ACG 2015

HONOLULU – New medications and more patient-focused strategies are changing the treatment of irritable bowel syndrome, as physicians move away from simply treating symptoms and gain a better understanding of IBS processes and mechanisms of action.

“I think there’s kind of an explosion in medications for functional bowel disease, specifically irritable bowel syndrome, over the last couple years, because we’ve gotten a lot smarter about how we think about these patients and how we treat these patients,” explained Dr. Darren M. Brenner, director of the functional bowel program at Northwestern University, Chicago.

In an interview at the annual meeting of the American College of Gastroenterology, Dr. Brenner discussed new approaches to target the syndrome’s mechanisms of action, new thinking by the Food and Drug Administration on IBS drug approval, and the wide range of traditional, complementary and alternative, and diet-related therapeutic options now available to patients.

HONOLULU – New medications and more patient-focused strategies are changing the treatment of irritable bowel syndrome, as physicians move away from simply treating symptoms and gain a better understanding of IBS processes and mechanisms of action.

“I think there’s kind of an explosion in medications for functional bowel disease, specifically irritable bowel syndrome, over the last couple years, because we’ve gotten a lot smarter about how we think about these patients and how we treat these patients,” explained Dr. Darren M. Brenner, director of the functional bowel program at Northwestern University, Chicago.

In an interview at the annual meeting of the American College of Gastroenterology, Dr. Brenner discussed new approaches to target the syndrome’s mechanisms of action, new thinking by the Food and Drug Administration on IBS drug approval, and the wide range of traditional, complementary and alternative, and diet-related therapeutic options now available to patients.

HONOLULU – New medications and more patient-focused strategies are changing the treatment of irritable bowel syndrome, as physicians move away from simply treating symptoms and gain a better understanding of IBS processes and mechanisms of action.

“I think there’s kind of an explosion in medications for functional bowel disease, specifically irritable bowel syndrome, over the last couple years, because we’ve gotten a lot smarter about how we think about these patients and how we treat these patients,” explained Dr. Darren M. Brenner, director of the functional bowel program at Northwestern University, Chicago.

In an interview at the annual meeting of the American College of Gastroenterology, Dr. Brenner discussed new approaches to target the syndrome’s mechanisms of action, new thinking by the Food and Drug Administration on IBS drug approval, and the wide range of traditional, complementary and alternative, and diet-related therapeutic options now available to patients.

HONOLULU – Serum amyloid A levels may offer an effective biomarker to gauge disease activity in inflammatory bowel disease, while baseline fecal calprotectin levels could help predict how patients with IBD will respond to anti-tumor necrosis factor therapy, according to two studies presented at the annual meeting of the American College of Gastroenterology.

“There’s a really high need for biomarkers in order to have a better assessment and better control of disease activity, before treatment and then throughout therapy,” explained the studies’ lead author, Dr. Andres Yarur of the University of Chicago.

In an interview at the meeting, Dr. Yarur discussed the two studies’ results, and how serum amyloid A levels, in combination with C-reactive protein levels, may improve clinicians’ ability to identify active endoscopic disease.

HONOLULU – Serum amyloid A levels may offer an effective biomarker to gauge disease activity in inflammatory bowel disease, while baseline fecal calprotectin levels could help predict how patients with IBD will respond to anti-tumor necrosis factor therapy, according to two studies presented at the annual meeting of the American College of Gastroenterology.

“There’s a really high need for biomarkers in order to have a better assessment and better control of disease activity, before treatment and then throughout therapy,” explained the studies’ lead author, Dr. Andres Yarur of the University of Chicago.

In an interview at the meeting, Dr. Yarur discussed the two studies’ results, and how serum amyloid A levels, in combination with C-reactive protein levels, may improve clinicians’ ability to identify active endoscopic disease.

HONOLULU – Serum amyloid A levels may offer an effective biomarker to gauge disease activity in inflammatory bowel disease, while baseline fecal calprotectin levels could help predict how patients with IBD will respond to anti-tumor necrosis factor therapy, according to two studies presented at the annual meeting of the American College of Gastroenterology.

“There’s a really high need for biomarkers in order to have a better assessment and better control of disease activity, before treatment and then throughout therapy,” explained the studies’ lead author, Dr. Andres Yarur of the University of Chicago.

In an interview at the meeting, Dr. Yarur discussed the two studies’ results, and how serum amyloid A levels, in combination with C-reactive protein levels, may improve clinicians’ ability to identify active endoscopic disease.

HONOLULU – Could gut microbiota be a better predictor than clinical factors of a patient’s response to treatment for Clostridium difficile infection?

In a study of 88 patients with C. difficile, the overall treatment failure rate was 12.5% – but clinical factors such as age, sex, ongoing antibiotic exposure, and hospitalization status failed to predict which patients wouldn’t respond to treatment.

So, “we aimed to identify if there are any gut microbiota signatures to predict treatment response and treatment failure,” explained the study’s lead author, Dr. Sahil Khanna of the Mayo Clinic, Rochester, Minn.

In an interview at the annual meeting of the American College of Gastroenterology, Dr. Khanna discussed the study results and why gut microbiota may be an effective predictor of treatment responders and nonresponders.

HONOLULU – Could gut microbiota be a better predictor than clinical factors of a patient’s response to treatment for Clostridium difficile infection?

In a study of 88 patients with C. difficile, the overall treatment failure rate was 12.5% – but clinical factors such as age, sex, ongoing antibiotic exposure, and hospitalization status failed to predict which patients wouldn’t respond to treatment.

So, “we aimed to identify if there are any gut microbiota signatures to predict treatment response and treatment failure,” explained the study’s lead author, Dr. Sahil Khanna of the Mayo Clinic, Rochester, Minn.

In an interview at the annual meeting of the American College of Gastroenterology, Dr. Khanna discussed the study results and why gut microbiota may be an effective predictor of treatment responders and nonresponders.

HONOLULU – Could gut microbiota be a better predictor than clinical factors of a patient’s response to treatment for Clostridium difficile infection?

In a study of 88 patients with C. difficile, the overall treatment failure rate was 12.5% – but clinical factors such as age, sex, ongoing antibiotic exposure, and hospitalization status failed to predict which patients wouldn’t respond to treatment.

So, “we aimed to identify if there are any gut microbiota signatures to predict treatment response and treatment failure,” explained the study’s lead author, Dr. Sahil Khanna of the Mayo Clinic, Rochester, Minn.

In an interview at the annual meeting of the American College of Gastroenterology, Dr. Khanna discussed the study results and why gut microbiota may be an effective predictor of treatment responders and nonresponders.

HONOLULU – Could gut microbiota be a better predictor than clinical factors of a patient’s response to treatment for Clostridium difficile infection?

In a study of 88 patients with C. difficile, the overall treatment failure rate was 12.5% – but clinical factors such as age, sex, ongoing antibiotic exposure, and hospitalization status failed to predict which patients wouldn’t respond to treatment.

So, “we aimed to identify if there are any gut microbiota signatures to predict treatment response and treatment failure,” explained the study’s lead author, Dr. Sahil Khanna of the Mayo Clinic, Rochester, Minn.

In an interview at the annual meeting of the American College of Gastroenterology, Dr. Khanna discussed the study results and why gut microbiota may be an effective predictor of treatment responders and nonresponders.

HONOLULU – Could gut microbiota be a better predictor than clinical factors of a patient’s response to treatment for Clostridium difficile infection?

In a study of 88 patients with C. difficile, the overall treatment failure rate was 12.5% – but clinical factors such as age, sex, ongoing antibiotic exposure, and hospitalization status failed to predict which patients wouldn’t respond to treatment.

So, “we aimed to identify if there are any gut microbiota signatures to predict treatment response and treatment failure,” explained the study’s lead author, Dr. Sahil Khanna of the Mayo Clinic, Rochester, Minn.

In an interview at the annual meeting of the American College of Gastroenterology, Dr. Khanna discussed the study results and why gut microbiota may be an effective predictor of treatment responders and nonresponders.

HONOLULU – Could gut microbiota be a better predictor than clinical factors of a patient’s response to treatment for Clostridium difficile infection?

In a study of 88 patients with C. difficile, the overall treatment failure rate was 12.5% – but clinical factors such as age, sex, ongoing antibiotic exposure, and hospitalization status failed to predict which patients wouldn’t respond to treatment.

So, “we aimed to identify if there are any gut microbiota signatures to predict treatment response and treatment failure,” explained the study’s lead author, Dr. Sahil Khanna of the Mayo Clinic, Rochester, Minn.

In an interview at the annual meeting of the American College of Gastroenterology, Dr. Khanna discussed the study results and why gut microbiota may be an effective predictor of treatment responders and nonresponders.

HONOLULU – Ustekinumab, a monoclonal antibody targeted against interleukins 12 and 23 (IL-12 and IL-23), met its primary endpoint for control of Crohn’s disease in a multinational phase III trial presented at the annual meeting of the American College of Gastroenterology.

The trial, called UNITI-2, enrolled patients with moderate to severe Crohn’s disease who had failed traditional therapies but were naive to or at least had not failed a tumor necrosis factor (TNF) inhibitor, reported Dr. Brian Feagan, professor of medicine, University of Western Ontario, London. Results of a second and parallel phase III trial with ustekinumab, called UNITI-1, which enrolled TNF inhibitor failures, have not yet been reported.

In UNITI-2, 628 patients were randomized to placebo, 130 mg of ustekinumab in a fixed subcutaneous dose of 130 mg, or a weight-based dose of 6 mg/kg of subcutaneous ustekinumab. Major enrollment criteria, other than failure of a non-TNF inhibitor therapy, included a Crohn’s disease activity index (CDAI) score between 220 and 450. The primary endpoint was a CDAI reduction of at least 100 points at 6 weeks. Clinical remission at 8 weeks, defined as CDAI less than 150, was a secondary endpoint.

The primary endpoint was reached by 28.7% randomized to placebo, 51.7% of those randomized to the fixed dose of ustekinumab, and 55.5% of those randomized to weight-based dosing. The advantage for the active treatment arms was statistically significant (both P less than .001). For the secondary endpoint of clinical remission at 8 weeks, the rates were 19.6% for placebo, 30.6% (P = .009 vs. placebo) for fixed-dose ustekinumab, and 40.2% (P less than .001 vs. placebo) for the weight-based dose.

The anti-inflammatory effect of ustekinumab, which inhibits signal transduction of IL-12 and IL-23 by binding to the p40 subunit that both cytokines employ for receptor binding, was reflected in the rapid reduction in C-reactive protein (CRP) concentrations observed with both doses but not with placebo, according to Dr. Feagan. He noted that the greater CRP reduction on the weight-based dosing, which nearly doubles ustekinumab exposure for some individuals, supports the dose-response anti-inflammatory mechanism of the drug.

Ustekinumab was well tolerated with similar rates and types of adverse events reported in the active treatment and placebo groups. This included infections, serious infections, and infusion reactions. There was a theoretical concern about an increased risk for cardiovascular events that was not substantiated in this study. No malignancies were observed in this short-term study.

Nearly 70% of the patients were naive to a biologic treatment. Of the 31.4% with prior exposure to a TNF inhibitor, none had met criteria for failure. About 80% had failed corticosteroids after what was considered to be an adequate course, while nearly 70% had failed one or more immunomodulators. About half had failed both.

Details about quality of life measures were not presented at the ACG, but Dr. Feagan said, summarizing the data, they “also confirmed the clinical efficacy of ustekinumab,” which was approved for the treatment of psoriatic arthritis more than 2 years ago.

The data, which suggest a level of efficacy comparable to other targeted therapies in Crohn’s disease, appear to encourage a filing for Food and Drug Administration approval in Crohn’s disease. However, data about the relative efficacy of this drug in those who have failed a TNF inhibitor is expected to provide greater insight about how this agent will add to current options.

“It is encouraging to see disease control with agents targeting novel cytokines in the inflammatory pathway, but we need to begin thinking about how these biologics fit with each other,” said Dr. David Rubin, chief, section of gastroenterology, hepatology, and nutrition, University of Chicago. Dr. Rubin was a moderator of the ACG session in which the UNITI-2 data were presented.

Dr. Feagan has financial relationships with Millennium, Merck, Centocor, Elan/Biogen, Janssen-Ortho, Teva Pharmaceuticals, Bristol-Myers Squibb, Celgene, and many other pharmaceutical companies.

HONOLULU – Ustekinumab, a monoclonal antibody targeted against interleukins 12 and 23 (IL-12 and IL-23), met its primary endpoint for control of Crohn’s disease in a multinational phase III trial presented at the annual meeting of the American College of Gastroenterology.

The trial, called UNITI-2, enrolled patients with moderate to severe Crohn’s disease who had failed traditional therapies but were naive to or at least had not failed a tumor necrosis factor (TNF) inhibitor, reported Dr. Brian Feagan, professor of medicine, University of Western Ontario, London. Results of a second and parallel phase III trial with ustekinumab, called UNITI-1, which enrolled TNF inhibitor failures, have not yet been reported.

In UNITI-2, 628 patients were randomized to placebo, 130 mg of ustekinumab in a fixed subcutaneous dose of 130 mg, or a weight-based dose of 6 mg/kg of subcutaneous ustekinumab. Major enrollment criteria, other than failure of a non-TNF inhibitor therapy, included a Crohn’s disease activity index (CDAI) score between 220 and 450. The primary endpoint was a CDAI reduction of at least 100 points at 6 weeks. Clinical remission at 8 weeks, defined as CDAI less than 150, was a secondary endpoint.

The primary endpoint was reached by 28.7% randomized to placebo, 51.7% of those randomized to the fixed dose of ustekinumab, and 55.5% of those randomized to weight-based dosing. The advantage for the active treatment arms was statistically significant (both P less than .001). For the secondary endpoint of clinical remission at 8 weeks, the rates were 19.6% for placebo, 30.6% (P = .009 vs. placebo) for fixed-dose ustekinumab, and 40.2% (P less than .001 vs. placebo) for the weight-based dose.

The anti-inflammatory effect of ustekinumab, which inhibits signal transduction of IL-12 and IL-23 by binding to the p40 subunit that both cytokines employ for receptor binding, was reflected in the rapid reduction in C-reactive protein (CRP) concentrations observed with both doses but not with placebo, according to Dr. Feagan. He noted that the greater CRP reduction on the weight-based dosing, which nearly doubles ustekinumab exposure for some individuals, supports the dose-response anti-inflammatory mechanism of the drug.

Ustekinumab was well tolerated with similar rates and types of adverse events reported in the active treatment and placebo groups. This included infections, serious infections, and infusion reactions. There was a theoretical concern about an increased risk for cardiovascular events that was not substantiated in this study. No malignancies were observed in this short-term study.

Nearly 70% of the patients were naive to a biologic treatment. Of the 31.4% with prior exposure to a TNF inhibitor, none had met criteria for failure. About 80% had failed corticosteroids after what was considered to be an adequate course, while nearly 70% had failed one or more immunomodulators. About half had failed both.

Details about quality of life measures were not presented at the ACG, but Dr. Feagan said, summarizing the data, they “also confirmed the clinical efficacy of ustekinumab,” which was approved for the treatment of psoriatic arthritis more than 2 years ago.

The data, which suggest a level of efficacy comparable to other targeted therapies in Crohn’s disease, appear to encourage a filing for Food and Drug Administration approval in Crohn’s disease. However, data about the relative efficacy of this drug in those who have failed a TNF inhibitor is expected to provide greater insight about how this agent will add to current options.

“It is encouraging to see disease control with agents targeting novel cytokines in the inflammatory pathway, but we need to begin thinking about how these biologics fit with each other,” said Dr. David Rubin, chief, section of gastroenterology, hepatology, and nutrition, University of Chicago. Dr. Rubin was a moderator of the ACG session in which the UNITI-2 data were presented.

Dr. Feagan has financial relationships with Millennium, Merck, Centocor, Elan/Biogen, Janssen-Ortho, Teva Pharmaceuticals, Bristol-Myers Squibb, Celgene, and many other pharmaceutical companies.

HONOLULU – Ustekinumab, a monoclonal antibody targeted against interleukins 12 and 23 (IL-12 and IL-23), met its primary endpoint for control of Crohn’s disease in a multinational phase III trial presented at the annual meeting of the American College of Gastroenterology.

The trial, called UNITI-2, enrolled patients with moderate to severe Crohn’s disease who had failed traditional therapies but were naive to or at least had not failed a tumor necrosis factor (TNF) inhibitor, reported Dr. Brian Feagan, professor of medicine, University of Western Ontario, London. Results of a second and parallel phase III trial with ustekinumab, called UNITI-1, which enrolled TNF inhibitor failures, have not yet been reported.

In UNITI-2, 628 patients were randomized to placebo, 130 mg of ustekinumab in a fixed subcutaneous dose of 130 mg, or a weight-based dose of 6 mg/kg of subcutaneous ustekinumab. Major enrollment criteria, other than failure of a non-TNF inhibitor therapy, included a Crohn’s disease activity index (CDAI) score between 220 and 450. The primary endpoint was a CDAI reduction of at least 100 points at 6 weeks. Clinical remission at 8 weeks, defined as CDAI less than 150, was a secondary endpoint.

The primary endpoint was reached by 28.7% randomized to placebo, 51.7% of those randomized to the fixed dose of ustekinumab, and 55.5% of those randomized to weight-based dosing. The advantage for the active treatment arms was statistically significant (both P less than .001). For the secondary endpoint of clinical remission at 8 weeks, the rates were 19.6% for placebo, 30.6% (P = .009 vs. placebo) for fixed-dose ustekinumab, and 40.2% (P less than .001 vs. placebo) for the weight-based dose.

The anti-inflammatory effect of ustekinumab, which inhibits signal transduction of IL-12 and IL-23 by binding to the p40 subunit that both cytokines employ for receptor binding, was reflected in the rapid reduction in C-reactive protein (CRP) concentrations observed with both doses but not with placebo, according to Dr. Feagan. He noted that the greater CRP reduction on the weight-based dosing, which nearly doubles ustekinumab exposure for some individuals, supports the dose-response anti-inflammatory mechanism of the drug.

Ustekinumab was well tolerated with similar rates and types of adverse events reported in the active treatment and placebo groups. This included infections, serious infections, and infusion reactions. There was a theoretical concern about an increased risk for cardiovascular events that was not substantiated in this study. No malignancies were observed in this short-term study.

Nearly 70% of the patients were naive to a biologic treatment. Of the 31.4% with prior exposure to a TNF inhibitor, none had met criteria for failure. About 80% had failed corticosteroids after what was considered to be an adequate course, while nearly 70% had failed one or more immunomodulators. About half had failed both.

Details about quality of life measures were not presented at the ACG, but Dr. Feagan said, summarizing the data, they “also confirmed the clinical efficacy of ustekinumab,” which was approved for the treatment of psoriatic arthritis more than 2 years ago.

The data, which suggest a level of efficacy comparable to other targeted therapies in Crohn’s disease, appear to encourage a filing for Food and Drug Administration approval in Crohn’s disease. However, data about the relative efficacy of this drug in those who have failed a TNF inhibitor is expected to provide greater insight about how this agent will add to current options.

“It is encouraging to see disease control with agents targeting novel cytokines in the inflammatory pathway, but we need to begin thinking about how these biologics fit with each other,” said Dr. David Rubin, chief, section of gastroenterology, hepatology, and nutrition, University of Chicago. Dr. Rubin was a moderator of the ACG session in which the UNITI-2 data were presented.

Dr. Feagan has financial relationships with Millennium, Merck, Centocor, Elan/Biogen, Janssen-Ortho, Teva Pharmaceuticals, Bristol-Myers Squibb, Celgene, and many other pharmaceutical companies.

HONOLULU – A DNA-based molecular diagnostic test that stratifies pancreatic cysts for their malignant potential better than current alternatives can help guide management, according to two sets of corroborating data presented at the annual meeting of the American College of Gastroenterology.

The test was associated with a high degree of accuracy for identifying those pancreatic cysts with a high as well as those with a low potential for malignant transformation, according to Dr. David E. Loren, codirector, pancreaticobiliary section, Thomas Jefferson University, Philadelphia.

©Kativ/iStockphoto

“This test can be recommended across the board to patients with a pancreatic cyst. The exception would be those with a positive cytology for malignancy in which no further diagnostic study is needed,” said Dr. Loren.

The proprietary test, marketed under the name PancraGEN (Interpace Diagnostics), uses genetic and molecular information, such as oncogene mutations and loss of heterozygosity (LOH) markers, to stratify pancreatic cysts as high risk on the basis of malignant transformation potential or low risk on the basis of characteristics predicting a benign course. It is commercially available and has been used in more than 14,000 patients worldwide, according to Dr. Loren.

In the first of two studies presented at ACG 2015, the performance of the diagnostic test was compared to AGA criteria for managing pancreatic cysts, which were published earlier this year (Gastroenterology 2015;148:819-22). Using registry data with known outcomes, researchers compared the performance of the AGA criteria and the PancraGEN test in 417 patients.

The AGA criteria, which require assessment of cytological atypia and endoscopic ultrasound imaging features, were falsely negative in 57% of cases and falsely positive in 4%, producing a positive predictive value of 59% and a negative predictive value of 93%. Of the 27 malignancies missed by the AGA criteria, the PancraGEN test identified 21. As a result, it generated far greater sensitivity (87% vs. 43%; P less than .0001) even though the specificity of the PancraGEN test and the AGA criteria were similar (92% vs. 96%, respectively).

“The DNA-based approach helped identify false-negative cases otherwise missed by AGA-recommended imaging and cytology,” Dr. Loren confirmed.

In a second study using the same registry data, the goal was to determine whether the DNA-based diagnostic test would provide more accurate management decisions. In this study, the DNA-based diagnostic test was compared to the International Consensus Guidelines (ICG), which were most recently updated in 2012 (Pancreatology 2012;12:183-197). The study evaluated outcomes in the context of recommendations by the ICG as well as the risk status established with the PancraGEN test.

In cysts recommended for surveillance by ICG but identified as high-risk by PancraGEN testing, 57% had malignant outcomes. In cysts recommended for Surgery by ICG guidelines but identified as low-risk by PancraGEN test, 99% had a benign outcome.

Whether compared to AGA or ICG criteria, the DNA-based test is more accurate for detecting malignant potential “without drastically overdiagnosing malignancy in patients with benign lesions,” said Dr. Loren, who said the second study confirmed its utility “in real-life management decisions.”

Cost efficacy data were not presented at the ACG meeting, but Dr. Loren said that models predict cost savings from PancraGEN testing because of more appropriate care, particularly a reduction in unnecessary surgeries. Although it is also theoretically possible that a reduction in false-negative diagnoses could lead to a mortality benefit through earlier treatment of lesions with a high likelihood of malignant transformation, Dr. Loren cautioned that this advantage would be difficult to show without extended follow-up because of the slow growth of many tumors.

It is estimated that about 120,000 pancreatic cysts are identified annually. On cytology, results are often ambiguous, complicating the decision to incur the risks and costs of surgery relative to a watch-and-wait approach. A more precise test has the potential both to avoid unnecessary surgeries and to ensure that those at high risk are treated appropriately. Overall, Dr. Loren said he believes that the PancraGEN test will improve care in this population.

“We think this is a better approach relative to current alternatives,” he asserted.

Dr. Loren received research support from Interpace Diagnostics

HONOLULU – A DNA-based molecular diagnostic test that stratifies pancreatic cysts for their malignant potential better than current alternatives can help guide management, according to two sets of corroborating data presented at the annual meeting of the American College of Gastroenterology.

The test was associated with a high degree of accuracy for identifying those pancreatic cysts with a high as well as those with a low potential for malignant transformation, according to Dr. David E. Loren, codirector, pancreaticobiliary section, Thomas Jefferson University, Philadelphia.

©Kativ/iStockphoto

“This test can be recommended across the board to patients with a pancreatic cyst. The exception would be those with a positive cytology for malignancy in which no further diagnostic study is needed,” said Dr. Loren.

The proprietary test, marketed under the name PancraGEN (Interpace Diagnostics), uses genetic and molecular information, such as oncogene mutations and loss of heterozygosity (LOH) markers, to stratify pancreatic cysts as high risk on the basis of malignant transformation potential or low risk on the basis of characteristics predicting a benign course. It is commercially available and has been used in more than 14,000 patients worldwide, according to Dr. Loren.

In the first of two studies presented at ACG 2015, the performance of the diagnostic test was compared to AGA criteria for managing pancreatic cysts, which were published earlier this year (Gastroenterology 2015;148:819-22). Using registry data with known outcomes, researchers compared the performance of the AGA criteria and the PancraGEN test in 417 patients.

The AGA criteria, which require assessment of cytological atypia and endoscopic ultrasound imaging features, were falsely negative in 57% of cases and falsely positive in 4%, producing a positive predictive value of 59% and a negative predictive value of 93%. Of the 27 malignancies missed by the AGA criteria, the PancraGEN test identified 21. As a result, it generated far greater sensitivity (87% vs. 43%; P less than .0001) even though the specificity of the PancraGEN test and the AGA criteria were similar (92% vs. 96%, respectively).

“The DNA-based approach helped identify false-negative cases otherwise missed by AGA-recommended imaging and cytology,” Dr. Loren confirmed.

In a second study using the same registry data, the goal was to determine whether the DNA-based diagnostic test would provide more accurate management decisions. In this study, the DNA-based diagnostic test was compared to the International Consensus Guidelines (ICG), which were most recently updated in 2012 (Pancreatology 2012;12:183-197). The study evaluated outcomes in the context of recommendations by the ICG as well as the risk status established with the PancraGEN test.

In cysts recommended for surveillance by ICG but identified as high-risk by PancraGEN testing, 57% had malignant outcomes. In cysts recommended for Surgery by ICG guidelines but identified as low-risk by PancraGEN test, 99% had a benign outcome.

Whether compared to AGA or ICG criteria, the DNA-based test is more accurate for detecting malignant potential “without drastically overdiagnosing malignancy in patients with benign lesions,” said Dr. Loren, who said the second study confirmed its utility “in real-life management decisions.”

Cost efficacy data were not presented at the ACG meeting, but Dr. Loren said that models predict cost savings from PancraGEN testing because of more appropriate care, particularly a reduction in unnecessary surgeries. Although it is also theoretically possible that a reduction in false-negative diagnoses could lead to a mortality benefit through earlier treatment of lesions with a high likelihood of malignant transformation, Dr. Loren cautioned that this advantage would be difficult to show without extended follow-up because of the slow growth of many tumors.

It is estimated that about 120,000 pancreatic cysts are identified annually. On cytology, results are often ambiguous, complicating the decision to incur the risks and costs of surgery relative to a watch-and-wait approach. A more precise test has the potential both to avoid unnecessary surgeries and to ensure that those at high risk are treated appropriately. Overall, Dr. Loren said he believes that the PancraGEN test will improve care in this population.

“We think this is a better approach relative to current alternatives,” he asserted.

Dr. Loren received research support from Interpace Diagnostics

HONOLULU – A DNA-based molecular diagnostic test that stratifies pancreatic cysts for their malignant potential better than current alternatives can help guide management, according to two sets of corroborating data presented at the annual meeting of the American College of Gastroenterology.

The test was associated with a high degree of accuracy for identifying those pancreatic cysts with a high as well as those with a low potential for malignant transformation, according to Dr. David E. Loren, codirector, pancreaticobiliary section, Thomas Jefferson University, Philadelphia.

©Kativ/iStockphoto

“This test can be recommended across the board to patients with a pancreatic cyst. The exception would be those with a positive cytology for malignancy in which no further diagnostic study is needed,” said Dr. Loren.

The proprietary test, marketed under the name PancraGEN (Interpace Diagnostics), uses genetic and molecular information, such as oncogene mutations and loss of heterozygosity (LOH) markers, to stratify pancreatic cysts as high risk on the basis of malignant transformation potential or low risk on the basis of characteristics predicting a benign course. It is commercially available and has been used in more than 14,000 patients worldwide, according to Dr. Loren.

In the first of two studies presented at ACG 2015, the performance of the diagnostic test was compared to AGA criteria for managing pancreatic cysts, which were published earlier this year (Gastroenterology 2015;148:819-22). Using registry data with known outcomes, researchers compared the performance of the AGA criteria and the PancraGEN test in 417 patients.

The AGA criteria, which require assessment of cytological atypia and endoscopic ultrasound imaging features, were falsely negative in 57% of cases and falsely positive in 4%, producing a positive predictive value of 59% and a negative predictive value of 93%. Of the 27 malignancies missed by the AGA criteria, the PancraGEN test identified 21. As a result, it generated far greater sensitivity (87% vs. 43%; P less than .0001) even though the specificity of the PancraGEN test and the AGA criteria were similar (92% vs. 96%, respectively).

“The DNA-based approach helped identify false-negative cases otherwise missed by AGA-recommended imaging and cytology,” Dr. Loren confirmed.

In a second study using the same registry data, the goal was to determine whether the DNA-based diagnostic test would provide more accurate management decisions. In this study, the DNA-based diagnostic test was compared to the International Consensus Guidelines (ICG), which were most recently updated in 2012 (Pancreatology 2012;12:183-197). The study evaluated outcomes in the context of recommendations by the ICG as well as the risk status established with the PancraGEN test.

In cysts recommended for surveillance by ICG but identified as high-risk by PancraGEN testing, 57% had malignant outcomes. In cysts recommended for Surgery by ICG guidelines but identified as low-risk by PancraGEN test, 99% had a benign outcome.

Whether compared to AGA or ICG criteria, the DNA-based test is more accurate for detecting malignant potential “without drastically overdiagnosing malignancy in patients with benign lesions,” said Dr. Loren, who said the second study confirmed its utility “in real-life management decisions.”

Cost efficacy data were not presented at the ACG meeting, but Dr. Loren said that models predict cost savings from PancraGEN testing because of more appropriate care, particularly a reduction in unnecessary surgeries. Although it is also theoretically possible that a reduction in false-negative diagnoses could lead to a mortality benefit through earlier treatment of lesions with a high likelihood of malignant transformation, Dr. Loren cautioned that this advantage would be difficult to show without extended follow-up because of the slow growth of many tumors.

It is estimated that about 120,000 pancreatic cysts are identified annually. On cytology, results are often ambiguous, complicating the decision to incur the risks and costs of surgery relative to a watch-and-wait approach. A more precise test has the potential both to avoid unnecessary surgeries and to ensure that those at high risk are treated appropriately. Overall, Dr. Loren said he believes that the PancraGEN test will improve care in this population.

“We think this is a better approach relative to current alternatives,” he asserted.

Dr. Loren received research support from Interpace Diagnostics

HONOLULU – Fecal transplant was shown to be effective in the treatment of recurrent or refractory episodes of Clostridium difficile infection in a double-blind trial for the first time, and a second study isolated predictors of treatment failure.

The results of the double-blind study were expected. Several studies, although none double blind, have previously shown this therapy to be efficacious. The study of predictors of failure may be of more immediate practical application, because it is relevant to patient selection, according to the investigators, some of whom were involved in both studies.

In the double-blind study, 46 patients were randomized at two centers to receive a fecal microbiota transplant from donor stool or to a placebo, which was a transplant of the patient’s own stool.

The primary outcome was clinical cure at the end of 8 weeks, achieved in 91% of those randomized to the active therapy and 63% of those randomized to placebo (P = .024). Most of those who had treatment failure, which occurred on average 10 days after the procedure (range, 1-62 days), received the active therapy subsequently and also achieved clinical cure after donor transplantation.

“There were no significant differences in any adverse event rates between the donor transplant and placebo groups,” Dr. Colleen Kelly reported at the annual meeting of the American College of Gastroenterology. Dr. Kelly, a gastroenterologist with the Miriam Hospital, Brown University, Providence, R.I., was also a coauthor of the study of risk factors for the failure of fecal transplant.

Underlining the importance of a double-blind trial to provide confirmation of the efficacy of fecal transplant, Dr. Christina M. Surawicz, who moderated the ACG session at which both studies were presented, said, “We have been waiting for these results.”

However, a disparity in results at the two participating centers is notable. In Providence, cure was achieved in 90% of those receiving fecal transplant versus 43% receiving placebo (P = .019). At the other participating institution, Montefiore Medical Center, New York, the cure rate was 92% with fecal transplant, but 90% of the placebo patients were also cured (P = .89). The data were not intended for a separate analysis, so Dr. Kelly said this did not affect her final conclusion that this trial confirmed the efficacy of this treatment.

In the separate study evaluating predictors of failure to achieve cure after fecal transplant, the retrospective analysis was performed with 345 patients treated for C. difficile infection with fecal transplant. In this population, the overall failure rate was 23.7%, but there was a wide variability observed upon univariate and multivariate analysis of risk factors, Dr. Monika Fischer, a gastroenterologist at Indiana University Hospital, Indianapolis, said at the meeting.

For example, in patients with nonsevere recurrent C. difficile infection, the failure rate was 18%. In contrast, the failure rate was approximately 50% among those with severe refractory C. difficile infection.

Upon multivariate analysis, three risk factors were independent predictors of fecal transplant failure: inpatient status, which was associated with an odds ratio of 6.92 (P = .001); being immunosuppressed (OR, 3.28; P = .0004); and previous hospitalization for C. difficile infection (OR, 1.45 for each prior hospitalization; P less than .001).

With the use of these three factors, a risk score was found to be highly predictive of failure. In this risk score, 5 points were attributed to inpatient status, 3 points to immunosuppression, and 1 point to each prior hospitalization for C. difficile infection. On a scale of 0-12 points, the risk of failure was 13% in those with 0 points, 17% in those with 1-3 points, and 44% in those with 4 or more points.

“Our data suggest that the risk of fecal transplant failure is predictable based on pretransplant characteristics. We hope that this risk stratification model will prove helpful,” said Dr. Fischer, whose coauthors included Dr. Kelly.

Although she did not directly endorse this risk stratification tool for patient management, Dr. Surawicz called this presentation “very clinically relevant.” Practical tools are needed to guide the use of this therapy as it becomes more widely used in the treatment of C. difficile, said Dr. Surawicz, professor of gastroenterology, University of Washington, Seattle.

Dr. Kelly reported no relevant financial conflicts. Dr. Fischer reported a financial relationship with Rebiotix.

HONOLULU – Fecal transplant was shown to be effective in the treatment of recurrent or refractory episodes of Clostridium difficile infection in a double-blind trial for the first time, and a second study isolated predictors of treatment failure.

The results of the double-blind study were expected. Several studies, although none double blind, have previously shown this therapy to be efficacious. The study of predictors of failure may be of more immediate practical application, because it is relevant to patient selection, according to the investigators, some of whom were involved in both studies.

In the double-blind study, 46 patients were randomized at two centers to receive a fecal microbiota transplant from donor stool or to a placebo, which was a transplant of the patient’s own stool.

The primary outcome was clinical cure at the end of 8 weeks, achieved in 91% of those randomized to the active therapy and 63% of those randomized to placebo (P = .024). Most of those who had treatment failure, which occurred on average 10 days after the procedure (range, 1-62 days), received the active therapy subsequently and also achieved clinical cure after donor transplantation.

“There were no significant differences in any adverse event rates between the donor transplant and placebo groups,” Dr. Colleen Kelly reported at the annual meeting of the American College of Gastroenterology. Dr. Kelly, a gastroenterologist with the Miriam Hospital, Brown University, Providence, R.I., was also a coauthor of the study of risk factors for the failure of fecal transplant.

Underlining the importance of a double-blind trial to provide confirmation of the efficacy of fecal transplant, Dr. Christina M. Surawicz, who moderated the ACG session at which both studies were presented, said, “We have been waiting for these results.”

However, a disparity in results at the two participating centers is notable. In Providence, cure was achieved in 90% of those receiving fecal transplant versus 43% receiving placebo (P = .019). At the other participating institution, Montefiore Medical Center, New York, the cure rate was 92% with fecal transplant, but 90% of the placebo patients were also cured (P = .89). The data were not intended for a separate analysis, so Dr. Kelly said this did not affect her final conclusion that this trial confirmed the efficacy of this treatment.

In the separate study evaluating predictors of failure to achieve cure after fecal transplant, the retrospective analysis was performed with 345 patients treated for C. difficile infection with fecal transplant. In this population, the overall failure rate was 23.7%, but there was a wide variability observed upon univariate and multivariate analysis of risk factors, Dr. Monika Fischer, a gastroenterologist at Indiana University Hospital, Indianapolis, said at the meeting.

For example, in patients with nonsevere recurrent C. difficile infection, the failure rate was 18%. In contrast, the failure rate was approximately 50% among those with severe refractory C. difficile infection.

Upon multivariate analysis, three risk factors were independent predictors of fecal transplant failure: inpatient status, which was associated with an odds ratio of 6.92 (P = .001); being immunosuppressed (OR, 3.28; P = .0004); and previous hospitalization for C. difficile infection (OR, 1.45 for each prior hospitalization; P less than .001).

With the use of these three factors, a risk score was found to be highly predictive of failure. In this risk score, 5 points were attributed to inpatient status, 3 points to immunosuppression, and 1 point to each prior hospitalization for C. difficile infection. On a scale of 0-12 points, the risk of failure was 13% in those with 0 points, 17% in those with 1-3 points, and 44% in those with 4 or more points.

“Our data suggest that the risk of fecal transplant failure is predictable based on pretransplant characteristics. We hope that this risk stratification model will prove helpful,” said Dr. Fischer, whose coauthors included Dr. Kelly.

Although she did not directly endorse this risk stratification tool for patient management, Dr. Surawicz called this presentation “very clinically relevant.” Practical tools are needed to guide the use of this therapy as it becomes more widely used in the treatment of C. difficile, said Dr. Surawicz, professor of gastroenterology, University of Washington, Seattle.

Dr. Kelly reported no relevant financial conflicts. Dr. Fischer reported a financial relationship with Rebiotix.

HONOLULU – Fecal transplant was shown to be effective in the treatment of recurrent or refractory episodes of Clostridium difficile infection in a double-blind trial for the first time, and a second study isolated predictors of treatment failure.

The results of the double-blind study were expected. Several studies, although none double blind, have previously shown this therapy to be efficacious. The study of predictors of failure may be of more immediate practical application, because it is relevant to patient selection, according to the investigators, some of whom were involved in both studies.

In the double-blind study, 46 patients were randomized at two centers to receive a fecal microbiota transplant from donor stool or to a placebo, which was a transplant of the patient’s own stool.

The primary outcome was clinical cure at the end of 8 weeks, achieved in 91% of those randomized to the active therapy and 63% of those randomized to placebo (P = .024). Most of those who had treatment failure, which occurred on average 10 days after the procedure (range, 1-62 days), received the active therapy subsequently and also achieved clinical cure after donor transplantation.

“There were no significant differences in any adverse event rates between the donor transplant and placebo groups,” Dr. Colleen Kelly reported at the annual meeting of the American College of Gastroenterology. Dr. Kelly, a gastroenterologist with the Miriam Hospital, Brown University, Providence, R.I., was also a coauthor of the study of risk factors for the failure of fecal transplant.

Underlining the importance of a double-blind trial to provide confirmation of the efficacy of fecal transplant, Dr. Christina M. Surawicz, who moderated the ACG session at which both studies were presented, said, “We have been waiting for these results.”

However, a disparity in results at the two participating centers is notable. In Providence, cure was achieved in 90% of those receiving fecal transplant versus 43% receiving placebo (P = .019). At the other participating institution, Montefiore Medical Center, New York, the cure rate was 92% with fecal transplant, but 90% of the placebo patients were also cured (P = .89). The data were not intended for a separate analysis, so Dr. Kelly said this did not affect her final conclusion that this trial confirmed the efficacy of this treatment.

In the separate study evaluating predictors of failure to achieve cure after fecal transplant, the retrospective analysis was performed with 345 patients treated for C. difficile infection with fecal transplant. In this population, the overall failure rate was 23.7%, but there was a wide variability observed upon univariate and multivariate analysis of risk factors, Dr. Monika Fischer, a gastroenterologist at Indiana University Hospital, Indianapolis, said at the meeting.

For example, in patients with nonsevere recurrent C. difficile infection, the failure rate was 18%. In contrast, the failure rate was approximately 50% among those with severe refractory C. difficile infection.

Upon multivariate analysis, three risk factors were independent predictors of fecal transplant failure: inpatient status, which was associated with an odds ratio of 6.92 (P = .001); being immunosuppressed (OR, 3.28; P = .0004); and previous hospitalization for C. difficile infection (OR, 1.45 for each prior hospitalization; P less than .001).

With the use of these three factors, a risk score was found to be highly predictive of failure. In this risk score, 5 points were attributed to inpatient status, 3 points to immunosuppression, and 1 point to each prior hospitalization for C. difficile infection. On a scale of 0-12 points, the risk of failure was 13% in those with 0 points, 17% in those with 1-3 points, and 44% in those with 4 or more points.

“Our data suggest that the risk of fecal transplant failure is predictable based on pretransplant characteristics. We hope that this risk stratification model will prove helpful,” said Dr. Fischer, whose coauthors included Dr. Kelly.

Although she did not directly endorse this risk stratification tool for patient management, Dr. Surawicz called this presentation “very clinically relevant.” Practical tools are needed to guide the use of this therapy as it becomes more widely used in the treatment of C. difficile, said Dr. Surawicz, professor of gastroenterology, University of Washington, Seattle.

Dr. Kelly reported no relevant financial conflicts. Dr. Fischer reported a financial relationship with Rebiotix.