Patients who did not survive hospitalization for COVID-19 in Wuhan were more likely to be older, have comorbidities, and elevated D-dimer, according to the first study to examine risk factors associated with death among adults hospitalized with COVID-19. “Older age, showing signs of sepsis on admission, underlying diseases like high blood pressure and diabetes, and the prolonged use of noninvasive ventilation were important factors in the deaths of these patients,” coauthor Zhibo Liu said in a news release. Abnormal blood clotting was part of the clinical picture too.

Fei Zhou, MD, from the Chinese Academy of Medical Sciences, and colleagues conducted a retrospective, observational, multicenter cohort study of 191 patients, 137 of whom were discharged and 54 of whom died in the hospital.

The study, published online today in The Lancet, included all adult inpatients with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital who had been discharged or died by January 31 of this year. Severely ill patients in the province were transferred to these hospitals until February 1.

The researchers compared demographic, clinical, treatment, and laboratory data from electronic medical records between survivors and those who succumbed to the disease. The analysis also tested serial samples for viral RNA. Overall, 91 (48%) of the 191 patients had comorbidity. Most common was hypertension (30%), followed by diabetes (19%) and coronary heart disease (8%).

The odds of dying in the hospital increased with age (odds ratio 1.10; 95% confidence interval, 1.03-1.17; per year increase in age), higher Sequential Organ Failure Assessment (SOFA) score (5.65, 2.61-12.23; P < .0001), and D-dimer level exceeding 1 mcg/L on admission. The SOFA was previously called the “sepsis-related organ failure assessment score” and assesses rate of organ failure in intensive care units. Elevated D-dimer indicates increased risk of abnormal blood clotting, such as deep vein thrombosis.

Nonsurvivors compared with survivors had higher frequencies of respiratory failure (98% vs 36%), sepsis (100%, vs 42%), and secondary infections (50% vs 1%).

The average age of survivors was 52 years compared to 69 for those who died. Liu cited weakening of the immune system and increased inflammation, which damages organs and also promotes viral replication, as explanations for the age effect.

From the time of initial symptoms, median time to discharge from the hospital was 22 days. Average time to death was 18.5 days.

Fever persisted for a median of 12 days among all patients, and cough persisted for a median 19 days; 45% of the survivors were still coughing on discharge. In survivors, shortness of breath improved after 13 days, but persisted until death in the others.

Viral shedding persisted for a median duration of 20 days in survivors, ranging from 8 to 37. The virus (SARS-CoV-2) was detectable in nonsurvivors until death. Antiviral treatment did not curtail viral shedding.

But the viral shedding data come with a caveat. “The extended viral shedding noted in our study has important implications for guiding decisions around isolation precautions and antiviral treatment in patients with confirmed COVID-19 infection. However, we need to be clear that viral shedding time should not be confused with other self-isolation guidance for people who may have been exposed to COVID-19 but do not have symptoms, as this guidance is based on the incubation time of the virus,” explained colead author Bin Cao.

“Older age, elevated D-dimer levels, and high SOFA score could help clinicians to identify at an early stage those patients with COVID-19 who have poor prognosis. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future,” the researchers conclude.

A limitation in interpreting the findings of the study is that hospitalized patients do not represent the entire infected population. The researchers caution that “the number of deaths does not reflect the true mortality of COVID-19.” They also note that they did not have enough genetic material to accurately assess duration of viral shedding.

This article first appeared on Medscape.com.

Patients who did not survive hospitalization for COVID-19 in Wuhan were more likely to be older, have comorbidities, and elevated D-dimer, according to the first study to examine risk factors associated with death among adults hospitalized with COVID-19. “Older age, showing signs of sepsis on admission, underlying diseases like high blood pressure and diabetes, and the prolonged use of noninvasive ventilation were important factors in the deaths of these patients,” coauthor Zhibo Liu said in a news release. Abnormal blood clotting was part of the clinical picture too.

Fei Zhou, MD, from the Chinese Academy of Medical Sciences, and colleagues conducted a retrospective, observational, multicenter cohort study of 191 patients, 137 of whom were discharged and 54 of whom died in the hospital.

The study, published online today in The Lancet, included all adult inpatients with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital who had been discharged or died by January 31 of this year. Severely ill patients in the province were transferred to these hospitals until February 1.

The researchers compared demographic, clinical, treatment, and laboratory data from electronic medical records between survivors and those who succumbed to the disease. The analysis also tested serial samples for viral RNA. Overall, 91 (48%) of the 191 patients had comorbidity. Most common was hypertension (30%), followed by diabetes (19%) and coronary heart disease (8%).

The odds of dying in the hospital increased with age (odds ratio 1.10; 95% confidence interval, 1.03-1.17; per year increase in age), higher Sequential Organ Failure Assessment (SOFA) score (5.65, 2.61-12.23; P < .0001), and D-dimer level exceeding 1 mcg/L on admission. The SOFA was previously called the “sepsis-related organ failure assessment score” and assesses rate of organ failure in intensive care units. Elevated D-dimer indicates increased risk of abnormal blood clotting, such as deep vein thrombosis.

Nonsurvivors compared with survivors had higher frequencies of respiratory failure (98% vs 36%), sepsis (100%, vs 42%), and secondary infections (50% vs 1%).

The average age of survivors was 52 years compared to 69 for those who died. Liu cited weakening of the immune system and increased inflammation, which damages organs and also promotes viral replication, as explanations for the age effect.

From the time of initial symptoms, median time to discharge from the hospital was 22 days. Average time to death was 18.5 days.

Fever persisted for a median of 12 days among all patients, and cough persisted for a median 19 days; 45% of the survivors were still coughing on discharge. In survivors, shortness of breath improved after 13 days, but persisted until death in the others.

Viral shedding persisted for a median duration of 20 days in survivors, ranging from 8 to 37. The virus (SARS-CoV-2) was detectable in nonsurvivors until death. Antiviral treatment did not curtail viral shedding.

But the viral shedding data come with a caveat. “The extended viral shedding noted in our study has important implications for guiding decisions around isolation precautions and antiviral treatment in patients with confirmed COVID-19 infection. However, we need to be clear that viral shedding time should not be confused with other self-isolation guidance for people who may have been exposed to COVID-19 but do not have symptoms, as this guidance is based on the incubation time of the virus,” explained colead author Bin Cao.

“Older age, elevated D-dimer levels, and high SOFA score could help clinicians to identify at an early stage those patients with COVID-19 who have poor prognosis. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future,” the researchers conclude.

A limitation in interpreting the findings of the study is that hospitalized patients do not represent the entire infected population. The researchers caution that “the number of deaths does not reflect the true mortality of COVID-19.” They also note that they did not have enough genetic material to accurately assess duration of viral shedding.

This article first appeared on Medscape.com.

Patients who did not survive hospitalization for COVID-19 in Wuhan were more likely to be older, have comorbidities, and elevated D-dimer, according to the first study to examine risk factors associated with death among adults hospitalized with COVID-19. “Older age, showing signs of sepsis on admission, underlying diseases like high blood pressure and diabetes, and the prolonged use of noninvasive ventilation were important factors in the deaths of these patients,” coauthor Zhibo Liu said in a news release. Abnormal blood clotting was part of the clinical picture too.

Fei Zhou, MD, from the Chinese Academy of Medical Sciences, and colleagues conducted a retrospective, observational, multicenter cohort study of 191 patients, 137 of whom were discharged and 54 of whom died in the hospital.

The study, published online today in The Lancet, included all adult inpatients with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital who had been discharged or died by January 31 of this year. Severely ill patients in the province were transferred to these hospitals until February 1.

The researchers compared demographic, clinical, treatment, and laboratory data from electronic medical records between survivors and those who succumbed to the disease. The analysis also tested serial samples for viral RNA. Overall, 91 (48%) of the 191 patients had comorbidity. Most common was hypertension (30%), followed by diabetes (19%) and coronary heart disease (8%).

The odds of dying in the hospital increased with age (odds ratio 1.10; 95% confidence interval, 1.03-1.17; per year increase in age), higher Sequential Organ Failure Assessment (SOFA) score (5.65, 2.61-12.23; P < .0001), and D-dimer level exceeding 1 mcg/L on admission. The SOFA was previously called the “sepsis-related organ failure assessment score” and assesses rate of organ failure in intensive care units. Elevated D-dimer indicates increased risk of abnormal blood clotting, such as deep vein thrombosis.

Nonsurvivors compared with survivors had higher frequencies of respiratory failure (98% vs 36%), sepsis (100%, vs 42%), and secondary infections (50% vs 1%).

The average age of survivors was 52 years compared to 69 for those who died. Liu cited weakening of the immune system and increased inflammation, which damages organs and also promotes viral replication, as explanations for the age effect.

From the time of initial symptoms, median time to discharge from the hospital was 22 days. Average time to death was 18.5 days.

Fever persisted for a median of 12 days among all patients, and cough persisted for a median 19 days; 45% of the survivors were still coughing on discharge. In survivors, shortness of breath improved after 13 days, but persisted until death in the others.

Viral shedding persisted for a median duration of 20 days in survivors, ranging from 8 to 37. The virus (SARS-CoV-2) was detectable in nonsurvivors until death. Antiviral treatment did not curtail viral shedding.

But the viral shedding data come with a caveat. “The extended viral shedding noted in our study has important implications for guiding decisions around isolation precautions and antiviral treatment in patients with confirmed COVID-19 infection. However, we need to be clear that viral shedding time should not be confused with other self-isolation guidance for people who may have been exposed to COVID-19 but do not have symptoms, as this guidance is based on the incubation time of the virus,” explained colead author Bin Cao.

“Older age, elevated D-dimer levels, and high SOFA score could help clinicians to identify at an early stage those patients with COVID-19 who have poor prognosis. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future,” the researchers conclude.

A limitation in interpreting the findings of the study is that hospitalized patients do not represent the entire infected population. The researchers caution that “the number of deaths does not reflect the true mortality of COVID-19.” They also note that they did not have enough genetic material to accurately assess duration of viral shedding.

This article first appeared on Medscape.com.

Recently, a study in the Journal of the American Heart Association found that taking statins and blood pressure medications doesn’t lead to healthier lifestyles.

copyright Jeffrey Hamilton/Thinkstock

This should surprise no one practicing medicine today. With absolutely no scientific data to back up the next statement, I’m willing to bet a study on oral antiglycemics for type 2 diabetes would yield similar results.

The problem here is that these drugs don’t change human nature, and I’m not belittling their ability to reduce morbidity and mortality.

Developed nations nowadays live in a world of plenty. For most of us, there’s not only no shortage of food options, but the majority of what’s out there is the worst stuff for your health. Salty, dense calories, high-fat, sweetened – for most of us that’s a normal day of eating. It tastes good. Two million years of evolution have programmed us to eat similar stuff because in the wild it sustains survival.

In the city and suburbs, however, that’s not the case.

Food manufacturers make it and stores sell it because, quite bluntly, it makes money. The profit margin for unhealthy stuff is higher than that for fruits and vegetables. If you’re trying to run a successful business, which one would you choose to sell?

As long as people are going to eat unhealthy stuff, others will sell it to them. All the medical breakthroughs in the world won’t change that.

Same with exercise. Some people love to exercise. Some people catch the bug to do it consistently. But most try for a few weeks, usually in January-February, then give up because they don’t have time, or the will, or both.

Medical breakthroughs won’t fix that, either.

There’s also, I suspect, a component of misplaced faith in modern medicine. Like the mysterious “anti-calories” in a can of diet soda. You really do encounter people who think that drinking a diet soda and having a slice of chocolate cake will cancel each other out. Any doctor or nutritionist will scoff at this, but it’s amazing how many people think that doing one good thing (health wise) means you can equally do one bad thing at no penalty. Humans love magical thinking like that.

Unintentionally, the medications contribute to this belief. People figure if they’re lowering blood sugar or lipids, maybe they can eat more steak and ice cream. That’s an unintended consequence of modern medicine. It’s not even limited to nonmedical people. When Lipitor came to market in the late 1990s, one of my attendings called it “a license to eat.” Sadly, as the new study proves, he wasn’t that far from the truth.

People want an easy cure. A pill that makes it all better. That’s human nature. But the real problem, for all the great work we’ve done in medications, is that many patients don’t want to be an active participant in their own care. Exercising and maintaining a healthy diet are hard work, in spite of all the evidence showing their benefits (especially when combined with modern medicine, which is the whole idea in the first place). So it’s much easier for them to place all the responsibility on doctors and medications, and just take a simple pill to fix everything.

As this study shows, it doesn’t work that way.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Recently, a study in the Journal of the American Heart Association found that taking statins and blood pressure medications doesn’t lead to healthier lifestyles.

copyright Jeffrey Hamilton/Thinkstock

This should surprise no one practicing medicine today. With absolutely no scientific data to back up the next statement, I’m willing to bet a study on oral antiglycemics for type 2 diabetes would yield similar results.

The problem here is that these drugs don’t change human nature, and I’m not belittling their ability to reduce morbidity and mortality.

Developed nations nowadays live in a world of plenty. For most of us, there’s not only no shortage of food options, but the majority of what’s out there is the worst stuff for your health. Salty, dense calories, high-fat, sweetened – for most of us that’s a normal day of eating. It tastes good. Two million years of evolution have programmed us to eat similar stuff because in the wild it sustains survival.

In the city and suburbs, however, that’s not the case.

Food manufacturers make it and stores sell it because, quite bluntly, it makes money. The profit margin for unhealthy stuff is higher than that for fruits and vegetables. If you’re trying to run a successful business, which one would you choose to sell?

As long as people are going to eat unhealthy stuff, others will sell it to them. All the medical breakthroughs in the world won’t change that.

Same with exercise. Some people love to exercise. Some people catch the bug to do it consistently. But most try for a few weeks, usually in January-February, then give up because they don’t have time, or the will, or both.

Medical breakthroughs won’t fix that, either.

There’s also, I suspect, a component of misplaced faith in modern medicine. Like the mysterious “anti-calories” in a can of diet soda. You really do encounter people who think that drinking a diet soda and having a slice of chocolate cake will cancel each other out. Any doctor or nutritionist will scoff at this, but it’s amazing how many people think that doing one good thing (health wise) means you can equally do one bad thing at no penalty. Humans love magical thinking like that.

Unintentionally, the medications contribute to this belief. People figure if they’re lowering blood sugar or lipids, maybe they can eat more steak and ice cream. That’s an unintended consequence of modern medicine. It’s not even limited to nonmedical people. When Lipitor came to market in the late 1990s, one of my attendings called it “a license to eat.” Sadly, as the new study proves, he wasn’t that far from the truth.

People want an easy cure. A pill that makes it all better. That’s human nature. But the real problem, for all the great work we’ve done in medications, is that many patients don’t want to be an active participant in their own care. Exercising and maintaining a healthy diet are hard work, in spite of all the evidence showing their benefits (especially when combined with modern medicine, which is the whole idea in the first place). So it’s much easier for them to place all the responsibility on doctors and medications, and just take a simple pill to fix everything.

As this study shows, it doesn’t work that way.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Recently, a study in the Journal of the American Heart Association found that taking statins and blood pressure medications doesn’t lead to healthier lifestyles.

copyright Jeffrey Hamilton/Thinkstock

This should surprise no one practicing medicine today. With absolutely no scientific data to back up the next statement, I’m willing to bet a study on oral antiglycemics for type 2 diabetes would yield similar results.

The problem here is that these drugs don’t change human nature, and I’m not belittling their ability to reduce morbidity and mortality.

Developed nations nowadays live in a world of plenty. For most of us, there’s not only no shortage of food options, but the majority of what’s out there is the worst stuff for your health. Salty, dense calories, high-fat, sweetened – for most of us that’s a normal day of eating. It tastes good. Two million years of evolution have programmed us to eat similar stuff because in the wild it sustains survival.

In the city and suburbs, however, that’s not the case.

Food manufacturers make it and stores sell it because, quite bluntly, it makes money. The profit margin for unhealthy stuff is higher than that for fruits and vegetables. If you’re trying to run a successful business, which one would you choose to sell?

As long as people are going to eat unhealthy stuff, others will sell it to them. All the medical breakthroughs in the world won’t change that.

Same with exercise. Some people love to exercise. Some people catch the bug to do it consistently. But most try for a few weeks, usually in January-February, then give up because they don’t have time, or the will, or both.

Medical breakthroughs won’t fix that, either.

There’s also, I suspect, a component of misplaced faith in modern medicine. Like the mysterious “anti-calories” in a can of diet soda. You really do encounter people who think that drinking a diet soda and having a slice of chocolate cake will cancel each other out. Any doctor or nutritionist will scoff at this, but it’s amazing how many people think that doing one good thing (health wise) means you can equally do one bad thing at no penalty. Humans love magical thinking like that.

Unintentionally, the medications contribute to this belief. People figure if they’re lowering blood sugar or lipids, maybe they can eat more steak and ice cream. That’s an unintended consequence of modern medicine. It’s not even limited to nonmedical people. When Lipitor came to market in the late 1990s, one of my attendings called it “a license to eat.” Sadly, as the new study proves, he wasn’t that far from the truth.

People want an easy cure. A pill that makes it all better. That’s human nature. But the real problem, for all the great work we’ve done in medications, is that many patients don’t want to be an active participant in their own care. Exercising and maintaining a healthy diet are hard work, in spite of all the evidence showing their benefits (especially when combined with modern medicine, which is the whole idea in the first place). So it’s much easier for them to place all the responsibility on doctors and medications, and just take a simple pill to fix everything.

As this study shows, it doesn’t work that way.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

For patients with nonalcoholic steatohepatitis (NASH) with cirrhosis and portal hypertension, belapectin therapy was safe but did not significantly improve fibrosis or hepatic venous pressure gradient, compared with placebo, according to the results of a multicenter phase 2b study.

After 52 weeks of infusions, the change in hepatic venous pressure gradient did not significantly differ between the 2-mg/kg group (–0.28 mm Hg) and the placebo group (0.10 mm Hg) or between the 8-mg/kg group (–0.25 mm Hg) and the placebo group (P = .1 for both comparisons). Belapectin also did not significantly improve fibrosis, nonalcoholic fatty liver disease activity score, or the frequency of various complications of cirrhosis. “However, in a subgroup analysis of patients without esophageal varices, 2 mg/kg belapectin did reduce hepatic venous pressure gradient and development of varices,” wrote Naga Chalasani, MD, of Indiana University in Indianapolis and his associates. The findings were published in Gastroenterology.

NASH leads to portal hypertension, variceal bleeding, ascites with bacterial peritonitis, hepatic encephalopathy, and liver-related death and is a leading reason for liver transplantation among women and men. Galectin-3, which is primarily secreted by macrophages, is elevated in patients with NASH and has been linked to the pathophysiology of liver fibrosis in mice. Belapectin (GR-MD-02), a complex carbohydrate that targets and disrupts galectin-3, has been found to reduce liver fibrosis and portal hypertension in rats and was safe and well tolerated in phase 1 studies.

For this double-blind trial, the researchers randomly assigned 162 patients with NASH, cirrhosis, and portal hypertension (hepatic venous pressure gradient at least 6 mm Hg) to receive biweekly infusions of belapectin 2 mg/kg (54 patients), belapectin 8 mg/kg (54 patients), or placebo (54 patients). Patients were treated for 52 weeks. The primary endpoint was change from baseline in hepatic venous pressure gradient.

In a post-hoc analysis of the 81 patients who had no esophageal varices at baseline, 2 mg/kg belapectin was associated with an average 1.61-mm Hg reduction in hepatic venous pressure gradient from baseline (P = .02) and with a reduction in the development of new varices (P = .03).These effects did not extend to subgroups of patients with varices at baseline, clinically significant portal hypertension, or mild portal hypertension. Moreover, 2 mg/kg belapectin did not improve fibrosis, and the higher dose of belapectin (8 mg/kg) met neither the primary endpoint nor the secondary endpoints in the overall cohort or in subgroup analyses. In the subgroup with no varices at baseline, Galectin Technologies is proceeding to initiating a phase 3 clinical trial.

“Interestingly and somewhat unexpectedly, belapectin was associated with an improvement in hepatocyte ballooning,” which “is considered fundamental to the pathogenesis of disease progression in nonalcoholic steatohepatitis,” the researchers wrote. “The significance of such improvement in hepatocyte ballooning in the absence of improvement of other histological components, especially inflammation, is unknown.”

Galectin Therapeutics provided funding. Dr. Chalasani disclosed grant support from Galectin Therapeutics and relevant consulting relationships with NuSirt, AbbVie, Afimmune (DS Biopharma), and several other pharmaceutical companies. Sixteen coinvestigators also disclosed relationships with pharmaceutical companies, of whom eight disclosed consulting relationships, received research funding, or were employed by Galectin.

SOURCE: Chalasani N et al. Gastroenterology. 2019 Dec 5. doi: 10.1053/j.gastro.2019.11.296.

*This story was updated on 3/18/2020.

For patients with nonalcoholic steatohepatitis (NASH) with cirrhosis and portal hypertension, belapectin therapy was safe but did not significantly improve fibrosis or hepatic venous pressure gradient, compared with placebo, according to the results of a multicenter phase 2b study.

After 52 weeks of infusions, the change in hepatic venous pressure gradient did not significantly differ between the 2-mg/kg group (–0.28 mm Hg) and the placebo group (0.10 mm Hg) or between the 8-mg/kg group (–0.25 mm Hg) and the placebo group (P = .1 for both comparisons). Belapectin also did not significantly improve fibrosis, nonalcoholic fatty liver disease activity score, or the frequency of various complications of cirrhosis. “However, in a subgroup analysis of patients without esophageal varices, 2 mg/kg belapectin did reduce hepatic venous pressure gradient and development of varices,” wrote Naga Chalasani, MD, of Indiana University in Indianapolis and his associates. The findings were published in Gastroenterology.

NASH leads to portal hypertension, variceal bleeding, ascites with bacterial peritonitis, hepatic encephalopathy, and liver-related death and is a leading reason for liver transplantation among women and men. Galectin-3, which is primarily secreted by macrophages, is elevated in patients with NASH and has been linked to the pathophysiology of liver fibrosis in mice. Belapectin (GR-MD-02), a complex carbohydrate that targets and disrupts galectin-3, has been found to reduce liver fibrosis and portal hypertension in rats and was safe and well tolerated in phase 1 studies.

For this double-blind trial, the researchers randomly assigned 162 patients with NASH, cirrhosis, and portal hypertension (hepatic venous pressure gradient at least 6 mm Hg) to receive biweekly infusions of belapectin 2 mg/kg (54 patients), belapectin 8 mg/kg (54 patients), or placebo (54 patients). Patients were treated for 52 weeks. The primary endpoint was change from baseline in hepatic venous pressure gradient.

In a post-hoc analysis of the 81 patients who had no esophageal varices at baseline, 2 mg/kg belapectin was associated with an average 1.61-mm Hg reduction in hepatic venous pressure gradient from baseline (P = .02) and with a reduction in the development of new varices (P = .03).These effects did not extend to subgroups of patients with varices at baseline, clinically significant portal hypertension, or mild portal hypertension. Moreover, 2 mg/kg belapectin did not improve fibrosis, and the higher dose of belapectin (8 mg/kg) met neither the primary endpoint nor the secondary endpoints in the overall cohort or in subgroup analyses. In the subgroup with no varices at baseline, Galectin Technologies is proceeding to initiating a phase 3 clinical trial.

“Interestingly and somewhat unexpectedly, belapectin was associated with an improvement in hepatocyte ballooning,” which “is considered fundamental to the pathogenesis of disease progression in nonalcoholic steatohepatitis,” the researchers wrote. “The significance of such improvement in hepatocyte ballooning in the absence of improvement of other histological components, especially inflammation, is unknown.”

Galectin Therapeutics provided funding. Dr. Chalasani disclosed grant support from Galectin Therapeutics and relevant consulting relationships with NuSirt, AbbVie, Afimmune (DS Biopharma), and several other pharmaceutical companies. Sixteen coinvestigators also disclosed relationships with pharmaceutical companies, of whom eight disclosed consulting relationships, received research funding, or were employed by Galectin.

SOURCE: Chalasani N et al. Gastroenterology. 2019 Dec 5. doi: 10.1053/j.gastro.2019.11.296.

*This story was updated on 3/18/2020.

For patients with nonalcoholic steatohepatitis (NASH) with cirrhosis and portal hypertension, belapectin therapy was safe but did not significantly improve fibrosis or hepatic venous pressure gradient, compared with placebo, according to the results of a multicenter phase 2b study.

After 52 weeks of infusions, the change in hepatic venous pressure gradient did not significantly differ between the 2-mg/kg group (–0.28 mm Hg) and the placebo group (0.10 mm Hg) or between the 8-mg/kg group (–0.25 mm Hg) and the placebo group (P = .1 for both comparisons). Belapectin also did not significantly improve fibrosis, nonalcoholic fatty liver disease activity score, or the frequency of various complications of cirrhosis. “However, in a subgroup analysis of patients without esophageal varices, 2 mg/kg belapectin did reduce hepatic venous pressure gradient and development of varices,” wrote Naga Chalasani, MD, of Indiana University in Indianapolis and his associates. The findings were published in Gastroenterology.

NASH leads to portal hypertension, variceal bleeding, ascites with bacterial peritonitis, hepatic encephalopathy, and liver-related death and is a leading reason for liver transplantation among women and men. Galectin-3, which is primarily secreted by macrophages, is elevated in patients with NASH and has been linked to the pathophysiology of liver fibrosis in mice. Belapectin (GR-MD-02), a complex carbohydrate that targets and disrupts galectin-3, has been found to reduce liver fibrosis and portal hypertension in rats and was safe and well tolerated in phase 1 studies.

For this double-blind trial, the researchers randomly assigned 162 patients with NASH, cirrhosis, and portal hypertension (hepatic venous pressure gradient at least 6 mm Hg) to receive biweekly infusions of belapectin 2 mg/kg (54 patients), belapectin 8 mg/kg (54 patients), or placebo (54 patients). Patients were treated for 52 weeks. The primary endpoint was change from baseline in hepatic venous pressure gradient.

In a post-hoc analysis of the 81 patients who had no esophageal varices at baseline, 2 mg/kg belapectin was associated with an average 1.61-mm Hg reduction in hepatic venous pressure gradient from baseline (P = .02) and with a reduction in the development of new varices (P = .03).These effects did not extend to subgroups of patients with varices at baseline, clinically significant portal hypertension, or mild portal hypertension. Moreover, 2 mg/kg belapectin did not improve fibrosis, and the higher dose of belapectin (8 mg/kg) met neither the primary endpoint nor the secondary endpoints in the overall cohort or in subgroup analyses. In the subgroup with no varices at baseline, Galectin Technologies is proceeding to initiating a phase 3 clinical trial.

“Interestingly and somewhat unexpectedly, belapectin was associated with an improvement in hepatocyte ballooning,” which “is considered fundamental to the pathogenesis of disease progression in nonalcoholic steatohepatitis,” the researchers wrote. “The significance of such improvement in hepatocyte ballooning in the absence of improvement of other histological components, especially inflammation, is unknown.”

Galectin Therapeutics provided funding. Dr. Chalasani disclosed grant support from Galectin Therapeutics and relevant consulting relationships with NuSirt, AbbVie, Afimmune (DS Biopharma), and several other pharmaceutical companies. Sixteen coinvestigators also disclosed relationships with pharmaceutical companies, of whom eight disclosed consulting relationships, received research funding, or were employed by Galectin.

SOURCE: Chalasani N et al. Gastroenterology. 2019 Dec 5. doi: 10.1053/j.gastro.2019.11.296.

*This story was updated on 3/18/2020.

Medicare Part D prescription drug plan beneficiaries could see lower out-of-pocket costs for insulin under a new model launched by the Centers for Medicare & Medicaid Services.

roobcio/Thinkstock

The plan, dubbed the Part D Senior Savings Model, would lower out-of-pocket costs to a maximum of a $35 copay for a 30-day supply throughout the plan year. The agency estimates that beneficiaries enrolling in a plan that is participating in the model would save an average of $446 annually in out-of-pocket costs for insulin.

The maximum copay will apply to all phases of the Part D benefit, including the deductible, initial coverage, and coverage gap phases, according to a fact sheet issued March 11 by the agency. CMS will be proving additional risk corridor protections to Part D plan sponsors to encourage participation in the voluntary model.

The agency has released two requests for application to participate in the model, one for Part D sponsors and one for insulin manufacturers, both of which can be found on a CMS web page providing more details on the program.

The agency said in the fact sheet that, on or around March 20, 2020, it will announce the manufacturers that are participating in the model for the 2021 plan year.

gtwachtman@mdedge.com

Medicare Part D prescription drug plan beneficiaries could see lower out-of-pocket costs for insulin under a new model launched by the Centers for Medicare & Medicaid Services.

roobcio/Thinkstock

The plan, dubbed the Part D Senior Savings Model, would lower out-of-pocket costs to a maximum of a $35 copay for a 30-day supply throughout the plan year. The agency estimates that beneficiaries enrolling in a plan that is participating in the model would save an average of $446 annually in out-of-pocket costs for insulin.

The maximum copay will apply to all phases of the Part D benefit, including the deductible, initial coverage, and coverage gap phases, according to a fact sheet issued March 11 by the agency. CMS will be proving additional risk corridor protections to Part D plan sponsors to encourage participation in the voluntary model.

The agency has released two requests for application to participate in the model, one for Part D sponsors and one for insulin manufacturers, both of which can be found on a CMS web page providing more details on the program.

The agency said in the fact sheet that, on or around March 20, 2020, it will announce the manufacturers that are participating in the model for the 2021 plan year.

gtwachtman@mdedge.com

Medicare Part D prescription drug plan beneficiaries could see lower out-of-pocket costs for insulin under a new model launched by the Centers for Medicare & Medicaid Services.

roobcio/Thinkstock

The plan, dubbed the Part D Senior Savings Model, would lower out-of-pocket costs to a maximum of a $35 copay for a 30-day supply throughout the plan year. The agency estimates that beneficiaries enrolling in a plan that is participating in the model would save an average of $446 annually in out-of-pocket costs for insulin.

The maximum copay will apply to all phases of the Part D benefit, including the deductible, initial coverage, and coverage gap phases, according to a fact sheet issued March 11 by the agency. CMS will be proving additional risk corridor protections to Part D plan sponsors to encourage participation in the voluntary model.

The agency has released two requests for application to participate in the model, one for Part D sponsors and one for insulin manufacturers, both of which can be found on a CMS web page providing more details on the program.

The agency said in the fact sheet that, on or around March 20, 2020, it will announce the manufacturers that are participating in the model for the 2021 plan year.

gtwachtman@mdedge.com

Patients with advanced liver cancer have a new treatment option – the immunotherapy combination of nivolumab (Opdivo, Bristol-Myers Squibb) and ipilimumab (Yervoy, Bristol-Myers Squibb).

The US Food and Drug Administration (FDA) granted an accelerated approval of the combination for use in patients with advanced hepatocellular carcinoma (HCC) who have previously been treated with sorafenib (Nexavar, Bayer). Nivolumab is already approved as monotherapy for use in advanced HCC in patients who have previously been treated with sorafenib.

The immunotherapy combination has shown a response rate that is more than twice that seen with nivolumab alone. The combination was tested at three different dosage schedules in the single-arm phase 1/2 trial known as CheckMate-040, which was conducted in 148 patients with advanced HCC who had previously been treated with sorafenib.

The approval was based on one arm of this trial, a cohort of 49 patients who were treated with nivolumab 1 mg/kg IV and ipilimumab 3 mg/kg IV every 3 weeks for four doses, followed by nivolumab 240 mg every 2 weeks until disease progression or unacceptable toxicity.

After a minimum follow-up of 28 months, 33% (16/49) of these patients showed a response, with 8% (4/49) showing a complete response and 24% (12/49) a partial response.

In terms of duration of responses, 88% of the responses lasted at least 6 months, 56% at least 12 months, and 31% at least 24 months, according to the company.

The results that led to the 2017 approval of nivolumab monotherapy for advanced HCC, as previously reported by Medscape Medical News, come from a cohort of 154 patients who received nivolumab 3 mg/kg administered intravenously every 2 weeks.

The overall response rate was 14.3% (22 of 154 patients), with three patients (1.9%) showing a complete response and 19 patients (12.3%) a partial response. The duration of the responses ranged from 3.2 to 38.2+ months; 91% of those patients had responses of 6 months or longer, and 55% had responses of 12 months or longer.

Notably, patient responses in all arms were achieved regardless of baseline tumor PD-L1 status.
 

Aggressive disease, incidence is rising

“HCC is an aggressive disease in need of different treatment approaches,” said Anthony B. El-Khoueiry, MD, of the Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, in a company press statement.“The overall response rate observed in the Opdivo + Yervoy cohort of the CheckMate-040 trial underscores the potential of this dual immunotherapy as a possible treatment option for patients,” he commented. El-Khoueiry was lead investigator of the study and has received honoraria and consulting fees from Bristol-Myers Squibb.

“The incidence of liver cancer is rising in the United States, and HCC is the most common and aggressive form of the disease,” said Andrea Wilson, president and founder, Blue Faery: The Adrienne Wilson Liver Cancer Association.

“Today’s approval provides a new option for patients with HCC previously treated with sorafenib, giving the community more hope,” she said in the company press statement.

Safety profile

The nivolumab-ipilimumab combination had an “acceptable” safety profile overall in the CheckMate-040 trial, wrote lead study author Thomas Yao, MD, of the University at Hong Kong, China, and colleagues in their study abstract, which was presented at the 2019 annual meeting of the American Society of Clinical Oncology. Yao has received honoraria from Bristol-Myers Squibb and has served as a consultant to the company.

According to those data, 37% of patients had a grade 3-4 treatment-related adverse event (TRAE), the most common of which were pruritus and rash; 5% had grade 3–4 TRAEs that led to discontinuation.

Nivolumab is associated with pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, renal dysfunction, skin adverse reactions, encephalitis, other adverse reactions, and infusion-related reactions, as well as embryo-fetal toxicity. Ipilimumab has a boxed warning for immune-mediated adverse reactions.

Nivolumab alone is approved for use in the treatment of unresectable or metastatic melanoma, non–small cell lung cancer, small cell lung cancer, and classical Hodgkin lymphoma.

The combination of nivolumab with ipilimumab is also approved for use in the treatment of melanoma and renal cell carcinoma.

This article first appeared on Medscape.com.

Patients with advanced liver cancer have a new treatment option – the immunotherapy combination of nivolumab (Opdivo, Bristol-Myers Squibb) and ipilimumab (Yervoy, Bristol-Myers Squibb).

The US Food and Drug Administration (FDA) granted an accelerated approval of the combination for use in patients with advanced hepatocellular carcinoma (HCC) who have previously been treated with sorafenib (Nexavar, Bayer). Nivolumab is already approved as monotherapy for use in advanced HCC in patients who have previously been treated with sorafenib.

The immunotherapy combination has shown a response rate that is more than twice that seen with nivolumab alone. The combination was tested at three different dosage schedules in the single-arm phase 1/2 trial known as CheckMate-040, which was conducted in 148 patients with advanced HCC who had previously been treated with sorafenib.

The approval was based on one arm of this trial, a cohort of 49 patients who were treated with nivolumab 1 mg/kg IV and ipilimumab 3 mg/kg IV every 3 weeks for four doses, followed by nivolumab 240 mg every 2 weeks until disease progression or unacceptable toxicity.

After a minimum follow-up of 28 months, 33% (16/49) of these patients showed a response, with 8% (4/49) showing a complete response and 24% (12/49) a partial response.

In terms of duration of responses, 88% of the responses lasted at least 6 months, 56% at least 12 months, and 31% at least 24 months, according to the company.

The results that led to the 2017 approval of nivolumab monotherapy for advanced HCC, as previously reported by Medscape Medical News, come from a cohort of 154 patients who received nivolumab 3 mg/kg administered intravenously every 2 weeks.

The overall response rate was 14.3% (22 of 154 patients), with three patients (1.9%) showing a complete response and 19 patients (12.3%) a partial response. The duration of the responses ranged from 3.2 to 38.2+ months; 91% of those patients had responses of 6 months or longer, and 55% had responses of 12 months or longer.

Notably, patient responses in all arms were achieved regardless of baseline tumor PD-L1 status.
 

Aggressive disease, incidence is rising

“HCC is an aggressive disease in need of different treatment approaches,” said Anthony B. El-Khoueiry, MD, of the Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, in a company press statement.“The overall response rate observed in the Opdivo + Yervoy cohort of the CheckMate-040 trial underscores the potential of this dual immunotherapy as a possible treatment option for patients,” he commented. El-Khoueiry was lead investigator of the study and has received honoraria and consulting fees from Bristol-Myers Squibb.

“The incidence of liver cancer is rising in the United States, and HCC is the most common and aggressive form of the disease,” said Andrea Wilson, president and founder, Blue Faery: The Adrienne Wilson Liver Cancer Association.

“Today’s approval provides a new option for patients with HCC previously treated with sorafenib, giving the community more hope,” she said in the company press statement.

Safety profile

The nivolumab-ipilimumab combination had an “acceptable” safety profile overall in the CheckMate-040 trial, wrote lead study author Thomas Yao, MD, of the University at Hong Kong, China, and colleagues in their study abstract, which was presented at the 2019 annual meeting of the American Society of Clinical Oncology. Yao has received honoraria from Bristol-Myers Squibb and has served as a consultant to the company.

According to those data, 37% of patients had a grade 3-4 treatment-related adverse event (TRAE), the most common of which were pruritus and rash; 5% had grade 3–4 TRAEs that led to discontinuation.

Nivolumab is associated with pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, renal dysfunction, skin adverse reactions, encephalitis, other adverse reactions, and infusion-related reactions, as well as embryo-fetal toxicity. Ipilimumab has a boxed warning for immune-mediated adverse reactions.

Nivolumab alone is approved for use in the treatment of unresectable or metastatic melanoma, non–small cell lung cancer, small cell lung cancer, and classical Hodgkin lymphoma.

The combination of nivolumab with ipilimumab is also approved for use in the treatment of melanoma and renal cell carcinoma.

This article first appeared on Medscape.com.

Patients with advanced liver cancer have a new treatment option – the immunotherapy combination of nivolumab (Opdivo, Bristol-Myers Squibb) and ipilimumab (Yervoy, Bristol-Myers Squibb).

The US Food and Drug Administration (FDA) granted an accelerated approval of the combination for use in patients with advanced hepatocellular carcinoma (HCC) who have previously been treated with sorafenib (Nexavar, Bayer). Nivolumab is already approved as monotherapy for use in advanced HCC in patients who have previously been treated with sorafenib.

The immunotherapy combination has shown a response rate that is more than twice that seen with nivolumab alone. The combination was tested at three different dosage schedules in the single-arm phase 1/2 trial known as CheckMate-040, which was conducted in 148 patients with advanced HCC who had previously been treated with sorafenib.

The approval was based on one arm of this trial, a cohort of 49 patients who were treated with nivolumab 1 mg/kg IV and ipilimumab 3 mg/kg IV every 3 weeks for four doses, followed by nivolumab 240 mg every 2 weeks until disease progression or unacceptable toxicity.

After a minimum follow-up of 28 months, 33% (16/49) of these patients showed a response, with 8% (4/49) showing a complete response and 24% (12/49) a partial response.

In terms of duration of responses, 88% of the responses lasted at least 6 months, 56% at least 12 months, and 31% at least 24 months, according to the company.

The results that led to the 2017 approval of nivolumab monotherapy for advanced HCC, as previously reported by Medscape Medical News, come from a cohort of 154 patients who received nivolumab 3 mg/kg administered intravenously every 2 weeks.

The overall response rate was 14.3% (22 of 154 patients), with three patients (1.9%) showing a complete response and 19 patients (12.3%) a partial response. The duration of the responses ranged from 3.2 to 38.2+ months; 91% of those patients had responses of 6 months or longer, and 55% had responses of 12 months or longer.

Notably, patient responses in all arms were achieved regardless of baseline tumor PD-L1 status.
 

Aggressive disease, incidence is rising

“HCC is an aggressive disease in need of different treatment approaches,” said Anthony B. El-Khoueiry, MD, of the Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, in a company press statement.“The overall response rate observed in the Opdivo + Yervoy cohort of the CheckMate-040 trial underscores the potential of this dual immunotherapy as a possible treatment option for patients,” he commented. El-Khoueiry was lead investigator of the study and has received honoraria and consulting fees from Bristol-Myers Squibb.

“The incidence of liver cancer is rising in the United States, and HCC is the most common and aggressive form of the disease,” said Andrea Wilson, president and founder, Blue Faery: The Adrienne Wilson Liver Cancer Association.

“Today’s approval provides a new option for patients with HCC previously treated with sorafenib, giving the community more hope,” she said in the company press statement.

Safety profile

The nivolumab-ipilimumab combination had an “acceptable” safety profile overall in the CheckMate-040 trial, wrote lead study author Thomas Yao, MD, of the University at Hong Kong, China, and colleagues in their study abstract, which was presented at the 2019 annual meeting of the American Society of Clinical Oncology. Yao has received honoraria from Bristol-Myers Squibb and has served as a consultant to the company.

According to those data, 37% of patients had a grade 3-4 treatment-related adverse event (TRAE), the most common of which were pruritus and rash; 5% had grade 3–4 TRAEs that led to discontinuation.

Nivolumab is associated with pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, renal dysfunction, skin adverse reactions, encephalitis, other adverse reactions, and infusion-related reactions, as well as embryo-fetal toxicity. Ipilimumab has a boxed warning for immune-mediated adverse reactions.

Nivolumab alone is approved for use in the treatment of unresectable or metastatic melanoma, non–small cell lung cancer, small cell lung cancer, and classical Hodgkin lymphoma.

The combination of nivolumab with ipilimumab is also approved for use in the treatment of melanoma and renal cell carcinoma.

This article first appeared on Medscape.com.

The American College of Rheumatology decided to cancel its upcoming Division & Program Directors Conference and State-of-the-Art Clinical Symposium because of “the escalation in the number of people affected [by the COVID-19 situation], and the likelihood of potentially increasing the exposure to COVID-19.”

The Division & Program Directors Conference was slated to take place March 13-14 in Chicago, while the State-of-the-Art Clinical Symposium was scheduled to happen March 27-29 in New Orleans. In both cases, the organizers are exploring alternative ways to deliver or present the content.

The ACR has not made a decision on the status of its Pediatric Rheumatology Symposium, April 29-May 2, New Orleans, but plans to do so by March 30.

jevans@mdedge.com

The American College of Rheumatology decided to cancel its upcoming Division & Program Directors Conference and State-of-the-Art Clinical Symposium because of “the escalation in the number of people affected [by the COVID-19 situation], and the likelihood of potentially increasing the exposure to COVID-19.”

The Division & Program Directors Conference was slated to take place March 13-14 in Chicago, while the State-of-the-Art Clinical Symposium was scheduled to happen March 27-29 in New Orleans. In both cases, the organizers are exploring alternative ways to deliver or present the content.

The ACR has not made a decision on the status of its Pediatric Rheumatology Symposium, April 29-May 2, New Orleans, but plans to do so by March 30.

jevans@mdedge.com

The American College of Rheumatology decided to cancel its upcoming Division & Program Directors Conference and State-of-the-Art Clinical Symposium because of “the escalation in the number of people affected [by the COVID-19 situation], and the likelihood of potentially increasing the exposure to COVID-19.”

The Division & Program Directors Conference was slated to take place March 13-14 in Chicago, while the State-of-the-Art Clinical Symposium was scheduled to happen March 27-29 in New Orleans. In both cases, the organizers are exploring alternative ways to deliver or present the content.

The ACR has not made a decision on the status of its Pediatric Rheumatology Symposium, April 29-May 2, New Orleans, but plans to do so by March 30.

jevans@mdedge.com

The World Health Organization has formally declared the COVID-19 outbreak a pandemic.

“WHO has been assessing this outbreak around the clock and we are deeply concerned both by the alarming levels of spread and severity, and by the alarming levels of inaction,” WHO Director-General Tedros Adhanom Ghebreyesus said during a March 11 press briefing. “We therefore made the assessment that COVID-19 can be characterized as a pandemic.”

He noted that this is the first time a coronavirus has been seen as a pandemic.

The Director-General cautioned that just looking at the number of countries affected, 114 countries, “does not tell the full story. ... We cannot say this loudly enough, or clearly enough, or often enough: All countries can still change the course of this pandemic.”

He reiterated the need for a whole-of-government and a whole-of-society approach to dealing with this, including taking precautions such as isolating, testing, and treating every case and tracing every contact, as well as readying hospitals and health care professionals.

“Let’s look out for each other, because we need each other,” he said.

gtwachtman@mdedge.com

The World Health Organization has formally declared the COVID-19 outbreak a pandemic.

“WHO has been assessing this outbreak around the clock and we are deeply concerned both by the alarming levels of spread and severity, and by the alarming levels of inaction,” WHO Director-General Tedros Adhanom Ghebreyesus said during a March 11 press briefing. “We therefore made the assessment that COVID-19 can be characterized as a pandemic.”

He noted that this is the first time a coronavirus has been seen as a pandemic.

The Director-General cautioned that just looking at the number of countries affected, 114 countries, “does not tell the full story. ... We cannot say this loudly enough, or clearly enough, or often enough: All countries can still change the course of this pandemic.”

He reiterated the need for a whole-of-government and a whole-of-society approach to dealing with this, including taking precautions such as isolating, testing, and treating every case and tracing every contact, as well as readying hospitals and health care professionals.

“Let’s look out for each other, because we need each other,” he said.

gtwachtman@mdedge.com

The World Health Organization has formally declared the COVID-19 outbreak a pandemic.

“WHO has been assessing this outbreak around the clock and we are deeply concerned both by the alarming levels of spread and severity, and by the alarming levels of inaction,” WHO Director-General Tedros Adhanom Ghebreyesus said during a March 11 press briefing. “We therefore made the assessment that COVID-19 can be characterized as a pandemic.”

He noted that this is the first time a coronavirus has been seen as a pandemic.

The Director-General cautioned that just looking at the number of countries affected, 114 countries, “does not tell the full story. ... We cannot say this loudly enough, or clearly enough, or often enough: All countries can still change the course of this pandemic.”

He reiterated the need for a whole-of-government and a whole-of-society approach to dealing with this, including taking precautions such as isolating, testing, and treating every case and tracing every contact, as well as readying hospitals and health care professionals.

“Let’s look out for each other, because we need each other,” he said.

gtwachtman@mdedge.com

A new indication for the tyrosine kinase inhibitor nintedanib approved by the Food and Drug Administration on March 9, 2020, broadened the drug’s targeted population to include patients with chronic fibrosing interstitial lung diseases with a progressive phenotype.

This new group of patients eligible for nintedanib treatment extends the drug’s labeling beyond patients with idiopathic pulmonary fibrosis (IPF) or interstitial lung disease (ILD) associated with systemic sclerosis or scleroderma, and may come close to doubling the total number of eligible patients.

The new, expanded indication “helps to fulfill an unmet treatment need, as patients with these life-threatening lung diseases have not had an approved medication until now,” said Banu Karimi-Shah, MD, acting deputy director of the division of pulmonary, allergy, and rheumatology products in the FDA’s Center for Drug Evaluation and Research, in a written agency statement that announced the new indication.

The FDA first approved nintedanib (Ofev) for treating IPF in October 2014, and then granted a second indication in September 2019 for ILD associated with systemic sclerosis or scleroderma.

A recent assessment of 1,285 Canadian patients diagnosed with fibrotic ILD and entered into a national registry (CARE-PF) showed that IPF was the associated diagnosis for 25% of patients, and that the majority of patients had other primary diagnoses such as connective tissue disease ILD in 33% of enrolled patients, unclassifiable ILD in 22%, chronic sensitivity pneumonitis in about 8%, sarcoidosis in 3%, as well as other types (BMC Pulm Med. 2019 Nov 27. doi: 10.1186/s12890-019-0986-4).

It remains unclear right now what percentage of patients with fibrotic ILD have the progressive form that would make them eligible for nintedanib treatment under the new indication, but it’s probably about another quarter of the entire ILD population, or roughly similar to the number of patients with an IPF etiology who are already eligible to get the drug, commented Martin Kolb, MD, a professor of respirology at McMaster University, Hamilton, Ont., and a coinvestigator on the CARE-PF registry. A goal of the registry, which has now enrolled nearly 3,700 ILD patients, is to track them serially to get a better handle on the prevalence of progressive disease. The percentage of patients with ILD associated with systemic sclerosis or scleroderma is “relatively small,” compared with these other two patients subgroups, Dr. Kolb said in an interview.

The evidence base for treating patients with progressive ILD is “really strong,” he noted, and comes primarily from a major trial reported last year – the INBUILD study – that randomized 663 patients to treatment with either nintedanib or placebo and showed that nintedanib treatment significantly cut the rate of decline in forced vital capacity during 1 year of treatment (New Engl J Med. 2019 Oct 31;381[18]:1718-27). The patients entered the study as referrals from routine practice with documented ILD with progressive fibrosis that was not responsive to treatment with steroids or other immunosuppressive drugs, and reflects real-world, community practice, Dr. Kolb said.

“Conceptually, it makes so much sense” to treat the patients enrolled in INBUILD, the same patients who fit the new indication, with an agent like nintedanib that slows fibrosis progression, and in some patients may bring progression to a virtual halt, said Dr. Kolb, a coinvestigator on the INBUILD study. Future treatment of these patients will likely involve coupling an antifibrotic drug like nintedanib with an anti-inflammatory agent, although combined treatment of this type needs more study, he noted. In the more than 5 years since nintedanib came onto the U.S. market, it has been used on more than 10,000 patients and has generated no new safety concerns beyond those first included in the drug’s label.

The INBUILD study was sponsored by Boehringer Ingelheim, the company that markets nintedanib. Dr. Kolb has been a consultant to, received honoraria from, and received research funding from Boehringer Ingelheim. He has also received consulting fees or honoraria from Genoa, Gilead, GlaxoSmithKline, Indalo, Prometic, Roche, and Third Pole, and he has received research funding from Actelion, Alkermes, Gilead, GlaxoSmithKline, Pharmaxis, Prometic, RespiVert, and Roche.

mzoler@mdedge.com

A new indication for the tyrosine kinase inhibitor nintedanib approved by the Food and Drug Administration on March 9, 2020, broadened the drug’s targeted population to include patients with chronic fibrosing interstitial lung diseases with a progressive phenotype.

This new group of patients eligible for nintedanib treatment extends the drug’s labeling beyond patients with idiopathic pulmonary fibrosis (IPF) or interstitial lung disease (ILD) associated with systemic sclerosis or scleroderma, and may come close to doubling the total number of eligible patients.

The new, expanded indication “helps to fulfill an unmet treatment need, as patients with these life-threatening lung diseases have not had an approved medication until now,” said Banu Karimi-Shah, MD, acting deputy director of the division of pulmonary, allergy, and rheumatology products in the FDA’s Center for Drug Evaluation and Research, in a written agency statement that announced the new indication.

The FDA first approved nintedanib (Ofev) for treating IPF in October 2014, and then granted a second indication in September 2019 for ILD associated with systemic sclerosis or scleroderma.

A recent assessment of 1,285 Canadian patients diagnosed with fibrotic ILD and entered into a national registry (CARE-PF) showed that IPF was the associated diagnosis for 25% of patients, and that the majority of patients had other primary diagnoses such as connective tissue disease ILD in 33% of enrolled patients, unclassifiable ILD in 22%, chronic sensitivity pneumonitis in about 8%, sarcoidosis in 3%, as well as other types (BMC Pulm Med. 2019 Nov 27. doi: 10.1186/s12890-019-0986-4).

It remains unclear right now what percentage of patients with fibrotic ILD have the progressive form that would make them eligible for nintedanib treatment under the new indication, but it’s probably about another quarter of the entire ILD population, or roughly similar to the number of patients with an IPF etiology who are already eligible to get the drug, commented Martin Kolb, MD, a professor of respirology at McMaster University, Hamilton, Ont., and a coinvestigator on the CARE-PF registry. A goal of the registry, which has now enrolled nearly 3,700 ILD patients, is to track them serially to get a better handle on the prevalence of progressive disease. The percentage of patients with ILD associated with systemic sclerosis or scleroderma is “relatively small,” compared with these other two patients subgroups, Dr. Kolb said in an interview.

The evidence base for treating patients with progressive ILD is “really strong,” he noted, and comes primarily from a major trial reported last year – the INBUILD study – that randomized 663 patients to treatment with either nintedanib or placebo and showed that nintedanib treatment significantly cut the rate of decline in forced vital capacity during 1 year of treatment (New Engl J Med. 2019 Oct 31;381[18]:1718-27). The patients entered the study as referrals from routine practice with documented ILD with progressive fibrosis that was not responsive to treatment with steroids or other immunosuppressive drugs, and reflects real-world, community practice, Dr. Kolb said.

“Conceptually, it makes so much sense” to treat the patients enrolled in INBUILD, the same patients who fit the new indication, with an agent like nintedanib that slows fibrosis progression, and in some patients may bring progression to a virtual halt, said Dr. Kolb, a coinvestigator on the INBUILD study. Future treatment of these patients will likely involve coupling an antifibrotic drug like nintedanib with an anti-inflammatory agent, although combined treatment of this type needs more study, he noted. In the more than 5 years since nintedanib came onto the U.S. market, it has been used on more than 10,000 patients and has generated no new safety concerns beyond those first included in the drug’s label.

The INBUILD study was sponsored by Boehringer Ingelheim, the company that markets nintedanib. Dr. Kolb has been a consultant to, received honoraria from, and received research funding from Boehringer Ingelheim. He has also received consulting fees or honoraria from Genoa, Gilead, GlaxoSmithKline, Indalo, Prometic, Roche, and Third Pole, and he has received research funding from Actelion, Alkermes, Gilead, GlaxoSmithKline, Pharmaxis, Prometic, RespiVert, and Roche.

mzoler@mdedge.com

A new indication for the tyrosine kinase inhibitor nintedanib approved by the Food and Drug Administration on March 9, 2020, broadened the drug’s targeted population to include patients with chronic fibrosing interstitial lung diseases with a progressive phenotype.

This new group of patients eligible for nintedanib treatment extends the drug’s labeling beyond patients with idiopathic pulmonary fibrosis (IPF) or interstitial lung disease (ILD) associated with systemic sclerosis or scleroderma, and may come close to doubling the total number of eligible patients.

The new, expanded indication “helps to fulfill an unmet treatment need, as patients with these life-threatening lung diseases have not had an approved medication until now,” said Banu Karimi-Shah, MD, acting deputy director of the division of pulmonary, allergy, and rheumatology products in the FDA’s Center for Drug Evaluation and Research, in a written agency statement that announced the new indication.

The FDA first approved nintedanib (Ofev) for treating IPF in October 2014, and then granted a second indication in September 2019 for ILD associated with systemic sclerosis or scleroderma.

A recent assessment of 1,285 Canadian patients diagnosed with fibrotic ILD and entered into a national registry (CARE-PF) showed that IPF was the associated diagnosis for 25% of patients, and that the majority of patients had other primary diagnoses such as connective tissue disease ILD in 33% of enrolled patients, unclassifiable ILD in 22%, chronic sensitivity pneumonitis in about 8%, sarcoidosis in 3%, as well as other types (BMC Pulm Med. 2019 Nov 27. doi: 10.1186/s12890-019-0986-4).

It remains unclear right now what percentage of patients with fibrotic ILD have the progressive form that would make them eligible for nintedanib treatment under the new indication, but it’s probably about another quarter of the entire ILD population, or roughly similar to the number of patients with an IPF etiology who are already eligible to get the drug, commented Martin Kolb, MD, a professor of respirology at McMaster University, Hamilton, Ont., and a coinvestigator on the CARE-PF registry. A goal of the registry, which has now enrolled nearly 3,700 ILD patients, is to track them serially to get a better handle on the prevalence of progressive disease. The percentage of patients with ILD associated with systemic sclerosis or scleroderma is “relatively small,” compared with these other two patients subgroups, Dr. Kolb said in an interview.

The evidence base for treating patients with progressive ILD is “really strong,” he noted, and comes primarily from a major trial reported last year – the INBUILD study – that randomized 663 patients to treatment with either nintedanib or placebo and showed that nintedanib treatment significantly cut the rate of decline in forced vital capacity during 1 year of treatment (New Engl J Med. 2019 Oct 31;381[18]:1718-27). The patients entered the study as referrals from routine practice with documented ILD with progressive fibrosis that was not responsive to treatment with steroids or other immunosuppressive drugs, and reflects real-world, community practice, Dr. Kolb said.

“Conceptually, it makes so much sense” to treat the patients enrolled in INBUILD, the same patients who fit the new indication, with an agent like nintedanib that slows fibrosis progression, and in some patients may bring progression to a virtual halt, said Dr. Kolb, a coinvestigator on the INBUILD study. Future treatment of these patients will likely involve coupling an antifibrotic drug like nintedanib with an anti-inflammatory agent, although combined treatment of this type needs more study, he noted. In the more than 5 years since nintedanib came onto the U.S. market, it has been used on more than 10,000 patients and has generated no new safety concerns beyond those first included in the drug’s label.

The INBUILD study was sponsored by Boehringer Ingelheim, the company that markets nintedanib. Dr. Kolb has been a consultant to, received honoraria from, and received research funding from Boehringer Ingelheim. He has also received consulting fees or honoraria from Genoa, Gilead, GlaxoSmithKline, Indalo, Prometic, Roche, and Third Pole, and he has received research funding from Actelion, Alkermes, Gilead, GlaxoSmithKline, Pharmaxis, Prometic, RespiVert, and Roche.

mzoler@mdedge.com

Pancreatic enzyme replacement therapy (PERT) did not significantly alter body weight after pancreatoduodenectomy in the intention-to-treat analysis of a randomized, placebo-controlled trial.

After 3 months of treatment, the PERT group lost an average of 0.68 kg, and the placebo group lost an average of 1.19 kg (P = .302). Low adherence might explain this missed primary endpoint – the 31% of patients who did not adhere to PERT were about four times more likely to lose weight, compared with patients who adhered to PERT (hazard ratio, 4.1, 95% confidence interval, 2.1-7.6), even after possible confounders were controlled for.

In the per-protocol analysis, PERT was associated with an average gain of 1.09 kg in body weight, whereas placebo was associated with an average loss of 2.28 kg (P < .001 for difference between groups). Therefore, clinicians should consider “active education and monitoring” to increase adherence to PERT among patients with pancreatic enzyme insufficiency after pancreatoduodenectomy, wrote Hongbeom Kim of Seoul (South Korea) National University College of Medicine. The findings were published in Clinical Gastroenterology and Hepatology.

Nutritional deficiencies, steatorrhea, bowel issues, and flatulence undermine health and quality of life among these patients, the researchers noted. Although guidelines recommend PERT, doses and indications are not standardized because of insufficient data. To date, most studies have focused on PERT for patients with pancreatic enzyme insufficiency attributable to chronic pancreatitis, not surgery.

This double-blind trial enrolled 304 patients who underwent pancreatoduodenectomy for benign or malignant indications at seven tertiary referral hospitals in South Korea. All patients had a preoperative or postoperative fecal elastase level of 200 mg/g or less. They were randomly assigned to receive thrice-daily capsules with meals consisting of PERT (40,000 FIP lipase, 25,000 FIP amylase, and 1,500 FIP protease) or placebo.

To assess adherence, patients filled out medication diaries and the investigators counted the number of capsules left at 3-month follow-up. “Patients who took more than two-thirds of the total [PERT or placebo] dose without taking other digestive enzymes were considered to have completed the protocol,” the researchers wrote.

In all, 67 patients were excluded from the intention-to-treat analysis because they withdrew consent or were lost to follow-up. Among the remaining 237 patients, PERT did not significantly outperform placebo for the primary endpoint of body weight or for secondary endpoints, including nutritional status and quality of life. The study was powered to assess the intention-to-treat population and hence missed its primary endpoint.

The per-protocol analysis included 71 patients who adhered to PERT and 93 who adhered to placebo. Among these patients, adherence to PERT versus placebo was associated with a 3.37-kg absolute mean increase in body weight (P < .001). [The use] of PERT [also significantly] increased prealbumin and transferrin levels, reflecting short-term nutritional status,” the researchers wrote. “However, no difference in quality of life was observed.”

Subgroup analyses also favored PERT in the per-protocol analysis but not the intention-to-treat analysis, the researchers said. The use of PERT did not significantly affect the frequency of defecation in either the intention-to-treat or the per-protocol analysis.

Korea Pharmbio and the Ministry of Science and ICT provided funding. The researchers reported having no conflicts of interest.

SOURCE: Kim H et al. Clin Gastroenterol Hepatol. 2019 Sep 12. doi: 10.1016/j.cgh.2019.08.061.

Pancreatic enzyme replacement therapy (PERT) did not significantly alter body weight after pancreatoduodenectomy in the intention-to-treat analysis of a randomized, placebo-controlled trial.

After 3 months of treatment, the PERT group lost an average of 0.68 kg, and the placebo group lost an average of 1.19 kg (P = .302). Low adherence might explain this missed primary endpoint – the 31% of patients who did not adhere to PERT were about four times more likely to lose weight, compared with patients who adhered to PERT (hazard ratio, 4.1, 95% confidence interval, 2.1-7.6), even after possible confounders were controlled for.

In the per-protocol analysis, PERT was associated with an average gain of 1.09 kg in body weight, whereas placebo was associated with an average loss of 2.28 kg (P < .001 for difference between groups). Therefore, clinicians should consider “active education and monitoring” to increase adherence to PERT among patients with pancreatic enzyme insufficiency after pancreatoduodenectomy, wrote Hongbeom Kim of Seoul (South Korea) National University College of Medicine. The findings were published in Clinical Gastroenterology and Hepatology.

Nutritional deficiencies, steatorrhea, bowel issues, and flatulence undermine health and quality of life among these patients, the researchers noted. Although guidelines recommend PERT, doses and indications are not standardized because of insufficient data. To date, most studies have focused on PERT for patients with pancreatic enzyme insufficiency attributable to chronic pancreatitis, not surgery.

This double-blind trial enrolled 304 patients who underwent pancreatoduodenectomy for benign or malignant indications at seven tertiary referral hospitals in South Korea. All patients had a preoperative or postoperative fecal elastase level of 200 mg/g or less. They were randomly assigned to receive thrice-daily capsules with meals consisting of PERT (40,000 FIP lipase, 25,000 FIP amylase, and 1,500 FIP protease) or placebo.

To assess adherence, patients filled out medication diaries and the investigators counted the number of capsules left at 3-month follow-up. “Patients who took more than two-thirds of the total [PERT or placebo] dose without taking other digestive enzymes were considered to have completed the protocol,” the researchers wrote.

In all, 67 patients were excluded from the intention-to-treat analysis because they withdrew consent or were lost to follow-up. Among the remaining 237 patients, PERT did not significantly outperform placebo for the primary endpoint of body weight or for secondary endpoints, including nutritional status and quality of life. The study was powered to assess the intention-to-treat population and hence missed its primary endpoint.

The per-protocol analysis included 71 patients who adhered to PERT and 93 who adhered to placebo. Among these patients, adherence to PERT versus placebo was associated with a 3.37-kg absolute mean increase in body weight (P < .001). [The use] of PERT [also significantly] increased prealbumin and transferrin levels, reflecting short-term nutritional status,” the researchers wrote. “However, no difference in quality of life was observed.”

Subgroup analyses also favored PERT in the per-protocol analysis but not the intention-to-treat analysis, the researchers said. The use of PERT did not significantly affect the frequency of defecation in either the intention-to-treat or the per-protocol analysis.

Korea Pharmbio and the Ministry of Science and ICT provided funding. The researchers reported having no conflicts of interest.

SOURCE: Kim H et al. Clin Gastroenterol Hepatol. 2019 Sep 12. doi: 10.1016/j.cgh.2019.08.061.

Pancreatic enzyme replacement therapy (PERT) did not significantly alter body weight after pancreatoduodenectomy in the intention-to-treat analysis of a randomized, placebo-controlled trial.

After 3 months of treatment, the PERT group lost an average of 0.68 kg, and the placebo group lost an average of 1.19 kg (P = .302). Low adherence might explain this missed primary endpoint – the 31% of patients who did not adhere to PERT were about four times more likely to lose weight, compared with patients who adhered to PERT (hazard ratio, 4.1, 95% confidence interval, 2.1-7.6), even after possible confounders were controlled for.

In the per-protocol analysis, PERT was associated with an average gain of 1.09 kg in body weight, whereas placebo was associated with an average loss of 2.28 kg (P < .001 for difference between groups). Therefore, clinicians should consider “active education and monitoring” to increase adherence to PERT among patients with pancreatic enzyme insufficiency after pancreatoduodenectomy, wrote Hongbeom Kim of Seoul (South Korea) National University College of Medicine. The findings were published in Clinical Gastroenterology and Hepatology.

Nutritional deficiencies, steatorrhea, bowel issues, and flatulence undermine health and quality of life among these patients, the researchers noted. Although guidelines recommend PERT, doses and indications are not standardized because of insufficient data. To date, most studies have focused on PERT for patients with pancreatic enzyme insufficiency attributable to chronic pancreatitis, not surgery.

This double-blind trial enrolled 304 patients who underwent pancreatoduodenectomy for benign or malignant indications at seven tertiary referral hospitals in South Korea. All patients had a preoperative or postoperative fecal elastase level of 200 mg/g or less. They were randomly assigned to receive thrice-daily capsules with meals consisting of PERT (40,000 FIP lipase, 25,000 FIP amylase, and 1,500 FIP protease) or placebo.

To assess adherence, patients filled out medication diaries and the investigators counted the number of capsules left at 3-month follow-up. “Patients who took more than two-thirds of the total [PERT or placebo] dose without taking other digestive enzymes were considered to have completed the protocol,” the researchers wrote.

In all, 67 patients were excluded from the intention-to-treat analysis because they withdrew consent or were lost to follow-up. Among the remaining 237 patients, PERT did not significantly outperform placebo for the primary endpoint of body weight or for secondary endpoints, including nutritional status and quality of life. The study was powered to assess the intention-to-treat population and hence missed its primary endpoint.

The per-protocol analysis included 71 patients who adhered to PERT and 93 who adhered to placebo. Among these patients, adherence to PERT versus placebo was associated with a 3.37-kg absolute mean increase in body weight (P < .001). [The use] of PERT [also significantly] increased prealbumin and transferrin levels, reflecting short-term nutritional status,” the researchers wrote. “However, no difference in quality of life was observed.”

Subgroup analyses also favored PERT in the per-protocol analysis but not the intention-to-treat analysis, the researchers said. The use of PERT did not significantly affect the frequency of defecation in either the intention-to-treat or the per-protocol analysis.

Korea Pharmbio and the Ministry of Science and ICT provided funding. The researchers reported having no conflicts of interest.

SOURCE: Kim H et al. Clin Gastroenterol Hepatol. 2019 Sep 12. doi: 10.1016/j.cgh.2019.08.061.

Insomnia symptoms and use of sleep medications is linked to motor vehicle accidents (MVA), and young women with insomnia and reported daytime sleepiness represent a subpopulation at specific risk, according to an analysis of a 5-year population sample. The new research was published online in Sleep and led by Charles Morin, PhD, of Laval University, Quebec City.

The risks of daytime sleepiness and MVA are generally thought of in the context of obstructive sleep apnea (OSA) or men, but the results of the new work suggest that insomnia should not be overlooked, according to Krishna Sundar, MD, clinical professor of pulmonary, critical care, and sleep medicine, and medical director of the Sleep-Wake Center, at the University of Utah, Salt Lake City.

“The notion has been that it may keep them more hypervigilant and less prone to motor vehicle accidents because they are less able to fall asleep even if they want to during the daytime, as compared to other conditions like sleep apnea where there is a higher tendency to doze off,” Dr. Sundar said in an interview.

It should also be remembered that patients aren’t always completely reliable when it comes to self-assessment, according to Brandon M. Seay, MD, a pediatric pulmonologist and sleep specialist at Children’s Healthcare of Atlanta. “Most people with insomnia won’t say they are sleepy in the daytime, but when you objectively look, you do see an element of daytime sleepiness even if it’s not perceived that well by insomnia patients,” said Dr. Seay.

SOURCE: Morin C et al. Sleep. 2020 Feb 29. DOI: 10.1093/sleep/zsaa032.

Insomnia symptoms and use of sleep medications is linked to motor vehicle accidents (MVA), and young women with insomnia and reported daytime sleepiness represent a subpopulation at specific risk, according to an analysis of a 5-year population sample. The new research was published online in Sleep and led by Charles Morin, PhD, of Laval University, Quebec City.

The risks of daytime sleepiness and MVA are generally thought of in the context of obstructive sleep apnea (OSA) or men, but the results of the new work suggest that insomnia should not be overlooked, according to Krishna Sundar, MD, clinical professor of pulmonary, critical care, and sleep medicine, and medical director of the Sleep-Wake Center, at the University of Utah, Salt Lake City.

“The notion has been that it may keep them more hypervigilant and less prone to motor vehicle accidents because they are less able to fall asleep even if they want to during the daytime, as compared to other conditions like sleep apnea where there is a higher tendency to doze off,” Dr. Sundar said in an interview.

It should also be remembered that patients aren’t always completely reliable when it comes to self-assessment, according to Brandon M. Seay, MD, a pediatric pulmonologist and sleep specialist at Children’s Healthcare of Atlanta. “Most people with insomnia won’t say they are sleepy in the daytime, but when you objectively look, you do see an element of daytime sleepiness even if it’s not perceived that well by insomnia patients,” said Dr. Seay.

SOURCE: Morin C et al. Sleep. 2020 Feb 29. DOI: 10.1093/sleep/zsaa032.

Insomnia symptoms and use of sleep medications is linked to motor vehicle accidents (MVA), and young women with insomnia and reported daytime sleepiness represent a subpopulation at specific risk, according to an analysis of a 5-year population sample. The new research was published online in Sleep and led by Charles Morin, PhD, of Laval University, Quebec City.

The risks of daytime sleepiness and MVA are generally thought of in the context of obstructive sleep apnea (OSA) or men, but the results of the new work suggest that insomnia should not be overlooked, according to Krishna Sundar, MD, clinical professor of pulmonary, critical care, and sleep medicine, and medical director of the Sleep-Wake Center, at the University of Utah, Salt Lake City.

“The notion has been that it may keep them more hypervigilant and less prone to motor vehicle accidents because they are less able to fall asleep even if they want to during the daytime, as compared to other conditions like sleep apnea where there is a higher tendency to doze off,” Dr. Sundar said in an interview.

It should also be remembered that patients aren’t always completely reliable when it comes to self-assessment, according to Brandon M. Seay, MD, a pediatric pulmonologist and sleep specialist at Children’s Healthcare of Atlanta. “Most people with insomnia won’t say they are sleepy in the daytime, but when you objectively look, you do see an element of daytime sleepiness even if it’s not perceived that well by insomnia patients,” said Dr. Seay.

SOURCE: Morin C et al. Sleep. 2020 Feb 29. DOI: 10.1093/sleep/zsaa032.