in New York City, called the tool “very promising.” However, she told GI & Hepatology News, “it was validated on a VA [Veterans Affairs] cohort, which is a bit different than the cohort of patients seen at Mount Sinai. Therefore, validation in more academic tertiary care medical centers with high volume liver transplant would be helpful.”

 

Furthermore, said Bansal, who was not involved in the study, “they excluded those that receiving a liver transplant, and while only a small number, this is an important limitation.”

Nevertheless, she added, “Artificial intelligence has great potential in predictive risk models and will likely be a tool that assists for risk stratification, clinical management, and hopefully improved clinical outcomes.”

This study was partly supported by a VA Merit review to Bajaj and the National Center for Advancing Translational Sciences, National Institutes of Health. No conflicts of interest were reported by any author.

A version of this article appeared on Medscape.com.

Among hospitalized patients with cirrhosis, a machine learning (ML) model enhanced mortality prediction compared with traditional methods and was consistent across country income levels in a large global study.

“This highly inclusive, representative, and globally derived model has been externally validated,” Jasmohan Bajaj, MD, AGAF, professor of medicine at Virginia Commonwealth University in Richmond, Virginia, told GI & Hepatology News. “This gives us a crystal ball. It helps hospital teams, transplant centers, gastroenterology and intensive care unit services triage and prioritize patients more effectively.”

The study supporting the model, which Bajaj said “could be used at this stage,” was published online in Gastroenterology. The model is available for downloading at https://silveys.shinyapps.io/app_cleared/.

 

CLEARED Cohort Analyzed

Wide variations across the world regarding available resources, outpatient services, reasons for admission, and etiologies of cirrhosis can influence patient outcomes, according to Bajaj and colleagues. Therefore, they sought to use ML approaches to improve prognostication for all countries.

They analyzed admission-day data from the prospective Chronic Liver Disease Evolution And Registry for Events and Decompensation (CLEARED) consortium, which includes inpatients with cirrhosis enrolled from six continents. The analysis compared ML approaches with logistical regression to predict inpatient mortality.

The researchers performed internal validation (75/25 split) and subdivision using World-Bank income status: low/low-middle (L-LMIC), upper middle (UMIC), and high (HIC). They determined that the ML model with the best area-under-the-curve (AUC) would be externally validated in a US-Veteran cirrhosis inpatient population.

The CLEARED cohort included 7239 cirrhosis inpatients (mean age, 56 years; 64% men; median MELD-Na, 25) from 115 centers globally; 22.5% of centers belonged to LMICs, 41% to UMICs, and 34% to HICs.

A total of 808 patients (11.1%) died in the hospital.

Random-Forest analysis showed the best AUC (0.815) with high calibration. This was significantly better than parametric logistic regression (AUC, 0.774) and LASSO (AUC, 0.787) models.

Random-Forest also was better than logistic regression regardless of country income-level: HIC (AUC,0.806), UMIC (AUC, 0.867), and L-LMICs (AUC, 0.768).

Of the top 15 important variables selected from Random-Forest, admission for acute kidney injury, hepatic encephalopathy, high MELD-Na/white blood count, and not being in high income country were variables most predictive of mortality.

In contrast, higher albumin, hemoglobin, diuretic use on admission, viral etiology, and being in a high-income country were most protective.

The Random-Forest model was validated in 28,670 veterans (mean age, 67 years; 96% men; median MELD-Na,15), with an inpatient mortality of 4% (1158 patients).

The final Random-Forest model, using 48 of the 67 original covariates, attained a strong AUC of 0.859. A refit version using only the top 15 variables achieved a comparable AUC of 0.851.

 

Clinical Relevance

“Cirrhosis and resultant organ failures remain a dynamic and multidisciplinary problem,” Bajaj noted. “Machine learning techniques are one part of multi-faceted management strategy that is required in this population.”

If patients fall into the high-risk category, he said, “careful consultation with patients, families, and clinical teams is needed before providing information, including where this model was derived from. The results of these discussions could be instructive regarding decisions for transfer, more aggressive monitoring/ICU transfer, palliative care or transplant assessments.”

Meena B. Bansal, MD, system chief, Division of Liver Diseases, Mount Sinai Health System in New York City, called the tool “very promising.” However, she told GI & Hepatology News, “it was validated on a VA [Veterans Affairs] cohort, which is a bit different than the cohort of patients seen at Mount Sinai. Therefore, validation in more academic tertiary care medical centers with high volume liver transplant would be helpful.”

 

Furthermore, said Bansal, who was not involved in the study, “they excluded those that receiving a liver transplant, and while only a small number, this is an important limitation.”

Nevertheless, she added, “Artificial intelligence has great potential in predictive risk models and will likely be a tool that assists for risk stratification, clinical management, and hopefully improved clinical outcomes.”

This study was partly supported by a VA Merit review to Bajaj and the National Center for Advancing Translational Sciences, National Institutes of Health. No conflicts of interest were reported by any author.

A version of this article appeared on Medscape.com.

Among hospitalized patients with cirrhosis, a machine learning (ML) model enhanced mortality prediction compared with traditional methods and was consistent across country income levels in a large global study.

“This highly inclusive, representative, and globally derived model has been externally validated,” Jasmohan Bajaj, MD, AGAF, professor of medicine at Virginia Commonwealth University in Richmond, Virginia, told GI & Hepatology News. “This gives us a crystal ball. It helps hospital teams, transplant centers, gastroenterology and intensive care unit services triage and prioritize patients more effectively.”

The study supporting the model, which Bajaj said “could be used at this stage,” was published online in Gastroenterology. The model is available for downloading at https://silveys.shinyapps.io/app_cleared/.

 

CLEARED Cohort Analyzed

Wide variations across the world regarding available resources, outpatient services, reasons for admission, and etiologies of cirrhosis can influence patient outcomes, according to Bajaj and colleagues. Therefore, they sought to use ML approaches to improve prognostication for all countries.

They analyzed admission-day data from the prospective Chronic Liver Disease Evolution And Registry for Events and Decompensation (CLEARED) consortium, which includes inpatients with cirrhosis enrolled from six continents. The analysis compared ML approaches with logistical regression to predict inpatient mortality.

The researchers performed internal validation (75/25 split) and subdivision using World-Bank income status: low/low-middle (L-LMIC), upper middle (UMIC), and high (HIC). They determined that the ML model with the best area-under-the-curve (AUC) would be externally validated in a US-Veteran cirrhosis inpatient population.

The CLEARED cohort included 7239 cirrhosis inpatients (mean age, 56 years; 64% men; median MELD-Na, 25) from 115 centers globally; 22.5% of centers belonged to LMICs, 41% to UMICs, and 34% to HICs.

A total of 808 patients (11.1%) died in the hospital.

Random-Forest analysis showed the best AUC (0.815) with high calibration. This was significantly better than parametric logistic regression (AUC, 0.774) and LASSO (AUC, 0.787) models.

Random-Forest also was better than logistic regression regardless of country income-level: HIC (AUC,0.806), UMIC (AUC, 0.867), and L-LMICs (AUC, 0.768).

Of the top 15 important variables selected from Random-Forest, admission for acute kidney injury, hepatic encephalopathy, high MELD-Na/white blood count, and not being in high income country were variables most predictive of mortality.

In contrast, higher albumin, hemoglobin, diuretic use on admission, viral etiology, and being in a high-income country were most protective.

The Random-Forest model was validated in 28,670 veterans (mean age, 67 years; 96% men; median MELD-Na,15), with an inpatient mortality of 4% (1158 patients).

The final Random-Forest model, using 48 of the 67 original covariates, attained a strong AUC of 0.859. A refit version using only the top 15 variables achieved a comparable AUC of 0.851.

 

Clinical Relevance

“Cirrhosis and resultant organ failures remain a dynamic and multidisciplinary problem,” Bajaj noted. “Machine learning techniques are one part of multi-faceted management strategy that is required in this population.”

If patients fall into the high-risk category, he said, “careful consultation with patients, families, and clinical teams is needed before providing information, including where this model was derived from. The results of these discussions could be instructive regarding decisions for transfer, more aggressive monitoring/ICU transfer, palliative care or transplant assessments.”

Meena B. Bansal, MD, system chief, Division of Liver Diseases, Mount Sinai Health System in New York City, called the tool “very promising.” However, she told GI & Hepatology News, “it was validated on a VA [Veterans Affairs] cohort, which is a bit different than the cohort of patients seen at Mount Sinai. Therefore, validation in more academic tertiary care medical centers with high volume liver transplant would be helpful.”

 

Furthermore, said Bansal, who was not involved in the study, “they excluded those that receiving a liver transplant, and while only a small number, this is an important limitation.”

Nevertheless, she added, “Artificial intelligence has great potential in predictive risk models and will likely be a tool that assists for risk stratification, clinical management, and hopefully improved clinical outcomes.”

This study was partly supported by a VA Merit review to Bajaj and the National Center for Advancing Translational Sciences, National Institutes of Health. No conflicts of interest were reported by any author.

A version of this article appeared on Medscape.com.

Changes in sleep metrics detected with wearable technology could serve as an inflammation marker and potentially predict inflammatory bowel disease (IBD) flareups, regardless of whether a patient has symptoms, an observational study suggested.

Sleep data from 101 study participants over a mean duration of about 228 days revealed that altered sleep architecture was only apparent when inflammation was present — symptoms alone did not impact sleep cycles or signal inflammation.

“We thought symptoms might have an impact on sleep, but interestingly, our data showed that measurable changes like reduced rapid eye movement (REM) sleep and increased light sleep only occurred during periods of active inflammation,” Robert Hirten, MD, associate professor of Medicine (Gastroenterology), and Artificial Intelligence and Human Health, at the Icahn School of Medicine at Mount Sinai, New York City, told GI & Hepatology News.

“It was also interesting to see distinct patterns in sleep metrics begin to shift over the 45 days before a flare, suggesting the potential for sleep to serve as an early indicator of disease activity,” he added.

“Sleep is often overlooked in the management of IBD, but it may provide valuable insights into a patient’s underlying disease state,” he said. “While sleep monitoring isn’t yet a standard part of IBD care, this study highlights its potential as a noninvasive window into disease activity, and a promising area for future clinical integration.”

The study was published online in Clinical Gastroenterology and Hepatology.

 

Less REM Sleep, More Light Sleep

Researchers assessed the impact of inflammation and symptoms on sleep architecture in IBD by analyzing data from 101 individuals who answered daily disease activity surveys and wore a wearable device.

The mean age of participants was 41 years and 65.3% were women. Sixty-three participants (62.4%) had Crohn’s disease (CD) and 38 (37.6%) had ulcerative colitis (UC).

Almost 40 (39.6%) participants used an Apple Watch; 50 (49.5%) used a Fitbit; and 11 (10.9%) used an Oura ring. Sleep architecture, sleep efficiency, and total hours asleep were collected from the devices. Participants were encouraged to wear their devices for at least 4 days per week and 8 hours per day and were not required to wear them at night. Participants provided data by linking their devices to ehive, Mount Sinai’s custom app.

Daily clinical disease activity was assessed using the UC or CD Patient Reported Outcome-2 survey. Participants were asked to answer at least four daily surveys each week.

Associations between sleep metrics and periods of symptomatic and inflammatory flares, and combinations of symptomatic and inflammatory activity, were compared to periods of symptomatic and inflammatory remission.

Furthermore, researchers explored the rate of change in sleep metrics for 45 days before and after inflammatory and symptomatic flares.

Participants contributed a mean duration of 228.16 nights of wearable data. During active inflammation, they spent a lower percentage of sleep time in REM (20% vs 21.59%) and a greater percentage of sleep time in light sleep (62.23% vs 59.95%) than during inflammatory remission. No differences were observed in the mean percentage of time in deep sleep, sleep efficiency, or total time asleep.

During symptomatic flares, there were no differences in the percentage of sleep time in REM sleep, deep sleep, light sleep, or sleep efficiency compared with periods of inflammatory remission. However, participants slept less overall during symptomatic flares compared with during symptomatic remission.

Compared with during asymptomatic and uninflamed periods, during asymptomatic but inflamed periods, participants spent a lower percentage of time in REM sleep, and more time in light sleep; however, there were no differences in sleep efficiency or total time asleep.

Similarly, participants had more light sleep and less REM sleep during symptomatic and inflammatory flares than during asymptomatic and uninflamed periods — but there were no differences in the percentage of time spent in deep sleep, in sleep efficiency, and the total time asleep.

Symptomatic flares alone, without inflammation, did not impact sleep metrics, the researchers concluded. However, periods with active inflammation were associated with a significantly smaller percentage of sleep time in REM sleep and a greater percentage of sleep time in light sleep.

The team also performed longitudinal mapping of sleep patterns before, during, and after disease exacerbations by analyzing sleep data for 6 weeks before and 6 weeks after flare episodes.

They found that sleep disturbances significantly worsen leading up to inflammatory flares and improve afterward, suggesting that sleep changes may signal upcoming increased disease activity. Evaluating the intersection of inflammatory and symptomatic flares, altered sleep architecture was only evident when inflammation was present.

“These findings raise important questions about whether intervening on sleep can actually impact inflammation or disease trajectory in IBD,” Hirten said. “Next steps include studying whether targeted sleep interventions can improve both sleep and IBD outcomes.”

While this research is still in the early stages, he said, “it suggests that sleep may have a relationship with inflammatory activity in IBD. For patients, it reinforces the value of paying attention to sleep changes.”

The findings also show the potential of wearable devices to guide more personalized monitoring, he added. “More work is needed before sleep metrics can be used routinely in clinical decision-making.”

 

Validates the Use of Wearables

Commenting on the study for GI & Hepatology News, Michael Mintz, MD, a gastroenterologist at Weill Cornell Medicine and NewYork-Presbyterian in New York City, observed, “Gastrointestinal symptoms often do not correlate with objective disease activity in IBD, creating a diagnostic challenge for gastroenterologists. Burdensome, expensive, and/or invasive testing, such as colonoscopies, stool tests, or imaging, are frequently required to monitor disease activity.” 

“This study is a first step in objectively monitoring inflammation in a patient-centric way that does not create undue burden to our patients,” he said. “It also provides longitudinal data that suggests changes in sleep patterns can pre-date disease flares, which ideally can lead to earlier intervention to prevent disease complications.”

Like Hirten, he noted that clinical decisions, such as changing IBD therapy, should not be based on the results of this study. “Rather this provides validation that wearable technology can provide useful objective data that correlates with disease activity.”

Furthermore, he said, it is not clear whether analyzing sleep data is a cost-effective way of monitoring IBD disease activity, or whether that data should be used alone or in combination with other objective disease markers, to influence clinical decision-making.

“This study provides proof of concept that there is a relationship between sleep characteristics and objective inflammation, but further studies are needed,” he said. “I am hopeful that this technology will give us another tool that we can use in clinical practice to monitor disease activity and improve outcomes in a way that is comfortable and convenient for our patients.”

This study was supported by a grant to Hirten from the US National Institutes of Health. Hirten reported receiving consulting fees from Bristol Meyers Squibb, AbbVie; stock options from Salvo Health; and research support from Janssen, Intralytix, EnLiSense, Crohn’s and Colitis Foundation. Mintz declared no competing interests.

A version of this article appeared on Medscape.com.

Changes in sleep metrics detected with wearable technology could serve as an inflammation marker and potentially predict inflammatory bowel disease (IBD) flareups, regardless of whether a patient has symptoms, an observational study suggested.

Sleep data from 101 study participants over a mean duration of about 228 days revealed that altered sleep architecture was only apparent when inflammation was present — symptoms alone did not impact sleep cycles or signal inflammation.

“We thought symptoms might have an impact on sleep, but interestingly, our data showed that measurable changes like reduced rapid eye movement (REM) sleep and increased light sleep only occurred during periods of active inflammation,” Robert Hirten, MD, associate professor of Medicine (Gastroenterology), and Artificial Intelligence and Human Health, at the Icahn School of Medicine at Mount Sinai, New York City, told GI & Hepatology News.

“It was also interesting to see distinct patterns in sleep metrics begin to shift over the 45 days before a flare, suggesting the potential for sleep to serve as an early indicator of disease activity,” he added.

“Sleep is often overlooked in the management of IBD, but it may provide valuable insights into a patient’s underlying disease state,” he said. “While sleep monitoring isn’t yet a standard part of IBD care, this study highlights its potential as a noninvasive window into disease activity, and a promising area for future clinical integration.”

The study was published online in Clinical Gastroenterology and Hepatology.

 

Less REM Sleep, More Light Sleep

Researchers assessed the impact of inflammation and symptoms on sleep architecture in IBD by analyzing data from 101 individuals who answered daily disease activity surveys and wore a wearable device.

The mean age of participants was 41 years and 65.3% were women. Sixty-three participants (62.4%) had Crohn’s disease (CD) and 38 (37.6%) had ulcerative colitis (UC).

Almost 40 (39.6%) participants used an Apple Watch; 50 (49.5%) used a Fitbit; and 11 (10.9%) used an Oura ring. Sleep architecture, sleep efficiency, and total hours asleep were collected from the devices. Participants were encouraged to wear their devices for at least 4 days per week and 8 hours per day and were not required to wear them at night. Participants provided data by linking their devices to ehive, Mount Sinai’s custom app.

Daily clinical disease activity was assessed using the UC or CD Patient Reported Outcome-2 survey. Participants were asked to answer at least four daily surveys each week.

Associations between sleep metrics and periods of symptomatic and inflammatory flares, and combinations of symptomatic and inflammatory activity, were compared to periods of symptomatic and inflammatory remission.

Furthermore, researchers explored the rate of change in sleep metrics for 45 days before and after inflammatory and symptomatic flares.

Participants contributed a mean duration of 228.16 nights of wearable data. During active inflammation, they spent a lower percentage of sleep time in REM (20% vs 21.59%) and a greater percentage of sleep time in light sleep (62.23% vs 59.95%) than during inflammatory remission. No differences were observed in the mean percentage of time in deep sleep, sleep efficiency, or total time asleep.

During symptomatic flares, there were no differences in the percentage of sleep time in REM sleep, deep sleep, light sleep, or sleep efficiency compared with periods of inflammatory remission. However, participants slept less overall during symptomatic flares compared with during symptomatic remission.

Compared with during asymptomatic and uninflamed periods, during asymptomatic but inflamed periods, participants spent a lower percentage of time in REM sleep, and more time in light sleep; however, there were no differences in sleep efficiency or total time asleep.

Similarly, participants had more light sleep and less REM sleep during symptomatic and inflammatory flares than during asymptomatic and uninflamed periods — but there were no differences in the percentage of time spent in deep sleep, in sleep efficiency, and the total time asleep.

Symptomatic flares alone, without inflammation, did not impact sleep metrics, the researchers concluded. However, periods with active inflammation were associated with a significantly smaller percentage of sleep time in REM sleep and a greater percentage of sleep time in light sleep.

The team also performed longitudinal mapping of sleep patterns before, during, and after disease exacerbations by analyzing sleep data for 6 weeks before and 6 weeks after flare episodes.

They found that sleep disturbances significantly worsen leading up to inflammatory flares and improve afterward, suggesting that sleep changes may signal upcoming increased disease activity. Evaluating the intersection of inflammatory and symptomatic flares, altered sleep architecture was only evident when inflammation was present.

“These findings raise important questions about whether intervening on sleep can actually impact inflammation or disease trajectory in IBD,” Hirten said. “Next steps include studying whether targeted sleep interventions can improve both sleep and IBD outcomes.”

While this research is still in the early stages, he said, “it suggests that sleep may have a relationship with inflammatory activity in IBD. For patients, it reinforces the value of paying attention to sleep changes.”

The findings also show the potential of wearable devices to guide more personalized monitoring, he added. “More work is needed before sleep metrics can be used routinely in clinical decision-making.”

 

Validates the Use of Wearables

Commenting on the study for GI & Hepatology News, Michael Mintz, MD, a gastroenterologist at Weill Cornell Medicine and NewYork-Presbyterian in New York City, observed, “Gastrointestinal symptoms often do not correlate with objective disease activity in IBD, creating a diagnostic challenge for gastroenterologists. Burdensome, expensive, and/or invasive testing, such as colonoscopies, stool tests, or imaging, are frequently required to monitor disease activity.” 

“This study is a first step in objectively monitoring inflammation in a patient-centric way that does not create undue burden to our patients,” he said. “It also provides longitudinal data that suggests changes in sleep patterns can pre-date disease flares, which ideally can lead to earlier intervention to prevent disease complications.”

Like Hirten, he noted that clinical decisions, such as changing IBD therapy, should not be based on the results of this study. “Rather this provides validation that wearable technology can provide useful objective data that correlates with disease activity.”

Furthermore, he said, it is not clear whether analyzing sleep data is a cost-effective way of monitoring IBD disease activity, or whether that data should be used alone or in combination with other objective disease markers, to influence clinical decision-making.

“This study provides proof of concept that there is a relationship between sleep characteristics and objective inflammation, but further studies are needed,” he said. “I am hopeful that this technology will give us another tool that we can use in clinical practice to monitor disease activity and improve outcomes in a way that is comfortable and convenient for our patients.”

This study was supported by a grant to Hirten from the US National Institutes of Health. Hirten reported receiving consulting fees from Bristol Meyers Squibb, AbbVie; stock options from Salvo Health; and research support from Janssen, Intralytix, EnLiSense, Crohn’s and Colitis Foundation. Mintz declared no competing interests.

A version of this article appeared on Medscape.com.

Changes in sleep metrics detected with wearable technology could serve as an inflammation marker and potentially predict inflammatory bowel disease (IBD) flareups, regardless of whether a patient has symptoms, an observational study suggested.

Sleep data from 101 study participants over a mean duration of about 228 days revealed that altered sleep architecture was only apparent when inflammation was present — symptoms alone did not impact sleep cycles or signal inflammation.

“We thought symptoms might have an impact on sleep, but interestingly, our data showed that measurable changes like reduced rapid eye movement (REM) sleep and increased light sleep only occurred during periods of active inflammation,” Robert Hirten, MD, associate professor of Medicine (Gastroenterology), and Artificial Intelligence and Human Health, at the Icahn School of Medicine at Mount Sinai, New York City, told GI & Hepatology News.

“It was also interesting to see distinct patterns in sleep metrics begin to shift over the 45 days before a flare, suggesting the potential for sleep to serve as an early indicator of disease activity,” he added.

“Sleep is often overlooked in the management of IBD, but it may provide valuable insights into a patient’s underlying disease state,” he said. “While sleep monitoring isn’t yet a standard part of IBD care, this study highlights its potential as a noninvasive window into disease activity, and a promising area for future clinical integration.”

The study was published online in Clinical Gastroenterology and Hepatology.

 

Less REM Sleep, More Light Sleep

Researchers assessed the impact of inflammation and symptoms on sleep architecture in IBD by analyzing data from 101 individuals who answered daily disease activity surveys and wore a wearable device.

The mean age of participants was 41 years and 65.3% were women. Sixty-three participants (62.4%) had Crohn’s disease (CD) and 38 (37.6%) had ulcerative colitis (UC).

Almost 40 (39.6%) participants used an Apple Watch; 50 (49.5%) used a Fitbit; and 11 (10.9%) used an Oura ring. Sleep architecture, sleep efficiency, and total hours asleep were collected from the devices. Participants were encouraged to wear their devices for at least 4 days per week and 8 hours per day and were not required to wear them at night. Participants provided data by linking their devices to ehive, Mount Sinai’s custom app.

Daily clinical disease activity was assessed using the UC or CD Patient Reported Outcome-2 survey. Participants were asked to answer at least four daily surveys each week.

Associations between sleep metrics and periods of symptomatic and inflammatory flares, and combinations of symptomatic and inflammatory activity, were compared to periods of symptomatic and inflammatory remission.

Furthermore, researchers explored the rate of change in sleep metrics for 45 days before and after inflammatory and symptomatic flares.

Participants contributed a mean duration of 228.16 nights of wearable data. During active inflammation, they spent a lower percentage of sleep time in REM (20% vs 21.59%) and a greater percentage of sleep time in light sleep (62.23% vs 59.95%) than during inflammatory remission. No differences were observed in the mean percentage of time in deep sleep, sleep efficiency, or total time asleep.

During symptomatic flares, there were no differences in the percentage of sleep time in REM sleep, deep sleep, light sleep, or sleep efficiency compared with periods of inflammatory remission. However, participants slept less overall during symptomatic flares compared with during symptomatic remission.

Compared with during asymptomatic and uninflamed periods, during asymptomatic but inflamed periods, participants spent a lower percentage of time in REM sleep, and more time in light sleep; however, there were no differences in sleep efficiency or total time asleep.

Similarly, participants had more light sleep and less REM sleep during symptomatic and inflammatory flares than during asymptomatic and uninflamed periods — but there were no differences in the percentage of time spent in deep sleep, in sleep efficiency, and the total time asleep.

Symptomatic flares alone, without inflammation, did not impact sleep metrics, the researchers concluded. However, periods with active inflammation were associated with a significantly smaller percentage of sleep time in REM sleep and a greater percentage of sleep time in light sleep.

The team also performed longitudinal mapping of sleep patterns before, during, and after disease exacerbations by analyzing sleep data for 6 weeks before and 6 weeks after flare episodes.

They found that sleep disturbances significantly worsen leading up to inflammatory flares and improve afterward, suggesting that sleep changes may signal upcoming increased disease activity. Evaluating the intersection of inflammatory and symptomatic flares, altered sleep architecture was only evident when inflammation was present.

“These findings raise important questions about whether intervening on sleep can actually impact inflammation or disease trajectory in IBD,” Hirten said. “Next steps include studying whether targeted sleep interventions can improve both sleep and IBD outcomes.”

While this research is still in the early stages, he said, “it suggests that sleep may have a relationship with inflammatory activity in IBD. For patients, it reinforces the value of paying attention to sleep changes.”

The findings also show the potential of wearable devices to guide more personalized monitoring, he added. “More work is needed before sleep metrics can be used routinely in clinical decision-making.”

 

Validates the Use of Wearables

Commenting on the study for GI & Hepatology News, Michael Mintz, MD, a gastroenterologist at Weill Cornell Medicine and NewYork-Presbyterian in New York City, observed, “Gastrointestinal symptoms often do not correlate with objective disease activity in IBD, creating a diagnostic challenge for gastroenterologists. Burdensome, expensive, and/or invasive testing, such as colonoscopies, stool tests, or imaging, are frequently required to monitor disease activity.” 

“This study is a first step in objectively monitoring inflammation in a patient-centric way that does not create undue burden to our patients,” he said. “It also provides longitudinal data that suggests changes in sleep patterns can pre-date disease flares, which ideally can lead to earlier intervention to prevent disease complications.”

Like Hirten, he noted that clinical decisions, such as changing IBD therapy, should not be based on the results of this study. “Rather this provides validation that wearable technology can provide useful objective data that correlates with disease activity.”

Furthermore, he said, it is not clear whether analyzing sleep data is a cost-effective way of monitoring IBD disease activity, or whether that data should be used alone or in combination with other objective disease markers, to influence clinical decision-making.

“This study provides proof of concept that there is a relationship between sleep characteristics and objective inflammation, but further studies are needed,” he said. “I am hopeful that this technology will give us another tool that we can use in clinical practice to monitor disease activity and improve outcomes in a way that is comfortable and convenient for our patients.”

This study was supported by a grant to Hirten from the US National Institutes of Health. Hirten reported receiving consulting fees from Bristol Meyers Squibb, AbbVie; stock options from Salvo Health; and research support from Janssen, Intralytix, EnLiSense, Crohn’s and Colitis Foundation. Mintz declared no competing interests.

A version of this article appeared on Medscape.com.

Neighborhood-level social determinants of health (SDOH) are associated with the burden, comorbidities, and mortality of metabolic dysfunction-associated steatotic disease (MASLD). These health mediators should be considered along with individual SDOH in clinical care and healthcare quality and equity improvement, a large retrospective study of adults with MASLD at a multi-state healthcare institution concluded.

Across quartiles, patients in the most disadvantaged neighborhoods (according to home addresses) vs the least disadvantaged had worse outcomes and were also disproportionately Hispanic, Black, and Native American/Alaska Native, more often Spanish-speaking in primary language, and more often uninsured or on Medicaid, according to Karn Wijarnpreecha, MD, MPH, of the Division of Gastroenterology and Hepatology at University of Arizona College of Medicine–Phoenix, and colleagues writing in Clinical Gastroenterology and Hepatology.

Even after adjustment for measures in the Social Deprivation Index (SDI), the incidence of death, cirrhosis, diabetes mellitus (DM), and major adverse cardiovascular events (MACE) was higher in Native American/Alaska Native patients compared with their non-Hispanic White counterparts. The SDI is a composite measure of seven demographic characteristics from the American Community Survey, with scores ranging from 1 to 100 and weighted based on characteristics from national percentile rankings.

Aligning with the growing prevalence of obesity and DM, MASLD has increased substantially over the past three decades, and is now the leading cause of chronic liver disease in this country and the world. 

This rise in prevalence has underscored health disparities in MASLD and prompted research into linkd between liver disease and SDOH, defined as the conditions under which people are born, grow, live, work, and age. These are fundamental drivers of health disparities, including those in MASLD.
 

Study Details

Primary outcomes were MASLD burden, mortality, and comorbidities by neighborhood SDOH, assessed using the SDI in cross-sectional and longitudinal analyses.

A total of 69,191 adult patients (more than 50% female) diagnosed with MASLD were included, 45,003 of whom had at least 365 days of follow-up. They were treated from July 2012 to June 2023 in Banner Health Systems, a network that includes primary-, secondary-, and tertiary-care centers in Arizona, Colorado, Wyoming, Nevada, Nebraska, and California.

The median follow-up time was 48 months. Among patients across SDI quartiles (age range 49 to 62 years), 1390 patients (3.1%) died, 902 (2.0%) developed cirrhosis, 1087 (2.4%) developed LRE, 6537 (14.5%) developed DM, 2057 (4.6%) developed cancer, and 5409 (12.0%) developed MACE.

Those living in the most disadvantaged quartile of neighborhoods compared with the least had the following higher odds:

• cirrhosis, adjusted odds ratio [aOR], 1.42 (P < .001)
• any cardiovascular (CVD) disease, aOR, 1.20 (P < .001),
• coronary artery disease, aOR, 1.17 (P < .001)
• congestive heart failure, aOR, 1.43 (P < .001)
• cerebrovascular accident, aOR, 1.19 (P = .001)
• DM, aOR, 1.57 (P < .001)
• hypertension, aOR, 1.38 (P < .001).

They also had increased incidence of death (adjusted hazard ratio [aHR], 1.47; P < .001), LRE (aHR, 1.31; P = .012), DM (aHR, 1.47; P < .001), and MACE (aHR, 1.24; P < .001). 

The study expands upon previous SDOH-related research in liver disease and is the largest analysis of neighborhood-level SDOH in patients with MASLD to date. “Our findings are consistent with a recent study by Chen et al of over 15,900 patients with MASLD in Michigan that found neighborhood-level social disadvantage was associated with increased mortality and incident LREs and CVD,” Wijarnpreecha and colleagues wrote. 

“Beyond screening patients for individual-level SDOH, neighborhood-level determinants of health should also be considered, as they are important mediators between the environment and the individual,” they added, calling for studies to better understand the specific neighborhood SDOH that drive the disparate outcomes. In practice, integration of these measures into medical records might inform clinicians which patients would benefit from social services or help guide quality improvement projects and community partnerships.

Wijarnpreecha had no conflicts of interest to disclose. Several coauthors reported research support, consulting/advisory work, or stock ownership for various private-sector companies.
 

Neighborhood-level social determinants of health (SDOH) are associated with the burden, comorbidities, and mortality of metabolic dysfunction-associated steatotic disease (MASLD). These health mediators should be considered along with individual SDOH in clinical care and healthcare quality and equity improvement, a large retrospective study of adults with MASLD at a multi-state healthcare institution concluded.

Across quartiles, patients in the most disadvantaged neighborhoods (according to home addresses) vs the least disadvantaged had worse outcomes and were also disproportionately Hispanic, Black, and Native American/Alaska Native, more often Spanish-speaking in primary language, and more often uninsured or on Medicaid, according to Karn Wijarnpreecha, MD, MPH, of the Division of Gastroenterology and Hepatology at University of Arizona College of Medicine–Phoenix, and colleagues writing in Clinical Gastroenterology and Hepatology.

Even after adjustment for measures in the Social Deprivation Index (SDI), the incidence of death, cirrhosis, diabetes mellitus (DM), and major adverse cardiovascular events (MACE) was higher in Native American/Alaska Native patients compared with their non-Hispanic White counterparts. The SDI is a composite measure of seven demographic characteristics from the American Community Survey, with scores ranging from 1 to 100 and weighted based on characteristics from national percentile rankings.

Aligning with the growing prevalence of obesity and DM, MASLD has increased substantially over the past three decades, and is now the leading cause of chronic liver disease in this country and the world. 

This rise in prevalence has underscored health disparities in MASLD and prompted research into linkd between liver disease and SDOH, defined as the conditions under which people are born, grow, live, work, and age. These are fundamental drivers of health disparities, including those in MASLD.
 

Study Details

Primary outcomes were MASLD burden, mortality, and comorbidities by neighborhood SDOH, assessed using the SDI in cross-sectional and longitudinal analyses.

A total of 69,191 adult patients (more than 50% female) diagnosed with MASLD were included, 45,003 of whom had at least 365 days of follow-up. They were treated from July 2012 to June 2023 in Banner Health Systems, a network that includes primary-, secondary-, and tertiary-care centers in Arizona, Colorado, Wyoming, Nevada, Nebraska, and California.

The median follow-up time was 48 months. Among patients across SDI quartiles (age range 49 to 62 years), 1390 patients (3.1%) died, 902 (2.0%) developed cirrhosis, 1087 (2.4%) developed LRE, 6537 (14.5%) developed DM, 2057 (4.6%) developed cancer, and 5409 (12.0%) developed MACE.

Those living in the most disadvantaged quartile of neighborhoods compared with the least had the following higher odds:

• cirrhosis, adjusted odds ratio [aOR], 1.42 (P < .001)
• any cardiovascular (CVD) disease, aOR, 1.20 (P < .001),
• coronary artery disease, aOR, 1.17 (P < .001)
• congestive heart failure, aOR, 1.43 (P < .001)
• cerebrovascular accident, aOR, 1.19 (P = .001)
• DM, aOR, 1.57 (P < .001)
• hypertension, aOR, 1.38 (P < .001).

They also had increased incidence of death (adjusted hazard ratio [aHR], 1.47; P < .001), LRE (aHR, 1.31; P = .012), DM (aHR, 1.47; P < .001), and MACE (aHR, 1.24; P < .001). 

The study expands upon previous SDOH-related research in liver disease and is the largest analysis of neighborhood-level SDOH in patients with MASLD to date. “Our findings are consistent with a recent study by Chen et al of over 15,900 patients with MASLD in Michigan that found neighborhood-level social disadvantage was associated with increased mortality and incident LREs and CVD,” Wijarnpreecha and colleagues wrote. 

“Beyond screening patients for individual-level SDOH, neighborhood-level determinants of health should also be considered, as they are important mediators between the environment and the individual,” they added, calling for studies to better understand the specific neighborhood SDOH that drive the disparate outcomes. In practice, integration of these measures into medical records might inform clinicians which patients would benefit from social services or help guide quality improvement projects and community partnerships.

Wijarnpreecha had no conflicts of interest to disclose. Several coauthors reported research support, consulting/advisory work, or stock ownership for various private-sector companies.
 

Neighborhood-level social determinants of health (SDOH) are associated with the burden, comorbidities, and mortality of metabolic dysfunction-associated steatotic disease (MASLD). These health mediators should be considered along with individual SDOH in clinical care and healthcare quality and equity improvement, a large retrospective study of adults with MASLD at a multi-state healthcare institution concluded.

Across quartiles, patients in the most disadvantaged neighborhoods (according to home addresses) vs the least disadvantaged had worse outcomes and were also disproportionately Hispanic, Black, and Native American/Alaska Native, more often Spanish-speaking in primary language, and more often uninsured or on Medicaid, according to Karn Wijarnpreecha, MD, MPH, of the Division of Gastroenterology and Hepatology at University of Arizona College of Medicine–Phoenix, and colleagues writing in Clinical Gastroenterology and Hepatology.

Even after adjustment for measures in the Social Deprivation Index (SDI), the incidence of death, cirrhosis, diabetes mellitus (DM), and major adverse cardiovascular events (MACE) was higher in Native American/Alaska Native patients compared with their non-Hispanic White counterparts. The SDI is a composite measure of seven demographic characteristics from the American Community Survey, with scores ranging from 1 to 100 and weighted based on characteristics from national percentile rankings.

Aligning with the growing prevalence of obesity and DM, MASLD has increased substantially over the past three decades, and is now the leading cause of chronic liver disease in this country and the world. 

This rise in prevalence has underscored health disparities in MASLD and prompted research into linkd between liver disease and SDOH, defined as the conditions under which people are born, grow, live, work, and age. These are fundamental drivers of health disparities, including those in MASLD.
 

Study Details

Primary outcomes were MASLD burden, mortality, and comorbidities by neighborhood SDOH, assessed using the SDI in cross-sectional and longitudinal analyses.

A total of 69,191 adult patients (more than 50% female) diagnosed with MASLD were included, 45,003 of whom had at least 365 days of follow-up. They were treated from July 2012 to June 2023 in Banner Health Systems, a network that includes primary-, secondary-, and tertiary-care centers in Arizona, Colorado, Wyoming, Nevada, Nebraska, and California.

The median follow-up time was 48 months. Among patients across SDI quartiles (age range 49 to 62 years), 1390 patients (3.1%) died, 902 (2.0%) developed cirrhosis, 1087 (2.4%) developed LRE, 6537 (14.5%) developed DM, 2057 (4.6%) developed cancer, and 5409 (12.0%) developed MACE.

Those living in the most disadvantaged quartile of neighborhoods compared with the least had the following higher odds:

• cirrhosis, adjusted odds ratio [aOR], 1.42 (P < .001)
• any cardiovascular (CVD) disease, aOR, 1.20 (P < .001),
• coronary artery disease, aOR, 1.17 (P < .001)
• congestive heart failure, aOR, 1.43 (P < .001)
• cerebrovascular accident, aOR, 1.19 (P = .001)
• DM, aOR, 1.57 (P < .001)
• hypertension, aOR, 1.38 (P < .001).

They also had increased incidence of death (adjusted hazard ratio [aHR], 1.47; P < .001), LRE (aHR, 1.31; P = .012), DM (aHR, 1.47; P < .001), and MACE (aHR, 1.24; P < .001). 

The study expands upon previous SDOH-related research in liver disease and is the largest analysis of neighborhood-level SDOH in patients with MASLD to date. “Our findings are consistent with a recent study by Chen et al of over 15,900 patients with MASLD in Michigan that found neighborhood-level social disadvantage was associated with increased mortality and incident LREs and CVD,” Wijarnpreecha and colleagues wrote. 

“Beyond screening patients for individual-level SDOH, neighborhood-level determinants of health should also be considered, as they are important mediators between the environment and the individual,” they added, calling for studies to better understand the specific neighborhood SDOH that drive the disparate outcomes. In practice, integration of these measures into medical records might inform clinicians which patients would benefit from social services or help guide quality improvement projects and community partnerships.

Wijarnpreecha had no conflicts of interest to disclose. Several coauthors reported research support, consulting/advisory work, or stock ownership for various private-sector companies.
 

A head-to-head comparison of the JAK inhibitor drug tofacitinib and chimeric monoclonal antibody infliximab in the treatment of acute severe ulcerative colitis (ASUC) shows that, contrary to concerns, tofacitinib is not associated with worse postoperative complications and in fact may reduce the risk of the need for colectomy.

“Tofacitinib has shown efficacy in managing ASUC, but concerns about postoperative complications have limited its adoption,” reported the authors in research published in Clinical Gastroenterology and Hepatology.“This study shows that tofacitinib is safe and doesn’t impair wound healing or lead to more infections if the patient needs an urgent colectomy, which is unfortunately common in this population,” senior author Jeffrey A. Berinstein, MD, of the Division of Gastroenterology and Hepatology, Michigan Medicine, Ann Arbor, Michigan, told GI & Hepatology News. 

Recent treatment advances for UC have provided significant benefits in reducing the severity of symptoms; however, about a quarter of patients go on to experience flares, with fecal urgency, rectal bleeding, and severe abdominal pain of ASUC potentially requiring hospitalization.

The standard of care for those patients is rapid induction with intravenous (IV) corticosteroids; however, up to 30% of patients don’t respond to those interventions, and even with subsequent treatment of cyclosporine and infliximab helping to reduce the risk for an urgent colectomy, patients often don’t respond, and ultimately, up to a third of patients with ASUC end up having to receive a colectomy.

While JAK inhibitor therapies, including tofacitinib and upadacitinib, have recently emerged as potentially important treatment options in such cases, showing reductions in the risk for colectomy, concerns about the drugs’ downstream biologic effects have given many clinicians reservations about their use.

“Anecdotally, gastroenterologists and surgeons have expressed concern about JAK inhibitors leading to poor wound healing, as well as increasing both intraoperative and postoperative complications, despite limited data to support these claims,” the authors wrote.

To better understand those possible risks, first author Charlotte Larson, MD, of the Department of Internal Medicine, Michigan Medicine, and colleagues conducted a multicenter, retrospective, case-control study of 109 patients hospitalized with ASUC at two centers in the US and 14 in France.

Of the patients, 41 were treated with tofacitinib and 68 with infliximab prior to colectomy. 

Among patients treated with tofacitinib, five (12.2%) received infliximab and four (9.8%) received cyclosporine rescue immediately prior to receiving tofacitinib during the index admission. In the infliximab group, one (1.5%) received rescue cyclosporine.

In a univariate analysis, the tofacitinib-treated patients showed significantly lower overall rates of postoperative complications than infliximab-treated patients (31.7% vs 64.7%; odds ratio [OR], 0.33; P = .006).

The tofacitinib-treated group also had lower rates of serious postoperative complications (12% vs 28.9; OR, 0.20; P = .016).

After adjusting for multivariate factors including age, inflammatory burden, nutrition status, 90-day cumulative corticosteroid exposure and open surgery, there was a trend favoring tofacitinib but no statistically significant difference between the two treatments in terms of serious postoperative complications (P = .061). 

However, a significantly lower rate of overall postoperative complications with tofacitinib was observed after the adjustment (odds ratio, 0.38; P = .023).

Importantly, a subanalysis showed that the 63.4% of tofacitinib-treated patients receiving the standard FDA-approved induction dose of 10 mg twice daily did indeed have significantly lower rates than infliximab-treated patients in terms of serious postoperative complications (OR, .10; P = .031), as well as overall postoperative complications (OR, 0.23; P = .003), whereas neither of the outcomes were significantly improved among the 36.6% of patients who received the higher-intensity thrice-daily tofacitinib dose (P = .3 and P = .4, respectively).

Further complicating the matter, in a previous case-control study that the research team conducted, it was the off-label, 10 mg thrice-daily dose of tofacitinib that performed favorably and was associated with a significantly lower risk for colectomy than the twice-daily dose (hazard ratio 0.28; P = .018); the twice-daily dose was not protective.

Berinstein added that a hypothesis for the benefits overall, with either dose, is that tofacitinib’s anti-inflammatory properties are key.

“We believe that lowering inflammation as much as possible, with the colon less inflamed, could be providing the benefit in lowering complications rate in surgery,” he explained.

Regarding the dosing, “it’s a careful trade-off,” Berinstein added. “Obviously, we want to avoid the need for a colectomy in the first place, as it is a life-changing surgery, but we don’t want to increase the risk of infections.” 

In other findings, the tofacitinib group had no increased risk for postoperative venous thrombotic embolisms (VTEs), which is important as tofacitinib exposure has previously been associated with an increased risk for VTEs independent of other prothrombotic factors common to patients with ASUC, including decreased ambulation, active inflammation, corticosteroid use, and major colorectal surgery.

“This observed absence of an increased VTE risk may alleviate some of the hypothetical postoperative safety concern attributed to JAK inhibitor therapy in this high-risk population,” the authors wrote.

Overall, the results underscore that “providers should feel comfortable using this medication if they need it and if they think it’s most likely to help their patients avoid colectomy,” Berinstein said.

“They should not give pause over concerns of postoperative complications because we didn’t show that,” he said.

Commenting on the study, Joseph D. Feuerstein, MD, AGAF, of the Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, noted that, in general, in patients with ASUC who fail on IV steroids, “the main treatments are infliximab, cyclosporine, or a JAK inhibitor like tofacitinib or upadacitinib, [and] knowing that if someone needs surgery, the complication rates are similar and that pre-operative use is okay is reassuring.”

Regarding the protective effect observed with some circumstances, “I don’t put too much weight into that,” he noted. “[One] could speculate that it is somehow related to faster half-life of the drug, and it might not sit around as long,” he said.

Feuerstein added that “the study design being retrospective is a limitation, but this is the best data we have to date.”

Berinstein and Feuerstein had no disclosures to report.

A version of this article appeared on Medscape.com . 

A head-to-head comparison of the JAK inhibitor drug tofacitinib and chimeric monoclonal antibody infliximab in the treatment of acute severe ulcerative colitis (ASUC) shows that, contrary to concerns, tofacitinib is not associated with worse postoperative complications and in fact may reduce the risk of the need for colectomy.

“Tofacitinib has shown efficacy in managing ASUC, but concerns about postoperative complications have limited its adoption,” reported the authors in research published in Clinical Gastroenterology and Hepatology.“This study shows that tofacitinib is safe and doesn’t impair wound healing or lead to more infections if the patient needs an urgent colectomy, which is unfortunately common in this population,” senior author Jeffrey A. Berinstein, MD, of the Division of Gastroenterology and Hepatology, Michigan Medicine, Ann Arbor, Michigan, told GI & Hepatology News. 

Recent treatment advances for UC have provided significant benefits in reducing the severity of symptoms; however, about a quarter of patients go on to experience flares, with fecal urgency, rectal bleeding, and severe abdominal pain of ASUC potentially requiring hospitalization.

The standard of care for those patients is rapid induction with intravenous (IV) corticosteroids; however, up to 30% of patients don’t respond to those interventions, and even with subsequent treatment of cyclosporine and infliximab helping to reduce the risk for an urgent colectomy, patients often don’t respond, and ultimately, up to a third of patients with ASUC end up having to receive a colectomy.

While JAK inhibitor therapies, including tofacitinib and upadacitinib, have recently emerged as potentially important treatment options in such cases, showing reductions in the risk for colectomy, concerns about the drugs’ downstream biologic effects have given many clinicians reservations about their use.

“Anecdotally, gastroenterologists and surgeons have expressed concern about JAK inhibitors leading to poor wound healing, as well as increasing both intraoperative and postoperative complications, despite limited data to support these claims,” the authors wrote.

To better understand those possible risks, first author Charlotte Larson, MD, of the Department of Internal Medicine, Michigan Medicine, and colleagues conducted a multicenter, retrospective, case-control study of 109 patients hospitalized with ASUC at two centers in the US and 14 in France.

Of the patients, 41 were treated with tofacitinib and 68 with infliximab prior to colectomy. 

Among patients treated with tofacitinib, five (12.2%) received infliximab and four (9.8%) received cyclosporine rescue immediately prior to receiving tofacitinib during the index admission. In the infliximab group, one (1.5%) received rescue cyclosporine.

In a univariate analysis, the tofacitinib-treated patients showed significantly lower overall rates of postoperative complications than infliximab-treated patients (31.7% vs 64.7%; odds ratio [OR], 0.33; P = .006).

The tofacitinib-treated group also had lower rates of serious postoperative complications (12% vs 28.9; OR, 0.20; P = .016).

After adjusting for multivariate factors including age, inflammatory burden, nutrition status, 90-day cumulative corticosteroid exposure and open surgery, there was a trend favoring tofacitinib but no statistically significant difference between the two treatments in terms of serious postoperative complications (P = .061). 

However, a significantly lower rate of overall postoperative complications with tofacitinib was observed after the adjustment (odds ratio, 0.38; P = .023).

Importantly, a subanalysis showed that the 63.4% of tofacitinib-treated patients receiving the standard FDA-approved induction dose of 10 mg twice daily did indeed have significantly lower rates than infliximab-treated patients in terms of serious postoperative complications (OR, .10; P = .031), as well as overall postoperative complications (OR, 0.23; P = .003), whereas neither of the outcomes were significantly improved among the 36.6% of patients who received the higher-intensity thrice-daily tofacitinib dose (P = .3 and P = .4, respectively).

Further complicating the matter, in a previous case-control study that the research team conducted, it was the off-label, 10 mg thrice-daily dose of tofacitinib that performed favorably and was associated with a significantly lower risk for colectomy than the twice-daily dose (hazard ratio 0.28; P = .018); the twice-daily dose was not protective.

Berinstein added that a hypothesis for the benefits overall, with either dose, is that tofacitinib’s anti-inflammatory properties are key.

“We believe that lowering inflammation as much as possible, with the colon less inflamed, could be providing the benefit in lowering complications rate in surgery,” he explained.

Regarding the dosing, “it’s a careful trade-off,” Berinstein added. “Obviously, we want to avoid the need for a colectomy in the first place, as it is a life-changing surgery, but we don’t want to increase the risk of infections.” 

In other findings, the tofacitinib group had no increased risk for postoperative venous thrombotic embolisms (VTEs), which is important as tofacitinib exposure has previously been associated with an increased risk for VTEs independent of other prothrombotic factors common to patients with ASUC, including decreased ambulation, active inflammation, corticosteroid use, and major colorectal surgery.

“This observed absence of an increased VTE risk may alleviate some of the hypothetical postoperative safety concern attributed to JAK inhibitor therapy in this high-risk population,” the authors wrote.

Overall, the results underscore that “providers should feel comfortable using this medication if they need it and if they think it’s most likely to help their patients avoid colectomy,” Berinstein said.

“They should not give pause over concerns of postoperative complications because we didn’t show that,” he said.

Commenting on the study, Joseph D. Feuerstein, MD, AGAF, of the Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, noted that, in general, in patients with ASUC who fail on IV steroids, “the main treatments are infliximab, cyclosporine, or a JAK inhibitor like tofacitinib or upadacitinib, [and] knowing that if someone needs surgery, the complication rates are similar and that pre-operative use is okay is reassuring.”

Regarding the protective effect observed with some circumstances, “I don’t put too much weight into that,” he noted. “[One] could speculate that it is somehow related to faster half-life of the drug, and it might not sit around as long,” he said.

Feuerstein added that “the study design being retrospective is a limitation, but this is the best data we have to date.”

Berinstein and Feuerstein had no disclosures to report.

A version of this article appeared on Medscape.com . 

A head-to-head comparison of the JAK inhibitor drug tofacitinib and chimeric monoclonal antibody infliximab in the treatment of acute severe ulcerative colitis (ASUC) shows that, contrary to concerns, tofacitinib is not associated with worse postoperative complications and in fact may reduce the risk of the need for colectomy.

“Tofacitinib has shown efficacy in managing ASUC, but concerns about postoperative complications have limited its adoption,” reported the authors in research published in Clinical Gastroenterology and Hepatology.“This study shows that tofacitinib is safe and doesn’t impair wound healing or lead to more infections if the patient needs an urgent colectomy, which is unfortunately common in this population,” senior author Jeffrey A. Berinstein, MD, of the Division of Gastroenterology and Hepatology, Michigan Medicine, Ann Arbor, Michigan, told GI & Hepatology News. 

Recent treatment advances for UC have provided significant benefits in reducing the severity of symptoms; however, about a quarter of patients go on to experience flares, with fecal urgency, rectal bleeding, and severe abdominal pain of ASUC potentially requiring hospitalization.

The standard of care for those patients is rapid induction with intravenous (IV) corticosteroids; however, up to 30% of patients don’t respond to those interventions, and even with subsequent treatment of cyclosporine and infliximab helping to reduce the risk for an urgent colectomy, patients often don’t respond, and ultimately, up to a third of patients with ASUC end up having to receive a colectomy.

While JAK inhibitor therapies, including tofacitinib and upadacitinib, have recently emerged as potentially important treatment options in such cases, showing reductions in the risk for colectomy, concerns about the drugs’ downstream biologic effects have given many clinicians reservations about their use.

“Anecdotally, gastroenterologists and surgeons have expressed concern about JAK inhibitors leading to poor wound healing, as well as increasing both intraoperative and postoperative complications, despite limited data to support these claims,” the authors wrote.

To better understand those possible risks, first author Charlotte Larson, MD, of the Department of Internal Medicine, Michigan Medicine, and colleagues conducted a multicenter, retrospective, case-control study of 109 patients hospitalized with ASUC at two centers in the US and 14 in France.

Of the patients, 41 were treated with tofacitinib and 68 with infliximab prior to colectomy. 

Among patients treated with tofacitinib, five (12.2%) received infliximab and four (9.8%) received cyclosporine rescue immediately prior to receiving tofacitinib during the index admission. In the infliximab group, one (1.5%) received rescue cyclosporine.

In a univariate analysis, the tofacitinib-treated patients showed significantly lower overall rates of postoperative complications than infliximab-treated patients (31.7% vs 64.7%; odds ratio [OR], 0.33; P = .006).

The tofacitinib-treated group also had lower rates of serious postoperative complications (12% vs 28.9; OR, 0.20; P = .016).

After adjusting for multivariate factors including age, inflammatory burden, nutrition status, 90-day cumulative corticosteroid exposure and open surgery, there was a trend favoring tofacitinib but no statistically significant difference between the two treatments in terms of serious postoperative complications (P = .061). 

However, a significantly lower rate of overall postoperative complications with tofacitinib was observed after the adjustment (odds ratio, 0.38; P = .023).

Importantly, a subanalysis showed that the 63.4% of tofacitinib-treated patients receiving the standard FDA-approved induction dose of 10 mg twice daily did indeed have significantly lower rates than infliximab-treated patients in terms of serious postoperative complications (OR, .10; P = .031), as well as overall postoperative complications (OR, 0.23; P = .003), whereas neither of the outcomes were significantly improved among the 36.6% of patients who received the higher-intensity thrice-daily tofacitinib dose (P = .3 and P = .4, respectively).

Further complicating the matter, in a previous case-control study that the research team conducted, it was the off-label, 10 mg thrice-daily dose of tofacitinib that performed favorably and was associated with a significantly lower risk for colectomy than the twice-daily dose (hazard ratio 0.28; P = .018); the twice-daily dose was not protective.

Berinstein added that a hypothesis for the benefits overall, with either dose, is that tofacitinib’s anti-inflammatory properties are key.

“We believe that lowering inflammation as much as possible, with the colon less inflamed, could be providing the benefit in lowering complications rate in surgery,” he explained.

Regarding the dosing, “it’s a careful trade-off,” Berinstein added. “Obviously, we want to avoid the need for a colectomy in the first place, as it is a life-changing surgery, but we don’t want to increase the risk of infections.” 

In other findings, the tofacitinib group had no increased risk for postoperative venous thrombotic embolisms (VTEs), which is important as tofacitinib exposure has previously been associated with an increased risk for VTEs independent of other prothrombotic factors common to patients with ASUC, including decreased ambulation, active inflammation, corticosteroid use, and major colorectal surgery.

“This observed absence of an increased VTE risk may alleviate some of the hypothetical postoperative safety concern attributed to JAK inhibitor therapy in this high-risk population,” the authors wrote.

Overall, the results underscore that “providers should feel comfortable using this medication if they need it and if they think it’s most likely to help their patients avoid colectomy,” Berinstein said.

“They should not give pause over concerns of postoperative complications because we didn’t show that,” he said.

Commenting on the study, Joseph D. Feuerstein, MD, AGAF, of the Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, noted that, in general, in patients with ASUC who fail on IV steroids, “the main treatments are infliximab, cyclosporine, or a JAK inhibitor like tofacitinib or upadacitinib, [and] knowing that if someone needs surgery, the complication rates are similar and that pre-operative use is okay is reassuring.”

Regarding the protective effect observed with some circumstances, “I don’t put too much weight into that,” he noted. “[One] could speculate that it is somehow related to faster half-life of the drug, and it might not sit around as long,” he said.

Feuerstein added that “the study design being retrospective is a limitation, but this is the best data we have to date.”

Berinstein and Feuerstein had no disclosures to report.

A version of this article appeared on Medscape.com . 

The American Gastroenterological Association (AGA) has released a comprehensive clinical practice update on lifting agents for endoscopic surgery.

Published in Clinical Gastroenterology and Hepatology, the commentary reviews available agents and provides clinically relevant commentary on their indications and use — with the caveat that it is not a formal systematic review but rather empirical advice for endoscopists. No formal rating of the quality of evidence or strength of recommendations was performed.

Led by Tobias Zuchelli, MD, a clinical associate professor at Michigan State University and a gastroenterologist at the Henry Ford Health System in Detroit, the expert panel noted that endoscopists are increasingly resecting precancerous lesions and early cancers of the gastrointestinal tract.

“Although new endoscopic procedures have been developed, there had not been much in terms of high-quality guidance on lifting agents,” panelist Amit V. Patel, MD, a professor of medicine at Duke University and director of Endoscopy at Durham Veterans Affairs Medical Center in Durham, North Carolina, told GI & Hepatology News. “With our better understanding and use of techniques, this commentary was timely. It summarizes the available data on the topic and includes our clinical experiences.”

Filling that knowledge gap, the document reviews in detail the timing and methods of agent injection according to procedure type, including the dynamic needle approach, the empirical merits of different agents such as saline (with or without blue contrast) and viscous agents, as well as lift-enhancing assistive devices — for example, the ERBEJET 2 high-pressure water jet, an adjustable hydrosurgical device to facilitate lifting. A chart provides an at-a-glance summary of agents and their pros and cons.

“The feedback from gastroenterologists so far has been quite positive on social media and on GI channels,” Patel said.

Endoscopic resection has evolved from snare polypectomy to endoscopic mucosal resection (EMR) and now, endoscopic submucosal dissection (ESD). The primary benefit of submucosal lifting is the creation of a separating submucosal cushion between the lesion and muscularis propria (MP), which reduces the risk for immediate or delayed perforation of the muscle. Adding a contrast agent also demarcates lesion margins and stains the submucosa, which is fundamental to ESD and allows for assessment of MP injury during EMR.

For decades, homemade solutions were used to lift lesions before removal, with the sentinel agent being normal saline, later mixed with a blue contrast agent, usually indigo carmine or methylene blue. The authors noted that some endoscopists performing ESD start the submucosal injection and incision using a prepackaged viscous solution. “The endoscopist may continue with the viscous fluid or transition to saline or another less expensive solution,” they wrote.

Saline tends to dissipate more quickly than viscous solutions, however. In 2015, the polymer compound SIC-8000 became the first FDA-approved submucosal injection agent. Since then, several other fluids have come on the market, although homemade agents remain available.

Among the update’s recommendations, the fluid selected for EMR should be determined by lesion size, predicted histology, and endoscopist preference. Based on the US Multi-Society Task Force (USMSTF) on Colorectal Cancer, submucosal injection is optional for nonpedunculated colorectal lesions (NPCRLs) of intermediate size (10-19 mm).

Cold snare polypectomy without submucosal injection was later found to be non-inferior to other resection methods utilizing submucosal injection for NPCRLs ≤ 15 mm. 

The update noted that the USMSTF considers EMR first-line therapy for most NPCRLs ≥ 20 mm and advocates viscous solutions as preferred, while the use of lifting agents for pedunculated polyps is generally at the discretion of the endoscopist.

For Patel, the main “clinical pearls” in the update are adding a contrast agent to normal saline, using a viscous agent for cold EMR, and manipulating the injection needle first tangentially and then dynamically toward the lumen to maximize separation of the lesion.

In terms of the ideal, an optimal lifting solution would be readily available, inexpensive, and premixed, providing a sustained submucosal cushion. “However, this ideal solution currently does not exist. Injection fluids should, therefore, be selected based on planned resection method, predicted histology, local expertise and preferences, and cost,” the panelists wrote.

Added Patel, “A lot of the agents out there check most of these boxes, but we’re hoping for further development toward the ideal.”

Offering a nonparticipant’s perspective on the overview, Wasseem Skef, MD, a gastroenterologist at UTHealth Houston, found the update very useful. “It always helps to have the literature summarized,” he told GI & Hepatology News. “It’s a pretty balanced review that pulls together the various options but allows people to stick to their preferred practice.”

In his practice, the lifting agent selected depends on the type of resection. “Viscous agents are generally more popular for EMR-type resections,” Skef said. One unanswered question, he noted, is whether adding a hemostatic agent would be superior to a viscous agent alone. “But overall, this is a nice summary of available agents. Gastroenterologists should consider these different options if doing procedures like EMR.”

This review was sponsored by the AGA Institute. 

Zuchelli is a consultant for Boston Scientific. Patel consults for Medpace, Renexxion, and Sanofi. Skef reported having no relevant disclosures.

A version of this article appeared on Medscape.com . 

The American Gastroenterological Association (AGA) has released a comprehensive clinical practice update on lifting agents for endoscopic surgery.

Published in Clinical Gastroenterology and Hepatology, the commentary reviews available agents and provides clinically relevant commentary on their indications and use — with the caveat that it is not a formal systematic review but rather empirical advice for endoscopists. No formal rating of the quality of evidence or strength of recommendations was performed.

Led by Tobias Zuchelli, MD, a clinical associate professor at Michigan State University and a gastroenterologist at the Henry Ford Health System in Detroit, the expert panel noted that endoscopists are increasingly resecting precancerous lesions and early cancers of the gastrointestinal tract.

“Although new endoscopic procedures have been developed, there had not been much in terms of high-quality guidance on lifting agents,” panelist Amit V. Patel, MD, a professor of medicine at Duke University and director of Endoscopy at Durham Veterans Affairs Medical Center in Durham, North Carolina, told GI & Hepatology News. “With our better understanding and use of techniques, this commentary was timely. It summarizes the available data on the topic and includes our clinical experiences.”

Filling that knowledge gap, the document reviews in detail the timing and methods of agent injection according to procedure type, including the dynamic needle approach, the empirical merits of different agents such as saline (with or without blue contrast) and viscous agents, as well as lift-enhancing assistive devices — for example, the ERBEJET 2 high-pressure water jet, an adjustable hydrosurgical device to facilitate lifting. A chart provides an at-a-glance summary of agents and their pros and cons.

“The feedback from gastroenterologists so far has been quite positive on social media and on GI channels,” Patel said.

Endoscopic resection has evolved from snare polypectomy to endoscopic mucosal resection (EMR) and now, endoscopic submucosal dissection (ESD). The primary benefit of submucosal lifting is the creation of a separating submucosal cushion between the lesion and muscularis propria (MP), which reduces the risk for immediate or delayed perforation of the muscle. Adding a contrast agent also demarcates lesion margins and stains the submucosa, which is fundamental to ESD and allows for assessment of MP injury during EMR.

For decades, homemade solutions were used to lift lesions before removal, with the sentinel agent being normal saline, later mixed with a blue contrast agent, usually indigo carmine or methylene blue. The authors noted that some endoscopists performing ESD start the submucosal injection and incision using a prepackaged viscous solution. “The endoscopist may continue with the viscous fluid or transition to saline or another less expensive solution,” they wrote.

Saline tends to dissipate more quickly than viscous solutions, however. In 2015, the polymer compound SIC-8000 became the first FDA-approved submucosal injection agent. Since then, several other fluids have come on the market, although homemade agents remain available.

Among the update’s recommendations, the fluid selected for EMR should be determined by lesion size, predicted histology, and endoscopist preference. Based on the US Multi-Society Task Force (USMSTF) on Colorectal Cancer, submucosal injection is optional for nonpedunculated colorectal lesions (NPCRLs) of intermediate size (10-19 mm).

Cold snare polypectomy without submucosal injection was later found to be non-inferior to other resection methods utilizing submucosal injection for NPCRLs ≤ 15 mm. 

The update noted that the USMSTF considers EMR first-line therapy for most NPCRLs ≥ 20 mm and advocates viscous solutions as preferred, while the use of lifting agents for pedunculated polyps is generally at the discretion of the endoscopist.

For Patel, the main “clinical pearls” in the update are adding a contrast agent to normal saline, using a viscous agent for cold EMR, and manipulating the injection needle first tangentially and then dynamically toward the lumen to maximize separation of the lesion.

In terms of the ideal, an optimal lifting solution would be readily available, inexpensive, and premixed, providing a sustained submucosal cushion. “However, this ideal solution currently does not exist. Injection fluids should, therefore, be selected based on planned resection method, predicted histology, local expertise and preferences, and cost,” the panelists wrote.

Added Patel, “A lot of the agents out there check most of these boxes, but we’re hoping for further development toward the ideal.”

Offering a nonparticipant’s perspective on the overview, Wasseem Skef, MD, a gastroenterologist at UTHealth Houston, found the update very useful. “It always helps to have the literature summarized,” he told GI & Hepatology News. “It’s a pretty balanced review that pulls together the various options but allows people to stick to their preferred practice.”

In his practice, the lifting agent selected depends on the type of resection. “Viscous agents are generally more popular for EMR-type resections,” Skef said. One unanswered question, he noted, is whether adding a hemostatic agent would be superior to a viscous agent alone. “But overall, this is a nice summary of available agents. Gastroenterologists should consider these different options if doing procedures like EMR.”

This review was sponsored by the AGA Institute. 

Zuchelli is a consultant for Boston Scientific. Patel consults for Medpace, Renexxion, and Sanofi. Skef reported having no relevant disclosures.

A version of this article appeared on Medscape.com . 

The American Gastroenterological Association (AGA) has released a comprehensive clinical practice update on lifting agents for endoscopic surgery.

Published in Clinical Gastroenterology and Hepatology, the commentary reviews available agents and provides clinically relevant commentary on their indications and use — with the caveat that it is not a formal systematic review but rather empirical advice for endoscopists. No formal rating of the quality of evidence or strength of recommendations was performed.

Led by Tobias Zuchelli, MD, a clinical associate professor at Michigan State University and a gastroenterologist at the Henry Ford Health System in Detroit, the expert panel noted that endoscopists are increasingly resecting precancerous lesions and early cancers of the gastrointestinal tract.

“Although new endoscopic procedures have been developed, there had not been much in terms of high-quality guidance on lifting agents,” panelist Amit V. Patel, MD, a professor of medicine at Duke University and director of Endoscopy at Durham Veterans Affairs Medical Center in Durham, North Carolina, told GI & Hepatology News. “With our better understanding and use of techniques, this commentary was timely. It summarizes the available data on the topic and includes our clinical experiences.”

Filling that knowledge gap, the document reviews in detail the timing and methods of agent injection according to procedure type, including the dynamic needle approach, the empirical merits of different agents such as saline (with or without blue contrast) and viscous agents, as well as lift-enhancing assistive devices — for example, the ERBEJET 2 high-pressure water jet, an adjustable hydrosurgical device to facilitate lifting. A chart provides an at-a-glance summary of agents and their pros and cons.

“The feedback from gastroenterologists so far has been quite positive on social media and on GI channels,” Patel said.

Endoscopic resection has evolved from snare polypectomy to endoscopic mucosal resection (EMR) and now, endoscopic submucosal dissection (ESD). The primary benefit of submucosal lifting is the creation of a separating submucosal cushion between the lesion and muscularis propria (MP), which reduces the risk for immediate or delayed perforation of the muscle. Adding a contrast agent also demarcates lesion margins and stains the submucosa, which is fundamental to ESD and allows for assessment of MP injury during EMR.

For decades, homemade solutions were used to lift lesions before removal, with the sentinel agent being normal saline, later mixed with a blue contrast agent, usually indigo carmine or methylene blue. The authors noted that some endoscopists performing ESD start the submucosal injection and incision using a prepackaged viscous solution. “The endoscopist may continue with the viscous fluid or transition to saline or another less expensive solution,” they wrote.

Saline tends to dissipate more quickly than viscous solutions, however. In 2015, the polymer compound SIC-8000 became the first FDA-approved submucosal injection agent. Since then, several other fluids have come on the market, although homemade agents remain available.

Among the update’s recommendations, the fluid selected for EMR should be determined by lesion size, predicted histology, and endoscopist preference. Based on the US Multi-Society Task Force (USMSTF) on Colorectal Cancer, submucosal injection is optional for nonpedunculated colorectal lesions (NPCRLs) of intermediate size (10-19 mm).

Cold snare polypectomy without submucosal injection was later found to be non-inferior to other resection methods utilizing submucosal injection for NPCRLs ≤ 15 mm. 

The update noted that the USMSTF considers EMR first-line therapy for most NPCRLs ≥ 20 mm and advocates viscous solutions as preferred, while the use of lifting agents for pedunculated polyps is generally at the discretion of the endoscopist.

For Patel, the main “clinical pearls” in the update are adding a contrast agent to normal saline, using a viscous agent for cold EMR, and manipulating the injection needle first tangentially and then dynamically toward the lumen to maximize separation of the lesion.

In terms of the ideal, an optimal lifting solution would be readily available, inexpensive, and premixed, providing a sustained submucosal cushion. “However, this ideal solution currently does not exist. Injection fluids should, therefore, be selected based on planned resection method, predicted histology, local expertise and preferences, and cost,” the panelists wrote.

Added Patel, “A lot of the agents out there check most of these boxes, but we’re hoping for further development toward the ideal.”

Offering a nonparticipant’s perspective on the overview, Wasseem Skef, MD, a gastroenterologist at UTHealth Houston, found the update very useful. “It always helps to have the literature summarized,” he told GI & Hepatology News. “It’s a pretty balanced review that pulls together the various options but allows people to stick to their preferred practice.”

In his practice, the lifting agent selected depends on the type of resection. “Viscous agents are generally more popular for EMR-type resections,” Skef said. One unanswered question, he noted, is whether adding a hemostatic agent would be superior to a viscous agent alone. “But overall, this is a nice summary of available agents. Gastroenterologists should consider these different options if doing procedures like EMR.”

This review was sponsored by the AGA Institute. 

Zuchelli is a consultant for Boston Scientific. Patel consults for Medpace, Renexxion, and Sanofi. Skef reported having no relevant disclosures.

A version of this article appeared on Medscape.com . 

AGA has issued an updated pragmatic review on sclerosing mesenteritis (SM). Published in Clinical Gastroenterology and Hepatology, the update evaluates available evidence for diagnosis and treatment and examines opportunities for future research in SM, previously known by such names as misty mesentery, mesenteric panniculitis, and inflammatory pseudotumor.

Led by Mark T. Worthington, MD, AGAF, a professor of medicine in the Division of Gastroenterology and Hepatology at the University of Virginia in Charlottesville, Virginia, an expert AGA panel described SM as an uncommon benign idiopathic autoimmune disease of the mesenteric fat. Although of poorly understood etiology, gastroenterologists need to be prepared to diagnose it.

“CT radiologists increasingly are reporting SM and related lesions, such as misty mesentery,” Worthington told GI & Hepatology News. “We are also seeing new SM cases caused by immune checkpoint inhibitors in cancer treatment, and the oncologists ask us to manage this because it interferes with the treatment of the underlying malignancy. Those are often readily treated because we catch them so early.” Metabolic syndrome and associated conditions increase the risk for SM, as does aging.

The recent changes are intended to help clinicians predict disease activity and the need for other testing or treatment. “For instance, most cases are indolent and do not require aggressive treatment — often no treatment at all — but for those that are aggressive, we want the clinician to be able to identify those and make sure the treatment is appropriate. The aggressive cases may warrant tertiary referral,” Worthington said. “A secondary cancer is a possibility in this condition, so drawing from the SM radiology studies, we try to help the clinician decide who needs other testing, such as PET-CT or biopsy, and who can be monitored.”

As many as 60% of cases are asymptomatic, requiring no treatment. Abdominal pain is the most frequent symptom and its location on clinical examination should correspond to the SM lesion on imaging. Treatment involves anti-inflammatory medications tailored to disease severity and clinical response.

No biopsy is not necessary if the lesion meets three of the five CT criteria reported by B. Coulier and has no features of more aggressive disease or malignancy. Although some have suggested that SM may be a paraneoplastic syndrome, current evidence does not support this. SM needs to be differentiated from other diagnoses such as non-Hodgkin’s lymphoma, peritoneal carcinomatosis, and mesenteric fibromatosis.

“There are now CT guidelines for who actually has SM, who needs a biopsy or a PET-CT to rule-out malignancy, and who doesn’t,” said Worthington. “Radiologists do not always use the Coulier criteria for diagnosis, but often they will with encouragement. From this review, a GI clinician should be able to identify SM on CT.”

Epidemiologically, retrospective CT studies have reported a frequency of 0.6%-1.1%, the panelists noted. And while demographic data are limited, a large early case series reported that SM patients had a mean age of 55 years and more likely to be men and of White race.

Patients with SM do not have a higher prevalence of autoimmunity in general, but may have increased rates of metabolic syndrome, obesity, coronary artery disease, and urolithiasis, the panelists noted.

The update allows room for differences in clinical judgment. “For instance, a longer or more frequent CT surveillance interval can be justified depending on the patient’s findings, and no one should feel locked in by these recommendations,” Worthington said.

 

Medical Therapy

Although there is no surgical cure, pharmacologic options are many. These include prednisone, tamoxifen, colchicine, azathioprine, thalidomide, cyclophosphamide, and methotrexate, as well as the biologics rituximab, infliximab and ustekinumab. Current corticosteroid-based therapies often require months to achieve a clinical response, however.

Bowel obstruction is managed nonoperatively when feasible, but medically refractory disease may require surgical bypass.

Offering his perspective on the guidance but not involved in its formulation, Gastroenterologist Stephen B. Hanauer, MD, AGAF, a professor of medicine at Northwestern Medicine in Chicago, said, “The most useful component of the practical review is the algorithm for diagnosis and determination when biopsy or follow-up imaging is reasonable in the absence of evidence.” He stressed that the recommendations are pragmatic rather than evidence-based “as there are no controlled trials and the presentation is heterogeneous.”

Hanauer added that none of the recommended treatments have been shown to impact reduction on imaging. “Hence, all of the treatments are empiric without biological or imaging endpoints.”

In his experience, patients with inflammatory features are the best candidates for immune-directed therapies as reduction in inflammatory markers is a potential endpoint, although no therapies have demonstrated an effect on imaging or progression. “As an IBD doctor, I favor steroids and azathioprine or anti-TNF directed therapy, but again, there is no evidence beyond reports of symptomatic improvement.” 

Worthington and colleagues agreed that treatment protocols have developed empirically. “Future investigation for symptomatic SM should focus on the nature of the inflammatory response, including causative cytokines and other proinflammatory mediators, the goal being targeted therapy with fewer side effects and a more rapid clinical response,” they wrote.

Currently, said Worthington, the biggest gaps remain in treatment. “Even the best studies are small and anecdotal, and we do not know the cytokine or other proinflammatory mediators.”

This guidance was supported by the AGA. Worthington reported renumeration from TriCity Surgery Center, Prescott, Ariz. Hanauer had no conflicts of interest relevant to their comments.

A version of this article appeared on Medscape.com.

AGA has issued an updated pragmatic review on sclerosing mesenteritis (SM). Published in Clinical Gastroenterology and Hepatology, the update evaluates available evidence for diagnosis and treatment and examines opportunities for future research in SM, previously known by such names as misty mesentery, mesenteric panniculitis, and inflammatory pseudotumor.

Led by Mark T. Worthington, MD, AGAF, a professor of medicine in the Division of Gastroenterology and Hepatology at the University of Virginia in Charlottesville, Virginia, an expert AGA panel described SM as an uncommon benign idiopathic autoimmune disease of the mesenteric fat. Although of poorly understood etiology, gastroenterologists need to be prepared to diagnose it.

“CT radiologists increasingly are reporting SM and related lesions, such as misty mesentery,” Worthington told GI & Hepatology News. “We are also seeing new SM cases caused by immune checkpoint inhibitors in cancer treatment, and the oncologists ask us to manage this because it interferes with the treatment of the underlying malignancy. Those are often readily treated because we catch them so early.” Metabolic syndrome and associated conditions increase the risk for SM, as does aging.

The recent changes are intended to help clinicians predict disease activity and the need for other testing or treatment. “For instance, most cases are indolent and do not require aggressive treatment — often no treatment at all — but for those that are aggressive, we want the clinician to be able to identify those and make sure the treatment is appropriate. The aggressive cases may warrant tertiary referral,” Worthington said. “A secondary cancer is a possibility in this condition, so drawing from the SM radiology studies, we try to help the clinician decide who needs other testing, such as PET-CT or biopsy, and who can be monitored.”

As many as 60% of cases are asymptomatic, requiring no treatment. Abdominal pain is the most frequent symptom and its location on clinical examination should correspond to the SM lesion on imaging. Treatment involves anti-inflammatory medications tailored to disease severity and clinical response.

No biopsy is not necessary if the lesion meets three of the five CT criteria reported by B. Coulier and has no features of more aggressive disease or malignancy. Although some have suggested that SM may be a paraneoplastic syndrome, current evidence does not support this. SM needs to be differentiated from other diagnoses such as non-Hodgkin’s lymphoma, peritoneal carcinomatosis, and mesenteric fibromatosis.

“There are now CT guidelines for who actually has SM, who needs a biopsy or a PET-CT to rule-out malignancy, and who doesn’t,” said Worthington. “Radiologists do not always use the Coulier criteria for diagnosis, but often they will with encouragement. From this review, a GI clinician should be able to identify SM on CT.”

Epidemiologically, retrospective CT studies have reported a frequency of 0.6%-1.1%, the panelists noted. And while demographic data are limited, a large early case series reported that SM patients had a mean age of 55 years and more likely to be men and of White race.

Patients with SM do not have a higher prevalence of autoimmunity in general, but may have increased rates of metabolic syndrome, obesity, coronary artery disease, and urolithiasis, the panelists noted.

The update allows room for differences in clinical judgment. “For instance, a longer or more frequent CT surveillance interval can be justified depending on the patient’s findings, and no one should feel locked in by these recommendations,” Worthington said.

 

Medical Therapy

Although there is no surgical cure, pharmacologic options are many. These include prednisone, tamoxifen, colchicine, azathioprine, thalidomide, cyclophosphamide, and methotrexate, as well as the biologics rituximab, infliximab and ustekinumab. Current corticosteroid-based therapies often require months to achieve a clinical response, however.

Bowel obstruction is managed nonoperatively when feasible, but medically refractory disease may require surgical bypass.

Offering his perspective on the guidance but not involved in its formulation, Gastroenterologist Stephen B. Hanauer, MD, AGAF, a professor of medicine at Northwestern Medicine in Chicago, said, “The most useful component of the practical review is the algorithm for diagnosis and determination when biopsy or follow-up imaging is reasonable in the absence of evidence.” He stressed that the recommendations are pragmatic rather than evidence-based “as there are no controlled trials and the presentation is heterogeneous.”

Hanauer added that none of the recommended treatments have been shown to impact reduction on imaging. “Hence, all of the treatments are empiric without biological or imaging endpoints.”

In his experience, patients with inflammatory features are the best candidates for immune-directed therapies as reduction in inflammatory markers is a potential endpoint, although no therapies have demonstrated an effect on imaging or progression. “As an IBD doctor, I favor steroids and azathioprine or anti-TNF directed therapy, but again, there is no evidence beyond reports of symptomatic improvement.” 

Worthington and colleagues agreed that treatment protocols have developed empirically. “Future investigation for symptomatic SM should focus on the nature of the inflammatory response, including causative cytokines and other proinflammatory mediators, the goal being targeted therapy with fewer side effects and a more rapid clinical response,” they wrote.

Currently, said Worthington, the biggest gaps remain in treatment. “Even the best studies are small and anecdotal, and we do not know the cytokine or other proinflammatory mediators.”

This guidance was supported by the AGA. Worthington reported renumeration from TriCity Surgery Center, Prescott, Ariz. Hanauer had no conflicts of interest relevant to their comments.

A version of this article appeared on Medscape.com.

AGA has issued an updated pragmatic review on sclerosing mesenteritis (SM). Published in Clinical Gastroenterology and Hepatology, the update evaluates available evidence for diagnosis and treatment and examines opportunities for future research in SM, previously known by such names as misty mesentery, mesenteric panniculitis, and inflammatory pseudotumor.

Led by Mark T. Worthington, MD, AGAF, a professor of medicine in the Division of Gastroenterology and Hepatology at the University of Virginia in Charlottesville, Virginia, an expert AGA panel described SM as an uncommon benign idiopathic autoimmune disease of the mesenteric fat. Although of poorly understood etiology, gastroenterologists need to be prepared to diagnose it.

“CT radiologists increasingly are reporting SM and related lesions, such as misty mesentery,” Worthington told GI & Hepatology News. “We are also seeing new SM cases caused by immune checkpoint inhibitors in cancer treatment, and the oncologists ask us to manage this because it interferes with the treatment of the underlying malignancy. Those are often readily treated because we catch them so early.” Metabolic syndrome and associated conditions increase the risk for SM, as does aging.

The recent changes are intended to help clinicians predict disease activity and the need for other testing or treatment. “For instance, most cases are indolent and do not require aggressive treatment — often no treatment at all — but for those that are aggressive, we want the clinician to be able to identify those and make sure the treatment is appropriate. The aggressive cases may warrant tertiary referral,” Worthington said. “A secondary cancer is a possibility in this condition, so drawing from the SM radiology studies, we try to help the clinician decide who needs other testing, such as PET-CT or biopsy, and who can be monitored.”

As many as 60% of cases are asymptomatic, requiring no treatment. Abdominal pain is the most frequent symptom and its location on clinical examination should correspond to the SM lesion on imaging. Treatment involves anti-inflammatory medications tailored to disease severity and clinical response.

No biopsy is not necessary if the lesion meets three of the five CT criteria reported by B. Coulier and has no features of more aggressive disease or malignancy. Although some have suggested that SM may be a paraneoplastic syndrome, current evidence does not support this. SM needs to be differentiated from other diagnoses such as non-Hodgkin’s lymphoma, peritoneal carcinomatosis, and mesenteric fibromatosis.

“There are now CT guidelines for who actually has SM, who needs a biopsy or a PET-CT to rule-out malignancy, and who doesn’t,” said Worthington. “Radiologists do not always use the Coulier criteria for diagnosis, but often they will with encouragement. From this review, a GI clinician should be able to identify SM on CT.”

Epidemiologically, retrospective CT studies have reported a frequency of 0.6%-1.1%, the panelists noted. And while demographic data are limited, a large early case series reported that SM patients had a mean age of 55 years and more likely to be men and of White race.

Patients with SM do not have a higher prevalence of autoimmunity in general, but may have increased rates of metabolic syndrome, obesity, coronary artery disease, and urolithiasis, the panelists noted.

The update allows room for differences in clinical judgment. “For instance, a longer or more frequent CT surveillance interval can be justified depending on the patient’s findings, and no one should feel locked in by these recommendations,” Worthington said.

 

Medical Therapy

Although there is no surgical cure, pharmacologic options are many. These include prednisone, tamoxifen, colchicine, azathioprine, thalidomide, cyclophosphamide, and methotrexate, as well as the biologics rituximab, infliximab and ustekinumab. Current corticosteroid-based therapies often require months to achieve a clinical response, however.

Bowel obstruction is managed nonoperatively when feasible, but medically refractory disease may require surgical bypass.

Offering his perspective on the guidance but not involved in its formulation, Gastroenterologist Stephen B. Hanauer, MD, AGAF, a professor of medicine at Northwestern Medicine in Chicago, said, “The most useful component of the practical review is the algorithm for diagnosis and determination when biopsy or follow-up imaging is reasonable in the absence of evidence.” He stressed that the recommendations are pragmatic rather than evidence-based “as there are no controlled trials and the presentation is heterogeneous.”

Hanauer added that none of the recommended treatments have been shown to impact reduction on imaging. “Hence, all of the treatments are empiric without biological or imaging endpoints.”

In his experience, patients with inflammatory features are the best candidates for immune-directed therapies as reduction in inflammatory markers is a potential endpoint, although no therapies have demonstrated an effect on imaging or progression. “As an IBD doctor, I favor steroids and azathioprine or anti-TNF directed therapy, but again, there is no evidence beyond reports of symptomatic improvement.” 

Worthington and colleagues agreed that treatment protocols have developed empirically. “Future investigation for symptomatic SM should focus on the nature of the inflammatory response, including causative cytokines and other proinflammatory mediators, the goal being targeted therapy with fewer side effects and a more rapid clinical response,” they wrote.

Currently, said Worthington, the biggest gaps remain in treatment. “Even the best studies are small and anecdotal, and we do not know the cytokine or other proinflammatory mediators.”

This guidance was supported by the AGA. Worthington reported renumeration from TriCity Surgery Center, Prescott, Ariz. Hanauer had no conflicts of interest relevant to their comments.

A version of this article appeared on Medscape.com.

Think your patient may have celiac disease? The harsh reality is that current diagnostic tests require patients to consume gluten for an accurate diagnosis, which poses challenges for individuals already avoiding gluten.

A more tolerable approach appears to be on the horizon. Researchers in Australia have developed a blood test that can identify celiac disease with high sensitivity and specificity, even without consuming gluten.

“This is a simple and accurate test that can provide a diagnosis within a very short time frame, without the need for patients to continue eating gluten and feeling sick, or to wait months for a gastroscopy,” Olivia Moscatelli, PhD candidate, Tye-Din Lab, Walter and Eliza Hall Institute and University of Melbourne, Parkville, Australia, told GI & Hepatology News.

The study was published in Gastroenterology.

 

Most Cases Go Undiagnosed

Celiac disease is an autoimmune disorder triggered by gluten found in wheat, rye, and barley. The only available treatment is a strict, life-long gluten-free diet.

The global prevalence of celiac disease is estimated at around 1%-2%, with 50%-80% of cases either undiagnosed or diagnosed late. That’s because the current reliable diagnosis of celiac disease requires the intake of gluten, which may deter people from seeking a diagnosis.

In earlier work, the researchers, working with Robert Anderson, MBChB, BMedSc, PhD, AGAF, now with Novoviah Pharmaceuticals, made the unexpected discovery that interleukin-2 (IL-2) spiked in the blood of people with celiac disease shortly after they ate gluten.

But would this signal be present when no gluten had been consumed?

The team developed and tested a simple whole blood assay measuring IL-2 release (WBAIL- 2) for detecting gluten-specific T cells to aid in diagnosing celiac disease.

They collected blood samples from 181 volunteers — 75 with treated celiac disease on a gluten-free diet, 13 with active untreated celiac disease, 32 with nonceliac gluten sensitivity and 61 healthy controls. The blood samples were mixed with gluten in a test tube for a day to see if the IL-2 signal appeared.

The WBAIL-2 assay demonstrated high accuracy for celiac disease, even in patients following a strict gluten-free diet.

For patients with HLA-DQ2.5+ genetics, sensitivity was 90% and specificity was 95%, with lower sensitivity (56%) for patients with HLA-DQ8+ celiac disease.

The WBAIL-2 assay correlated strongly with the frequency of tetramer-positive gluten-specific CD4+ T cells used to diagnose celiac disease and monitor treatment effectiveness, and with serum IL-2 levels after gluten challenge.

The strength of the IL-2 signal correlated with the severity of a patient’s symptoms, “allowing us to predict how severely a person with celiac disease might react to gluten, without them actually having to eat it,” Moscatelli said in a news release.

“Current diagnostic practice involves a blood-based serology test followed by a confirmatory gastroscopy if positive. Both tests require the patient to eat gluten daily for 6-12 weeks prior for accurate results. We envision the new blood test (IL-2 whole blood assay) will replace the invasive gastroscopy as the confirmatory test following positive serology,” Moscatelli told GI & Hepatology News.

“In people already following a gluten-free diet, we propose they would have this new blood test done on two separate occasions and two positive results would be required for a celiac diagnosis. This would allow a large number of people who previously have been unable to go through the current diagnostic process to receive a diagnosis,” Moscatelli said.

 

Practice Changing Potential 

A blood-based test that can accurately detect celiac disease without the need for a gluten challenge would be “welcome and practice changing,” said Christopher Cao, MD, director, Celiac Disease Program, Division of Gastroenterology, Mount Sinai Health System, New York City.

“A typical ‘gluten challenge’ involves eating the equivalent of 1-2 slices of bread daily for the course of 6 weeks, and this may be incredibly difficult for patients who have already been on a gluten-free diet prior to an official celiac disease diagnosis. Inability to perform a gluten challenge limits the ability to make an accurate celiac disease diagnosis,” Cao told GI & Hepatology News.

“This study shows that gluten-stimulated interleukin release 2 assays may correlate with the presence of pathogenic gluten-specific CD4+ T cell response in celiac disease,” Cao noted.

He cautioned that “further large cohort, multicenter prospective studies are needed to assess generalizability and may be helpful in evaluating the accuracy of WBAIL-2 in non-HLA DQ2.5 genotypes.” 

Other considerations prior to implementation may include reproducibility across different laboratories and overall cost effectiveness, Cao said. “Ultimately in clinic, the role of WBAIL-2 will need to be better defined within the algorithm of celiac disease testing,” he added.

 

The Path Ahead

The researchers plan to test the performance of the IL-2 whole blood assay in a pediatric cohort, as well as in other countries to demonstrate the reproducibility of the test. In these studies, the test will likely be performed alongside the current diagnostic tests (serology and gastroscopy), Moscatelli told GI & Hepatology News.

“There are some validation studies starting in other countries already as many celiac clinicians globally are interested in bringing this test to their clinical practice. I believe the plan is to have this as an approved diagnostic test for celiac disease worldwide,” she said.

Novoviah Pharmaceuticals is managing the commercialization of the test, and the plan is to get it into clinical practice in the next 2 years, Moscatelli said.

The research was supported by Coeliac Australia, Novoviah Pharmaceuticals (who provided the proprietary test for this study), Beck Family Foundation, Butterfield Family, the Veith Foundation. A complete list of author disclosures is available with the original article. Cao had no relevant disclosures.

A version of this article appeared on Medscape.com.

Think your patient may have celiac disease? The harsh reality is that current diagnostic tests require patients to consume gluten for an accurate diagnosis, which poses challenges for individuals already avoiding gluten.

A more tolerable approach appears to be on the horizon. Researchers in Australia have developed a blood test that can identify celiac disease with high sensitivity and specificity, even without consuming gluten.

“This is a simple and accurate test that can provide a diagnosis within a very short time frame, without the need for patients to continue eating gluten and feeling sick, or to wait months for a gastroscopy,” Olivia Moscatelli, PhD candidate, Tye-Din Lab, Walter and Eliza Hall Institute and University of Melbourne, Parkville, Australia, told GI & Hepatology News.

The study was published in Gastroenterology.

 

Most Cases Go Undiagnosed

Celiac disease is an autoimmune disorder triggered by gluten found in wheat, rye, and barley. The only available treatment is a strict, life-long gluten-free diet.

The global prevalence of celiac disease is estimated at around 1%-2%, with 50%-80% of cases either undiagnosed or diagnosed late. That’s because the current reliable diagnosis of celiac disease requires the intake of gluten, which may deter people from seeking a diagnosis.

In earlier work, the researchers, working with Robert Anderson, MBChB, BMedSc, PhD, AGAF, now with Novoviah Pharmaceuticals, made the unexpected discovery that interleukin-2 (IL-2) spiked in the blood of people with celiac disease shortly after they ate gluten.

But would this signal be present when no gluten had been consumed?

The team developed and tested a simple whole blood assay measuring IL-2 release (WBAIL- 2) for detecting gluten-specific T cells to aid in diagnosing celiac disease.

They collected blood samples from 181 volunteers — 75 with treated celiac disease on a gluten-free diet, 13 with active untreated celiac disease, 32 with nonceliac gluten sensitivity and 61 healthy controls. The blood samples were mixed with gluten in a test tube for a day to see if the IL-2 signal appeared.

The WBAIL-2 assay demonstrated high accuracy for celiac disease, even in patients following a strict gluten-free diet.

For patients with HLA-DQ2.5+ genetics, sensitivity was 90% and specificity was 95%, with lower sensitivity (56%) for patients with HLA-DQ8+ celiac disease.

The WBAIL-2 assay correlated strongly with the frequency of tetramer-positive gluten-specific CD4+ T cells used to diagnose celiac disease and monitor treatment effectiveness, and with serum IL-2 levels after gluten challenge.

The strength of the IL-2 signal correlated with the severity of a patient’s symptoms, “allowing us to predict how severely a person with celiac disease might react to gluten, without them actually having to eat it,” Moscatelli said in a news release.

“Current diagnostic practice involves a blood-based serology test followed by a confirmatory gastroscopy if positive. Both tests require the patient to eat gluten daily for 6-12 weeks prior for accurate results. We envision the new blood test (IL-2 whole blood assay) will replace the invasive gastroscopy as the confirmatory test following positive serology,” Moscatelli told GI & Hepatology News.

“In people already following a gluten-free diet, we propose they would have this new blood test done on two separate occasions and two positive results would be required for a celiac diagnosis. This would allow a large number of people who previously have been unable to go through the current diagnostic process to receive a diagnosis,” Moscatelli said.

 

Practice Changing Potential 

A blood-based test that can accurately detect celiac disease without the need for a gluten challenge would be “welcome and practice changing,” said Christopher Cao, MD, director, Celiac Disease Program, Division of Gastroenterology, Mount Sinai Health System, New York City.

“A typical ‘gluten challenge’ involves eating the equivalent of 1-2 slices of bread daily for the course of 6 weeks, and this may be incredibly difficult for patients who have already been on a gluten-free diet prior to an official celiac disease diagnosis. Inability to perform a gluten challenge limits the ability to make an accurate celiac disease diagnosis,” Cao told GI & Hepatology News.

“This study shows that gluten-stimulated interleukin release 2 assays may correlate with the presence of pathogenic gluten-specific CD4+ T cell response in celiac disease,” Cao noted.

He cautioned that “further large cohort, multicenter prospective studies are needed to assess generalizability and may be helpful in evaluating the accuracy of WBAIL-2 in non-HLA DQ2.5 genotypes.” 

Other considerations prior to implementation may include reproducibility across different laboratories and overall cost effectiveness, Cao said. “Ultimately in clinic, the role of WBAIL-2 will need to be better defined within the algorithm of celiac disease testing,” he added.

 

The Path Ahead

The researchers plan to test the performance of the IL-2 whole blood assay in a pediatric cohort, as well as in other countries to demonstrate the reproducibility of the test. In these studies, the test will likely be performed alongside the current diagnostic tests (serology and gastroscopy), Moscatelli told GI & Hepatology News.

“There are some validation studies starting in other countries already as many celiac clinicians globally are interested in bringing this test to their clinical practice. I believe the plan is to have this as an approved diagnostic test for celiac disease worldwide,” she said.

Novoviah Pharmaceuticals is managing the commercialization of the test, and the plan is to get it into clinical practice in the next 2 years, Moscatelli said.

The research was supported by Coeliac Australia, Novoviah Pharmaceuticals (who provided the proprietary test for this study), Beck Family Foundation, Butterfield Family, the Veith Foundation. A complete list of author disclosures is available with the original article. Cao had no relevant disclosures.

A version of this article appeared on Medscape.com.

Think your patient may have celiac disease? The harsh reality is that current diagnostic tests require patients to consume gluten for an accurate diagnosis, which poses challenges for individuals already avoiding gluten.

A more tolerable approach appears to be on the horizon. Researchers in Australia have developed a blood test that can identify celiac disease with high sensitivity and specificity, even without consuming gluten.

“This is a simple and accurate test that can provide a diagnosis within a very short time frame, without the need for patients to continue eating gluten and feeling sick, or to wait months for a gastroscopy,” Olivia Moscatelli, PhD candidate, Tye-Din Lab, Walter and Eliza Hall Institute and University of Melbourne, Parkville, Australia, told GI & Hepatology News.

The study was published in Gastroenterology.

 

Most Cases Go Undiagnosed

Celiac disease is an autoimmune disorder triggered by gluten found in wheat, rye, and barley. The only available treatment is a strict, life-long gluten-free diet.

The global prevalence of celiac disease is estimated at around 1%-2%, with 50%-80% of cases either undiagnosed or diagnosed late. That’s because the current reliable diagnosis of celiac disease requires the intake of gluten, which may deter people from seeking a diagnosis.

In earlier work, the researchers, working with Robert Anderson, MBChB, BMedSc, PhD, AGAF, now with Novoviah Pharmaceuticals, made the unexpected discovery that interleukin-2 (IL-2) spiked in the blood of people with celiac disease shortly after they ate gluten.

But would this signal be present when no gluten had been consumed?

The team developed and tested a simple whole blood assay measuring IL-2 release (WBAIL- 2) for detecting gluten-specific T cells to aid in diagnosing celiac disease.

They collected blood samples from 181 volunteers — 75 with treated celiac disease on a gluten-free diet, 13 with active untreated celiac disease, 32 with nonceliac gluten sensitivity and 61 healthy controls. The blood samples were mixed with gluten in a test tube for a day to see if the IL-2 signal appeared.

The WBAIL-2 assay demonstrated high accuracy for celiac disease, even in patients following a strict gluten-free diet.

For patients with HLA-DQ2.5+ genetics, sensitivity was 90% and specificity was 95%, with lower sensitivity (56%) for patients with HLA-DQ8+ celiac disease.

The WBAIL-2 assay correlated strongly with the frequency of tetramer-positive gluten-specific CD4+ T cells used to diagnose celiac disease and monitor treatment effectiveness, and with serum IL-2 levels after gluten challenge.

The strength of the IL-2 signal correlated with the severity of a patient’s symptoms, “allowing us to predict how severely a person with celiac disease might react to gluten, without them actually having to eat it,” Moscatelli said in a news release.

“Current diagnostic practice involves a blood-based serology test followed by a confirmatory gastroscopy if positive. Both tests require the patient to eat gluten daily for 6-12 weeks prior for accurate results. We envision the new blood test (IL-2 whole blood assay) will replace the invasive gastroscopy as the confirmatory test following positive serology,” Moscatelli told GI & Hepatology News.

“In people already following a gluten-free diet, we propose they would have this new blood test done on two separate occasions and two positive results would be required for a celiac diagnosis. This would allow a large number of people who previously have been unable to go through the current diagnostic process to receive a diagnosis,” Moscatelli said.

 

Practice Changing Potential 

A blood-based test that can accurately detect celiac disease without the need for a gluten challenge would be “welcome and practice changing,” said Christopher Cao, MD, director, Celiac Disease Program, Division of Gastroenterology, Mount Sinai Health System, New York City.

“A typical ‘gluten challenge’ involves eating the equivalent of 1-2 slices of bread daily for the course of 6 weeks, and this may be incredibly difficult for patients who have already been on a gluten-free diet prior to an official celiac disease diagnosis. Inability to perform a gluten challenge limits the ability to make an accurate celiac disease diagnosis,” Cao told GI & Hepatology News.

“This study shows that gluten-stimulated interleukin release 2 assays may correlate with the presence of pathogenic gluten-specific CD4+ T cell response in celiac disease,” Cao noted.

He cautioned that “further large cohort, multicenter prospective studies are needed to assess generalizability and may be helpful in evaluating the accuracy of WBAIL-2 in non-HLA DQ2.5 genotypes.” 

Other considerations prior to implementation may include reproducibility across different laboratories and overall cost effectiveness, Cao said. “Ultimately in clinic, the role of WBAIL-2 will need to be better defined within the algorithm of celiac disease testing,” he added.

 

The Path Ahead

The researchers plan to test the performance of the IL-2 whole blood assay in a pediatric cohort, as well as in other countries to demonstrate the reproducibility of the test. In these studies, the test will likely be performed alongside the current diagnostic tests (serology and gastroscopy), Moscatelli told GI & Hepatology News.

“There are some validation studies starting in other countries already as many celiac clinicians globally are interested in bringing this test to their clinical practice. I believe the plan is to have this as an approved diagnostic test for celiac disease worldwide,” she said.

Novoviah Pharmaceuticals is managing the commercialization of the test, and the plan is to get it into clinical practice in the next 2 years, Moscatelli said.

The research was supported by Coeliac Australia, Novoviah Pharmaceuticals (who provided the proprietary test for this study), Beck Family Foundation, Butterfield Family, the Veith Foundation. A complete list of author disclosures is available with the original article. Cao had no relevant disclosures.

A version of this article appeared on Medscape.com.

A treat-to target (T2T) strategy based on video capsule endoscopy (VCE) identified Crohn’s disease (CD) patients in clinical remission but with small bowel inflammation, resulting in fewer clinical flares versus a treat-by-symptoms standard approach.

“A VCE-guided treat-to-target strategy for patients with CD in remission confers superior clinical outcomes compared with continued standard care,” investigators led by Shomron Ben-Horin, MD, director of gastroenterology at Sheba Medical Center in Ramat-Gan, Israel.

Published in Gastroenterology, the CURE-CD (Comprehensive Individualized Proactive Therapy of Crohn’s Disease), a prospective, temporally blinded, randomized controled trial, looked at 60 adult patients with quiescent CD involving the small bowel (either L1 or L3 iof the terminal ileum and upper colon).

The researchers defined quiescent disease as corticosteroid-free clinical remission with a Crohn’s Disease Activity Index (CDAI) of <50 for the past 3 months on a stable regimen.

Patients ingested a VCE at baseline and those with a Lewis inflammatory score (LS) of ≥350 were designated high risk (n = 40) and randomized to either T2T optimization (n = 20) or continuing standard care (n = 20). 

T2T was optimized with repeat VCE results every 6 months. Patients with LS <350 (“low risk”) continued standard care. The primary outcome was the rate of disease exacerbation, demonstrated by a CDAI increase of >70 points and a score >150, or hospitalization/surgery, in high-risk standard care vs T2T groups at 24 months.

Treatment intensification in the high-risk group allocated to a proactive strategy comprised biologic dose escalation (n = 11 of 20), starting a biologic (n = 8 of 20), or swapping biologics (n = 1 of 20). 

The primary outcome, clinical flare by 24 months, occurred in 5 of 20 (25%) of high-risk treat-to-target patients vs 14 of 20 (70%) of the high-risk standard-care group (odds ratio [OR], .14; 95% confidence interval [CI], .04–.57, P = .006). 

Mucosal healing was significantly more common in the T2T group when determined by a cutoff LS < 350 (OR, 4.5, 95% CI, 1.7–17.4, nominal P value = .03), but not by the combined scores of total LS < 450 and highest-segment LS < 350. 

Among all patients continuing standard care (n = 40), baseline LS was numerically higher among relapsers vs nonrelapsers (450, 225–900 vs 225, 135–600, respectively, P = .07). 

As to safety, of 221 VCEs ingested, there was a single (.4%) temporary retention, which spontaneously resolved.

“VCE monitoring of CD was approved into government reimbursement in Israel last year, and I know several European countries are also considering the inclusion of this new indication for VCE in their payer reimbursement,” Ben-Horin told GI & Hepatology News. “Uptake in Israel is still baby-stepping. In our center it’s much more common to monitor T2T for small bowel patients, but this approach is still not widely applied.”

The authors cautioned that since the focus was the small bowel, the findings are not necessarily generalizable to patients with Crohn’s colitis.

The study was supported by the Leona M. & Harry B. Helmsley Charitable Trust, Medtronic (USA), AbbVie (Israel), and Takeda. The funders did not intervene in the design or interpretation of the study.

Ben-Horin reported advisory, consulting fees, research support, and/or stocks/options from several pharmaceutical firms. Several coauthors disclosed similar relations with private-sector companies.
 

A treat-to target (T2T) strategy based on video capsule endoscopy (VCE) identified Crohn’s disease (CD) patients in clinical remission but with small bowel inflammation, resulting in fewer clinical flares versus a treat-by-symptoms standard approach.

“A VCE-guided treat-to-target strategy for patients with CD in remission confers superior clinical outcomes compared with continued standard care,” investigators led by Shomron Ben-Horin, MD, director of gastroenterology at Sheba Medical Center in Ramat-Gan, Israel.

Published in Gastroenterology, the CURE-CD (Comprehensive Individualized Proactive Therapy of Crohn’s Disease), a prospective, temporally blinded, randomized controled trial, looked at 60 adult patients with quiescent CD involving the small bowel (either L1 or L3 iof the terminal ileum and upper colon).

The researchers defined quiescent disease as corticosteroid-free clinical remission with a Crohn’s Disease Activity Index (CDAI) of <50 for the past 3 months on a stable regimen.

Patients ingested a VCE at baseline and those with a Lewis inflammatory score (LS) of ≥350 were designated high risk (n = 40) and randomized to either T2T optimization (n = 20) or continuing standard care (n = 20). 

T2T was optimized with repeat VCE results every 6 months. Patients with LS <350 (“low risk”) continued standard care. The primary outcome was the rate of disease exacerbation, demonstrated by a CDAI increase of >70 points and a score >150, or hospitalization/surgery, in high-risk standard care vs T2T groups at 24 months.

Treatment intensification in the high-risk group allocated to a proactive strategy comprised biologic dose escalation (n = 11 of 20), starting a biologic (n = 8 of 20), or swapping biologics (n = 1 of 20). 

The primary outcome, clinical flare by 24 months, occurred in 5 of 20 (25%) of high-risk treat-to-target patients vs 14 of 20 (70%) of the high-risk standard-care group (odds ratio [OR], .14; 95% confidence interval [CI], .04–.57, P = .006). 

Mucosal healing was significantly more common in the T2T group when determined by a cutoff LS < 350 (OR, 4.5, 95% CI, 1.7–17.4, nominal P value = .03), but not by the combined scores of total LS < 450 and highest-segment LS < 350. 

Among all patients continuing standard care (n = 40), baseline LS was numerically higher among relapsers vs nonrelapsers (450, 225–900 vs 225, 135–600, respectively, P = .07). 

As to safety, of 221 VCEs ingested, there was a single (.4%) temporary retention, which spontaneously resolved.

“VCE monitoring of CD was approved into government reimbursement in Israel last year, and I know several European countries are also considering the inclusion of this new indication for VCE in their payer reimbursement,” Ben-Horin told GI & Hepatology News. “Uptake in Israel is still baby-stepping. In our center it’s much more common to monitor T2T for small bowel patients, but this approach is still not widely applied.”

The authors cautioned that since the focus was the small bowel, the findings are not necessarily generalizable to patients with Crohn’s colitis.

The study was supported by the Leona M. & Harry B. Helmsley Charitable Trust, Medtronic (USA), AbbVie (Israel), and Takeda. The funders did not intervene in the design or interpretation of the study.

Ben-Horin reported advisory, consulting fees, research support, and/or stocks/options from several pharmaceutical firms. Several coauthors disclosed similar relations with private-sector companies.
 

A treat-to target (T2T) strategy based on video capsule endoscopy (VCE) identified Crohn’s disease (CD) patients in clinical remission but with small bowel inflammation, resulting in fewer clinical flares versus a treat-by-symptoms standard approach.

“A VCE-guided treat-to-target strategy for patients with CD in remission confers superior clinical outcomes compared with continued standard care,” investigators led by Shomron Ben-Horin, MD, director of gastroenterology at Sheba Medical Center in Ramat-Gan, Israel.

Published in Gastroenterology, the CURE-CD (Comprehensive Individualized Proactive Therapy of Crohn’s Disease), a prospective, temporally blinded, randomized controled trial, looked at 60 adult patients with quiescent CD involving the small bowel (either L1 or L3 iof the terminal ileum and upper colon).

The researchers defined quiescent disease as corticosteroid-free clinical remission with a Crohn’s Disease Activity Index (CDAI) of <50 for the past 3 months on a stable regimen.

Patients ingested a VCE at baseline and those with a Lewis inflammatory score (LS) of ≥350 were designated high risk (n = 40) and randomized to either T2T optimization (n = 20) or continuing standard care (n = 20). 

T2T was optimized with repeat VCE results every 6 months. Patients with LS <350 (“low risk”) continued standard care. The primary outcome was the rate of disease exacerbation, demonstrated by a CDAI increase of >70 points and a score >150, or hospitalization/surgery, in high-risk standard care vs T2T groups at 24 months.

Treatment intensification in the high-risk group allocated to a proactive strategy comprised biologic dose escalation (n = 11 of 20), starting a biologic (n = 8 of 20), or swapping biologics (n = 1 of 20). 

The primary outcome, clinical flare by 24 months, occurred in 5 of 20 (25%) of high-risk treat-to-target patients vs 14 of 20 (70%) of the high-risk standard-care group (odds ratio [OR], .14; 95% confidence interval [CI], .04–.57, P = .006). 

Mucosal healing was significantly more common in the T2T group when determined by a cutoff LS < 350 (OR, 4.5, 95% CI, 1.7–17.4, nominal P value = .03), but not by the combined scores of total LS < 450 and highest-segment LS < 350. 

Among all patients continuing standard care (n = 40), baseline LS was numerically higher among relapsers vs nonrelapsers (450, 225–900 vs 225, 135–600, respectively, P = .07). 

As to safety, of 221 VCEs ingested, there was a single (.4%) temporary retention, which spontaneously resolved.

“VCE monitoring of CD was approved into government reimbursement in Israel last year, and I know several European countries are also considering the inclusion of this new indication for VCE in their payer reimbursement,” Ben-Horin told GI & Hepatology News. “Uptake in Israel is still baby-stepping. In our center it’s much more common to monitor T2T for small bowel patients, but this approach is still not widely applied.”

The authors cautioned that since the focus was the small bowel, the findings are not necessarily generalizable to patients with Crohn’s colitis.

The study was supported by the Leona M. & Harry B. Helmsley Charitable Trust, Medtronic (USA), AbbVie (Israel), and Takeda. The funders did not intervene in the design or interpretation of the study.

Ben-Horin reported advisory, consulting fees, research support, and/or stocks/options from several pharmaceutical firms. Several coauthors disclosed similar relations with private-sector companies.