Amy Karon

Eight weeks of a mindfulness intervention known as acceptance and commitment therapy (ACT) significantly improved stress and depression among patients with inflammatory bowel disease, and these improvements persisted for at least 12 weeks after therapy ended, according to the results of a randomized, controlled trial.

Source: The American Gastroenterological Association

In the intention-to-treat analysis, stress symptoms, as measured by the Depression Anxiety and Stress Scales (DASS-21), improved by 39% at week 8 and by 45% at week 20, reported Brona Wynne, PhD, of University College Dublin together with her associates. These improvements were highly significant compared with baseline and treatment as usual (P = .001 for both comparisons). “Post hoc analyses indicated that baseline stress levels were similar in control and treatment groups,” the researchers wrote in Gastroenterology. “The results of the per protocol analysis were comparable, with a 43% and 49% reduction in stress in the treatment group from baseline to 8 and 20 weeks.”

Multiple studies have documented high levels of stress and psychological dysfunction among patients with Crohn’s disease and ulcerative colitis. Studies of various mindfulness therapy, relaxation, stress management, cognitive-behavioral therapy, and hypnotherapy interventions often failed to collect key clinical data or were underpowered, uncontrolled, and unrandomized. Acceptance and commitment therapy uses mindfulness to identify adverse thoughts and experiences, accept these as part of life, and recommit to “move towards values that have been identified and adopted by the individual,” the investigators wrote. “This can be defined as the ability to contact the present moment more fully as a conscious human being and to change, or persist in, behavior when doing so serves valued ends.”

Their single-center study, which they said was the first to evaluate ACT in IBD patients, included 79 individuals with stable or mildly active Crohn’s disease (38 patients) or ulcerative colitis (41 patients) who were randomly assigned to ACT (37 patients) or control treatment as usual (42 patients). The two comparison groups were demographically and clinically similar. The ACT program involved eight 90-minute, weekly sessions of groups of 14-16 individuals, led by a single psychologist who tailored the course material toward IBD with a focus on lowering stress. An independent psychologist observed each session to assess adherence to protocol.

Not only did ACT meet the primary study endpoint, it also produced a 25% decrease in perceived stress (on a 1-10 scale) by week 8 and a 27% decrease in perceived stress by week 20 (P less than .001 versus treatment as usual). Depression scores in the ACT group also fell by 47% by week 8 and by 45% at week 20 (P = .01 versus treatment as usual). Anxiety levels decreased by 29% at week 8 and by 31% at week 20, but these improvements did not significantly differ from those in the control group (P = .39).

Interestingly, ACT did not significantly improve symptom burden, activities of daily living, disease-related worry, general well-being, C-reactive protein (CRP) levels, fecal calprotectin levels, or scores on the version used of the Clinical Assessment of Depression (CAD) or the short Mayo assessment. Hair cortisol levels showed an association with baseline stress and anxiety, but not with treatment response.

Care programs for IBD increasingly emphasize mental health services despite a lack of robust trials to support these interventions, the investigators noted. Thus, their findings highlight “the need for researchers and clinicians to further develop and optimize the content and delivery of psychological programs for IBD patients.”

Tillotts Pharma and Boston Scientific provided partial funding, but had no other role in the study. The researchers reported having no relevant conflicts of interest.

SOURCE: Wynne B et al. Gastroenterology. 2018 Nov 16. doi: 10.1053/j.gastro.2018.11.030.

Eight weeks of a mindfulness intervention known as acceptance and commitment therapy (ACT) significantly improved stress and depression among patients with inflammatory bowel disease, and these improvements persisted for at least 12 weeks after therapy ended, according to the results of a randomized, controlled trial.

Source: The American Gastroenterological Association

In the intention-to-treat analysis, stress symptoms, as measured by the Depression Anxiety and Stress Scales (DASS-21), improved by 39% at week 8 and by 45% at week 20, reported Brona Wynne, PhD, of University College Dublin together with her associates. These improvements were highly significant compared with baseline and treatment as usual (P = .001 for both comparisons). “Post hoc analyses indicated that baseline stress levels were similar in control and treatment groups,” the researchers wrote in Gastroenterology. “The results of the per protocol analysis were comparable, with a 43% and 49% reduction in stress in the treatment group from baseline to 8 and 20 weeks.”

Multiple studies have documented high levels of stress and psychological dysfunction among patients with Crohn’s disease and ulcerative colitis. Studies of various mindfulness therapy, relaxation, stress management, cognitive-behavioral therapy, and hypnotherapy interventions often failed to collect key clinical data or were underpowered, uncontrolled, and unrandomized. Acceptance and commitment therapy uses mindfulness to identify adverse thoughts and experiences, accept these as part of life, and recommit to “move towards values that have been identified and adopted by the individual,” the investigators wrote. “This can be defined as the ability to contact the present moment more fully as a conscious human being and to change, or persist in, behavior when doing so serves valued ends.”

Their single-center study, which they said was the first to evaluate ACT in IBD patients, included 79 individuals with stable or mildly active Crohn’s disease (38 patients) or ulcerative colitis (41 patients) who were randomly assigned to ACT (37 patients) or control treatment as usual (42 patients). The two comparison groups were demographically and clinically similar. The ACT program involved eight 90-minute, weekly sessions of groups of 14-16 individuals, led by a single psychologist who tailored the course material toward IBD with a focus on lowering stress. An independent psychologist observed each session to assess adherence to protocol.

Not only did ACT meet the primary study endpoint, it also produced a 25% decrease in perceived stress (on a 1-10 scale) by week 8 and a 27% decrease in perceived stress by week 20 (P less than .001 versus treatment as usual). Depression scores in the ACT group also fell by 47% by week 8 and by 45% at week 20 (P = .01 versus treatment as usual). Anxiety levels decreased by 29% at week 8 and by 31% at week 20, but these improvements did not significantly differ from those in the control group (P = .39).

Interestingly, ACT did not significantly improve symptom burden, activities of daily living, disease-related worry, general well-being, C-reactive protein (CRP) levels, fecal calprotectin levels, or scores on the version used of the Clinical Assessment of Depression (CAD) or the short Mayo assessment. Hair cortisol levels showed an association with baseline stress and anxiety, but not with treatment response.

Care programs for IBD increasingly emphasize mental health services despite a lack of robust trials to support these interventions, the investigators noted. Thus, their findings highlight “the need for researchers and clinicians to further develop and optimize the content and delivery of psychological programs for IBD patients.”

Tillotts Pharma and Boston Scientific provided partial funding, but had no other role in the study. The researchers reported having no relevant conflicts of interest.

SOURCE: Wynne B et al. Gastroenterology. 2018 Nov 16. doi: 10.1053/j.gastro.2018.11.030.

Eight weeks of a mindfulness intervention known as acceptance and commitment therapy (ACT) significantly improved stress and depression among patients with inflammatory bowel disease, and these improvements persisted for at least 12 weeks after therapy ended, according to the results of a randomized, controlled trial.

Source: The American Gastroenterological Association

In the intention-to-treat analysis, stress symptoms, as measured by the Depression Anxiety and Stress Scales (DASS-21), improved by 39% at week 8 and by 45% at week 20, reported Brona Wynne, PhD, of University College Dublin together with her associates. These improvements were highly significant compared with baseline and treatment as usual (P = .001 for both comparisons). “Post hoc analyses indicated that baseline stress levels were similar in control and treatment groups,” the researchers wrote in Gastroenterology. “The results of the per protocol analysis were comparable, with a 43% and 49% reduction in stress in the treatment group from baseline to 8 and 20 weeks.”

Multiple studies have documented high levels of stress and psychological dysfunction among patients with Crohn’s disease and ulcerative colitis. Studies of various mindfulness therapy, relaxation, stress management, cognitive-behavioral therapy, and hypnotherapy interventions often failed to collect key clinical data or were underpowered, uncontrolled, and unrandomized. Acceptance and commitment therapy uses mindfulness to identify adverse thoughts and experiences, accept these as part of life, and recommit to “move towards values that have been identified and adopted by the individual,” the investigators wrote. “This can be defined as the ability to contact the present moment more fully as a conscious human being and to change, or persist in, behavior when doing so serves valued ends.”

Their single-center study, which they said was the first to evaluate ACT in IBD patients, included 79 individuals with stable or mildly active Crohn’s disease (38 patients) or ulcerative colitis (41 patients) who were randomly assigned to ACT (37 patients) or control treatment as usual (42 patients). The two comparison groups were demographically and clinically similar. The ACT program involved eight 90-minute, weekly sessions of groups of 14-16 individuals, led by a single psychologist who tailored the course material toward IBD with a focus on lowering stress. An independent psychologist observed each session to assess adherence to protocol.

Not only did ACT meet the primary study endpoint, it also produced a 25% decrease in perceived stress (on a 1-10 scale) by week 8 and a 27% decrease in perceived stress by week 20 (P less than .001 versus treatment as usual). Depression scores in the ACT group also fell by 47% by week 8 and by 45% at week 20 (P = .01 versus treatment as usual). Anxiety levels decreased by 29% at week 8 and by 31% at week 20, but these improvements did not significantly differ from those in the control group (P = .39).

Interestingly, ACT did not significantly improve symptom burden, activities of daily living, disease-related worry, general well-being, C-reactive protein (CRP) levels, fecal calprotectin levels, or scores on the version used of the Clinical Assessment of Depression (CAD) or the short Mayo assessment. Hair cortisol levels showed an association with baseline stress and anxiety, but not with treatment response.

Care programs for IBD increasingly emphasize mental health services despite a lack of robust trials to support these interventions, the investigators noted. Thus, their findings highlight “the need for researchers and clinicians to further develop and optimize the content and delivery of psychological programs for IBD patients.”

Tillotts Pharma and Boston Scientific provided partial funding, but had no other role in the study. The researchers reported having no relevant conflicts of interest.

SOURCE: Wynne B et al. Gastroenterology. 2018 Nov 16. doi: 10.1053/j.gastro.2018.11.030.

Higher (more severe) Liver Imaging Reporting and Data System (LI-RADS) categories contained increasing proportions of hepatocellular carcinomas and overall malignancies, supporting the general reliability of the system, according to a systematic review and meta-analysis of 17 retrospective studies.

But 13% of LR-2 (“probably benign”) observations were actually hepatocellular carcinomas, as were 38% of LR-3 (“intermediate probability of malignancy”) observations, reported Christian B. van der Pol, MD, of McMaster University, Hamilton, Ont., and Christopher S. Lim, BBS, of Harvard Medical School, Boston, and their associates. Thus, clinicians should consider biopsy of many LR-3s, and LR-2s might need “more active management” than the currently recommended “return to surveillance,” including consideration for biopsy of solid LR-2 nodules measuring 1 cm or more, they wrote in Gastroenterology.

Histopathology confirmed that 93% of CT and MRI observations designated as LR-M (“definite or probable malignancy”) were indeed malignancies and that 36% were hepatocellular carcinomas,

The LI-RADS system, like its counterparts in breast and prostate imaging (BI-RADS and PI-RADS), classifies CT and MRI findings based on level of suspicion for malignancy. These categories include LR-M, LR-3, LR-2, LR-1 (“definitely benign”), LR-TIV (“definitely tumor in vein”), and LR-4 and LR-5 (“probably” and “definitely” hepatocellular carcinoma). However, CT and MRI interpretation is only as useful as it is accurate. To calculate actual percentages of hepatocellular carcinomas and overall malignancies within each LI-RADS category, the investigators analyzed aggregate data from studies found by searching MEDLINE, Embase, Cochrane CENTRAL, and Scopus during 2014-2018.

These 17 studies included 2,760 patients and 3,556 imaging observations. Pathology was the reference standard for LR-M, but for other LI-RADS categories, the researchers accepted strong clinical indicators of hepatocellular carcinoma, such as a 50% increase in lesion size within 6 months, or posttreatment recurrence of a previously confirmed malignancy. They classified observations as negative if they stayed stable in size for at least 12 months, spontaneously diminished in size, or disappeared without treatment.

In all, 94% and 97% of LR-5 observations were (respectively) hepatocellular carcinomas and other malignancies, as were 79% and 92% of LR-TIVs, 36% and 93% of LR-Ms, 74% and 80% of LR-4s, 38% and 40% of LR-3s, and 13% and 14% of LR-2s. No LR-1s were confirmed as malignant.

“Our data suggest biopsy of LI-RADS 3 observations should be considered in many patients, as a risk of 38% of HCC would usually provoke biopsy of a lesion elsewhere in the body,” the researchers wrote. They suggested consideration for biopsy of certain LR-2 lesions, but added that many “are small, perfusional alterations caused by arterioportal shunts, which are often not reported” and would be difficult or impossible to biopsy.

The study did not cover the most recent (2018) LI-RADS system, which featured several changes to simplify and better align it with American Association for the Study of Liver Diseases criteria, the researchers noted. They called for prospective studies to help confirm the accuracy of the LI-RADS system, particularly with regard to intermediate categories, such as LR-2.

The researchers disclosed no funding sources. Dr. van der Pol, Dr. Lim, and three other investigators reported having no conflicts of interest. Five researchers reported that they are members of the LI-RADS Steering Committee and four disclosed ties to pharmaceutical companies.

SOURCE: Van der Pol CB et al. Gastroenterology. 2018 Nov 13. doi: 10.1053/j.gastro.2018.11.020.

Higher (more severe) Liver Imaging Reporting and Data System (LI-RADS) categories contained increasing proportions of hepatocellular carcinomas and overall malignancies, supporting the general reliability of the system, according to a systematic review and meta-analysis of 17 retrospective studies.

But 13% of LR-2 (“probably benign”) observations were actually hepatocellular carcinomas, as were 38% of LR-3 (“intermediate probability of malignancy”) observations, reported Christian B. van der Pol, MD, of McMaster University, Hamilton, Ont., and Christopher S. Lim, BBS, of Harvard Medical School, Boston, and their associates. Thus, clinicians should consider biopsy of many LR-3s, and LR-2s might need “more active management” than the currently recommended “return to surveillance,” including consideration for biopsy of solid LR-2 nodules measuring 1 cm or more, they wrote in Gastroenterology.

Histopathology confirmed that 93% of CT and MRI observations designated as LR-M (“definite or probable malignancy”) were indeed malignancies and that 36% were hepatocellular carcinomas,

The LI-RADS system, like its counterparts in breast and prostate imaging (BI-RADS and PI-RADS), classifies CT and MRI findings based on level of suspicion for malignancy. These categories include LR-M, LR-3, LR-2, LR-1 (“definitely benign”), LR-TIV (“definitely tumor in vein”), and LR-4 and LR-5 (“probably” and “definitely” hepatocellular carcinoma). However, CT and MRI interpretation is only as useful as it is accurate. To calculate actual percentages of hepatocellular carcinomas and overall malignancies within each LI-RADS category, the investigators analyzed aggregate data from studies found by searching MEDLINE, Embase, Cochrane CENTRAL, and Scopus during 2014-2018.

These 17 studies included 2,760 patients and 3,556 imaging observations. Pathology was the reference standard for LR-M, but for other LI-RADS categories, the researchers accepted strong clinical indicators of hepatocellular carcinoma, such as a 50% increase in lesion size within 6 months, or posttreatment recurrence of a previously confirmed malignancy. They classified observations as negative if they stayed stable in size for at least 12 months, spontaneously diminished in size, or disappeared without treatment.

In all, 94% and 97% of LR-5 observations were (respectively) hepatocellular carcinomas and other malignancies, as were 79% and 92% of LR-TIVs, 36% and 93% of LR-Ms, 74% and 80% of LR-4s, 38% and 40% of LR-3s, and 13% and 14% of LR-2s. No LR-1s were confirmed as malignant.

“Our data suggest biopsy of LI-RADS 3 observations should be considered in many patients, as a risk of 38% of HCC would usually provoke biopsy of a lesion elsewhere in the body,” the researchers wrote. They suggested consideration for biopsy of certain LR-2 lesions, but added that many “are small, perfusional alterations caused by arterioportal shunts, which are often not reported” and would be difficult or impossible to biopsy.

The study did not cover the most recent (2018) LI-RADS system, which featured several changes to simplify and better align it with American Association for the Study of Liver Diseases criteria, the researchers noted. They called for prospective studies to help confirm the accuracy of the LI-RADS system, particularly with regard to intermediate categories, such as LR-2.

The researchers disclosed no funding sources. Dr. van der Pol, Dr. Lim, and three other investigators reported having no conflicts of interest. Five researchers reported that they are members of the LI-RADS Steering Committee and four disclosed ties to pharmaceutical companies.

SOURCE: Van der Pol CB et al. Gastroenterology. 2018 Nov 13. doi: 10.1053/j.gastro.2018.11.020.

Higher (more severe) Liver Imaging Reporting and Data System (LI-RADS) categories contained increasing proportions of hepatocellular carcinomas and overall malignancies, supporting the general reliability of the system, according to a systematic review and meta-analysis of 17 retrospective studies.

But 13% of LR-2 (“probably benign”) observations were actually hepatocellular carcinomas, as were 38% of LR-3 (“intermediate probability of malignancy”) observations, reported Christian B. van der Pol, MD, of McMaster University, Hamilton, Ont., and Christopher S. Lim, BBS, of Harvard Medical School, Boston, and their associates. Thus, clinicians should consider biopsy of many LR-3s, and LR-2s might need “more active management” than the currently recommended “return to surveillance,” including consideration for biopsy of solid LR-2 nodules measuring 1 cm or more, they wrote in Gastroenterology.

Histopathology confirmed that 93% of CT and MRI observations designated as LR-M (“definite or probable malignancy”) were indeed malignancies and that 36% were hepatocellular carcinomas,

The LI-RADS system, like its counterparts in breast and prostate imaging (BI-RADS and PI-RADS), classifies CT and MRI findings based on level of suspicion for malignancy. These categories include LR-M, LR-3, LR-2, LR-1 (“definitely benign”), LR-TIV (“definitely tumor in vein”), and LR-4 and LR-5 (“probably” and “definitely” hepatocellular carcinoma). However, CT and MRI interpretation is only as useful as it is accurate. To calculate actual percentages of hepatocellular carcinomas and overall malignancies within each LI-RADS category, the investigators analyzed aggregate data from studies found by searching MEDLINE, Embase, Cochrane CENTRAL, and Scopus during 2014-2018.

These 17 studies included 2,760 patients and 3,556 imaging observations. Pathology was the reference standard for LR-M, but for other LI-RADS categories, the researchers accepted strong clinical indicators of hepatocellular carcinoma, such as a 50% increase in lesion size within 6 months, or posttreatment recurrence of a previously confirmed malignancy. They classified observations as negative if they stayed stable in size for at least 12 months, spontaneously diminished in size, or disappeared without treatment.

In all, 94% and 97% of LR-5 observations were (respectively) hepatocellular carcinomas and other malignancies, as were 79% and 92% of LR-TIVs, 36% and 93% of LR-Ms, 74% and 80% of LR-4s, 38% and 40% of LR-3s, and 13% and 14% of LR-2s. No LR-1s were confirmed as malignant.

“Our data suggest biopsy of LI-RADS 3 observations should be considered in many patients, as a risk of 38% of HCC would usually provoke biopsy of a lesion elsewhere in the body,” the researchers wrote. They suggested consideration for biopsy of certain LR-2 lesions, but added that many “are small, perfusional alterations caused by arterioportal shunts, which are often not reported” and would be difficult or impossible to biopsy.

The study did not cover the most recent (2018) LI-RADS system, which featured several changes to simplify and better align it with American Association for the Study of Liver Diseases criteria, the researchers noted. They called for prospective studies to help confirm the accuracy of the LI-RADS system, particularly with regard to intermediate categories, such as LR-2.

The researchers disclosed no funding sources. Dr. van der Pol, Dr. Lim, and three other investigators reported having no conflicts of interest. Five researchers reported that they are members of the LI-RADS Steering Committee and four disclosed ties to pharmaceutical companies.

SOURCE: Van der Pol CB et al. Gastroenterology. 2018 Nov 13. doi: 10.1053/j.gastro.2018.11.020.

Nonalcoholic steatohepatitis may soon supplant chronic hepatitis C as the leading cause of hepatocellular carcinoma among patients awaiting liver transplantation, according to the findings of a national longitudinal registry study.

The proportion of affected patients with nonalcoholic steatohepatitis (NASH) rose nearly 700% between 2002 and 2017 (P less than .0001), making NASH the only etiology to significantly rise in prevalence, reported Zobair Younossi, MD, MPH, of Inova Health System in Falls Church, Va., and his associates. Chronic hepatitis C remained the most common cause of liver cancer during the study period, but its prevalence fell by more than 10% in the last 3 years (2014-2017). These trends reflect the advent of “new, highly effective antiviral regimens” for hepatitis C, the global epidemic of obesity and metabolic syndrome, and the urgent need for effective, safe treatments for NASH, they wrote in Clinical Gastroenterology and Hepatology.

Historically, hepatocellular carcinoma is usually caused by chronic hepatitis C or B infection, but the global rise of obesity and type 2 diabetes mellitus has led to epidemic levels of NASH, a progressive form of nonalcoholic fatty liver disease that lacks useful predictive noninvasive biomarkers or safe treatments. This phenomenon, coupled with the advent of new, often-curative treatments for viral hepatitis, is making NASH a leading driver of both fibrosis and liver transplantation in the United States. To compare trends in liver cancer etiologies among transplant candidates, Dr. Younossi and his associates analyzed data on 158,347 adults who were wait-listed between 2002 and 2017 and captured by the national Scientific Registry of Transplant Recipients.

A total of 26,121 (16.5%) patients awaiting liver transplant had hepatocellular carcinoma. This proportion nearly quadrupled over the study period, from 6% to 23% (P less than .0001) and rose significantly (P less than .0001) for all liver cancer etiologies (hepatitis C and B, alcoholic liver disease, and NASH). However, the absolute rise in prevalence was far greater for NASH (1050%) than for chronic hepatitis C (more than 500%) or any other etiology.

Furthermore, while most (65%) liver cancer cases involved chronic hepatitis C, the proportion of cases involving NASH rose from 2% in 2002 to 18% in 2017 (P less than .0001). By 2017, NASH topped alcoholic liver disease, comorbid hepatitis C with alcoholic liver disease, and chronic hepatitis B as an etiology of hepatocellular carcinoma among patients listed for transplant. Conversely, by 2017, less than 50% of liver cancers were caused by hepatitis C – a more than 10% drop from 2014. Over the study period, NASH was the only etiology whose prevalence significantly increased among transplant-listed patients with hepatocellular carcinoma.

In this study, etiology of liver cancer did not seem to affect the likelihood of either death or transplantation. However, serious cardiovascular disease or late-stage cancer diagnosis might exclude many NASH patients from transplantation, the researchers wrote. “Thus, the population reported here actually may underestimate the true proportion of hepatocellular carcinoma cases related to nonalcoholic fatty liver disease and NASH in the United States. Because NASH is on a trajectory to become the most common cause of hepatocellular carcinoma in the United States, effective prevention strategies and treatment options are urgently needed for this currently underserved patient population.”

Minneapolis Medical Research Foundation is the contractor for the registry and supplied the data. Dr. Younossi reported ties to Bristol-Myers Squibb, Gilead Sciences, AbbVie, Intercept Pharmaceuticals, and GlaxoSmithKline.

SOURCE: Younossi Z et al. Clin Gastroenterol Hepatol. 2018 Jun 14. doi: 10.1016/j.cgh.2018.05.057.

Nonalcoholic steatohepatitis may soon supplant chronic hepatitis C as the leading cause of hepatocellular carcinoma among patients awaiting liver transplantation, according to the findings of a national longitudinal registry study.

The proportion of affected patients with nonalcoholic steatohepatitis (NASH) rose nearly 700% between 2002 and 2017 (P less than .0001), making NASH the only etiology to significantly rise in prevalence, reported Zobair Younossi, MD, MPH, of Inova Health System in Falls Church, Va., and his associates. Chronic hepatitis C remained the most common cause of liver cancer during the study period, but its prevalence fell by more than 10% in the last 3 years (2014-2017). These trends reflect the advent of “new, highly effective antiviral regimens” for hepatitis C, the global epidemic of obesity and metabolic syndrome, and the urgent need for effective, safe treatments for NASH, they wrote in Clinical Gastroenterology and Hepatology.

Historically, hepatocellular carcinoma is usually caused by chronic hepatitis C or B infection, but the global rise of obesity and type 2 diabetes mellitus has led to epidemic levels of NASH, a progressive form of nonalcoholic fatty liver disease that lacks useful predictive noninvasive biomarkers or safe treatments. This phenomenon, coupled with the advent of new, often-curative treatments for viral hepatitis, is making NASH a leading driver of both fibrosis and liver transplantation in the United States. To compare trends in liver cancer etiologies among transplant candidates, Dr. Younossi and his associates analyzed data on 158,347 adults who were wait-listed between 2002 and 2017 and captured by the national Scientific Registry of Transplant Recipients.

A total of 26,121 (16.5%) patients awaiting liver transplant had hepatocellular carcinoma. This proportion nearly quadrupled over the study period, from 6% to 23% (P less than .0001) and rose significantly (P less than .0001) for all liver cancer etiologies (hepatitis C and B, alcoholic liver disease, and NASH). However, the absolute rise in prevalence was far greater for NASH (1050%) than for chronic hepatitis C (more than 500%) or any other etiology.

Furthermore, while most (65%) liver cancer cases involved chronic hepatitis C, the proportion of cases involving NASH rose from 2% in 2002 to 18% in 2017 (P less than .0001). By 2017, NASH topped alcoholic liver disease, comorbid hepatitis C with alcoholic liver disease, and chronic hepatitis B as an etiology of hepatocellular carcinoma among patients listed for transplant. Conversely, by 2017, less than 50% of liver cancers were caused by hepatitis C – a more than 10% drop from 2014. Over the study period, NASH was the only etiology whose prevalence significantly increased among transplant-listed patients with hepatocellular carcinoma.

In this study, etiology of liver cancer did not seem to affect the likelihood of either death or transplantation. However, serious cardiovascular disease or late-stage cancer diagnosis might exclude many NASH patients from transplantation, the researchers wrote. “Thus, the population reported here actually may underestimate the true proportion of hepatocellular carcinoma cases related to nonalcoholic fatty liver disease and NASH in the United States. Because NASH is on a trajectory to become the most common cause of hepatocellular carcinoma in the United States, effective prevention strategies and treatment options are urgently needed for this currently underserved patient population.”

Minneapolis Medical Research Foundation is the contractor for the registry and supplied the data. Dr. Younossi reported ties to Bristol-Myers Squibb, Gilead Sciences, AbbVie, Intercept Pharmaceuticals, and GlaxoSmithKline.

SOURCE: Younossi Z et al. Clin Gastroenterol Hepatol. 2018 Jun 14. doi: 10.1016/j.cgh.2018.05.057.

Nonalcoholic steatohepatitis may soon supplant chronic hepatitis C as the leading cause of hepatocellular carcinoma among patients awaiting liver transplantation, according to the findings of a national longitudinal registry study.

The proportion of affected patients with nonalcoholic steatohepatitis (NASH) rose nearly 700% between 2002 and 2017 (P less than .0001), making NASH the only etiology to significantly rise in prevalence, reported Zobair Younossi, MD, MPH, of Inova Health System in Falls Church, Va., and his associates. Chronic hepatitis C remained the most common cause of liver cancer during the study period, but its prevalence fell by more than 10% in the last 3 years (2014-2017). These trends reflect the advent of “new, highly effective antiviral regimens” for hepatitis C, the global epidemic of obesity and metabolic syndrome, and the urgent need for effective, safe treatments for NASH, they wrote in Clinical Gastroenterology and Hepatology.

Historically, hepatocellular carcinoma is usually caused by chronic hepatitis C or B infection, but the global rise of obesity and type 2 diabetes mellitus has led to epidemic levels of NASH, a progressive form of nonalcoholic fatty liver disease that lacks useful predictive noninvasive biomarkers or safe treatments. This phenomenon, coupled with the advent of new, often-curative treatments for viral hepatitis, is making NASH a leading driver of both fibrosis and liver transplantation in the United States. To compare trends in liver cancer etiologies among transplant candidates, Dr. Younossi and his associates analyzed data on 158,347 adults who were wait-listed between 2002 and 2017 and captured by the national Scientific Registry of Transplant Recipients.

A total of 26,121 (16.5%) patients awaiting liver transplant had hepatocellular carcinoma. This proportion nearly quadrupled over the study period, from 6% to 23% (P less than .0001) and rose significantly (P less than .0001) for all liver cancer etiologies (hepatitis C and B, alcoholic liver disease, and NASH). However, the absolute rise in prevalence was far greater for NASH (1050%) than for chronic hepatitis C (more than 500%) or any other etiology.

Furthermore, while most (65%) liver cancer cases involved chronic hepatitis C, the proportion of cases involving NASH rose from 2% in 2002 to 18% in 2017 (P less than .0001). By 2017, NASH topped alcoholic liver disease, comorbid hepatitis C with alcoholic liver disease, and chronic hepatitis B as an etiology of hepatocellular carcinoma among patients listed for transplant. Conversely, by 2017, less than 50% of liver cancers were caused by hepatitis C – a more than 10% drop from 2014. Over the study period, NASH was the only etiology whose prevalence significantly increased among transplant-listed patients with hepatocellular carcinoma.

In this study, etiology of liver cancer did not seem to affect the likelihood of either death or transplantation. However, serious cardiovascular disease or late-stage cancer diagnosis might exclude many NASH patients from transplantation, the researchers wrote. “Thus, the population reported here actually may underestimate the true proportion of hepatocellular carcinoma cases related to nonalcoholic fatty liver disease and NASH in the United States. Because NASH is on a trajectory to become the most common cause of hepatocellular carcinoma in the United States, effective prevention strategies and treatment options are urgently needed for this currently underserved patient population.”

Minneapolis Medical Research Foundation is the contractor for the registry and supplied the data. Dr. Younossi reported ties to Bristol-Myers Squibb, Gilead Sciences, AbbVie, Intercept Pharmaceuticals, and GlaxoSmithKline.

SOURCE: Younossi Z et al. Clin Gastroenterol Hepatol. 2018 Jun 14. doi: 10.1016/j.cgh.2018.05.057.

Treatment with budesonide oral suspension (BOS) was generally well tolerated and maintained a histologic response in some patients with eosinophilic esophagitis (EoE), according to the results of the 24-week, open-label extension phase of a multicenter, randomized, placebo-controlled, industry-sponsored trial.

Rates of histologic response (up to 6 eosinophils per high-power field) were “modest” – 23% among patients who stayed on BOS throughout the study and 48.5% among patients who initiated BOS after 12 weeks on placebo, reported Evan S. Dellon, MD, MPH, of the University of North Carolina in Chapel Hill and his associates. However, these rates “need to be viewed in the context of a highly symptomatic and histologically severe population with eosinophilic esophagitis,” they contended. A total of 11% of budesonide initiators developed esophageal candidiasis, they reported in Clinical Gastroenterology and Hepatology.

Budesonide oral suspension is a mucoadherent formulation of topical corticosteroid that has recently been developed to treat EoE. Previously, during the randomized, double-blind component of this phase 2 trial, 93 patients aged 11-40 years with active EoE and dysphagia received either BOS (2 mg) or placebo twice daily (Gastroenterology. 2017 Mar;157[4]:776-86). After 12 weeks, rates of histologic response were 39% for BOS versus 3% for placebo, and BOS significantly improved patients’ mean peak eosinophil count and scores on the Dysphagia Symptom Questionnaire, compared with baseline and compared with the response in the placebo group. During the open-label extension phase, 45 BOS continuers and 37 BOS initiators received 2 mg once daily for 12 weeks and then had the option to increase the BOS dose to 1.5-2.0 mg twice daily.

The rate of drug-related adverse events was 19% among BOS initiators and 4% among BOS continuers. One patient in each group developed oral candidiasis, while four BOS initiators (11%) developed esophageal candidiasis. Three BOS continuers had subnormal morning cortisol levels; while these were subclinical cases, they merit attention since long-term corticosteroids for EoE have been linked with possible hypothalamic–pituitary–adrenal axis suppression, the researchers noted.

In addition, while BOS initiators tended to maintain their endoscopic response, only 42% of those with an initial histologic response maintained a histologic response after 36 weeks of treatment or when leaving the study. Post hoc analyses confirmed that prolonged BOS treatment does not increase the chances of histologic or endoscopic response. Prior studies have suggested that EoE can become steroid-refractory over time and that certain molecular and histologic markers might predict resistance, the investigators noted.

Meritage Pharma (now part of Shire) was involved in the study design and conduct, data collection and management, and manuscript review. Dr. Dellon disclosed research funding from Meritage and Shire and a consulting relationship with Shire, along with ties to several other pharmaceutical companies. All six coinvestigators also disclosed ties to Meritage, Shire, or both, and two are Shire employees and stockholders.

*This story was updated on Feb. 7, 2019.

SOURCE: Dellon ES et al. Clin Gastroenterol Hepatol. 2018 Jun 11. doi: 10.1016/j.cgh.2018.05.051.

Treatment with budesonide oral suspension (BOS) was generally well tolerated and maintained a histologic response in some patients with eosinophilic esophagitis (EoE), according to the results of the 24-week, open-label extension phase of a multicenter, randomized, placebo-controlled, industry-sponsored trial.

Rates of histologic response (up to 6 eosinophils per high-power field) were “modest” – 23% among patients who stayed on BOS throughout the study and 48.5% among patients who initiated BOS after 12 weeks on placebo, reported Evan S. Dellon, MD, MPH, of the University of North Carolina in Chapel Hill and his associates. However, these rates “need to be viewed in the context of a highly symptomatic and histologically severe population with eosinophilic esophagitis,” they contended. A total of 11% of budesonide initiators developed esophageal candidiasis, they reported in Clinical Gastroenterology and Hepatology.

Budesonide oral suspension is a mucoadherent formulation of topical corticosteroid that has recently been developed to treat EoE. Previously, during the randomized, double-blind component of this phase 2 trial, 93 patients aged 11-40 years with active EoE and dysphagia received either BOS (2 mg) or placebo twice daily (Gastroenterology. 2017 Mar;157[4]:776-86). After 12 weeks, rates of histologic response were 39% for BOS versus 3% for placebo, and BOS significantly improved patients’ mean peak eosinophil count and scores on the Dysphagia Symptom Questionnaire, compared with baseline and compared with the response in the placebo group. During the open-label extension phase, 45 BOS continuers and 37 BOS initiators received 2 mg once daily for 12 weeks and then had the option to increase the BOS dose to 1.5-2.0 mg twice daily.

The rate of drug-related adverse events was 19% among BOS initiators and 4% among BOS continuers. One patient in each group developed oral candidiasis, while four BOS initiators (11%) developed esophageal candidiasis. Three BOS continuers had subnormal morning cortisol levels; while these were subclinical cases, they merit attention since long-term corticosteroids for EoE have been linked with possible hypothalamic–pituitary–adrenal axis suppression, the researchers noted.

In addition, while BOS initiators tended to maintain their endoscopic response, only 42% of those with an initial histologic response maintained a histologic response after 36 weeks of treatment or when leaving the study. Post hoc analyses confirmed that prolonged BOS treatment does not increase the chances of histologic or endoscopic response. Prior studies have suggested that EoE can become steroid-refractory over time and that certain molecular and histologic markers might predict resistance, the investigators noted.

Meritage Pharma (now part of Shire) was involved in the study design and conduct, data collection and management, and manuscript review. Dr. Dellon disclosed research funding from Meritage and Shire and a consulting relationship with Shire, along with ties to several other pharmaceutical companies. All six coinvestigators also disclosed ties to Meritage, Shire, or both, and two are Shire employees and stockholders.

*This story was updated on Feb. 7, 2019.

SOURCE: Dellon ES et al. Clin Gastroenterol Hepatol. 2018 Jun 11. doi: 10.1016/j.cgh.2018.05.051.

Treatment with budesonide oral suspension (BOS) was generally well tolerated and maintained a histologic response in some patients with eosinophilic esophagitis (EoE), according to the results of the 24-week, open-label extension phase of a multicenter, randomized, placebo-controlled, industry-sponsored trial.

Rates of histologic response (up to 6 eosinophils per high-power field) were “modest” – 23% among patients who stayed on BOS throughout the study and 48.5% among patients who initiated BOS after 12 weeks on placebo, reported Evan S. Dellon, MD, MPH, of the University of North Carolina in Chapel Hill and his associates. However, these rates “need to be viewed in the context of a highly symptomatic and histologically severe population with eosinophilic esophagitis,” they contended. A total of 11% of budesonide initiators developed esophageal candidiasis, they reported in Clinical Gastroenterology and Hepatology.

Budesonide oral suspension is a mucoadherent formulation of topical corticosteroid that has recently been developed to treat EoE. Previously, during the randomized, double-blind component of this phase 2 trial, 93 patients aged 11-40 years with active EoE and dysphagia received either BOS (2 mg) or placebo twice daily (Gastroenterology. 2017 Mar;157[4]:776-86). After 12 weeks, rates of histologic response were 39% for BOS versus 3% for placebo, and BOS significantly improved patients’ mean peak eosinophil count and scores on the Dysphagia Symptom Questionnaire, compared with baseline and compared with the response in the placebo group. During the open-label extension phase, 45 BOS continuers and 37 BOS initiators received 2 mg once daily for 12 weeks and then had the option to increase the BOS dose to 1.5-2.0 mg twice daily.

The rate of drug-related adverse events was 19% among BOS initiators and 4% among BOS continuers. One patient in each group developed oral candidiasis, while four BOS initiators (11%) developed esophageal candidiasis. Three BOS continuers had subnormal morning cortisol levels; while these were subclinical cases, they merit attention since long-term corticosteroids for EoE have been linked with possible hypothalamic–pituitary–adrenal axis suppression, the researchers noted.

In addition, while BOS initiators tended to maintain their endoscopic response, only 42% of those with an initial histologic response maintained a histologic response after 36 weeks of treatment or when leaving the study. Post hoc analyses confirmed that prolonged BOS treatment does not increase the chances of histologic or endoscopic response. Prior studies have suggested that EoE can become steroid-refractory over time and that certain molecular and histologic markers might predict resistance, the investigators noted.

Meritage Pharma (now part of Shire) was involved in the study design and conduct, data collection and management, and manuscript review. Dr. Dellon disclosed research funding from Meritage and Shire and a consulting relationship with Shire, along with ties to several other pharmaceutical companies. All six coinvestigators also disclosed ties to Meritage, Shire, or both, and two are Shire employees and stockholders.

*This story was updated on Feb. 7, 2019.

SOURCE: Dellon ES et al. Clin Gastroenterol Hepatol. 2018 Jun 11. doi: 10.1016/j.cgh.2018.05.051.

When patients with inflammatory bowel disease report persistent gastrointestinal symptoms, clinicians should perform a thorough clinical assessment and then take a stepwise approach to rule out ongoing inflammation, according to a clinical practice update from the American Gastroenterological Association.

A fecal calprotectin test can be useful because values under 50 mcg/mL may suggest endoscopic remission, which may, in turn, point to another etiology of gastrointestinal symptoms, wrote Jean-Frederic Colombel, MD, of the Icahn School of Medicine at Mount Sinai, New York, together with his associates in Clinical Gastroenterology and Hepatology.

However, a result between 50 and 250 mcg/mL is harder to interpret because the upper limit of normal varies and mild increases can occur secondary to nonspecific low-grade inflammation, according to the experts. For mild gastrointestinal symptoms, they suggested testing fecal calprotectin every 3-6 months to identify flares as early as possible. If a flare is suspected, they advised considering cross-sectional imaging or endoscopy with biopsy.

Imaging also is indicated for patients with obstructive symptoms such as abdominal pain, obstipation, or constipation, the practice update states. Such symptoms can indicate fecal stasis proximal to distal colitis in patients with ulcerative colitis, or intestinal stenosis in patients with Crohn’s disease.

Other pathophysiologies of gastrointestinal symptoms also should be considered based on constellations of symptoms. For example, steatorrhea with chronic abdominal pain may indicate pancreatic exocrine insufficiency, which fecal elastase testing can help confirm. Symptoms of diarrhea-predominant irritable bowel syndrome can result from bile acid diarrhea, for which several screening tests are available. Diarrhea, abdominal pain, and bloating may indicate carbohydrate malabsorption or small-intestinal bacterial overgrowth, which can be evaluated with breath testing.

If patients with inflammatory bowel disease have persistent gastrointestinal symptoms but lack objective evidence of ongoing inflammation or another etiology, then clinicians should increase their suspicion of an overlapping functional gastrointestinal disorder. These conditions actually “share many common pathophysiologic disturbances that, in some inflammatory bowel disease patients, may be a consequence of prior structural and functional bowel damage,” the experts wrote.

For patients with chronic constipation who do not have an underlying obstruction, they suggest osmotic or stimulant laxatives. For chronic diarrhea, they recommend hypomobility agents or bile-acid sequestrants. Patients with fecal symptoms of irritable bowel syndrome also should be evaluated for pelvic floor disorders, which may improve with biofeedback therapy, the experts state.

A low-FODMAP diet (a diet low in lactose, fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) also can improve symptoms of irritable bowel syndrome, including patients with inflammatory bowel disease. However, a dietitian always should deliver this restrictive diet because patients with inflammatory bowel disease already are at increased risk for undernutrition.

Patients with functional gastrointestinal pain may benefit from antispasmodics, neuropathic-directed agents, and antidepressants, but they should not receive opiates, the experts emphasized. Anxiety and depression are common in both inflammatory bowel disease and irritable bowel syndrome, and patients may benefit from psychotherapy (cognitive-behavioral therapy, hypnotherapy, and mindfulness therapy), antidepressants, anxiolytics, or combinations of these treatments. The practice update also recommends physical exercise, which has been shown to decrease the risk of recurrent active disease in the setting of inflammatory bowel disease.

Finally, persistent gut symptoms can indicate intestinal barrier dysfunction, even if endoscopy shows mucosal healing. Barrier dysfunction is a potential therapeutic target that needs further study in this setting, the experts noted. They also called for studies of the potential benefits and risks of probiotics and other alternative approaches, such as herbal treatments and supplements, yoga, acupuncture, and moxibustion. Until further evidence, however, they have recommended against complementary or alternative medicine or fecal microbiota transplantation.

Dr. Colombel has served as consultant, advisory board member, or speaker for AbbVie, Amgen, Boehringer-Ingelheim, Celgene Corporation, and many other pharmaceutical companies. He has received research grants from AbbVie, Takeda, and Janssen and Janssen.

SOURCE: Colombel J-F et al. Clin Gastroenterol Hepatol. 2018 Aug 9. doi: 10.1016/j.cgh.2018.08.001.

When patients with inflammatory bowel disease report persistent gastrointestinal symptoms, clinicians should perform a thorough clinical assessment and then take a stepwise approach to rule out ongoing inflammation, according to a clinical practice update from the American Gastroenterological Association.

A fecal calprotectin test can be useful because values under 50 mcg/mL may suggest endoscopic remission, which may, in turn, point to another etiology of gastrointestinal symptoms, wrote Jean-Frederic Colombel, MD, of the Icahn School of Medicine at Mount Sinai, New York, together with his associates in Clinical Gastroenterology and Hepatology.

However, a result between 50 and 250 mcg/mL is harder to interpret because the upper limit of normal varies and mild increases can occur secondary to nonspecific low-grade inflammation, according to the experts. For mild gastrointestinal symptoms, they suggested testing fecal calprotectin every 3-6 months to identify flares as early as possible. If a flare is suspected, they advised considering cross-sectional imaging or endoscopy with biopsy.

Imaging also is indicated for patients with obstructive symptoms such as abdominal pain, obstipation, or constipation, the practice update states. Such symptoms can indicate fecal stasis proximal to distal colitis in patients with ulcerative colitis, or intestinal stenosis in patients with Crohn’s disease.

Other pathophysiologies of gastrointestinal symptoms also should be considered based on constellations of symptoms. For example, steatorrhea with chronic abdominal pain may indicate pancreatic exocrine insufficiency, which fecal elastase testing can help confirm. Symptoms of diarrhea-predominant irritable bowel syndrome can result from bile acid diarrhea, for which several screening tests are available. Diarrhea, abdominal pain, and bloating may indicate carbohydrate malabsorption or small-intestinal bacterial overgrowth, which can be evaluated with breath testing.

If patients with inflammatory bowel disease have persistent gastrointestinal symptoms but lack objective evidence of ongoing inflammation or another etiology, then clinicians should increase their suspicion of an overlapping functional gastrointestinal disorder. These conditions actually “share many common pathophysiologic disturbances that, in some inflammatory bowel disease patients, may be a consequence of prior structural and functional bowel damage,” the experts wrote.

For patients with chronic constipation who do not have an underlying obstruction, they suggest osmotic or stimulant laxatives. For chronic diarrhea, they recommend hypomobility agents or bile-acid sequestrants. Patients with fecal symptoms of irritable bowel syndrome also should be evaluated for pelvic floor disorders, which may improve with biofeedback therapy, the experts state.

A low-FODMAP diet (a diet low in lactose, fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) also can improve symptoms of irritable bowel syndrome, including patients with inflammatory bowel disease. However, a dietitian always should deliver this restrictive diet because patients with inflammatory bowel disease already are at increased risk for undernutrition.

Patients with functional gastrointestinal pain may benefit from antispasmodics, neuropathic-directed agents, and antidepressants, but they should not receive opiates, the experts emphasized. Anxiety and depression are common in both inflammatory bowel disease and irritable bowel syndrome, and patients may benefit from psychotherapy (cognitive-behavioral therapy, hypnotherapy, and mindfulness therapy), antidepressants, anxiolytics, or combinations of these treatments. The practice update also recommends physical exercise, which has been shown to decrease the risk of recurrent active disease in the setting of inflammatory bowel disease.

Finally, persistent gut symptoms can indicate intestinal barrier dysfunction, even if endoscopy shows mucosal healing. Barrier dysfunction is a potential therapeutic target that needs further study in this setting, the experts noted. They also called for studies of the potential benefits and risks of probiotics and other alternative approaches, such as herbal treatments and supplements, yoga, acupuncture, and moxibustion. Until further evidence, however, they have recommended against complementary or alternative medicine or fecal microbiota transplantation.

Dr. Colombel has served as consultant, advisory board member, or speaker for AbbVie, Amgen, Boehringer-Ingelheim, Celgene Corporation, and many other pharmaceutical companies. He has received research grants from AbbVie, Takeda, and Janssen and Janssen.

SOURCE: Colombel J-F et al. Clin Gastroenterol Hepatol. 2018 Aug 9. doi: 10.1016/j.cgh.2018.08.001.

When patients with inflammatory bowel disease report persistent gastrointestinal symptoms, clinicians should perform a thorough clinical assessment and then take a stepwise approach to rule out ongoing inflammation, according to a clinical practice update from the American Gastroenterological Association.

A fecal calprotectin test can be useful because values under 50 mcg/mL may suggest endoscopic remission, which may, in turn, point to another etiology of gastrointestinal symptoms, wrote Jean-Frederic Colombel, MD, of the Icahn School of Medicine at Mount Sinai, New York, together with his associates in Clinical Gastroenterology and Hepatology.

However, a result between 50 and 250 mcg/mL is harder to interpret because the upper limit of normal varies and mild increases can occur secondary to nonspecific low-grade inflammation, according to the experts. For mild gastrointestinal symptoms, they suggested testing fecal calprotectin every 3-6 months to identify flares as early as possible. If a flare is suspected, they advised considering cross-sectional imaging or endoscopy with biopsy.

Imaging also is indicated for patients with obstructive symptoms such as abdominal pain, obstipation, or constipation, the practice update states. Such symptoms can indicate fecal stasis proximal to distal colitis in patients with ulcerative colitis, or intestinal stenosis in patients with Crohn’s disease.

Other pathophysiologies of gastrointestinal symptoms also should be considered based on constellations of symptoms. For example, steatorrhea with chronic abdominal pain may indicate pancreatic exocrine insufficiency, which fecal elastase testing can help confirm. Symptoms of diarrhea-predominant irritable bowel syndrome can result from bile acid diarrhea, for which several screening tests are available. Diarrhea, abdominal pain, and bloating may indicate carbohydrate malabsorption or small-intestinal bacterial overgrowth, which can be evaluated with breath testing.

If patients with inflammatory bowel disease have persistent gastrointestinal symptoms but lack objective evidence of ongoing inflammation or another etiology, then clinicians should increase their suspicion of an overlapping functional gastrointestinal disorder. These conditions actually “share many common pathophysiologic disturbances that, in some inflammatory bowel disease patients, may be a consequence of prior structural and functional bowel damage,” the experts wrote.

For patients with chronic constipation who do not have an underlying obstruction, they suggest osmotic or stimulant laxatives. For chronic diarrhea, they recommend hypomobility agents or bile-acid sequestrants. Patients with fecal symptoms of irritable bowel syndrome also should be evaluated for pelvic floor disorders, which may improve with biofeedback therapy, the experts state.

A low-FODMAP diet (a diet low in lactose, fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) also can improve symptoms of irritable bowel syndrome, including patients with inflammatory bowel disease. However, a dietitian always should deliver this restrictive diet because patients with inflammatory bowel disease already are at increased risk for undernutrition.

Patients with functional gastrointestinal pain may benefit from antispasmodics, neuropathic-directed agents, and antidepressants, but they should not receive opiates, the experts emphasized. Anxiety and depression are common in both inflammatory bowel disease and irritable bowel syndrome, and patients may benefit from psychotherapy (cognitive-behavioral therapy, hypnotherapy, and mindfulness therapy), antidepressants, anxiolytics, or combinations of these treatments. The practice update also recommends physical exercise, which has been shown to decrease the risk of recurrent active disease in the setting of inflammatory bowel disease.

Finally, persistent gut symptoms can indicate intestinal barrier dysfunction, even if endoscopy shows mucosal healing. Barrier dysfunction is a potential therapeutic target that needs further study in this setting, the experts noted. They also called for studies of the potential benefits and risks of probiotics and other alternative approaches, such as herbal treatments and supplements, yoga, acupuncture, and moxibustion. Until further evidence, however, they have recommended against complementary or alternative medicine or fecal microbiota transplantation.

Dr. Colombel has served as consultant, advisory board member, or speaker for AbbVie, Amgen, Boehringer-Ingelheim, Celgene Corporation, and many other pharmaceutical companies. He has received research grants from AbbVie, Takeda, and Janssen and Janssen.

SOURCE: Colombel J-F et al. Clin Gastroenterol Hepatol. 2018 Aug 9. doi: 10.1016/j.cgh.2018.08.001.

For patients with extensive mild to moderate ulcerative colitis, numerous randomized controlled trials support the use of either standard-dose mesalamine (2-3 grams per day) or diazo-bonded 5-aminosalicylic acid (ASA) instead of low-dose mesalamine, sulfasalazine, or no therapy, state new guidelines from the American Gastroenterological Association, published in Gastroenterology.

©selvanegra/thinkstockphotos.com

Sulfasalazine (2-4 grams per day) is less likely to be tolerated but remains a “reasonable option” for remitted patients who are already on it and for patients with prominent arthritis symptoms, especially if alternative treatments are cost prohibitive, wrote Cynthia W. Ko, MD, MS, of the University of Washington, Seattle, and her associates.

According to the guideline, patients with mild to moderate ulcerative colitis have less than four to six bowel movements per day, only mild or moderate rectal bleeding, no constitutional symptoms, and no high overall inflammatory burden or signs of high inflammatory activity on the Mayo Clinic score and Truelove and Witt’s criteria. These patients usually do not require colectomy, but this outcome is more likely when patients are diagnosed before age 40 years or have extensive disease or deep ulcers, extraintestinal manifestations, or elevated inflammatory markers. These higher-risk patients need more aggressive initial treatment and faster treatment intensification in cases of inadequate response, the guideline emphasizes. Even for cases of mild to moderate ulcerative colitis, treatment intensification is preferable to repeated courses of corticosteroids.

The guideline recommends adding rectal mesalamine to oral 5-ASA if patients have extensive or left-sided mild to moderate ulcerative colitis. In randomized controlled trials, this combination was significantly more likely to induce and maintain remission than was standard-dose oral mesalamine monotherapy, the authors noted. “In the maintenance trials, enemas were used twice per week or for 1 week per month. Both oral and topical mesalamine were well tolerated.”

For patients with moderate disease activity or a suboptimal response to standard-dose mesalamine or diazo-bonded 5-ASA, the guideline recommends adding rectal mesalamine to high-dose oral mesalamine (more than 3 grams daily). Combination therapy maximizes the delivery of mesalamine to the affected area of the colon, which optimizes the trial of 5-ASA before opting for treatment escalation, the authors noted. They recommend once-daily oral mesalamine dosing, since this is easier to adhere to and studies have found no benefit of more frequent dosing.

For inducing remission of mild to moderate ulcerative colitis, the guideline recommends standard-dose oral mesalamine or diazo-bonded 5-ASA over budesonide. “Overall, the budesonide preparations are not superior to mesalamine for induction of remission,” the authors wrote. Oral 5-ASAs are preferred, especially given the absence of data on the efficacy or safety of maintenance budesonide therapy.

SOURCE: Crocket SD et al.  Gastro 2019;156(2).  doi: org/10.1053/j.gastro.2018.12.009.

For patients with extensive mild to moderate ulcerative colitis, numerous randomized controlled trials support the use of either standard-dose mesalamine (2-3 grams per day) or diazo-bonded 5-aminosalicylic acid (ASA) instead of low-dose mesalamine, sulfasalazine, or no therapy, state new guidelines from the American Gastroenterological Association, published in Gastroenterology.

©selvanegra/thinkstockphotos.com

Sulfasalazine (2-4 grams per day) is less likely to be tolerated but remains a “reasonable option” for remitted patients who are already on it and for patients with prominent arthritis symptoms, especially if alternative treatments are cost prohibitive, wrote Cynthia W. Ko, MD, MS, of the University of Washington, Seattle, and her associates.

According to the guideline, patients with mild to moderate ulcerative colitis have less than four to six bowel movements per day, only mild or moderate rectal bleeding, no constitutional symptoms, and no high overall inflammatory burden or signs of high inflammatory activity on the Mayo Clinic score and Truelove and Witt’s criteria. These patients usually do not require colectomy, but this outcome is more likely when patients are diagnosed before age 40 years or have extensive disease or deep ulcers, extraintestinal manifestations, or elevated inflammatory markers. These higher-risk patients need more aggressive initial treatment and faster treatment intensification in cases of inadequate response, the guideline emphasizes. Even for cases of mild to moderate ulcerative colitis, treatment intensification is preferable to repeated courses of corticosteroids.

The guideline recommends adding rectal mesalamine to oral 5-ASA if patients have extensive or left-sided mild to moderate ulcerative colitis. In randomized controlled trials, this combination was significantly more likely to induce and maintain remission than was standard-dose oral mesalamine monotherapy, the authors noted. “In the maintenance trials, enemas were used twice per week or for 1 week per month. Both oral and topical mesalamine were well tolerated.”

For patients with moderate disease activity or a suboptimal response to standard-dose mesalamine or diazo-bonded 5-ASA, the guideline recommends adding rectal mesalamine to high-dose oral mesalamine (more than 3 grams daily). Combination therapy maximizes the delivery of mesalamine to the affected area of the colon, which optimizes the trial of 5-ASA before opting for treatment escalation, the authors noted. They recommend once-daily oral mesalamine dosing, since this is easier to adhere to and studies have found no benefit of more frequent dosing.

For inducing remission of mild to moderate ulcerative colitis, the guideline recommends standard-dose oral mesalamine or diazo-bonded 5-ASA over budesonide. “Overall, the budesonide preparations are not superior to mesalamine for induction of remission,” the authors wrote. Oral 5-ASAs are preferred, especially given the absence of data on the efficacy or safety of maintenance budesonide therapy.

SOURCE: Crocket SD et al.  Gastro 2019;156(2).  doi: org/10.1053/j.gastro.2018.12.009.

For patients with extensive mild to moderate ulcerative colitis, numerous randomized controlled trials support the use of either standard-dose mesalamine (2-3 grams per day) or diazo-bonded 5-aminosalicylic acid (ASA) instead of low-dose mesalamine, sulfasalazine, or no therapy, state new guidelines from the American Gastroenterological Association, published in Gastroenterology.

©selvanegra/thinkstockphotos.com

Sulfasalazine (2-4 grams per day) is less likely to be tolerated but remains a “reasonable option” for remitted patients who are already on it and for patients with prominent arthritis symptoms, especially if alternative treatments are cost prohibitive, wrote Cynthia W. Ko, MD, MS, of the University of Washington, Seattle, and her associates.

According to the guideline, patients with mild to moderate ulcerative colitis have less than four to six bowel movements per day, only mild or moderate rectal bleeding, no constitutional symptoms, and no high overall inflammatory burden or signs of high inflammatory activity on the Mayo Clinic score and Truelove and Witt’s criteria. These patients usually do not require colectomy, but this outcome is more likely when patients are diagnosed before age 40 years or have extensive disease or deep ulcers, extraintestinal manifestations, or elevated inflammatory markers. These higher-risk patients need more aggressive initial treatment and faster treatment intensification in cases of inadequate response, the guideline emphasizes. Even for cases of mild to moderate ulcerative colitis, treatment intensification is preferable to repeated courses of corticosteroids.

The guideline recommends adding rectal mesalamine to oral 5-ASA if patients have extensive or left-sided mild to moderate ulcerative colitis. In randomized controlled trials, this combination was significantly more likely to induce and maintain remission than was standard-dose oral mesalamine monotherapy, the authors noted. “In the maintenance trials, enemas were used twice per week or for 1 week per month. Both oral and topical mesalamine were well tolerated.”

For patients with moderate disease activity or a suboptimal response to standard-dose mesalamine or diazo-bonded 5-ASA, the guideline recommends adding rectal mesalamine to high-dose oral mesalamine (more than 3 grams daily). Combination therapy maximizes the delivery of mesalamine to the affected area of the colon, which optimizes the trial of 5-ASA before opting for treatment escalation, the authors noted. They recommend once-daily oral mesalamine dosing, since this is easier to adhere to and studies have found no benefit of more frequent dosing.

For inducing remission of mild to moderate ulcerative colitis, the guideline recommends standard-dose oral mesalamine or diazo-bonded 5-ASA over budesonide. “Overall, the budesonide preparations are not superior to mesalamine for induction of remission,” the authors wrote. Oral 5-ASAs are preferred, especially given the absence of data on the efficacy or safety of maintenance budesonide therapy.

SOURCE: Crocket SD et al.  Gastro 2019;156(2).  doi: org/10.1053/j.gastro.2018.12.009.

Single-dose tafenoquine therapy safely reduces the risk of Plasmodium vivax relapse in patients with normal glucose-6-phosphate dehydrogenase (G6PD) activity, according to the results of two phase 3, double-blind, randomized controlled trials.

Courtesy NIAID

Findings from both studies were published in two separate reports in the New England Journal of Medicine.

In the first study, the Dose and Efficacy Trial Evaluating Chloroquine and Tafenoquine in Vivax Elimination (DETECTIVE), the risk of P. vivax recurrence was approximately 70% lower with tafenoquine versus placebo, wrote Marcus V.G. Lacerda, MD, of Fundação de Medicina Tropical Doutor Heitor Vieira Dourado in Manaus, Brazil, and his colleagues.

The study included 522 patients with confirmed P. vivax infection from Peru, Brazil, Ethiopia, Cambodia, Thailand, and the Philippines. Patients received 3 days of chloroquine therapy (600 mg on days 1 and 2, and 300 mg on day 3) and were randomly assigned on a 2:1:1 basis to receive a single 300-mg dose of tafenoquine on day 1 or 2, primaquine once daily for 14 days, or placebo.

Since primaquine and tafenoquine can cause clinically significant hemolysis in individuals with G6PD deficiency, the study included only patients with normal G6PD activity.

In the second study, Global Assessment of Tafenoquine Hemolytic Risk (GATHER), Alejandro Llanos-Cuentas, MD, of Universidad Peruana Cayetano Heredia, Lima, Peru, and his colleagues enrolled 251 patients with confirmed P. vivax infection from Peru, Brazil, Columbia, Vietnam, and Thailand. They attempted to recruit women with moderate G6PD levels, but only one participant met this criterion – all others had normal G6PD activity.

Patients received 3-day course of chloroquine and were randomly assigned on a 2:1 basis to either tafenoquine or primaquine at the same doses as in the DETECTIVE trial.

At 6 months, 2% (95% CI, 1%-6%) of tafenoquine recipients and 1% (95% CI, 0.2%-6%) of primaquine recipients had decreased hemoglobin levels, but none consequently needed treatment. The medications also caused a similar degree and time course of hemoglobin decrease, the investigators noted.

A meta-analysis of GATHER and DETECTIVE confirmed that tafenoquine more often led to a decreased hemoglobin level (4% versus 1.5% with primaquine). Tafenoquine also did not meet prespecified criteria for noninferiority compared with primaquine, with respective 6-month recurrence rates of 67% versus 73%.

However, GATHER deployed “extensive” support to help patients adhere to the 15-day primaquine course, Dr. Llanos-Cuentas and his colleagues wrote. “Without such interventions, adherence to primaquine has been reported to be as low as 24% in Southeast Asia, with a corresponding attenuation of efficacy.”

GlaxoSmithKline and Medicines for Malaria Venture funded both studies, and GSK funded and conducted the meta-analysis. Dr. Llanos-Cuentas and several coinvestigators reported ties to GSK, Medicines for Malaria Venture, the Gambia, and LSTMH. Dr. Lacerda reported having no conflicts of interest.

SOURCES: Lacerda MVG et al. N Engl J Med 2019;380:215-28, and Llanos-Cuentas A et al. N Engl J Med 2019;380:229-41.

Single-dose tafenoquine therapy safely reduces the risk of Plasmodium vivax relapse in patients with normal glucose-6-phosphate dehydrogenase (G6PD) activity, according to the results of two phase 3, double-blind, randomized controlled trials.

Courtesy NIAID

Findings from both studies were published in two separate reports in the New England Journal of Medicine.

In the first study, the Dose and Efficacy Trial Evaluating Chloroquine and Tafenoquine in Vivax Elimination (DETECTIVE), the risk of P. vivax recurrence was approximately 70% lower with tafenoquine versus placebo, wrote Marcus V.G. Lacerda, MD, of Fundação de Medicina Tropical Doutor Heitor Vieira Dourado in Manaus, Brazil, and his colleagues.

The study included 522 patients with confirmed P. vivax infection from Peru, Brazil, Ethiopia, Cambodia, Thailand, and the Philippines. Patients received 3 days of chloroquine therapy (600 mg on days 1 and 2, and 300 mg on day 3) and were randomly assigned on a 2:1:1 basis to receive a single 300-mg dose of tafenoquine on day 1 or 2, primaquine once daily for 14 days, or placebo.

Since primaquine and tafenoquine can cause clinically significant hemolysis in individuals with G6PD deficiency, the study included only patients with normal G6PD activity.

In the second study, Global Assessment of Tafenoquine Hemolytic Risk (GATHER), Alejandro Llanos-Cuentas, MD, of Universidad Peruana Cayetano Heredia, Lima, Peru, and his colleagues enrolled 251 patients with confirmed P. vivax infection from Peru, Brazil, Columbia, Vietnam, and Thailand. They attempted to recruit women with moderate G6PD levels, but only one participant met this criterion – all others had normal G6PD activity.

Patients received 3-day course of chloroquine and were randomly assigned on a 2:1 basis to either tafenoquine or primaquine at the same doses as in the DETECTIVE trial.

At 6 months, 2% (95% CI, 1%-6%) of tafenoquine recipients and 1% (95% CI, 0.2%-6%) of primaquine recipients had decreased hemoglobin levels, but none consequently needed treatment. The medications also caused a similar degree and time course of hemoglobin decrease, the investigators noted.

A meta-analysis of GATHER and DETECTIVE confirmed that tafenoquine more often led to a decreased hemoglobin level (4% versus 1.5% with primaquine). Tafenoquine also did not meet prespecified criteria for noninferiority compared with primaquine, with respective 6-month recurrence rates of 67% versus 73%.

However, GATHER deployed “extensive” support to help patients adhere to the 15-day primaquine course, Dr. Llanos-Cuentas and his colleagues wrote. “Without such interventions, adherence to primaquine has been reported to be as low as 24% in Southeast Asia, with a corresponding attenuation of efficacy.”

GlaxoSmithKline and Medicines for Malaria Venture funded both studies, and GSK funded and conducted the meta-analysis. Dr. Llanos-Cuentas and several coinvestigators reported ties to GSK, Medicines for Malaria Venture, the Gambia, and LSTMH. Dr. Lacerda reported having no conflicts of interest.

SOURCES: Lacerda MVG et al. N Engl J Med 2019;380:215-28, and Llanos-Cuentas A et al. N Engl J Med 2019;380:229-41.

Single-dose tafenoquine therapy safely reduces the risk of Plasmodium vivax relapse in patients with normal glucose-6-phosphate dehydrogenase (G6PD) activity, according to the results of two phase 3, double-blind, randomized controlled trials.

Courtesy NIAID

Findings from both studies were published in two separate reports in the New England Journal of Medicine.

In the first study, the Dose and Efficacy Trial Evaluating Chloroquine and Tafenoquine in Vivax Elimination (DETECTIVE), the risk of P. vivax recurrence was approximately 70% lower with tafenoquine versus placebo, wrote Marcus V.G. Lacerda, MD, of Fundação de Medicina Tropical Doutor Heitor Vieira Dourado in Manaus, Brazil, and his colleagues.

The study included 522 patients with confirmed P. vivax infection from Peru, Brazil, Ethiopia, Cambodia, Thailand, and the Philippines. Patients received 3 days of chloroquine therapy (600 mg on days 1 and 2, and 300 mg on day 3) and were randomly assigned on a 2:1:1 basis to receive a single 300-mg dose of tafenoquine on day 1 or 2, primaquine once daily for 14 days, or placebo.

Since primaquine and tafenoquine can cause clinically significant hemolysis in individuals with G6PD deficiency, the study included only patients with normal G6PD activity.

In the second study, Global Assessment of Tafenoquine Hemolytic Risk (GATHER), Alejandro Llanos-Cuentas, MD, of Universidad Peruana Cayetano Heredia, Lima, Peru, and his colleagues enrolled 251 patients with confirmed P. vivax infection from Peru, Brazil, Columbia, Vietnam, and Thailand. They attempted to recruit women with moderate G6PD levels, but only one participant met this criterion – all others had normal G6PD activity.

Patients received 3-day course of chloroquine and were randomly assigned on a 2:1 basis to either tafenoquine or primaquine at the same doses as in the DETECTIVE trial.

At 6 months, 2% (95% CI, 1%-6%) of tafenoquine recipients and 1% (95% CI, 0.2%-6%) of primaquine recipients had decreased hemoglobin levels, but none consequently needed treatment. The medications also caused a similar degree and time course of hemoglobin decrease, the investigators noted.

A meta-analysis of GATHER and DETECTIVE confirmed that tafenoquine more often led to a decreased hemoglobin level (4% versus 1.5% with primaquine). Tafenoquine also did not meet prespecified criteria for noninferiority compared with primaquine, with respective 6-month recurrence rates of 67% versus 73%.

However, GATHER deployed “extensive” support to help patients adhere to the 15-day primaquine course, Dr. Llanos-Cuentas and his colleagues wrote. “Without such interventions, adherence to primaquine has been reported to be as low as 24% in Southeast Asia, with a corresponding attenuation of efficacy.”

GlaxoSmithKline and Medicines for Malaria Venture funded both studies, and GSK funded and conducted the meta-analysis. Dr. Llanos-Cuentas and several coinvestigators reported ties to GSK, Medicines for Malaria Venture, the Gambia, and LSTMH. Dr. Lacerda reported having no conflicts of interest.

SOURCES: Lacerda MVG et al. N Engl J Med 2019;380:215-28, and Llanos-Cuentas A et al. N Engl J Med 2019;380:229-41.

For patients with mild to moderate ulcerative colitis, a three-dose, 1-week induction course of anaerobically prepared donor fecal microbiota transplantation (FMT) produced steroid-free remission in 32% of patients, compared with 9% of those who received autologous aerobically prepared FMT in a randomized, double-blind, clinical trial.

Eight weeks after FMT, the odds of steroid-free remission were fivefold higher with anaerobically prepared donor versus aerobically prepared autologous FMT (odds ratio, 5; 95% confidence interval, 1.2-20.1; P = .03), reported Samuel P. Costello, MD, of the Queen Elizabeth Hospital in Woodville, Australia, and his associates. Donor FMT also significantly increased the likelihood of clinical remission and clinical response, the researchers said. “Further research is needed to assess longer-term maintenance of remission and safety,” they wrote in JAMA.

In prior studies, high-intensity FMT with aerobically prepared donor material remitted some cases of mild to moderate ulcerative colitis. However, anaerobic processing has been found to improve microbial viability, which might allow patients to remit with less intensive FMT, the researchers wrote. In their multicenter study, 73 adults with mildly to moderately active ulcerative colitis (total Mayo score, 3-10 points, with endoscopic subscore of at least 2) received either anaerobically prepared stool pooled from three to four highly screened donors or aerobically processed autologous stool. Patients in both arms received two enemas in the 7 days after FMT – a less dose-intensive treatment protocol than in prior FMT trials of patients with ulcerative colitis.

Among 38 patients in the intervention group, 12 (32%) achieved remission, defined as total Mayo score no greater than 2 with an endoscopic score no greater than 1. Strikingly, five (42%) of these patients remained in remission at 12 months, the researchers said. Additionally, 55% of the intervention group but only 23% of the comparator group (P = .007) achieved clinical response at 8 weeks, defined as at least a 3-point decrease in total Mayo score. Rates of clinical remission (Simple Colitis Activity Index score no greater than 2) were 47% and 17%, respectively (P = .01).

The study population averaged 39 years of age, 45% were women, and 95% completed the trial. Serious adverse events included one case each of worsening colitis, Clostridium difficile colitis requiring colectomy, and pneumonia in the donor FMT group, and two cases of worsening colitis in the comparator group. However, the study “was not powered to assess safety, and and thus further larger studies are required to assess this,” the researchers said. The study also suffered from a significant loss to follow-up at 12 months, so additional studies should assess long-term remission, they added.

The National Health and Medical Research Council and the Gutsy Foundation provided funding. Dr. Costello disclosed ties to Janssen, Shire, Ferring, Microbiotica, and Pfizer.

SOURCE: Costello SP et al. JAMA. 2019;321(2):156-64. doi: 10.1001/jama.2018.20046.

For patients with mild to moderate ulcerative colitis, a three-dose, 1-week induction course of anaerobically prepared donor fecal microbiota transplantation (FMT) produced steroid-free remission in 32% of patients, compared with 9% of those who received autologous aerobically prepared FMT in a randomized, double-blind, clinical trial.

Eight weeks after FMT, the odds of steroid-free remission were fivefold higher with anaerobically prepared donor versus aerobically prepared autologous FMT (odds ratio, 5; 95% confidence interval, 1.2-20.1; P = .03), reported Samuel P. Costello, MD, of the Queen Elizabeth Hospital in Woodville, Australia, and his associates. Donor FMT also significantly increased the likelihood of clinical remission and clinical response, the researchers said. “Further research is needed to assess longer-term maintenance of remission and safety,” they wrote in JAMA.

In prior studies, high-intensity FMT with aerobically prepared donor material remitted some cases of mild to moderate ulcerative colitis. However, anaerobic processing has been found to improve microbial viability, which might allow patients to remit with less intensive FMT, the researchers wrote. In their multicenter study, 73 adults with mildly to moderately active ulcerative colitis (total Mayo score, 3-10 points, with endoscopic subscore of at least 2) received either anaerobically prepared stool pooled from three to four highly screened donors or aerobically processed autologous stool. Patients in both arms received two enemas in the 7 days after FMT – a less dose-intensive treatment protocol than in prior FMT trials of patients with ulcerative colitis.

Among 38 patients in the intervention group, 12 (32%) achieved remission, defined as total Mayo score no greater than 2 with an endoscopic score no greater than 1. Strikingly, five (42%) of these patients remained in remission at 12 months, the researchers said. Additionally, 55% of the intervention group but only 23% of the comparator group (P = .007) achieved clinical response at 8 weeks, defined as at least a 3-point decrease in total Mayo score. Rates of clinical remission (Simple Colitis Activity Index score no greater than 2) were 47% and 17%, respectively (P = .01).

The study population averaged 39 years of age, 45% were women, and 95% completed the trial. Serious adverse events included one case each of worsening colitis, Clostridium difficile colitis requiring colectomy, and pneumonia in the donor FMT group, and two cases of worsening colitis in the comparator group. However, the study “was not powered to assess safety, and and thus further larger studies are required to assess this,” the researchers said. The study also suffered from a significant loss to follow-up at 12 months, so additional studies should assess long-term remission, they added.

The National Health and Medical Research Council and the Gutsy Foundation provided funding. Dr. Costello disclosed ties to Janssen, Shire, Ferring, Microbiotica, and Pfizer.

SOURCE: Costello SP et al. JAMA. 2019;321(2):156-64. doi: 10.1001/jama.2018.20046.

For patients with mild to moderate ulcerative colitis, a three-dose, 1-week induction course of anaerobically prepared donor fecal microbiota transplantation (FMT) produced steroid-free remission in 32% of patients, compared with 9% of those who received autologous aerobically prepared FMT in a randomized, double-blind, clinical trial.

Eight weeks after FMT, the odds of steroid-free remission were fivefold higher with anaerobically prepared donor versus aerobically prepared autologous FMT (odds ratio, 5; 95% confidence interval, 1.2-20.1; P = .03), reported Samuel P. Costello, MD, of the Queen Elizabeth Hospital in Woodville, Australia, and his associates. Donor FMT also significantly increased the likelihood of clinical remission and clinical response, the researchers said. “Further research is needed to assess longer-term maintenance of remission and safety,” they wrote in JAMA.

In prior studies, high-intensity FMT with aerobically prepared donor material remitted some cases of mild to moderate ulcerative colitis. However, anaerobic processing has been found to improve microbial viability, which might allow patients to remit with less intensive FMT, the researchers wrote. In their multicenter study, 73 adults with mildly to moderately active ulcerative colitis (total Mayo score, 3-10 points, with endoscopic subscore of at least 2) received either anaerobically prepared stool pooled from three to four highly screened donors or aerobically processed autologous stool. Patients in both arms received two enemas in the 7 days after FMT – a less dose-intensive treatment protocol than in prior FMT trials of patients with ulcerative colitis.

Among 38 patients in the intervention group, 12 (32%) achieved remission, defined as total Mayo score no greater than 2 with an endoscopic score no greater than 1. Strikingly, five (42%) of these patients remained in remission at 12 months, the researchers said. Additionally, 55% of the intervention group but only 23% of the comparator group (P = .007) achieved clinical response at 8 weeks, defined as at least a 3-point decrease in total Mayo score. Rates of clinical remission (Simple Colitis Activity Index score no greater than 2) were 47% and 17%, respectively (P = .01).

The study population averaged 39 years of age, 45% were women, and 95% completed the trial. Serious adverse events included one case each of worsening colitis, Clostridium difficile colitis requiring colectomy, and pneumonia in the donor FMT group, and two cases of worsening colitis in the comparator group. However, the study “was not powered to assess safety, and and thus further larger studies are required to assess this,” the researchers said. The study also suffered from a significant loss to follow-up at 12 months, so additional studies should assess long-term remission, they added.

The National Health and Medical Research Council and the Gutsy Foundation provided funding. Dr. Costello disclosed ties to Janssen, Shire, Ferring, Microbiotica, and Pfizer.

SOURCE: Costello SP et al. JAMA. 2019;321(2):156-64. doi: 10.1001/jama.2018.20046.

For patients with idiopathic pulmonary fibrosis, up to 68 months of treatment with nintedanib showed acceptable safety and tolerability and might have slowed disease progression, according to the results of the open-label INPULSIS-ON trial.

Purestock/thinkstockphotos

No new safety signals were identified among patients who continued nintedanib or switched from placebo to the medication after completing one of the two 52-week phase 3 INPULSIS trials, reported Bruno Crestani, MD, of Hôpital Bichat, Paris, and his associates. The safety profile otherwise resembled that seen in the INPULSIS trials they added. “Patients with idiopathic pulmonary fibrosis could use nintedanib over the long term to slow disease progression,” they wrote in Lancet Respiratory Medicine.

Idiopathic pulmonary fibrosis has had a poor prognosis – before antifibrotic therapy became available in the United States, median survival after diagnosis was estimated at 3-5 years, the researchers noted. Patients often die or deteriorate because of acute declines in respiratory function, often from unknown causes. Nintedanib (Ofev) is an intracellular tyrosine kinase inhibitor first approved for idiopathic pulmonary fibrosis in the United States in 2014, based on the results of the replicate randomized, placebo-controlled, double-blind, phase 3 INPULSIS trials, in which nintedanib (150 mg twice daily) was usually tolerable, showed an acceptable overall toxicity profile, and significantly lessened the annual rate of decline in forced vital capacity (FVC), compared with placebo.

Because idiopathic pulmonary fibrosis has a chronic trajectory, data on long-term safety and efficacy were clearly desirable. “Results from the open-label extension of the [foundational] phase 2 TOMORROW trial [also] identified no new safety signals and suggested an effect of nintedanib on slowing the progression of idiopathic pulmonary fibrosis beyond 52 weeks; however, only 35 patients treated with nintedanib 150 mg twice daily entered the extension study,” Dr. Crestani and his associates noted.

The open-label INPULSIS-ON extension trial included 734 patients, which was 91% of the population that completed the INPULSIS trials. A total of 59% patients in the open-label trial continued nintedanib while the rest switched to nintedanib from placebo. When considering both cohorts, the median duration of exposure to nintedanib was 44.7 months (range, 1.9-68.3 months).

Rates of major adverse cardiovascular events were 2.4 per 100 person-years of drug exposure among treatment initiators and 3.6 per 100 person-years among continuers, the researchers reported. Rates of bleeding were 6.7 and 8.4 events per 100 person-years, respectively, while rates of myocardial infarction, using the broadest possible definition, were 0.7 and 1.3 events per 100 person-years, respectively. The most common adverse event was diarrhea, with 60.1 and 71.2 events per 100 person-years among treatment initiators and continuers, respectively. In all, 10% of treatment initiators and 5% of continuers stopped nintedanib because of diarrhea. A total of 14% of treatment initiators and 12% of continuers stopped treatment because they experienced progression of idiopathic pulmonary fibrosis, making this adverse event the most common reason to stop treatment.

The adjusted annual rate of decline in FVC was −135.1 mL overall, –145 mL in nintedanib continuers, and –119.7 mL in nintedanib initiators, which resembled the findings of the INPULSIS trials, the researcher said. They added that the difference in FVC decline between INPULSIS-ON nintedanib initiators and continuers does not seem clinically meaningful, especially given that the average FVC decline in the INPULSIS placebo group was −223.5 mL per year, and the minimal clinically important difference in FVC is thought to be 2%-6% predicted, a difference of at least 75 mL-80 mL.

Boehringer Ingelheim funded the study. Dr. Crestani disclosed grants and personal fees from Boehringer Ingelheim and Roche, grants from Apellis and MedImmune, and personal fees from AstraZeneca and Sanofi.

SOURCE: Crestani B et al. Lancet Respir Med. 2018 Sep 14. doi: 10.1016/S2213-2600(18)30339-4.

For patients with idiopathic pulmonary fibrosis, up to 68 months of treatment with nintedanib showed acceptable safety and tolerability and might have slowed disease progression, according to the results of the open-label INPULSIS-ON trial.

Purestock/thinkstockphotos

No new safety signals were identified among patients who continued nintedanib or switched from placebo to the medication after completing one of the two 52-week phase 3 INPULSIS trials, reported Bruno Crestani, MD, of Hôpital Bichat, Paris, and his associates. The safety profile otherwise resembled that seen in the INPULSIS trials they added. “Patients with idiopathic pulmonary fibrosis could use nintedanib over the long term to slow disease progression,” they wrote in Lancet Respiratory Medicine.

Idiopathic pulmonary fibrosis has had a poor prognosis – before antifibrotic therapy became available in the United States, median survival after diagnosis was estimated at 3-5 years, the researchers noted. Patients often die or deteriorate because of acute declines in respiratory function, often from unknown causes. Nintedanib (Ofev) is an intracellular tyrosine kinase inhibitor first approved for idiopathic pulmonary fibrosis in the United States in 2014, based on the results of the replicate randomized, placebo-controlled, double-blind, phase 3 INPULSIS trials, in which nintedanib (150 mg twice daily) was usually tolerable, showed an acceptable overall toxicity profile, and significantly lessened the annual rate of decline in forced vital capacity (FVC), compared with placebo.

Because idiopathic pulmonary fibrosis has a chronic trajectory, data on long-term safety and efficacy were clearly desirable. “Results from the open-label extension of the [foundational] phase 2 TOMORROW trial [also] identified no new safety signals and suggested an effect of nintedanib on slowing the progression of idiopathic pulmonary fibrosis beyond 52 weeks; however, only 35 patients treated with nintedanib 150 mg twice daily entered the extension study,” Dr. Crestani and his associates noted.

The open-label INPULSIS-ON extension trial included 734 patients, which was 91% of the population that completed the INPULSIS trials. A total of 59% patients in the open-label trial continued nintedanib while the rest switched to nintedanib from placebo. When considering both cohorts, the median duration of exposure to nintedanib was 44.7 months (range, 1.9-68.3 months).

Rates of major adverse cardiovascular events were 2.4 per 100 person-years of drug exposure among treatment initiators and 3.6 per 100 person-years among continuers, the researchers reported. Rates of bleeding were 6.7 and 8.4 events per 100 person-years, respectively, while rates of myocardial infarction, using the broadest possible definition, were 0.7 and 1.3 events per 100 person-years, respectively. The most common adverse event was diarrhea, with 60.1 and 71.2 events per 100 person-years among treatment initiators and continuers, respectively. In all, 10% of treatment initiators and 5% of continuers stopped nintedanib because of diarrhea. A total of 14% of treatment initiators and 12% of continuers stopped treatment because they experienced progression of idiopathic pulmonary fibrosis, making this adverse event the most common reason to stop treatment.

The adjusted annual rate of decline in FVC was −135.1 mL overall, –145 mL in nintedanib continuers, and –119.7 mL in nintedanib initiators, which resembled the findings of the INPULSIS trials, the researcher said. They added that the difference in FVC decline between INPULSIS-ON nintedanib initiators and continuers does not seem clinically meaningful, especially given that the average FVC decline in the INPULSIS placebo group was −223.5 mL per year, and the minimal clinically important difference in FVC is thought to be 2%-6% predicted, a difference of at least 75 mL-80 mL.

Boehringer Ingelheim funded the study. Dr. Crestani disclosed grants and personal fees from Boehringer Ingelheim and Roche, grants from Apellis and MedImmune, and personal fees from AstraZeneca and Sanofi.

SOURCE: Crestani B et al. Lancet Respir Med. 2018 Sep 14. doi: 10.1016/S2213-2600(18)30339-4.

For patients with idiopathic pulmonary fibrosis, up to 68 months of treatment with nintedanib showed acceptable safety and tolerability and might have slowed disease progression, according to the results of the open-label INPULSIS-ON trial.

Purestock/thinkstockphotos

No new safety signals were identified among patients who continued nintedanib or switched from placebo to the medication after completing one of the two 52-week phase 3 INPULSIS trials, reported Bruno Crestani, MD, of Hôpital Bichat, Paris, and his associates. The safety profile otherwise resembled that seen in the INPULSIS trials they added. “Patients with idiopathic pulmonary fibrosis could use nintedanib over the long term to slow disease progression,” they wrote in Lancet Respiratory Medicine.

Idiopathic pulmonary fibrosis has had a poor prognosis – before antifibrotic therapy became available in the United States, median survival after diagnosis was estimated at 3-5 years, the researchers noted. Patients often die or deteriorate because of acute declines in respiratory function, often from unknown causes. Nintedanib (Ofev) is an intracellular tyrosine kinase inhibitor first approved for idiopathic pulmonary fibrosis in the United States in 2014, based on the results of the replicate randomized, placebo-controlled, double-blind, phase 3 INPULSIS trials, in which nintedanib (150 mg twice daily) was usually tolerable, showed an acceptable overall toxicity profile, and significantly lessened the annual rate of decline in forced vital capacity (FVC), compared with placebo.

Because idiopathic pulmonary fibrosis has a chronic trajectory, data on long-term safety and efficacy were clearly desirable. “Results from the open-label extension of the [foundational] phase 2 TOMORROW trial [also] identified no new safety signals and suggested an effect of nintedanib on slowing the progression of idiopathic pulmonary fibrosis beyond 52 weeks; however, only 35 patients treated with nintedanib 150 mg twice daily entered the extension study,” Dr. Crestani and his associates noted.

The open-label INPULSIS-ON extension trial included 734 patients, which was 91% of the population that completed the INPULSIS trials. A total of 59% patients in the open-label trial continued nintedanib while the rest switched to nintedanib from placebo. When considering both cohorts, the median duration of exposure to nintedanib was 44.7 months (range, 1.9-68.3 months).

Rates of major adverse cardiovascular events were 2.4 per 100 person-years of drug exposure among treatment initiators and 3.6 per 100 person-years among continuers, the researchers reported. Rates of bleeding were 6.7 and 8.4 events per 100 person-years, respectively, while rates of myocardial infarction, using the broadest possible definition, were 0.7 and 1.3 events per 100 person-years, respectively. The most common adverse event was diarrhea, with 60.1 and 71.2 events per 100 person-years among treatment initiators and continuers, respectively. In all, 10% of treatment initiators and 5% of continuers stopped nintedanib because of diarrhea. A total of 14% of treatment initiators and 12% of continuers stopped treatment because they experienced progression of idiopathic pulmonary fibrosis, making this adverse event the most common reason to stop treatment.

The adjusted annual rate of decline in FVC was −135.1 mL overall, –145 mL in nintedanib continuers, and –119.7 mL in nintedanib initiators, which resembled the findings of the INPULSIS trials, the researcher said. They added that the difference in FVC decline between INPULSIS-ON nintedanib initiators and continuers does not seem clinically meaningful, especially given that the average FVC decline in the INPULSIS placebo group was −223.5 mL per year, and the minimal clinically important difference in FVC is thought to be 2%-6% predicted, a difference of at least 75 mL-80 mL.

Boehringer Ingelheim funded the study. Dr. Crestani disclosed grants and personal fees from Boehringer Ingelheim and Roche, grants from Apellis and MedImmune, and personal fees from AstraZeneca and Sanofi.

SOURCE: Crestani B et al. Lancet Respir Med. 2018 Sep 14. doi: 10.1016/S2213-2600(18)30339-4.

Epidermal growth factor receptor (EGFR)–mutant non–small cell lung tumors transformed to small cell disease an average of 17.8 months after diagnosis, and this shift often involved Rb1, TP53, and PIK3CA mutations, according to the findings of a multicenter retrospective study of 67 patients.

After transformation, platinum-etoposide, paclitaxel, and nab-paclitaxel each yielded clinical response rates of 71%, while patients did not respond to programmed death-1 or programmed death-ligand 1 checkpoint inhibition, reported Nicolas Marcoux, MD, of Massachusetts General Hospital in Boston and his associates. “Indeed, none of the 17 patients [who received a checkpoint inhibitor] even seemed to derive clinical benefit from these therapies, as the longest time to progression was only 9 weeks,” the researchers wrote in the Journal of Clinical Oncology.

Interestingly, docetaxel produced no responses among six treated patients. Transformation often led to central nervous system metastases and patients survived a median of 10.7 months after transformation (95% confidence interval, 8.0-13.7 months).

Repeat biopsies showed that 3%-10% of EGFR-mutant non–small cell lung cancers transformed to small cell lung cancers. However, the subsequent clinical course has not been well characterized. Patients in this study were treated at eight cancer centers, had a history of EGFR-mutant small cell lung cancer, and most (87%) had non–small cell histology at diagnosis and received at least one EGFR tyrosine kinase inhibitor. The other nine patients had de novo small cell lung cancer or mixed histology.

All 59 patients with tissue genotyping at first evidence of small cell lung cancer retained their founder EGFR mutations, Dr. Marcoux and his associates reported. Among 19 patients with a history of EGFR T790M positivity, 15 patients were T790 wild-type at transformation. “Other recurrent mutations included TP53, Rb1, and PIK3CA,” they wrote.

The study supports the first-line use of platinum-etoposide for EGFR-mutant lung cancers that transform to small cell lung cancer, the researchers concluded. “Conversely, these tumors do not respond well to checkpoint inhibitors and the use of these therapies outside of a clinical trial should currently be discouraged.”

Funders included the National Institutes of Health, LungStrong, Targeting a Cure for Lung Cancer, Be a Piece of the Solution, the Susanne E. Coyne Memorial Fund, and a STOP Cancer Carrie Scott Grant. Dr. Marcoux disclosed honoraria from Bristol-Myers Squibb.

SOURCE: Marcoux N et al. J Clin Oncol. 2018 Dec 14. doi: 10.1200/JCO.18.01585.

Epidermal growth factor receptor (EGFR)–mutant non–small cell lung tumors transformed to small cell disease an average of 17.8 months after diagnosis, and this shift often involved Rb1, TP53, and PIK3CA mutations, according to the findings of a multicenter retrospective study of 67 patients.

After transformation, platinum-etoposide, paclitaxel, and nab-paclitaxel each yielded clinical response rates of 71%, while patients did not respond to programmed death-1 or programmed death-ligand 1 checkpoint inhibition, reported Nicolas Marcoux, MD, of Massachusetts General Hospital in Boston and his associates. “Indeed, none of the 17 patients [who received a checkpoint inhibitor] even seemed to derive clinical benefit from these therapies, as the longest time to progression was only 9 weeks,” the researchers wrote in the Journal of Clinical Oncology.

Interestingly, docetaxel produced no responses among six treated patients. Transformation often led to central nervous system metastases and patients survived a median of 10.7 months after transformation (95% confidence interval, 8.0-13.7 months).

Repeat biopsies showed that 3%-10% of EGFR-mutant non–small cell lung cancers transformed to small cell lung cancers. However, the subsequent clinical course has not been well characterized. Patients in this study were treated at eight cancer centers, had a history of EGFR-mutant small cell lung cancer, and most (87%) had non–small cell histology at diagnosis and received at least one EGFR tyrosine kinase inhibitor. The other nine patients had de novo small cell lung cancer or mixed histology.

All 59 patients with tissue genotyping at first evidence of small cell lung cancer retained their founder EGFR mutations, Dr. Marcoux and his associates reported. Among 19 patients with a history of EGFR T790M positivity, 15 patients were T790 wild-type at transformation. “Other recurrent mutations included TP53, Rb1, and PIK3CA,” they wrote.

The study supports the first-line use of platinum-etoposide for EGFR-mutant lung cancers that transform to small cell lung cancer, the researchers concluded. “Conversely, these tumors do not respond well to checkpoint inhibitors and the use of these therapies outside of a clinical trial should currently be discouraged.”

Funders included the National Institutes of Health, LungStrong, Targeting a Cure for Lung Cancer, Be a Piece of the Solution, the Susanne E. Coyne Memorial Fund, and a STOP Cancer Carrie Scott Grant. Dr. Marcoux disclosed honoraria from Bristol-Myers Squibb.

SOURCE: Marcoux N et al. J Clin Oncol. 2018 Dec 14. doi: 10.1200/JCO.18.01585.

Epidermal growth factor receptor (EGFR)–mutant non–small cell lung tumors transformed to small cell disease an average of 17.8 months after diagnosis, and this shift often involved Rb1, TP53, and PIK3CA mutations, according to the findings of a multicenter retrospective study of 67 patients.

After transformation, platinum-etoposide, paclitaxel, and nab-paclitaxel each yielded clinical response rates of 71%, while patients did not respond to programmed death-1 or programmed death-ligand 1 checkpoint inhibition, reported Nicolas Marcoux, MD, of Massachusetts General Hospital in Boston and his associates. “Indeed, none of the 17 patients [who received a checkpoint inhibitor] even seemed to derive clinical benefit from these therapies, as the longest time to progression was only 9 weeks,” the researchers wrote in the Journal of Clinical Oncology.

Interestingly, docetaxel produced no responses among six treated patients. Transformation often led to central nervous system metastases and patients survived a median of 10.7 months after transformation (95% confidence interval, 8.0-13.7 months).

Repeat biopsies showed that 3%-10% of EGFR-mutant non–small cell lung cancers transformed to small cell lung cancers. However, the subsequent clinical course has not been well characterized. Patients in this study were treated at eight cancer centers, had a history of EGFR-mutant small cell lung cancer, and most (87%) had non–small cell histology at diagnosis and received at least one EGFR tyrosine kinase inhibitor. The other nine patients had de novo small cell lung cancer or mixed histology.

All 59 patients with tissue genotyping at first evidence of small cell lung cancer retained their founder EGFR mutations, Dr. Marcoux and his associates reported. Among 19 patients with a history of EGFR T790M positivity, 15 patients were T790 wild-type at transformation. “Other recurrent mutations included TP53, Rb1, and PIK3CA,” they wrote.

The study supports the first-line use of platinum-etoposide for EGFR-mutant lung cancers that transform to small cell lung cancer, the researchers concluded. “Conversely, these tumors do not respond well to checkpoint inhibitors and the use of these therapies outside of a clinical trial should currently be discouraged.”

Funders included the National Institutes of Health, LungStrong, Targeting a Cure for Lung Cancer, Be a Piece of the Solution, the Susanne E. Coyne Memorial Fund, and a STOP Cancer Carrie Scott Grant. Dr. Marcoux disclosed honoraria from Bristol-Myers Squibb.

SOURCE: Marcoux N et al. J Clin Oncol. 2018 Dec 14. doi: 10.1200/JCO.18.01585.