User login
AKI doubles risk of death for those with acute pancreatitis
CHICAGO – Acute kidney injury (AKI) doubles the risk of death among patients hospitalized for acute pancreatitis, Kalpit Devani, MD, reported at the annual Digestive Disease Week®.
This severe complication of acute pancreatitis also significantly increases the length of stay and drives up hospital costs, said Dr. Devani of East Tennessee State University, Johnson City. Fortunately, although the risks associated with it remain high, death from AKI in the setting of acute pancreatitis has decreased significantly, from a high of 17% in 2002 to 6.4% in 2012, Dr. Devani determined in his database review.
“Increasing awareness and prompt diagnosis of AKI could be the reason for the increasing trend of prevalence of AKI in acute pancreatitis patients,” he said in an interview. “Decreasing mortality can be related to adherence to recent advances in the management approach of acute pancreatitis, such as early (within 24 hours) and aggressive intravenous hydration and early enteral feeding.”
Dr. Devani examined these trends in data extracted from the National Inpatient Sample, 2002-2012. During that 10-year period, almost 3.5 million adults were hospitalized for acute pancreatitis. These patients were a mean of 53 years old, and half were women. Their mean length of stay was just over 5 days, at a mean cost of about $12,000. Of these, 273,687 (7.9%) also developed AKI.
There were some significant differences between those who did and did not develop AKI. AKI patients were significantly older (61 vs. 53 years), and less likely to be women (43% vs. 51%). They had a higher Charlson Comorbidity Index score (1.49 vs. 0.84). They were also significantly more likely to develop a number of complications, including systemic inflammatory response syndrome (2% vs. 0.4%), septic shock (6% vs. 0.3%), sepsis (8.7% vs. 1.4%), acute respiratory failure (18% vs. 2%), and electrolyte disorder (72% vs. 30%).
Not surprisingly, their length of stay was significantly longer (10 vs. 5 days), as was hospitalization cost ($25,923 vs. $10,889). Mortality was much higher, at almost 9% vs. 0.7%.
In a propensity matching analysis, Dr. Devani matched 53,000 pairs of acute pancreatitis patients with and without AKI. This determined that those with AKI faced a doubling in the risk of in-hospital mortality.
He also examined temporal trends with regard to the complication. The rate of diagnosed AKI in hospitalized acute pancreatitis cases rose dramatically, from 4% in 2002 to 11.6% in 2012. However, mortality in acute pancreatitis patients decreased among both those with AKI (17%-6%) and those without (1%-0.4%).
The mean length of stay in patients with AKI and pancreatitis likewise fell, from 14.8 to 8.6 days. Not surprisingly, total hospitalization cost for these patients fell as well ($42,975-$20,716).
Among pancreatitis patients without AKI, length of stay and costs declined, although not as dramatically as they did among AKI patients (6-5 days; $13,654-$10,895).
Dr. Devani had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
CHICAGO – Acute kidney injury (AKI) doubles the risk of death among patients hospitalized for acute pancreatitis, Kalpit Devani, MD, reported at the annual Digestive Disease Week®.
This severe complication of acute pancreatitis also significantly increases the length of stay and drives up hospital costs, said Dr. Devani of East Tennessee State University, Johnson City. Fortunately, although the risks associated with it remain high, death from AKI in the setting of acute pancreatitis has decreased significantly, from a high of 17% in 2002 to 6.4% in 2012, Dr. Devani determined in his database review.
“Increasing awareness and prompt diagnosis of AKI could be the reason for the increasing trend of prevalence of AKI in acute pancreatitis patients,” he said in an interview. “Decreasing mortality can be related to adherence to recent advances in the management approach of acute pancreatitis, such as early (within 24 hours) and aggressive intravenous hydration and early enteral feeding.”
Dr. Devani examined these trends in data extracted from the National Inpatient Sample, 2002-2012. During that 10-year period, almost 3.5 million adults were hospitalized for acute pancreatitis. These patients were a mean of 53 years old, and half were women. Their mean length of stay was just over 5 days, at a mean cost of about $12,000. Of these, 273,687 (7.9%) also developed AKI.
There were some significant differences between those who did and did not develop AKI. AKI patients were significantly older (61 vs. 53 years), and less likely to be women (43% vs. 51%). They had a higher Charlson Comorbidity Index score (1.49 vs. 0.84). They were also significantly more likely to develop a number of complications, including systemic inflammatory response syndrome (2% vs. 0.4%), septic shock (6% vs. 0.3%), sepsis (8.7% vs. 1.4%), acute respiratory failure (18% vs. 2%), and electrolyte disorder (72% vs. 30%).
Not surprisingly, their length of stay was significantly longer (10 vs. 5 days), as was hospitalization cost ($25,923 vs. $10,889). Mortality was much higher, at almost 9% vs. 0.7%.
In a propensity matching analysis, Dr. Devani matched 53,000 pairs of acute pancreatitis patients with and without AKI. This determined that those with AKI faced a doubling in the risk of in-hospital mortality.
He also examined temporal trends with regard to the complication. The rate of diagnosed AKI in hospitalized acute pancreatitis cases rose dramatically, from 4% in 2002 to 11.6% in 2012. However, mortality in acute pancreatitis patients decreased among both those with AKI (17%-6%) and those without (1%-0.4%).
The mean length of stay in patients with AKI and pancreatitis likewise fell, from 14.8 to 8.6 days. Not surprisingly, total hospitalization cost for these patients fell as well ($42,975-$20,716).
Among pancreatitis patients without AKI, length of stay and costs declined, although not as dramatically as they did among AKI patients (6-5 days; $13,654-$10,895).
Dr. Devani had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
CHICAGO – Acute kidney injury (AKI) doubles the risk of death among patients hospitalized for acute pancreatitis, Kalpit Devani, MD, reported at the annual Digestive Disease Week®.
This severe complication of acute pancreatitis also significantly increases the length of stay and drives up hospital costs, said Dr. Devani of East Tennessee State University, Johnson City. Fortunately, although the risks associated with it remain high, death from AKI in the setting of acute pancreatitis has decreased significantly, from a high of 17% in 2002 to 6.4% in 2012, Dr. Devani determined in his database review.
“Increasing awareness and prompt diagnosis of AKI could be the reason for the increasing trend of prevalence of AKI in acute pancreatitis patients,” he said in an interview. “Decreasing mortality can be related to adherence to recent advances in the management approach of acute pancreatitis, such as early (within 24 hours) and aggressive intravenous hydration and early enteral feeding.”
Dr. Devani examined these trends in data extracted from the National Inpatient Sample, 2002-2012. During that 10-year period, almost 3.5 million adults were hospitalized for acute pancreatitis. These patients were a mean of 53 years old, and half were women. Their mean length of stay was just over 5 days, at a mean cost of about $12,000. Of these, 273,687 (7.9%) also developed AKI.
There were some significant differences between those who did and did not develop AKI. AKI patients were significantly older (61 vs. 53 years), and less likely to be women (43% vs. 51%). They had a higher Charlson Comorbidity Index score (1.49 vs. 0.84). They were also significantly more likely to develop a number of complications, including systemic inflammatory response syndrome (2% vs. 0.4%), septic shock (6% vs. 0.3%), sepsis (8.7% vs. 1.4%), acute respiratory failure (18% vs. 2%), and electrolyte disorder (72% vs. 30%).
Not surprisingly, their length of stay was significantly longer (10 vs. 5 days), as was hospitalization cost ($25,923 vs. $10,889). Mortality was much higher, at almost 9% vs. 0.7%.
In a propensity matching analysis, Dr. Devani matched 53,000 pairs of acute pancreatitis patients with and without AKI. This determined that those with AKI faced a doubling in the risk of in-hospital mortality.
He also examined temporal trends with regard to the complication. The rate of diagnosed AKI in hospitalized acute pancreatitis cases rose dramatically, from 4% in 2002 to 11.6% in 2012. However, mortality in acute pancreatitis patients decreased among both those with AKI (17%-6%) and those without (1%-0.4%).
The mean length of stay in patients with AKI and pancreatitis likewise fell, from 14.8 to 8.6 days. Not surprisingly, total hospitalization cost for these patients fell as well ($42,975-$20,716).
Among pancreatitis patients without AKI, length of stay and costs declined, although not as dramatically as they did among AKI patients (6-5 days; $13,654-$10,895).
Dr. Devani had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
AT DDW
Key clinical point:
Major finding: Mortality among those with AKI was 9% vs. 0.7% among those without. After controlling for confounders, the risk of death was doubled.
Data source: A 10-year National Inpatient Sample database review comprising 3.5 million patients with pancreatitis.
Disclosures: Dr. Devani had no financial disclosures.
Recurrent acute pancreatitis significantly impairs both mental and physical quality of life
CHICAGO – Despite its intermittent and unpredictable nature, recurrent acute pancreatitis exacts a significant toll on patients’ physical and mental quality of life.
It is well-known that patients with chronic pancreatitis suffer physically and emotionally. However, the same understanding has not been engendered for those who experience recurrent acute pancreatitis (RAP), Gregory A. Cote, MD, said at the annual Digestive Disease Week®. Sporadic episodes of acute pancreatitis may cause persistent declines in quality of life.
“RAP clearly leads to a significant reduction in physical and mental quality of life, despite its erratic and sporadic nature,” Dr. Cote said. “Smoking and self-reported disability are very important drivers of these reductions, and a concomitant diagnosis of diabetes exacerbates that even further.”
To explore RAP’s impact on mental and physical quality of life, Dr. Cote examined data from three related cross-sectional North American Pancreatitis Studies (NAPS): the NAPS2, NAPS2-CV (Continuation and Validation), and NAPS2-AS (Ancillary Study).
These studies comprised 2,619 subjects who were enrolled at 27 U.S. sites from 2000 to 2014. Both patients and their physicians completed detailed baseline questionnaires that included personal and family history, risk factors, symptoms, and the 12-Item Short Form Health Survey (SF-12), a detailed quality of life measure.
A score of 50 is the mean for the U.S. general population, and a difference of 3 points or more is considered clinically relevant, Dr. Cote noted.
He parsed the cohort into three groups: those with RAP (508), those with chronic pancreatitis (1,086), and a reference group of healthy controls who were also in the database (1,025).
Some significant between-group differences were immediately obvious, Dr. Cote said. Patients with RAP were significantly younger than both chronic pancreatitis patients (CP) and controls (45 vs. 51 and 49 years, respectively). They also experienced their first bout of acute pancreatitis sooner than CP patients became symptomatic (40 vs. 44 years). Gender was a factor as well: CP patients were more often men (55% vs. 46%).
The pattern of alcohol use between the groups was difficult to interpret, he said. About one-quarter of RAP patients abstained, another fourth were light drinkers, and another fourth moderate drinkers – 12% drank heavily and 7% very heavily. In contrast, frequent drinking was more common among CP patients, with 12% reporting that they drank heavily and 33% very heavily.
CP patients were significantly more likely to be smokers, with 75% reporting current or past tobacco use, compared with 55% of RAP patients. More RAP patients reported never smoking (44% vs. 25%).
RAP patients fell between CP patients and controls in terms of medical comorbidities, including diabetes, renal disease or kidney failure, heart disease, and liver disease.
On the SF-12 physical component section, RAP patients scored a mean of 41 points – significantly worse than controls (51) but significantly better than CP patients (37). The findings were similar for the mental component score: RAP patients scored a mean of 45, compared with 52 in controls and 43 in CP patients.
Dr. Cote performed a multivariate analysis that controlled for age, sex, tobacco and alcohol use, and diabetes. Again, he found that, compared with controls, RAP was associated with significantly reduced scores on both the physical and mental components (mean 8.5 and 6.5 points, respectively).
“The magnitude of reduction was even greater for chronic pancreatitis, with an 11-point reduction on the physical component score and a 7.6-point reduction on the mental component score.
He then sought to identify which clinical characteristics most contributed to this impact on quality of life.
On the physical component score, several were significant, including female sex, which was associated with a 4.4-point decrease; prior pancreatic surgery (–3.3); endocrine insufficiency (–4.6); past smoking (–2.5); current smoking (–3.6); and self-reported physical disability (–9.5).
The mental component score breakdown echoed some of these. Self-reported disability exerted the largest impact, bringing the mental score down by a mean of 5.4 points. Other significant factors were smoking less than a pack a day (–2.5) and smoking more than a pack a day (–4.6). Any suspicion of chronic pancreatitis by the treating physician was associated with a 2.9-point decrease on the score.
“Our findings stress that this is not a disease that can be followed conservatively. We have to investigate interventions that will attenuate it, not only because these patients may go on to develop chronic pancreatitis but because, in their current state, most are experiencing significant reductions in their quality of life.”
Dr Cote had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
CHICAGO – Despite its intermittent and unpredictable nature, recurrent acute pancreatitis exacts a significant toll on patients’ physical and mental quality of life.
It is well-known that patients with chronic pancreatitis suffer physically and emotionally. However, the same understanding has not been engendered for those who experience recurrent acute pancreatitis (RAP), Gregory A. Cote, MD, said at the annual Digestive Disease Week®. Sporadic episodes of acute pancreatitis may cause persistent declines in quality of life.
“RAP clearly leads to a significant reduction in physical and mental quality of life, despite its erratic and sporadic nature,” Dr. Cote said. “Smoking and self-reported disability are very important drivers of these reductions, and a concomitant diagnosis of diabetes exacerbates that even further.”
To explore RAP’s impact on mental and physical quality of life, Dr. Cote examined data from three related cross-sectional North American Pancreatitis Studies (NAPS): the NAPS2, NAPS2-CV (Continuation and Validation), and NAPS2-AS (Ancillary Study).
These studies comprised 2,619 subjects who were enrolled at 27 U.S. sites from 2000 to 2014. Both patients and their physicians completed detailed baseline questionnaires that included personal and family history, risk factors, symptoms, and the 12-Item Short Form Health Survey (SF-12), a detailed quality of life measure.
A score of 50 is the mean for the U.S. general population, and a difference of 3 points or more is considered clinically relevant, Dr. Cote noted.
He parsed the cohort into three groups: those with RAP (508), those with chronic pancreatitis (1,086), and a reference group of healthy controls who were also in the database (1,025).
Some significant between-group differences were immediately obvious, Dr. Cote said. Patients with RAP were significantly younger than both chronic pancreatitis patients (CP) and controls (45 vs. 51 and 49 years, respectively). They also experienced their first bout of acute pancreatitis sooner than CP patients became symptomatic (40 vs. 44 years). Gender was a factor as well: CP patients were more often men (55% vs. 46%).
The pattern of alcohol use between the groups was difficult to interpret, he said. About one-quarter of RAP patients abstained, another fourth were light drinkers, and another fourth moderate drinkers – 12% drank heavily and 7% very heavily. In contrast, frequent drinking was more common among CP patients, with 12% reporting that they drank heavily and 33% very heavily.
CP patients were significantly more likely to be smokers, with 75% reporting current or past tobacco use, compared with 55% of RAP patients. More RAP patients reported never smoking (44% vs. 25%).
RAP patients fell between CP patients and controls in terms of medical comorbidities, including diabetes, renal disease or kidney failure, heart disease, and liver disease.
On the SF-12 physical component section, RAP patients scored a mean of 41 points – significantly worse than controls (51) but significantly better than CP patients (37). The findings were similar for the mental component score: RAP patients scored a mean of 45, compared with 52 in controls and 43 in CP patients.
Dr. Cote performed a multivariate analysis that controlled for age, sex, tobacco and alcohol use, and diabetes. Again, he found that, compared with controls, RAP was associated with significantly reduced scores on both the physical and mental components (mean 8.5 and 6.5 points, respectively).
“The magnitude of reduction was even greater for chronic pancreatitis, with an 11-point reduction on the physical component score and a 7.6-point reduction on the mental component score.
He then sought to identify which clinical characteristics most contributed to this impact on quality of life.
On the physical component score, several were significant, including female sex, which was associated with a 4.4-point decrease; prior pancreatic surgery (–3.3); endocrine insufficiency (–4.6); past smoking (–2.5); current smoking (–3.6); and self-reported physical disability (–9.5).
The mental component score breakdown echoed some of these. Self-reported disability exerted the largest impact, bringing the mental score down by a mean of 5.4 points. Other significant factors were smoking less than a pack a day (–2.5) and smoking more than a pack a day (–4.6). Any suspicion of chronic pancreatitis by the treating physician was associated with a 2.9-point decrease on the score.
“Our findings stress that this is not a disease that can be followed conservatively. We have to investigate interventions that will attenuate it, not only because these patients may go on to develop chronic pancreatitis but because, in their current state, most are experiencing significant reductions in their quality of life.”
Dr Cote had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
CHICAGO – Despite its intermittent and unpredictable nature, recurrent acute pancreatitis exacts a significant toll on patients’ physical and mental quality of life.
It is well-known that patients with chronic pancreatitis suffer physically and emotionally. However, the same understanding has not been engendered for those who experience recurrent acute pancreatitis (RAP), Gregory A. Cote, MD, said at the annual Digestive Disease Week®. Sporadic episodes of acute pancreatitis may cause persistent declines in quality of life.
“RAP clearly leads to a significant reduction in physical and mental quality of life, despite its erratic and sporadic nature,” Dr. Cote said. “Smoking and self-reported disability are very important drivers of these reductions, and a concomitant diagnosis of diabetes exacerbates that even further.”
To explore RAP’s impact on mental and physical quality of life, Dr. Cote examined data from three related cross-sectional North American Pancreatitis Studies (NAPS): the NAPS2, NAPS2-CV (Continuation and Validation), and NAPS2-AS (Ancillary Study).
These studies comprised 2,619 subjects who were enrolled at 27 U.S. sites from 2000 to 2014. Both patients and their physicians completed detailed baseline questionnaires that included personal and family history, risk factors, symptoms, and the 12-Item Short Form Health Survey (SF-12), a detailed quality of life measure.
A score of 50 is the mean for the U.S. general population, and a difference of 3 points or more is considered clinically relevant, Dr. Cote noted.
He parsed the cohort into three groups: those with RAP (508), those with chronic pancreatitis (1,086), and a reference group of healthy controls who were also in the database (1,025).
Some significant between-group differences were immediately obvious, Dr. Cote said. Patients with RAP were significantly younger than both chronic pancreatitis patients (CP) and controls (45 vs. 51 and 49 years, respectively). They also experienced their first bout of acute pancreatitis sooner than CP patients became symptomatic (40 vs. 44 years). Gender was a factor as well: CP patients were more often men (55% vs. 46%).
The pattern of alcohol use between the groups was difficult to interpret, he said. About one-quarter of RAP patients abstained, another fourth were light drinkers, and another fourth moderate drinkers – 12% drank heavily and 7% very heavily. In contrast, frequent drinking was more common among CP patients, with 12% reporting that they drank heavily and 33% very heavily.
CP patients were significantly more likely to be smokers, with 75% reporting current or past tobacco use, compared with 55% of RAP patients. More RAP patients reported never smoking (44% vs. 25%).
RAP patients fell between CP patients and controls in terms of medical comorbidities, including diabetes, renal disease or kidney failure, heart disease, and liver disease.
On the SF-12 physical component section, RAP patients scored a mean of 41 points – significantly worse than controls (51) but significantly better than CP patients (37). The findings were similar for the mental component score: RAP patients scored a mean of 45, compared with 52 in controls and 43 in CP patients.
Dr. Cote performed a multivariate analysis that controlled for age, sex, tobacco and alcohol use, and diabetes. Again, he found that, compared with controls, RAP was associated with significantly reduced scores on both the physical and mental components (mean 8.5 and 6.5 points, respectively).
“The magnitude of reduction was even greater for chronic pancreatitis, with an 11-point reduction on the physical component score and a 7.6-point reduction on the mental component score.
He then sought to identify which clinical characteristics most contributed to this impact on quality of life.
On the physical component score, several were significant, including female sex, which was associated with a 4.4-point decrease; prior pancreatic surgery (–3.3); endocrine insufficiency (–4.6); past smoking (–2.5); current smoking (–3.6); and self-reported physical disability (–9.5).
The mental component score breakdown echoed some of these. Self-reported disability exerted the largest impact, bringing the mental score down by a mean of 5.4 points. Other significant factors were smoking less than a pack a day (–2.5) and smoking more than a pack a day (–4.6). Any suspicion of chronic pancreatitis by the treating physician was associated with a 2.9-point decrease on the score.
“Our findings stress that this is not a disease that can be followed conservatively. We have to investigate interventions that will attenuate it, not only because these patients may go on to develop chronic pancreatitis but because, in their current state, most are experiencing significant reductions in their quality of life.”
Dr Cote had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
AT DDW
Key clinical point:
Major finding: On a physical QOL scale, patients scored a mean of 41 points – 10 points lower than controls. The mental QOL score was 7 points lower.
Data source: The database review comprised 2,619 subjects.
Disclosures: Dr. Cote had no financial disclosures.
IL-2 and IL-8 elevated after gluten ingestion on gluten-free diet
CHICAGO – A gluten-free diet is often implemented by patients before they are evaluated for celiac disease, which, in turn, does not allow for accurate celiac disease testing.
A new study shows, however, that measuring serum cytokines following a gluten challenge may allow an accurate diagnosis of celiac disease to be made, even after patients have been on a gluten-free diet.
Levels of IL-2 and IL-8 were increased 2-4 hours after ingestion of gluten. Elevations in other cytokines occurred less frequently, and changes in cytokine levels were similar in both serum and plasma.
“IL-2 is a cytokine produced exclusively by T cells and goes up from 2 hours after gluten consumption in celiac patients and is highly specific,” said study author Robert P. Anderson, MD, of Immusant, Cambridge, Mass., who presented the findings of his study at Digestive Disease Week®. “Rises in IL 8 are less but significant as well.”
The authors note that individuals who are already on a gluten-free diet and who would like a definitive diagnosis of celiac disease all too often refuse or are unable to tolerate a gluten challenge for the time period that is needed – usually 4 or more weeks – for the serologic and histologic markers of celiac disease to become abnormal.
Dr. Anderson pointed out that elevated plasma levels of IL-2 and IL-8 accompanied by gastrointestinal symptoms have been observed 4 hours after receiving a single dose of Nexvax2, a therapeutic vaccine being developed by Immusant. The peptide-based vaccine is intended to protect against the effects of gluten exposure while maintaining a gluten-free diet in HLA-DQ2.5+ patients with celiac disease.
In this study, Dr. Anderson and his colleagues hypothesized that patients with celiac disease who were on a gluten-free diet would also exhibit elevated serum IL-2 and IL-8 after an oral gluten versus placebo challenge.
The cohort was comprised of 21 adults with HLA-DQ2.5+ celiac disease who were compliant with a gluten-free diet and who were randomized to consume either vital wheat gluten flour (5 g; ~ 3 g gluten) or a matched gluten-free flour drink (placebo) over 10 minutes.
Blood was collected prior to the challenge and then at 4, 6, and 24 hours afterwards. In addition, patient vital signs and reported outcomes were recorded hourly, and adverse events were tracked from day 1 to day 6.
At 4 hours after ingesting gluten, serum IL-2 and IL-8 were both significantly higher, compared with placebo.
“There was a 20-fold increase in IL-2 after gluten was consumed, between 3 and 5 hours afterwards,” said Dr. Anderson. “IL-8 went up but not as much.”
The median change from baseline for IL-2 after gluten intake was 19.5 ([7.0-47.1], vs. 0.7 [0.5-1.2] for placebo; P = .0001). For IL-8 it was 2.4 (1.2-4.9) vs. 1.1 (0.8-1.2) (P = .012).
Patient-reported outcomes were worse among those in the gluten group (7/12), compared with the placebo group (3/9), after 3 hours but did not reach statistical significance.
He added that his team is in the process of conducting a further study to assess the diagnostic utility of measuring cytokine activity.
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
CHICAGO – A gluten-free diet is often implemented by patients before they are evaluated for celiac disease, which, in turn, does not allow for accurate celiac disease testing.
A new study shows, however, that measuring serum cytokines following a gluten challenge may allow an accurate diagnosis of celiac disease to be made, even after patients have been on a gluten-free diet.
Levels of IL-2 and IL-8 were increased 2-4 hours after ingestion of gluten. Elevations in other cytokines occurred less frequently, and changes in cytokine levels were similar in both serum and plasma.
“IL-2 is a cytokine produced exclusively by T cells and goes up from 2 hours after gluten consumption in celiac patients and is highly specific,” said study author Robert P. Anderson, MD, of Immusant, Cambridge, Mass., who presented the findings of his study at Digestive Disease Week®. “Rises in IL 8 are less but significant as well.”
The authors note that individuals who are already on a gluten-free diet and who would like a definitive diagnosis of celiac disease all too often refuse or are unable to tolerate a gluten challenge for the time period that is needed – usually 4 or more weeks – for the serologic and histologic markers of celiac disease to become abnormal.
Dr. Anderson pointed out that elevated plasma levels of IL-2 and IL-8 accompanied by gastrointestinal symptoms have been observed 4 hours after receiving a single dose of Nexvax2, a therapeutic vaccine being developed by Immusant. The peptide-based vaccine is intended to protect against the effects of gluten exposure while maintaining a gluten-free diet in HLA-DQ2.5+ patients with celiac disease.
In this study, Dr. Anderson and his colleagues hypothesized that patients with celiac disease who were on a gluten-free diet would also exhibit elevated serum IL-2 and IL-8 after an oral gluten versus placebo challenge.
The cohort was comprised of 21 adults with HLA-DQ2.5+ celiac disease who were compliant with a gluten-free diet and who were randomized to consume either vital wheat gluten flour (5 g; ~ 3 g gluten) or a matched gluten-free flour drink (placebo) over 10 minutes.
Blood was collected prior to the challenge and then at 4, 6, and 24 hours afterwards. In addition, patient vital signs and reported outcomes were recorded hourly, and adverse events were tracked from day 1 to day 6.
At 4 hours after ingesting gluten, serum IL-2 and IL-8 were both significantly higher, compared with placebo.
“There was a 20-fold increase in IL-2 after gluten was consumed, between 3 and 5 hours afterwards,” said Dr. Anderson. “IL-8 went up but not as much.”
The median change from baseline for IL-2 after gluten intake was 19.5 ([7.0-47.1], vs. 0.7 [0.5-1.2] for placebo; P = .0001). For IL-8 it was 2.4 (1.2-4.9) vs. 1.1 (0.8-1.2) (P = .012).
Patient-reported outcomes were worse among those in the gluten group (7/12), compared with the placebo group (3/9), after 3 hours but did not reach statistical significance.
He added that his team is in the process of conducting a further study to assess the diagnostic utility of measuring cytokine activity.
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
CHICAGO – A gluten-free diet is often implemented by patients before they are evaluated for celiac disease, which, in turn, does not allow for accurate celiac disease testing.
A new study shows, however, that measuring serum cytokines following a gluten challenge may allow an accurate diagnosis of celiac disease to be made, even after patients have been on a gluten-free diet.
Levels of IL-2 and IL-8 were increased 2-4 hours after ingestion of gluten. Elevations in other cytokines occurred less frequently, and changes in cytokine levels were similar in both serum and plasma.
“IL-2 is a cytokine produced exclusively by T cells and goes up from 2 hours after gluten consumption in celiac patients and is highly specific,” said study author Robert P. Anderson, MD, of Immusant, Cambridge, Mass., who presented the findings of his study at Digestive Disease Week®. “Rises in IL 8 are less but significant as well.”
The authors note that individuals who are already on a gluten-free diet and who would like a definitive diagnosis of celiac disease all too often refuse or are unable to tolerate a gluten challenge for the time period that is needed – usually 4 or more weeks – for the serologic and histologic markers of celiac disease to become abnormal.
Dr. Anderson pointed out that elevated plasma levels of IL-2 and IL-8 accompanied by gastrointestinal symptoms have been observed 4 hours after receiving a single dose of Nexvax2, a therapeutic vaccine being developed by Immusant. The peptide-based vaccine is intended to protect against the effects of gluten exposure while maintaining a gluten-free diet in HLA-DQ2.5+ patients with celiac disease.
In this study, Dr. Anderson and his colleagues hypothesized that patients with celiac disease who were on a gluten-free diet would also exhibit elevated serum IL-2 and IL-8 after an oral gluten versus placebo challenge.
The cohort was comprised of 21 adults with HLA-DQ2.5+ celiac disease who were compliant with a gluten-free diet and who were randomized to consume either vital wheat gluten flour (5 g; ~ 3 g gluten) or a matched gluten-free flour drink (placebo) over 10 minutes.
Blood was collected prior to the challenge and then at 4, 6, and 24 hours afterwards. In addition, patient vital signs and reported outcomes were recorded hourly, and adverse events were tracked from day 1 to day 6.
At 4 hours after ingesting gluten, serum IL-2 and IL-8 were both significantly higher, compared with placebo.
“There was a 20-fold increase in IL-2 after gluten was consumed, between 3 and 5 hours afterwards,” said Dr. Anderson. “IL-8 went up but not as much.”
The median change from baseline for IL-2 after gluten intake was 19.5 ([7.0-47.1], vs. 0.7 [0.5-1.2] for placebo; P = .0001). For IL-8 it was 2.4 (1.2-4.9) vs. 1.1 (0.8-1.2) (P = .012).
Patient-reported outcomes were worse among those in the gluten group (7/12), compared with the placebo group (3/9), after 3 hours but did not reach statistical significance.
He added that his team is in the process of conducting a further study to assess the diagnostic utility of measuring cytokine activity.
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
AT DDW
Key clinical point: Measuring serum cytokines can potentially be used to diagnose celiac disease after the patient has been on a gluten-free diet.
Major finding: There was a median 19.5-fold change from baseline for IL-2 after gluten intake (7.0-fold to 47.1-fold) and 24-fold for IL-8 (1.2-fold to 4.9-fold).
Data source: Randomized trial comprising 21 volunteers with celiac disease.
Disclosures: Dr. Anderson is employed by Immusant.
Plecanatide improves bowel function, abdominal pain
CHICAGO – Plecanatide, a drug recently approved for chronic idiopathic constipation, bested placebo in two randomized studies evaluating its effect in irritable bowel syndrome with constipation.
Results of the identical, 12-week, phase III studies propelled plecanatide (Trulance; Synergy Pharmaceuticals) into a supplemental new drug application for adult irritable bowel syndrome–constipation predominant (IBS-C), Ronald Fogel, MD, said at the annual Digestive Disease Week®.
During the question-and-answer period, though, clinicians didn’t quite echo the corporate enthusiasm for plecanatide. Several pointed out that overall responder rates were somewhat low for both the 3-mg and 6-mg dose (study -04, 30% both doses; study -05, 21% and 24%), with a drug-placebo differential of about 12% and 7%, respectively. When questioned, Dr. Fogel didn’t have data on the number needed to treat to improve one case. But, he asserted, such response numbers are typical for drug trials in patients with functional bowel disorders and meaningful to those who did respond.
“The differences were statistically significant, and, as someone who was there for both trials, I would say they are also clinically significant,” said Dr. Fogel, founder of the Digestive Health Center of Michigan, Chesterfield. “Patients who did respond were very happy.”
The drug was also quite well-tolerated, with diarrhea as the only important treatment-related adverse event and. This occurred in less than 2% of patients, and only about 1% of either cohort discontinued the medication because of severe diarrhea.
Plecanatide, structurally, is almost identical to uroguanylin, a peptide that regulates sodium and bicarbonate secretion into the intestine but with 8 times greater binding potential to the guanylate cyclase-C receptor. Both the natural and manmade molecules promote fluid secretion into the lumen and inhibit fluid absorption. Uroguanylin is most active in an acidic environment; therefore, plecanatide exerts most of its action in the proximal small intestine.
Synergy also asserts on its website that activation of the GC-C-receptor “may lead to decreased inflammation and pain sensation in the GI tract.” Abdominal pain was not a primary outcome in the pivotal trials for plecanatide’s idiopathic constipation studies, but it was a coprimary endpoint, with stool frequency, for the IBS-C trials.
The studies enrolled a total of 2,189 patients with a diagnosis of IBS-S. They were equally randomized to placebo or plecanatide 3 mg or 6 mg, once daily. Most (75%) were women. The mean age was about 43 years. At baseline, they reported less than one complete, spontaneous bowel movement per week. They also completed an 11-point scale on abdominal symptoms of pain (mean, 6), discomfort (mean, 6.2), and bloating (mean, 6.5).
The study included a 2-week pretreatment assessment period, 12 weeks of daily therapy during which patients filled out an electronic diary of stool frequency and abdominal pain/discomfort, and a 2-week follow-up. The primary endpoint was the number of overall responders, who had to experience both a decrease of at least 30% in their weekly abdominal pain score and an increase of at least one complete, spontaneous bowel movement per week.
Both studies posted statistically significant overall responder rates, relative to placebo, in both doses.
In study -04, the final overall placebo response rate was 17.8%, compared with 30% in the plecanatide 3-mg group and 29.5% in the plecanatide 6-mg group. In study -05, the placebo responder rate was 14%, compared with 21.5% in the 3-mg group and 24% in the 6-mg group.
Dr. Fogel showed stool frequency data but not abdominal pain data. About 41% of patients taking the study drug had increased bowel movements for at least 6 weeks of treatment, compared with 31.4% of those taking placebo. This 9% absolute difference was remarked on during the question-and-answer period as a surprisingly small separation. However, Dr. Fogel said that it was clinically significant as well as statistically so, with a P value of less than 0.001.
Plecanatide worked quickly. By the end of treatment week 1, the placebo and both active groups had already significantly separated, and that separation remained significant throughout the entire treatment period. During the 2-week follow-up period, the effect of both active doses tailed off and fell to the same as placebo by the end of 2 weeks.
One of the drug’s strongest points was its low rate of treatment-related diarrhea. Any diarrhea occurred in about 4% of both dosage groups, compared to 1% of the placebo group. Severe diarrhea occurred in 1% of the 3-mg and 0.4% of the 6-mg group, compared with 0.1% of the placebo group. This caused about 1% of patients to discontinue the study medication.
The adverse event profile was notably better than that of linaclotide (Linzess; Allergan), plecanatide’s close competitor. Also a guanylate cyclase–C agonist, linaclotide provoked diarrhea in almost 20% of patients in its pivotal phase III trials. Symptoms were severe in 2%. Lincalotide’s effectiveness in promoting bowel movements was slightly higher than that of plecanatide (about 48% in the pivotal trials), with a similar placebo response rate.
Plecanatide was approved earlier this year for chronic idiopathic constipation in adults.
Synergy Pharmaceuticals sponsored the study. Dr. Fogel has no financial interest in the company or in plecanatide.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
CHICAGO – Plecanatide, a drug recently approved for chronic idiopathic constipation, bested placebo in two randomized studies evaluating its effect in irritable bowel syndrome with constipation.
Results of the identical, 12-week, phase III studies propelled plecanatide (Trulance; Synergy Pharmaceuticals) into a supplemental new drug application for adult irritable bowel syndrome–constipation predominant (IBS-C), Ronald Fogel, MD, said at the annual Digestive Disease Week®.
During the question-and-answer period, though, clinicians didn’t quite echo the corporate enthusiasm for plecanatide. Several pointed out that overall responder rates were somewhat low for both the 3-mg and 6-mg dose (study -04, 30% both doses; study -05, 21% and 24%), with a drug-placebo differential of about 12% and 7%, respectively. When questioned, Dr. Fogel didn’t have data on the number needed to treat to improve one case. But, he asserted, such response numbers are typical for drug trials in patients with functional bowel disorders and meaningful to those who did respond.
“The differences were statistically significant, and, as someone who was there for both trials, I would say they are also clinically significant,” said Dr. Fogel, founder of the Digestive Health Center of Michigan, Chesterfield. “Patients who did respond were very happy.”
The drug was also quite well-tolerated, with diarrhea as the only important treatment-related adverse event and. This occurred in less than 2% of patients, and only about 1% of either cohort discontinued the medication because of severe diarrhea.
Plecanatide, structurally, is almost identical to uroguanylin, a peptide that regulates sodium and bicarbonate secretion into the intestine but with 8 times greater binding potential to the guanylate cyclase-C receptor. Both the natural and manmade molecules promote fluid secretion into the lumen and inhibit fluid absorption. Uroguanylin is most active in an acidic environment; therefore, plecanatide exerts most of its action in the proximal small intestine.
Synergy also asserts on its website that activation of the GC-C-receptor “may lead to decreased inflammation and pain sensation in the GI tract.” Abdominal pain was not a primary outcome in the pivotal trials for plecanatide’s idiopathic constipation studies, but it was a coprimary endpoint, with stool frequency, for the IBS-C trials.
The studies enrolled a total of 2,189 patients with a diagnosis of IBS-S. They were equally randomized to placebo or plecanatide 3 mg or 6 mg, once daily. Most (75%) were women. The mean age was about 43 years. At baseline, they reported less than one complete, spontaneous bowel movement per week. They also completed an 11-point scale on abdominal symptoms of pain (mean, 6), discomfort (mean, 6.2), and bloating (mean, 6.5).
The study included a 2-week pretreatment assessment period, 12 weeks of daily therapy during which patients filled out an electronic diary of stool frequency and abdominal pain/discomfort, and a 2-week follow-up. The primary endpoint was the number of overall responders, who had to experience both a decrease of at least 30% in their weekly abdominal pain score and an increase of at least one complete, spontaneous bowel movement per week.
Both studies posted statistically significant overall responder rates, relative to placebo, in both doses.
In study -04, the final overall placebo response rate was 17.8%, compared with 30% in the plecanatide 3-mg group and 29.5% in the plecanatide 6-mg group. In study -05, the placebo responder rate was 14%, compared with 21.5% in the 3-mg group and 24% in the 6-mg group.
Dr. Fogel showed stool frequency data but not abdominal pain data. About 41% of patients taking the study drug had increased bowel movements for at least 6 weeks of treatment, compared with 31.4% of those taking placebo. This 9% absolute difference was remarked on during the question-and-answer period as a surprisingly small separation. However, Dr. Fogel said that it was clinically significant as well as statistically so, with a P value of less than 0.001.
Plecanatide worked quickly. By the end of treatment week 1, the placebo and both active groups had already significantly separated, and that separation remained significant throughout the entire treatment period. During the 2-week follow-up period, the effect of both active doses tailed off and fell to the same as placebo by the end of 2 weeks.
One of the drug’s strongest points was its low rate of treatment-related diarrhea. Any diarrhea occurred in about 4% of both dosage groups, compared to 1% of the placebo group. Severe diarrhea occurred in 1% of the 3-mg and 0.4% of the 6-mg group, compared with 0.1% of the placebo group. This caused about 1% of patients to discontinue the study medication.
The adverse event profile was notably better than that of linaclotide (Linzess; Allergan), plecanatide’s close competitor. Also a guanylate cyclase–C agonist, linaclotide provoked diarrhea in almost 20% of patients in its pivotal phase III trials. Symptoms were severe in 2%. Lincalotide’s effectiveness in promoting bowel movements was slightly higher than that of plecanatide (about 48% in the pivotal trials), with a similar placebo response rate.
Plecanatide was approved earlier this year for chronic idiopathic constipation in adults.
Synergy Pharmaceuticals sponsored the study. Dr. Fogel has no financial interest in the company or in plecanatide.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
CHICAGO – Plecanatide, a drug recently approved for chronic idiopathic constipation, bested placebo in two randomized studies evaluating its effect in irritable bowel syndrome with constipation.
Results of the identical, 12-week, phase III studies propelled plecanatide (Trulance; Synergy Pharmaceuticals) into a supplemental new drug application for adult irritable bowel syndrome–constipation predominant (IBS-C), Ronald Fogel, MD, said at the annual Digestive Disease Week®.
During the question-and-answer period, though, clinicians didn’t quite echo the corporate enthusiasm for plecanatide. Several pointed out that overall responder rates were somewhat low for both the 3-mg and 6-mg dose (study -04, 30% both doses; study -05, 21% and 24%), with a drug-placebo differential of about 12% and 7%, respectively. When questioned, Dr. Fogel didn’t have data on the number needed to treat to improve one case. But, he asserted, such response numbers are typical for drug trials in patients with functional bowel disorders and meaningful to those who did respond.
“The differences were statistically significant, and, as someone who was there for both trials, I would say they are also clinically significant,” said Dr. Fogel, founder of the Digestive Health Center of Michigan, Chesterfield. “Patients who did respond were very happy.”
The drug was also quite well-tolerated, with diarrhea as the only important treatment-related adverse event and. This occurred in less than 2% of patients, and only about 1% of either cohort discontinued the medication because of severe diarrhea.
Plecanatide, structurally, is almost identical to uroguanylin, a peptide that regulates sodium and bicarbonate secretion into the intestine but with 8 times greater binding potential to the guanylate cyclase-C receptor. Both the natural and manmade molecules promote fluid secretion into the lumen and inhibit fluid absorption. Uroguanylin is most active in an acidic environment; therefore, plecanatide exerts most of its action in the proximal small intestine.
Synergy also asserts on its website that activation of the GC-C-receptor “may lead to decreased inflammation and pain sensation in the GI tract.” Abdominal pain was not a primary outcome in the pivotal trials for plecanatide’s idiopathic constipation studies, but it was a coprimary endpoint, with stool frequency, for the IBS-C trials.
The studies enrolled a total of 2,189 patients with a diagnosis of IBS-S. They were equally randomized to placebo or plecanatide 3 mg or 6 mg, once daily. Most (75%) were women. The mean age was about 43 years. At baseline, they reported less than one complete, spontaneous bowel movement per week. They also completed an 11-point scale on abdominal symptoms of pain (mean, 6), discomfort (mean, 6.2), and bloating (mean, 6.5).
The study included a 2-week pretreatment assessment period, 12 weeks of daily therapy during which patients filled out an electronic diary of stool frequency and abdominal pain/discomfort, and a 2-week follow-up. The primary endpoint was the number of overall responders, who had to experience both a decrease of at least 30% in their weekly abdominal pain score and an increase of at least one complete, spontaneous bowel movement per week.
Both studies posted statistically significant overall responder rates, relative to placebo, in both doses.
In study -04, the final overall placebo response rate was 17.8%, compared with 30% in the plecanatide 3-mg group and 29.5% in the plecanatide 6-mg group. In study -05, the placebo responder rate was 14%, compared with 21.5% in the 3-mg group and 24% in the 6-mg group.
Dr. Fogel showed stool frequency data but not abdominal pain data. About 41% of patients taking the study drug had increased bowel movements for at least 6 weeks of treatment, compared with 31.4% of those taking placebo. This 9% absolute difference was remarked on during the question-and-answer period as a surprisingly small separation. However, Dr. Fogel said that it was clinically significant as well as statistically so, with a P value of less than 0.001.
Plecanatide worked quickly. By the end of treatment week 1, the placebo and both active groups had already significantly separated, and that separation remained significant throughout the entire treatment period. During the 2-week follow-up period, the effect of both active doses tailed off and fell to the same as placebo by the end of 2 weeks.
One of the drug’s strongest points was its low rate of treatment-related diarrhea. Any diarrhea occurred in about 4% of both dosage groups, compared to 1% of the placebo group. Severe diarrhea occurred in 1% of the 3-mg and 0.4% of the 6-mg group, compared with 0.1% of the placebo group. This caused about 1% of patients to discontinue the study medication.
The adverse event profile was notably better than that of linaclotide (Linzess; Allergan), plecanatide’s close competitor. Also a guanylate cyclase–C agonist, linaclotide provoked diarrhea in almost 20% of patients in its pivotal phase III trials. Symptoms were severe in 2%. Lincalotide’s effectiveness in promoting bowel movements was slightly higher than that of plecanatide (about 48% in the pivotal trials), with a similar placebo response rate.
Plecanatide was approved earlier this year for chronic idiopathic constipation in adults.
Synergy Pharmaceuticals sponsored the study. Dr. Fogel has no financial interest in the company or in plecanatide.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
Key clinical point:
Major finding: In study -04, the placebo response rate was 17.8%, compared with 30% in the plecanatide 3-mg group and 29.5% in the plecanatide 6-mg group. In study -05, the placebo responder rate was 14%, compared with 21.5% in the 3-mg group and 24% in the 6-mg group.
Data source: The studies enrolled almost 2,200 patients.
Disclosures: Synergy Pharmaceuticals sponsored the trials. Dr. Fogel has no financial interest in the company or in plecanatide.
JAK-1 inhibitor upadacitinib advances to phase III for refractory Crohn’s
CHICAGO – An investigational inhibitor of the Janus-1 kinase receptor induced clinical and endoscopic remission at several doses in patients with long-standing, treatment-resistant Crohn’s disease.
The two highest doses of upadacitinib (ABT-494; AbbVie) also allowed about 30% of patients to rapidly withdraw systemic steroids and stay in remission during the 16-week dose-finding induction trial, William J. Sandborn, MD, said at the annual Digestive Disease Week®.
“This rapid steroid tapering was a unique feature of the trial,” said Dr. Sandborn of the University of California, San Diego. “Usually during induction trials, steroids are held fixed at 20 mg-30 mg throughout the trial and then withdrawn to maintenance levels.”
The preplanned analysis used a unique composite outcome of 7-day stool frequency and abdominal pain. At the time of trial design, the scale had only been validated in patients with mild-moderate Crohn’s, so the investigators used the validated stool frequency cutpoint of 1.5 per day as a measure of clinical remission.
That was not an appropriate target for this unique study group, Dr. Sandborn said.
“CELEST was the most refractory patient population ever recruited into a Crohn’s disease clinical trial. If we could do this over now, we would use a cutpoint of less than 3 instead of 1.5 or less. This is a really tough clinical endpoint” that probably isn’t a realistic clinical goal for patients in this category. “There’s no way we would do it this way today. A number of studies since then now suggest that the right cutpoint for remission in these patients would be about 3 per day.”
CELEST enrolled 220 patients who were randomized to five treatment arms comprising 30-35 patients each: placebo; twice daily upadacitinib at 3 mg, 6 mg, 12 mg, and 24 mg (24 mg BID); and 24 mg once daily (24 mg OD). The study lasted 16 weeks and was followed by 36 weeks of blinded extension treatment. Dr. Sandborn reported the 16-week induction phase data.
The patients had moderate to severe Crohn’s disease, with a mean baseline Crohn’s Disease Activity Index (CDAI) score of about 300 and a Simple Endoscopic Score-Crohns disease (SES-CD) of about 15. About 95% had already failed at least one anti–tumor necrosis factor (TNF) drug. Half had failed at least two.
The coprimary endpoints were the proportion of patients who achieved clinical remission (stool frequency of 1.5 or less per day and abdominal pain of 1 or lower) at week 16 and endoscopic remission at weeks 12 or 16. Secondary endpoints included CDAI response, clinical response (at least a 30% reduction from baseline in stool frequency or abdominal pain), and endoscopic response.
In the primary analysis, the rate of endoscopic remission was significant (P less than .05) in both the 24-mg BID and the 24-mg OD groups. However, clinical remission with the original stool frequency cutpoint of 1.5/day or less wasn’t significantly different from placebo in any group. Dr. Sandborn did point out a 27% rate of clinical remission in those taking 12 mg, which had a P value of less than 0.1, relative to placebo.
Among the secondary endpoints, remission as measured by the CDAI score (less than 150) occurred in 39% of those taking 12 mg – the only significant response in that category.
The rate of endoscopic response (at least a 50% improvement in endoscopic findings) was 21% in the 6-mg group and 25% in the 24-mg OD group (P less than 0.05) and in about 30% of the 12-mg and 24-mg BID group (P less than 0.01).
When the clinical remission analysis employed the revised stool frequency cutpoint of less than 2.8/day, clinical remission rates improved somewhat. Almost 40% of those taking 24-mg BID achieved clinical remission (P less than 0.01), and 30% of those taking 6 mg achieved clinical remission, but the significance was marginal (P less than 0.1).
Steroid-free remission rates were significantly better than placebo in the 18-mg group (39%) and the 15-mg group (33%), both with a P value less than 0.05.
Dr. Sandborn also showed dramatic changes in C-reactive protein and fecal calprotectin. These dropped precipitously in all active groups by week 2, in a dose-respondent manner, and stayed well-suppressed in the two highest-dose groups. In the placebo groups, C-reactive protein rose over the 16 weeks, and fecal calprotectin remained unchanged from baseline.
The drug was reasonably well-tolerated and safe. About 80% of each dosing group reported at least one adverse event. The 12-mg dose appeared particularly troublesome, with 25% stopping because of an adverse event. By comparison, the discontinuation rate was 8% in the 24-mg BID group and 14% in the 24-mg OD group.
Serious adverse events were consistent with what is known about the JAK1-inhibitor safety profile, Dr. Sandborn said. There were nine serious infections, including Escherichia coli bacteremia, subcutaneous abscess, and sepsis (3-mg group); anorectal abscess, urinary tract infection, and sepsis (12-mg group); sepsis (24 mg BID); and peritonitis and sepsis (24 mg QD). There was one nonmelanoma skin cancer, which Dr. Sandborn said was probably pre-existing but not recognized at baseline. Three cases of herpes zoster occurred, all in the 24-mg BID group.
One patient experienced a gastrointestinal perforation, which sometimes occurs in Crohn’s disease. Two patients experienced a myocardial infarction, a number “too small to understand fully,” Dr. Sandborn said.
The drug will move forward into phase III trials, but the final dose hasn’t been decided on.
Dr. Sandborn has received consulting fees from AbbVie, which is developing the drug and sponsored CELEST.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
CHICAGO – An investigational inhibitor of the Janus-1 kinase receptor induced clinical and endoscopic remission at several doses in patients with long-standing, treatment-resistant Crohn’s disease.
The two highest doses of upadacitinib (ABT-494; AbbVie) also allowed about 30% of patients to rapidly withdraw systemic steroids and stay in remission during the 16-week dose-finding induction trial, William J. Sandborn, MD, said at the annual Digestive Disease Week®.
“This rapid steroid tapering was a unique feature of the trial,” said Dr. Sandborn of the University of California, San Diego. “Usually during induction trials, steroids are held fixed at 20 mg-30 mg throughout the trial and then withdrawn to maintenance levels.”
The preplanned analysis used a unique composite outcome of 7-day stool frequency and abdominal pain. At the time of trial design, the scale had only been validated in patients with mild-moderate Crohn’s, so the investigators used the validated stool frequency cutpoint of 1.5 per day as a measure of clinical remission.
That was not an appropriate target for this unique study group, Dr. Sandborn said.
“CELEST was the most refractory patient population ever recruited into a Crohn’s disease clinical trial. If we could do this over now, we would use a cutpoint of less than 3 instead of 1.5 or less. This is a really tough clinical endpoint” that probably isn’t a realistic clinical goal for patients in this category. “There’s no way we would do it this way today. A number of studies since then now suggest that the right cutpoint for remission in these patients would be about 3 per day.”
CELEST enrolled 220 patients who were randomized to five treatment arms comprising 30-35 patients each: placebo; twice daily upadacitinib at 3 mg, 6 mg, 12 mg, and 24 mg (24 mg BID); and 24 mg once daily (24 mg OD). The study lasted 16 weeks and was followed by 36 weeks of blinded extension treatment. Dr. Sandborn reported the 16-week induction phase data.
The patients had moderate to severe Crohn’s disease, with a mean baseline Crohn’s Disease Activity Index (CDAI) score of about 300 and a Simple Endoscopic Score-Crohns disease (SES-CD) of about 15. About 95% had already failed at least one anti–tumor necrosis factor (TNF) drug. Half had failed at least two.
The coprimary endpoints were the proportion of patients who achieved clinical remission (stool frequency of 1.5 or less per day and abdominal pain of 1 or lower) at week 16 and endoscopic remission at weeks 12 or 16. Secondary endpoints included CDAI response, clinical response (at least a 30% reduction from baseline in stool frequency or abdominal pain), and endoscopic response.
In the primary analysis, the rate of endoscopic remission was significant (P less than .05) in both the 24-mg BID and the 24-mg OD groups. However, clinical remission with the original stool frequency cutpoint of 1.5/day or less wasn’t significantly different from placebo in any group. Dr. Sandborn did point out a 27% rate of clinical remission in those taking 12 mg, which had a P value of less than 0.1, relative to placebo.
Among the secondary endpoints, remission as measured by the CDAI score (less than 150) occurred in 39% of those taking 12 mg – the only significant response in that category.
The rate of endoscopic response (at least a 50% improvement in endoscopic findings) was 21% in the 6-mg group and 25% in the 24-mg OD group (P less than 0.05) and in about 30% of the 12-mg and 24-mg BID group (P less than 0.01).
When the clinical remission analysis employed the revised stool frequency cutpoint of less than 2.8/day, clinical remission rates improved somewhat. Almost 40% of those taking 24-mg BID achieved clinical remission (P less than 0.01), and 30% of those taking 6 mg achieved clinical remission, but the significance was marginal (P less than 0.1).
Steroid-free remission rates were significantly better than placebo in the 18-mg group (39%) and the 15-mg group (33%), both with a P value less than 0.05.
Dr. Sandborn also showed dramatic changes in C-reactive protein and fecal calprotectin. These dropped precipitously in all active groups by week 2, in a dose-respondent manner, and stayed well-suppressed in the two highest-dose groups. In the placebo groups, C-reactive protein rose over the 16 weeks, and fecal calprotectin remained unchanged from baseline.
The drug was reasonably well-tolerated and safe. About 80% of each dosing group reported at least one adverse event. The 12-mg dose appeared particularly troublesome, with 25% stopping because of an adverse event. By comparison, the discontinuation rate was 8% in the 24-mg BID group and 14% in the 24-mg OD group.
Serious adverse events were consistent with what is known about the JAK1-inhibitor safety profile, Dr. Sandborn said. There were nine serious infections, including Escherichia coli bacteremia, subcutaneous abscess, and sepsis (3-mg group); anorectal abscess, urinary tract infection, and sepsis (12-mg group); sepsis (24 mg BID); and peritonitis and sepsis (24 mg QD). There was one nonmelanoma skin cancer, which Dr. Sandborn said was probably pre-existing but not recognized at baseline. Three cases of herpes zoster occurred, all in the 24-mg BID group.
One patient experienced a gastrointestinal perforation, which sometimes occurs in Crohn’s disease. Two patients experienced a myocardial infarction, a number “too small to understand fully,” Dr. Sandborn said.
The drug will move forward into phase III trials, but the final dose hasn’t been decided on.
Dr. Sandborn has received consulting fees from AbbVie, which is developing the drug and sponsored CELEST.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
CHICAGO – An investigational inhibitor of the Janus-1 kinase receptor induced clinical and endoscopic remission at several doses in patients with long-standing, treatment-resistant Crohn’s disease.
The two highest doses of upadacitinib (ABT-494; AbbVie) also allowed about 30% of patients to rapidly withdraw systemic steroids and stay in remission during the 16-week dose-finding induction trial, William J. Sandborn, MD, said at the annual Digestive Disease Week®.
“This rapid steroid tapering was a unique feature of the trial,” said Dr. Sandborn of the University of California, San Diego. “Usually during induction trials, steroids are held fixed at 20 mg-30 mg throughout the trial and then withdrawn to maintenance levels.”
The preplanned analysis used a unique composite outcome of 7-day stool frequency and abdominal pain. At the time of trial design, the scale had only been validated in patients with mild-moderate Crohn’s, so the investigators used the validated stool frequency cutpoint of 1.5 per day as a measure of clinical remission.
That was not an appropriate target for this unique study group, Dr. Sandborn said.
“CELEST was the most refractory patient population ever recruited into a Crohn’s disease clinical trial. If we could do this over now, we would use a cutpoint of less than 3 instead of 1.5 or less. This is a really tough clinical endpoint” that probably isn’t a realistic clinical goal for patients in this category. “There’s no way we would do it this way today. A number of studies since then now suggest that the right cutpoint for remission in these patients would be about 3 per day.”
CELEST enrolled 220 patients who were randomized to five treatment arms comprising 30-35 patients each: placebo; twice daily upadacitinib at 3 mg, 6 mg, 12 mg, and 24 mg (24 mg BID); and 24 mg once daily (24 mg OD). The study lasted 16 weeks and was followed by 36 weeks of blinded extension treatment. Dr. Sandborn reported the 16-week induction phase data.
The patients had moderate to severe Crohn’s disease, with a mean baseline Crohn’s Disease Activity Index (CDAI) score of about 300 and a Simple Endoscopic Score-Crohns disease (SES-CD) of about 15. About 95% had already failed at least one anti–tumor necrosis factor (TNF) drug. Half had failed at least two.
The coprimary endpoints were the proportion of patients who achieved clinical remission (stool frequency of 1.5 or less per day and abdominal pain of 1 or lower) at week 16 and endoscopic remission at weeks 12 or 16. Secondary endpoints included CDAI response, clinical response (at least a 30% reduction from baseline in stool frequency or abdominal pain), and endoscopic response.
In the primary analysis, the rate of endoscopic remission was significant (P less than .05) in both the 24-mg BID and the 24-mg OD groups. However, clinical remission with the original stool frequency cutpoint of 1.5/day or less wasn’t significantly different from placebo in any group. Dr. Sandborn did point out a 27% rate of clinical remission in those taking 12 mg, which had a P value of less than 0.1, relative to placebo.
Among the secondary endpoints, remission as measured by the CDAI score (less than 150) occurred in 39% of those taking 12 mg – the only significant response in that category.
The rate of endoscopic response (at least a 50% improvement in endoscopic findings) was 21% in the 6-mg group and 25% in the 24-mg OD group (P less than 0.05) and in about 30% of the 12-mg and 24-mg BID group (P less than 0.01).
When the clinical remission analysis employed the revised stool frequency cutpoint of less than 2.8/day, clinical remission rates improved somewhat. Almost 40% of those taking 24-mg BID achieved clinical remission (P less than 0.01), and 30% of those taking 6 mg achieved clinical remission, but the significance was marginal (P less than 0.1).
Steroid-free remission rates were significantly better than placebo in the 18-mg group (39%) and the 15-mg group (33%), both with a P value less than 0.05.
Dr. Sandborn also showed dramatic changes in C-reactive protein and fecal calprotectin. These dropped precipitously in all active groups by week 2, in a dose-respondent manner, and stayed well-suppressed in the two highest-dose groups. In the placebo groups, C-reactive protein rose over the 16 weeks, and fecal calprotectin remained unchanged from baseline.
The drug was reasonably well-tolerated and safe. About 80% of each dosing group reported at least one adverse event. The 12-mg dose appeared particularly troublesome, with 25% stopping because of an adverse event. By comparison, the discontinuation rate was 8% in the 24-mg BID group and 14% in the 24-mg OD group.
Serious adverse events were consistent with what is known about the JAK1-inhibitor safety profile, Dr. Sandborn said. There were nine serious infections, including Escherichia coli bacteremia, subcutaneous abscess, and sepsis (3-mg group); anorectal abscess, urinary tract infection, and sepsis (12-mg group); sepsis (24 mg BID); and peritonitis and sepsis (24 mg QD). There was one nonmelanoma skin cancer, which Dr. Sandborn said was probably pre-existing but not recognized at baseline. Three cases of herpes zoster occurred, all in the 24-mg BID group.
One patient experienced a gastrointestinal perforation, which sometimes occurs in Crohn’s disease. Two patients experienced a myocardial infarction, a number “too small to understand fully,” Dr. Sandborn said.
The drug will move forward into phase III trials, but the final dose hasn’t been decided on.
Dr. Sandborn has received consulting fees from AbbVie, which is developing the drug and sponsored CELEST.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
AT DDW
Key clinical point:
Major finding: Several doses achieved statistically significant effects in endoscopic and clinical response. About 30% of patients taking a higher dose achieved steroid-free remission.
Data source: The phase II dose-ranging study comprised 220 patients.
Disclosures: AbbVie is developing the drug and sponsored the study. Dr. Sandborn is a consultant for the company.
VIDEO: LINX magnetic band beats omeprazole for GERD regurgitation
CHICAGO – Persistent reflux symptoms resolved in 93% of patients who underwent laparoscopic deployment of a circlet of magnet beads to the lower esophageal juncture, but in just 9% of those who doubled their dose of omeprazole, Reginald Bell, MD, said at the annual Digestive Disease Week®.
In addition to bolstering positive device data, the results of this ongoing randomized study suggest that it may be time to rethink the treatment algorithm for patients who don’t respond optimally to medical therapy, Dr. Bell said in an interview.
“We found that relatively few patients respond well to the typical doubling of PPIs,” said Dr. Bell of the SOFI SurgOne Foregut Institute, Englewood, Colo. “In light of these strong results, it’s my opinion that we should consider going straight to surgery for at least some of these patients”
The LINX Reflux Management System (TORAX Medical; Shoreview, Minn.) is a small, flexible band of interlinked titanium beads with magnetic cores. The magnetic attraction between the beads keeps them joined when the lower esophageal sphincter is at rest. It exerts just enough resistance, however, to keep the sphincter from opening under gastric pressures of less than about 20 mm Hg, preventing reflux into the esophagus. Reflux typically occurs at an opening pressure of 10-12 mm Hg. Swallowing pressures, however, generally exceed 20 mm Hg, Dr. Bell said, allowing the circlet to expand enough to allow free passage of the bolus. The magnetic forces then bring the beads back together, again keeping the sphincter in a closed position.
This variable pressure is a big advantage over the Nissen fundoplication, which creates a pseudoflap that isn’t as yielding to intragastric pressure, Dr. Bell said. Nissen patients frequently have trouble belching or vomiting, and can experience bloating and distention from a reduced ability to vent gases. That is generally not a problem with LINX patients. And while some do initially experience dysphagia, this is typically transient. In the pivotal trial, bloating occurred in 7% of patients by 24 months.
The study comprised 150 patients with persistent symptoms of gastroesophageal reflux disease (GERD), despite at least 8 weeks of taking 20 mg omeprazole daily. These patients were randomized on a 2:1 scheme to either a doubling of omeprazole (20 mg twice a day) or surgery with LINX. Dr. Bell reported 6-month outcomes on 80 patients, 25 of whom had the LINX procedure and 55 of whom began double-dose omeprazole.
These patients were a mean of 47 years old, and had used a proton pump inhibitor (PPI) for a mean of 8 years. Baseline work-ups confirmed moderate to severe GERD, with about 12% of gastric measurement times at less than pH 4. The mean DeMeester Score was about 40. On the GERD Health-Related Quality of Life Questionnaire, patients scored about 24 while on medical therapy and 31 while off. They reported moderate to severe heartburn and regurgitation.
The study’s primary endpoint was relief of moderate to severe regurgitation. This was reached in 93% of the LINX group and 9% of the double-dose PPI group – a significant difference. Significantly more LINX patients also achieved at least a 50% reduction in their baseline GERD-HRQL score (90% vs.7%). The mean score dropped from about 32-5 in the LINX group and 30-24 in the PPI group.
Mean scores on the Reflux Disease Questionnaire improved significantly more in the LINX group than in the PPI group, including regurgitation (4.2.-1.4; 4.4 at both time points), and heartburn (3.4-1.6; 3.6-3.9).
An independent, blinded laboratory conducted pH/impedance testing on the cohort; the normal values were less than 57 reflux episodes/24 hours. At 6 months, the LINX group experienced a mean of 30 episodes vs. 70 in the PPI group.
When the investigators examined a combined measure of the number of reflux episodes and the change in DeMeester scores, they found normal reflux in 92% of the LINX group and 36% of the PPI group.
There was one adverse event related to the LINX procedure. A 66-year-old man was hospitalized and medically treated for esophageal spasms. The incident resolved with no sequelae, Dr. Bell said. So far, one LINX patient has needed to add PPI therapy; other studies typically show that 2%-3% of patients with the device do so.
Dr. Bell disclosed that he is a consultant for TORAX.
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
msullivan@frontlinemedcom.com
On Twitter @Alz_gal
CHICAGO – Persistent reflux symptoms resolved in 93% of patients who underwent laparoscopic deployment of a circlet of magnet beads to the lower esophageal juncture, but in just 9% of those who doubled their dose of omeprazole, Reginald Bell, MD, said at the annual Digestive Disease Week®.
In addition to bolstering positive device data, the results of this ongoing randomized study suggest that it may be time to rethink the treatment algorithm for patients who don’t respond optimally to medical therapy, Dr. Bell said in an interview.
“We found that relatively few patients respond well to the typical doubling of PPIs,” said Dr. Bell of the SOFI SurgOne Foregut Institute, Englewood, Colo. “In light of these strong results, it’s my opinion that we should consider going straight to surgery for at least some of these patients”
The LINX Reflux Management System (TORAX Medical; Shoreview, Minn.) is a small, flexible band of interlinked titanium beads with magnetic cores. The magnetic attraction between the beads keeps them joined when the lower esophageal sphincter is at rest. It exerts just enough resistance, however, to keep the sphincter from opening under gastric pressures of less than about 20 mm Hg, preventing reflux into the esophagus. Reflux typically occurs at an opening pressure of 10-12 mm Hg. Swallowing pressures, however, generally exceed 20 mm Hg, Dr. Bell said, allowing the circlet to expand enough to allow free passage of the bolus. The magnetic forces then bring the beads back together, again keeping the sphincter in a closed position.
This variable pressure is a big advantage over the Nissen fundoplication, which creates a pseudoflap that isn’t as yielding to intragastric pressure, Dr. Bell said. Nissen patients frequently have trouble belching or vomiting, and can experience bloating and distention from a reduced ability to vent gases. That is generally not a problem with LINX patients. And while some do initially experience dysphagia, this is typically transient. In the pivotal trial, bloating occurred in 7% of patients by 24 months.
The study comprised 150 patients with persistent symptoms of gastroesophageal reflux disease (GERD), despite at least 8 weeks of taking 20 mg omeprazole daily. These patients were randomized on a 2:1 scheme to either a doubling of omeprazole (20 mg twice a day) or surgery with LINX. Dr. Bell reported 6-month outcomes on 80 patients, 25 of whom had the LINX procedure and 55 of whom began double-dose omeprazole.
These patients were a mean of 47 years old, and had used a proton pump inhibitor (PPI) for a mean of 8 years. Baseline work-ups confirmed moderate to severe GERD, with about 12% of gastric measurement times at less than pH 4. The mean DeMeester Score was about 40. On the GERD Health-Related Quality of Life Questionnaire, patients scored about 24 while on medical therapy and 31 while off. They reported moderate to severe heartburn and regurgitation.
The study’s primary endpoint was relief of moderate to severe regurgitation. This was reached in 93% of the LINX group and 9% of the double-dose PPI group – a significant difference. Significantly more LINX patients also achieved at least a 50% reduction in their baseline GERD-HRQL score (90% vs.7%). The mean score dropped from about 32-5 in the LINX group and 30-24 in the PPI group.
Mean scores on the Reflux Disease Questionnaire improved significantly more in the LINX group than in the PPI group, including regurgitation (4.2.-1.4; 4.4 at both time points), and heartburn (3.4-1.6; 3.6-3.9).
An independent, blinded laboratory conducted pH/impedance testing on the cohort; the normal values were less than 57 reflux episodes/24 hours. At 6 months, the LINX group experienced a mean of 30 episodes vs. 70 in the PPI group.
When the investigators examined a combined measure of the number of reflux episodes and the change in DeMeester scores, they found normal reflux in 92% of the LINX group and 36% of the PPI group.
There was one adverse event related to the LINX procedure. A 66-year-old man was hospitalized and medically treated for esophageal spasms. The incident resolved with no sequelae, Dr. Bell said. So far, one LINX patient has needed to add PPI therapy; other studies typically show that 2%-3% of patients with the device do so.
Dr. Bell disclosed that he is a consultant for TORAX.
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
msullivan@frontlinemedcom.com
On Twitter @Alz_gal
CHICAGO – Persistent reflux symptoms resolved in 93% of patients who underwent laparoscopic deployment of a circlet of magnet beads to the lower esophageal juncture, but in just 9% of those who doubled their dose of omeprazole, Reginald Bell, MD, said at the annual Digestive Disease Week®.
In addition to bolstering positive device data, the results of this ongoing randomized study suggest that it may be time to rethink the treatment algorithm for patients who don’t respond optimally to medical therapy, Dr. Bell said in an interview.
“We found that relatively few patients respond well to the typical doubling of PPIs,” said Dr. Bell of the SOFI SurgOne Foregut Institute, Englewood, Colo. “In light of these strong results, it’s my opinion that we should consider going straight to surgery for at least some of these patients”
The LINX Reflux Management System (TORAX Medical; Shoreview, Minn.) is a small, flexible band of interlinked titanium beads with magnetic cores. The magnetic attraction between the beads keeps them joined when the lower esophageal sphincter is at rest. It exerts just enough resistance, however, to keep the sphincter from opening under gastric pressures of less than about 20 mm Hg, preventing reflux into the esophagus. Reflux typically occurs at an opening pressure of 10-12 mm Hg. Swallowing pressures, however, generally exceed 20 mm Hg, Dr. Bell said, allowing the circlet to expand enough to allow free passage of the bolus. The magnetic forces then bring the beads back together, again keeping the sphincter in a closed position.
This variable pressure is a big advantage over the Nissen fundoplication, which creates a pseudoflap that isn’t as yielding to intragastric pressure, Dr. Bell said. Nissen patients frequently have trouble belching or vomiting, and can experience bloating and distention from a reduced ability to vent gases. That is generally not a problem with LINX patients. And while some do initially experience dysphagia, this is typically transient. In the pivotal trial, bloating occurred in 7% of patients by 24 months.
The study comprised 150 patients with persistent symptoms of gastroesophageal reflux disease (GERD), despite at least 8 weeks of taking 20 mg omeprazole daily. These patients were randomized on a 2:1 scheme to either a doubling of omeprazole (20 mg twice a day) or surgery with LINX. Dr. Bell reported 6-month outcomes on 80 patients, 25 of whom had the LINX procedure and 55 of whom began double-dose omeprazole.
These patients were a mean of 47 years old, and had used a proton pump inhibitor (PPI) for a mean of 8 years. Baseline work-ups confirmed moderate to severe GERD, with about 12% of gastric measurement times at less than pH 4. The mean DeMeester Score was about 40. On the GERD Health-Related Quality of Life Questionnaire, patients scored about 24 while on medical therapy and 31 while off. They reported moderate to severe heartburn and regurgitation.
The study’s primary endpoint was relief of moderate to severe regurgitation. This was reached in 93% of the LINX group and 9% of the double-dose PPI group – a significant difference. Significantly more LINX patients also achieved at least a 50% reduction in their baseline GERD-HRQL score (90% vs.7%). The mean score dropped from about 32-5 in the LINX group and 30-24 in the PPI group.
Mean scores on the Reflux Disease Questionnaire improved significantly more in the LINX group than in the PPI group, including regurgitation (4.2.-1.4; 4.4 at both time points), and heartburn (3.4-1.6; 3.6-3.9).
An independent, blinded laboratory conducted pH/impedance testing on the cohort; the normal values were less than 57 reflux episodes/24 hours. At 6 months, the LINX group experienced a mean of 30 episodes vs. 70 in the PPI group.
When the investigators examined a combined measure of the number of reflux episodes and the change in DeMeester scores, they found normal reflux in 92% of the LINX group and 36% of the PPI group.
There was one adverse event related to the LINX procedure. A 66-year-old man was hospitalized and medically treated for esophageal spasms. The incident resolved with no sequelae, Dr. Bell said. So far, one LINX patient has needed to add PPI therapy; other studies typically show that 2%-3% of patients with the device do so.
Dr. Bell disclosed that he is a consultant for TORAX.
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
msullivan@frontlinemedcom.com
On Twitter @Alz_gal
AT DDW 2017
Key clinical point:
Major finding: Symptoms resolved in 93% of patients, compared to 9% of those who took the proton pump inhibitor.
Data source: An ongoing randomized study of 150 patients; Dr. Bell reported 6-month outcomes on 80.
Disclosures: Dr. Bell is a consultant for TORAX Medical, which developed and manufactures the device.
Misoprostol effective in healing aspirin-induced small bowel bleeding
CHICAGO – , a small study showed.
Compared with placebo, it was superior in healing small bowel ulcers. A total of 12 patients who received misoprostol had complete healing at 8 weeks, compared with 4 in the placebo group (P = .017).
“Among patients with overt bleeding or anemia from small bowel lesions who receive continuous aspirin therapy, misoprostol is superior to placebo in achieving complete mucosal healing,” said lead author Francis Chan, MD, professor of gastroenterology and hepatology at the Chinese University of Hong Kong, who presented the findings at the annual Digestive Disease Week®.
Millions of individuals use low-dose aspirin daily to lower their risk of stroke and cardiovascular events, but they face a risk of gastrointestinal bleeding. In fact, Dr. Chan pointed out, continuous aspirin use has been associated with a threefold risk of a lower GI bleed.
“But to date, there is no effective pharmacological treatment for small bowel ulcers that are associated with use of low-dose aspirin,” he said.
Misoprostol is a synthetic prostaglandin E1 analog that is indicated for reducing the risk of NSAID–induced gastric ulcers in individuals who are at high risk of complications from gastric ulcers. In their study, Dr. Chan and his colleagues assessed the efficacy of misoprostol for healing small bowel ulcers in patients with GI bleeding who were using continuous aspirin therapy.
The primary endpoint was complete mucosal healing in 8 weeks, and secondary endpoints included changes in the number of GI erosions.
The double-blind, randomized, placebo-controlled trial included 35 patients assigned to misoprostol and 37 to placebo. All patients were on regular aspirin (at least 160 mg/day) for established cardiothrombotic diseases and had either overt bleeding of the small bowel or anemia. No bleeding source was identified on gastroscopy and colonoscopy. They had a score of 3 (more than four erosions) or 4 (large erosion or ulcer) that was confirmed by capsule endoscopy.
Those randomized to the active therapy arm received 200 mg misoprostol four times daily, and all patients continued aspirin 80 mg/day for the duration of the trial. During the study period, concomitant NSAIDs, proton pump inhibitors, sucralfate, rebamipide, antibiotics, corticosteroids, or iron supplement was prohibited.
A follow-up capsule endoscopy was performed at 8 weeks to assess mucosal healing, and all images were evaluated by a blinded panel.
The intention-to-treat population included all patients who took at least one dose of the study drug and returned for follow-up capsule endoscopy (n = 72).
In this population, 33% of patients in the misoprostol group and 10.5% on placebo had complete mucosal healing at 8 weeks.
“For the secondary endpoint of changes in small bowel erosions, there was a significant difference between the misoprostol group and placebo group with a P value of .025,” said Dr. Chan.
The study was supported by a competitive grant from the Research Grant Council of Hong Kong. Dr. Chan reported relationships with AstraZeneca, Eisai, Pfizer, and Takeda.
CHICAGO – , a small study showed.
Compared with placebo, it was superior in healing small bowel ulcers. A total of 12 patients who received misoprostol had complete healing at 8 weeks, compared with 4 in the placebo group (P = .017).
“Among patients with overt bleeding or anemia from small bowel lesions who receive continuous aspirin therapy, misoprostol is superior to placebo in achieving complete mucosal healing,” said lead author Francis Chan, MD, professor of gastroenterology and hepatology at the Chinese University of Hong Kong, who presented the findings at the annual Digestive Disease Week®.
Millions of individuals use low-dose aspirin daily to lower their risk of stroke and cardiovascular events, but they face a risk of gastrointestinal bleeding. In fact, Dr. Chan pointed out, continuous aspirin use has been associated with a threefold risk of a lower GI bleed.
“But to date, there is no effective pharmacological treatment for small bowel ulcers that are associated with use of low-dose aspirin,” he said.
Misoprostol is a synthetic prostaglandin E1 analog that is indicated for reducing the risk of NSAID–induced gastric ulcers in individuals who are at high risk of complications from gastric ulcers. In their study, Dr. Chan and his colleagues assessed the efficacy of misoprostol for healing small bowel ulcers in patients with GI bleeding who were using continuous aspirin therapy.
The primary endpoint was complete mucosal healing in 8 weeks, and secondary endpoints included changes in the number of GI erosions.
The double-blind, randomized, placebo-controlled trial included 35 patients assigned to misoprostol and 37 to placebo. All patients were on regular aspirin (at least 160 mg/day) for established cardiothrombotic diseases and had either overt bleeding of the small bowel or anemia. No bleeding source was identified on gastroscopy and colonoscopy. They had a score of 3 (more than four erosions) or 4 (large erosion or ulcer) that was confirmed by capsule endoscopy.
Those randomized to the active therapy arm received 200 mg misoprostol four times daily, and all patients continued aspirin 80 mg/day for the duration of the trial. During the study period, concomitant NSAIDs, proton pump inhibitors, sucralfate, rebamipide, antibiotics, corticosteroids, or iron supplement was prohibited.
A follow-up capsule endoscopy was performed at 8 weeks to assess mucosal healing, and all images were evaluated by a blinded panel.
The intention-to-treat population included all patients who took at least one dose of the study drug and returned for follow-up capsule endoscopy (n = 72).
In this population, 33% of patients in the misoprostol group and 10.5% on placebo had complete mucosal healing at 8 weeks.
“For the secondary endpoint of changes in small bowel erosions, there was a significant difference between the misoprostol group and placebo group with a P value of .025,” said Dr. Chan.
The study was supported by a competitive grant from the Research Grant Council of Hong Kong. Dr. Chan reported relationships with AstraZeneca, Eisai, Pfizer, and Takeda.
CHICAGO – , a small study showed.
Compared with placebo, it was superior in healing small bowel ulcers. A total of 12 patients who received misoprostol had complete healing at 8 weeks, compared with 4 in the placebo group (P = .017).
“Among patients with overt bleeding or anemia from small bowel lesions who receive continuous aspirin therapy, misoprostol is superior to placebo in achieving complete mucosal healing,” said lead author Francis Chan, MD, professor of gastroenterology and hepatology at the Chinese University of Hong Kong, who presented the findings at the annual Digestive Disease Week®.
Millions of individuals use low-dose aspirin daily to lower their risk of stroke and cardiovascular events, but they face a risk of gastrointestinal bleeding. In fact, Dr. Chan pointed out, continuous aspirin use has been associated with a threefold risk of a lower GI bleed.
“But to date, there is no effective pharmacological treatment for small bowel ulcers that are associated with use of low-dose aspirin,” he said.
Misoprostol is a synthetic prostaglandin E1 analog that is indicated for reducing the risk of NSAID–induced gastric ulcers in individuals who are at high risk of complications from gastric ulcers. In their study, Dr. Chan and his colleagues assessed the efficacy of misoprostol for healing small bowel ulcers in patients with GI bleeding who were using continuous aspirin therapy.
The primary endpoint was complete mucosal healing in 8 weeks, and secondary endpoints included changes in the number of GI erosions.
The double-blind, randomized, placebo-controlled trial included 35 patients assigned to misoprostol and 37 to placebo. All patients were on regular aspirin (at least 160 mg/day) for established cardiothrombotic diseases and had either overt bleeding of the small bowel or anemia. No bleeding source was identified on gastroscopy and colonoscopy. They had a score of 3 (more than four erosions) or 4 (large erosion or ulcer) that was confirmed by capsule endoscopy.
Those randomized to the active therapy arm received 200 mg misoprostol four times daily, and all patients continued aspirin 80 mg/day for the duration of the trial. During the study period, concomitant NSAIDs, proton pump inhibitors, sucralfate, rebamipide, antibiotics, corticosteroids, or iron supplement was prohibited.
A follow-up capsule endoscopy was performed at 8 weeks to assess mucosal healing, and all images were evaluated by a blinded panel.
The intention-to-treat population included all patients who took at least one dose of the study drug and returned for follow-up capsule endoscopy (n = 72).
In this population, 33% of patients in the misoprostol group and 10.5% on placebo had complete mucosal healing at 8 weeks.
“For the secondary endpoint of changes in small bowel erosions, there was a significant difference between the misoprostol group and placebo group with a P value of .025,” said Dr. Chan.
The study was supported by a competitive grant from the Research Grant Council of Hong Kong. Dr. Chan reported relationships with AstraZeneca, Eisai, Pfizer, and Takeda.
AT DDW
Key clinical point: Misoprostol was more effective than placebo in healing small bowel ulcers in patients who used daily low-dose aspirin.
Major finding: 33% of patients in the misoprostol group and 10.5% on placebo had complete mucosal healing at 8 weeks.
Data source: An 8-week, double-blind, randomized placebo-controlled trial of 72 patients that assessed misoprostol vs. placebo for healing small bowel ulcers.
Disclosures: The study was supported by a competitive grant from the Research Grant Council of Hong Kong. Dr. Chan reported relationships with AstraZeneca, Eisai, Pfizer, and Takeda.
CRC in Lynch syndrome is lower than previously reported
CHICAGO – Lynch syndrome can predispose individuals to a number of different cancer types, including colorectal tumors, but the results of a preliminary study found that the incidence may be lower than what has been previously reported.
New findings presented at Digestive Disease Week® showed that the incidence of colorectal cancer after screening with colonoscopy ranged from 6.3% to 25.9%, depending on the specific mutated gene. This is in contrast to other reports which have found a 50% increase in the incidence of colorectal cancer in individuals with Lynch syndrome.
“We looked at the incidence of colorectal cancer and other associated cancers in individuals with Lynch syndrome and how screening can have an impact on that,” said study author Ariadna Sanchez, MD, from the Hospital Clínic de Barcelona, Spain.
She emphasized that the results being presented at the meeting are preliminary and, thus, will need further confirmation, but it is a multicenter study and is being conducted in more than 1,100 patients.
“The diagnosis of colorectal cancer with screening colonoscopy is lower than results that have been previously published,” she said. “This finding reinforces the importance of screening colonoscopies in patients with Lynch syndrome.”
As to why their rates are lower, Dr. Sanchez speculated that it may be because precancerous polyps are being removed with screening.
“Our thinking is that, as we perform screening and remove the polyps, then in theory, cancer will be prevented,” she explained, “since they didn’t have the opportunity to continue to progress into cancer.”
In other words, screening this high-risk population may not only identify those who have cancer but may prevent it from developing in others.
Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC), is an inherited disorder that increases the risk of many types of cancer, including colorectal and cancers of the stomach, small intestine, liver, gallbladder ducts, upper urinary tract, brain, skin, ovaries, and endometrium.
Caused by germline mutations in the mismatch DNA repair system (MLH1, MSH2, MSH6, PMS2), it has been difficult to make precise estimates of cancer risk in individuals with the syndrome because of retrospective studies and small cohorts.
Dr. Sanchez and her colleagues conducted a multicenter nation-wide study in Spain with the goal of establishing the cumulative incidence of colorectal cancer and other tumor types in Lynch syndrome and to evaluate the effect of screening surveillance on cancer incidence. Cancer-specific survival will also be assessed.
The cohort included 1,108 patients with Lynch syndrome from 25 centers, who were followed-up for a mean of 67.5 (± 57.8 months).
The first colonoscopy screening detected cancer in 49 patients (MLH1, n = 23/268; MSH2, n = 18/249; MSH6, n = 4/154; PMS2, n = 2/47; EPCAM, n = 2/13), extrapolating to a cumulative incidence of 25.6% for MLH1, 22.1% for MSH2, 6.3% for MSH6, and 25.9% for PMS2 mutation carriers.
Most patients were diagnosed with stage 1 disease (45.7%) and, to a lesser degree, with stage II (28.6%), stage III (22.9%), and stage IV (2.9%).
The 10-year cumulative incidences for subsequent colorectal cancers for patients who had a previous diagnosis of the disease were 9.4% (95% CI, 5-17) for MLH1, 12.6% (95% CI, 5.6-27.6) for MSH2, and 17.2% (95% CI, 6.6-40) for MSH6.
Digestive Disease Week is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
CHICAGO – Lynch syndrome can predispose individuals to a number of different cancer types, including colorectal tumors, but the results of a preliminary study found that the incidence may be lower than what has been previously reported.
New findings presented at Digestive Disease Week® showed that the incidence of colorectal cancer after screening with colonoscopy ranged from 6.3% to 25.9%, depending on the specific mutated gene. This is in contrast to other reports which have found a 50% increase in the incidence of colorectal cancer in individuals with Lynch syndrome.
“We looked at the incidence of colorectal cancer and other associated cancers in individuals with Lynch syndrome and how screening can have an impact on that,” said study author Ariadna Sanchez, MD, from the Hospital Clínic de Barcelona, Spain.
She emphasized that the results being presented at the meeting are preliminary and, thus, will need further confirmation, but it is a multicenter study and is being conducted in more than 1,100 patients.
“The diagnosis of colorectal cancer with screening colonoscopy is lower than results that have been previously published,” she said. “This finding reinforces the importance of screening colonoscopies in patients with Lynch syndrome.”
As to why their rates are lower, Dr. Sanchez speculated that it may be because precancerous polyps are being removed with screening.
“Our thinking is that, as we perform screening and remove the polyps, then in theory, cancer will be prevented,” she explained, “since they didn’t have the opportunity to continue to progress into cancer.”
In other words, screening this high-risk population may not only identify those who have cancer but may prevent it from developing in others.
Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC), is an inherited disorder that increases the risk of many types of cancer, including colorectal and cancers of the stomach, small intestine, liver, gallbladder ducts, upper urinary tract, brain, skin, ovaries, and endometrium.
Caused by germline mutations in the mismatch DNA repair system (MLH1, MSH2, MSH6, PMS2), it has been difficult to make precise estimates of cancer risk in individuals with the syndrome because of retrospective studies and small cohorts.
Dr. Sanchez and her colleagues conducted a multicenter nation-wide study in Spain with the goal of establishing the cumulative incidence of colorectal cancer and other tumor types in Lynch syndrome and to evaluate the effect of screening surveillance on cancer incidence. Cancer-specific survival will also be assessed.
The cohort included 1,108 patients with Lynch syndrome from 25 centers, who were followed-up for a mean of 67.5 (± 57.8 months).
The first colonoscopy screening detected cancer in 49 patients (MLH1, n = 23/268; MSH2, n = 18/249; MSH6, n = 4/154; PMS2, n = 2/47; EPCAM, n = 2/13), extrapolating to a cumulative incidence of 25.6% for MLH1, 22.1% for MSH2, 6.3% for MSH6, and 25.9% for PMS2 mutation carriers.
Most patients were diagnosed with stage 1 disease (45.7%) and, to a lesser degree, with stage II (28.6%), stage III (22.9%), and stage IV (2.9%).
The 10-year cumulative incidences for subsequent colorectal cancers for patients who had a previous diagnosis of the disease were 9.4% (95% CI, 5-17) for MLH1, 12.6% (95% CI, 5.6-27.6) for MSH2, and 17.2% (95% CI, 6.6-40) for MSH6.
Digestive Disease Week is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
CHICAGO – Lynch syndrome can predispose individuals to a number of different cancer types, including colorectal tumors, but the results of a preliminary study found that the incidence may be lower than what has been previously reported.
New findings presented at Digestive Disease Week® showed that the incidence of colorectal cancer after screening with colonoscopy ranged from 6.3% to 25.9%, depending on the specific mutated gene. This is in contrast to other reports which have found a 50% increase in the incidence of colorectal cancer in individuals with Lynch syndrome.
“We looked at the incidence of colorectal cancer and other associated cancers in individuals with Lynch syndrome and how screening can have an impact on that,” said study author Ariadna Sanchez, MD, from the Hospital Clínic de Barcelona, Spain.
She emphasized that the results being presented at the meeting are preliminary and, thus, will need further confirmation, but it is a multicenter study and is being conducted in more than 1,100 patients.
“The diagnosis of colorectal cancer with screening colonoscopy is lower than results that have been previously published,” she said. “This finding reinforces the importance of screening colonoscopies in patients with Lynch syndrome.”
As to why their rates are lower, Dr. Sanchez speculated that it may be because precancerous polyps are being removed with screening.
“Our thinking is that, as we perform screening and remove the polyps, then in theory, cancer will be prevented,” she explained, “since they didn’t have the opportunity to continue to progress into cancer.”
In other words, screening this high-risk population may not only identify those who have cancer but may prevent it from developing in others.
Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC), is an inherited disorder that increases the risk of many types of cancer, including colorectal and cancers of the stomach, small intestine, liver, gallbladder ducts, upper urinary tract, brain, skin, ovaries, and endometrium.
Caused by germline mutations in the mismatch DNA repair system (MLH1, MSH2, MSH6, PMS2), it has been difficult to make precise estimates of cancer risk in individuals with the syndrome because of retrospective studies and small cohorts.
Dr. Sanchez and her colleagues conducted a multicenter nation-wide study in Spain with the goal of establishing the cumulative incidence of colorectal cancer and other tumor types in Lynch syndrome and to evaluate the effect of screening surveillance on cancer incidence. Cancer-specific survival will also be assessed.
The cohort included 1,108 patients with Lynch syndrome from 25 centers, who were followed-up for a mean of 67.5 (± 57.8 months).
The first colonoscopy screening detected cancer in 49 patients (MLH1, n = 23/268; MSH2, n = 18/249; MSH6, n = 4/154; PMS2, n = 2/47; EPCAM, n = 2/13), extrapolating to a cumulative incidence of 25.6% for MLH1, 22.1% for MSH2, 6.3% for MSH6, and 25.9% for PMS2 mutation carriers.
Most patients were diagnosed with stage 1 disease (45.7%) and, to a lesser degree, with stage II (28.6%), stage III (22.9%), and stage IV (2.9%).
The 10-year cumulative incidences for subsequent colorectal cancers for patients who had a previous diagnosis of the disease were 9.4% (95% CI, 5-17) for MLH1, 12.6% (95% CI, 5.6-27.6) for MSH2, and 17.2% (95% CI, 6.6-40) for MSH6.
Digestive Disease Week is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
Key clinical point: Colorectal cancer screening may lower the incidence of disease in a high-risk population of individuals with Lynch syndrome.
Major finding: The incidence of colorectal cancer was lower than has been previously reported in Lynch syndrome, possibly because of the removal of polyps during screening.
Data source: Prospective multicenter study that included 1,108 patients with Lynch syndrome who underwent colonoscopy screening.
Disclosures: Dr. Sanchez has no disclosures.
Anti-TNF drugs reduce mortality in Crohn’s disease
CHICAGO – As compared with prolonged use of corticosteroids, the use of anti–tumor necrosis factor (TNF) drugs was associated with reduced mortality in patients with Crohn’s disease, according to new findings presented here at Digestive Disease Week®.
The reduced mortality seen in this population may be secondary to the lower rates of major adverse cardiovascular events and hip fracture that are associated with anti-TNF use as compared to corticosteroid use. However, the same reduction in mortality risk was not observed in patients with ulcerative colitis using anti-TNF drugs.
Anti-TNF therapy has become a cornerstone in the management of inflammatory bowel disease (IBD), and Dr. Lewis noted that these agents have been shown to be useful for induction, maintenance, and remission, and to reduce surgical and hospitalization rates.
“However, fear of adverse events and cost has deterred greater use of these agents,” he told attendees.
In their study, Dr. Lewis and his colleagues compared the mortality risk with prolonged corticosteroids use versus anti-TNF drugs in patients with IBD.
They conducted a retrospective cohort study using data from 2006-2013 of a population of Medicaid and Medicare beneficiaries in the United States. The cohort included individuals who had received treatment with corticosteroids within the prior year and subsequently had been treated with either additional corticosteroid therapy for a total of greater than 3,000 mg of prednisone or equivalent within 12 months or newly initiated anti-TNF therapy.
The primary outcome of the study was all-cause mortality and secondary outcomes included common causes of death.
Dr. Lewis explained that 57 potential confounding variables were thought to be associated with the choice between corticosteroid use or anti-TNF therapy. These variables, which included demographic characteristics, medications, diagnostic tests, and comorbidities, were measured.
Among Crohn’s disease patients, 7,694 who were prolonged corticosteroid users and 1,879 were new to anti-TNF therapy. Among patients with ulcerative colitis, 3,224 were long-term corticosteroid users and 459 were new anti-TNF users.
The researchers found that the weighted annual incidences of death per 1,000 Crohn’s disease treated patients were 21.4 for those using anti-TNF therapy and 30.1 for those with prolonged corticosteroid use. For those with ulcerative colitis, these figures were 23.0 and 30.9, respectively.
The risk of death was statistically significantly reduced in Crohn’s disease patients who used anti-TNF therapy (odds ratio, 0.78; 95% confidence interval, 0.65-0.93). However, the benefit was not as pronounced in ulcerative colitis.
“We did not see the same effect for ulcerative colitis but for mortality, it was in the same direction, with a hazard ratio of 0.87,” he said.
Among the Crohn’s disease patients, anti-TNF therapy was associated with lower rates of major adverse cardiovascular events (OR, 0.68; 95% CI, 0.55-0.85) and hip fracture (OR, 0.5; 95% CI, 0.34-0.83), which were statistically significant. The use of anti-TNF therapy also reduced the risk of stroke in Crohn’s disease patients (OR, 0.72; 95% CI, 0.51-1.03), but there was also an increase in the risk of cancer (OR, 0.27; 95% CI, 0.98-1.65). Both of these findings nearly reached statistical significance.
In the model that censored for any of the secondary outcomes, the lower mortality risk was attenuated and very close to a null result (OR, 0.97; 95% CI 0.63-1.47).
Dr. Lewis also pointed out that in some of their models, the magnitude of benefit with anti-TNF therapy appears to be greatest in the patients with the most comorbidities.
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
Dr. Lewis has disclosed financial relationships with Takeda, Pfizer, Lilly, Gilead, Johnson and Johnson, Samsung Bioepis, AbbVie, and Dark Canyon Laboratories.
CHICAGO – As compared with prolonged use of corticosteroids, the use of anti–tumor necrosis factor (TNF) drugs was associated with reduced mortality in patients with Crohn’s disease, according to new findings presented here at Digestive Disease Week®.
The reduced mortality seen in this population may be secondary to the lower rates of major adverse cardiovascular events and hip fracture that are associated with anti-TNF use as compared to corticosteroid use. However, the same reduction in mortality risk was not observed in patients with ulcerative colitis using anti-TNF drugs.
Anti-TNF therapy has become a cornerstone in the management of inflammatory bowel disease (IBD), and Dr. Lewis noted that these agents have been shown to be useful for induction, maintenance, and remission, and to reduce surgical and hospitalization rates.
“However, fear of adverse events and cost has deterred greater use of these agents,” he told attendees.
In their study, Dr. Lewis and his colleagues compared the mortality risk with prolonged corticosteroids use versus anti-TNF drugs in patients with IBD.
They conducted a retrospective cohort study using data from 2006-2013 of a population of Medicaid and Medicare beneficiaries in the United States. The cohort included individuals who had received treatment with corticosteroids within the prior year and subsequently had been treated with either additional corticosteroid therapy for a total of greater than 3,000 mg of prednisone or equivalent within 12 months or newly initiated anti-TNF therapy.
The primary outcome of the study was all-cause mortality and secondary outcomes included common causes of death.
Dr. Lewis explained that 57 potential confounding variables were thought to be associated with the choice between corticosteroid use or anti-TNF therapy. These variables, which included demographic characteristics, medications, diagnostic tests, and comorbidities, were measured.
Among Crohn’s disease patients, 7,694 who were prolonged corticosteroid users and 1,879 were new to anti-TNF therapy. Among patients with ulcerative colitis, 3,224 were long-term corticosteroid users and 459 were new anti-TNF users.
The researchers found that the weighted annual incidences of death per 1,000 Crohn’s disease treated patients were 21.4 for those using anti-TNF therapy and 30.1 for those with prolonged corticosteroid use. For those with ulcerative colitis, these figures were 23.0 and 30.9, respectively.
The risk of death was statistically significantly reduced in Crohn’s disease patients who used anti-TNF therapy (odds ratio, 0.78; 95% confidence interval, 0.65-0.93). However, the benefit was not as pronounced in ulcerative colitis.
“We did not see the same effect for ulcerative colitis but for mortality, it was in the same direction, with a hazard ratio of 0.87,” he said.
Among the Crohn’s disease patients, anti-TNF therapy was associated with lower rates of major adverse cardiovascular events (OR, 0.68; 95% CI, 0.55-0.85) and hip fracture (OR, 0.5; 95% CI, 0.34-0.83), which were statistically significant. The use of anti-TNF therapy also reduced the risk of stroke in Crohn’s disease patients (OR, 0.72; 95% CI, 0.51-1.03), but there was also an increase in the risk of cancer (OR, 0.27; 95% CI, 0.98-1.65). Both of these findings nearly reached statistical significance.
In the model that censored for any of the secondary outcomes, the lower mortality risk was attenuated and very close to a null result (OR, 0.97; 95% CI 0.63-1.47).
Dr. Lewis also pointed out that in some of their models, the magnitude of benefit with anti-TNF therapy appears to be greatest in the patients with the most comorbidities.
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
Dr. Lewis has disclosed financial relationships with Takeda, Pfizer, Lilly, Gilead, Johnson and Johnson, Samsung Bioepis, AbbVie, and Dark Canyon Laboratories.
CHICAGO – As compared with prolonged use of corticosteroids, the use of anti–tumor necrosis factor (TNF) drugs was associated with reduced mortality in patients with Crohn’s disease, according to new findings presented here at Digestive Disease Week®.
The reduced mortality seen in this population may be secondary to the lower rates of major adverse cardiovascular events and hip fracture that are associated with anti-TNF use as compared to corticosteroid use. However, the same reduction in mortality risk was not observed in patients with ulcerative colitis using anti-TNF drugs.
Anti-TNF therapy has become a cornerstone in the management of inflammatory bowel disease (IBD), and Dr. Lewis noted that these agents have been shown to be useful for induction, maintenance, and remission, and to reduce surgical and hospitalization rates.
“However, fear of adverse events and cost has deterred greater use of these agents,” he told attendees.
In their study, Dr. Lewis and his colleagues compared the mortality risk with prolonged corticosteroids use versus anti-TNF drugs in patients with IBD.
They conducted a retrospective cohort study using data from 2006-2013 of a population of Medicaid and Medicare beneficiaries in the United States. The cohort included individuals who had received treatment with corticosteroids within the prior year and subsequently had been treated with either additional corticosteroid therapy for a total of greater than 3,000 mg of prednisone or equivalent within 12 months or newly initiated anti-TNF therapy.
The primary outcome of the study was all-cause mortality and secondary outcomes included common causes of death.
Dr. Lewis explained that 57 potential confounding variables were thought to be associated with the choice between corticosteroid use or anti-TNF therapy. These variables, which included demographic characteristics, medications, diagnostic tests, and comorbidities, were measured.
Among Crohn’s disease patients, 7,694 who were prolonged corticosteroid users and 1,879 were new to anti-TNF therapy. Among patients with ulcerative colitis, 3,224 were long-term corticosteroid users and 459 were new anti-TNF users.
The researchers found that the weighted annual incidences of death per 1,000 Crohn’s disease treated patients were 21.4 for those using anti-TNF therapy and 30.1 for those with prolonged corticosteroid use. For those with ulcerative colitis, these figures were 23.0 and 30.9, respectively.
The risk of death was statistically significantly reduced in Crohn’s disease patients who used anti-TNF therapy (odds ratio, 0.78; 95% confidence interval, 0.65-0.93). However, the benefit was not as pronounced in ulcerative colitis.
“We did not see the same effect for ulcerative colitis but for mortality, it was in the same direction, with a hazard ratio of 0.87,” he said.
Among the Crohn’s disease patients, anti-TNF therapy was associated with lower rates of major adverse cardiovascular events (OR, 0.68; 95% CI, 0.55-0.85) and hip fracture (OR, 0.5; 95% CI, 0.34-0.83), which were statistically significant. The use of anti-TNF therapy also reduced the risk of stroke in Crohn’s disease patients (OR, 0.72; 95% CI, 0.51-1.03), but there was also an increase in the risk of cancer (OR, 0.27; 95% CI, 0.98-1.65). Both of these findings nearly reached statistical significance.
In the model that censored for any of the secondary outcomes, the lower mortality risk was attenuated and very close to a null result (OR, 0.97; 95% CI 0.63-1.47).
Dr. Lewis also pointed out that in some of their models, the magnitude of benefit with anti-TNF therapy appears to be greatest in the patients with the most comorbidities.
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
Dr. Lewis has disclosed financial relationships with Takeda, Pfizer, Lilly, Gilead, Johnson and Johnson, Samsung Bioepis, AbbVie, and Dark Canyon Laboratories.
AT DDW
Key clinical point:
Major finding: Anti-TNF drugs were associated with reduced mortality in patients with Crohn’s disease (OR, 0.78) but to a much lesser extent in ulcerative colitis (OR, 0.87).
Data source: Database of Medicare and Medicaid recipients with 9,573 patients with Crohn’s disease and 3,683 with ulcerative colitis.
Disclosures: Dr. Lewis has disclosed financial relationships with Takeda, Pfizer, Lilly, Gilead, Johnson and Johnson, Samsung Bioepis, AbbVie, and Dark Canyon Laboratories.
Novel robotic camera photographs colon
A novel robotically driven capsule successfully navigated a colon in a pig model in 100% of 30 retroflexion maneuvers, setting the stage for further study of robotics in colonoscopy. The data were presented at the annual Digestive Disease Week.
Although capsule technology has expanded exploration of the GI tract, current capsules are limited by passive movement and lack therapeutic capability, said Keith L. Obstein, MD, of Vanderbilt University in Nashville, Tenn.
The researchers developed a capsule with an 18-mm head and interior permanent magnets designed to be automatically controlled by an external robotic arm in difficult areas.
“Retroflexion is a common but mechanically complex maneuver during colonoscopy, and therefore serves as an excellent subject for autonomous control,” the researchers noted.
Logistically, the capsule is soft-tethered after it is introduced through the rectum, which allows the potential for therapeutic procedures such as biopsies and polyp removal. In addition, the use of an external magnet to pull the robot with the tether may reduce the pressure on the colon that typically created when a physician pushes the colonoscope from behind. Therefore, use of a robotic capsule may help reduce patients’ discomfort and make them more amenable to the procedure, Dr. Obstein said.
In the study, an endoscopist performed the first retroflexion with a standard colonoscope at 15 cm from the anal sphincter, and these parameters were used to set the robotic system for autonomous retroflexion at 15 cm from the anal sphincter.
The success rate was 100% for both the standard endoscope and the automatically controlled robot for each of 30 maneuvers. The average time for a robotic maneuver was 12 seconds, and no leaks or histologic abnormalities were noted.
Studies to evaluate additional control algorithms are in progress, and the robot capsule may be ready for human trials in 2018, Dr. Obstein said.
This study was supported by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health under award number R01EB018992. Dr. Obstein had no relevant financial conflicts to disclose.
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the Alimentary Tract (SSAT).
A novel robotically driven capsule successfully navigated a colon in a pig model in 100% of 30 retroflexion maneuvers, setting the stage for further study of robotics in colonoscopy. The data were presented at the annual Digestive Disease Week.
Although capsule technology has expanded exploration of the GI tract, current capsules are limited by passive movement and lack therapeutic capability, said Keith L. Obstein, MD, of Vanderbilt University in Nashville, Tenn.
The researchers developed a capsule with an 18-mm head and interior permanent magnets designed to be automatically controlled by an external robotic arm in difficult areas.
“Retroflexion is a common but mechanically complex maneuver during colonoscopy, and therefore serves as an excellent subject for autonomous control,” the researchers noted.
Logistically, the capsule is soft-tethered after it is introduced through the rectum, which allows the potential for therapeutic procedures such as biopsies and polyp removal. In addition, the use of an external magnet to pull the robot with the tether may reduce the pressure on the colon that typically created when a physician pushes the colonoscope from behind. Therefore, use of a robotic capsule may help reduce patients’ discomfort and make them more amenable to the procedure, Dr. Obstein said.
In the study, an endoscopist performed the first retroflexion with a standard colonoscope at 15 cm from the anal sphincter, and these parameters were used to set the robotic system for autonomous retroflexion at 15 cm from the anal sphincter.
The success rate was 100% for both the standard endoscope and the automatically controlled robot for each of 30 maneuvers. The average time for a robotic maneuver was 12 seconds, and no leaks or histologic abnormalities were noted.
Studies to evaluate additional control algorithms are in progress, and the robot capsule may be ready for human trials in 2018, Dr. Obstein said.
This study was supported by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health under award number R01EB018992. Dr. Obstein had no relevant financial conflicts to disclose.
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the Alimentary Tract (SSAT).
A novel robotically driven capsule successfully navigated a colon in a pig model in 100% of 30 retroflexion maneuvers, setting the stage for further study of robotics in colonoscopy. The data were presented at the annual Digestive Disease Week.
Although capsule technology has expanded exploration of the GI tract, current capsules are limited by passive movement and lack therapeutic capability, said Keith L. Obstein, MD, of Vanderbilt University in Nashville, Tenn.
The researchers developed a capsule with an 18-mm head and interior permanent magnets designed to be automatically controlled by an external robotic arm in difficult areas.
“Retroflexion is a common but mechanically complex maneuver during colonoscopy, and therefore serves as an excellent subject for autonomous control,” the researchers noted.
Logistically, the capsule is soft-tethered after it is introduced through the rectum, which allows the potential for therapeutic procedures such as biopsies and polyp removal. In addition, the use of an external magnet to pull the robot with the tether may reduce the pressure on the colon that typically created when a physician pushes the colonoscope from behind. Therefore, use of a robotic capsule may help reduce patients’ discomfort and make them more amenable to the procedure, Dr. Obstein said.
In the study, an endoscopist performed the first retroflexion with a standard colonoscope at 15 cm from the anal sphincter, and these parameters were used to set the robotic system for autonomous retroflexion at 15 cm from the anal sphincter.
The success rate was 100% for both the standard endoscope and the automatically controlled robot for each of 30 maneuvers. The average time for a robotic maneuver was 12 seconds, and no leaks or histologic abnormalities were noted.
Studies to evaluate additional control algorithms are in progress, and the robot capsule may be ready for human trials in 2018, Dr. Obstein said.
This study was supported by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health under award number R01EB018992. Dr. Obstein had no relevant financial conflicts to disclose.
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the Alimentary Tract (SSAT).
FROM DDW
Key clinical point: An 18-mm magnetized capsule colonoscope successfully navigated a pig colon, and researchers are planning human trials for 2018.
Major finding: An automated robot capsule successfully completed 30 retroflexion maneuvers in a pig colon with an average time of 12 seconds.
Data source: The data come from a test of 30 maneuvers.
Disclosures: This study was supported by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health under award number R01EB018992. Dr. Obstein had no relevant financial conflicts to disclose.