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Ledipasvir-sofosbuvir plus ribavirin in advanced HCV does well
Combination treatment with ledipasvir, sofosbuvir, and ribavirin for chronic hepatitis C virus infection led to sustained viral response (SVR) rates of 86%-89% among nontransplanted patients and 60%-100% among transplant recipients, according to a study published in the September issue of Gastroenterology.
“Rates of SVR were over 85% in every group of patients with Child-Pugh class [CPC] B decompensated cirrhosis – in those who had and had not undergone liver transplantation, as well as those who were receiving 12 and 24 weeks of treatment,” said Dr. Michael Charlton of Intermountain Medical Center in Salt Lake City, and his associates. “Similar response rates were observed in Child-Pugh class C patients who had not undergone liver transplantation. Rates of response were numerically lower in liver transplant recipients with Child-Pugh class C disease, but the small sample size ... makes this a preliminary observation.”
Patients with chronic HCV infection and advanced liver disease have a poor prognosis because of their risk of liver failure and hepatocellular carcinoma and because they have very limited treatment options. Chances of reinfection are 100% if patients have detectable virus at transplantation, and reinfection increases rates of subsequent graft loss, morbidity, and mortality, the investigators noted.
To assess the recently approved sofosbuvir-ledipasvir regimen, they conducted an open-label, phase II trial (SOLAR-1) of the combination plus ribavirin in 337 HCV-infected patients with advanced liver disease, including transplant recipients. Nearly all (99%) of the patients had HCV genotype 1 infection, while 1% had genotype 4 infection. The investigators randomized patients to receive 90 mg ledipasvir and 400 mg sofosbuvir in a fixed-dose daily regimen for either 12 or 24 weeks in combination with ribavirin, which was dosed based on body weight, tolerance of side effects, and extent of liver disease. Patients with CPC C cirrhosis received lower doses of ribavirin because of increased risk of hemotoxicity (Gastroenterology 2015 May 15. doi:10.1053/j.gastro.2015.05.010).
Nontransplanted patients who had decompensated cirrhosis achieved SVR12 or SVR24 rates of 86%-89%, even if they had CPC C decompensated disease, the researchers reported. “Our results also demonstrate that SVR12 in patients with decompensated cirrhosis is associated with early improvements in CPC and MELD [Model for End-Stage Liver Disease] scores, suggesting that eradication of the virus can rapidly improve hepatic function by attenuating the injury and inflammation due to HCV replication,” they said. Patients with CPC B disease also had significant improvements in albumin and bilirubin levels after 4 weeks of treatment.
Among transplant recipients who were noncirrhotic or were in compensated cirrhosis, SVR rates ranged from 96% to 98%, regardless of treatment duration or presence of cirrhosis, Dr. Charlton and associates reported. Among transplant recipients with decompensated cirrhosis, SVR rates were 86%-88% for the subgroup with CPC B disease, but were 60% for CPC C patients who were treated for 12 weeks, and were 75% for CPC C patients who were treated for 24 weeks. In contrast, all six patients with fibrosing cholestatic hepatitis achieved SVR and also experienced large drops in total bilirubin levels within 2-4 weeks of starting treatment, the researchers said. Finally, among the seven patients who underwent liver transplantation either during treatment or before posttreatment week 12, six achieved virologic response after surgery, and one died of multiorgan failure and septic shock 1 day after testing negative for HCV RNA.
In all, 13 patients (4%) discontinued treatment because of adverse events, primarily liver decompensation, the researchers reported. Adverse events that led more than one patient to stop treatment included sepsis, renal failure, dyspnea, and gastrointestinal hemorrhage. Patients were more likely to stop taking ribavirin if they were treated for 24 weeks or had worsening disease. Ten patients died on study, but none of the deaths were thought to be related to treatment, the researchers wrote.
Dr. Charlton disclosed ties with Gilead Sciences, maker of sofosbuvir and ledipasvir. Gilead funded the study. Four coauthors reported having no conflicts; the other 25 investigators reported employment or other financial ties with numerous pharmaceutical companies.
Combination treatment with ledipasvir, sofosbuvir, and ribavirin for chronic hepatitis C virus infection led to sustained viral response (SVR) rates of 86%-89% among nontransplanted patients and 60%-100% among transplant recipients, according to a study published in the September issue of Gastroenterology.
“Rates of SVR were over 85% in every group of patients with Child-Pugh class [CPC] B decompensated cirrhosis – in those who had and had not undergone liver transplantation, as well as those who were receiving 12 and 24 weeks of treatment,” said Dr. Michael Charlton of Intermountain Medical Center in Salt Lake City, and his associates. “Similar response rates were observed in Child-Pugh class C patients who had not undergone liver transplantation. Rates of response were numerically lower in liver transplant recipients with Child-Pugh class C disease, but the small sample size ... makes this a preliminary observation.”
Patients with chronic HCV infection and advanced liver disease have a poor prognosis because of their risk of liver failure and hepatocellular carcinoma and because they have very limited treatment options. Chances of reinfection are 100% if patients have detectable virus at transplantation, and reinfection increases rates of subsequent graft loss, morbidity, and mortality, the investigators noted.
To assess the recently approved sofosbuvir-ledipasvir regimen, they conducted an open-label, phase II trial (SOLAR-1) of the combination plus ribavirin in 337 HCV-infected patients with advanced liver disease, including transplant recipients. Nearly all (99%) of the patients had HCV genotype 1 infection, while 1% had genotype 4 infection. The investigators randomized patients to receive 90 mg ledipasvir and 400 mg sofosbuvir in a fixed-dose daily regimen for either 12 or 24 weeks in combination with ribavirin, which was dosed based on body weight, tolerance of side effects, and extent of liver disease. Patients with CPC C cirrhosis received lower doses of ribavirin because of increased risk of hemotoxicity (Gastroenterology 2015 May 15. doi:10.1053/j.gastro.2015.05.010).
Nontransplanted patients who had decompensated cirrhosis achieved SVR12 or SVR24 rates of 86%-89%, even if they had CPC C decompensated disease, the researchers reported. “Our results also demonstrate that SVR12 in patients with decompensated cirrhosis is associated with early improvements in CPC and MELD [Model for End-Stage Liver Disease] scores, suggesting that eradication of the virus can rapidly improve hepatic function by attenuating the injury and inflammation due to HCV replication,” they said. Patients with CPC B disease also had significant improvements in albumin and bilirubin levels after 4 weeks of treatment.
Among transplant recipients who were noncirrhotic or were in compensated cirrhosis, SVR rates ranged from 96% to 98%, regardless of treatment duration or presence of cirrhosis, Dr. Charlton and associates reported. Among transplant recipients with decompensated cirrhosis, SVR rates were 86%-88% for the subgroup with CPC B disease, but were 60% for CPC C patients who were treated for 12 weeks, and were 75% for CPC C patients who were treated for 24 weeks. In contrast, all six patients with fibrosing cholestatic hepatitis achieved SVR and also experienced large drops in total bilirubin levels within 2-4 weeks of starting treatment, the researchers said. Finally, among the seven patients who underwent liver transplantation either during treatment or before posttreatment week 12, six achieved virologic response after surgery, and one died of multiorgan failure and septic shock 1 day after testing negative for HCV RNA.
In all, 13 patients (4%) discontinued treatment because of adverse events, primarily liver decompensation, the researchers reported. Adverse events that led more than one patient to stop treatment included sepsis, renal failure, dyspnea, and gastrointestinal hemorrhage. Patients were more likely to stop taking ribavirin if they were treated for 24 weeks or had worsening disease. Ten patients died on study, but none of the deaths were thought to be related to treatment, the researchers wrote.
Dr. Charlton disclosed ties with Gilead Sciences, maker of sofosbuvir and ledipasvir. Gilead funded the study. Four coauthors reported having no conflicts; the other 25 investigators reported employment or other financial ties with numerous pharmaceutical companies.
Combination treatment with ledipasvir, sofosbuvir, and ribavirin for chronic hepatitis C virus infection led to sustained viral response (SVR) rates of 86%-89% among nontransplanted patients and 60%-100% among transplant recipients, according to a study published in the September issue of Gastroenterology.
“Rates of SVR were over 85% in every group of patients with Child-Pugh class [CPC] B decompensated cirrhosis – in those who had and had not undergone liver transplantation, as well as those who were receiving 12 and 24 weeks of treatment,” said Dr. Michael Charlton of Intermountain Medical Center in Salt Lake City, and his associates. “Similar response rates were observed in Child-Pugh class C patients who had not undergone liver transplantation. Rates of response were numerically lower in liver transplant recipients with Child-Pugh class C disease, but the small sample size ... makes this a preliminary observation.”
Patients with chronic HCV infection and advanced liver disease have a poor prognosis because of their risk of liver failure and hepatocellular carcinoma and because they have very limited treatment options. Chances of reinfection are 100% if patients have detectable virus at transplantation, and reinfection increases rates of subsequent graft loss, morbidity, and mortality, the investigators noted.
To assess the recently approved sofosbuvir-ledipasvir regimen, they conducted an open-label, phase II trial (SOLAR-1) of the combination plus ribavirin in 337 HCV-infected patients with advanced liver disease, including transplant recipients. Nearly all (99%) of the patients had HCV genotype 1 infection, while 1% had genotype 4 infection. The investigators randomized patients to receive 90 mg ledipasvir and 400 mg sofosbuvir in a fixed-dose daily regimen for either 12 or 24 weeks in combination with ribavirin, which was dosed based on body weight, tolerance of side effects, and extent of liver disease. Patients with CPC C cirrhosis received lower doses of ribavirin because of increased risk of hemotoxicity (Gastroenterology 2015 May 15. doi:10.1053/j.gastro.2015.05.010).
Nontransplanted patients who had decompensated cirrhosis achieved SVR12 or SVR24 rates of 86%-89%, even if they had CPC C decompensated disease, the researchers reported. “Our results also demonstrate that SVR12 in patients with decompensated cirrhosis is associated with early improvements in CPC and MELD [Model for End-Stage Liver Disease] scores, suggesting that eradication of the virus can rapidly improve hepatic function by attenuating the injury and inflammation due to HCV replication,” they said. Patients with CPC B disease also had significant improvements in albumin and bilirubin levels after 4 weeks of treatment.
Among transplant recipients who were noncirrhotic or were in compensated cirrhosis, SVR rates ranged from 96% to 98%, regardless of treatment duration or presence of cirrhosis, Dr. Charlton and associates reported. Among transplant recipients with decompensated cirrhosis, SVR rates were 86%-88% for the subgroup with CPC B disease, but were 60% for CPC C patients who were treated for 12 weeks, and were 75% for CPC C patients who were treated for 24 weeks. In contrast, all six patients with fibrosing cholestatic hepatitis achieved SVR and also experienced large drops in total bilirubin levels within 2-4 weeks of starting treatment, the researchers said. Finally, among the seven patients who underwent liver transplantation either during treatment or before posttreatment week 12, six achieved virologic response after surgery, and one died of multiorgan failure and septic shock 1 day after testing negative for HCV RNA.
In all, 13 patients (4%) discontinued treatment because of adverse events, primarily liver decompensation, the researchers reported. Adverse events that led more than one patient to stop treatment included sepsis, renal failure, dyspnea, and gastrointestinal hemorrhage. Patients were more likely to stop taking ribavirin if they were treated for 24 weeks or had worsening disease. Ten patients died on study, but none of the deaths were thought to be related to treatment, the researchers wrote.
Dr. Charlton disclosed ties with Gilead Sciences, maker of sofosbuvir and ledipasvir. Gilead funded the study. Four coauthors reported having no conflicts; the other 25 investigators reported employment or other financial ties with numerous pharmaceutical companies.
FROM GASTROENTEROLOGY
Key clinical point: Ledipasvir-sofosbuvir plus ribavirin for 12 weeks achieved high SVR rates among patients with hepatitis C virus infection and advanced liver disease.
Major finding: Rates of SVR exceeded 85% in every cohort of Child-Pugh class B decompensated cirrhosis, regardless of treatment duration or transplantation status.
Data source: Randomized open-label phase II study of 337 patients with chronic HCV infection and advanced liver disease.
Disclosures: Dr. Charlton disclosed ties with Gilead Sciences, maker of sofosbuvir and ledipasvir. Gilead funded the study. Four coauthors reported having no conflicts; the other 25 investigators reported employment or other financial ties with numerous pharmaceutical companies.
Assessing progression, impact of radiofrequency ablation in Barrett’s esophagus
Patients with Barrett’s esophagus have about a 0.2% annual chance of developing esophageal adenocarcinoma in the 5 years after initial diagnosis, but the likelihood then rises so that about 9% of all patients will develop cancer by 20 years out, according to a study in the September issue of Gastroenterology.
The modeled rates of progression for the early years after diagnosis are substantially lower than are those reported by prospective studies, which involve more intensive surveillance and therefore suffer from detection bias, said Dr. Sonja Kroep of Erasmus Medical Center, Rotterdam, the Netherlands, and her associates. “Clinicians informing their patients about their cancer risk can best use this clinical progression rate, which is not influenced by surveillance-detected cancers,” they wrote.
Past analyses have yielded varying results for the rate at which Barrett’s esophagus with low-grade dysplasia progresses to high-grade dysplasia and esophageal carcinoma. For their study, Dr. Kroep and her associates calibrated a model based on the annual rate of 0.18% reported by population-level studies, and used it to simulate prospective studies and to predict results from both population-based and prospective studies for various follow-up periods (Gastroenterology 2015 Apr 29. pii: S0016-5085(15)00601-0).
For the first 5 years of follow-up, the model predicted a 0.19% annual rate of transformation to esophageal adenocarcinoma for population-based studies and a 0.36% annual rate for prospective studies, the researchers reported. At 20 years, these rates rose to 0.63% and 0.65% annually, for a cumulative incidence rate of 9.1% to 9.5%. Between the 5-year and 20-year thresholds, the gap between rates of progression for the two types of studies narrowed from 91% to 5%. Taken together, the findings suggest that for the first 5 years after a diagnosis of Barrett’s esophagus, rates of progression to esophageal adenocarcinoma reflect those from population-level studies instead of surveillance-based prospective studies, the investigators said. “Clinicians should use this information to explain to patients their short-term and long-term risks if no action is taken, and then discuss the risks and benefits of surveillance,” they added.
In a separate retrospective study, radiofrequency ablation of low-grade esophageal dysplasia was linked to substantially lower rates of progression compared with watchful waiting in the form of endoscopic surveillance, said Dr. Aaron Small of the University of Pennsylvania, Philadelphia, and his associates. Their study included 125 patients with Barrett’s esophagus and low-grade dysplasia who underwent surveillance only, and 45 patients who underwent radiofrequency ablation at three university medical centers.
Over median follow-up periods of more than 2 years, the risk of progression with radiofrequency ablation was significantly lower than with endoscopic surveillance only, even after the researchers controlled for year of diagnosis (adjusted hazard ratio, 0.06; 95% confidence interval, 0.008-0.48; P = .008). The ablation group also had fewer visible macroscopic lesions, although the difference was not significant. “We estimate that for every three patients treated with radiofrequency ablation, one additional patient with low-grade dysplasia will avoid progression to high-grade dysplasia or esophageal adenocarcinoma within 3 years,” the researchers wrote. “Although selection bias cannot be excluded, these findings provide additional evidence for the use of endoscopic ablation therapy for low-grade dysplasia” (Gastroenterology 2015 Apr 24. pii: S0016-5085(15)00569-7).
The study by Dr. Kroep and her associates was funded by grant U01 CA152926, and the investigators reported having no conflicts of interest. The study by Dr. Small and his associates was supported by the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases and by institutional funds. Dr. Small reported no conflicts of interest, but seven coauthors reported ties with a number of pharmaceutical companies.
These two studies highlight two different hot topics in the management of patients with a Barrett’s esophagus. The first is the low rate of neoplastic progression in patients undergoing surveillance for nondysplastic BE. The second relates to the management of patients with low-grade dysplasia (LG
 |
| Dr. Jacques Bergman |
Population-based BE surveillance studies have shown lower progression rates than have prospective surveillance studies. The biggest difference between these two is that not all patients in population-based studies actually undergo subsequent surveillance endoscopies and/or surveillance is carried out less rigorously than in prospective surveillance studies. Patients who have undergone a baseline endoscopy showing no neoplasia first need to develop early neoplasia (which is generally asymptomatic) that then needs to progress to a symptomatic stage before they are diagnosed. During this interval they may die from other causes or may be lost to follow-up. Patients in strict surveillance programs will be diagnosed at an earlier stage and at a higher rate. This is especially true in the first years of follow-up, when the initial screening endoscopy has its largest effect. Over time, the difference then fades away as suggested by the 9% progression rate of both types of studies at 20 years of follow-up. Both perspectives are relevant for patients. For elderly patients with significant comorbidity, the 5-year data from population-based studies reassure them not to undergo surveillance endoscopies because even when an early cancer develops it is unlikely to bear any clinical relevance, whereas for patients with a long life expectancy, the 9% cancer risk at 20 years and the dismal prognosis of a symptomatic Barrett’s cancer may be strong arguments for participating in a surveillance program.
For patients with LGD, the situation is different: The rate of progression is much higher than that reported for nondysplastic BE, and with radiofrequency ablation (RFA), an effective and safe tool is at hand to significantly reduce this rate of neoplastic progression. Small et al. reported that only three patients need to be treated with RFA to prevent one patient from progressing to high-grade dysplasia or cancer. These data are in agreement with data from a prospective randomized study on the use of RFA for patients with a confirmed diagnosis of LGD. Most societies therefore consider a confirmed histologic diagnosis of LGD a justified indication for prophylactic ablation with RFA.
However, this does not imply that all patients with LGD should be ablated. First, only patients in whom the histologic diagnosis of LGD is confirmed by an expert BE pathologist should be considered for RFA. In approximately 75% of patients, the LGD diagnosis will be downstaged to nondysplastic BE upon expert review. Second, the lessons learned from the Kroep study also apply here: For an elderly LGD patient with or without significant comorbidity, the decision to proceed to RFA is different from the decision for patients with a longer life expectancy, especially if an intermediate solution – to continue endoscopic surveillance and proceed to endoscopic management in case neoplasia is diagnosed – is also considered.
Jacques Bergman, M.D., Ph.D., is professor of gastrointestinal endoscopy, director of endoscopy, at the Academic Medical Center, Amsterdam. He received research support for clinical studies and consulted for Covidien/Medtronic GI solutions.
These two studies highlight two different hot topics in the management of patients with a Barrett’s esophagus. The first is the low rate of neoplastic progression in patients undergoing surveillance for nondysplastic BE. The second relates to the management of patients with low-grade dysplasia (LG
|
| Dr. Jacques Bergman |
Population-based BE surveillance studies have shown lower progression rates than have prospective surveillance studies. The biggest difference between these two is that not all patients in population-based studies actually undergo subsequent surveillance endoscopies and/or surveillance is carried out less rigorously than in prospective surveillance studies. Patients who have undergone a baseline endoscopy showing no neoplasia first need to develop early neoplasia (which is generally asymptomatic) that then needs to progress to a symptomatic stage before they are diagnosed. During this interval they may die from other causes or may be lost to follow-up. Patients in strict surveillance programs will be diagnosed at an earlier stage and at a higher rate. This is especially true in the first years of follow-up, when the initial screening endoscopy has its largest effect. Over time, the difference then fades away as suggested by the 9% progression rate of both types of studies at 20 years of follow-up. Both perspectives are relevant for patients. For elderly patients with significant comorbidity, the 5-year data from population-based studies reassure them not to undergo surveillance endoscopies because even when an early cancer develops it is unlikely to bear any clinical relevance, whereas for patients with a long life expectancy, the 9% cancer risk at 20 years and the dismal prognosis of a symptomatic Barrett’s cancer may be strong arguments for participating in a surveillance program.
For patients with LGD, the situation is different: The rate of progression is much higher than that reported for nondysplastic BE, and with radiofrequency ablation (RFA), an effective and safe tool is at hand to significantly reduce this rate of neoplastic progression. Small et al. reported that only three patients need to be treated with RFA to prevent one patient from progressing to high-grade dysplasia or cancer. These data are in agreement with data from a prospective randomized study on the use of RFA for patients with a confirmed diagnosis of LGD. Most societies therefore consider a confirmed histologic diagnosis of LGD a justified indication for prophylactic ablation with RFA.
However, this does not imply that all patients with LGD should be ablated. First, only patients in whom the histologic diagnosis of LGD is confirmed by an expert BE pathologist should be considered for RFA. In approximately 75% of patients, the LGD diagnosis will be downstaged to nondysplastic BE upon expert review. Second, the lessons learned from the Kroep study also apply here: For an elderly LGD patient with or without significant comorbidity, the decision to proceed to RFA is different from the decision for patients with a longer life expectancy, especially if an intermediate solution – to continue endoscopic surveillance and proceed to endoscopic management in case neoplasia is diagnosed – is also considered.
Jacques Bergman, M.D., Ph.D., is professor of gastrointestinal endoscopy, director of endoscopy, at the Academic Medical Center, Amsterdam. He received research support for clinical studies and consulted for Covidien/Medtronic GI solutions.
These two studies highlight two different hot topics in the management of patients with a Barrett’s esophagus. The first is the low rate of neoplastic progression in patients undergoing surveillance for nondysplastic BE. The second relates to the management of patients with low-grade dysplasia (LG
|
| Dr. Jacques Bergman |
Population-based BE surveillance studies have shown lower progression rates than have prospective surveillance studies. The biggest difference between these two is that not all patients in population-based studies actually undergo subsequent surveillance endoscopies and/or surveillance is carried out less rigorously than in prospective surveillance studies. Patients who have undergone a baseline endoscopy showing no neoplasia first need to develop early neoplasia (which is generally asymptomatic) that then needs to progress to a symptomatic stage before they are diagnosed. During this interval they may die from other causes or may be lost to follow-up. Patients in strict surveillance programs will be diagnosed at an earlier stage and at a higher rate. This is especially true in the first years of follow-up, when the initial screening endoscopy has its largest effect. Over time, the difference then fades away as suggested by the 9% progression rate of both types of studies at 20 years of follow-up. Both perspectives are relevant for patients. For elderly patients with significant comorbidity, the 5-year data from population-based studies reassure them not to undergo surveillance endoscopies because even when an early cancer develops it is unlikely to bear any clinical relevance, whereas for patients with a long life expectancy, the 9% cancer risk at 20 years and the dismal prognosis of a symptomatic Barrett’s cancer may be strong arguments for participating in a surveillance program.
For patients with LGD, the situation is different: The rate of progression is much higher than that reported for nondysplastic BE, and with radiofrequency ablation (RFA), an effective and safe tool is at hand to significantly reduce this rate of neoplastic progression. Small et al. reported that only three patients need to be treated with RFA to prevent one patient from progressing to high-grade dysplasia or cancer. These data are in agreement with data from a prospective randomized study on the use of RFA for patients with a confirmed diagnosis of LGD. Most societies therefore consider a confirmed histologic diagnosis of LGD a justified indication for prophylactic ablation with RFA.
However, this does not imply that all patients with LGD should be ablated. First, only patients in whom the histologic diagnosis of LGD is confirmed by an expert BE pathologist should be considered for RFA. In approximately 75% of patients, the LGD diagnosis will be downstaged to nondysplastic BE upon expert review. Second, the lessons learned from the Kroep study also apply here: For an elderly LGD patient with or without significant comorbidity, the decision to proceed to RFA is different from the decision for patients with a longer life expectancy, especially if an intermediate solution – to continue endoscopic surveillance and proceed to endoscopic management in case neoplasia is diagnosed – is also considered.
Jacques Bergman, M.D., Ph.D., is professor of gastrointestinal endoscopy, director of endoscopy, at the Academic Medical Center, Amsterdam. He received research support for clinical studies and consulted for Covidien/Medtronic GI solutions.
Patients with Barrett’s esophagus have about a 0.2% annual chance of developing esophageal adenocarcinoma in the 5 years after initial diagnosis, but the likelihood then rises so that about 9% of all patients will develop cancer by 20 years out, according to a study in the September issue of Gastroenterology.
The modeled rates of progression for the early years after diagnosis are substantially lower than are those reported by prospective studies, which involve more intensive surveillance and therefore suffer from detection bias, said Dr. Sonja Kroep of Erasmus Medical Center, Rotterdam, the Netherlands, and her associates. “Clinicians informing their patients about their cancer risk can best use this clinical progression rate, which is not influenced by surveillance-detected cancers,” they wrote.
Past analyses have yielded varying results for the rate at which Barrett’s esophagus with low-grade dysplasia progresses to high-grade dysplasia and esophageal carcinoma. For their study, Dr. Kroep and her associates calibrated a model based on the annual rate of 0.18% reported by population-level studies, and used it to simulate prospective studies and to predict results from both population-based and prospective studies for various follow-up periods (Gastroenterology 2015 Apr 29. pii: S0016-5085(15)00601-0).
For the first 5 years of follow-up, the model predicted a 0.19% annual rate of transformation to esophageal adenocarcinoma for population-based studies and a 0.36% annual rate for prospective studies, the researchers reported. At 20 years, these rates rose to 0.63% and 0.65% annually, for a cumulative incidence rate of 9.1% to 9.5%. Between the 5-year and 20-year thresholds, the gap between rates of progression for the two types of studies narrowed from 91% to 5%. Taken together, the findings suggest that for the first 5 years after a diagnosis of Barrett’s esophagus, rates of progression to esophageal adenocarcinoma reflect those from population-level studies instead of surveillance-based prospective studies, the investigators said. “Clinicians should use this information to explain to patients their short-term and long-term risks if no action is taken, and then discuss the risks and benefits of surveillance,” they added.
In a separate retrospective study, radiofrequency ablation of low-grade esophageal dysplasia was linked to substantially lower rates of progression compared with watchful waiting in the form of endoscopic surveillance, said Dr. Aaron Small of the University of Pennsylvania, Philadelphia, and his associates. Their study included 125 patients with Barrett’s esophagus and low-grade dysplasia who underwent surveillance only, and 45 patients who underwent radiofrequency ablation at three university medical centers.
Over median follow-up periods of more than 2 years, the risk of progression with radiofrequency ablation was significantly lower than with endoscopic surveillance only, even after the researchers controlled for year of diagnosis (adjusted hazard ratio, 0.06; 95% confidence interval, 0.008-0.48; P = .008). The ablation group also had fewer visible macroscopic lesions, although the difference was not significant. “We estimate that for every three patients treated with radiofrequency ablation, one additional patient with low-grade dysplasia will avoid progression to high-grade dysplasia or esophageal adenocarcinoma within 3 years,” the researchers wrote. “Although selection bias cannot be excluded, these findings provide additional evidence for the use of endoscopic ablation therapy for low-grade dysplasia” (Gastroenterology 2015 Apr 24. pii: S0016-5085(15)00569-7).
The study by Dr. Kroep and her associates was funded by grant U01 CA152926, and the investigators reported having no conflicts of interest. The study by Dr. Small and his associates was supported by the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases and by institutional funds. Dr. Small reported no conflicts of interest, but seven coauthors reported ties with a number of pharmaceutical companies.
Patients with Barrett’s esophagus have about a 0.2% annual chance of developing esophageal adenocarcinoma in the 5 years after initial diagnosis, but the likelihood then rises so that about 9% of all patients will develop cancer by 20 years out, according to a study in the September issue of Gastroenterology.
The modeled rates of progression for the early years after diagnosis are substantially lower than are those reported by prospective studies, which involve more intensive surveillance and therefore suffer from detection bias, said Dr. Sonja Kroep of Erasmus Medical Center, Rotterdam, the Netherlands, and her associates. “Clinicians informing their patients about their cancer risk can best use this clinical progression rate, which is not influenced by surveillance-detected cancers,” they wrote.
Past analyses have yielded varying results for the rate at which Barrett’s esophagus with low-grade dysplasia progresses to high-grade dysplasia and esophageal carcinoma. For their study, Dr. Kroep and her associates calibrated a model based on the annual rate of 0.18% reported by population-level studies, and used it to simulate prospective studies and to predict results from both population-based and prospective studies for various follow-up periods (Gastroenterology 2015 Apr 29. pii: S0016-5085(15)00601-0).
For the first 5 years of follow-up, the model predicted a 0.19% annual rate of transformation to esophageal adenocarcinoma for population-based studies and a 0.36% annual rate for prospective studies, the researchers reported. At 20 years, these rates rose to 0.63% and 0.65% annually, for a cumulative incidence rate of 9.1% to 9.5%. Between the 5-year and 20-year thresholds, the gap between rates of progression for the two types of studies narrowed from 91% to 5%. Taken together, the findings suggest that for the first 5 years after a diagnosis of Barrett’s esophagus, rates of progression to esophageal adenocarcinoma reflect those from population-level studies instead of surveillance-based prospective studies, the investigators said. “Clinicians should use this information to explain to patients their short-term and long-term risks if no action is taken, and then discuss the risks and benefits of surveillance,” they added.
In a separate retrospective study, radiofrequency ablation of low-grade esophageal dysplasia was linked to substantially lower rates of progression compared with watchful waiting in the form of endoscopic surveillance, said Dr. Aaron Small of the University of Pennsylvania, Philadelphia, and his associates. Their study included 125 patients with Barrett’s esophagus and low-grade dysplasia who underwent surveillance only, and 45 patients who underwent radiofrequency ablation at three university medical centers.
Over median follow-up periods of more than 2 years, the risk of progression with radiofrequency ablation was significantly lower than with endoscopic surveillance only, even after the researchers controlled for year of diagnosis (adjusted hazard ratio, 0.06; 95% confidence interval, 0.008-0.48; P = .008). The ablation group also had fewer visible macroscopic lesions, although the difference was not significant. “We estimate that for every three patients treated with radiofrequency ablation, one additional patient with low-grade dysplasia will avoid progression to high-grade dysplasia or esophageal adenocarcinoma within 3 years,” the researchers wrote. “Although selection bias cannot be excluded, these findings provide additional evidence for the use of endoscopic ablation therapy for low-grade dysplasia” (Gastroenterology 2015 Apr 24. pii: S0016-5085(15)00569-7).
The study by Dr. Kroep and her associates was funded by grant U01 CA152926, and the investigators reported having no conflicts of interest. The study by Dr. Small and his associates was supported by the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases and by institutional funds. Dr. Small reported no conflicts of interest, but seven coauthors reported ties with a number of pharmaceutical companies.
FROM GASTROENTEROLOGY
Key clinical point: Barrett’s esophagus with low-grade dysplasia had a lower rate of progression to cancer than that suggested by prospective surveillance studies, but radiofrequency ablation might further cut the risk.
Major finding: About 0.2% of cases progress during the 5 years after diagnosis, and RFA might significantly decrease risk of progression (adjusted hazard ratio, 0.06).
Data source: A model of rates of progression based on population-level studies, and a multicenter retrospective study of 170 patients with Barrett’s esophagus and low-grade dysplasia.
Disclosures: The study by Dr. Small and associates was supported by the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases and by institutional funds. Dr. Small reported no conflicts of interest; seven coauthors reported ties with a number of pharmaceutical companies. The study by Dr. Kroep and her associates was funded by grant U01 CA152926, and the investigators reported having no conflicts of interest.
No link found between vaccinations, IBD
Neither childhood immunizations nor H1N1 influenza vaccination increased the risk of inflammatory bowel disease, according to a meta-analysis of 11 studies in the August issue of Clinical Gastroenterology and Hepatology published online (2015 [doi:10.1016/j.cgh.2015.04.179]).
“Overall, our results did not find any significant increased risk of developing IBD after childhood immunization with BCG [bacille Calmette-Guérin], diphtheria, tetanus, poliomyelitis, smallpox, pertussis, measles, mumps, and rubella-containing vaccines,” said Dr. Guillaume Pineton de Chambrun of Lille (France) University Hospital and his associates. “The results of this meta-analysis are globally reassuring regarding the risk of developing IBD after childhood vaccination. Vaccines that are developed to protect against an infectious disease or its consequences are, for the majority, not a risk for the subsequent development of intestinal inflammatory disease.”
Besides the childhood vaccines, H1N1 vaccination was not linked to IBD in a single large study of adults (risk ratio, 1.13; 95% confidence interval, 0.97-1.32), the investigators said.
Controversies about immunizations and IBD date to at least 1995, when a report by Thompson et al. linked live measles vaccine to the disease (Lancet 1995;345:1071-4), said the investigators. “However, many publications after this report investigating vaccination with measles-containing vaccines did not show any association between immunization and IBD,” they emphasized. “Epidemiologic studies also investigated other vaccines such as BCG, diphtheria, tetanus, poliomyelitis, smallpox, pertussis, rubella, and mumps, reporting conflicting results.”
To further clarify the issue, they compared rates of IBD, Crohn’s disease, and ulcerative colitis among vaccinated and unvaccinated patients from eight case-control and three cohort studies published between 1970 and June 2014. When looking at IBD overall, 95% CIs for RRs all crossed 1.0, indicating no significant associations, they said. A subgroup analysis did link poliomyelitis vaccination with increased risk of developing Crohn’s disease (RR, 2.28; 95% CI, 1.12-4.63) or ulcerative colitis (RR, 3.48; 95% CI, 1.2-9.71), but the studies were dissimilar enough that the results need to be interpreted cautiously, they added.
To find the studies, the researchers searched MEDLINE, EMBASE, and the Cochrane central trials registry for randomized controlled trials, controlled clinical trials, cohort studies, and case-control studies published in any language and that included the terms ulcerative colitis, Crohn’s disease, inflammatory bowel disease, colitis, or ileitis. This approach yielded six population-based and two hospital-based case-control studies, and three population-based cohort studies. The studies of childhood immunizations included 2,399 patients with IBD and 33,747 controls, and the H1N1 study included 14,842 patients with IBD and almost 2 million controls, said the investigators.
The studies were “extremely heterogeneous” in terms of design, sample size, geographic location, and methods used to help patients recall their vaccination history, the investigators noted. “Vaccination protocols varied between countries and evolved through the years, with different types of vaccines and schedules leading to difficulties in risk evaluation,” they said. “Moreover, some vaccines used were live attenuated vaccines such as measles, oral poliomyelitis, or whole-cell pertussis vaccines, and may have a different effect on immune system activation and dysregulation, compared with other inactivated acellular vaccines.”
The Digitscience Foundation supported the research. The researchers declared having no conflicts of interest.
Neither childhood immunizations nor H1N1 influenza vaccination increased the risk of inflammatory bowel disease, according to a meta-analysis of 11 studies in the August issue of Clinical Gastroenterology and Hepatology published online (2015 [doi:10.1016/j.cgh.2015.04.179]).
“Overall, our results did not find any significant increased risk of developing IBD after childhood immunization with BCG [bacille Calmette-Guérin], diphtheria, tetanus, poliomyelitis, smallpox, pertussis, measles, mumps, and rubella-containing vaccines,” said Dr. Guillaume Pineton de Chambrun of Lille (France) University Hospital and his associates. “The results of this meta-analysis are globally reassuring regarding the risk of developing IBD after childhood vaccination. Vaccines that are developed to protect against an infectious disease or its consequences are, for the majority, not a risk for the subsequent development of intestinal inflammatory disease.”
Besides the childhood vaccines, H1N1 vaccination was not linked to IBD in a single large study of adults (risk ratio, 1.13; 95% confidence interval, 0.97-1.32), the investigators said.
Controversies about immunizations and IBD date to at least 1995, when a report by Thompson et al. linked live measles vaccine to the disease (Lancet 1995;345:1071-4), said the investigators. “However, many publications after this report investigating vaccination with measles-containing vaccines did not show any association between immunization and IBD,” they emphasized. “Epidemiologic studies also investigated other vaccines such as BCG, diphtheria, tetanus, poliomyelitis, smallpox, pertussis, rubella, and mumps, reporting conflicting results.”
To further clarify the issue, they compared rates of IBD, Crohn’s disease, and ulcerative colitis among vaccinated and unvaccinated patients from eight case-control and three cohort studies published between 1970 and June 2014. When looking at IBD overall, 95% CIs for RRs all crossed 1.0, indicating no significant associations, they said. A subgroup analysis did link poliomyelitis vaccination with increased risk of developing Crohn’s disease (RR, 2.28; 95% CI, 1.12-4.63) or ulcerative colitis (RR, 3.48; 95% CI, 1.2-9.71), but the studies were dissimilar enough that the results need to be interpreted cautiously, they added.
To find the studies, the researchers searched MEDLINE, EMBASE, and the Cochrane central trials registry for randomized controlled trials, controlled clinical trials, cohort studies, and case-control studies published in any language and that included the terms ulcerative colitis, Crohn’s disease, inflammatory bowel disease, colitis, or ileitis. This approach yielded six population-based and two hospital-based case-control studies, and three population-based cohort studies. The studies of childhood immunizations included 2,399 patients with IBD and 33,747 controls, and the H1N1 study included 14,842 patients with IBD and almost 2 million controls, said the investigators.
The studies were “extremely heterogeneous” in terms of design, sample size, geographic location, and methods used to help patients recall their vaccination history, the investigators noted. “Vaccination protocols varied between countries and evolved through the years, with different types of vaccines and schedules leading to difficulties in risk evaluation,” they said. “Moreover, some vaccines used were live attenuated vaccines such as measles, oral poliomyelitis, or whole-cell pertussis vaccines, and may have a different effect on immune system activation and dysregulation, compared with other inactivated acellular vaccines.”
The Digitscience Foundation supported the research. The researchers declared having no conflicts of interest.
Neither childhood immunizations nor H1N1 influenza vaccination increased the risk of inflammatory bowel disease, according to a meta-analysis of 11 studies in the August issue of Clinical Gastroenterology and Hepatology published online (2015 [doi:10.1016/j.cgh.2015.04.179]).
“Overall, our results did not find any significant increased risk of developing IBD after childhood immunization with BCG [bacille Calmette-Guérin], diphtheria, tetanus, poliomyelitis, smallpox, pertussis, measles, mumps, and rubella-containing vaccines,” said Dr. Guillaume Pineton de Chambrun of Lille (France) University Hospital and his associates. “The results of this meta-analysis are globally reassuring regarding the risk of developing IBD after childhood vaccination. Vaccines that are developed to protect against an infectious disease or its consequences are, for the majority, not a risk for the subsequent development of intestinal inflammatory disease.”
Besides the childhood vaccines, H1N1 vaccination was not linked to IBD in a single large study of adults (risk ratio, 1.13; 95% confidence interval, 0.97-1.32), the investigators said.
Controversies about immunizations and IBD date to at least 1995, when a report by Thompson et al. linked live measles vaccine to the disease (Lancet 1995;345:1071-4), said the investigators. “However, many publications after this report investigating vaccination with measles-containing vaccines did not show any association between immunization and IBD,” they emphasized. “Epidemiologic studies also investigated other vaccines such as BCG, diphtheria, tetanus, poliomyelitis, smallpox, pertussis, rubella, and mumps, reporting conflicting results.”
To further clarify the issue, they compared rates of IBD, Crohn’s disease, and ulcerative colitis among vaccinated and unvaccinated patients from eight case-control and three cohort studies published between 1970 and June 2014. When looking at IBD overall, 95% CIs for RRs all crossed 1.0, indicating no significant associations, they said. A subgroup analysis did link poliomyelitis vaccination with increased risk of developing Crohn’s disease (RR, 2.28; 95% CI, 1.12-4.63) or ulcerative colitis (RR, 3.48; 95% CI, 1.2-9.71), but the studies were dissimilar enough that the results need to be interpreted cautiously, they added.
To find the studies, the researchers searched MEDLINE, EMBASE, and the Cochrane central trials registry for randomized controlled trials, controlled clinical trials, cohort studies, and case-control studies published in any language and that included the terms ulcerative colitis, Crohn’s disease, inflammatory bowel disease, colitis, or ileitis. This approach yielded six population-based and two hospital-based case-control studies, and three population-based cohort studies. The studies of childhood immunizations included 2,399 patients with IBD and 33,747 controls, and the H1N1 study included 14,842 patients with IBD and almost 2 million controls, said the investigators.
The studies were “extremely heterogeneous” in terms of design, sample size, geographic location, and methods used to help patients recall their vaccination history, the investigators noted. “Vaccination protocols varied between countries and evolved through the years, with different types of vaccines and schedules leading to difficulties in risk evaluation,” they said. “Moreover, some vaccines used were live attenuated vaccines such as measles, oral poliomyelitis, or whole-cell pertussis vaccines, and may have a different effect on immune system activation and dysregulation, compared with other inactivated acellular vaccines.”
The Digitscience Foundation supported the research. The researchers declared having no conflicts of interest.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: A meta-analysis found no link between childhood vaccinations or H1N1 immunization in adults and inflammatory bowel disease.
Major finding: Risk ratios showed no significant associations between IBD and vaccines for BCG infection, diphtheria, tetanus, smallpox, poliomyelitis, measles, rubella, mumps, or H1N1 influenza.
Data source: Systematic review and meta-analysis of eight case-control studies and three cohort studies, encompassing 50,988 total patients.
Disclosures: The Digitscience Foundation supported the research. The researchers declared having no conflicts of interest.
Curcumin and mesalamine top mesalamine alone in ulcerative colitis
More than half of patients with mild to moderate ulcerative colitis who had not responded to optimized mesalamine treatment achieved clinical remission with the addition of 3 grams of curcumin daily, according to a multicenter randomized controlled trial.
In contrast, at week 4, none of the placebo-plus-mesalamine control group had remitted (odds ratio, 42; 95% confidence interval, 2.3-760; P = .01), reported Dr. Alon Lang of Tel-Aviv University, Israel and his associates. The study appears in the August issue of Clinical Gastroenterology and Hepatology.
Mesalamine and curcumin might have “different but potentially synergistic mechanisms of action, hence producing a better outcome” than monotherapy, wrote Dr. Lang and his coinvestigators.
Mesalamine agents are the backbone of treatment for mild to moderate ulcerative colitis, and patients who do not respond to optimized oral and topical therapy are usually stepped up to corticosteroids or immunomodulators, which can have significant side effects, Dr. Lang and his associates noted.
Based on in vitro data supporting the anti-inflammatory and antioxidative properties of curcumin (a phytochemical derived from turmeric), the researchers randomized 50 mesalamine nonresponders who had scored at least 5 but less than 12 on the Simple Clinical Colitis Activity Index to either optimized mesalamine and placebo or optimized mesalamine and 3 grams of curcumin per day. The study excluded patients who had received corticosteroids in the past 12 weeks, were currently receiving anti–tumor necrosis factor agents or cyclosporine, had laboratory abnormalities or significant comorbidities, or had a positive stool culture for Clostridium difficile or enteric pathogens (Clin. Gastroenterol. Hepatol. 2015 [doi:10.1016/j.cgh.2015.02.019])
At week 4, 14 patients (53.8%) in the curcumin-mesalamine group scored 2 or less on the SCCAI, and 17 patients (65.3%) experienced a clinical response, defined as a SCCAI score of 3 or less, the researchers reported. But none of the control group remitted and only three (12.5%) responded clinically (OR, 13.2; 95% CI, 3.1 to 56.6; P < .001), they added. “Admittedly, such nil rate of remission in the placebo arm is much lower than that observed in trials of mesalamine therapy for this indication,” they said. “However, in contrast with prior trials, all patients in the present study were already receiving and failing to respond to optimized oral and topical mesalamine treatment ... it is likely that the zero remission rate and the low (12%) rate of clinical improvement in the placebo arm are a result of this design.”
Use of the SCCAI also could have explained the low remission rate in placebo-treated patients, the researchers said. “Indeed, the SCCAI was recently suggested to be more reflective of actual disease activity compared with other clinical scores, and the strict definition of clinical remission requiring an SCCAI was recently shown to correlate with patients’ genuine sense of remission,” they noted.
In the study, 38% of the intervention group achieved endoscopic remission (a partial Mayo score of 1 or less), compared with none of 16 patients evaluated in the placebo group (OR, 20.7; 95% CI, 1.1 to 393; P = .043). Adverse events were rare and similar between the two groups, the researchers noted.
The trial design lacked a dose-finding component, the sample size was “modest,” and the researchers did not perform a power calculation because no previous studies had looked at the efficacy of curcumin in ulcerative colitis, they wrote.
Sheba Medical Center and the Leona M. and Harry B. Helmsley Charitable Trust helped fund the research. Dr. Lang reported no relevant conflicts of interest, and five coauthors reported relationships with numerous pharmaceutical companies.
Curcumin (diferuloylmethane, a polyphenol) is derived from the Curcuma longa plant. Curcumin has been described as “pharmacodynamically fierce” (owing to its interference in multiple inflammatory and cancer pathways) but “pharmacokinetically feeble” (owing to its chemical instability, poor systemic uptake, and extensive biotransformation) (Pharmacol. Rev. 2013;66:222-307). However, the poor bioavailability of curcumin may be an advantageous property in the treatment of inflammatory bowel disease. In one previous study in ulcerative colitis, oral curcumin (2 g/day) was more effective than was placebo in maintaining remission at 6 months (relapse rates of 5% vs. 21%; P = .04) (Clin. Gastroenterol. Hepatol. 2006;4:1502-6). In another study of patients with mild to moderate distal UC, there was no benefit of rectal curcumin (140 mg dissolved in 20 mL of water taken once daily) over placebo for the induction of remission at 8 weeks (J. Crohns Colitis 2014;8:208-14).
 |
| Dr. Themistocles Dassopoulos |
Lang and colleagues performed a methodologically sound trial in patients with mild to moderate UC failing optimized, combined, oral, and topical mesalamine therapy. Fifty subjects were treated with curcumin (3 g/day; n = 26) vs. placebo (n = 24) for 4 weeks.
The trial met the primary endpoint of clinical remission at week 4, which was 53.8% in the curcumin arm vs. 0% in the placebo arm (odds ratio, 42; 95% confidence interval, 2.3-760). The trial also met all the secondary endpoints of clinical response, endoscopic remission and endoscopic improvement. In this small study, adverse events were rare and comparable between the two arms. More studies are needed to assess the therapeutic efficacy of oral and rectal curcumin, explore the dose-response curve, and assess safety. If proven effective in UC, curcumin is poised to become an especially attractive treatment option given its low cost, tolerability, and (apparent) safety at pharmacologic doses.
Dr. Themistocles Dassopoulos, director of the Baylor Center for Inflammatory Bowel Diseases, Dallas. He has no conflicts of interest.
Curcumin (diferuloylmethane, a polyphenol) is derived from the Curcuma longa plant. Curcumin has been described as “pharmacodynamically fierce” (owing to its interference in multiple inflammatory and cancer pathways) but “pharmacokinetically feeble” (owing to its chemical instability, poor systemic uptake, and extensive biotransformation) (Pharmacol. Rev. 2013;66:222-307). However, the poor bioavailability of curcumin may be an advantageous property in the treatment of inflammatory bowel disease. In one previous study in ulcerative colitis, oral curcumin (2 g/day) was more effective than was placebo in maintaining remission at 6 months (relapse rates of 5% vs. 21%; P = .04) (Clin. Gastroenterol. Hepatol. 2006;4:1502-6). In another study of patients with mild to moderate distal UC, there was no benefit of rectal curcumin (140 mg dissolved in 20 mL of water taken once daily) over placebo for the induction of remission at 8 weeks (J. Crohns Colitis 2014;8:208-14).
|
| Dr. Themistocles Dassopoulos |
Lang and colleagues performed a methodologically sound trial in patients with mild to moderate UC failing optimized, combined, oral, and topical mesalamine therapy. Fifty subjects were treated with curcumin (3 g/day; n = 26) vs. placebo (n = 24) for 4 weeks.
The trial met the primary endpoint of clinical remission at week 4, which was 53.8% in the curcumin arm vs. 0% in the placebo arm (odds ratio, 42; 95% confidence interval, 2.3-760). The trial also met all the secondary endpoints of clinical response, endoscopic remission and endoscopic improvement. In this small study, adverse events were rare and comparable between the two arms. More studies are needed to assess the therapeutic efficacy of oral and rectal curcumin, explore the dose-response curve, and assess safety. If proven effective in UC, curcumin is poised to become an especially attractive treatment option given its low cost, tolerability, and (apparent) safety at pharmacologic doses.
Dr. Themistocles Dassopoulos, director of the Baylor Center for Inflammatory Bowel Diseases, Dallas. He has no conflicts of interest.
Curcumin (diferuloylmethane, a polyphenol) is derived from the Curcuma longa plant. Curcumin has been described as “pharmacodynamically fierce” (owing to its interference in multiple inflammatory and cancer pathways) but “pharmacokinetically feeble” (owing to its chemical instability, poor systemic uptake, and extensive biotransformation) (Pharmacol. Rev. 2013;66:222-307). However, the poor bioavailability of curcumin may be an advantageous property in the treatment of inflammatory bowel disease. In one previous study in ulcerative colitis, oral curcumin (2 g/day) was more effective than was placebo in maintaining remission at 6 months (relapse rates of 5% vs. 21%; P = .04) (Clin. Gastroenterol. Hepatol. 2006;4:1502-6). In another study of patients with mild to moderate distal UC, there was no benefit of rectal curcumin (140 mg dissolved in 20 mL of water taken once daily) over placebo for the induction of remission at 8 weeks (J. Crohns Colitis 2014;8:208-14).
|
| Dr. Themistocles Dassopoulos |
Lang and colleagues performed a methodologically sound trial in patients with mild to moderate UC failing optimized, combined, oral, and topical mesalamine therapy. Fifty subjects were treated with curcumin (3 g/day; n = 26) vs. placebo (n = 24) for 4 weeks.
The trial met the primary endpoint of clinical remission at week 4, which was 53.8% in the curcumin arm vs. 0% in the placebo arm (odds ratio, 42; 95% confidence interval, 2.3-760). The trial also met all the secondary endpoints of clinical response, endoscopic remission and endoscopic improvement. In this small study, adverse events were rare and comparable between the two arms. More studies are needed to assess the therapeutic efficacy of oral and rectal curcumin, explore the dose-response curve, and assess safety. If proven effective in UC, curcumin is poised to become an especially attractive treatment option given its low cost, tolerability, and (apparent) safety at pharmacologic doses.
Dr. Themistocles Dassopoulos, director of the Baylor Center for Inflammatory Bowel Diseases, Dallas. He has no conflicts of interest.
More than half of patients with mild to moderate ulcerative colitis who had not responded to optimized mesalamine treatment achieved clinical remission with the addition of 3 grams of curcumin daily, according to a multicenter randomized controlled trial.
In contrast, at week 4, none of the placebo-plus-mesalamine control group had remitted (odds ratio, 42; 95% confidence interval, 2.3-760; P = .01), reported Dr. Alon Lang of Tel-Aviv University, Israel and his associates. The study appears in the August issue of Clinical Gastroenterology and Hepatology.
Mesalamine and curcumin might have “different but potentially synergistic mechanisms of action, hence producing a better outcome” than monotherapy, wrote Dr. Lang and his coinvestigators.
Mesalamine agents are the backbone of treatment for mild to moderate ulcerative colitis, and patients who do not respond to optimized oral and topical therapy are usually stepped up to corticosteroids or immunomodulators, which can have significant side effects, Dr. Lang and his associates noted.
Based on in vitro data supporting the anti-inflammatory and antioxidative properties of curcumin (a phytochemical derived from turmeric), the researchers randomized 50 mesalamine nonresponders who had scored at least 5 but less than 12 on the Simple Clinical Colitis Activity Index to either optimized mesalamine and placebo or optimized mesalamine and 3 grams of curcumin per day. The study excluded patients who had received corticosteroids in the past 12 weeks, were currently receiving anti–tumor necrosis factor agents or cyclosporine, had laboratory abnormalities or significant comorbidities, or had a positive stool culture for Clostridium difficile or enteric pathogens (Clin. Gastroenterol. Hepatol. 2015 [doi:10.1016/j.cgh.2015.02.019])
At week 4, 14 patients (53.8%) in the curcumin-mesalamine group scored 2 or less on the SCCAI, and 17 patients (65.3%) experienced a clinical response, defined as a SCCAI score of 3 or less, the researchers reported. But none of the control group remitted and only three (12.5%) responded clinically (OR, 13.2; 95% CI, 3.1 to 56.6; P < .001), they added. “Admittedly, such nil rate of remission in the placebo arm is much lower than that observed in trials of mesalamine therapy for this indication,” they said. “However, in contrast with prior trials, all patients in the present study were already receiving and failing to respond to optimized oral and topical mesalamine treatment ... it is likely that the zero remission rate and the low (12%) rate of clinical improvement in the placebo arm are a result of this design.”
Use of the SCCAI also could have explained the low remission rate in placebo-treated patients, the researchers said. “Indeed, the SCCAI was recently suggested to be more reflective of actual disease activity compared with other clinical scores, and the strict definition of clinical remission requiring an SCCAI was recently shown to correlate with patients’ genuine sense of remission,” they noted.
In the study, 38% of the intervention group achieved endoscopic remission (a partial Mayo score of 1 or less), compared with none of 16 patients evaluated in the placebo group (OR, 20.7; 95% CI, 1.1 to 393; P = .043). Adverse events were rare and similar between the two groups, the researchers noted.
The trial design lacked a dose-finding component, the sample size was “modest,” and the researchers did not perform a power calculation because no previous studies had looked at the efficacy of curcumin in ulcerative colitis, they wrote.
Sheba Medical Center and the Leona M. and Harry B. Helmsley Charitable Trust helped fund the research. Dr. Lang reported no relevant conflicts of interest, and five coauthors reported relationships with numerous pharmaceutical companies.
More than half of patients with mild to moderate ulcerative colitis who had not responded to optimized mesalamine treatment achieved clinical remission with the addition of 3 grams of curcumin daily, according to a multicenter randomized controlled trial.
In contrast, at week 4, none of the placebo-plus-mesalamine control group had remitted (odds ratio, 42; 95% confidence interval, 2.3-760; P = .01), reported Dr. Alon Lang of Tel-Aviv University, Israel and his associates. The study appears in the August issue of Clinical Gastroenterology and Hepatology.
Mesalamine and curcumin might have “different but potentially synergistic mechanisms of action, hence producing a better outcome” than monotherapy, wrote Dr. Lang and his coinvestigators.
Mesalamine agents are the backbone of treatment for mild to moderate ulcerative colitis, and patients who do not respond to optimized oral and topical therapy are usually stepped up to corticosteroids or immunomodulators, which can have significant side effects, Dr. Lang and his associates noted.
Based on in vitro data supporting the anti-inflammatory and antioxidative properties of curcumin (a phytochemical derived from turmeric), the researchers randomized 50 mesalamine nonresponders who had scored at least 5 but less than 12 on the Simple Clinical Colitis Activity Index to either optimized mesalamine and placebo or optimized mesalamine and 3 grams of curcumin per day. The study excluded patients who had received corticosteroids in the past 12 weeks, were currently receiving anti–tumor necrosis factor agents or cyclosporine, had laboratory abnormalities or significant comorbidities, or had a positive stool culture for Clostridium difficile or enteric pathogens (Clin. Gastroenterol. Hepatol. 2015 [doi:10.1016/j.cgh.2015.02.019])
At week 4, 14 patients (53.8%) in the curcumin-mesalamine group scored 2 or less on the SCCAI, and 17 patients (65.3%) experienced a clinical response, defined as a SCCAI score of 3 or less, the researchers reported. But none of the control group remitted and only three (12.5%) responded clinically (OR, 13.2; 95% CI, 3.1 to 56.6; P < .001), they added. “Admittedly, such nil rate of remission in the placebo arm is much lower than that observed in trials of mesalamine therapy for this indication,” they said. “However, in contrast with prior trials, all patients in the present study were already receiving and failing to respond to optimized oral and topical mesalamine treatment ... it is likely that the zero remission rate and the low (12%) rate of clinical improvement in the placebo arm are a result of this design.”
Use of the SCCAI also could have explained the low remission rate in placebo-treated patients, the researchers said. “Indeed, the SCCAI was recently suggested to be more reflective of actual disease activity compared with other clinical scores, and the strict definition of clinical remission requiring an SCCAI was recently shown to correlate with patients’ genuine sense of remission,” they noted.
In the study, 38% of the intervention group achieved endoscopic remission (a partial Mayo score of 1 or less), compared with none of 16 patients evaluated in the placebo group (OR, 20.7; 95% CI, 1.1 to 393; P = .043). Adverse events were rare and similar between the two groups, the researchers noted.
The trial design lacked a dose-finding component, the sample size was “modest,” and the researchers did not perform a power calculation because no previous studies had looked at the efficacy of curcumin in ulcerative colitis, they wrote.
Sheba Medical Center and the Leona M. and Harry B. Helmsley Charitable Trust helped fund the research. Dr. Lang reported no relevant conflicts of interest, and five coauthors reported relationships with numerous pharmaceutical companies.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: About half of mesalamine nonresponders with active mild to moderate ulcerative colitis remitted after adding curcumin.
Major finding: Week 4 remission rates were 53.8% for the curcumin-mesalamine group and 0% for the placebo-mesalamine group (P = .01).
Data source: Multicenter randomized, placebo-controlled trial of 50 patients with mild to moderate ulcerative colitis that had failed to respond to optimized mesalamine.
Disclosures: Sheba Medical Center and the Leona M. and Harry B. Helmsley Charitable Trust helped fund the research. Dr. Lang reported no relevant conflicts of interest; five coauthors reported relationships with numerous pharmaceutical companies.
Pentoxifylline beat placebo in acute pancreatitis trial
Patients with acute pancreatitis who received pentoxifylline had fewer ICU admissions and shorter ICU and hospital stays than placebo-treated controls, according to a small, randomized double-blind trial reported in Gastroenterology.
“We showed that a single-institution drug trial for acute pancreatitis is feasible and that pentoxifylline is safe, cheap, and might have efficacy,” wrote Dr. Santhi Vege and his associates at the Mayo Clinic in Rochester, Minn. “This sets the stage for a larger trial of this drug in all patients with acute pancreatitis, to realize the goal of finding an effective drug that can be given within 24 hours of diagnosis in any setting.”
Tumor necrosis factor–alpha is a key culprit in severe acute pancreatitis, including pancreatic and peripancreatic necrosis, systemic inflammatory response syndrome, and persistent organ failure, the researchers noted. Pentoxifylline is a nonselective phosphodiesterase inhibitor that has been found safe and effective in other TNF-alpha–mediated diseases such as acute alcoholic hepatitis, but few studies in humans have evaluated the drug for acute pancreatitis, they said (Gastroenterology 2015 June 22 [doi:10.1053/j.gastro.2015.04.019]). For their study, the investigators randomized 28 patients with predicted severe acute pancreatitis to either placebo or 400 mg pentoxifylline given orally at enrollment and then three times a day for 72 hours. Both groups also received standard of care treatments such as antibiotics and fluid therapy, and had comparable baseline characteristics including age, sex, body mass index, Acute Physiology and Chronic Health Evaluation scores, systemic inflammatory response syndrome scores, and inflammatory marker levels, the researchers said.
Significantly fewer patients who received pentoxifylline needed to stay in the hospital for more than 4 days (14% vs. 57% for the placebo group; P = .046), and the maximum length of ICU stay was 0 days for the intervention group, compared with 13 days for the control group (P = .03), the investigators reported. Analyses of several other outcome measures also favored pentoxifylline over placebo, but did not reach statistical significance in the small study, including the need for ICU transfer (0% for pentoxifylline patients vs. 28% of the placebo group; P = .098) and the median length of hospitalization (for pentoxifylline: 3 days, range 1-5 days; for placebo: 5 days; range 1-30 days; P = .06).
The treatment and control groups did not significantly differ in terms of levels of inflammatory markers, including circulating TNF-alpha, said the investigators. Differences in levels of TNF-alpha, interleukin-6, IL-8, and C-reactive protein “may be significant if the sample size is larger,” they added.
The exact mechanism by which pentoxifylline affects acute pancreatitis is unclear, but the production of pancreatic TNF-alpha peaks about 24-36 hours into an episode of the disease, so patients might benefit from receiving pentoxifylline sooner than the 72-hour window dictated by the study protocol, said Dr. Vege and his associates. “Initiating drug therapy within a few hours is challenging, although a 24-hour cutoff time may be feasible in appropriate settings,” they wrote.
A scholarly opportunity award from the Mayo Clinic helped fund the work. The investigators reported having no relevant financial conflicts of interest.
The study of acute pancreatitis (AP) is economically and scientifically essential because acute pancreatitis is the most common reason for hospitalization among patients with GI diseases, consumes considerable resources, and is treated primarily with supportive measures. The pilot study by Dr. Vege and his colleagues reports that pentoxifylline treatment is safe for patients with severe acute pancreatitis and is associated with a promising reduction in ICU utilization and duration in patients requiring a hospital stay >4 days.
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| Dr. Matthew J. DiMagno |
This study is not only provocative but also raises the hypothesis-generating question of how pentoxifylline might exert a salutary effect without reducing blood tumor necrosis factor–alpha levels (or IL-6, IL-8, or C-reactive protein levels). The authors ascribe this discordance to the timing of administering pentoxifylline and to potential TNF-alpha independent effects. Biologically, pancreatic TNF-alpha levels increase within the first 30-60 minutes of onset of acute pancreatitis (Am. J. Surg. 1998;175:76-83). In experimental AP, pentoxifylline ameliorates severity, but data are conflicting about whether prophylactic or delayed (Surgery 1996;120:515-21) antagonism of TNF-alpha signaling is more protective. Clinically relevant data suggest that prophylactic administration of pentoxifylline does not prevent postendoscopic retrograde cholangiopancreatography pancreatitis (Gastrointest. Endosc. 2007;66:513-8), but nonprophylactic administration of pentoxifylline improves short-term survival in alcoholic hepatitis without significantly reducing blood TNF-alpha levels (Gastroenterology 2000;119:1637-48). Hence, pentoxifylline appears to ameliorate AP and alcoholic hepatitis through TNF-alpha independent signaling, conceivably by targeting the microcirculation, as described for patients with claudication (Angiology 1994;45:339-45).
Future studies might test this hypothesis by determining whether pentoxifylline blunts increases in deleterious vascular factors (for example, angiopoietin-2) [Am. J. Gastroenterol. 2010;105:2287-92; J. Am. Coll. Surg. 2014;218:26-32; Am. J. Gastroenterol. 2011;106:1859-61]) and reduces vascular complications that correlate with the need for ICU care and more severe AP.
Dr. Matthew J. DiMagno is in the division of gastroenterology and hepatology, department of internal medicine, University of Michigan, Ann Arbor. He serves as chair of the American Gastroenterological Association Institute Council Section on Pancreatic Disorders. He declared no relevant financial conflicts of interest.
The study of acute pancreatitis (AP) is economically and scientifically essential because acute pancreatitis is the most common reason for hospitalization among patients with GI diseases, consumes considerable resources, and is treated primarily with supportive measures. The pilot study by Dr. Vege and his colleagues reports that pentoxifylline treatment is safe for patients with severe acute pancreatitis and is associated with a promising reduction in ICU utilization and duration in patients requiring a hospital stay >4 days.
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| Dr. Matthew J. DiMagno |
This study is not only provocative but also raises the hypothesis-generating question of how pentoxifylline might exert a salutary effect without reducing blood tumor necrosis factor–alpha levels (or IL-6, IL-8, or C-reactive protein levels). The authors ascribe this discordance to the timing of administering pentoxifylline and to potential TNF-alpha independent effects. Biologically, pancreatic TNF-alpha levels increase within the first 30-60 minutes of onset of acute pancreatitis (Am. J. Surg. 1998;175:76-83). In experimental AP, pentoxifylline ameliorates severity, but data are conflicting about whether prophylactic or delayed (Surgery 1996;120:515-21) antagonism of TNF-alpha signaling is more protective. Clinically relevant data suggest that prophylactic administration of pentoxifylline does not prevent postendoscopic retrograde cholangiopancreatography pancreatitis (Gastrointest. Endosc. 2007;66:513-8), but nonprophylactic administration of pentoxifylline improves short-term survival in alcoholic hepatitis without significantly reducing blood TNF-alpha levels (Gastroenterology 2000;119:1637-48). Hence, pentoxifylline appears to ameliorate AP and alcoholic hepatitis through TNF-alpha independent signaling, conceivably by targeting the microcirculation, as described for patients with claudication (Angiology 1994;45:339-45).
Future studies might test this hypothesis by determining whether pentoxifylline blunts increases in deleterious vascular factors (for example, angiopoietin-2) [Am. J. Gastroenterol. 2010;105:2287-92; J. Am. Coll. Surg. 2014;218:26-32; Am. J. Gastroenterol. 2011;106:1859-61]) and reduces vascular complications that correlate with the need for ICU care and more severe AP.
Dr. Matthew J. DiMagno is in the division of gastroenterology and hepatology, department of internal medicine, University of Michigan, Ann Arbor. He serves as chair of the American Gastroenterological Association Institute Council Section on Pancreatic Disorders. He declared no relevant financial conflicts of interest.
The study of acute pancreatitis (AP) is economically and scientifically essential because acute pancreatitis is the most common reason for hospitalization among patients with GI diseases, consumes considerable resources, and is treated primarily with supportive measures. The pilot study by Dr. Vege and his colleagues reports that pentoxifylline treatment is safe for patients with severe acute pancreatitis and is associated with a promising reduction in ICU utilization and duration in patients requiring a hospital stay >4 days.
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| Dr. Matthew J. DiMagno |
This study is not only provocative but also raises the hypothesis-generating question of how pentoxifylline might exert a salutary effect without reducing blood tumor necrosis factor–alpha levels (or IL-6, IL-8, or C-reactive protein levels). The authors ascribe this discordance to the timing of administering pentoxifylline and to potential TNF-alpha independent effects. Biologically, pancreatic TNF-alpha levels increase within the first 30-60 minutes of onset of acute pancreatitis (Am. J. Surg. 1998;175:76-83). In experimental AP, pentoxifylline ameliorates severity, but data are conflicting about whether prophylactic or delayed (Surgery 1996;120:515-21) antagonism of TNF-alpha signaling is more protective. Clinically relevant data suggest that prophylactic administration of pentoxifylline does not prevent postendoscopic retrograde cholangiopancreatography pancreatitis (Gastrointest. Endosc. 2007;66:513-8), but nonprophylactic administration of pentoxifylline improves short-term survival in alcoholic hepatitis without significantly reducing blood TNF-alpha levels (Gastroenterology 2000;119:1637-48). Hence, pentoxifylline appears to ameliorate AP and alcoholic hepatitis through TNF-alpha independent signaling, conceivably by targeting the microcirculation, as described for patients with claudication (Angiology 1994;45:339-45).
Future studies might test this hypothesis by determining whether pentoxifylline blunts increases in deleterious vascular factors (for example, angiopoietin-2) [Am. J. Gastroenterol. 2010;105:2287-92; J. Am. Coll. Surg. 2014;218:26-32; Am. J. Gastroenterol. 2011;106:1859-61]) and reduces vascular complications that correlate with the need for ICU care and more severe AP.
Dr. Matthew J. DiMagno is in the division of gastroenterology and hepatology, department of internal medicine, University of Michigan, Ann Arbor. He serves as chair of the American Gastroenterological Association Institute Council Section on Pancreatic Disorders. He declared no relevant financial conflicts of interest.
Patients with acute pancreatitis who received pentoxifylline had fewer ICU admissions and shorter ICU and hospital stays than placebo-treated controls, according to a small, randomized double-blind trial reported in Gastroenterology.
“We showed that a single-institution drug trial for acute pancreatitis is feasible and that pentoxifylline is safe, cheap, and might have efficacy,” wrote Dr. Santhi Vege and his associates at the Mayo Clinic in Rochester, Minn. “This sets the stage for a larger trial of this drug in all patients with acute pancreatitis, to realize the goal of finding an effective drug that can be given within 24 hours of diagnosis in any setting.”
Tumor necrosis factor–alpha is a key culprit in severe acute pancreatitis, including pancreatic and peripancreatic necrosis, systemic inflammatory response syndrome, and persistent organ failure, the researchers noted. Pentoxifylline is a nonselective phosphodiesterase inhibitor that has been found safe and effective in other TNF-alpha–mediated diseases such as acute alcoholic hepatitis, but few studies in humans have evaluated the drug for acute pancreatitis, they said (Gastroenterology 2015 June 22 [doi:10.1053/j.gastro.2015.04.019]). For their study, the investigators randomized 28 patients with predicted severe acute pancreatitis to either placebo or 400 mg pentoxifylline given orally at enrollment and then three times a day for 72 hours. Both groups also received standard of care treatments such as antibiotics and fluid therapy, and had comparable baseline characteristics including age, sex, body mass index, Acute Physiology and Chronic Health Evaluation scores, systemic inflammatory response syndrome scores, and inflammatory marker levels, the researchers said.
Significantly fewer patients who received pentoxifylline needed to stay in the hospital for more than 4 days (14% vs. 57% for the placebo group; P = .046), and the maximum length of ICU stay was 0 days for the intervention group, compared with 13 days for the control group (P = .03), the investigators reported. Analyses of several other outcome measures also favored pentoxifylline over placebo, but did not reach statistical significance in the small study, including the need for ICU transfer (0% for pentoxifylline patients vs. 28% of the placebo group; P = .098) and the median length of hospitalization (for pentoxifylline: 3 days, range 1-5 days; for placebo: 5 days; range 1-30 days; P = .06).
The treatment and control groups did not significantly differ in terms of levels of inflammatory markers, including circulating TNF-alpha, said the investigators. Differences in levels of TNF-alpha, interleukin-6, IL-8, and C-reactive protein “may be significant if the sample size is larger,” they added.
The exact mechanism by which pentoxifylline affects acute pancreatitis is unclear, but the production of pancreatic TNF-alpha peaks about 24-36 hours into an episode of the disease, so patients might benefit from receiving pentoxifylline sooner than the 72-hour window dictated by the study protocol, said Dr. Vege and his associates. “Initiating drug therapy within a few hours is challenging, although a 24-hour cutoff time may be feasible in appropriate settings,” they wrote.
A scholarly opportunity award from the Mayo Clinic helped fund the work. The investigators reported having no relevant financial conflicts of interest.
Patients with acute pancreatitis who received pentoxifylline had fewer ICU admissions and shorter ICU and hospital stays than placebo-treated controls, according to a small, randomized double-blind trial reported in Gastroenterology.
“We showed that a single-institution drug trial for acute pancreatitis is feasible and that pentoxifylline is safe, cheap, and might have efficacy,” wrote Dr. Santhi Vege and his associates at the Mayo Clinic in Rochester, Minn. “This sets the stage for a larger trial of this drug in all patients with acute pancreatitis, to realize the goal of finding an effective drug that can be given within 24 hours of diagnosis in any setting.”
Tumor necrosis factor–alpha is a key culprit in severe acute pancreatitis, including pancreatic and peripancreatic necrosis, systemic inflammatory response syndrome, and persistent organ failure, the researchers noted. Pentoxifylline is a nonselective phosphodiesterase inhibitor that has been found safe and effective in other TNF-alpha–mediated diseases such as acute alcoholic hepatitis, but few studies in humans have evaluated the drug for acute pancreatitis, they said (Gastroenterology 2015 June 22 [doi:10.1053/j.gastro.2015.04.019]). For their study, the investigators randomized 28 patients with predicted severe acute pancreatitis to either placebo or 400 mg pentoxifylline given orally at enrollment and then three times a day for 72 hours. Both groups also received standard of care treatments such as antibiotics and fluid therapy, and had comparable baseline characteristics including age, sex, body mass index, Acute Physiology and Chronic Health Evaluation scores, systemic inflammatory response syndrome scores, and inflammatory marker levels, the researchers said.
Significantly fewer patients who received pentoxifylline needed to stay in the hospital for more than 4 days (14% vs. 57% for the placebo group; P = .046), and the maximum length of ICU stay was 0 days for the intervention group, compared with 13 days for the control group (P = .03), the investigators reported. Analyses of several other outcome measures also favored pentoxifylline over placebo, but did not reach statistical significance in the small study, including the need for ICU transfer (0% for pentoxifylline patients vs. 28% of the placebo group; P = .098) and the median length of hospitalization (for pentoxifylline: 3 days, range 1-5 days; for placebo: 5 days; range 1-30 days; P = .06).
The treatment and control groups did not significantly differ in terms of levels of inflammatory markers, including circulating TNF-alpha, said the investigators. Differences in levels of TNF-alpha, interleukin-6, IL-8, and C-reactive protein “may be significant if the sample size is larger,” they added.
The exact mechanism by which pentoxifylline affects acute pancreatitis is unclear, but the production of pancreatic TNF-alpha peaks about 24-36 hours into an episode of the disease, so patients might benefit from receiving pentoxifylline sooner than the 72-hour window dictated by the study protocol, said Dr. Vege and his associates. “Initiating drug therapy within a few hours is challenging, although a 24-hour cutoff time may be feasible in appropriate settings,” they wrote.
A scholarly opportunity award from the Mayo Clinic helped fund the work. The investigators reported having no relevant financial conflicts of interest.
FROM GASTROENTEROLOGY
Key clinical point: Pentoxifylline topped placebo for several outcome measures among patients with severe acute pancreatitis.
Major finding: Significantly fewer patients who received pentoxifylline needed to stay in the hospital for more than 4 days (14% vs. 57% for the placebo group; P = .046).
Data source: A single-center, randomized placebo-controlled trial of 28 patients with predicted severe acute pancreatitis.
Disclosures: A scholarly opportunity award from the Mayo Clinic supported the work. The investigators reported having no relevant financial conflicts of interest.
Lifestyle changes, surgical weight loss benefit NAFLD
Losing weight through lifestyle changes can significantly improve several measures of nonalcoholic fatty liver disease, particularly if patients lose at least 10% of their body weight, and bariatric surgery is a valid alternative if diet and exercise fail, according to two studies reported in the August issue of Gastroenterology (2015 Apr. 9 [doi:10.1053/j.gastro.2015.04.005]).
Global rates of nonalcoholic fatty liver disease (NAFLD) are up because of the “parallel epidemics” of obesity and type 2 diabetes mellitus, said Dr. Eduardo Vilar-Gomez of the National Institute of Hepatology in Havana, Cuba, who authored the study of lifestyle changes. There are no approved therapies for the more aggressive form of NAFLD, steatohepatitis, he and his associates said. In past studies, patients who lost about 7%-10% of their body weight substantially improved their NAFLD activity score and had reductions in steatosis, lobular inflammation, and ballooning, but the results did not extend to fibrosis, and prospective studies of the effect of lifestyle changes on histology are lacking, the researchers added .
To fill the gap, they followed 293 adults with histologically confirmed nonalcoholic steatohepatitis who completed a 52-week lifestyle intervention program that included keeping a food diary, restricting saturated fats to less than 10% of total intake, and walking at least 200 minutes a week. Patients had not received hypolipidemic treatment in the preceding 3 months and were not allowed to take insulin sensitizers or vitamin E, both of which are potentially beneficial for nonalcoholic steatohepatitis, the investigators said.
At the end of the yearlong program, steatohepatitis had resolved in 25% of patients, 47% had lower NAFLD activity scores, and 19% had regression of fibrosis, the researchers reported. Although only 30% of participants lost at least 5% of their body weight, weight loss correlated positively with resolution of steatohepatitis and with 2-point reductions in histologic activity scores (P <.001). Among patients who lost at least 10% of their body weight, 90% had resolution of steatohepatitis, 45% had regression of fibrosis, and all had improved histologic activity scores, even if they had negative risk factors such as female sex, a baseline body mass index of at least 35 kg/m2, and a baseline fasting glucose level of at least 5.5 mmol/L, the investigators added. “Our findings support the current recommendation for weight loss using lifestyle modification as the first step in the management of patients with nonalcoholic steatohepatitis,” they wrote.
But what if lifestyle changes fail? The impact of bariatric surgery on nonalcoholic steatohepatitis has not been well studied, said Dr. Guillaume Lassailly at CHRU Lille (France). He and his associates therefore followed 109 morbidly obese patients (BMI ≥40 kg/m2) with biopsy-confirmed nonalcoholic steatohepatitis who underwent bariatric surgery at a single tertiary hospital (Gastroenterology 2015 Apr. 25 [doi:10.1053/j.gastro.2015.04.014]) .
One year after surgery, 85% of patients had achieved disease resolution (95% confidence interval, 75.8%-92.2%), the investigators reported. Stratifying patients by baseline Brunt scores showed that those with milder presurgical disease were more likely to have complete resolution than were patients whose disease was severe (94% vs. 70%; P <.05), the researchers added. Histologic analyses supported the findings, revealing steatosis in 60% of presurgical tissue samples, compared with 10% of samples taken a year after surgery. In addition, average NAFLD disease scores dropped from 5 to 1 (P <.001), hepatocyte ballooning decreased in 84% of samples, lobular inflammation decreased in 67%, and Metavir fibrosis scores dropped in one-third of specimens.
Notably, BMI scores for patients with persistent postsurgical disease dropped by an average of only 9.1, compared with 12.3 for patients whose disease resolved (P = .005), said the researchers. Gastric bypass surgery achieved greater weight loss and improvements in disease status, compared with laparoscopic banding, they added. “The encouraging results of the present study suggest that bariatric surgery should be tested in multicenter, randomized controlled trials in morbidly or severely obese patients with nonalcoholic steatohepatitis who did not respond to lifestyle therapy,” they wrote.
The Cuban National Institute of Gastroenterology and Ministry of Health partially funded the study by Dr. Vilar-Gomez and his associates. The French Ministry of Health and the Conseil Regional Nord-Pas de Calais supported the work by Dr. Lassailly and his colleagues. All investigators declared having no relevant financial conflicts of interest.
Losing weight through lifestyle changes can significantly improve several measures of nonalcoholic fatty liver disease, particularly if patients lose at least 10% of their body weight, and bariatric surgery is a valid alternative if diet and exercise fail, according to two studies reported in the August issue of Gastroenterology (2015 Apr. 9 [doi:10.1053/j.gastro.2015.04.005]).
Global rates of nonalcoholic fatty liver disease (NAFLD) are up because of the “parallel epidemics” of obesity and type 2 diabetes mellitus, said Dr. Eduardo Vilar-Gomez of the National Institute of Hepatology in Havana, Cuba, who authored the study of lifestyle changes. There are no approved therapies for the more aggressive form of NAFLD, steatohepatitis, he and his associates said. In past studies, patients who lost about 7%-10% of their body weight substantially improved their NAFLD activity score and had reductions in steatosis, lobular inflammation, and ballooning, but the results did not extend to fibrosis, and prospective studies of the effect of lifestyle changes on histology are lacking, the researchers added .
To fill the gap, they followed 293 adults with histologically confirmed nonalcoholic steatohepatitis who completed a 52-week lifestyle intervention program that included keeping a food diary, restricting saturated fats to less than 10% of total intake, and walking at least 200 minutes a week. Patients had not received hypolipidemic treatment in the preceding 3 months and were not allowed to take insulin sensitizers or vitamin E, both of which are potentially beneficial for nonalcoholic steatohepatitis, the investigators said.
At the end of the yearlong program, steatohepatitis had resolved in 25% of patients, 47% had lower NAFLD activity scores, and 19% had regression of fibrosis, the researchers reported. Although only 30% of participants lost at least 5% of their body weight, weight loss correlated positively with resolution of steatohepatitis and with 2-point reductions in histologic activity scores (P <.001). Among patients who lost at least 10% of their body weight, 90% had resolution of steatohepatitis, 45% had regression of fibrosis, and all had improved histologic activity scores, even if they had negative risk factors such as female sex, a baseline body mass index of at least 35 kg/m2, and a baseline fasting glucose level of at least 5.5 mmol/L, the investigators added. “Our findings support the current recommendation for weight loss using lifestyle modification as the first step in the management of patients with nonalcoholic steatohepatitis,” they wrote.
But what if lifestyle changes fail? The impact of bariatric surgery on nonalcoholic steatohepatitis has not been well studied, said Dr. Guillaume Lassailly at CHRU Lille (France). He and his associates therefore followed 109 morbidly obese patients (BMI ≥40 kg/m2) with biopsy-confirmed nonalcoholic steatohepatitis who underwent bariatric surgery at a single tertiary hospital (Gastroenterology 2015 Apr. 25 [doi:10.1053/j.gastro.2015.04.014]) .
One year after surgery, 85% of patients had achieved disease resolution (95% confidence interval, 75.8%-92.2%), the investigators reported. Stratifying patients by baseline Brunt scores showed that those with milder presurgical disease were more likely to have complete resolution than were patients whose disease was severe (94% vs. 70%; P <.05), the researchers added. Histologic analyses supported the findings, revealing steatosis in 60% of presurgical tissue samples, compared with 10% of samples taken a year after surgery. In addition, average NAFLD disease scores dropped from 5 to 1 (P <.001), hepatocyte ballooning decreased in 84% of samples, lobular inflammation decreased in 67%, and Metavir fibrosis scores dropped in one-third of specimens.
Notably, BMI scores for patients with persistent postsurgical disease dropped by an average of only 9.1, compared with 12.3 for patients whose disease resolved (P = .005), said the researchers. Gastric bypass surgery achieved greater weight loss and improvements in disease status, compared with laparoscopic banding, they added. “The encouraging results of the present study suggest that bariatric surgery should be tested in multicenter, randomized controlled trials in morbidly or severely obese patients with nonalcoholic steatohepatitis who did not respond to lifestyle therapy,” they wrote.
The Cuban National Institute of Gastroenterology and Ministry of Health partially funded the study by Dr. Vilar-Gomez and his associates. The French Ministry of Health and the Conseil Regional Nord-Pas de Calais supported the work by Dr. Lassailly and his colleagues. All investigators declared having no relevant financial conflicts of interest.
Losing weight through lifestyle changes can significantly improve several measures of nonalcoholic fatty liver disease, particularly if patients lose at least 10% of their body weight, and bariatric surgery is a valid alternative if diet and exercise fail, according to two studies reported in the August issue of Gastroenterology (2015 Apr. 9 [doi:10.1053/j.gastro.2015.04.005]).
Global rates of nonalcoholic fatty liver disease (NAFLD) are up because of the “parallel epidemics” of obesity and type 2 diabetes mellitus, said Dr. Eduardo Vilar-Gomez of the National Institute of Hepatology in Havana, Cuba, who authored the study of lifestyle changes. There are no approved therapies for the more aggressive form of NAFLD, steatohepatitis, he and his associates said. In past studies, patients who lost about 7%-10% of their body weight substantially improved their NAFLD activity score and had reductions in steatosis, lobular inflammation, and ballooning, but the results did not extend to fibrosis, and prospective studies of the effect of lifestyle changes on histology are lacking, the researchers added .
To fill the gap, they followed 293 adults with histologically confirmed nonalcoholic steatohepatitis who completed a 52-week lifestyle intervention program that included keeping a food diary, restricting saturated fats to less than 10% of total intake, and walking at least 200 minutes a week. Patients had not received hypolipidemic treatment in the preceding 3 months and were not allowed to take insulin sensitizers or vitamin E, both of which are potentially beneficial for nonalcoholic steatohepatitis, the investigators said.
At the end of the yearlong program, steatohepatitis had resolved in 25% of patients, 47% had lower NAFLD activity scores, and 19% had regression of fibrosis, the researchers reported. Although only 30% of participants lost at least 5% of their body weight, weight loss correlated positively with resolution of steatohepatitis and with 2-point reductions in histologic activity scores (P <.001). Among patients who lost at least 10% of their body weight, 90% had resolution of steatohepatitis, 45% had regression of fibrosis, and all had improved histologic activity scores, even if they had negative risk factors such as female sex, a baseline body mass index of at least 35 kg/m2, and a baseline fasting glucose level of at least 5.5 mmol/L, the investigators added. “Our findings support the current recommendation for weight loss using lifestyle modification as the first step in the management of patients with nonalcoholic steatohepatitis,” they wrote.
But what if lifestyle changes fail? The impact of bariatric surgery on nonalcoholic steatohepatitis has not been well studied, said Dr. Guillaume Lassailly at CHRU Lille (France). He and his associates therefore followed 109 morbidly obese patients (BMI ≥40 kg/m2) with biopsy-confirmed nonalcoholic steatohepatitis who underwent bariatric surgery at a single tertiary hospital (Gastroenterology 2015 Apr. 25 [doi:10.1053/j.gastro.2015.04.014]) .
One year after surgery, 85% of patients had achieved disease resolution (95% confidence interval, 75.8%-92.2%), the investigators reported. Stratifying patients by baseline Brunt scores showed that those with milder presurgical disease were more likely to have complete resolution than were patients whose disease was severe (94% vs. 70%; P <.05), the researchers added. Histologic analyses supported the findings, revealing steatosis in 60% of presurgical tissue samples, compared with 10% of samples taken a year after surgery. In addition, average NAFLD disease scores dropped from 5 to 1 (P <.001), hepatocyte ballooning decreased in 84% of samples, lobular inflammation decreased in 67%, and Metavir fibrosis scores dropped in one-third of specimens.
Notably, BMI scores for patients with persistent postsurgical disease dropped by an average of only 9.1, compared with 12.3 for patients whose disease resolved (P = .005), said the researchers. Gastric bypass surgery achieved greater weight loss and improvements in disease status, compared with laparoscopic banding, they added. “The encouraging results of the present study suggest that bariatric surgery should be tested in multicenter, randomized controlled trials in morbidly or severely obese patients with nonalcoholic steatohepatitis who did not respond to lifestyle therapy,” they wrote.
The Cuban National Institute of Gastroenterology and Ministry of Health partially funded the study by Dr. Vilar-Gomez and his associates. The French Ministry of Health and the Conseil Regional Nord-Pas de Calais supported the work by Dr. Lassailly and his colleagues. All investigators declared having no relevant financial conflicts of interest.
FROM GASTROENTEROLOGY
Key clinical point: Losing weight through lifestyle changes or bariatric surgery can significantly improve several measures of nonalcoholic steatohepatitis.
Major finding: A yearlong diet and exercise program led to resolution of nonalcoholic steatohepatitis in 25% of patients, while bariatric surgery achieved that outcome for 85% of patients in a separate study.
Data source: Two prospective uncontrolled cohort studies of 402 total adults with nonalcoholic steatohepatitis (the more severe form of nonalcoholic fatty liver disease).
Disclosures: The Cuban National Institute of Gastroenterology and Ministry of Health partially funded the study by Dr. Vilar-Gomez and his associates. The French Ministry of Health and the Conseil Regional Nord-Pas de Calais supported the work by Dr. Lassailly and his colleagues. All investigators declared having no relevant financial conflicts of interest.
Adding enhanced MR to CT might improve diagnosis, outcomes in hepatocellular carcinoma
Among patients with single-nodule hepatocellular carcinomas diagnosed by computed tomography, further imaging with gadoxetic acid–enhanced magnetic resonance (MR) revealed more tumors and was tied to a 28% drop in cancer recurrence and a 35% drop in mortality, a retrospective cohort study reported in the June issue of Gastroenterology (doi.org/10.1053/j.gastro.2015.02.051) found.
“To the best of our knowledge, this is the first study to demonstrate that evaluation of hepatocellular carcinoma [HCC] with gadoxetic acid–enhanced MR imaging is associated with an improvement in the clinical outcome of patients, compared with that of a standard evaluation with dynamic CT,” said Dr. Hyung-Don Kim at the University of Ulsan in Seoul, South Korea and his associates. “This is clinically meaningful, given that the prognosis of patients with early-stage HCC is poor even after a curative treatment, mainly because of the high rate of early intrahepatic recurrence, and because there is no form of adjuvant therapy with a proven clinical benefit.” At least a third of early HCC recurrences might result from dissemination of primary tumor that went undetected at initial treatment, the researchers noted. To investigate the effects of gadoxetic acid–enhanced magnetic resonance imaging on HCC detection and subsequent survival, they retrospectively studied 700 patients in Seoul, South Korea, who had single-nodule HCCs diagnosed by dynamic four-phase CT. A total of 323 patients underwent additional imaging with gadoxetic acid–enhanced MR. These patients resembled CT-only patients in terms of baseline demographic characteristics, except that they were an average of 3 years younger (P < .001), had significantly higher median ALT levels (66 vs. 57 IU/mL; P < .006) and significantly higher platelet counts and lower alpha-fetoprotein levels, the investigators said.Gadoxetic acid–enhanced MR detected additional small HCC nodules in 16% of patients, and was tied to a 28% drop in likelihood of recurrence (hazard ratio, 0.72; 95% confidence interval, 0.54-0.96) and a 35% drop in risk of mortality (HR, 0.65; 95% CI, 0.44-0.96), the investigators reported. Rates of both recurrence-free and overall survival also were significantly higher for patients who underwent contrast-enhanced MR in addition to CT, compared with patients who underwent CT alone, and the differences held true in univariate, multivariate, inverse probability weighting analyses, and propensity score-matched analyses, they added.
“The major limitation of this study is that it was based on observational data,” commented the researchers. “Further studies that evaluate the effectiveness of gadoxetic acid–enhanced MR imaging for the evaluation of HCC in patients in other clinical settings are warranted.” The findings also need cautious interpretation because of the chance that selection bias led to more curable cases among patients who underwent MR in addition to CT, they said. The Korean Ministry of Health & Welfare and the Korean Association for the Study of Liver helped fund the research. One coauthor reported serving on the advisory boards of Bayer Healthcare, Bristol-Myers Squibb, and Gilead Science, and receiving research funding from Bayer, Gilead, and Novartis. The other investigators reported no conflicts of interest.
Courtesy American Gastroenterological Association
Among patients with single-nodule hepatocellular carcinomas diagnosed by computed tomography, further imaging with gadoxetic acid–enhanced magnetic resonance (MR) revealed more tumors and was tied to a 28% drop in cancer recurrence and a 35% drop in mortality, a retrospective cohort study reported in the June issue of Gastroenterology (doi.org/10.1053/j.gastro.2015.02.051) found.
“To the best of our knowledge, this is the first study to demonstrate that evaluation of hepatocellular carcinoma [HCC] with gadoxetic acid–enhanced MR imaging is associated with an improvement in the clinical outcome of patients, compared with that of a standard evaluation with dynamic CT,” said Dr. Hyung-Don Kim at the University of Ulsan in Seoul, South Korea and his associates. “This is clinically meaningful, given that the prognosis of patients with early-stage HCC is poor even after a curative treatment, mainly because of the high rate of early intrahepatic recurrence, and because there is no form of adjuvant therapy with a proven clinical benefit.” At least a third of early HCC recurrences might result from dissemination of primary tumor that went undetected at initial treatment, the researchers noted. To investigate the effects of gadoxetic acid–enhanced magnetic resonance imaging on HCC detection and subsequent survival, they retrospectively studied 700 patients in Seoul, South Korea, who had single-nodule HCCs diagnosed by dynamic four-phase CT. A total of 323 patients underwent additional imaging with gadoxetic acid–enhanced MR. These patients resembled CT-only patients in terms of baseline demographic characteristics, except that they were an average of 3 years younger (P < .001), had significantly higher median ALT levels (66 vs. 57 IU/mL; P < .006) and significantly higher platelet counts and lower alpha-fetoprotein levels, the investigators said.Gadoxetic acid–enhanced MR detected additional small HCC nodules in 16% of patients, and was tied to a 28% drop in likelihood of recurrence (hazard ratio, 0.72; 95% confidence interval, 0.54-0.96) and a 35% drop in risk of mortality (HR, 0.65; 95% CI, 0.44-0.96), the investigators reported. Rates of both recurrence-free and overall survival also were significantly higher for patients who underwent contrast-enhanced MR in addition to CT, compared with patients who underwent CT alone, and the differences held true in univariate, multivariate, inverse probability weighting analyses, and propensity score-matched analyses, they added.
“The major limitation of this study is that it was based on observational data,” commented the researchers. “Further studies that evaluate the effectiveness of gadoxetic acid–enhanced MR imaging for the evaluation of HCC in patients in other clinical settings are warranted.” The findings also need cautious interpretation because of the chance that selection bias led to more curable cases among patients who underwent MR in addition to CT, they said. The Korean Ministry of Health & Welfare and the Korean Association for the Study of Liver helped fund the research. One coauthor reported serving on the advisory boards of Bayer Healthcare, Bristol-Myers Squibb, and Gilead Science, and receiving research funding from Bayer, Gilead, and Novartis. The other investigators reported no conflicts of interest.
Courtesy American Gastroenterological Association
Among patients with single-nodule hepatocellular carcinomas diagnosed by computed tomography, further imaging with gadoxetic acid–enhanced magnetic resonance (MR) revealed more tumors and was tied to a 28% drop in cancer recurrence and a 35% drop in mortality, a retrospective cohort study reported in the June issue of Gastroenterology (doi.org/10.1053/j.gastro.2015.02.051) found.
“To the best of our knowledge, this is the first study to demonstrate that evaluation of hepatocellular carcinoma [HCC] with gadoxetic acid–enhanced MR imaging is associated with an improvement in the clinical outcome of patients, compared with that of a standard evaluation with dynamic CT,” said Dr. Hyung-Don Kim at the University of Ulsan in Seoul, South Korea and his associates. “This is clinically meaningful, given that the prognosis of patients with early-stage HCC is poor even after a curative treatment, mainly because of the high rate of early intrahepatic recurrence, and because there is no form of adjuvant therapy with a proven clinical benefit.” At least a third of early HCC recurrences might result from dissemination of primary tumor that went undetected at initial treatment, the researchers noted. To investigate the effects of gadoxetic acid–enhanced magnetic resonance imaging on HCC detection and subsequent survival, they retrospectively studied 700 patients in Seoul, South Korea, who had single-nodule HCCs diagnosed by dynamic four-phase CT. A total of 323 patients underwent additional imaging with gadoxetic acid–enhanced MR. These patients resembled CT-only patients in terms of baseline demographic characteristics, except that they were an average of 3 years younger (P < .001), had significantly higher median ALT levels (66 vs. 57 IU/mL; P < .006) and significantly higher platelet counts and lower alpha-fetoprotein levels, the investigators said.Gadoxetic acid–enhanced MR detected additional small HCC nodules in 16% of patients, and was tied to a 28% drop in likelihood of recurrence (hazard ratio, 0.72; 95% confidence interval, 0.54-0.96) and a 35% drop in risk of mortality (HR, 0.65; 95% CI, 0.44-0.96), the investigators reported. Rates of both recurrence-free and overall survival also were significantly higher for patients who underwent contrast-enhanced MR in addition to CT, compared with patients who underwent CT alone, and the differences held true in univariate, multivariate, inverse probability weighting analyses, and propensity score-matched analyses, they added.
“The major limitation of this study is that it was based on observational data,” commented the researchers. “Further studies that evaluate the effectiveness of gadoxetic acid–enhanced MR imaging for the evaluation of HCC in patients in other clinical settings are warranted.” The findings also need cautious interpretation because of the chance that selection bias led to more curable cases among patients who underwent MR in addition to CT, they said. The Korean Ministry of Health & Welfare and the Korean Association for the Study of Liver helped fund the research. One coauthor reported serving on the advisory boards of Bayer Healthcare, Bristol-Myers Squibb, and Gilead Science, and receiving research funding from Bayer, Gilead, and Novartis. The other investigators reported no conflicts of interest.
Courtesy American Gastroenterological Association
Key clinical point: Gadoxetic acid–enhanced magnetic resonance (MR) imaging revealed smaller masses and was tied to better outcomes in patients with single-nodule hepatocellular carcinoma (HCC) diagnosed by computed tomography (CT).
Major finding: MR enhanced with gadoxetic acid detected additional HCC nodules in 16% of patients, and was tied to lower recurrence and mortality rates.
Data source: Retrospective study of 700 patients diagnosed with single-nodule HCC by dynamic four-phase CT.
Disclosures: The Korean Ministry of Health & Welfare and the Korean Association for the Study of Liver helped fund the research. One coauthor reported serving on the advisory boards of Bayer Healthcare, Bristol-Myers Squibb, and Gilead Science, and receiving research funding from Bayer, Gilead, and Novartis. The other investigators reported no conflicts of interest.
Referral centers varied significantly in IBD treatment approaches
Even high-volume referral centers varied significantly in their use of immunomodulators and some other therapies for patients with inflammatory bowel disease, particularly Crohn’s disease, a prospective cohort study found.
“The development and implementation of evidence-based standards of care may reduce variations and improve patient outcomes,” Dr. Ashwin Ananthakrishnan of Massachusetts General Hospital in Boston and his associates wrote in the June issue of Clinical Gastroenterology and Hepatology (2014 Nov. 21 [doi: 10.1016/j.cgh.2014.11.020]). “Because adherence to guidelines frequently is inadequate, a reduction of practice variation also requires continual improvement, including setting goals and repeated measurement of processes to identify how standardizing care impacts outcomes.”
New biologics have created increasingly diverse treatment options for patients with inflammatory bowel disease (IBD), but few studies have looked at how clinicians and patients choose treatment regimens in daily practice, the researchers noted. To explore the issue, they prospectively studied 1,659 adults with Crohn’s disease (CD) and 946 patients with ulcerative colitis who were treated at one of seven academic medical centers, all of which see a high volume of IBD patients.
Referral centers varied about threefold in their use of immunomodulators for CD (odds ratio for between-center differences, 3.34; 95% confidence interval, 2.09-5.32) in a model that controlled for age at diagnosis, sex, race, smoking status, and duration and extent or behavior of disease, the researchers reported. Use of immunomodulators for ulcerative colitis varied by more than twofold, they found (OR, 2.32; 95% CI, 1.05 to 5.13). Furthermore, they uncovered significant differences in use of oral mesalamine in both forms of IBD, and in the use of corticosteroids and immunomodulator-tumor necrosis factor antagonist combinations for CD, they said.
Treatment practices tended to vary more for CD than for ulcerative colitis, perhaps because CD spans a broader spectrum of pathologies or because clinicians have not yet reached consensus on early aggressive therapy or treatment strategies for CD, the researchers said. “Variations in treatment generally occur when there is uncertainty about the best practice,” they commented. “It is possible that the variations will diminish as evidence on effective IBD therapy grows and evidence-based guidelines become available and are implemented. The continued variation suggests that there is significant potential for standardization of care across referral and community practices.”
The study did not pinpoint reasons for discrepancies in practice, which could have reflected differences related to referring physicians’ or patients’ behaviors or expectations, the researchers said. But the findings did not reflect a single outlier center, and the cohort was not chosen to study variations between centers, which should have helped eliminate selection bias, they added.
The Leona M. and Harry B. Helmsley Charitable Trust funded the study. Dr. Ananthakrishnan reported advisory board payments from Cubist Pharmaceuticals and AbbVe. One coauthor reported financial conflicts of interest with numerous pharmaceutical companies. The other authors reported no conflicts of interest.
Jack Wennberg, a pioneer in quality improvement, was the first to recognize the association between significant variation in health care utilization and poor quality of care. The problem is that Wennberg published this in Science in 1973 (182:1102-8), and now, over 40 years later, we are just making progress for patients with Crohn’s disease and ulcerative colitis.
As a field, we now need to catch up and learn how to address this variation. It won’t be by solely measuring the differences between practices. As a proverb that was taught to me by experts at the Institute for Healthcare Improvement says, “You can’t fatten a cow by weighing it.” We could measure our practice patterns, quality metrics, and report them every day to claim our appropriate reimbursement from the Centers for Medicare & Medicaid Services, but this won’t improve patient outcomes or our understanding of what drives a better quality of life for our patients.
We need to take what Dr. Ananthakrishnan and his team have taught us to the next level. We need to learn from the Model for Improvement (Langley G.J., The improvement guide: A practical approach to enhancing organizational performance. San Francisco: Jossey-Bass, 2009), which teaches us that, to improve, we need to answer three questions: What are we trying to accomplish? How will we know that a change is an improvement? and What changes can we make that will result in an improvement? If we can apply these questions to changes that we want to make in our practices and systematically pursue answers, we will start to improve the quality of care delivered to our patients, as opposed to simply reporting that it is poor.
Dr. Corey A. Siegel, M.S., is director of the Dartmouth-Hitchcock Inflammatory Bowel Disease Center at Dartmouth-Hitchcock Medical Center, Lebanon, N.H. He is supported by AHRQ grant 1R01HS021747-01 and serves as consultant or on an advisory board for Abbvie, Amgen, Lilly, Janssen, Salix, Pfizer, Prometheus, Takeda, Theradiag, and UCB. He serves as a speaker for CME activities for AbbVie, Janssen, and Takeda, and has received grant support from Abbvie, Janssen, Salix, Takeda, and UCB. He is cochair of the Crohn’s and Colitis Foundation of America’s Quality of Care Program.
Jack Wennberg, a pioneer in quality improvement, was the first to recognize the association between significant variation in health care utilization and poor quality of care. The problem is that Wennberg published this in Science in 1973 (182:1102-8), and now, over 40 years later, we are just making progress for patients with Crohn’s disease and ulcerative colitis.
As a field, we now need to catch up and learn how to address this variation. It won’t be by solely measuring the differences between practices. As a proverb that was taught to me by experts at the Institute for Healthcare Improvement says, “You can’t fatten a cow by weighing it.” We could measure our practice patterns, quality metrics, and report them every day to claim our appropriate reimbursement from the Centers for Medicare & Medicaid Services, but this won’t improve patient outcomes or our understanding of what drives a better quality of life for our patients.
We need to take what Dr. Ananthakrishnan and his team have taught us to the next level. We need to learn from the Model for Improvement (Langley G.J., The improvement guide: A practical approach to enhancing organizational performance. San Francisco: Jossey-Bass, 2009), which teaches us that, to improve, we need to answer three questions: What are we trying to accomplish? How will we know that a change is an improvement? and What changes can we make that will result in an improvement? If we can apply these questions to changes that we want to make in our practices and systematically pursue answers, we will start to improve the quality of care delivered to our patients, as opposed to simply reporting that it is poor.
Dr. Corey A. Siegel, M.S., is director of the Dartmouth-Hitchcock Inflammatory Bowel Disease Center at Dartmouth-Hitchcock Medical Center, Lebanon, N.H. He is supported by AHRQ grant 1R01HS021747-01 and serves as consultant or on an advisory board for Abbvie, Amgen, Lilly, Janssen, Salix, Pfizer, Prometheus, Takeda, Theradiag, and UCB. He serves as a speaker for CME activities for AbbVie, Janssen, and Takeda, and has received grant support from Abbvie, Janssen, Salix, Takeda, and UCB. He is cochair of the Crohn’s and Colitis Foundation of America’s Quality of Care Program.
Jack Wennberg, a pioneer in quality improvement, was the first to recognize the association between significant variation in health care utilization and poor quality of care. The problem is that Wennberg published this in Science in 1973 (182:1102-8), and now, over 40 years later, we are just making progress for patients with Crohn’s disease and ulcerative colitis.
As a field, we now need to catch up and learn how to address this variation. It won’t be by solely measuring the differences between practices. As a proverb that was taught to me by experts at the Institute for Healthcare Improvement says, “You can’t fatten a cow by weighing it.” We could measure our practice patterns, quality metrics, and report them every day to claim our appropriate reimbursement from the Centers for Medicare & Medicaid Services, but this won’t improve patient outcomes or our understanding of what drives a better quality of life for our patients.
We need to take what Dr. Ananthakrishnan and his team have taught us to the next level. We need to learn from the Model for Improvement (Langley G.J., The improvement guide: A practical approach to enhancing organizational performance. San Francisco: Jossey-Bass, 2009), which teaches us that, to improve, we need to answer three questions: What are we trying to accomplish? How will we know that a change is an improvement? and What changes can we make that will result in an improvement? If we can apply these questions to changes that we want to make in our practices and systematically pursue answers, we will start to improve the quality of care delivered to our patients, as opposed to simply reporting that it is poor.
Dr. Corey A. Siegel, M.S., is director of the Dartmouth-Hitchcock Inflammatory Bowel Disease Center at Dartmouth-Hitchcock Medical Center, Lebanon, N.H. He is supported by AHRQ grant 1R01HS021747-01 and serves as consultant or on an advisory board for Abbvie, Amgen, Lilly, Janssen, Salix, Pfizer, Prometheus, Takeda, Theradiag, and UCB. He serves as a speaker for CME activities for AbbVie, Janssen, and Takeda, and has received grant support from Abbvie, Janssen, Salix, Takeda, and UCB. He is cochair of the Crohn’s and Colitis Foundation of America’s Quality of Care Program.
Even high-volume referral centers varied significantly in their use of immunomodulators and some other therapies for patients with inflammatory bowel disease, particularly Crohn’s disease, a prospective cohort study found.
“The development and implementation of evidence-based standards of care may reduce variations and improve patient outcomes,” Dr. Ashwin Ananthakrishnan of Massachusetts General Hospital in Boston and his associates wrote in the June issue of Clinical Gastroenterology and Hepatology (2014 Nov. 21 [doi: 10.1016/j.cgh.2014.11.020]). “Because adherence to guidelines frequently is inadequate, a reduction of practice variation also requires continual improvement, including setting goals and repeated measurement of processes to identify how standardizing care impacts outcomes.”
New biologics have created increasingly diverse treatment options for patients with inflammatory bowel disease (IBD), but few studies have looked at how clinicians and patients choose treatment regimens in daily practice, the researchers noted. To explore the issue, they prospectively studied 1,659 adults with Crohn’s disease (CD) and 946 patients with ulcerative colitis who were treated at one of seven academic medical centers, all of which see a high volume of IBD patients.
Referral centers varied about threefold in their use of immunomodulators for CD (odds ratio for between-center differences, 3.34; 95% confidence interval, 2.09-5.32) in a model that controlled for age at diagnosis, sex, race, smoking status, and duration and extent or behavior of disease, the researchers reported. Use of immunomodulators for ulcerative colitis varied by more than twofold, they found (OR, 2.32; 95% CI, 1.05 to 5.13). Furthermore, they uncovered significant differences in use of oral mesalamine in both forms of IBD, and in the use of corticosteroids and immunomodulator-tumor necrosis factor antagonist combinations for CD, they said.
Treatment practices tended to vary more for CD than for ulcerative colitis, perhaps because CD spans a broader spectrum of pathologies or because clinicians have not yet reached consensus on early aggressive therapy or treatment strategies for CD, the researchers said. “Variations in treatment generally occur when there is uncertainty about the best practice,” they commented. “It is possible that the variations will diminish as evidence on effective IBD therapy grows and evidence-based guidelines become available and are implemented. The continued variation suggests that there is significant potential for standardization of care across referral and community practices.”
The study did not pinpoint reasons for discrepancies in practice, which could have reflected differences related to referring physicians’ or patients’ behaviors or expectations, the researchers said. But the findings did not reflect a single outlier center, and the cohort was not chosen to study variations between centers, which should have helped eliminate selection bias, they added.
The Leona M. and Harry B. Helmsley Charitable Trust funded the study. Dr. Ananthakrishnan reported advisory board payments from Cubist Pharmaceuticals and AbbVe. One coauthor reported financial conflicts of interest with numerous pharmaceutical companies. The other authors reported no conflicts of interest.
Even high-volume referral centers varied significantly in their use of immunomodulators and some other therapies for patients with inflammatory bowel disease, particularly Crohn’s disease, a prospective cohort study found.
“The development and implementation of evidence-based standards of care may reduce variations and improve patient outcomes,” Dr. Ashwin Ananthakrishnan of Massachusetts General Hospital in Boston and his associates wrote in the June issue of Clinical Gastroenterology and Hepatology (2014 Nov. 21 [doi: 10.1016/j.cgh.2014.11.020]). “Because adherence to guidelines frequently is inadequate, a reduction of practice variation also requires continual improvement, including setting goals and repeated measurement of processes to identify how standardizing care impacts outcomes.”
New biologics have created increasingly diverse treatment options for patients with inflammatory bowel disease (IBD), but few studies have looked at how clinicians and patients choose treatment regimens in daily practice, the researchers noted. To explore the issue, they prospectively studied 1,659 adults with Crohn’s disease (CD) and 946 patients with ulcerative colitis who were treated at one of seven academic medical centers, all of which see a high volume of IBD patients.
Referral centers varied about threefold in their use of immunomodulators for CD (odds ratio for between-center differences, 3.34; 95% confidence interval, 2.09-5.32) in a model that controlled for age at diagnosis, sex, race, smoking status, and duration and extent or behavior of disease, the researchers reported. Use of immunomodulators for ulcerative colitis varied by more than twofold, they found (OR, 2.32; 95% CI, 1.05 to 5.13). Furthermore, they uncovered significant differences in use of oral mesalamine in both forms of IBD, and in the use of corticosteroids and immunomodulator-tumor necrosis factor antagonist combinations for CD, they said.
Treatment practices tended to vary more for CD than for ulcerative colitis, perhaps because CD spans a broader spectrum of pathologies or because clinicians have not yet reached consensus on early aggressive therapy or treatment strategies for CD, the researchers said. “Variations in treatment generally occur when there is uncertainty about the best practice,” they commented. “It is possible that the variations will diminish as evidence on effective IBD therapy grows and evidence-based guidelines become available and are implemented. The continued variation suggests that there is significant potential for standardization of care across referral and community practices.”
The study did not pinpoint reasons for discrepancies in practice, which could have reflected differences related to referring physicians’ or patients’ behaviors or expectations, the researchers said. But the findings did not reflect a single outlier center, and the cohort was not chosen to study variations between centers, which should have helped eliminate selection bias, they added.
The Leona M. and Harry B. Helmsley Charitable Trust funded the study. Dr. Ananthakrishnan reported advisory board payments from Cubist Pharmaceuticals and AbbVe. One coauthor reported financial conflicts of interest with numerous pharmaceutical companies. The other authors reported no conflicts of interest.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: High-volume referral centers varied significantly in use of immunomodulators and other therapies for inflammatory bowel disease, especially Crohn’s disease.
Major finding: Centers varied as much as threefold in use of immunomodulators for CD (OR, 3.34; 95% CI, 2.09-4.32).
Data source: Prospective cohort study of 1,659 patients with Crohn’s disease and 946 patients with ulcerative colitis.
Disclosures: The Leona M. and Harry B. Helmsley Charitable Trust funded the study. Dr. Ananthakrishnan reported advisory board payments from Cubist Pharmaceuticals and AbbVie. One coauthor reported financial conflicts of interest with numerous pharmaceutical companies. The other authors reported no conflicts of interest.
Experts advocate ‘treat-to-target’ approach for Crohn’s disease
Patients with Crohn’s disease could benefit from a “treat-to-target” approach based on intervening early to reverse inflammation and gathering objective data to guide clinical decisions, according to a review article published in the June issue of Clinical Gastroenterology and Hepatology (2015 [doi:10.1016/j.cgh.2013.09.006]).
“In spite of available effective treatments, the development of complications such as stricture, fistula, and abscess that result in surgery and lead to a disabling course of Crohn’s disease remain common,” said Dr. Guillame Bouguen at the University of California, San Diego, and his associates. “This ‘natural history’ is not likely to improve unless the overall symptom-based therapeutic strategy for Crohn’s disease is changed,” they wrote.
Clinicians have historically managed Crohn’s disease (CD) by gradually intensifying treatments based on patients’ symptoms, but this approach has failed to achieve good long-term outcomes and puts patients at risk of bowel damage, the reviewers said. The advent of better drugs for other chronic inflammatory diseases, such as rheumatoid arthritis, “reinvigorated” treatment strategies to focus on intervening earlier and controlling inflammation as much as possible, including by augmenting the novel biologics with methotrexate or other older disease-modifying antirheumatic drugs, they said.A similar “treat-to-target” approach to CD would mean responding to objective evidence of inflammation before patients developed irreversible bowel damage, Dr. Bouguen and his associates said. The main treatment goal would be mucosal healing, but the target level would reflect individual comorbidities, demographic and behavioral factors, and risks of side effects. After refining the mucosal healing target, gastroenterologists would stick to it throughout treatment, and would adjust treatment based on imaging and other objective measures of bowel inflammation. Colonoscopies and related procedures would be performed every 6 months until ulcerations resolved, and every 1-2 years after that. To improve trust and adherence to treatment, gastroenterologists also would need to educate patients about the mucosal healing target and the plan for achieving that goal, the reviewers said.
Based on preliminary data, patients on azathioprine and tumor necrosis factor antagonists might be able to taper them after achieving sustained mucosal healing, although larger studies on the topic are lacking, said the reviewers. A treat-to-target approach also might help symptomatic CD patients who already have permanent bowel damage enhance their long-term quality of life and prevent worsening disability, the investigators said.The International Organization on Inflammatory Bowel Disease is leading a consensus effort to define the therapeutic target in the treatment of inflammatory bowel disease. “However, the principles of the treat-to-target strategy that uses both systematic follow-up of patients and therapy optimization focusing on inflammation and damage may persist,” they added. To better clarify whether a treat-to-target approach is useful in CD, researchers are enrolling patients in the REACT II trial, which will compare treatments that target mucosal healing with the conventional symptoms-based paradigm, they noted.The authors reported no funding sources. Dr. Bouguen reported receiving lecture fees from Abbott Laboratories, Ferring, and MSD Pharma. The other authors reported financial relationships with numerous pharmaceutical companies.
Patients with Crohn’s disease could benefit from a “treat-to-target” approach based on intervening early to reverse inflammation and gathering objective data to guide clinical decisions, according to a review article published in the June issue of Clinical Gastroenterology and Hepatology (2015 [doi:10.1016/j.cgh.2013.09.006]).
“In spite of available effective treatments, the development of complications such as stricture, fistula, and abscess that result in surgery and lead to a disabling course of Crohn’s disease remain common,” said Dr. Guillame Bouguen at the University of California, San Diego, and his associates. “This ‘natural history’ is not likely to improve unless the overall symptom-based therapeutic strategy for Crohn’s disease is changed,” they wrote.
Clinicians have historically managed Crohn’s disease (CD) by gradually intensifying treatments based on patients’ symptoms, but this approach has failed to achieve good long-term outcomes and puts patients at risk of bowel damage, the reviewers said. The advent of better drugs for other chronic inflammatory diseases, such as rheumatoid arthritis, “reinvigorated” treatment strategies to focus on intervening earlier and controlling inflammation as much as possible, including by augmenting the novel biologics with methotrexate or other older disease-modifying antirheumatic drugs, they said.A similar “treat-to-target” approach to CD would mean responding to objective evidence of inflammation before patients developed irreversible bowel damage, Dr. Bouguen and his associates said. The main treatment goal would be mucosal healing, but the target level would reflect individual comorbidities, demographic and behavioral factors, and risks of side effects. After refining the mucosal healing target, gastroenterologists would stick to it throughout treatment, and would adjust treatment based on imaging and other objective measures of bowel inflammation. Colonoscopies and related procedures would be performed every 6 months until ulcerations resolved, and every 1-2 years after that. To improve trust and adherence to treatment, gastroenterologists also would need to educate patients about the mucosal healing target and the plan for achieving that goal, the reviewers said.
Based on preliminary data, patients on azathioprine and tumor necrosis factor antagonists might be able to taper them after achieving sustained mucosal healing, although larger studies on the topic are lacking, said the reviewers. A treat-to-target approach also might help symptomatic CD patients who already have permanent bowel damage enhance their long-term quality of life and prevent worsening disability, the investigators said.The International Organization on Inflammatory Bowel Disease is leading a consensus effort to define the therapeutic target in the treatment of inflammatory bowel disease. “However, the principles of the treat-to-target strategy that uses both systematic follow-up of patients and therapy optimization focusing on inflammation and damage may persist,” they added. To better clarify whether a treat-to-target approach is useful in CD, researchers are enrolling patients in the REACT II trial, which will compare treatments that target mucosal healing with the conventional symptoms-based paradigm, they noted.The authors reported no funding sources. Dr. Bouguen reported receiving lecture fees from Abbott Laboratories, Ferring, and MSD Pharma. The other authors reported financial relationships with numerous pharmaceutical companies.
Patients with Crohn’s disease could benefit from a “treat-to-target” approach based on intervening early to reverse inflammation and gathering objective data to guide clinical decisions, according to a review article published in the June issue of Clinical Gastroenterology and Hepatology (2015 [doi:10.1016/j.cgh.2013.09.006]).
“In spite of available effective treatments, the development of complications such as stricture, fistula, and abscess that result in surgery and lead to a disabling course of Crohn’s disease remain common,” said Dr. Guillame Bouguen at the University of California, San Diego, and his associates. “This ‘natural history’ is not likely to improve unless the overall symptom-based therapeutic strategy for Crohn’s disease is changed,” they wrote.
Clinicians have historically managed Crohn’s disease (CD) by gradually intensifying treatments based on patients’ symptoms, but this approach has failed to achieve good long-term outcomes and puts patients at risk of bowel damage, the reviewers said. The advent of better drugs for other chronic inflammatory diseases, such as rheumatoid arthritis, “reinvigorated” treatment strategies to focus on intervening earlier and controlling inflammation as much as possible, including by augmenting the novel biologics with methotrexate or other older disease-modifying antirheumatic drugs, they said.A similar “treat-to-target” approach to CD would mean responding to objective evidence of inflammation before patients developed irreversible bowel damage, Dr. Bouguen and his associates said. The main treatment goal would be mucosal healing, but the target level would reflect individual comorbidities, demographic and behavioral factors, and risks of side effects. After refining the mucosal healing target, gastroenterologists would stick to it throughout treatment, and would adjust treatment based on imaging and other objective measures of bowel inflammation. Colonoscopies and related procedures would be performed every 6 months until ulcerations resolved, and every 1-2 years after that. To improve trust and adherence to treatment, gastroenterologists also would need to educate patients about the mucosal healing target and the plan for achieving that goal, the reviewers said.
Based on preliminary data, patients on azathioprine and tumor necrosis factor antagonists might be able to taper them after achieving sustained mucosal healing, although larger studies on the topic are lacking, said the reviewers. A treat-to-target approach also might help symptomatic CD patients who already have permanent bowel damage enhance their long-term quality of life and prevent worsening disability, the investigators said.The International Organization on Inflammatory Bowel Disease is leading a consensus effort to define the therapeutic target in the treatment of inflammatory bowel disease. “However, the principles of the treat-to-target strategy that uses both systematic follow-up of patients and therapy optimization focusing on inflammation and damage may persist,” they added. To better clarify whether a treat-to-target approach is useful in CD, researchers are enrolling patients in the REACT II trial, which will compare treatments that target mucosal healing with the conventional symptoms-based paradigm, they noted.The authors reported no funding sources. Dr. Bouguen reported receiving lecture fees from Abbott Laboratories, Ferring, and MSD Pharma. The other authors reported financial relationships with numerous pharmaceutical companies.
Key clinical point: A treat-to-target approach based on early control of inflammation and objective clinical data might benefit patients with Crohn’s disease.
Major finding: Using only symptoms to guide treatment decisions in Crohn’s disease has failed to achieve good long-term outcomes.
Data source: A review of 15 primary research and review articles.
Disclosures: The authors reported no funding sources. Dr. Bouguen reported receiving lecture fees from Abbott Laboratories, Ferring, and MSD Pharma. The other authors reported financial disclosures from numerous pharmaceutical companies.
Capsule colonoscopy improved, but limitations persist
When compared with conventional colonoscopy, capsule colonoscopy had a sensitivity of 88% and a specificity of 82% for detecting adenomas of at least 6 mm in asymptomatic subjects, a multicenter prospective study showed.
But the capsule detected only 29% of subjects who had sessile serrated polyps of at least 6 mm, and required more extensive bowel preparation than did conventional colonoscopy, Dr. Douglas K. Rex at Indiana University Hospital in Indianapolis and his associates reported in the May issue of Gastroenterology (2015 [doi:10.1053/j.gastro.2015.01.025]). “Given these considerations ... colonoscopy remains the gold standard for the detection of colorectal polyps,” said the researchers. “The capsule is a good test for the detection of patients with conventional adenomas 6 mm or larger in size and appears to be an appropriate imaging choice for patients who cannot undergo colonoscopy or had incomplete colonoscopy.”
Capsule endoscopy is useful for small-bowel imaging, but adapting the technology for colorectal studies has been difficult. A first-generation capsule detected only 74% of advanced adenomas in one prospective multicenter trial, the researchers noted. Since then, the PillCam COLON 2 capsule has been updated with motion detection, variable frame speed, and a wider angle view, they said. In smaller studies, it detected up to 89% of subjects with polyps of at least 6 mm, but its specificity was as low as 64%.
To further investigate the technology, researchers at 16 centers in the United States and Israel compared the second-generation capsule with conventional colonoscopy in an average-risk screening population of 884 asymptomatic subjects. Endoscopists were blinded as to technique, but performed unblinded follow-up colonoscopies in subjects who were positive on capsule but negative on conventional colonoscopy.
The capsule’s sensitivity was 81% (95% confidence interval, 77%-84%) and its specificity was 93% (91%-95%) for detecting subjects who had polyps of at least 6 mm, the researchers reported. Sensitivity was 80% (74%-86%) and specificity was 97% (96%-98%) for detecting subjects with polyps of at least 10 mm. For conventional adenomas of at least 6 mm, sensitivity was 88% (82%-93%) and specificity was 82% (80%-83%), and for adenomas of 10 mm or larger, sensitivity was 92% (82%-97%) and specificity was 95% (94%-95%).
“Lesions in the serrated class were not detected well by the capsule in this study, compared with conventional adenomas,” the researchers reported. Prior studies of the capsule did not look for serrated lesions, and in the current study sensitivities were only 29% and 33% for 6-mm and 10-mm lesions, respectively.
The software used to measure polyps during capsule colonoscopy had a 40% error range when tested on balls of known size, the researchers said. Therefore, there is a strict location-matching rule within the colon, but a liberal size rule that only required measurements to fall within 50% of one another to be considered a match. “Any set of matching rules for polyps detected by the capsule and colonoscopy might operate to increase or decrease the calculated sensitivity of the capsule incorrectly,” they added. Also, the adenoma detection rate for conventional colonoscopy was only 39%, and some polyps that were clearly seen on capsule were not visualized on regular colonoscopy. “In these cases, a polyp that should be a true positive for the capsule was counted as false,” they added. “Both colonoscopy and capsule are inferior for localization, compared with CT colonography. Inaccurate localization by one or both tests in this study could have reduced the sensitivity of the capsule.”
The investigators also had to exclude 77 patients because of inadequate cleansing and short transit times related to using sodium phosphate as a boost, they noted. The Food and Drug Administration label for the capsule is expected to reflect those limitations, they added.
Given Imaging funded the study and paid consulting or other fees to Dr. Rex and six coauthors. The other authors reported having no relevant conflicts of interest.
In the United States, colonoscopy is the primary screening test for colorectal cancer. However, because of issues with colonoscopy uptake, costs, and the small but finite risk of complications, the concept of a relatively noninvasive structural examination of the colon that can detect colorectal neoplasia is appealing to both patients and physicians.
Although capsule colonoscopy has emerged as a potential noninvasive tool for examining the entire colon, there are limited data on its accuracy for detecting conventional adenomas or sessile serrated polyps, particularly in an average-risk screening population.
In the May issue of Gastroenterology, Dr. Rex and colleagues report their results from a large, multicenter, prospective study evaluating the new second-generation capsule colonoscopy (PillCam COLON 2, Given Imaging) for detecting colorectal neoplasia in an average-risk screening population. Using optical colonoscopy as the reference standard, the capsule colonoscopy performed well for detecting conventional adenomas 6 mm or larger with a sensitivity and specificity of 88% and 82%, respectively.
In addition, the sensitivity and specificity of capsule colonoscopy for conventional adenomas 10 mm or larger were 92% and 95%, respectively. However, despite the high performance characteristics for detection of conventional adenomas, the capsule colonoscopy had limited accuracy for detecting sessile serrated polyps 10 mm or larger, with a sensitivity of 33%. Furthermore, nearly 10% of the enrolled subjects were excluded from the analysis due to poor bowel preparation and rapid transit time.
These issues aside, the Rex study provides important information about alternative screening modalities for detection of colorectal neoplasia, particularly for gastroenterologists who may be hesitant or unwilling to perform an optical colonoscopy in high-risk patients with significant co-morbidities or in patients who had an incomplete colonoscopy.
Dr. Jeffrey Lee, MAS is assistant clinical professor of medicine, division of gastroenterology, University of California, San Francisco. He has no conflicts of interest.
In the United States, colonoscopy is the primary screening test for colorectal cancer. However, because of issues with colonoscopy uptake, costs, and the small but finite risk of complications, the concept of a relatively noninvasive structural examination of the colon that can detect colorectal neoplasia is appealing to both patients and physicians.
Although capsule colonoscopy has emerged as a potential noninvasive tool for examining the entire colon, there are limited data on its accuracy for detecting conventional adenomas or sessile serrated polyps, particularly in an average-risk screening population.
In the May issue of Gastroenterology, Dr. Rex and colleagues report their results from a large, multicenter, prospective study evaluating the new second-generation capsule colonoscopy (PillCam COLON 2, Given Imaging) for detecting colorectal neoplasia in an average-risk screening population. Using optical colonoscopy as the reference standard, the capsule colonoscopy performed well for detecting conventional adenomas 6 mm or larger with a sensitivity and specificity of 88% and 82%, respectively.
In addition, the sensitivity and specificity of capsule colonoscopy for conventional adenomas 10 mm or larger were 92% and 95%, respectively. However, despite the high performance characteristics for detection of conventional adenomas, the capsule colonoscopy had limited accuracy for detecting sessile serrated polyps 10 mm or larger, with a sensitivity of 33%. Furthermore, nearly 10% of the enrolled subjects were excluded from the analysis due to poor bowel preparation and rapid transit time.
These issues aside, the Rex study provides important information about alternative screening modalities for detection of colorectal neoplasia, particularly for gastroenterologists who may be hesitant or unwilling to perform an optical colonoscopy in high-risk patients with significant co-morbidities or in patients who had an incomplete colonoscopy.
Dr. Jeffrey Lee, MAS is assistant clinical professor of medicine, division of gastroenterology, University of California, San Francisco. He has no conflicts of interest.
In the United States, colonoscopy is the primary screening test for colorectal cancer. However, because of issues with colonoscopy uptake, costs, and the small but finite risk of complications, the concept of a relatively noninvasive structural examination of the colon that can detect colorectal neoplasia is appealing to both patients and physicians.
Although capsule colonoscopy has emerged as a potential noninvasive tool for examining the entire colon, there are limited data on its accuracy for detecting conventional adenomas or sessile serrated polyps, particularly in an average-risk screening population.
In the May issue of Gastroenterology, Dr. Rex and colleagues report their results from a large, multicenter, prospective study evaluating the new second-generation capsule colonoscopy (PillCam COLON 2, Given Imaging) for detecting colorectal neoplasia in an average-risk screening population. Using optical colonoscopy as the reference standard, the capsule colonoscopy performed well for detecting conventional adenomas 6 mm or larger with a sensitivity and specificity of 88% and 82%, respectively.
In addition, the sensitivity and specificity of capsule colonoscopy for conventional adenomas 10 mm or larger were 92% and 95%, respectively. However, despite the high performance characteristics for detection of conventional adenomas, the capsule colonoscopy had limited accuracy for detecting sessile serrated polyps 10 mm or larger, with a sensitivity of 33%. Furthermore, nearly 10% of the enrolled subjects were excluded from the analysis due to poor bowel preparation and rapid transit time.
These issues aside, the Rex study provides important information about alternative screening modalities for detection of colorectal neoplasia, particularly for gastroenterologists who may be hesitant or unwilling to perform an optical colonoscopy in high-risk patients with significant co-morbidities or in patients who had an incomplete colonoscopy.
Dr. Jeffrey Lee, MAS is assistant clinical professor of medicine, division of gastroenterology, University of California, San Francisco. He has no conflicts of interest.
When compared with conventional colonoscopy, capsule colonoscopy had a sensitivity of 88% and a specificity of 82% for detecting adenomas of at least 6 mm in asymptomatic subjects, a multicenter prospective study showed.
But the capsule detected only 29% of subjects who had sessile serrated polyps of at least 6 mm, and required more extensive bowel preparation than did conventional colonoscopy, Dr. Douglas K. Rex at Indiana University Hospital in Indianapolis and his associates reported in the May issue of Gastroenterology (2015 [doi:10.1053/j.gastro.2015.01.025]). “Given these considerations ... colonoscopy remains the gold standard for the detection of colorectal polyps,” said the researchers. “The capsule is a good test for the detection of patients with conventional adenomas 6 mm or larger in size and appears to be an appropriate imaging choice for patients who cannot undergo colonoscopy or had incomplete colonoscopy.”
Capsule endoscopy is useful for small-bowel imaging, but adapting the technology for colorectal studies has been difficult. A first-generation capsule detected only 74% of advanced adenomas in one prospective multicenter trial, the researchers noted. Since then, the PillCam COLON 2 capsule has been updated with motion detection, variable frame speed, and a wider angle view, they said. In smaller studies, it detected up to 89% of subjects with polyps of at least 6 mm, but its specificity was as low as 64%.
To further investigate the technology, researchers at 16 centers in the United States and Israel compared the second-generation capsule with conventional colonoscopy in an average-risk screening population of 884 asymptomatic subjects. Endoscopists were blinded as to technique, but performed unblinded follow-up colonoscopies in subjects who were positive on capsule but negative on conventional colonoscopy.
The capsule’s sensitivity was 81% (95% confidence interval, 77%-84%) and its specificity was 93% (91%-95%) for detecting subjects who had polyps of at least 6 mm, the researchers reported. Sensitivity was 80% (74%-86%) and specificity was 97% (96%-98%) for detecting subjects with polyps of at least 10 mm. For conventional adenomas of at least 6 mm, sensitivity was 88% (82%-93%) and specificity was 82% (80%-83%), and for adenomas of 10 mm or larger, sensitivity was 92% (82%-97%) and specificity was 95% (94%-95%).
“Lesions in the serrated class were not detected well by the capsule in this study, compared with conventional adenomas,” the researchers reported. Prior studies of the capsule did not look for serrated lesions, and in the current study sensitivities were only 29% and 33% for 6-mm and 10-mm lesions, respectively.
The software used to measure polyps during capsule colonoscopy had a 40% error range when tested on balls of known size, the researchers said. Therefore, there is a strict location-matching rule within the colon, but a liberal size rule that only required measurements to fall within 50% of one another to be considered a match. “Any set of matching rules for polyps detected by the capsule and colonoscopy might operate to increase or decrease the calculated sensitivity of the capsule incorrectly,” they added. Also, the adenoma detection rate for conventional colonoscopy was only 39%, and some polyps that were clearly seen on capsule were not visualized on regular colonoscopy. “In these cases, a polyp that should be a true positive for the capsule was counted as false,” they added. “Both colonoscopy and capsule are inferior for localization, compared with CT colonography. Inaccurate localization by one or both tests in this study could have reduced the sensitivity of the capsule.”
The investigators also had to exclude 77 patients because of inadequate cleansing and short transit times related to using sodium phosphate as a boost, they noted. The Food and Drug Administration label for the capsule is expected to reflect those limitations, they added.
Given Imaging funded the study and paid consulting or other fees to Dr. Rex and six coauthors. The other authors reported having no relevant conflicts of interest.
When compared with conventional colonoscopy, capsule colonoscopy had a sensitivity of 88% and a specificity of 82% for detecting adenomas of at least 6 mm in asymptomatic subjects, a multicenter prospective study showed.
But the capsule detected only 29% of subjects who had sessile serrated polyps of at least 6 mm, and required more extensive bowel preparation than did conventional colonoscopy, Dr. Douglas K. Rex at Indiana University Hospital in Indianapolis and his associates reported in the May issue of Gastroenterology (2015 [doi:10.1053/j.gastro.2015.01.025]). “Given these considerations ... colonoscopy remains the gold standard for the detection of colorectal polyps,” said the researchers. “The capsule is a good test for the detection of patients with conventional adenomas 6 mm or larger in size and appears to be an appropriate imaging choice for patients who cannot undergo colonoscopy or had incomplete colonoscopy.”
Capsule endoscopy is useful for small-bowel imaging, but adapting the technology for colorectal studies has been difficult. A first-generation capsule detected only 74% of advanced adenomas in one prospective multicenter trial, the researchers noted. Since then, the PillCam COLON 2 capsule has been updated with motion detection, variable frame speed, and a wider angle view, they said. In smaller studies, it detected up to 89% of subjects with polyps of at least 6 mm, but its specificity was as low as 64%.
To further investigate the technology, researchers at 16 centers in the United States and Israel compared the second-generation capsule with conventional colonoscopy in an average-risk screening population of 884 asymptomatic subjects. Endoscopists were blinded as to technique, but performed unblinded follow-up colonoscopies in subjects who were positive on capsule but negative on conventional colonoscopy.
The capsule’s sensitivity was 81% (95% confidence interval, 77%-84%) and its specificity was 93% (91%-95%) for detecting subjects who had polyps of at least 6 mm, the researchers reported. Sensitivity was 80% (74%-86%) and specificity was 97% (96%-98%) for detecting subjects with polyps of at least 10 mm. For conventional adenomas of at least 6 mm, sensitivity was 88% (82%-93%) and specificity was 82% (80%-83%), and for adenomas of 10 mm or larger, sensitivity was 92% (82%-97%) and specificity was 95% (94%-95%).
“Lesions in the serrated class were not detected well by the capsule in this study, compared with conventional adenomas,” the researchers reported. Prior studies of the capsule did not look for serrated lesions, and in the current study sensitivities were only 29% and 33% for 6-mm and 10-mm lesions, respectively.
The software used to measure polyps during capsule colonoscopy had a 40% error range when tested on balls of known size, the researchers said. Therefore, there is a strict location-matching rule within the colon, but a liberal size rule that only required measurements to fall within 50% of one another to be considered a match. “Any set of matching rules for polyps detected by the capsule and colonoscopy might operate to increase or decrease the calculated sensitivity of the capsule incorrectly,” they added. Also, the adenoma detection rate for conventional colonoscopy was only 39%, and some polyps that were clearly seen on capsule were not visualized on regular colonoscopy. “In these cases, a polyp that should be a true positive for the capsule was counted as false,” they added. “Both colonoscopy and capsule are inferior for localization, compared with CT colonography. Inaccurate localization by one or both tests in this study could have reduced the sensitivity of the capsule.”
The investigators also had to exclude 77 patients because of inadequate cleansing and short transit times related to using sodium phosphate as a boost, they noted. The Food and Drug Administration label for the capsule is expected to reflect those limitations, they added.
Given Imaging funded the study and paid consulting or other fees to Dr. Rex and six coauthors. The other authors reported having no relevant conflicts of interest.
FROM GASTROENTEROLOGY
Key clinical point: Despite improvements in second-generation capsules, colonoscopy remains the gold standard for colorectal adenoma detection.
Major finding: Compared with conventional colonoscopy, the capsule showed 88% sensitivity and 82% specificity for detecting subjects who had adenomas of at least 6 mm.
Data source: Prospective, multicenter, single-blinded comparison of capsule and conventional colonoscopy in 884 asymptomatic subjects.
Disclosures: Given Imaging makes the capsule technology, funded the study, and paid consulting or other fees to Dr. Rex and six coauthors. The other authors reported no relevant conflicts of interest.
