Factors including older age and certain comorbidities have been linked to more serious COVID-19 outcomes in previous research, and now a large dataset collected from hundreds of hospitals nationwide provides more detailed data regarding risk for mechanical ventilation and death.

Comorbidities such as cardiovascular disease, chronic kidney disease, and obesity also were associated with more severe COVID-19 outcomes in this observational study of 11,721 adults. History of pulmonary disease or smoking, interestingly, were not.

One expert urges caution when interpreting the results, however. Although the study found a number of risk factors for ventilation and mortality, she says the dataset lacks information on race and disease severity, and the sample may not be nationally representative. 

The investigators hope their level of granularity will further assist researchers searching for effective treatments and clinicians seeking to triage patients during the COVID-19 pandemic.

The study was published online August 28 in Clinical Infectious Diseases.
 

COVID-19 and comorbidities

“What I found most illuminating was this whole concept of comorbid conditions. This provides suggestive data about who we need to worry about most and who we may need to worry about less,” study author Robert S. Brown Jr, MD, MPH, told Medscape Medical News.

Comorbid conditions included hypertension in 47% of patients, diabetes in 28%, and cardiovascular disease in 19%. Another 16% were obese and 12% had chronic kidney disease. People with comorbid obesity, chronic kidney disease, and cardiovascular disease were more likely to receive mechanical ventilation compared to those without a history of these conditions in an adjusted, multivariable logistic analysis.

With the exception of obesity, the same factors were associated with risk for death during hospitalization.

In contrast, hypertension, history of smoking, and history of pulmonary disease were associated with a lower risk of needing mechanical ventilation and/or lower risk for mortality.

Furthermore, people with liver disease, gastrointestinal diseases, and even autoimmune diseases – which are likely associated with immunosuppression – “are not at that much of an increased risk that we noticed it in our data,” Brown said.

“As I tell many of my patients who have mild liver disease, for example, I would rather have mild liver disease and be on immunosuppressant therapy than be an older, obese male,” he added.

Assessing data for people in 38 U.S. states, and not limiting outcomes to patients in a particular COVID-19 hot spot, was a unique aspect of the research, said Brown, clinical chief of the Division of Gastroenterology and Hepatology at Weill Cornell Medicine in New York City.

Brown, lead author Michael W. Fried, MD, from TARGET PharmaSolutions in Durham, North Carolina, and colleagues studied adults from a commercially available Target Real-World Evidence (RWE) dataset of nearly 70,000 patients. They examined hospital chargemaster data and ICD-10 codes for COVID-19 inpatients between February 15 and April 20.

This population tended to be older, with 60% older than 60 years. A little more than half of participants, 53%, were men.
 

Key findings

A total of 21% of patients died after a median hospital length of stay of 8 days.

Older patients were significantly more likely to die, particularly those older than 60 years (P < .0001).

“This confirms some of the things we know about age and its impact on outcome,” Brown said.

The risk for mortality among patients older than 60 years was 7.2 times that of patients between 18 and 40 years in an adjusted multivariate analysis. The risk for death for those between 41 and 60 years of age was lower (odds ratio [OR], 2.6), compared with the youngest cohort.  

Men were more likely to die than women (OR, 1.5).

When asked if he was surprised by the high mortality rates, Brown said, “Having worked here in New York? No, I was not.”
 

Mechanical ventilation and mortality

Male sex, age older than 40 years, obesity, and presence of cardiovascular or chronic kidney disease were risk factors for mechanical ventilation.

Among the nearly 2,000 hospitalized adults requiring mechanical ventilation in the current report, only 27% were discharged alive. “The outcomes of people who are mechanically ventilated are really quite sobering,” Brown said.

People who ever required mechanical ventilation were 32 times more likely to die compared with others whose highest level of oxygenation was low-flow, high-flow, or no-oxygen therapy in an analysis that controlled for demographics and comorbidities.

Furthermore, patients placed on mechanical ventilation earlier – within 24 hours of admission – tended to experience better outcomes.
 

COVID-19 therapies?

Brown and colleagues also evaluated outcomes in patients who were taking either remdesivir or hydroxychloroquine. A total of 48 people were treated with remdesivir.

The four individuals receiving remdesivir who died were among 11 who were taking remdesivir and also on mechanical ventilation.

“The data for remdesivir is very encouraging,” Brown said.

Many more participants were treated with hydroxychloroquine, more than 4,200 or 36% of the total study population.

A higher proportion of people treated with hydroxychloroquine received mechanical ventilation, at 25%, versus 12% not treated with hydroxychloroquine.

The unadjusted mortality rate was also higher among those treated with the agent, at 25%, compared to 20% not receiving hydroxychloroquine.

The data with hydroxychloroquine can lead to two conclusions, Brown said: “One, it doesn’t work. Or two, it doesn’t work in the way that we use it.”

The researchers cautioned that their hydroxychloroquine findings must be interpreted carefully because those treated with the agent were also more likely to have comorbidities and greater COVID-19 disease severity.

“This study greatly contributes to understanding the natural course of COVID-19 infection by describing characteristics and outcomes of patients with COVID-19 hospitalized throughout the US,” the investigators note. “It identified categories of patients at greatest risk for poor outcomes, which should be used to prioritize prevention and treatment strategies in the future.”
 

Some limitations

“The findings that patients with hypertension and who were smokers had lower ventilation rates, and patients with hypertension, pulmonary disease, who were smokers had lower mortality risks was very surprising,” Ninez A. Ponce, PhD, MPP, told Medscape Medical News when asked to comment on the study.

Although the study identified multiple risk factors for ventilation and mortality, “unfortunately the dataset did not have race available or disease severity,” said Ponce, director of the UCLA Center for Health Policy Research and professor in the Department of Health Policy and Management at the UCLA Fielding School of Public Health.

“These omitted variables could have a considerable effect on the significance, magnitude, and direction of point estimates provided, so I would be cautious in interpreting the results as a picture of a nationally representative sample,” she said.

On a positive note, the study and dataset could illuminate the utility of medications used to treat COVID-19, Ponce said. In addition, as the authors note, “the data will expand over time.” 

Brown has reported receiving grants and consulting for Gilead. Ponce has disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

Factors including older age and certain comorbidities have been linked to more serious COVID-19 outcomes in previous research, and now a large dataset collected from hundreds of hospitals nationwide provides more detailed data regarding risk for mechanical ventilation and death.

Comorbidities such as cardiovascular disease, chronic kidney disease, and obesity also were associated with more severe COVID-19 outcomes in this observational study of 11,721 adults. History of pulmonary disease or smoking, interestingly, were not.

One expert urges caution when interpreting the results, however. Although the study found a number of risk factors for ventilation and mortality, she says the dataset lacks information on race and disease severity, and the sample may not be nationally representative. 

The investigators hope their level of granularity will further assist researchers searching for effective treatments and clinicians seeking to triage patients during the COVID-19 pandemic.

The study was published online August 28 in Clinical Infectious Diseases.
 

COVID-19 and comorbidities

“What I found most illuminating was this whole concept of comorbid conditions. This provides suggestive data about who we need to worry about most and who we may need to worry about less,” study author Robert S. Brown Jr, MD, MPH, told Medscape Medical News.

Comorbid conditions included hypertension in 47% of patients, diabetes in 28%, and cardiovascular disease in 19%. Another 16% were obese and 12% had chronic kidney disease. People with comorbid obesity, chronic kidney disease, and cardiovascular disease were more likely to receive mechanical ventilation compared to those without a history of these conditions in an adjusted, multivariable logistic analysis.

With the exception of obesity, the same factors were associated with risk for death during hospitalization.

In contrast, hypertension, history of smoking, and history of pulmonary disease were associated with a lower risk of needing mechanical ventilation and/or lower risk for mortality.

Furthermore, people with liver disease, gastrointestinal diseases, and even autoimmune diseases – which are likely associated with immunosuppression – “are not at that much of an increased risk that we noticed it in our data,” Brown said.

“As I tell many of my patients who have mild liver disease, for example, I would rather have mild liver disease and be on immunosuppressant therapy than be an older, obese male,” he added.

Assessing data for people in 38 U.S. states, and not limiting outcomes to patients in a particular COVID-19 hot spot, was a unique aspect of the research, said Brown, clinical chief of the Division of Gastroenterology and Hepatology at Weill Cornell Medicine in New York City.

Brown, lead author Michael W. Fried, MD, from TARGET PharmaSolutions in Durham, North Carolina, and colleagues studied adults from a commercially available Target Real-World Evidence (RWE) dataset of nearly 70,000 patients. They examined hospital chargemaster data and ICD-10 codes for COVID-19 inpatients between February 15 and April 20.

This population tended to be older, with 60% older than 60 years. A little more than half of participants, 53%, were men.
 

Key findings

A total of 21% of patients died after a median hospital length of stay of 8 days.

Older patients were significantly more likely to die, particularly those older than 60 years (P < .0001).

“This confirms some of the things we know about age and its impact on outcome,” Brown said.

The risk for mortality among patients older than 60 years was 7.2 times that of patients between 18 and 40 years in an adjusted multivariate analysis. The risk for death for those between 41 and 60 years of age was lower (odds ratio [OR], 2.6), compared with the youngest cohort.  

Men were more likely to die than women (OR, 1.5).

When asked if he was surprised by the high mortality rates, Brown said, “Having worked here in New York? No, I was not.”
 

Mechanical ventilation and mortality

Male sex, age older than 40 years, obesity, and presence of cardiovascular or chronic kidney disease were risk factors for mechanical ventilation.

Among the nearly 2,000 hospitalized adults requiring mechanical ventilation in the current report, only 27% were discharged alive. “The outcomes of people who are mechanically ventilated are really quite sobering,” Brown said.

People who ever required mechanical ventilation were 32 times more likely to die compared with others whose highest level of oxygenation was low-flow, high-flow, or no-oxygen therapy in an analysis that controlled for demographics and comorbidities.

Furthermore, patients placed on mechanical ventilation earlier – within 24 hours of admission – tended to experience better outcomes.
 

COVID-19 therapies?

Brown and colleagues also evaluated outcomes in patients who were taking either remdesivir or hydroxychloroquine. A total of 48 people were treated with remdesivir.

The four individuals receiving remdesivir who died were among 11 who were taking remdesivir and also on mechanical ventilation.

“The data for remdesivir is very encouraging,” Brown said.

Many more participants were treated with hydroxychloroquine, more than 4,200 or 36% of the total study population.

A higher proportion of people treated with hydroxychloroquine received mechanical ventilation, at 25%, versus 12% not treated with hydroxychloroquine.

The unadjusted mortality rate was also higher among those treated with the agent, at 25%, compared to 20% not receiving hydroxychloroquine.

The data with hydroxychloroquine can lead to two conclusions, Brown said: “One, it doesn’t work. Or two, it doesn’t work in the way that we use it.”

The researchers cautioned that their hydroxychloroquine findings must be interpreted carefully because those treated with the agent were also more likely to have comorbidities and greater COVID-19 disease severity.

“This study greatly contributes to understanding the natural course of COVID-19 infection by describing characteristics and outcomes of patients with COVID-19 hospitalized throughout the US,” the investigators note. “It identified categories of patients at greatest risk for poor outcomes, which should be used to prioritize prevention and treatment strategies in the future.”
 

Some limitations

“The findings that patients with hypertension and who were smokers had lower ventilation rates, and patients with hypertension, pulmonary disease, who were smokers had lower mortality risks was very surprising,” Ninez A. Ponce, PhD, MPP, told Medscape Medical News when asked to comment on the study.

Although the study identified multiple risk factors for ventilation and mortality, “unfortunately the dataset did not have race available or disease severity,” said Ponce, director of the UCLA Center for Health Policy Research and professor in the Department of Health Policy and Management at the UCLA Fielding School of Public Health.

“These omitted variables could have a considerable effect on the significance, magnitude, and direction of point estimates provided, so I would be cautious in interpreting the results as a picture of a nationally representative sample,” she said.

On a positive note, the study and dataset could illuminate the utility of medications used to treat COVID-19, Ponce said. In addition, as the authors note, “the data will expand over time.” 

Brown has reported receiving grants and consulting for Gilead. Ponce has disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

Factors including older age and certain comorbidities have been linked to more serious COVID-19 outcomes in previous research, and now a large dataset collected from hundreds of hospitals nationwide provides more detailed data regarding risk for mechanical ventilation and death.

Comorbidities such as cardiovascular disease, chronic kidney disease, and obesity also were associated with more severe COVID-19 outcomes in this observational study of 11,721 adults. History of pulmonary disease or smoking, interestingly, were not.

One expert urges caution when interpreting the results, however. Although the study found a number of risk factors for ventilation and mortality, she says the dataset lacks information on race and disease severity, and the sample may not be nationally representative. 

The investigators hope their level of granularity will further assist researchers searching for effective treatments and clinicians seeking to triage patients during the COVID-19 pandemic.

The study was published online August 28 in Clinical Infectious Diseases.
 

COVID-19 and comorbidities

“What I found most illuminating was this whole concept of comorbid conditions. This provides suggestive data about who we need to worry about most and who we may need to worry about less,” study author Robert S. Brown Jr, MD, MPH, told Medscape Medical News.

Comorbid conditions included hypertension in 47% of patients, diabetes in 28%, and cardiovascular disease in 19%. Another 16% were obese and 12% had chronic kidney disease. People with comorbid obesity, chronic kidney disease, and cardiovascular disease were more likely to receive mechanical ventilation compared to those without a history of these conditions in an adjusted, multivariable logistic analysis.

With the exception of obesity, the same factors were associated with risk for death during hospitalization.

In contrast, hypertension, history of smoking, and history of pulmonary disease were associated with a lower risk of needing mechanical ventilation and/or lower risk for mortality.

Furthermore, people with liver disease, gastrointestinal diseases, and even autoimmune diseases – which are likely associated with immunosuppression – “are not at that much of an increased risk that we noticed it in our data,” Brown said.

“As I tell many of my patients who have mild liver disease, for example, I would rather have mild liver disease and be on immunosuppressant therapy than be an older, obese male,” he added.

Assessing data for people in 38 U.S. states, and not limiting outcomes to patients in a particular COVID-19 hot spot, was a unique aspect of the research, said Brown, clinical chief of the Division of Gastroenterology and Hepatology at Weill Cornell Medicine in New York City.

Brown, lead author Michael W. Fried, MD, from TARGET PharmaSolutions in Durham, North Carolina, and colleagues studied adults from a commercially available Target Real-World Evidence (RWE) dataset of nearly 70,000 patients. They examined hospital chargemaster data and ICD-10 codes for COVID-19 inpatients between February 15 and April 20.

This population tended to be older, with 60% older than 60 years. A little more than half of participants, 53%, were men.
 

Key findings

A total of 21% of patients died after a median hospital length of stay of 8 days.

Older patients were significantly more likely to die, particularly those older than 60 years (P < .0001).

“This confirms some of the things we know about age and its impact on outcome,” Brown said.

The risk for mortality among patients older than 60 years was 7.2 times that of patients between 18 and 40 years in an adjusted multivariate analysis. The risk for death for those between 41 and 60 years of age was lower (odds ratio [OR], 2.6), compared with the youngest cohort.  

Men were more likely to die than women (OR, 1.5).

When asked if he was surprised by the high mortality rates, Brown said, “Having worked here in New York? No, I was not.”
 

Mechanical ventilation and mortality

Male sex, age older than 40 years, obesity, and presence of cardiovascular or chronic kidney disease were risk factors for mechanical ventilation.

Among the nearly 2,000 hospitalized adults requiring mechanical ventilation in the current report, only 27% were discharged alive. “The outcomes of people who are mechanically ventilated are really quite sobering,” Brown said.

People who ever required mechanical ventilation were 32 times more likely to die compared with others whose highest level of oxygenation was low-flow, high-flow, or no-oxygen therapy in an analysis that controlled for demographics and comorbidities.

Furthermore, patients placed on mechanical ventilation earlier – within 24 hours of admission – tended to experience better outcomes.
 

COVID-19 therapies?

Brown and colleagues also evaluated outcomes in patients who were taking either remdesivir or hydroxychloroquine. A total of 48 people were treated with remdesivir.

The four individuals receiving remdesivir who died were among 11 who were taking remdesivir and also on mechanical ventilation.

“The data for remdesivir is very encouraging,” Brown said.

Many more participants were treated with hydroxychloroquine, more than 4,200 or 36% of the total study population.

A higher proportion of people treated with hydroxychloroquine received mechanical ventilation, at 25%, versus 12% not treated with hydroxychloroquine.

The unadjusted mortality rate was also higher among those treated with the agent, at 25%, compared to 20% not receiving hydroxychloroquine.

The data with hydroxychloroquine can lead to two conclusions, Brown said: “One, it doesn’t work. Or two, it doesn’t work in the way that we use it.”

The researchers cautioned that their hydroxychloroquine findings must be interpreted carefully because those treated with the agent were also more likely to have comorbidities and greater COVID-19 disease severity.

“This study greatly contributes to understanding the natural course of COVID-19 infection by describing characteristics and outcomes of patients with COVID-19 hospitalized throughout the US,” the investigators note. “It identified categories of patients at greatest risk for poor outcomes, which should be used to prioritize prevention and treatment strategies in the future.”
 

Some limitations

“The findings that patients with hypertension and who were smokers had lower ventilation rates, and patients with hypertension, pulmonary disease, who were smokers had lower mortality risks was very surprising,” Ninez A. Ponce, PhD, MPP, told Medscape Medical News when asked to comment on the study.

Although the study identified multiple risk factors for ventilation and mortality, “unfortunately the dataset did not have race available or disease severity,” said Ponce, director of the UCLA Center for Health Policy Research and professor in the Department of Health Policy and Management at the UCLA Fielding School of Public Health.

“These omitted variables could have a considerable effect on the significance, magnitude, and direction of point estimates provided, so I would be cautious in interpreting the results as a picture of a nationally representative sample,” she said.

On a positive note, the study and dataset could illuminate the utility of medications used to treat COVID-19, Ponce said. In addition, as the authors note, “the data will expand over time.” 

Brown has reported receiving grants and consulting for Gilead. Ponce has disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

Frequent nightmares are independently linked to an increased risk for cardiovascular disease (CVD), new research shows. In what researchers describe as “surprising” findings, results from a large study of relatively young military veterans showed those who had nightmares two or more times per week had significantly increased risks for hypertension, myocardial infarction, or other heart problems.  

“A diagnosis of PTSD incorporates sleep disturbance as a symptom. Thus, we were surprised to find that nightmares continued to be associated with CVD after controlling not only for PTSD and demographic factors, but also smoking and depression diagnosis,” said Christi Ulmer, PhD, of the department of psychiatry and behavioral sciences, Duke University Medical Center, Durham, N.C.

The findings were presented at the virtual annual meeting of the Associated Professional Sleep Societies.
 

Unclear mechanism

The study included 3,468 veterans (77% male) with a mean age of 38 years who had served one or two tours of duty since Sept. 11, 2001. Nearly one-third (31%) met criteria for PTSD, and 33% self-reported having at least one cardiovascular condition, such as heart problems, hypertension, stroke, and MI.

Nightmare frequency and severity was assessed using the Davidson Trauma Scale. Nightmares were considered frequent if they occurred two or more times per week and moderate to severe if they were at least moderately distressing. About 31% of veterans reported having frequent nightmares, and 35% reported moderately distressing nightmares over the past week.

After adjusting for age, race, and sex, frequent nightmares were associated with hypertension (odds ratio, 1.51; 95% confidence interval, 1.28-1.78), heart problems (OR, 1.50; 95% CI, 1.11-2.02), and MI (OR, 2.32; 95% CI, 1.18-4.54).

Associations between frequent nightmares and hypertension (OR, 1.43; 95% CI, 1.17-1.73) and heart problems (OR, 1.43; 95% CI, 1.00-2.05) remained significant after further adjusting for smoking, depression, and PTSD.

“Our cross-sectional findings set the stage for future research examining the possibility that nightmares may confer cardiovascular disease risks beyond those conferred by PTSD diagnosis alone,” Dr. Ulmer said in a news release.

Dr. Ulmer also said that, because the study was based on self-reported data, the findings are “very preliminary.” Before doctors adjust clinical practices, it’s important that our findings be replicated using longitudinal studies, clinically diagnosed medical conditions, and objectively assessed sleep,” she said.

She added that more research is needed to uncover mechanisms explaining these associations and determine if reducing the frequency and severity of nightmares can lead to improved cardiovascular health.
 

Timely research

Reached for comment, Rajkumar (Raj) Dasgupta, MD, of the University of Southern California, Los Angeles, noted “the correlation between nightmares and heart disease is a timely topic right now with COVID-19 as more people may be having nightmares.”

“If a patient mentions nightmares, I do think it’s important not to just glaze over it, but to talk more about it and document it in the patient record, especially in patients with cardiovascular disease, atrial fibrillation, diabetes, and hypertension,” said Dr. Dasgupta, who wasn’t involved in the study.

The research was supported by the Veterans Integrated Service Network 6 Mental Illness Research, Education and Clinical Center and the Department of Veterans Affairs HSR&D ADAPT Center at the Durham VA Health Care System. Dr. Ulmer and Dr. Dasgupta have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Frequent nightmares are independently linked to an increased risk for cardiovascular disease (CVD), new research shows. In what researchers describe as “surprising” findings, results from a large study of relatively young military veterans showed those who had nightmares two or more times per week had significantly increased risks for hypertension, myocardial infarction, or other heart problems.  

“A diagnosis of PTSD incorporates sleep disturbance as a symptom. Thus, we were surprised to find that nightmares continued to be associated with CVD after controlling not only for PTSD and demographic factors, but also smoking and depression diagnosis,” said Christi Ulmer, PhD, of the department of psychiatry and behavioral sciences, Duke University Medical Center, Durham, N.C.

The findings were presented at the virtual annual meeting of the Associated Professional Sleep Societies.
 

Unclear mechanism

The study included 3,468 veterans (77% male) with a mean age of 38 years who had served one or two tours of duty since Sept. 11, 2001. Nearly one-third (31%) met criteria for PTSD, and 33% self-reported having at least one cardiovascular condition, such as heart problems, hypertension, stroke, and MI.

Nightmare frequency and severity was assessed using the Davidson Trauma Scale. Nightmares were considered frequent if they occurred two or more times per week and moderate to severe if they were at least moderately distressing. About 31% of veterans reported having frequent nightmares, and 35% reported moderately distressing nightmares over the past week.

After adjusting for age, race, and sex, frequent nightmares were associated with hypertension (odds ratio, 1.51; 95% confidence interval, 1.28-1.78), heart problems (OR, 1.50; 95% CI, 1.11-2.02), and MI (OR, 2.32; 95% CI, 1.18-4.54).

Associations between frequent nightmares and hypertension (OR, 1.43; 95% CI, 1.17-1.73) and heart problems (OR, 1.43; 95% CI, 1.00-2.05) remained significant after further adjusting for smoking, depression, and PTSD.

“Our cross-sectional findings set the stage for future research examining the possibility that nightmares may confer cardiovascular disease risks beyond those conferred by PTSD diagnosis alone,” Dr. Ulmer said in a news release.

Dr. Ulmer also said that, because the study was based on self-reported data, the findings are “very preliminary.” Before doctors adjust clinical practices, it’s important that our findings be replicated using longitudinal studies, clinically diagnosed medical conditions, and objectively assessed sleep,” she said.

She added that more research is needed to uncover mechanisms explaining these associations and determine if reducing the frequency and severity of nightmares can lead to improved cardiovascular health.
 

Timely research

Reached for comment, Rajkumar (Raj) Dasgupta, MD, of the University of Southern California, Los Angeles, noted “the correlation between nightmares and heart disease is a timely topic right now with COVID-19 as more people may be having nightmares.”

“If a patient mentions nightmares, I do think it’s important not to just glaze over it, but to talk more about it and document it in the patient record, especially in patients with cardiovascular disease, atrial fibrillation, diabetes, and hypertension,” said Dr. Dasgupta, who wasn’t involved in the study.

The research was supported by the Veterans Integrated Service Network 6 Mental Illness Research, Education and Clinical Center and the Department of Veterans Affairs HSR&D ADAPT Center at the Durham VA Health Care System. Dr. Ulmer and Dr. Dasgupta have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Frequent nightmares are independently linked to an increased risk for cardiovascular disease (CVD), new research shows. In what researchers describe as “surprising” findings, results from a large study of relatively young military veterans showed those who had nightmares two or more times per week had significantly increased risks for hypertension, myocardial infarction, or other heart problems.  

“A diagnosis of PTSD incorporates sleep disturbance as a symptom. Thus, we were surprised to find that nightmares continued to be associated with CVD after controlling not only for PTSD and demographic factors, but also smoking and depression diagnosis,” said Christi Ulmer, PhD, of the department of psychiatry and behavioral sciences, Duke University Medical Center, Durham, N.C.

The findings were presented at the virtual annual meeting of the Associated Professional Sleep Societies.
 

Unclear mechanism

The study included 3,468 veterans (77% male) with a mean age of 38 years who had served one or two tours of duty since Sept. 11, 2001. Nearly one-third (31%) met criteria for PTSD, and 33% self-reported having at least one cardiovascular condition, such as heart problems, hypertension, stroke, and MI.

Nightmare frequency and severity was assessed using the Davidson Trauma Scale. Nightmares were considered frequent if they occurred two or more times per week and moderate to severe if they were at least moderately distressing. About 31% of veterans reported having frequent nightmares, and 35% reported moderately distressing nightmares over the past week.

After adjusting for age, race, and sex, frequent nightmares were associated with hypertension (odds ratio, 1.51; 95% confidence interval, 1.28-1.78), heart problems (OR, 1.50; 95% CI, 1.11-2.02), and MI (OR, 2.32; 95% CI, 1.18-4.54).

Associations between frequent nightmares and hypertension (OR, 1.43; 95% CI, 1.17-1.73) and heart problems (OR, 1.43; 95% CI, 1.00-2.05) remained significant after further adjusting for smoking, depression, and PTSD.

“Our cross-sectional findings set the stage for future research examining the possibility that nightmares may confer cardiovascular disease risks beyond those conferred by PTSD diagnosis alone,” Dr. Ulmer said in a news release.

Dr. Ulmer also said that, because the study was based on self-reported data, the findings are “very preliminary.” Before doctors adjust clinical practices, it’s important that our findings be replicated using longitudinal studies, clinically diagnosed medical conditions, and objectively assessed sleep,” she said.

She added that more research is needed to uncover mechanisms explaining these associations and determine if reducing the frequency and severity of nightmares can lead to improved cardiovascular health.
 

Timely research

Reached for comment, Rajkumar (Raj) Dasgupta, MD, of the University of Southern California, Los Angeles, noted “the correlation between nightmares and heart disease is a timely topic right now with COVID-19 as more people may be having nightmares.”

“If a patient mentions nightmares, I do think it’s important not to just glaze over it, but to talk more about it and document it in the patient record, especially in patients with cardiovascular disease, atrial fibrillation, diabetes, and hypertension,” said Dr. Dasgupta, who wasn’t involved in the study.

The research was supported by the Veterans Integrated Service Network 6 Mental Illness Research, Education and Clinical Center and the Department of Veterans Affairs HSR&D ADAPT Center at the Durham VA Health Care System. Dr. Ulmer and Dr. Dasgupta have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Malignant melanomas in children and adolescents are thankfully rare, but they can be challenging to diagnose, and fatal disease can manifest itself in any of several different ways, results of a retrospective multicenter study showed.

“The most striking thing that we learned from this study is that pediatric melanoma can present in so many different ways, and it’s distinct from the adult population in that we see more presentations associated with congenital nevi, or spitz melanoma, which is a special class of pigmented lesions that looks a little different under the microscope,” Elena B. Hawryluk, MD, PhD, of the department of dermatology at Massachusetts General Hospital (MGH) and Harvard University, Boston, said in an interview. Dr. Hawryluk is lead author of the study, which was published online ahead of print in the Journal of the American Academy of Dermatology.

Dr. Hawryluk and colleagues at MGH and 11 other centers conducted a retrospective review of all cases of fatal pediatric melanoma among patients younger than 20 years diagnosed from late 1994 through early 2017.

They identified a total of 38 fatal cases over more than 2 decades. The cases were distinguished primarily by their heterogeneous clinical presentation and by the diversity of the patients, their precursor lesions, and the tumor histopathology, she said in an interview.

“We were surprised to find that patients with each of these presentations could end up with a fatal course, it wasn’t just all the adolescents, or all the patients with giant congenital nevi; it really presented quite diversely.”
 

Rare malignancy

Melanoma is far less common in the pediatric population than in adults, with an annual incidence of 18 per 1 million among adolescents aged 15-18 years, and 1 per 1 million in children under 10 years, the authors noted.

“Melanoma in children and adolescents often has distinct clinical presentations such as association with a congenital melanocytic nevus (CMN), spitzoid melanoma, or amelanotic melanoma, which are more rarely observed in adult melanoma patients. Unique pediatric-specific clinical detection criteria have been proposed to highlight these differences, such as a tendency to present amelanotically,” they wrote.

Factors associated with worse prognosis, such as higher Breslow thickness and mitotic index, are more frequently present at the time of diagnosis in children compared with adults, particularly those diagnosed before age 11 years.

“It is unclear if this difference is secondary to diagnostic delays due to low clinical suspicion, atypical clinical presentations, or more rapid tumor growth rate, as many childhood melanomas are of nodular or spitzoid subtypes,” Dr. Hawryluk and her coauthors wrote.
 

Study details

The investigators sought to characterize the clinical and histopathologic features of fatal pediatric melanomas.

They found that 21 of the 38 patients (57%) were of White heritage, 7 (19%) were of Hispanic or Latino background, 1 (3%) was of Asian lineage, and 1 each were of Black African American or Black Hispanic background. The remaining children were classified as “other” or did not have their ethnic backgrounds recorded.

The “striking prevalence” of Hispanic patients observed in the study is consistent with surveillance reports of an increasing incidence of melanoma among children of Hispanic background, they noted.

The mean age at diagnosis was 12.7 years, and the mean age at death was 15.6 years.

Of the 16 cases with known identifiable disease subtypes, 8 (50%) were nodular, 5 (31%) were superficial spreading, and 3 (19%) were spitzoid melanomas. Of the 38 fatal melanomas, 10 were thought to have originated from congenital melanocytic nevi.
 

Outlook improving

Recent therapeutic breakthroughs such as targeted agents and immunotherapy with checkpoint inhibitors augur well for children diagnosed with melanoma, Dr. Hawryluk said.

“Fortunately, it’s not superaggressive in children at high frequency, so we generally use adult algorithms to inform treatment decisions,” she said. “It’s just important to note that melanomas that arise in congenital nevi tend to have different driver mutations than those that arise in older patients who may have lots of sun exposure.”

“Nowadays, we’re lucky to have a lot of extra tests and workups so that, if a patient does have metastatic or advance disease, they can have a better genetic profile that would guide our choice of medications,” she added.

The study was supported by a Pediatric Dermatology Research Alliance Study Support grant and Society for Pediatric Dermatology, Pediatric Dermatology Research Alliance Pilot award. Dr. Hawryluk is supported by the Dermatology Foundation and the Harvard Medical School Eleanor and Miles Shore Fellowship award. The authors reported no conflicts of interest.

SOURCE: Hawryluk EB et al. J Am Acad Dermatol. 2020 Jul 1. doi: 10.1016/j.jaad.2020.06.1010.

Malignant melanomas in children and adolescents are thankfully rare, but they can be challenging to diagnose, and fatal disease can manifest itself in any of several different ways, results of a retrospective multicenter study showed.

“The most striking thing that we learned from this study is that pediatric melanoma can present in so many different ways, and it’s distinct from the adult population in that we see more presentations associated with congenital nevi, or spitz melanoma, which is a special class of pigmented lesions that looks a little different under the microscope,” Elena B. Hawryluk, MD, PhD, of the department of dermatology at Massachusetts General Hospital (MGH) and Harvard University, Boston, said in an interview. Dr. Hawryluk is lead author of the study, which was published online ahead of print in the Journal of the American Academy of Dermatology.

Dr. Hawryluk and colleagues at MGH and 11 other centers conducted a retrospective review of all cases of fatal pediatric melanoma among patients younger than 20 years diagnosed from late 1994 through early 2017.

They identified a total of 38 fatal cases over more than 2 decades. The cases were distinguished primarily by their heterogeneous clinical presentation and by the diversity of the patients, their precursor lesions, and the tumor histopathology, she said in an interview.

“We were surprised to find that patients with each of these presentations could end up with a fatal course, it wasn’t just all the adolescents, or all the patients with giant congenital nevi; it really presented quite diversely.”
 

Rare malignancy

Melanoma is far less common in the pediatric population than in adults, with an annual incidence of 18 per 1 million among adolescents aged 15-18 years, and 1 per 1 million in children under 10 years, the authors noted.

“Melanoma in children and adolescents often has distinct clinical presentations such as association with a congenital melanocytic nevus (CMN), spitzoid melanoma, or amelanotic melanoma, which are more rarely observed in adult melanoma patients. Unique pediatric-specific clinical detection criteria have been proposed to highlight these differences, such as a tendency to present amelanotically,” they wrote.

Factors associated with worse prognosis, such as higher Breslow thickness and mitotic index, are more frequently present at the time of diagnosis in children compared with adults, particularly those diagnosed before age 11 years.

“It is unclear if this difference is secondary to diagnostic delays due to low clinical suspicion, atypical clinical presentations, or more rapid tumor growth rate, as many childhood melanomas are of nodular or spitzoid subtypes,” Dr. Hawryluk and her coauthors wrote.
 

Study details

The investigators sought to characterize the clinical and histopathologic features of fatal pediatric melanomas.

They found that 21 of the 38 patients (57%) were of White heritage, 7 (19%) were of Hispanic or Latino background, 1 (3%) was of Asian lineage, and 1 each were of Black African American or Black Hispanic background. The remaining children were classified as “other” or did not have their ethnic backgrounds recorded.

The “striking prevalence” of Hispanic patients observed in the study is consistent with surveillance reports of an increasing incidence of melanoma among children of Hispanic background, they noted.

The mean age at diagnosis was 12.7 years, and the mean age at death was 15.6 years.

Of the 16 cases with known identifiable disease subtypes, 8 (50%) were nodular, 5 (31%) were superficial spreading, and 3 (19%) were spitzoid melanomas. Of the 38 fatal melanomas, 10 were thought to have originated from congenital melanocytic nevi.
 

Outlook improving

Recent therapeutic breakthroughs such as targeted agents and immunotherapy with checkpoint inhibitors augur well for children diagnosed with melanoma, Dr. Hawryluk said.

“Fortunately, it’s not superaggressive in children at high frequency, so we generally use adult algorithms to inform treatment decisions,” she said. “It’s just important to note that melanomas that arise in congenital nevi tend to have different driver mutations than those that arise in older patients who may have lots of sun exposure.”

“Nowadays, we’re lucky to have a lot of extra tests and workups so that, if a patient does have metastatic or advance disease, they can have a better genetic profile that would guide our choice of medications,” she added.

The study was supported by a Pediatric Dermatology Research Alliance Study Support grant and Society for Pediatric Dermatology, Pediatric Dermatology Research Alliance Pilot award. Dr. Hawryluk is supported by the Dermatology Foundation and the Harvard Medical School Eleanor and Miles Shore Fellowship award. The authors reported no conflicts of interest.

SOURCE: Hawryluk EB et al. J Am Acad Dermatol. 2020 Jul 1. doi: 10.1016/j.jaad.2020.06.1010.

Malignant melanomas in children and adolescents are thankfully rare, but they can be challenging to diagnose, and fatal disease can manifest itself in any of several different ways, results of a retrospective multicenter study showed.

“The most striking thing that we learned from this study is that pediatric melanoma can present in so many different ways, and it’s distinct from the adult population in that we see more presentations associated with congenital nevi, or spitz melanoma, which is a special class of pigmented lesions that looks a little different under the microscope,” Elena B. Hawryluk, MD, PhD, of the department of dermatology at Massachusetts General Hospital (MGH) and Harvard University, Boston, said in an interview. Dr. Hawryluk is lead author of the study, which was published online ahead of print in the Journal of the American Academy of Dermatology.

Dr. Hawryluk and colleagues at MGH and 11 other centers conducted a retrospective review of all cases of fatal pediatric melanoma among patients younger than 20 years diagnosed from late 1994 through early 2017.

They identified a total of 38 fatal cases over more than 2 decades. The cases were distinguished primarily by their heterogeneous clinical presentation and by the diversity of the patients, their precursor lesions, and the tumor histopathology, she said in an interview.

“We were surprised to find that patients with each of these presentations could end up with a fatal course, it wasn’t just all the adolescents, or all the patients with giant congenital nevi; it really presented quite diversely.”
 

Rare malignancy

Melanoma is far less common in the pediatric population than in adults, with an annual incidence of 18 per 1 million among adolescents aged 15-18 years, and 1 per 1 million in children under 10 years, the authors noted.

“Melanoma in children and adolescents often has distinct clinical presentations such as association with a congenital melanocytic nevus (CMN), spitzoid melanoma, or amelanotic melanoma, which are more rarely observed in adult melanoma patients. Unique pediatric-specific clinical detection criteria have been proposed to highlight these differences, such as a tendency to present amelanotically,” they wrote.

Factors associated with worse prognosis, such as higher Breslow thickness and mitotic index, are more frequently present at the time of diagnosis in children compared with adults, particularly those diagnosed before age 11 years.

“It is unclear if this difference is secondary to diagnostic delays due to low clinical suspicion, atypical clinical presentations, or more rapid tumor growth rate, as many childhood melanomas are of nodular or spitzoid subtypes,” Dr. Hawryluk and her coauthors wrote.
 

Study details

The investigators sought to characterize the clinical and histopathologic features of fatal pediatric melanomas.

They found that 21 of the 38 patients (57%) were of White heritage, 7 (19%) were of Hispanic or Latino background, 1 (3%) was of Asian lineage, and 1 each were of Black African American or Black Hispanic background. The remaining children were classified as “other” or did not have their ethnic backgrounds recorded.

The “striking prevalence” of Hispanic patients observed in the study is consistent with surveillance reports of an increasing incidence of melanoma among children of Hispanic background, they noted.

The mean age at diagnosis was 12.7 years, and the mean age at death was 15.6 years.

Of the 16 cases with known identifiable disease subtypes, 8 (50%) were nodular, 5 (31%) were superficial spreading, and 3 (19%) were spitzoid melanomas. Of the 38 fatal melanomas, 10 were thought to have originated from congenital melanocytic nevi.
 

Outlook improving

Recent therapeutic breakthroughs such as targeted agents and immunotherapy with checkpoint inhibitors augur well for children diagnosed with melanoma, Dr. Hawryluk said.

“Fortunately, it’s not superaggressive in children at high frequency, so we generally use adult algorithms to inform treatment decisions,” she said. “It’s just important to note that melanomas that arise in congenital nevi tend to have different driver mutations than those that arise in older patients who may have lots of sun exposure.”

“Nowadays, we’re lucky to have a lot of extra tests and workups so that, if a patient does have metastatic or advance disease, they can have a better genetic profile that would guide our choice of medications,” she added.

The study was supported by a Pediatric Dermatology Research Alliance Study Support grant and Society for Pediatric Dermatology, Pediatric Dermatology Research Alliance Pilot award. Dr. Hawryluk is supported by the Dermatology Foundation and the Harvard Medical School Eleanor and Miles Shore Fellowship award. The authors reported no conflicts of interest.

SOURCE: Hawryluk EB et al. J Am Acad Dermatol. 2020 Jul 1. doi: 10.1016/j.jaad.2020.06.1010.

A study of more than 60,000 prostate cancer patients suggests it is safe to delay radiation therapy (RT) for at least 6 months for localized higher-risk disease being treated with androgen deprivation therapy.

These findings are relevant to oncology care in the COVID-19 era, as the pandemic has complicated delivery of radiation therapy (RT) in several ways, the study authors wrote in JAMA Oncology.

“Daily hospital trips for RT create many possible points of COVID-19 transmission, and patients with cancer are at high risk of COVID-19 mortality,” Edward Christopher Dee, a research fellow at Dana-Farber Cancer Institute in Boston, and colleagues wrote.

To assess the safety of delaying RT, the investigators analyzed National Cancer Database data for 63,858 men with localized but unfavorable intermediate-risk, high-risk, or very-high-risk prostate cancer diagnosed during 2004-2014 and managed with external beam RT and androgen deprivation therapy (ADT).

Only 5.6% of patients (n = 3,572) initiated their RT 0-60 days before starting ADT. Another 36.3% (n = 23,207) initiated RT 1-60 days after starting ADT, 47.4% (n = 30,285) initiated RT 61-120 days after starting ADT, and 10.6% (n = 6,794) initiated RT 121-180 days after starting ADT.

The investigators found that 10-year overall survival rates were similar regardless of when patients started RT.

Multivariate analysis in the unfavorable intermediate-risk group showed that, relative to peers who started RT before ADT, men initiating RT later did not have significantly poorer overall survival, regardless of whether RT was initiated 1-60 days after starting ADT (hazard ratio for death, 1.03; P = .64), 61-120 days after (HR, 0.95; P = .42), or 121-180 days after (HR, 0.99; P = .90).

Findings were similar in the combined high-risk and very-high-risk group, with no significant elevation of mortality risk for patients initiating RT 1-60 days after starting ADT (HR, 1.07; P = .12), 61-120 days after (HR, 1.04; P = .36), or 121-180 days after (HR, 1.07; P = .17).

“These results validate the findings of two prior randomized trials and possibly justify the delay of prostate RT for patients currently receiving ADT until COVID-19 infection rates in the community and hospitals are lower,” the authors wrote.

Despite the fairly short follow-up period and other study limitations, “if COVID-19 outbreaks continue to occur sporadically during the coming months to years, these data could allow future flexibility about the timing of RT initiation,” the authors concluded.
 

Experts weigh in

“Overall, this study is asking a good question given the COVID situation and the fact that many providers are delaying RT due to COVID concerns of patients and providers,” Colleen A. Lawton, MD, of the Medical College of Wisconsin, Milwaukee, commented in an interview.

At the same time, Dr. Lawton cautioned about oversimplifying the issue, noting that results of the Radiation Therapy Oncology Group (RTOG) 9413 trial suggest important interactions between the anatomic extent of RT and the timing of ADT on outcomes (Int J Radiat Oncol Biol Phys. 2007 Nov 1;69[3]:646-55).

“I have certainly delayed some of my own patients with ADT during the COVID pandemic,” she reported. “No one knows what the maximum acceptable delay should be. A few months is likely not a problem, and a year is probably too much, but scientifically, we just don’t know.”

The interplay of volume irradiated and ADT timing is relevant here, agreed Mack Roach III, MD, of University of California, San Francisco.

In addition, the study did not address why ADT was given when it was, the duration of this therapy, and endpoints other than overall survival (such as prostate-specific antigen failure rate) that may better reflect the effectiveness of cancer treatment.

“Yes, delays are safe for patients on ADT, but not for the reasons stated. A more appropriate source of data is RTOG 9910, which compared 28 versus 8 weeks of ADT prior to RT for mostly intermediate-risk prostate cancer patients with comparable results,” Dr. Roach noted (J Clin Oncol. 2015 Feb 1;33[4]:332-9).

“Delay duration should be based on the risk of disease, but 6 months is probably safe, especially if on ADT,” he said.

Michael J. Zelefsky, MD, of Memorial Sloan Kettering Cancer Center in New York, said he agreed with the investigators’ main conclusions. “Once ADT suppression is achieved, maintaining patients on this regimen for 6 months would not likely lead to the development of a castrate-resistant state where radiotherapy would be less effective,” he elaborated.

However, limitations of the database used preclude conclusions about the safety of longer delays or the impact on other outcomes, he cautioned.

“This study provides further support to the accepted notion that delays of up to 6 months prior to initiation of planned prostate radiation would be safe and appropriate, especially where concerns of COVID outbreaks may present significant logistic challenges and concerns for the patient, who needs to commit to a course of daily radiation treatments, which could span for 5-8 weeks,” Dr. Zelefsky said.

“We have, in fact, adopted this approach in our clinics during the COVID outbreaks in New York,” he reported. “Most of our patients with unfavorable intermediate- or high-risk disease were initiated on ADT planned for at least 4-6 months before the radiotherapy was initiated. In addition, for these reasons, our preference has been to also offer such patients, if feasible, an ultrahypofractionated treatment course where the radiotherapy course is completed in five fractions over 1-2 weeks.”

This research was funded by the National Institutes of Health. The authors disclosed various grants and personal fees outside the submitted work. Dr. Lawton disclosed that she was a coauthor on RTOG 9413. Dr. Roach and Dr. Zelefsky disclosed no relevant conflicts of interest.

SOURCE: Dee EC et al. JAMA Oncol. 2020 Aug 13. doi: 10.1001/jamaoncol.2020.3545.

A study of more than 60,000 prostate cancer patients suggests it is safe to delay radiation therapy (RT) for at least 6 months for localized higher-risk disease being treated with androgen deprivation therapy.

These findings are relevant to oncology care in the COVID-19 era, as the pandemic has complicated delivery of radiation therapy (RT) in several ways, the study authors wrote in JAMA Oncology.

“Daily hospital trips for RT create many possible points of COVID-19 transmission, and patients with cancer are at high risk of COVID-19 mortality,” Edward Christopher Dee, a research fellow at Dana-Farber Cancer Institute in Boston, and colleagues wrote.

To assess the safety of delaying RT, the investigators analyzed National Cancer Database data for 63,858 men with localized but unfavorable intermediate-risk, high-risk, or very-high-risk prostate cancer diagnosed during 2004-2014 and managed with external beam RT and androgen deprivation therapy (ADT).

Only 5.6% of patients (n = 3,572) initiated their RT 0-60 days before starting ADT. Another 36.3% (n = 23,207) initiated RT 1-60 days after starting ADT, 47.4% (n = 30,285) initiated RT 61-120 days after starting ADT, and 10.6% (n = 6,794) initiated RT 121-180 days after starting ADT.

The investigators found that 10-year overall survival rates were similar regardless of when patients started RT.

Multivariate analysis in the unfavorable intermediate-risk group showed that, relative to peers who started RT before ADT, men initiating RT later did not have significantly poorer overall survival, regardless of whether RT was initiated 1-60 days after starting ADT (hazard ratio for death, 1.03; P = .64), 61-120 days after (HR, 0.95; P = .42), or 121-180 days after (HR, 0.99; P = .90).

Findings were similar in the combined high-risk and very-high-risk group, with no significant elevation of mortality risk for patients initiating RT 1-60 days after starting ADT (HR, 1.07; P = .12), 61-120 days after (HR, 1.04; P = .36), or 121-180 days after (HR, 1.07; P = .17).

“These results validate the findings of two prior randomized trials and possibly justify the delay of prostate RT for patients currently receiving ADT until COVID-19 infection rates in the community and hospitals are lower,” the authors wrote.

Despite the fairly short follow-up period and other study limitations, “if COVID-19 outbreaks continue to occur sporadically during the coming months to years, these data could allow future flexibility about the timing of RT initiation,” the authors concluded.
 

Experts weigh in

“Overall, this study is asking a good question given the COVID situation and the fact that many providers are delaying RT due to COVID concerns of patients and providers,” Colleen A. Lawton, MD, of the Medical College of Wisconsin, Milwaukee, commented in an interview.

At the same time, Dr. Lawton cautioned about oversimplifying the issue, noting that results of the Radiation Therapy Oncology Group (RTOG) 9413 trial suggest important interactions between the anatomic extent of RT and the timing of ADT on outcomes (Int J Radiat Oncol Biol Phys. 2007 Nov 1;69[3]:646-55).

“I have certainly delayed some of my own patients with ADT during the COVID pandemic,” she reported. “No one knows what the maximum acceptable delay should be. A few months is likely not a problem, and a year is probably too much, but scientifically, we just don’t know.”

The interplay of volume irradiated and ADT timing is relevant here, agreed Mack Roach III, MD, of University of California, San Francisco.

In addition, the study did not address why ADT was given when it was, the duration of this therapy, and endpoints other than overall survival (such as prostate-specific antigen failure rate) that may better reflect the effectiveness of cancer treatment.

“Yes, delays are safe for patients on ADT, but not for the reasons stated. A more appropriate source of data is RTOG 9910, which compared 28 versus 8 weeks of ADT prior to RT for mostly intermediate-risk prostate cancer patients with comparable results,” Dr. Roach noted (J Clin Oncol. 2015 Feb 1;33[4]:332-9).

“Delay duration should be based on the risk of disease, but 6 months is probably safe, especially if on ADT,” he said.

Michael J. Zelefsky, MD, of Memorial Sloan Kettering Cancer Center in New York, said he agreed with the investigators’ main conclusions. “Once ADT suppression is achieved, maintaining patients on this regimen for 6 months would not likely lead to the development of a castrate-resistant state where radiotherapy would be less effective,” he elaborated.

However, limitations of the database used preclude conclusions about the safety of longer delays or the impact on other outcomes, he cautioned.

“This study provides further support to the accepted notion that delays of up to 6 months prior to initiation of planned prostate radiation would be safe and appropriate, especially where concerns of COVID outbreaks may present significant logistic challenges and concerns for the patient, who needs to commit to a course of daily radiation treatments, which could span for 5-8 weeks,” Dr. Zelefsky said.

“We have, in fact, adopted this approach in our clinics during the COVID outbreaks in New York,” he reported. “Most of our patients with unfavorable intermediate- or high-risk disease were initiated on ADT planned for at least 4-6 months before the radiotherapy was initiated. In addition, for these reasons, our preference has been to also offer such patients, if feasible, an ultrahypofractionated treatment course where the radiotherapy course is completed in five fractions over 1-2 weeks.”

This research was funded by the National Institutes of Health. The authors disclosed various grants and personal fees outside the submitted work. Dr. Lawton disclosed that she was a coauthor on RTOG 9413. Dr. Roach and Dr. Zelefsky disclosed no relevant conflicts of interest.

SOURCE: Dee EC et al. JAMA Oncol. 2020 Aug 13. doi: 10.1001/jamaoncol.2020.3545.

A study of more than 60,000 prostate cancer patients suggests it is safe to delay radiation therapy (RT) for at least 6 months for localized higher-risk disease being treated with androgen deprivation therapy.

These findings are relevant to oncology care in the COVID-19 era, as the pandemic has complicated delivery of radiation therapy (RT) in several ways, the study authors wrote in JAMA Oncology.

“Daily hospital trips for RT create many possible points of COVID-19 transmission, and patients with cancer are at high risk of COVID-19 mortality,” Edward Christopher Dee, a research fellow at Dana-Farber Cancer Institute in Boston, and colleagues wrote.

To assess the safety of delaying RT, the investigators analyzed National Cancer Database data for 63,858 men with localized but unfavorable intermediate-risk, high-risk, or very-high-risk prostate cancer diagnosed during 2004-2014 and managed with external beam RT and androgen deprivation therapy (ADT).

Only 5.6% of patients (n = 3,572) initiated their RT 0-60 days before starting ADT. Another 36.3% (n = 23,207) initiated RT 1-60 days after starting ADT, 47.4% (n = 30,285) initiated RT 61-120 days after starting ADT, and 10.6% (n = 6,794) initiated RT 121-180 days after starting ADT.

The investigators found that 10-year overall survival rates were similar regardless of when patients started RT.

Multivariate analysis in the unfavorable intermediate-risk group showed that, relative to peers who started RT before ADT, men initiating RT later did not have significantly poorer overall survival, regardless of whether RT was initiated 1-60 days after starting ADT (hazard ratio for death, 1.03; P = .64), 61-120 days after (HR, 0.95; P = .42), or 121-180 days after (HR, 0.99; P = .90).

Findings were similar in the combined high-risk and very-high-risk group, with no significant elevation of mortality risk for patients initiating RT 1-60 days after starting ADT (HR, 1.07; P = .12), 61-120 days after (HR, 1.04; P = .36), or 121-180 days after (HR, 1.07; P = .17).

“These results validate the findings of two prior randomized trials and possibly justify the delay of prostate RT for patients currently receiving ADT until COVID-19 infection rates in the community and hospitals are lower,” the authors wrote.

Despite the fairly short follow-up period and other study limitations, “if COVID-19 outbreaks continue to occur sporadically during the coming months to years, these data could allow future flexibility about the timing of RT initiation,” the authors concluded.
 

Experts weigh in

“Overall, this study is asking a good question given the COVID situation and the fact that many providers are delaying RT due to COVID concerns of patients and providers,” Colleen A. Lawton, MD, of the Medical College of Wisconsin, Milwaukee, commented in an interview.

At the same time, Dr. Lawton cautioned about oversimplifying the issue, noting that results of the Radiation Therapy Oncology Group (RTOG) 9413 trial suggest important interactions between the anatomic extent of RT and the timing of ADT on outcomes (Int J Radiat Oncol Biol Phys. 2007 Nov 1;69[3]:646-55).

“I have certainly delayed some of my own patients with ADT during the COVID pandemic,” she reported. “No one knows what the maximum acceptable delay should be. A few months is likely not a problem, and a year is probably too much, but scientifically, we just don’t know.”

The interplay of volume irradiated and ADT timing is relevant here, agreed Mack Roach III, MD, of University of California, San Francisco.

In addition, the study did not address why ADT was given when it was, the duration of this therapy, and endpoints other than overall survival (such as prostate-specific antigen failure rate) that may better reflect the effectiveness of cancer treatment.

“Yes, delays are safe for patients on ADT, but not for the reasons stated. A more appropriate source of data is RTOG 9910, which compared 28 versus 8 weeks of ADT prior to RT for mostly intermediate-risk prostate cancer patients with comparable results,” Dr. Roach noted (J Clin Oncol. 2015 Feb 1;33[4]:332-9).

“Delay duration should be based on the risk of disease, but 6 months is probably safe, especially if on ADT,” he said.

Michael J. Zelefsky, MD, of Memorial Sloan Kettering Cancer Center in New York, said he agreed with the investigators’ main conclusions. “Once ADT suppression is achieved, maintaining patients on this regimen for 6 months would not likely lead to the development of a castrate-resistant state where radiotherapy would be less effective,” he elaborated.

However, limitations of the database used preclude conclusions about the safety of longer delays or the impact on other outcomes, he cautioned.

“This study provides further support to the accepted notion that delays of up to 6 months prior to initiation of planned prostate radiation would be safe and appropriate, especially where concerns of COVID outbreaks may present significant logistic challenges and concerns for the patient, who needs to commit to a course of daily radiation treatments, which could span for 5-8 weeks,” Dr. Zelefsky said.

“We have, in fact, adopted this approach in our clinics during the COVID outbreaks in New York,” he reported. “Most of our patients with unfavorable intermediate- or high-risk disease were initiated on ADT planned for at least 4-6 months before the radiotherapy was initiated. In addition, for these reasons, our preference has been to also offer such patients, if feasible, an ultrahypofractionated treatment course where the radiotherapy course is completed in five fractions over 1-2 weeks.”

This research was funded by the National Institutes of Health. The authors disclosed various grants and personal fees outside the submitted work. Dr. Lawton disclosed that she was a coauthor on RTOG 9413. Dr. Roach and Dr. Zelefsky disclosed no relevant conflicts of interest.

SOURCE: Dee EC et al. JAMA Oncol. 2020 Aug 13. doi: 10.1001/jamaoncol.2020.3545.

Fecal microbiota transplantation results in a short-term reduction in alcohol craving in patients with alcohol-induced cirrhosis who can’t stop drinking, results from a new study show.

And that reduction could lead to a better psychosocial quality of life for patients with cirrhosis and alcohol use disorder, said investigator Jasmohan Bajaj, MD, from Virginia Commonwealth University, Richmond.

“This is the most common addiction disorder worldwide, but we have nothing to treat these patients with,” he said.

Cirrhosis is associated with an altered gut-brain axis. It leads to organ damage in several parts of the body, including the brain, gut, pancreas, and liver. This makes changing the gut microbes “an attractive target,” Dr. Bajaj said at the Digital International Liver Congress 2020.

For their phase 1, double-blind study, he and his colleagues assessed 20 men from a Virginia veteran’s hospital with untreatable alcohol use disorder who were not eligible for liver transplantation.

All had failed behavioral or pharmacologic therapy and were unwilling to try again. “That’s what made them good candidates to try something new,” Dr. Bajaj said during a press briefing.

Mean age in the study cohort was 65 years, mean Model for End-Stage Liver disease score was 8.9, and demographic characteristics were similar between the 10 men randomly assigned to fecal transplantation and the 10 assigned to placebo. One man in each group dropped out of the study.

The investigators evaluated cravings, microbiota, and quality of life during the 30-day study period.

At day 15, significantly more men in the transplant group than in the placebo group experienced a reduction in alcohol cravings (90% vs. 30%).

At 30 days, levels of creatinine, serum interleukin-6, and lipopolysaccharide-binding protein were lower in the transplant group than in the placebo group. In addition, levels of butyrate and isobutyrate increased, as did cognition and quality of life scores.

There was also a decrease in urinary ethyl glucuronide in the transplant group, which “is the objective criteria for alcohol intake,” Dr. Bajaj reported, noting that there was no change in ethyl glucuronide in the placebo group.

The increase in microbiota diversity was significant in the transplant group but not in the placebo group. Alistipes, Odoribacter, and Roseburia were more abundant in the transplant group than in the placebo group.

During the 30-day study period, two men in the placebo group required medical attention, one for hyponatremia and the other for atrial fibrillation. However, no adverse events were seen in any men in the transplant group. “This was the No. 1 result,” Dr. Bajaj said.
 

Liver disease and the microbiome

“Understanding of interactions between the human and microbiome genome [metagenome] in health and disease has represented one of the major areas of progress in the last few years,” said Luca Valenti, MD, from the University of Milan, who is a member of the scientific committee of the European Association the Study of the Liver, which organized the congress.

“These studies lay the groundwork for the exploitation of this new knowledge for the treatment of liver disease,” he said.

“We are [now] diagnosing liver disease and the stages of liver disease based on microbiome changes,” said Jonel Trebicka, MD, PhD, from University Hospital Frankfurt (Germany), who chaired a session at the congress on the role of the microbiome in liver disease.

“This and other studies have shown us that the microbiome itself may influence liver disease,” he added.

Dr. Bajaj is considered one of the world’s experts on cirrhosis and the microbiome, Dr. Trebicka explained. Last year, Dr. Bajaj and his team demonstrated that fecal microbiota transplantation can reduce the incidence of recurrent hepatic encephalopathy, as reported by Medscape Medical News.

The current study also “shows clearly that the microbiome plays a role in craving. FMT reduces the desire for alcohol,” said Dr. Trebicka.

“The way to the brain is through the gut,” Dr. Bajaj said.

Dr. Bajaj, Dr. Trebicka, and Dr. Valenti disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Fecal microbiota transplantation results in a short-term reduction in alcohol craving in patients with alcohol-induced cirrhosis who can’t stop drinking, results from a new study show.

And that reduction could lead to a better psychosocial quality of life for patients with cirrhosis and alcohol use disorder, said investigator Jasmohan Bajaj, MD, from Virginia Commonwealth University, Richmond.

“This is the most common addiction disorder worldwide, but we have nothing to treat these patients with,” he said.

Cirrhosis is associated with an altered gut-brain axis. It leads to organ damage in several parts of the body, including the brain, gut, pancreas, and liver. This makes changing the gut microbes “an attractive target,” Dr. Bajaj said at the Digital International Liver Congress 2020.

For their phase 1, double-blind study, he and his colleagues assessed 20 men from a Virginia veteran’s hospital with untreatable alcohol use disorder who were not eligible for liver transplantation.

All had failed behavioral or pharmacologic therapy and were unwilling to try again. “That’s what made them good candidates to try something new,” Dr. Bajaj said during a press briefing.

Mean age in the study cohort was 65 years, mean Model for End-Stage Liver disease score was 8.9, and demographic characteristics were similar between the 10 men randomly assigned to fecal transplantation and the 10 assigned to placebo. One man in each group dropped out of the study.

The investigators evaluated cravings, microbiota, and quality of life during the 30-day study period.

At day 15, significantly more men in the transplant group than in the placebo group experienced a reduction in alcohol cravings (90% vs. 30%).

At 30 days, levels of creatinine, serum interleukin-6, and lipopolysaccharide-binding protein were lower in the transplant group than in the placebo group. In addition, levels of butyrate and isobutyrate increased, as did cognition and quality of life scores.

There was also a decrease in urinary ethyl glucuronide in the transplant group, which “is the objective criteria for alcohol intake,” Dr. Bajaj reported, noting that there was no change in ethyl glucuronide in the placebo group.

The increase in microbiota diversity was significant in the transplant group but not in the placebo group. Alistipes, Odoribacter, and Roseburia were more abundant in the transplant group than in the placebo group.

During the 30-day study period, two men in the placebo group required medical attention, one for hyponatremia and the other for atrial fibrillation. However, no adverse events were seen in any men in the transplant group. “This was the No. 1 result,” Dr. Bajaj said.
 

Liver disease and the microbiome

“Understanding of interactions between the human and microbiome genome [metagenome] in health and disease has represented one of the major areas of progress in the last few years,” said Luca Valenti, MD, from the University of Milan, who is a member of the scientific committee of the European Association the Study of the Liver, which organized the congress.

“These studies lay the groundwork for the exploitation of this new knowledge for the treatment of liver disease,” he said.

“We are [now] diagnosing liver disease and the stages of liver disease based on microbiome changes,” said Jonel Trebicka, MD, PhD, from University Hospital Frankfurt (Germany), who chaired a session at the congress on the role of the microbiome in liver disease.

“This and other studies have shown us that the microbiome itself may influence liver disease,” he added.

Dr. Bajaj is considered one of the world’s experts on cirrhosis and the microbiome, Dr. Trebicka explained. Last year, Dr. Bajaj and his team demonstrated that fecal microbiota transplantation can reduce the incidence of recurrent hepatic encephalopathy, as reported by Medscape Medical News.

The current study also “shows clearly that the microbiome plays a role in craving. FMT reduces the desire for alcohol,” said Dr. Trebicka.

“The way to the brain is through the gut,” Dr. Bajaj said.

Dr. Bajaj, Dr. Trebicka, and Dr. Valenti disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Fecal microbiota transplantation results in a short-term reduction in alcohol craving in patients with alcohol-induced cirrhosis who can’t stop drinking, results from a new study show.

And that reduction could lead to a better psychosocial quality of life for patients with cirrhosis and alcohol use disorder, said investigator Jasmohan Bajaj, MD, from Virginia Commonwealth University, Richmond.

“This is the most common addiction disorder worldwide, but we have nothing to treat these patients with,” he said.

Cirrhosis is associated with an altered gut-brain axis. It leads to organ damage in several parts of the body, including the brain, gut, pancreas, and liver. This makes changing the gut microbes “an attractive target,” Dr. Bajaj said at the Digital International Liver Congress 2020.

For their phase 1, double-blind study, he and his colleagues assessed 20 men from a Virginia veteran’s hospital with untreatable alcohol use disorder who were not eligible for liver transplantation.

All had failed behavioral or pharmacologic therapy and were unwilling to try again. “That’s what made them good candidates to try something new,” Dr. Bajaj said during a press briefing.

Mean age in the study cohort was 65 years, mean Model for End-Stage Liver disease score was 8.9, and demographic characteristics were similar between the 10 men randomly assigned to fecal transplantation and the 10 assigned to placebo. One man in each group dropped out of the study.

The investigators evaluated cravings, microbiota, and quality of life during the 30-day study period.

At day 15, significantly more men in the transplant group than in the placebo group experienced a reduction in alcohol cravings (90% vs. 30%).

At 30 days, levels of creatinine, serum interleukin-6, and lipopolysaccharide-binding protein were lower in the transplant group than in the placebo group. In addition, levels of butyrate and isobutyrate increased, as did cognition and quality of life scores.

There was also a decrease in urinary ethyl glucuronide in the transplant group, which “is the objective criteria for alcohol intake,” Dr. Bajaj reported, noting that there was no change in ethyl glucuronide in the placebo group.

The increase in microbiota diversity was significant in the transplant group but not in the placebo group. Alistipes, Odoribacter, and Roseburia were more abundant in the transplant group than in the placebo group.

During the 30-day study period, two men in the placebo group required medical attention, one for hyponatremia and the other for atrial fibrillation. However, no adverse events were seen in any men in the transplant group. “This was the No. 1 result,” Dr. Bajaj said.
 

Liver disease and the microbiome

“Understanding of interactions between the human and microbiome genome [metagenome] in health and disease has represented one of the major areas of progress in the last few years,” said Luca Valenti, MD, from the University of Milan, who is a member of the scientific committee of the European Association the Study of the Liver, which organized the congress.

“These studies lay the groundwork for the exploitation of this new knowledge for the treatment of liver disease,” he said.

“We are [now] diagnosing liver disease and the stages of liver disease based on microbiome changes,” said Jonel Trebicka, MD, PhD, from University Hospital Frankfurt (Germany), who chaired a session at the congress on the role of the microbiome in liver disease.

“This and other studies have shown us that the microbiome itself may influence liver disease,” he added.

Dr. Bajaj is considered one of the world’s experts on cirrhosis and the microbiome, Dr. Trebicka explained. Last year, Dr. Bajaj and his team demonstrated that fecal microbiota transplantation can reduce the incidence of recurrent hepatic encephalopathy, as reported by Medscape Medical News.

The current study also “shows clearly that the microbiome plays a role in craving. FMT reduces the desire for alcohol,” said Dr. Trebicka.

“The way to the brain is through the gut,” Dr. Bajaj said.

Dr. Bajaj, Dr. Trebicka, and Dr. Valenti disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

With an average age of diagnosis of 28 years, and one of two incidence peaks occurring at 15-30 years, psoriasis affects many women in the midst of their reproductive years. The prospect of pregnancy – or the reality of a surprise pregnancy – drives questions about heritability of the disease in offspring, the impact of the disease on pregnancy outcomes and breastfeeding, and how to best balance risks of treatments with risks of uncontrolled psoriasis and/or psoriatic arthritis (PsA).

shironosov/Getty Images

While answers to these questions are not always clear, discussions about pregnancy and psoriasis management “shouldn’t be scary,” said Jenny E. Murase, MD, a dermatologist who speaks and writes widely about her research and experience with psoriasis and pregnancy. “We have access to information and data and educational resources to [work with] and reassure our patients – we just need to use it. Right now, there’s unnecessary suffering [with some patients unnecessarily stopping all treatment].”

Much has been learned in the past 2 decades about the course of psoriasis in pregnancy, and pregnancy outcomes data on the safety of biologics during pregnancy are increasingly emerging – particularly for tumor necrosis factor (TNF)–alpha inhibitors.

Ideally, since half of all pregnancies are unplanned, the implications of therapeutic options should be discussed with all women with psoriasis who are of reproductive age, whether they are sexually active or not. “The onus is on us to make sure that we’re considering the possibility [that our patient] could become pregnant without consulting us first,” said Dr. Murase, associate professor of dermatology at the University of California, San Francisco, and director of medical consultative dermatology for the Palo Alto Foundation Medical Group in Mountain View, Calif.

Lisa R. Sammaritano, MD, associate professor of clinical medicine at Weill Cornell Medicine and a rheumatologist at the Hospital for Special Surgery, both in New York, urges similar attention for PsA. “Pregnancy is best planned while patients have quiescent disease on pregnancy-compatible medications,” she said. “We encourage [more] rheumatologists to be actively involved in pregnancy planning [in order] to guide therapy.”

The impact of estrogen

Dr. Murase was inspired to study psoriasis and pregnancy in part by a patient she met as a medical student. “She had severe psoriasis covering her body, and she said that the only times her psoriasis cleared was during her three pregnancies,” Dr. Murase recalled. “I wondered: What about the pregnancies resulted in such a substantial reduction of her psoriasis?”

She subsequently led a study, published in 2005, of 47 pregnant and 27 nonpregnant patients with psoriasis. More than half of the patients – 55% – reported improvements in their psoriasis during pregnancy, 21% reported no change, and 23% reported worsening. Among the 16 patients who had 10% or greater psoriatic body surface area (BSA) involvement and reported improvements, lesions decreased by 84%.

In the postpartum period, only 9% reported improvement, 26% reported no change, and 65% reported worsening. The increased BSA values observed 6 weeks postpartum did not exceed those of the first trimester, suggesting a return to the patients’ baseline status.

Earlier and smaller retrospective studies had also shown that approximately half of patients improve during pregnancy, and it was believed that progesterone was most likely responsible for this improvement. Dr. Murase’s study moved the needle in that it examined BSA in pregnancy and the postpartum period. It also turned the spotlight on estrogen: Patients who had higher levels of improvement also had higher levels of estradiol, estrone, and the ratio of estrogen to progesterone. However, there was no correlation between psoriatic change and levels of progesterone.

To promote fetal survival, pregnancy triggers a shift from Th1 cell–mediated immunity – and Th17 immunity – to Th2 immunity. While there’s no proof of a causative effect, increased estrogen appears to play a role in this shift and in the reduced production of Th1 and Th17 cytokines. Psoriasis is believed to be primarily a Th17-mediated disease, with some Th1 involvement, so this down-regulation can result in improved disease status, Dr. Murase said. (A host of other autoimmune diseases categorized as Th1 mediated similarly tend to improve during pregnancy, she added.)

Information on the effect of pregnancy on PsA is “conflicting,” Dr. Sammaritano said. “Some [of a limited number of studies] suggest a beneficial effect as is generally seen for rheumatoid arthritis. Others, however, have found an increased risk of disease activity during pregnancy ... It may be that psoriatic arthritis can be quite variable from patient to patient in its clinical presentation.”

At least one study, Dr. Sammaritano added, “has shown that the arthritis in pregnancy patients with PsA did not improve, compared to control nonpregnant patients, while the psoriasis rash did improve.”

The mixed findings don’t surprise Dr. Murase. “It harder to quantify joint disease in general,” she said. “And during pregnancy, physiologic changes relating to the pregnancy itself can cause discomfort – your joints ache. The numbers [of improved] cases aren’t as high with PsA, but it’s a more complex question.”

In the postpartum period, however, research findings “all suggest an increased risk of flare” of PsA, Dr. Sammaritano said, just as with psoriasis.
 

Assessing risk of treatment

Understanding the immunologic effects of pregnancy on psoriasis and PsA – and appreciating the concept of a hormonal component – is an important part of treatment decision making. So is understanding pregnancy outcomes data.

Researchers have looked at a host of pregnancy outcomes – including congenital malformations, preterm birth, spontaneous abortion, low birth weight, macrosomia, and gestational diabetes and hypertension – in women with psoriasis or psoriasis/PsA, compared with control groups. Some studies have suggested a link between disease activity and pregnancy complications or adverse pregnancy outcomes, “just as a result of having moderate to severe disease,” while others have found no evidence of increased risk, Dr. Murase said.

“It’s a bit unclear and a difficult question to answer; it depends on what study you look at and what data you believe. It would be nice to have some clarity, but basically the jury is still out,” said Dr. Murase, who, with coauthors Alice B. Gottlieb, MD, PhD, of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and Caitriona Ryan, MD, of the Blackrock Clinic and Charles Institute of Dermatology, University College Dublin, discussed the pregnancy outcomes data in a recently published review of psoriasis in women.

“In my opinion, because we have therapies that are so low risk and well tolerated, it’s better to make sure that the inflammatory cascade and inflammation created by psoriasis is under control,” she said. “So whether or not the pregnancy itself causes the patient to go into remission, or whether you have to use therapy to help the patient stay in remission, it’s important to control the inflammation.”

Contraindicated in pregnancy are oral psoralen, methotrexate, and acitretin, the latter of which should be avoided for several years before pregnancy and “therefore shouldn’t be used in a woman of childbearing age,” said Dr. Murase. Methotrexate, said Dr. Sammaritano, should generally be stopped 1-3 months prior to conception.

For psoriasis, the therapy that’s “classically considered the safest in pregnancy is UVB light therapy, specifically the 300-nm wavelength of light, which works really well as an anti-inflammatory,” Dr. Murase said. Because of the potential for maternal folate degradation with phototherapy and the long-known association of folate deficiency with neural tube defects, women of childbearing age who are receiving light therapy should take daily folic acid supplementation. (She prescribes a daily prenatal vitamin containing at least 1 mg of folic acid for women who are utilizing light therapy.)

Many topical agents can be used during pregnancy, Dr. Murase said. Topical corticosteroids, she noted, have the most safety-affirming data of any topical medication.

Regarding oral therapies, Dr. Murase recommends against the use of apremilast (Otezla) for her patients. “It’s not contraindicated, but the animal studies don’t look promising, so I don’t use that one in women of childbearing age just in case. There’s just very little data to support the safety of this medication [in pregnancy].”

There are no therapeutic guidelines in the United States for guiding the management of psoriasis in women who are considering pregnancy. In 2012, the medical board of the National Psoriasis Foundation published a review of treatment options for psoriasis in pregnant or lactating women, the “closest thing to guidelines that we’ve had,” said Dr. Murase. (Now almost a decade old, the review addresses TNF inhibitors but does not cover the anti-interleukin agents more recently approved for moderate to severe psoriasis and PsA.)

For treating PsA, rheumatologists now have the American College of Rheumatology’s first guideline for the management of reproductive health in rheumatic and musculoskeletal diseases to reference. The 2020 guideline does not address PsA specifically, but its section on pregnancy and lactation includes recommendations on biologic and other therapies used to treat the disease.

Guidelines aside, physician-patient discussions over drug safety have the potential to be much more meaningful now that drug labels offer clinical summaries, data, and risk summaries regarding potential use in pregnancy. The labels have “more of a narrative, which is a more useful way to counsel patients and make risk-benefit decisions” than the former system of five-letter categories, said Dr. Murase. (The changes were made per the Pregnancy and Lactation Labeling Rule of 2015.)

MothertoBaby, a service of the nonprofit Organization of Teratology Information Specialists, also provides good evidence-based information to physicians and mothers, Dr. Sammaritano noted.

The use of biologic therapies

In a 2017 review of biologic safety for patients with psoriasis during pregnancy, Alexa B. Kimball, MD, MPH, professor of dermatology at Harvard Medical School, Boston; Martina L. Porter, MD, currently with the department of dermatology at Beth Israel Deaconess Medical Center, Boston; and Stephen J. Lockwood, MD, MPH, of the department of dermatology at Harvard Medical School, concluded that an increasing body of literature suggests that biologic agents can be used during pregnancy and breastfeeding. Anti-TNF agents “should be considered over IL-12/23 and IL-17 inhibitors due to the increased availability of long-term data,” they wrote.

“In general,” said Dr. Murase, “there’s more and more data coming out from gastroenterology and rheumatology to reassure patients and prescribing physicians that the TNF-blocker class is likely safe to use in pregnancy,” particularly during the first trimester and early second trimester, when the transport of maternal antibodies across the placenta is “essentially nonexistent.” In the third trimester, the active transport of IgG antibodies increases rapidly.

If possible, said Dr. Sammaritano, who served as lead author of the ACR’s reproductive health guideline, TNF inhibitors “will be stopped prior to the third trimester to avoid [the possibility of] high drug levels in the infant at birth, which raises concern for immunosuppression in the newborn. If disease is very active, however, they can be continued throughout the pregnancy.”

The TNF inhibitor certolizumab pegol (Cimzia) has the advantage of being transported only minimally across the placenta, if at all, she and Dr. Murase both explained. “To be actively carried across, antibodies need what’s called an Fc region for the placenta to grab onto,” Dr. Murase said. Certolizumab – a pegylated anti–binding fragment antibody – lacks this Fc region.

Two recent studies – CRIB and a UCB Pharma safety database analysis – showed “essentially no medication crossing – there were barely detectable levels,” Dr. Murase said. Certolizumab’s label contains this information and other clinical trial data as well as findings from safety database analyses/surveillance registries.

“Before we had much data for the biologics, I’d advise transitioning patients to light therapy from their biologics and a lot of times their psoriasis would improve, but it was more of a dance,” she said. “Now we tend to look at [certolizumab] when they’re of childbearing age and keep them on the treatment. I know that the baby is not being immunosuppressed.”

Consideration of the use of certolizumab when treatment with biologic agents is required throughout the pregnancy is a recommendation included in Dr. Kimball’s 2017 review.

As newer anti-interleukin agents – the IL-12/23 and IL-17 inhibitors – play a growing role in the treatment of psoriasis and PsA, questions loom about their safety profile. Dr. Murase and Dr. Sammaritano are waiting for more data. “In general,” Dr. Sammaritano said, “we recommend stopping them at the time pregnancy is detected, based on a lack of data at this time.”

Small-molecule drugs are also less well studied, she noted. “Because of their low molecular weight, we anticipate they will easily cross the placenta, so we recommend avoiding use during pregnancy until more information is available.”

Postpartum care

The good news, both experts say, is that the vast majority of medications, including biologics, are safe to use during breastfeeding. Methotrexate should be avoided, Dr. Sammaritano pointed out, and the impact of novel small-molecule therapies on breast milk has not been studied.

In her 2019 review of psoriasis in women, Dr. Murase and coauthors wrote that too many dermatologists believe that breastfeeding women should either not be on biologics or are uncertain about biologic use during breastfeeding. However, “biologics are considered compatible for use while breastfeeding due to their large molecular size and the proteolytic environment in the neonatal gastrointestinal tract,” they added.

Counseling and support for breastfeeding is especially important for women with psoriasis, Dr. Murase emphasized. “Breastfeeding is very traumatizing to the skin, and psoriasis can form in skin that’s injured. I have my patients set up an office visit very soon after the pregnancy to make sure they’re doing alright with their breastfeeding and that they’re coating their nipple area with some type of moisturizer and keeping the health of their nipples in good shape.”

Timely reviews of therapy and adjustments are also a priority, she said. “We need to prepare for 6 weeks post partum” when psoriasis will often flare without treatment.

Dr. Murase disclosed that she is a consultant for Dermira, UCB Pharma, Sanofi, Ferndale, and Regeneron. She is also coeditor in chief of the International Journal of Women’s Dermatology. Dr. Sammaritano reported that she has no disclosures relating to the treatment of PsA.

With an average age of diagnosis of 28 years, and one of two incidence peaks occurring at 15-30 years, psoriasis affects many women in the midst of their reproductive years. The prospect of pregnancy – or the reality of a surprise pregnancy – drives questions about heritability of the disease in offspring, the impact of the disease on pregnancy outcomes and breastfeeding, and how to best balance risks of treatments with risks of uncontrolled psoriasis and/or psoriatic arthritis (PsA).

shironosov/Getty Images

While answers to these questions are not always clear, discussions about pregnancy and psoriasis management “shouldn’t be scary,” said Jenny E. Murase, MD, a dermatologist who speaks and writes widely about her research and experience with psoriasis and pregnancy. “We have access to information and data and educational resources to [work with] and reassure our patients – we just need to use it. Right now, there’s unnecessary suffering [with some patients unnecessarily stopping all treatment].”

Much has been learned in the past 2 decades about the course of psoriasis in pregnancy, and pregnancy outcomes data on the safety of biologics during pregnancy are increasingly emerging – particularly for tumor necrosis factor (TNF)–alpha inhibitors.

Ideally, since half of all pregnancies are unplanned, the implications of therapeutic options should be discussed with all women with psoriasis who are of reproductive age, whether they are sexually active or not. “The onus is on us to make sure that we’re considering the possibility [that our patient] could become pregnant without consulting us first,” said Dr. Murase, associate professor of dermatology at the University of California, San Francisco, and director of medical consultative dermatology for the Palo Alto Foundation Medical Group in Mountain View, Calif.

Lisa R. Sammaritano, MD, associate professor of clinical medicine at Weill Cornell Medicine and a rheumatologist at the Hospital for Special Surgery, both in New York, urges similar attention for PsA. “Pregnancy is best planned while patients have quiescent disease on pregnancy-compatible medications,” she said. “We encourage [more] rheumatologists to be actively involved in pregnancy planning [in order] to guide therapy.”

The impact of estrogen

Dr. Murase was inspired to study psoriasis and pregnancy in part by a patient she met as a medical student. “She had severe psoriasis covering her body, and she said that the only times her psoriasis cleared was during her three pregnancies,” Dr. Murase recalled. “I wondered: What about the pregnancies resulted in such a substantial reduction of her psoriasis?”

She subsequently led a study, published in 2005, of 47 pregnant and 27 nonpregnant patients with psoriasis. More than half of the patients – 55% – reported improvements in their psoriasis during pregnancy, 21% reported no change, and 23% reported worsening. Among the 16 patients who had 10% or greater psoriatic body surface area (BSA) involvement and reported improvements, lesions decreased by 84%.

In the postpartum period, only 9% reported improvement, 26% reported no change, and 65% reported worsening. The increased BSA values observed 6 weeks postpartum did not exceed those of the first trimester, suggesting a return to the patients’ baseline status.

Earlier and smaller retrospective studies had also shown that approximately half of patients improve during pregnancy, and it was believed that progesterone was most likely responsible for this improvement. Dr. Murase’s study moved the needle in that it examined BSA in pregnancy and the postpartum period. It also turned the spotlight on estrogen: Patients who had higher levels of improvement also had higher levels of estradiol, estrone, and the ratio of estrogen to progesterone. However, there was no correlation between psoriatic change and levels of progesterone.

To promote fetal survival, pregnancy triggers a shift from Th1 cell–mediated immunity – and Th17 immunity – to Th2 immunity. While there’s no proof of a causative effect, increased estrogen appears to play a role in this shift and in the reduced production of Th1 and Th17 cytokines. Psoriasis is believed to be primarily a Th17-mediated disease, with some Th1 involvement, so this down-regulation can result in improved disease status, Dr. Murase said. (A host of other autoimmune diseases categorized as Th1 mediated similarly tend to improve during pregnancy, she added.)

Information on the effect of pregnancy on PsA is “conflicting,” Dr. Sammaritano said. “Some [of a limited number of studies] suggest a beneficial effect as is generally seen for rheumatoid arthritis. Others, however, have found an increased risk of disease activity during pregnancy ... It may be that psoriatic arthritis can be quite variable from patient to patient in its clinical presentation.”

At least one study, Dr. Sammaritano added, “has shown that the arthritis in pregnancy patients with PsA did not improve, compared to control nonpregnant patients, while the psoriasis rash did improve.”

The mixed findings don’t surprise Dr. Murase. “It harder to quantify joint disease in general,” she said. “And during pregnancy, physiologic changes relating to the pregnancy itself can cause discomfort – your joints ache. The numbers [of improved] cases aren’t as high with PsA, but it’s a more complex question.”

In the postpartum period, however, research findings “all suggest an increased risk of flare” of PsA, Dr. Sammaritano said, just as with psoriasis.
 

Assessing risk of treatment

Understanding the immunologic effects of pregnancy on psoriasis and PsA – and appreciating the concept of a hormonal component – is an important part of treatment decision making. So is understanding pregnancy outcomes data.

Researchers have looked at a host of pregnancy outcomes – including congenital malformations, preterm birth, spontaneous abortion, low birth weight, macrosomia, and gestational diabetes and hypertension – in women with psoriasis or psoriasis/PsA, compared with control groups. Some studies have suggested a link between disease activity and pregnancy complications or adverse pregnancy outcomes, “just as a result of having moderate to severe disease,” while others have found no evidence of increased risk, Dr. Murase said.

“It’s a bit unclear and a difficult question to answer; it depends on what study you look at and what data you believe. It would be nice to have some clarity, but basically the jury is still out,” said Dr. Murase, who, with coauthors Alice B. Gottlieb, MD, PhD, of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and Caitriona Ryan, MD, of the Blackrock Clinic and Charles Institute of Dermatology, University College Dublin, discussed the pregnancy outcomes data in a recently published review of psoriasis in women.

“In my opinion, because we have therapies that are so low risk and well tolerated, it’s better to make sure that the inflammatory cascade and inflammation created by psoriasis is under control,” she said. “So whether or not the pregnancy itself causes the patient to go into remission, or whether you have to use therapy to help the patient stay in remission, it’s important to control the inflammation.”

Contraindicated in pregnancy are oral psoralen, methotrexate, and acitretin, the latter of which should be avoided for several years before pregnancy and “therefore shouldn’t be used in a woman of childbearing age,” said Dr. Murase. Methotrexate, said Dr. Sammaritano, should generally be stopped 1-3 months prior to conception.

For psoriasis, the therapy that’s “classically considered the safest in pregnancy is UVB light therapy, specifically the 300-nm wavelength of light, which works really well as an anti-inflammatory,” Dr. Murase said. Because of the potential for maternal folate degradation with phototherapy and the long-known association of folate deficiency with neural tube defects, women of childbearing age who are receiving light therapy should take daily folic acid supplementation. (She prescribes a daily prenatal vitamin containing at least 1 mg of folic acid for women who are utilizing light therapy.)

Many topical agents can be used during pregnancy, Dr. Murase said. Topical corticosteroids, she noted, have the most safety-affirming data of any topical medication.

Regarding oral therapies, Dr. Murase recommends against the use of apremilast (Otezla) for her patients. “It’s not contraindicated, but the animal studies don’t look promising, so I don’t use that one in women of childbearing age just in case. There’s just very little data to support the safety of this medication [in pregnancy].”

There are no therapeutic guidelines in the United States for guiding the management of psoriasis in women who are considering pregnancy. In 2012, the medical board of the National Psoriasis Foundation published a review of treatment options for psoriasis in pregnant or lactating women, the “closest thing to guidelines that we’ve had,” said Dr. Murase. (Now almost a decade old, the review addresses TNF inhibitors but does not cover the anti-interleukin agents more recently approved for moderate to severe psoriasis and PsA.)

For treating PsA, rheumatologists now have the American College of Rheumatology’s first guideline for the management of reproductive health in rheumatic and musculoskeletal diseases to reference. The 2020 guideline does not address PsA specifically, but its section on pregnancy and lactation includes recommendations on biologic and other therapies used to treat the disease.

Guidelines aside, physician-patient discussions over drug safety have the potential to be much more meaningful now that drug labels offer clinical summaries, data, and risk summaries regarding potential use in pregnancy. The labels have “more of a narrative, which is a more useful way to counsel patients and make risk-benefit decisions” than the former system of five-letter categories, said Dr. Murase. (The changes were made per the Pregnancy and Lactation Labeling Rule of 2015.)

MothertoBaby, a service of the nonprofit Organization of Teratology Information Specialists, also provides good evidence-based information to physicians and mothers, Dr. Sammaritano noted.

The use of biologic therapies

In a 2017 review of biologic safety for patients with psoriasis during pregnancy, Alexa B. Kimball, MD, MPH, professor of dermatology at Harvard Medical School, Boston; Martina L. Porter, MD, currently with the department of dermatology at Beth Israel Deaconess Medical Center, Boston; and Stephen J. Lockwood, MD, MPH, of the department of dermatology at Harvard Medical School, concluded that an increasing body of literature suggests that biologic agents can be used during pregnancy and breastfeeding. Anti-TNF agents “should be considered over IL-12/23 and IL-17 inhibitors due to the increased availability of long-term data,” they wrote.

“In general,” said Dr. Murase, “there’s more and more data coming out from gastroenterology and rheumatology to reassure patients and prescribing physicians that the TNF-blocker class is likely safe to use in pregnancy,” particularly during the first trimester and early second trimester, when the transport of maternal antibodies across the placenta is “essentially nonexistent.” In the third trimester, the active transport of IgG antibodies increases rapidly.

If possible, said Dr. Sammaritano, who served as lead author of the ACR’s reproductive health guideline, TNF inhibitors “will be stopped prior to the third trimester to avoid [the possibility of] high drug levels in the infant at birth, which raises concern for immunosuppression in the newborn. If disease is very active, however, they can be continued throughout the pregnancy.”

The TNF inhibitor certolizumab pegol (Cimzia) has the advantage of being transported only minimally across the placenta, if at all, she and Dr. Murase both explained. “To be actively carried across, antibodies need what’s called an Fc region for the placenta to grab onto,” Dr. Murase said. Certolizumab – a pegylated anti–binding fragment antibody – lacks this Fc region.

Two recent studies – CRIB and a UCB Pharma safety database analysis – showed “essentially no medication crossing – there were barely detectable levels,” Dr. Murase said. Certolizumab’s label contains this information and other clinical trial data as well as findings from safety database analyses/surveillance registries.

“Before we had much data for the biologics, I’d advise transitioning patients to light therapy from their biologics and a lot of times their psoriasis would improve, but it was more of a dance,” she said. “Now we tend to look at [certolizumab] when they’re of childbearing age and keep them on the treatment. I know that the baby is not being immunosuppressed.”

Consideration of the use of certolizumab when treatment with biologic agents is required throughout the pregnancy is a recommendation included in Dr. Kimball’s 2017 review.

As newer anti-interleukin agents – the IL-12/23 and IL-17 inhibitors – play a growing role in the treatment of psoriasis and PsA, questions loom about their safety profile. Dr. Murase and Dr. Sammaritano are waiting for more data. “In general,” Dr. Sammaritano said, “we recommend stopping them at the time pregnancy is detected, based on a lack of data at this time.”

Small-molecule drugs are also less well studied, she noted. “Because of their low molecular weight, we anticipate they will easily cross the placenta, so we recommend avoiding use during pregnancy until more information is available.”

Postpartum care

The good news, both experts say, is that the vast majority of medications, including biologics, are safe to use during breastfeeding. Methotrexate should be avoided, Dr. Sammaritano pointed out, and the impact of novel small-molecule therapies on breast milk has not been studied.

In her 2019 review of psoriasis in women, Dr. Murase and coauthors wrote that too many dermatologists believe that breastfeeding women should either not be on biologics or are uncertain about biologic use during breastfeeding. However, “biologics are considered compatible for use while breastfeeding due to their large molecular size and the proteolytic environment in the neonatal gastrointestinal tract,” they added.

Counseling and support for breastfeeding is especially important for women with psoriasis, Dr. Murase emphasized. “Breastfeeding is very traumatizing to the skin, and psoriasis can form in skin that’s injured. I have my patients set up an office visit very soon after the pregnancy to make sure they’re doing alright with their breastfeeding and that they’re coating their nipple area with some type of moisturizer and keeping the health of their nipples in good shape.”

Timely reviews of therapy and adjustments are also a priority, she said. “We need to prepare for 6 weeks post partum” when psoriasis will often flare without treatment.

Dr. Murase disclosed that she is a consultant for Dermira, UCB Pharma, Sanofi, Ferndale, and Regeneron. She is also coeditor in chief of the International Journal of Women’s Dermatology. Dr. Sammaritano reported that she has no disclosures relating to the treatment of PsA.

With an average age of diagnosis of 28 years, and one of two incidence peaks occurring at 15-30 years, psoriasis affects many women in the midst of their reproductive years. The prospect of pregnancy – or the reality of a surprise pregnancy – drives questions about heritability of the disease in offspring, the impact of the disease on pregnancy outcomes and breastfeeding, and how to best balance risks of treatments with risks of uncontrolled psoriasis and/or psoriatic arthritis (PsA).

shironosov/Getty Images

While answers to these questions are not always clear, discussions about pregnancy and psoriasis management “shouldn’t be scary,” said Jenny E. Murase, MD, a dermatologist who speaks and writes widely about her research and experience with psoriasis and pregnancy. “We have access to information and data and educational resources to [work with] and reassure our patients – we just need to use it. Right now, there’s unnecessary suffering [with some patients unnecessarily stopping all treatment].”

Much has been learned in the past 2 decades about the course of psoriasis in pregnancy, and pregnancy outcomes data on the safety of biologics during pregnancy are increasingly emerging – particularly for tumor necrosis factor (TNF)–alpha inhibitors.

Ideally, since half of all pregnancies are unplanned, the implications of therapeutic options should be discussed with all women with psoriasis who are of reproductive age, whether they are sexually active or not. “The onus is on us to make sure that we’re considering the possibility [that our patient] could become pregnant without consulting us first,” said Dr. Murase, associate professor of dermatology at the University of California, San Francisco, and director of medical consultative dermatology for the Palo Alto Foundation Medical Group in Mountain View, Calif.

Lisa R. Sammaritano, MD, associate professor of clinical medicine at Weill Cornell Medicine and a rheumatologist at the Hospital for Special Surgery, both in New York, urges similar attention for PsA. “Pregnancy is best planned while patients have quiescent disease on pregnancy-compatible medications,” she said. “We encourage [more] rheumatologists to be actively involved in pregnancy planning [in order] to guide therapy.”

The impact of estrogen

Dr. Murase was inspired to study psoriasis and pregnancy in part by a patient she met as a medical student. “She had severe psoriasis covering her body, and she said that the only times her psoriasis cleared was during her three pregnancies,” Dr. Murase recalled. “I wondered: What about the pregnancies resulted in such a substantial reduction of her psoriasis?”

She subsequently led a study, published in 2005, of 47 pregnant and 27 nonpregnant patients with psoriasis. More than half of the patients – 55% – reported improvements in their psoriasis during pregnancy, 21% reported no change, and 23% reported worsening. Among the 16 patients who had 10% or greater psoriatic body surface area (BSA) involvement and reported improvements, lesions decreased by 84%.

In the postpartum period, only 9% reported improvement, 26% reported no change, and 65% reported worsening. The increased BSA values observed 6 weeks postpartum did not exceed those of the first trimester, suggesting a return to the patients’ baseline status.

Earlier and smaller retrospective studies had also shown that approximately half of patients improve during pregnancy, and it was believed that progesterone was most likely responsible for this improvement. Dr. Murase’s study moved the needle in that it examined BSA in pregnancy and the postpartum period. It also turned the spotlight on estrogen: Patients who had higher levels of improvement also had higher levels of estradiol, estrone, and the ratio of estrogen to progesterone. However, there was no correlation between psoriatic change and levels of progesterone.

To promote fetal survival, pregnancy triggers a shift from Th1 cell–mediated immunity – and Th17 immunity – to Th2 immunity. While there’s no proof of a causative effect, increased estrogen appears to play a role in this shift and in the reduced production of Th1 and Th17 cytokines. Psoriasis is believed to be primarily a Th17-mediated disease, with some Th1 involvement, so this down-regulation can result in improved disease status, Dr. Murase said. (A host of other autoimmune diseases categorized as Th1 mediated similarly tend to improve during pregnancy, she added.)

Information on the effect of pregnancy on PsA is “conflicting,” Dr. Sammaritano said. “Some [of a limited number of studies] suggest a beneficial effect as is generally seen for rheumatoid arthritis. Others, however, have found an increased risk of disease activity during pregnancy ... It may be that psoriatic arthritis can be quite variable from patient to patient in its clinical presentation.”

At least one study, Dr. Sammaritano added, “has shown that the arthritis in pregnancy patients with PsA did not improve, compared to control nonpregnant patients, while the psoriasis rash did improve.”

The mixed findings don’t surprise Dr. Murase. “It harder to quantify joint disease in general,” she said. “And during pregnancy, physiologic changes relating to the pregnancy itself can cause discomfort – your joints ache. The numbers [of improved] cases aren’t as high with PsA, but it’s a more complex question.”

In the postpartum period, however, research findings “all suggest an increased risk of flare” of PsA, Dr. Sammaritano said, just as with psoriasis.
 

Assessing risk of treatment

Understanding the immunologic effects of pregnancy on psoriasis and PsA – and appreciating the concept of a hormonal component – is an important part of treatment decision making. So is understanding pregnancy outcomes data.

Researchers have looked at a host of pregnancy outcomes – including congenital malformations, preterm birth, spontaneous abortion, low birth weight, macrosomia, and gestational diabetes and hypertension – in women with psoriasis or psoriasis/PsA, compared with control groups. Some studies have suggested a link between disease activity and pregnancy complications or adverse pregnancy outcomes, “just as a result of having moderate to severe disease,” while others have found no evidence of increased risk, Dr. Murase said.

“It’s a bit unclear and a difficult question to answer; it depends on what study you look at and what data you believe. It would be nice to have some clarity, but basically the jury is still out,” said Dr. Murase, who, with coauthors Alice B. Gottlieb, MD, PhD, of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and Caitriona Ryan, MD, of the Blackrock Clinic and Charles Institute of Dermatology, University College Dublin, discussed the pregnancy outcomes data in a recently published review of psoriasis in women.

“In my opinion, because we have therapies that are so low risk and well tolerated, it’s better to make sure that the inflammatory cascade and inflammation created by psoriasis is under control,” she said. “So whether or not the pregnancy itself causes the patient to go into remission, or whether you have to use therapy to help the patient stay in remission, it’s important to control the inflammation.”

Contraindicated in pregnancy are oral psoralen, methotrexate, and acitretin, the latter of which should be avoided for several years before pregnancy and “therefore shouldn’t be used in a woman of childbearing age,” said Dr. Murase. Methotrexate, said Dr. Sammaritano, should generally be stopped 1-3 months prior to conception.

For psoriasis, the therapy that’s “classically considered the safest in pregnancy is UVB light therapy, specifically the 300-nm wavelength of light, which works really well as an anti-inflammatory,” Dr. Murase said. Because of the potential for maternal folate degradation with phototherapy and the long-known association of folate deficiency with neural tube defects, women of childbearing age who are receiving light therapy should take daily folic acid supplementation. (She prescribes a daily prenatal vitamin containing at least 1 mg of folic acid for women who are utilizing light therapy.)

Many topical agents can be used during pregnancy, Dr. Murase said. Topical corticosteroids, she noted, have the most safety-affirming data of any topical medication.

Regarding oral therapies, Dr. Murase recommends against the use of apremilast (Otezla) for her patients. “It’s not contraindicated, but the animal studies don’t look promising, so I don’t use that one in women of childbearing age just in case. There’s just very little data to support the safety of this medication [in pregnancy].”

There are no therapeutic guidelines in the United States for guiding the management of psoriasis in women who are considering pregnancy. In 2012, the medical board of the National Psoriasis Foundation published a review of treatment options for psoriasis in pregnant or lactating women, the “closest thing to guidelines that we’ve had,” said Dr. Murase. (Now almost a decade old, the review addresses TNF inhibitors but does not cover the anti-interleukin agents more recently approved for moderate to severe psoriasis and PsA.)

For treating PsA, rheumatologists now have the American College of Rheumatology’s first guideline for the management of reproductive health in rheumatic and musculoskeletal diseases to reference. The 2020 guideline does not address PsA specifically, but its section on pregnancy and lactation includes recommendations on biologic and other therapies used to treat the disease.

Guidelines aside, physician-patient discussions over drug safety have the potential to be much more meaningful now that drug labels offer clinical summaries, data, and risk summaries regarding potential use in pregnancy. The labels have “more of a narrative, which is a more useful way to counsel patients and make risk-benefit decisions” than the former system of five-letter categories, said Dr. Murase. (The changes were made per the Pregnancy and Lactation Labeling Rule of 2015.)

MothertoBaby, a service of the nonprofit Organization of Teratology Information Specialists, also provides good evidence-based information to physicians and mothers, Dr. Sammaritano noted.

The use of biologic therapies

In a 2017 review of biologic safety for patients with psoriasis during pregnancy, Alexa B. Kimball, MD, MPH, professor of dermatology at Harvard Medical School, Boston; Martina L. Porter, MD, currently with the department of dermatology at Beth Israel Deaconess Medical Center, Boston; and Stephen J. Lockwood, MD, MPH, of the department of dermatology at Harvard Medical School, concluded that an increasing body of literature suggests that biologic agents can be used during pregnancy and breastfeeding. Anti-TNF agents “should be considered over IL-12/23 and IL-17 inhibitors due to the increased availability of long-term data,” they wrote.

“In general,” said Dr. Murase, “there’s more and more data coming out from gastroenterology and rheumatology to reassure patients and prescribing physicians that the TNF-blocker class is likely safe to use in pregnancy,” particularly during the first trimester and early second trimester, when the transport of maternal antibodies across the placenta is “essentially nonexistent.” In the third trimester, the active transport of IgG antibodies increases rapidly.

If possible, said Dr. Sammaritano, who served as lead author of the ACR’s reproductive health guideline, TNF inhibitors “will be stopped prior to the third trimester to avoid [the possibility of] high drug levels in the infant at birth, which raises concern for immunosuppression in the newborn. If disease is very active, however, they can be continued throughout the pregnancy.”

The TNF inhibitor certolizumab pegol (Cimzia) has the advantage of being transported only minimally across the placenta, if at all, she and Dr. Murase both explained. “To be actively carried across, antibodies need what’s called an Fc region for the placenta to grab onto,” Dr. Murase said. Certolizumab – a pegylated anti–binding fragment antibody – lacks this Fc region.

Two recent studies – CRIB and a UCB Pharma safety database analysis – showed “essentially no medication crossing – there were barely detectable levels,” Dr. Murase said. Certolizumab’s label contains this information and other clinical trial data as well as findings from safety database analyses/surveillance registries.

“Before we had much data for the biologics, I’d advise transitioning patients to light therapy from their biologics and a lot of times their psoriasis would improve, but it was more of a dance,” she said. “Now we tend to look at [certolizumab] when they’re of childbearing age and keep them on the treatment. I know that the baby is not being immunosuppressed.”

Consideration of the use of certolizumab when treatment with biologic agents is required throughout the pregnancy is a recommendation included in Dr. Kimball’s 2017 review.

As newer anti-interleukin agents – the IL-12/23 and IL-17 inhibitors – play a growing role in the treatment of psoriasis and PsA, questions loom about their safety profile. Dr. Murase and Dr. Sammaritano are waiting for more data. “In general,” Dr. Sammaritano said, “we recommend stopping them at the time pregnancy is detected, based on a lack of data at this time.”

Small-molecule drugs are also less well studied, she noted. “Because of their low molecular weight, we anticipate they will easily cross the placenta, so we recommend avoiding use during pregnancy until more information is available.”

Postpartum care

The good news, both experts say, is that the vast majority of medications, including biologics, are safe to use during breastfeeding. Methotrexate should be avoided, Dr. Sammaritano pointed out, and the impact of novel small-molecule therapies on breast milk has not been studied.

In her 2019 review of psoriasis in women, Dr. Murase and coauthors wrote that too many dermatologists believe that breastfeeding women should either not be on biologics or are uncertain about biologic use during breastfeeding. However, “biologics are considered compatible for use while breastfeeding due to their large molecular size and the proteolytic environment in the neonatal gastrointestinal tract,” they added.

Counseling and support for breastfeeding is especially important for women with psoriasis, Dr. Murase emphasized. “Breastfeeding is very traumatizing to the skin, and psoriasis can form in skin that’s injured. I have my patients set up an office visit very soon after the pregnancy to make sure they’re doing alright with their breastfeeding and that they’re coating their nipple area with some type of moisturizer and keeping the health of their nipples in good shape.”

Timely reviews of therapy and adjustments are also a priority, she said. “We need to prepare for 6 weeks post partum” when psoriasis will often flare without treatment.

Dr. Murase disclosed that she is a consultant for Dermira, UCB Pharma, Sanofi, Ferndale, and Regeneron. She is also coeditor in chief of the International Journal of Women’s Dermatology. Dr. Sammaritano reported that she has no disclosures relating to the treatment of PsA.

Patients with chronic obstructive pulmonary disease who also had certain interstitial lung abnormalities experienced more exacerbations and reduced lung function than those without such abnormalities, findings from a retrospective study has shown.

Interstitial lung abnormalities (ILA) are considered precursor lesions of interstitial lung disease and previous studies suggested an association with poor outcomes among chronic obstructive pulmonary disease (COPD) patients, but data on long-term clinical relevance are limited, wrote Tae Seung Lee, MD, of Seoul (South Korea) National University Hospital, and colleagues.

In a study published in Chest, the researchers reviewed data from 363 COPD patients including 44 with equivocal ILA and 103 with definite ILA. Overall, the ILA patients were older and had poorer lung function than non-ILA patients. Patients received chest CT scan and longitudinal pulmonary function tests between January 2013 and December 2018.

Over an average follow-up period of 5.4 years, patients with ILA experienced significantly more acute COPD exacerbations than did those without ILA (adjusted odds ratio, 2.03). The percentages of frequent exacerbators among patients with no ILA, equivocal ILA, and definite ILA were 8.3%, 15.9%, and 20.4%, respectively.

“Acute exacerbation is an important event during the clinical course of COPD, because it is associated with temporary or persistent reductions in lung function, lower quality of life, hospitalization, and mortality,” the researchers noted.

In a multivariate analysis, the annual decline in lung function (FEV₁) was –35.7 in patients with equivocal ILA, compared with –28.0 in patients with no ILA and –15.9 in those with definite ILA.

“This may be due to the distribution of the spirometric stages in each group, and to the resulting changes in lung function,” the researchers wrote. In this study, “the equivocal ILA group had a significantly lower baseline FEV₁ than the other groups. In our study population, the lower the spirometric stage, the faster the annual decline in FEV₁, consistent with the results of a prior prospective study of a COPD cohort.”

The findings were limited by several factors including the retrospective design and relatively small number of ILA patients, as well as the limited evaluation of ILA and potential for selection bias, the researchers noted. However, the result support the impact of ILA on exacerbations and accelerated decline in lung function in COPD patients.

The study received no outside funding. The researchers had no financial conflicts to disclose.

SOURCE: Lee TS et al. Chest. 2020 Aug 13. doi: 10.1016/j.chest.2020.08.017.

Patients with chronic obstructive pulmonary disease who also had certain interstitial lung abnormalities experienced more exacerbations and reduced lung function than those without such abnormalities, findings from a retrospective study has shown.

Interstitial lung abnormalities (ILA) are considered precursor lesions of interstitial lung disease and previous studies suggested an association with poor outcomes among chronic obstructive pulmonary disease (COPD) patients, but data on long-term clinical relevance are limited, wrote Tae Seung Lee, MD, of Seoul (South Korea) National University Hospital, and colleagues.

In a study published in Chest, the researchers reviewed data from 363 COPD patients including 44 with equivocal ILA and 103 with definite ILA. Overall, the ILA patients were older and had poorer lung function than non-ILA patients. Patients received chest CT scan and longitudinal pulmonary function tests between January 2013 and December 2018.

Over an average follow-up period of 5.4 years, patients with ILA experienced significantly more acute COPD exacerbations than did those without ILA (adjusted odds ratio, 2.03). The percentages of frequent exacerbators among patients with no ILA, equivocal ILA, and definite ILA were 8.3%, 15.9%, and 20.4%, respectively.

“Acute exacerbation is an important event during the clinical course of COPD, because it is associated with temporary or persistent reductions in lung function, lower quality of life, hospitalization, and mortality,” the researchers noted.

In a multivariate analysis, the annual decline in lung function (FEV₁) was –35.7 in patients with equivocal ILA, compared with –28.0 in patients with no ILA and –15.9 in those with definite ILA.

“This may be due to the distribution of the spirometric stages in each group, and to the resulting changes in lung function,” the researchers wrote. In this study, “the equivocal ILA group had a significantly lower baseline FEV₁ than the other groups. In our study population, the lower the spirometric stage, the faster the annual decline in FEV₁, consistent with the results of a prior prospective study of a COPD cohort.”

The findings were limited by several factors including the retrospective design and relatively small number of ILA patients, as well as the limited evaluation of ILA and potential for selection bias, the researchers noted. However, the result support the impact of ILA on exacerbations and accelerated decline in lung function in COPD patients.

The study received no outside funding. The researchers had no financial conflicts to disclose.

SOURCE: Lee TS et al. Chest. 2020 Aug 13. doi: 10.1016/j.chest.2020.08.017.

Patients with chronic obstructive pulmonary disease who also had certain interstitial lung abnormalities experienced more exacerbations and reduced lung function than those without such abnormalities, findings from a retrospective study has shown.

Interstitial lung abnormalities (ILA) are considered precursor lesions of interstitial lung disease and previous studies suggested an association with poor outcomes among chronic obstructive pulmonary disease (COPD) patients, but data on long-term clinical relevance are limited, wrote Tae Seung Lee, MD, of Seoul (South Korea) National University Hospital, and colleagues.

In a study published in Chest, the researchers reviewed data from 363 COPD patients including 44 with equivocal ILA and 103 with definite ILA. Overall, the ILA patients were older and had poorer lung function than non-ILA patients. Patients received chest CT scan and longitudinal pulmonary function tests between January 2013 and December 2018.

Over an average follow-up period of 5.4 years, patients with ILA experienced significantly more acute COPD exacerbations than did those without ILA (adjusted odds ratio, 2.03). The percentages of frequent exacerbators among patients with no ILA, equivocal ILA, and definite ILA were 8.3%, 15.9%, and 20.4%, respectively.

“Acute exacerbation is an important event during the clinical course of COPD, because it is associated with temporary or persistent reductions in lung function, lower quality of life, hospitalization, and mortality,” the researchers noted.

In a multivariate analysis, the annual decline in lung function (FEV₁) was –35.7 in patients with equivocal ILA, compared with –28.0 in patients with no ILA and –15.9 in those with definite ILA.

“This may be due to the distribution of the spirometric stages in each group, and to the resulting changes in lung function,” the researchers wrote. In this study, “the equivocal ILA group had a significantly lower baseline FEV₁ than the other groups. In our study population, the lower the spirometric stage, the faster the annual decline in FEV₁, consistent with the results of a prior prospective study of a COPD cohort.”

The findings were limited by several factors including the retrospective design and relatively small number of ILA patients, as well as the limited evaluation of ILA and potential for selection bias, the researchers noted. However, the result support the impact of ILA on exacerbations and accelerated decline in lung function in COPD patients.

The study received no outside funding. The researchers had no financial conflicts to disclose.

SOURCE: Lee TS et al. Chest. 2020 Aug 13. doi: 10.1016/j.chest.2020.08.017.

The STAT3 pathway is important to the development of many cancers, but so far, no Food and Drug Administration–approved drugs are ready for clinical use. Napabucasin, a novel oral small-molecule inhibitor of signal transducer and activator of transcription 3 (STAT3), blocks tumor growth and resists metastasis in a broad spectrum of solid tumors. Napabucasin was now found to be effective in inhibiting diffuse large beta cell lymphoma (DLBCL) in cell lines and in in vitro testing, as reported by Xue Li of the West China Hospital, Sichuan (China) University, and colleagues.

In addition, the effects of napabucasin were found to be synergistic with the use of doxorubicin, a standard DLBCL therapy agent, according to the report, published online in Cancer Letters.
 

‘Dramatic’ results

The researchers found that 34% (23/69) of DLBCL patients expressed STAT3 in tumor tissues. When they tested napabucasin in a variety of DLBCL cell lines they found that the drug exhibited potent cytotoxicity in a dose-dependent manner. In addition, they found that napabucasin induced intrinsic and extrinsic cell apoptosis, downregulated the expression of STAT3 target genes, including the antiapoptotic protein Mcl-1, and regulated the mitogen-activated protein kinase (MAPK) pathway, all important indicators of antitumor effectiveness in vitro.

In cells treated with napabucasin and doxorubicin alone and in combination, napabucasin alone significantly suppressed tumor growth, compared with that of the control (P < .01), achieving tumor growth inhibition (TGI) of 78.8%. The combination treatment, “with a dramatic TGI of 98.2%,” was more effective than doxorubicin monotherapy (TGI = 63.2%; P < .05), according to the researchers.

“Our study provided evidence that napabucasin is an attractive candidate drug either as a monotherapy or in combination therapies for DLBCL treatment. Further work studying the clinical efficacy and combination treatment schedule should be performed for personalized therapy,” the researchers concluded.

The work was supported by grants from the Chinese government. The authors stated that they had no conflicts of interest.

[email protected]

SOURCE: Li X et al. Cancer Lett. 2020 Aug 14. doi: 10.1016/j.canlet.2020.07.032.

The STAT3 pathway is important to the development of many cancers, but so far, no Food and Drug Administration–approved drugs are ready for clinical use. Napabucasin, a novel oral small-molecule inhibitor of signal transducer and activator of transcription 3 (STAT3), blocks tumor growth and resists metastasis in a broad spectrum of solid tumors. Napabucasin was now found to be effective in inhibiting diffuse large beta cell lymphoma (DLBCL) in cell lines and in in vitro testing, as reported by Xue Li of the West China Hospital, Sichuan (China) University, and colleagues.

In addition, the effects of napabucasin were found to be synergistic with the use of doxorubicin, a standard DLBCL therapy agent, according to the report, published online in Cancer Letters.
 

‘Dramatic’ results

The researchers found that 34% (23/69) of DLBCL patients expressed STAT3 in tumor tissues. When they tested napabucasin in a variety of DLBCL cell lines they found that the drug exhibited potent cytotoxicity in a dose-dependent manner. In addition, they found that napabucasin induced intrinsic and extrinsic cell apoptosis, downregulated the expression of STAT3 target genes, including the antiapoptotic protein Mcl-1, and regulated the mitogen-activated protein kinase (MAPK) pathway, all important indicators of antitumor effectiveness in vitro.

In cells treated with napabucasin and doxorubicin alone and in combination, napabucasin alone significantly suppressed tumor growth, compared with that of the control (P < .01), achieving tumor growth inhibition (TGI) of 78.8%. The combination treatment, “with a dramatic TGI of 98.2%,” was more effective than doxorubicin monotherapy (TGI = 63.2%; P < .05), according to the researchers.

“Our study provided evidence that napabucasin is an attractive candidate drug either as a monotherapy or in combination therapies for DLBCL treatment. Further work studying the clinical efficacy and combination treatment schedule should be performed for personalized therapy,” the researchers concluded.

The work was supported by grants from the Chinese government. The authors stated that they had no conflicts of interest.

[email protected]

SOURCE: Li X et al. Cancer Lett. 2020 Aug 14. doi: 10.1016/j.canlet.2020.07.032.

The STAT3 pathway is important to the development of many cancers, but so far, no Food and Drug Administration–approved drugs are ready for clinical use. Napabucasin, a novel oral small-molecule inhibitor of signal transducer and activator of transcription 3 (STAT3), blocks tumor growth and resists metastasis in a broad spectrum of solid tumors. Napabucasin was now found to be effective in inhibiting diffuse large beta cell lymphoma (DLBCL) in cell lines and in in vitro testing, as reported by Xue Li of the West China Hospital, Sichuan (China) University, and colleagues.

In addition, the effects of napabucasin were found to be synergistic with the use of doxorubicin, a standard DLBCL therapy agent, according to the report, published online in Cancer Letters.
 

‘Dramatic’ results

The researchers found that 34% (23/69) of DLBCL patients expressed STAT3 in tumor tissues. When they tested napabucasin in a variety of DLBCL cell lines they found that the drug exhibited potent cytotoxicity in a dose-dependent manner. In addition, they found that napabucasin induced intrinsic and extrinsic cell apoptosis, downregulated the expression of STAT3 target genes, including the antiapoptotic protein Mcl-1, and regulated the mitogen-activated protein kinase (MAPK) pathway, all important indicators of antitumor effectiveness in vitro.

In cells treated with napabucasin and doxorubicin alone and in combination, napabucasin alone significantly suppressed tumor growth, compared with that of the control (P < .01), achieving tumor growth inhibition (TGI) of 78.8%. The combination treatment, “with a dramatic TGI of 98.2%,” was more effective than doxorubicin monotherapy (TGI = 63.2%; P < .05), according to the researchers.

“Our study provided evidence that napabucasin is an attractive candidate drug either as a monotherapy or in combination therapies for DLBCL treatment. Further work studying the clinical efficacy and combination treatment schedule should be performed for personalized therapy,” the researchers concluded.

The work was supported by grants from the Chinese government. The authors stated that they had no conflicts of interest.

[email protected]

SOURCE: Li X et al. Cancer Lett. 2020 Aug 14. doi: 10.1016/j.canlet.2020.07.032.

A single educational mailing sent by several U.S. health plans to their patients with atrial fibrillation who were candidates for oral anticoagulation, but had not yet started a regimen, failed to boost them over their prescription hurdle and facilitate starting an antithrombotic regimen.

By 1 year following the intervention, a mere 10% of patients in both the intervention and a control arm of the randomized trial had begun treatment, with no signal of incremental uptake because of the mailing, Sean D. Pokorney, MD, said at the virtual annual congress of the European Society of Cardiology. Included in the mailing was an educational letter citing the patient’s atrial fibrillation (AFib) diagnosis, a statement regarding their suitability for oral anticoagulation, some information about the treatment, and a suggestion that recipients discuss this with their personal physician.

Dr. Pokorney acknowledged that the single mailing to patients may not have been adequate to capture patients’ attention and trigger an action, and that repeated messaging via multiple platforms and in coordination with interventions aimed at their health care providers may be what’s needed.

“It will take repeated interventions and engagements. We will need different methods to move the needle,” said Dr. Pokorney, a cardiac electrophysiologist at Duke University in Durham, N.C. The goal is to “empower patients to talk with their health care providers, and to become agents of change” in their care, he explained, but the single, mailed prod wasn’t enough.

An earlier study run by Dr. Pokorney and several of his colleagues used a broader panel of interventions aimed at both patients and clinicians to encourage increased prescribing of oral anticoagulants in five middle income countries, and documented successfully increasing the uptake rate by threefold compared with control patients (Lancet. 2017 Oct 14;390[10104]:1737-46). The current study tested the efficacy of a “much lower-impact intervention,” he admitted.

“The data are “sobering and eye-opening,” said Kalyanam Shivkumar, MD, a cardiac electrophysiologist and professor of medicine at the University of California, Los Angeles. “We’re stuck with this big challenge,” the gap between “what medicine can do and what it actually does” when evidence-based interventions fail to gain traction in everyday practice, he said in an interview.

The numbers collected during the new study highlighted the treatment gap. The IMPACT-AFib study randomized 23,546 patients with AFib and a CHA2DS2-VASc score of at least 2, denoting a stroke risk that warrants oral anticoagulation, to the intervention group, and 23,787 patients to the control arm. The patient selection process began with nearly 200,000 patients who met these criteria, but the researchers excluded 67% because they were already on an oral anticoagulant regimen, an uptake level that roughly matched the 50%-60% level usually seen among U.S. patients, Dr. Pokorney noted. That number coupled with the incremental uptake rate of only 10% of the enrolled patients during the trial, despite their uniform suitability for treatment, underscored how low uptake rates tend to remain stuck over time.

Enrolled patients averaged 78 years of age, with nearly two-thirds at least 75 years old, and with an average CHA2DS2-VASc score of 4.5.

The trial featured a novel design as the first clinical trial to take advantage of the Sentinel program for phase 4 data collection and study devised by the Food and Drug Administration, said Dr. Pokorney. The Sentinel program relies on data partners to provide information; for the IMPACT-AFib study, data came from five large U.S. health systems: Aetna, HealthCore, Humana, Harvard Pilgrim Healthcare, and Optum. Each of these systems sent the mailing to their targeted member patients.

In addition to sending just a single, mailed intervention, the study may have also been limited by the mailing’s content. The educational text, presented by Dr. Pokorney during his talk, focused largely on the potential risks of oral anticoagulation, the limited availability of antidote agents, potential drug and food interactions, and a brief entry about the risk for stroke associated with AFib along with a chart that a patient could use to hand calculate their CHA₂DS₂-VASc score. What the mailing lacked was discussion of the benefits of oral anticoagulation, noted study discussant Christophe LeClercq, MD, a cardiac electrophysiologist and professor of cardiology at the University of Rennes, France.

IMPACT-AFib received no commercial funding, and Dr. Pokorney and Dr. Shivkumar had no disclosures. Dr. Leclercq has received honoraria from Abbott, Biotronik, Boston Scientific, Livanova, and Medtronic.

[email protected]

A single educational mailing sent by several U.S. health plans to their patients with atrial fibrillation who were candidates for oral anticoagulation, but had not yet started a regimen, failed to boost them over their prescription hurdle and facilitate starting an antithrombotic regimen.

By 1 year following the intervention, a mere 10% of patients in both the intervention and a control arm of the randomized trial had begun treatment, with no signal of incremental uptake because of the mailing, Sean D. Pokorney, MD, said at the virtual annual congress of the European Society of Cardiology. Included in the mailing was an educational letter citing the patient’s atrial fibrillation (AFib) diagnosis, a statement regarding their suitability for oral anticoagulation, some information about the treatment, and a suggestion that recipients discuss this with their personal physician.

Dr. Pokorney acknowledged that the single mailing to patients may not have been adequate to capture patients’ attention and trigger an action, and that repeated messaging via multiple platforms and in coordination with interventions aimed at their health care providers may be what’s needed.

“It will take repeated interventions and engagements. We will need different methods to move the needle,” said Dr. Pokorney, a cardiac electrophysiologist at Duke University in Durham, N.C. The goal is to “empower patients to talk with their health care providers, and to become agents of change” in their care, he explained, but the single, mailed prod wasn’t enough.

An earlier study run by Dr. Pokorney and several of his colleagues used a broader panel of interventions aimed at both patients and clinicians to encourage increased prescribing of oral anticoagulants in five middle income countries, and documented successfully increasing the uptake rate by threefold compared with control patients (Lancet. 2017 Oct 14;390[10104]:1737-46). The current study tested the efficacy of a “much lower-impact intervention,” he admitted.

“The data are “sobering and eye-opening,” said Kalyanam Shivkumar, MD, a cardiac electrophysiologist and professor of medicine at the University of California, Los Angeles. “We’re stuck with this big challenge,” the gap between “what medicine can do and what it actually does” when evidence-based interventions fail to gain traction in everyday practice, he said in an interview.

The numbers collected during the new study highlighted the treatment gap. The IMPACT-AFib study randomized 23,546 patients with AFib and a CHA2DS2-VASc score of at least 2, denoting a stroke risk that warrants oral anticoagulation, to the intervention group, and 23,787 patients to the control arm. The patient selection process began with nearly 200,000 patients who met these criteria, but the researchers excluded 67% because they were already on an oral anticoagulant regimen, an uptake level that roughly matched the 50%-60% level usually seen among U.S. patients, Dr. Pokorney noted. That number coupled with the incremental uptake rate of only 10% of the enrolled patients during the trial, despite their uniform suitability for treatment, underscored how low uptake rates tend to remain stuck over time.

Enrolled patients averaged 78 years of age, with nearly two-thirds at least 75 years old, and with an average CHA2DS2-VASc score of 4.5.

The trial featured a novel design as the first clinical trial to take advantage of the Sentinel program for phase 4 data collection and study devised by the Food and Drug Administration, said Dr. Pokorney. The Sentinel program relies on data partners to provide information; for the IMPACT-AFib study, data came from five large U.S. health systems: Aetna, HealthCore, Humana, Harvard Pilgrim Healthcare, and Optum. Each of these systems sent the mailing to their targeted member patients.

In addition to sending just a single, mailed intervention, the study may have also been limited by the mailing’s content. The educational text, presented by Dr. Pokorney during his talk, focused largely on the potential risks of oral anticoagulation, the limited availability of antidote agents, potential drug and food interactions, and a brief entry about the risk for stroke associated with AFib along with a chart that a patient could use to hand calculate their CHA₂DS₂-VASc score. What the mailing lacked was discussion of the benefits of oral anticoagulation, noted study discussant Christophe LeClercq, MD, a cardiac electrophysiologist and professor of cardiology at the University of Rennes, France.

IMPACT-AFib received no commercial funding, and Dr. Pokorney and Dr. Shivkumar had no disclosures. Dr. Leclercq has received honoraria from Abbott, Biotronik, Boston Scientific, Livanova, and Medtronic.

[email protected]

A single educational mailing sent by several U.S. health plans to their patients with atrial fibrillation who were candidates for oral anticoagulation, but had not yet started a regimen, failed to boost them over their prescription hurdle and facilitate starting an antithrombotic regimen.

By 1 year following the intervention, a mere 10% of patients in both the intervention and a control arm of the randomized trial had begun treatment, with no signal of incremental uptake because of the mailing, Sean D. Pokorney, MD, said at the virtual annual congress of the European Society of Cardiology. Included in the mailing was an educational letter citing the patient’s atrial fibrillation (AFib) diagnosis, a statement regarding their suitability for oral anticoagulation, some information about the treatment, and a suggestion that recipients discuss this with their personal physician.

Dr. Pokorney acknowledged that the single mailing to patients may not have been adequate to capture patients’ attention and trigger an action, and that repeated messaging via multiple platforms and in coordination with interventions aimed at their health care providers may be what’s needed.

“It will take repeated interventions and engagements. We will need different methods to move the needle,” said Dr. Pokorney, a cardiac electrophysiologist at Duke University in Durham, N.C. The goal is to “empower patients to talk with their health care providers, and to become agents of change” in their care, he explained, but the single, mailed prod wasn’t enough.

An earlier study run by Dr. Pokorney and several of his colleagues used a broader panel of interventions aimed at both patients and clinicians to encourage increased prescribing of oral anticoagulants in five middle income countries, and documented successfully increasing the uptake rate by threefold compared with control patients (Lancet. 2017 Oct 14;390[10104]:1737-46). The current study tested the efficacy of a “much lower-impact intervention,” he admitted.

“The data are “sobering and eye-opening,” said Kalyanam Shivkumar, MD, a cardiac electrophysiologist and professor of medicine at the University of California, Los Angeles. “We’re stuck with this big challenge,” the gap between “what medicine can do and what it actually does” when evidence-based interventions fail to gain traction in everyday practice, he said in an interview.

The numbers collected during the new study highlighted the treatment gap. The IMPACT-AFib study randomized 23,546 patients with AFib and a CHA2DS2-VASc score of at least 2, denoting a stroke risk that warrants oral anticoagulation, to the intervention group, and 23,787 patients to the control arm. The patient selection process began with nearly 200,000 patients who met these criteria, but the researchers excluded 67% because they were already on an oral anticoagulant regimen, an uptake level that roughly matched the 50%-60% level usually seen among U.S. patients, Dr. Pokorney noted. That number coupled with the incremental uptake rate of only 10% of the enrolled patients during the trial, despite their uniform suitability for treatment, underscored how low uptake rates tend to remain stuck over time.

Enrolled patients averaged 78 years of age, with nearly two-thirds at least 75 years old, and with an average CHA2DS2-VASc score of 4.5.

The trial featured a novel design as the first clinical trial to take advantage of the Sentinel program for phase 4 data collection and study devised by the Food and Drug Administration, said Dr. Pokorney. The Sentinel program relies on data partners to provide information; for the IMPACT-AFib study, data came from five large U.S. health systems: Aetna, HealthCore, Humana, Harvard Pilgrim Healthcare, and Optum. Each of these systems sent the mailing to their targeted member patients.

In addition to sending just a single, mailed intervention, the study may have also been limited by the mailing’s content. The educational text, presented by Dr. Pokorney during his talk, focused largely on the potential risks of oral anticoagulation, the limited availability of antidote agents, potential drug and food interactions, and a brief entry about the risk for stroke associated with AFib along with a chart that a patient could use to hand calculate their CHA₂DS₂-VASc score. What the mailing lacked was discussion of the benefits of oral anticoagulation, noted study discussant Christophe LeClercq, MD, a cardiac electrophysiologist and professor of cardiology at the University of Rennes, France.

IMPACT-AFib received no commercial funding, and Dr. Pokorney and Dr. Shivkumar had no disclosures. Dr. Leclercq has received honoraria from Abbott, Biotronik, Boston Scientific, Livanova, and Medtronic.

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