Heidi Splete

Cesarean deliveries in women in the United States who were at low risk for the procedure declined overall during the 2 decades from 2000 to 2019, based on data from more than 40 million deliveries.

Although clinically indicated cesarean deliveries may improve outcomes for mothers and infants, “when not clinically indicated, cesarean delivery is a major surgical intervention that increases risk for adverse outcomes,” wrote Anna M. Frappaolo of Columbia University College of Physicians and Surgeons, New York, and colleagues.

The Healthy People 2030 campaign includes the reduction of cesarean deliveries, but trends in these procedures, especially with regard to diagnoses of labor arrest, have not been well studied, the researchers said.

In an analysis published in JAMA Network Open, the researchers reviewed delivery hospitalizations using data from the National Inpatient Sample from 2000 to 2019.

Births deemed low risk for cesarean delivery were identified by using criteria of the Society for Maternal-Fetal Medicine and additional criteria, and joinpoint regression analysis was used to estimate changes.

The researchers examined overall trends in cesarean deliveries as well as trends for three specific diagnoses: nonreassuring fetal status, labor arrest, and obstructed labor.

The final analysis included 40,517,867 deliveries; of these, 4,885,716 (12.1%) were cesarean deliveries.

Overall, cesarean deliveries in patients deemed at low risk increased from 9.7% in 2000 to 13.9% in 2009, then plateaued and decreased from 13.0% in 2012 to 11.1% in 2019. The average annual percentage change (AAPC) for cesarean delivery was 6.4% for the years from 2000 to 2005, 1.2% from 2005 to 2009, and −2.2% from 2009 to 2019.

Cesarean delivery for nonreassuring fetal status increased over the entire study period, from 3.4% in 2000 to 5.1% in 2019. By contrast, overall cesarean delivery for labor arrest increased from 3.6% in 2000 to a high of 4.8% in 2009, then decreased to 2.7% in 2019. Cesarean deliveries with a diagnosis of obstructed labor decreased from 0.9% in 2008 to 0.3% in 2019.

More specifically, cesarean deliveries for labor arrest in the active phase, latent phase, and second stage of labor increased from 1.5% to 2.1%, 1.1% to 1.5%, and 0.9% to 1.3%, respectively, from 2000 to 2009, and decreased from 2.1% to 1.7% for the active phase, from 1.5% to 1.2% for the latent phase, and from 1.2% to 0.9% for the second stage between 2010 and 2019.

Patients with increased odds of cesarean delivery were older (aged 35-39 years vs. 25-29 years, adjusted odds ratio 1.27), delivered in a hospital in the South vs. the Northeast of the United States (aOR 1.11), and were more likely to be non-Hispanic Black vs. non-Hispanic White (OR 1.23).

Notably, changes in nomenclature and interpretation of intrapartum electronic fetal heart monitoring occurred during the study period, with recommendations for the adoption of a three-tiered system for fetal heart rate patterns in 2008. “It is possible that current evidence and nomenclature related to intrapartum FHR interpretation may result in identification of a larger number of fetuses deemed at indeterminate risk for abnormal acid-base status,” the researchers wrote in their discussion.

The study findings were limited by several factors including the use of administrative discharge data rather than clinical records, the exclusion of patients with chronic conditions associated with cesarean delivery, changes in billing codes during the study period, and the inability to account for the effect of health factors, maternal age, and use of assisted reproductive technology, the researchers noted.

However, the results were strengthened by the large sample size and 20-year study period, as well as the stratification of labor arrest by stage, and suggest uptake of newer recommendations, they said. “Future reductions in cesarean deliveries among patients at low risk for cesarean delivery may be dependent on improved assessment of intrapartum fetal status,” they concluded.

Consider populations and outcomes in cesarean risk assessment

The decreasing rates of cesarean deliveries in the current study can be seen as positive, but more research is needed to examine maternal and neonatal outcomes, and to consider other conditions that affect risk for cesarean delivery, Paolo Ivo Cavoretto, MD, and Massimo Candiani, MD, of IRCCS San Raffaele Scientific Institute, and Antonio Farina, MD, of the University of Bologna, Italy, wrote in an accompanying editorial.

Notably, the study authors identified a population aged 15-39 years as low risk, and an increased risk for cesarean delivery within this range increased with age. “Maternal age remains a major risk factor associated with the risk of cesarean delivery, both from results of this study and those of previous analyses assessing its independence from other related risk factors,” the editorialists said.

The study findings also reflect the changes in standards for labor duration during the study period, they noted. The longer duration of labor may reduce cesarean delivery rates, but it is not without maternal and fetal-neonatal risks, they wrote.

“To be sure that the described trend of cesarean delivery rate reduction can be considered positive, there would be the theoretical need to analyze other maternal-fetal-neonatal outcomes (e.g., rates of operative deliveries, neonatal acidemia, intensive care unit use, maternal hemorrhage, pelvic floor trauma and dysfunction, and psychological distress),” the editorialists concluded.
 

More research needed to explore clinical decisions

“Reducing the cesarean delivery rate is a top priority, but evidence is lacking on an optimal rate that improves maternal and neonatal outcomes,” Iris Krishna, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, said in an interview.

“Hospital quality and safety committees have been working to decrease cesarean deliveries amongst low-risk women, and identifying contemporary trends gives us insight on whether some of these efforts have translated to a lower cesarean delivery rate,” she said.

Dr. Krishna said she was not surprised by the higher cesarean section rate in the South. “The decision for cesarean delivery is multifaceted, and although this study was not able to assess clinical indications for cesarean delivery or maternal and fetal outcomes, we cannot ignore that social determinants of health contribute greatly to overall health outcomes,” she said. The trends in the current study further underscore the geographic disparities in access to health care present in the South, she added.

“This study notes that cesarean delivery for nonreassuring fetal status increased; however, nonreassuring fetal status as an indication for cesarean delivery can be subjective,” Dr. Krishna said. “Hospital quality and safety committees should consider reviewing the clinical scenarios that led to this decision to identify opportunities for improvement and further education,” she said.

“Defining contemporary trends in cesarean delivery for low-risk patients has merit, but the study findings should be interpreted with caution,” said Dr. Krishna, who is a member of the Ob.Gyn. News advisory board. More research is needed to define an optimal cesarean section rate that promotes positive maternal and fetal outcomes, and to determine whether identifying an optimal rate should be based on patient risk profiles, she said.

The study received no outside funding. Lead author Ms. Frappaolo had no financial conflicts to disclose; nor did the editorial authors or Dr. Krishna.

Cesarean deliveries in women in the United States who were at low risk for the procedure declined overall during the 2 decades from 2000 to 2019, based on data from more than 40 million deliveries.

Although clinically indicated cesarean deliveries may improve outcomes for mothers and infants, “when not clinically indicated, cesarean delivery is a major surgical intervention that increases risk for adverse outcomes,” wrote Anna M. Frappaolo of Columbia University College of Physicians and Surgeons, New York, and colleagues.

The Healthy People 2030 campaign includes the reduction of cesarean deliveries, but trends in these procedures, especially with regard to diagnoses of labor arrest, have not been well studied, the researchers said.

In an analysis published in JAMA Network Open, the researchers reviewed delivery hospitalizations using data from the National Inpatient Sample from 2000 to 2019.

Births deemed low risk for cesarean delivery were identified by using criteria of the Society for Maternal-Fetal Medicine and additional criteria, and joinpoint regression analysis was used to estimate changes.

The researchers examined overall trends in cesarean deliveries as well as trends for three specific diagnoses: nonreassuring fetal status, labor arrest, and obstructed labor.

The final analysis included 40,517,867 deliveries; of these, 4,885,716 (12.1%) were cesarean deliveries.

Overall, cesarean deliveries in patients deemed at low risk increased from 9.7% in 2000 to 13.9% in 2009, then plateaued and decreased from 13.0% in 2012 to 11.1% in 2019. The average annual percentage change (AAPC) for cesarean delivery was 6.4% for the years from 2000 to 2005, 1.2% from 2005 to 2009, and −2.2% from 2009 to 2019.

Cesarean delivery for nonreassuring fetal status increased over the entire study period, from 3.4% in 2000 to 5.1% in 2019. By contrast, overall cesarean delivery for labor arrest increased from 3.6% in 2000 to a high of 4.8% in 2009, then decreased to 2.7% in 2019. Cesarean deliveries with a diagnosis of obstructed labor decreased from 0.9% in 2008 to 0.3% in 2019.

More specifically, cesarean deliveries for labor arrest in the active phase, latent phase, and second stage of labor increased from 1.5% to 2.1%, 1.1% to 1.5%, and 0.9% to 1.3%, respectively, from 2000 to 2009, and decreased from 2.1% to 1.7% for the active phase, from 1.5% to 1.2% for the latent phase, and from 1.2% to 0.9% for the second stage between 2010 and 2019.

Patients with increased odds of cesarean delivery were older (aged 35-39 years vs. 25-29 years, adjusted odds ratio 1.27), delivered in a hospital in the South vs. the Northeast of the United States (aOR 1.11), and were more likely to be non-Hispanic Black vs. non-Hispanic White (OR 1.23).

Notably, changes in nomenclature and interpretation of intrapartum electronic fetal heart monitoring occurred during the study period, with recommendations for the adoption of a three-tiered system for fetal heart rate patterns in 2008. “It is possible that current evidence and nomenclature related to intrapartum FHR interpretation may result in identification of a larger number of fetuses deemed at indeterminate risk for abnormal acid-base status,” the researchers wrote in their discussion.

The study findings were limited by several factors including the use of administrative discharge data rather than clinical records, the exclusion of patients with chronic conditions associated with cesarean delivery, changes in billing codes during the study period, and the inability to account for the effect of health factors, maternal age, and use of assisted reproductive technology, the researchers noted.

However, the results were strengthened by the large sample size and 20-year study period, as well as the stratification of labor arrest by stage, and suggest uptake of newer recommendations, they said. “Future reductions in cesarean deliveries among patients at low risk for cesarean delivery may be dependent on improved assessment of intrapartum fetal status,” they concluded.

Consider populations and outcomes in cesarean risk assessment

The decreasing rates of cesarean deliveries in the current study can be seen as positive, but more research is needed to examine maternal and neonatal outcomes, and to consider other conditions that affect risk for cesarean delivery, Paolo Ivo Cavoretto, MD, and Massimo Candiani, MD, of IRCCS San Raffaele Scientific Institute, and Antonio Farina, MD, of the University of Bologna, Italy, wrote in an accompanying editorial.

Notably, the study authors identified a population aged 15-39 years as low risk, and an increased risk for cesarean delivery within this range increased with age. “Maternal age remains a major risk factor associated with the risk of cesarean delivery, both from results of this study and those of previous analyses assessing its independence from other related risk factors,” the editorialists said.

The study findings also reflect the changes in standards for labor duration during the study period, they noted. The longer duration of labor may reduce cesarean delivery rates, but it is not without maternal and fetal-neonatal risks, they wrote.

“To be sure that the described trend of cesarean delivery rate reduction can be considered positive, there would be the theoretical need to analyze other maternal-fetal-neonatal outcomes (e.g., rates of operative deliveries, neonatal acidemia, intensive care unit use, maternal hemorrhage, pelvic floor trauma and dysfunction, and psychological distress),” the editorialists concluded.
 

More research needed to explore clinical decisions

“Reducing the cesarean delivery rate is a top priority, but evidence is lacking on an optimal rate that improves maternal and neonatal outcomes,” Iris Krishna, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, said in an interview.

“Hospital quality and safety committees have been working to decrease cesarean deliveries amongst low-risk women, and identifying contemporary trends gives us insight on whether some of these efforts have translated to a lower cesarean delivery rate,” she said.

Dr. Krishna said she was not surprised by the higher cesarean section rate in the South. “The decision for cesarean delivery is multifaceted, and although this study was not able to assess clinical indications for cesarean delivery or maternal and fetal outcomes, we cannot ignore that social determinants of health contribute greatly to overall health outcomes,” she said. The trends in the current study further underscore the geographic disparities in access to health care present in the South, she added.

“This study notes that cesarean delivery for nonreassuring fetal status increased; however, nonreassuring fetal status as an indication for cesarean delivery can be subjective,” Dr. Krishna said. “Hospital quality and safety committees should consider reviewing the clinical scenarios that led to this decision to identify opportunities for improvement and further education,” she said.

“Defining contemporary trends in cesarean delivery for low-risk patients has merit, but the study findings should be interpreted with caution,” said Dr. Krishna, who is a member of the Ob.Gyn. News advisory board. More research is needed to define an optimal cesarean section rate that promotes positive maternal and fetal outcomes, and to determine whether identifying an optimal rate should be based on patient risk profiles, she said.

The study received no outside funding. Lead author Ms. Frappaolo had no financial conflicts to disclose; nor did the editorial authors or Dr. Krishna.

Cesarean deliveries in women in the United States who were at low risk for the procedure declined overall during the 2 decades from 2000 to 2019, based on data from more than 40 million deliveries.

Although clinically indicated cesarean deliveries may improve outcomes for mothers and infants, “when not clinically indicated, cesarean delivery is a major surgical intervention that increases risk for adverse outcomes,” wrote Anna M. Frappaolo of Columbia University College of Physicians and Surgeons, New York, and colleagues.

The Healthy People 2030 campaign includes the reduction of cesarean deliveries, but trends in these procedures, especially with regard to diagnoses of labor arrest, have not been well studied, the researchers said.

In an analysis published in JAMA Network Open, the researchers reviewed delivery hospitalizations using data from the National Inpatient Sample from 2000 to 2019.

Births deemed low risk for cesarean delivery were identified by using criteria of the Society for Maternal-Fetal Medicine and additional criteria, and joinpoint regression analysis was used to estimate changes.

The researchers examined overall trends in cesarean deliveries as well as trends for three specific diagnoses: nonreassuring fetal status, labor arrest, and obstructed labor.

The final analysis included 40,517,867 deliveries; of these, 4,885,716 (12.1%) were cesarean deliveries.

Overall, cesarean deliveries in patients deemed at low risk increased from 9.7% in 2000 to 13.9% in 2009, then plateaued and decreased from 13.0% in 2012 to 11.1% in 2019. The average annual percentage change (AAPC) for cesarean delivery was 6.4% for the years from 2000 to 2005, 1.2% from 2005 to 2009, and −2.2% from 2009 to 2019.

Cesarean delivery for nonreassuring fetal status increased over the entire study period, from 3.4% in 2000 to 5.1% in 2019. By contrast, overall cesarean delivery for labor arrest increased from 3.6% in 2000 to a high of 4.8% in 2009, then decreased to 2.7% in 2019. Cesarean deliveries with a diagnosis of obstructed labor decreased from 0.9% in 2008 to 0.3% in 2019.

More specifically, cesarean deliveries for labor arrest in the active phase, latent phase, and second stage of labor increased from 1.5% to 2.1%, 1.1% to 1.5%, and 0.9% to 1.3%, respectively, from 2000 to 2009, and decreased from 2.1% to 1.7% for the active phase, from 1.5% to 1.2% for the latent phase, and from 1.2% to 0.9% for the second stage between 2010 and 2019.

Patients with increased odds of cesarean delivery were older (aged 35-39 years vs. 25-29 years, adjusted odds ratio 1.27), delivered in a hospital in the South vs. the Northeast of the United States (aOR 1.11), and were more likely to be non-Hispanic Black vs. non-Hispanic White (OR 1.23).

Notably, changes in nomenclature and interpretation of intrapartum electronic fetal heart monitoring occurred during the study period, with recommendations for the adoption of a three-tiered system for fetal heart rate patterns in 2008. “It is possible that current evidence and nomenclature related to intrapartum FHR interpretation may result in identification of a larger number of fetuses deemed at indeterminate risk for abnormal acid-base status,” the researchers wrote in their discussion.

The study findings were limited by several factors including the use of administrative discharge data rather than clinical records, the exclusion of patients with chronic conditions associated with cesarean delivery, changes in billing codes during the study period, and the inability to account for the effect of health factors, maternal age, and use of assisted reproductive technology, the researchers noted.

However, the results were strengthened by the large sample size and 20-year study period, as well as the stratification of labor arrest by stage, and suggest uptake of newer recommendations, they said. “Future reductions in cesarean deliveries among patients at low risk for cesarean delivery may be dependent on improved assessment of intrapartum fetal status,” they concluded.

Consider populations and outcomes in cesarean risk assessment

The decreasing rates of cesarean deliveries in the current study can be seen as positive, but more research is needed to examine maternal and neonatal outcomes, and to consider other conditions that affect risk for cesarean delivery, Paolo Ivo Cavoretto, MD, and Massimo Candiani, MD, of IRCCS San Raffaele Scientific Institute, and Antonio Farina, MD, of the University of Bologna, Italy, wrote in an accompanying editorial.

Notably, the study authors identified a population aged 15-39 years as low risk, and an increased risk for cesarean delivery within this range increased with age. “Maternal age remains a major risk factor associated with the risk of cesarean delivery, both from results of this study and those of previous analyses assessing its independence from other related risk factors,” the editorialists said.

The study findings also reflect the changes in standards for labor duration during the study period, they noted. The longer duration of labor may reduce cesarean delivery rates, but it is not without maternal and fetal-neonatal risks, they wrote.

“To be sure that the described trend of cesarean delivery rate reduction can be considered positive, there would be the theoretical need to analyze other maternal-fetal-neonatal outcomes (e.g., rates of operative deliveries, neonatal acidemia, intensive care unit use, maternal hemorrhage, pelvic floor trauma and dysfunction, and psychological distress),” the editorialists concluded.
 

More research needed to explore clinical decisions

“Reducing the cesarean delivery rate is a top priority, but evidence is lacking on an optimal rate that improves maternal and neonatal outcomes,” Iris Krishna, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, said in an interview.

“Hospital quality and safety committees have been working to decrease cesarean deliveries amongst low-risk women, and identifying contemporary trends gives us insight on whether some of these efforts have translated to a lower cesarean delivery rate,” she said.

Dr. Krishna said she was not surprised by the higher cesarean section rate in the South. “The decision for cesarean delivery is multifaceted, and although this study was not able to assess clinical indications for cesarean delivery or maternal and fetal outcomes, we cannot ignore that social determinants of health contribute greatly to overall health outcomes,” she said. The trends in the current study further underscore the geographic disparities in access to health care present in the South, she added.

“This study notes that cesarean delivery for nonreassuring fetal status increased; however, nonreassuring fetal status as an indication for cesarean delivery can be subjective,” Dr. Krishna said. “Hospital quality and safety committees should consider reviewing the clinical scenarios that led to this decision to identify opportunities for improvement and further education,” she said.

“Defining contemporary trends in cesarean delivery for low-risk patients has merit, but the study findings should be interpreted with caution,” said Dr. Krishna, who is a member of the Ob.Gyn. News advisory board. More research is needed to define an optimal cesarean section rate that promotes positive maternal and fetal outcomes, and to determine whether identifying an optimal rate should be based on patient risk profiles, she said.

The study received no outside funding. Lead author Ms. Frappaolo had no financial conflicts to disclose; nor did the editorial authors or Dr. Krishna.

High-dose prophylactic anticoagulation or therapeutic anticoagulation reduced de novo thrombosis in patients with hypoxemic COVID-19 pneumonia, based on data from 334 adults.

Patients with hypoxemic COVID-19 pneumonia are at increased risk of thrombosis and anticoagulation-related bleeding, therefore data to identify the lowest effective anticoagulant dose are needed, wrote Vincent Labbé, MD, of Sorbonne University, Paris, and colleagues.

Previous studies of different anticoagulation strategies for noncritically ill and critically ill patients with COVID-19 pneumonia have shown contrasting results, but some institutions recommend a high-dose regimen in the wake of data showing macrovascular thrombosis in patients with COVID-19 who were treated with standard anticoagulation, the authors wrote.

However, no previously published studies have compared the effectiveness of the three anticoagulation strategies: high-dose prophylactic anticoagulation (HD-PA), standard dose prophylactic anticoagulation (SD-PA), and therapeutic anticoagulation (TA), they said.

In the open-label Anticoagulation COVID-19 (ANTICOVID) trial, published in JAMA Internal Medicine, the researchers identified consecutively hospitalized adults aged 18 years and older being treated for hypoxemic COVID-19 pneumonia in 23 centers in France between April 2021 and December 2021.

The patients were randomly assigned to SD-PA (116 patients), HD-PA (111 patients), and TA (112 patients) using low-molecular-weight heparin for 14 days, or until either hospital discharge or weaning from supplemental oxygen for 48 consecutive hours, whichever outcome occurred first.  The HD-PA patients received two times the SD-PA dose. The mean age of the patients was 58.3 years, and approximately two-thirds were men; race and ethnicity data were not collected. Participants had no macrovascular thrombosis at the start of the study.

The primary outcomes were all-cause mortality and time to clinical improvement (defined as the time from randomization to a 2-point improvement on a 7-category respiratory function scale).

The secondary outcome was a combination of safety and efficacy at day 28 that included a composite of thrombosis (ischemic stroke, noncerebrovascular arterial thrombosis, deep venous thrombosis, pulmonary artery thrombosis, and central venous catheter–related deep venous thrombosis), major bleeding, or all-cause death.

For the primary outcome, results were similar among the groups; HD-PA had no significant benefit over SD-PA or TA. All-cause death rates for SD-PA, HD-PA, and TA patients were 14%, 12%, and 13%, respectively. The time to clinical improvement for the three groups was approximately 8 days, 9 days, and 8 days, respectively. Results for the primary outcome were consistent across all prespecified subgroups.

However, HD-PA was associated with a significant fourfold reduced risk of de novo thrombosis compared with SD-PA (5.5% vs. 20.2%) with no observed increase in major bleeding. TA was not associated with any significant improvement in primary or secondary outcomes compared with HD-PA or SD-PA.

The current study findings of no improvement in survival or disease resolution in patients with a higher anticoagulant dose reflects data from previous studies, the researchers wrote in their discussion. “Our study results together with those of previous RCTs support the premise that the role of microvascular thrombosis in worsening organ dysfunction may be narrower than estimated,” they said.

The findings were limited by several factors including the open-label design and the relatively small sample size, the lack of data on microvascular (vs. macrovascular) thrombosis at baseline, and the predominance of the Delta variant of COVID-19 among the study participants, which may have contributed to a lower mortality rate, the researchers noted.

However, given the significant reduction in de novo thrombosis, the results support the routine use of HD-PA in patients with severe hypoxemic COVID-19 pneumonia, they concluded.
 

Results inform current clinical practice

Over the course of the COVID-19 pandemic, “Patients hospitalized with COVID-19 manifested the highest risk for thromboembolic complications, especially patients in the intensive care setting,” and early reports suggested that standard prophylactic doses of anticoagulant therapy might be insufficient to prevent thrombotic events, Richard C. Becker, MD, of the University of Cincinnati, and Thomas L. Ortel, MD, of Duke University, Durham, N.C., wrote in an accompanying editorial.

“Although there have been several studies that have investigated the role of anticoagulant therapy in hospitalized patients with COVID-19, this is the first study that specifically compared a standard, prophylactic dose of low-molecular-weight heparin to a ‘high-dose’ prophylactic regimen and to a full therapeutic dose regimen,” Dr. Ortel said in an interview.

“Given the concerns about an increased thrombotic risk with prophylactic dose anticoagulation, and the potential bleeding risk associated with a full therapeutic dose of anticoagulation, this approach enabled the investigators to explore the efficacy and safety of an intermediate dose between these two extremes,” he said.

In the current study, “It was notable that the primary driver of the improved outcomes with the ‘high-dose’ prophylactic regimen reflected the fourfold reduction in macrovascular thrombosis, a finding that was not observed in other studies investigating anticoagulant therapy in hospitalized patients with severe COVID-19,” Dr. Ortel told this news organization. “Much initial concern about progression of disease in patients hospitalized with severe COVID-19 focused on the role of microvascular thrombosis, which appears to be less important in this process, or, alternatively, less responsive to anticoagulant therapy.”

The clinical takeaway from the study, Dr. Ortel said, is the decreased risk for venous thromboembolism with a high-dose prophylactic anticoagulation strategy compared with a standard-dose prophylactic regimen for patients hospitalized with hypoxemic COVID-19 pneumonia, “leading to an improved net clinical outcome.”

Looking ahead, “Additional research is needed to determine whether a higher dose of prophylactic anticoagulation would be beneficial for patients hospitalized with COVID-19 pneumonia who are not in an intensive care unit setting,” Dr. Ortel said. Studies are needed to determine whether therapeutic interventions are equally beneficial in patients with different coronavirus variants, since most patients in the current study were infected with the Delta variant, he added.

The study was supported by LEO Pharma. Dr. Labbé disclosed grants from LEO Pharma during the study and fees from AOP Health unrelated to the current study.

Dr. Becker disclosed personal fees from Novartis Data Safety Monitoring Board, Ionis Data Safety Monitoring Board, and Basking Biosciences Scientific Advisory Board unrelated to the current study. Dr. Ortel disclosed grants from the National Institutes of Health, Instrumentation Laboratory, Stago, and Siemens; contract fees from the Centers for Disease Control and Prevention; and honoraria from UpToDate unrelated to the current study.
 

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

High-dose prophylactic anticoagulation or therapeutic anticoagulation reduced de novo thrombosis in patients with hypoxemic COVID-19 pneumonia, based on data from 334 adults.

Patients with hypoxemic COVID-19 pneumonia are at increased risk of thrombosis and anticoagulation-related bleeding, therefore data to identify the lowest effective anticoagulant dose are needed, wrote Vincent Labbé, MD, of Sorbonne University, Paris, and colleagues.

Previous studies of different anticoagulation strategies for noncritically ill and critically ill patients with COVID-19 pneumonia have shown contrasting results, but some institutions recommend a high-dose regimen in the wake of data showing macrovascular thrombosis in patients with COVID-19 who were treated with standard anticoagulation, the authors wrote.

However, no previously published studies have compared the effectiveness of the three anticoagulation strategies: high-dose prophylactic anticoagulation (HD-PA), standard dose prophylactic anticoagulation (SD-PA), and therapeutic anticoagulation (TA), they said.

In the open-label Anticoagulation COVID-19 (ANTICOVID) trial, published in JAMA Internal Medicine, the researchers identified consecutively hospitalized adults aged 18 years and older being treated for hypoxemic COVID-19 pneumonia in 23 centers in France between April 2021 and December 2021.

The patients were randomly assigned to SD-PA (116 patients), HD-PA (111 patients), and TA (112 patients) using low-molecular-weight heparin for 14 days, or until either hospital discharge or weaning from supplemental oxygen for 48 consecutive hours, whichever outcome occurred first.  The HD-PA patients received two times the SD-PA dose. The mean age of the patients was 58.3 years, and approximately two-thirds were men; race and ethnicity data were not collected. Participants had no macrovascular thrombosis at the start of the study.

The primary outcomes were all-cause mortality and time to clinical improvement (defined as the time from randomization to a 2-point improvement on a 7-category respiratory function scale).

The secondary outcome was a combination of safety and efficacy at day 28 that included a composite of thrombosis (ischemic stroke, noncerebrovascular arterial thrombosis, deep venous thrombosis, pulmonary artery thrombosis, and central venous catheter–related deep venous thrombosis), major bleeding, or all-cause death.

For the primary outcome, results were similar among the groups; HD-PA had no significant benefit over SD-PA or TA. All-cause death rates for SD-PA, HD-PA, and TA patients were 14%, 12%, and 13%, respectively. The time to clinical improvement for the three groups was approximately 8 days, 9 days, and 8 days, respectively. Results for the primary outcome were consistent across all prespecified subgroups.

However, HD-PA was associated with a significant fourfold reduced risk of de novo thrombosis compared with SD-PA (5.5% vs. 20.2%) with no observed increase in major bleeding. TA was not associated with any significant improvement in primary or secondary outcomes compared with HD-PA or SD-PA.

The current study findings of no improvement in survival or disease resolution in patients with a higher anticoagulant dose reflects data from previous studies, the researchers wrote in their discussion. “Our study results together with those of previous RCTs support the premise that the role of microvascular thrombosis in worsening organ dysfunction may be narrower than estimated,” they said.

The findings were limited by several factors including the open-label design and the relatively small sample size, the lack of data on microvascular (vs. macrovascular) thrombosis at baseline, and the predominance of the Delta variant of COVID-19 among the study participants, which may have contributed to a lower mortality rate, the researchers noted.

However, given the significant reduction in de novo thrombosis, the results support the routine use of HD-PA in patients with severe hypoxemic COVID-19 pneumonia, they concluded.
 

Results inform current clinical practice

Over the course of the COVID-19 pandemic, “Patients hospitalized with COVID-19 manifested the highest risk for thromboembolic complications, especially patients in the intensive care setting,” and early reports suggested that standard prophylactic doses of anticoagulant therapy might be insufficient to prevent thrombotic events, Richard C. Becker, MD, of the University of Cincinnati, and Thomas L. Ortel, MD, of Duke University, Durham, N.C., wrote in an accompanying editorial.

“Although there have been several studies that have investigated the role of anticoagulant therapy in hospitalized patients with COVID-19, this is the first study that specifically compared a standard, prophylactic dose of low-molecular-weight heparin to a ‘high-dose’ prophylactic regimen and to a full therapeutic dose regimen,” Dr. Ortel said in an interview.

“Given the concerns about an increased thrombotic risk with prophylactic dose anticoagulation, and the potential bleeding risk associated with a full therapeutic dose of anticoagulation, this approach enabled the investigators to explore the efficacy and safety of an intermediate dose between these two extremes,” he said.

In the current study, “It was notable that the primary driver of the improved outcomes with the ‘high-dose’ prophylactic regimen reflected the fourfold reduction in macrovascular thrombosis, a finding that was not observed in other studies investigating anticoagulant therapy in hospitalized patients with severe COVID-19,” Dr. Ortel told this news organization. “Much initial concern about progression of disease in patients hospitalized with severe COVID-19 focused on the role of microvascular thrombosis, which appears to be less important in this process, or, alternatively, less responsive to anticoagulant therapy.”

The clinical takeaway from the study, Dr. Ortel said, is the decreased risk for venous thromboembolism with a high-dose prophylactic anticoagulation strategy compared with a standard-dose prophylactic regimen for patients hospitalized with hypoxemic COVID-19 pneumonia, “leading to an improved net clinical outcome.”

Looking ahead, “Additional research is needed to determine whether a higher dose of prophylactic anticoagulation would be beneficial for patients hospitalized with COVID-19 pneumonia who are not in an intensive care unit setting,” Dr. Ortel said. Studies are needed to determine whether therapeutic interventions are equally beneficial in patients with different coronavirus variants, since most patients in the current study were infected with the Delta variant, he added.

The study was supported by LEO Pharma. Dr. Labbé disclosed grants from LEO Pharma during the study and fees from AOP Health unrelated to the current study.

Dr. Becker disclosed personal fees from Novartis Data Safety Monitoring Board, Ionis Data Safety Monitoring Board, and Basking Biosciences Scientific Advisory Board unrelated to the current study. Dr. Ortel disclosed grants from the National Institutes of Health, Instrumentation Laboratory, Stago, and Siemens; contract fees from the Centers for Disease Control and Prevention; and honoraria from UpToDate unrelated to the current study.
 

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

High-dose prophylactic anticoagulation or therapeutic anticoagulation reduced de novo thrombosis in patients with hypoxemic COVID-19 pneumonia, based on data from 334 adults.

Patients with hypoxemic COVID-19 pneumonia are at increased risk of thrombosis and anticoagulation-related bleeding, therefore data to identify the lowest effective anticoagulant dose are needed, wrote Vincent Labbé, MD, of Sorbonne University, Paris, and colleagues.

Previous studies of different anticoagulation strategies for noncritically ill and critically ill patients with COVID-19 pneumonia have shown contrasting results, but some institutions recommend a high-dose regimen in the wake of data showing macrovascular thrombosis in patients with COVID-19 who were treated with standard anticoagulation, the authors wrote.

However, no previously published studies have compared the effectiveness of the three anticoagulation strategies: high-dose prophylactic anticoagulation (HD-PA), standard dose prophylactic anticoagulation (SD-PA), and therapeutic anticoagulation (TA), they said.

In the open-label Anticoagulation COVID-19 (ANTICOVID) trial, published in JAMA Internal Medicine, the researchers identified consecutively hospitalized adults aged 18 years and older being treated for hypoxemic COVID-19 pneumonia in 23 centers in France between April 2021 and December 2021.

The patients were randomly assigned to SD-PA (116 patients), HD-PA (111 patients), and TA (112 patients) using low-molecular-weight heparin for 14 days, or until either hospital discharge or weaning from supplemental oxygen for 48 consecutive hours, whichever outcome occurred first.  The HD-PA patients received two times the SD-PA dose. The mean age of the patients was 58.3 years, and approximately two-thirds were men; race and ethnicity data were not collected. Participants had no macrovascular thrombosis at the start of the study.

The primary outcomes were all-cause mortality and time to clinical improvement (defined as the time from randomization to a 2-point improvement on a 7-category respiratory function scale).

The secondary outcome was a combination of safety and efficacy at day 28 that included a composite of thrombosis (ischemic stroke, noncerebrovascular arterial thrombosis, deep venous thrombosis, pulmonary artery thrombosis, and central venous catheter–related deep venous thrombosis), major bleeding, or all-cause death.

For the primary outcome, results were similar among the groups; HD-PA had no significant benefit over SD-PA or TA. All-cause death rates for SD-PA, HD-PA, and TA patients were 14%, 12%, and 13%, respectively. The time to clinical improvement for the three groups was approximately 8 days, 9 days, and 8 days, respectively. Results for the primary outcome were consistent across all prespecified subgroups.

However, HD-PA was associated with a significant fourfold reduced risk of de novo thrombosis compared with SD-PA (5.5% vs. 20.2%) with no observed increase in major bleeding. TA was not associated with any significant improvement in primary or secondary outcomes compared with HD-PA or SD-PA.

The current study findings of no improvement in survival or disease resolution in patients with a higher anticoagulant dose reflects data from previous studies, the researchers wrote in their discussion. “Our study results together with those of previous RCTs support the premise that the role of microvascular thrombosis in worsening organ dysfunction may be narrower than estimated,” they said.

The findings were limited by several factors including the open-label design and the relatively small sample size, the lack of data on microvascular (vs. macrovascular) thrombosis at baseline, and the predominance of the Delta variant of COVID-19 among the study participants, which may have contributed to a lower mortality rate, the researchers noted.

However, given the significant reduction in de novo thrombosis, the results support the routine use of HD-PA in patients with severe hypoxemic COVID-19 pneumonia, they concluded.
 

Results inform current clinical practice

Over the course of the COVID-19 pandemic, “Patients hospitalized with COVID-19 manifested the highest risk for thromboembolic complications, especially patients in the intensive care setting,” and early reports suggested that standard prophylactic doses of anticoagulant therapy might be insufficient to prevent thrombotic events, Richard C. Becker, MD, of the University of Cincinnati, and Thomas L. Ortel, MD, of Duke University, Durham, N.C., wrote in an accompanying editorial.

“Although there have been several studies that have investigated the role of anticoagulant therapy in hospitalized patients with COVID-19, this is the first study that specifically compared a standard, prophylactic dose of low-molecular-weight heparin to a ‘high-dose’ prophylactic regimen and to a full therapeutic dose regimen,” Dr. Ortel said in an interview.

“Given the concerns about an increased thrombotic risk with prophylactic dose anticoagulation, and the potential bleeding risk associated with a full therapeutic dose of anticoagulation, this approach enabled the investigators to explore the efficacy and safety of an intermediate dose between these two extremes,” he said.

In the current study, “It was notable that the primary driver of the improved outcomes with the ‘high-dose’ prophylactic regimen reflected the fourfold reduction in macrovascular thrombosis, a finding that was not observed in other studies investigating anticoagulant therapy in hospitalized patients with severe COVID-19,” Dr. Ortel told this news organization. “Much initial concern about progression of disease in patients hospitalized with severe COVID-19 focused on the role of microvascular thrombosis, which appears to be less important in this process, or, alternatively, less responsive to anticoagulant therapy.”

The clinical takeaway from the study, Dr. Ortel said, is the decreased risk for venous thromboembolism with a high-dose prophylactic anticoagulation strategy compared with a standard-dose prophylactic regimen for patients hospitalized with hypoxemic COVID-19 pneumonia, “leading to an improved net clinical outcome.”

Looking ahead, “Additional research is needed to determine whether a higher dose of prophylactic anticoagulation would be beneficial for patients hospitalized with COVID-19 pneumonia who are not in an intensive care unit setting,” Dr. Ortel said. Studies are needed to determine whether therapeutic interventions are equally beneficial in patients with different coronavirus variants, since most patients in the current study were infected with the Delta variant, he added.

The study was supported by LEO Pharma. Dr. Labbé disclosed grants from LEO Pharma during the study and fees from AOP Health unrelated to the current study.

Dr. Becker disclosed personal fees from Novartis Data Safety Monitoring Board, Ionis Data Safety Monitoring Board, and Basking Biosciences Scientific Advisory Board unrelated to the current study. Dr. Ortel disclosed grants from the National Institutes of Health, Instrumentation Laboratory, Stago, and Siemens; contract fees from the Centers for Disease Control and Prevention; and honoraria from UpToDate unrelated to the current study.
 

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

Complex polypharmacy in patients with bipolar disorder was associated with sociodemographic and clinical features, including older age, single status, and psychiatric comorbidities, based on data from more than 500 individuals.

Patients with bipolar disorder (BD) often receive prescriptions for multiple medications to manage a range of medical and psychiatric symptoms, but the definition of polypharmacy in these patients is inconsistent, and characteristics associated with complex polypharmacy have not been well studied, wrote Andrea Aguglia, MD, of the University of Genoa, Italy, and colleagues.

Previous studies have shown an increased risk for comorbid medical and psychiatric illnesses in BD patients, the researchers noted, and changes in prescribing trends have prompted greater use of combination therapies such as mood stabilizers with or without antipsychotics.

In a study published in Psychiatry Research, the investigators reviewed data from 556 adults with BD. Participants were aged 18 and older with a primary diagnosis of BD type I or II based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria. The mean age of the participants was 49.17 years, 43.7% were male, and 34.2% were employed. A total of 327 patients (58.8%) had a medical comorbidity, and 193 (34.7%) used an illicit substance.

A total of 225 patients (40.5%) met the criteria for complex polypharmacy by taking at least 4 medications.

BD patients with complex polypharmacy were significantly more likely than those without complex polypharmacy to be single (50.7% vs. 37.8%, P = .025) and unemployed (25.3% vs. 40.2%, P < .001).

On the clinical side, complex polypharmacy in BD patients was significantly associated with a higher prevalence of both medical and psychiatric comorbidities (65.3% vs. 54.4%, P = .010; and 50.7% vs. 34.1%, P < .001, respectively). The association with medical comorbidities and complex polypharmacy in BD was unexpected, the researchers said, “as psychotropic medications should be used with cautiousness in patients suffering from medical conditions.”

BD patients with complex polypharmacy also had a significantly earlier age of onset, longer duration of illness, and increased number of hospitalizations than those without complex polypharmacy.

Rates of at least one substance including alcohol, cannabinoids, and cocaine/amphetamines were significantly higher among BD patients with complex polypharmacy, compared with those without, but no differences in heroin use were noted between the groups.

In a logistic regression analysis, single status, older age, number of hospitalizations, and the presence of psychiatric comorbidities were significantly associated with complex polypharmacy.

The study findings were limited by several factors including the focus on an inpatient population, inability to consider clinical factors such as type of mood episode and bipolar cycle, and the cross-sectional design that prevented conclusions of causality, the researchers noted.

However, the study is the first known to focus on both sociodemographic and clinical factors associated with polypharmacy in BD, and the results suggest that implementing complementary psychosocial strategies might help reduce medication use in these patients, they concluded. Data from further longitudinal studies may help guide long-term management of BD, “especially when pharmacological discontinuation is needed,” they said.

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

Complex polypharmacy in patients with bipolar disorder was associated with sociodemographic and clinical features, including older age, single status, and psychiatric comorbidities, based on data from more than 500 individuals.

Patients with bipolar disorder (BD) often receive prescriptions for multiple medications to manage a range of medical and psychiatric symptoms, but the definition of polypharmacy in these patients is inconsistent, and characteristics associated with complex polypharmacy have not been well studied, wrote Andrea Aguglia, MD, of the University of Genoa, Italy, and colleagues.

Previous studies have shown an increased risk for comorbid medical and psychiatric illnesses in BD patients, the researchers noted, and changes in prescribing trends have prompted greater use of combination therapies such as mood stabilizers with or without antipsychotics.

In a study published in Psychiatry Research, the investigators reviewed data from 556 adults with BD. Participants were aged 18 and older with a primary diagnosis of BD type I or II based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria. The mean age of the participants was 49.17 years, 43.7% were male, and 34.2% were employed. A total of 327 patients (58.8%) had a medical comorbidity, and 193 (34.7%) used an illicit substance.

A total of 225 patients (40.5%) met the criteria for complex polypharmacy by taking at least 4 medications.

BD patients with complex polypharmacy were significantly more likely than those without complex polypharmacy to be single (50.7% vs. 37.8%, P = .025) and unemployed (25.3% vs. 40.2%, P < .001).

On the clinical side, complex polypharmacy in BD patients was significantly associated with a higher prevalence of both medical and psychiatric comorbidities (65.3% vs. 54.4%, P = .010; and 50.7% vs. 34.1%, P < .001, respectively). The association with medical comorbidities and complex polypharmacy in BD was unexpected, the researchers said, “as psychotropic medications should be used with cautiousness in patients suffering from medical conditions.”

BD patients with complex polypharmacy also had a significantly earlier age of onset, longer duration of illness, and increased number of hospitalizations than those without complex polypharmacy.

Rates of at least one substance including alcohol, cannabinoids, and cocaine/amphetamines were significantly higher among BD patients with complex polypharmacy, compared with those without, but no differences in heroin use were noted between the groups.

In a logistic regression analysis, single status, older age, number of hospitalizations, and the presence of psychiatric comorbidities were significantly associated with complex polypharmacy.

The study findings were limited by several factors including the focus on an inpatient population, inability to consider clinical factors such as type of mood episode and bipolar cycle, and the cross-sectional design that prevented conclusions of causality, the researchers noted.

However, the study is the first known to focus on both sociodemographic and clinical factors associated with polypharmacy in BD, and the results suggest that implementing complementary psychosocial strategies might help reduce medication use in these patients, they concluded. Data from further longitudinal studies may help guide long-term management of BD, “especially when pharmacological discontinuation is needed,” they said.

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

Complex polypharmacy in patients with bipolar disorder was associated with sociodemographic and clinical features, including older age, single status, and psychiatric comorbidities, based on data from more than 500 individuals.

Patients with bipolar disorder (BD) often receive prescriptions for multiple medications to manage a range of medical and psychiatric symptoms, but the definition of polypharmacy in these patients is inconsistent, and characteristics associated with complex polypharmacy have not been well studied, wrote Andrea Aguglia, MD, of the University of Genoa, Italy, and colleagues.

Previous studies have shown an increased risk for comorbid medical and psychiatric illnesses in BD patients, the researchers noted, and changes in prescribing trends have prompted greater use of combination therapies such as mood stabilizers with or without antipsychotics.

In a study published in Psychiatry Research, the investigators reviewed data from 556 adults with BD. Participants were aged 18 and older with a primary diagnosis of BD type I or II based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria. The mean age of the participants was 49.17 years, 43.7% were male, and 34.2% were employed. A total of 327 patients (58.8%) had a medical comorbidity, and 193 (34.7%) used an illicit substance.

A total of 225 patients (40.5%) met the criteria for complex polypharmacy by taking at least 4 medications.

BD patients with complex polypharmacy were significantly more likely than those without complex polypharmacy to be single (50.7% vs. 37.8%, P = .025) and unemployed (25.3% vs. 40.2%, P < .001).

On the clinical side, complex polypharmacy in BD patients was significantly associated with a higher prevalence of both medical and psychiatric comorbidities (65.3% vs. 54.4%, P = .010; and 50.7% vs. 34.1%, P < .001, respectively). The association with medical comorbidities and complex polypharmacy in BD was unexpected, the researchers said, “as psychotropic medications should be used with cautiousness in patients suffering from medical conditions.”

BD patients with complex polypharmacy also had a significantly earlier age of onset, longer duration of illness, and increased number of hospitalizations than those without complex polypharmacy.

Rates of at least one substance including alcohol, cannabinoids, and cocaine/amphetamines were significantly higher among BD patients with complex polypharmacy, compared with those without, but no differences in heroin use were noted between the groups.

In a logistic regression analysis, single status, older age, number of hospitalizations, and the presence of psychiatric comorbidities were significantly associated with complex polypharmacy.

The study findings were limited by several factors including the focus on an inpatient population, inability to consider clinical factors such as type of mood episode and bipolar cycle, and the cross-sectional design that prevented conclusions of causality, the researchers noted.

However, the study is the first known to focus on both sociodemographic and clinical factors associated with polypharmacy in BD, and the results suggest that implementing complementary psychosocial strategies might help reduce medication use in these patients, they concluded. Data from further longitudinal studies may help guide long-term management of BD, “especially when pharmacological discontinuation is needed,” they said.

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

Taking 8,000 steps or more for just 1 or 2 days a week was linked to a significant reduction in all-cause and cardiovascular mortality, according to a study of about 3,000 adults.

Previous research has shown lower mortality rates among individuals who walk consistently, especially those who log at least 8,000 steps daily, but the benefit of intense walking just once or twice a week on long-term health outcomes has not been examined, wrote Kosuke Inoue, MD, of Kyoto University, Japan, and colleagues.

iStock/thinkstockphotos

In a study published in JAMA Network Open, the researchers reviewed 10-year follow-up data for 3,101 adults aged 20 years and older who were part of the 2005 and 2006 National Health and Nutrition Examination Survey (NHANES).

The participants were asked to wear accelerometers to track their steps for 7 consecutive days. The researchers assessed the dose-response relationship between days of taking 8,000 steps or more (about 4 miles) during 1 week, and the primary outcome of all-cause mortality risk after 10 years. Cardiovascular mortality risk after 10 years was a secondary outcome.

The mean age of the participants was 50.5 years and 51% were women. The breakdown by ethnicity was 51% White, 21% Black, 24% Hispanic, and 4% other races/ethnicities. A total of 632 individuals took 8,000 steps or more 0 days a week, 532 took at least 8,000 steps 1-2 days per week, and 1,937 took at least 8,000 steps 3-7 days a week.

During the 10-year follow-up period, overall all-cause mortality was 14.2% and cardiovascular mortality was 5.3% across all step groups.

In an adjusted analysis, individuals who took at least 8,000 steps 1-2 days a week had a 14.9% lower all-cause mortality risk compared with those who never reached 8,000 daily steps. This difference was similar to the 16.5% reduced mortality risk for those who took at least 8,000 steps 3-7 days a week.

Similarly, compared with the group with no days of at least 8,000 steps, cardiovascular mortality risk was 8.1% lower for those who took 8,000 steps 1-2 days per week and 8.4% lower for those who took at least 8,000 steps 3-7 days per week. The decreased mortality risk plateaued at 3-4 days.

These patterns in reduced all-cause mortality risk persisted in a stratified analysis by age (younger than 65 years and 65 years and older) and sex. Similar patterns in reduced mortality also emerged when the researchers used different thresholds of daily steps, such as a minimum of 10,000 steps instead of 8,000. The adjusted all-cause mortality for groups who took at least 10,000 steps 1-2 days a week, 3-7 days a week, and no days a week were 8.1%, 7.3%, and 16.7%, respectively, with corresponding cardiovascular mortality risks of 2.4%, 2.3%, and 7.0%, respectively.

“Given the simplicity and ease of counting daily steps, our findings indicate that the recommended number of steps taken on as few as 1 to 2 days per week may be a feasible option for individuals who are striving to achieve some health benefits through adhering to a recommended daily step count but are unable to accomplish this on a daily basis,” the researchers wrote in their discussion.

The findings were limited by several factors including the use daily step measures for 1 week only at baseline, with no data on how physical activity changes might impact mortality risk, the researchers noted. Other limitations included possible accelerometer error and misclassification of activity, possible selection bias, and lack of data on cause-specific mortality outside of cardiovascular death, they said.

However, the results were strengthened by the use of accelerometers as objective measures of activity and by the availability of 10-year follow-up data for nearly 100% of the participants, they said.

“Although our findings might suffer from residual confounding that should be addressed in future research, they suggest that people may receive substantial health benefits even if a sufficient number of steps are taken on only a couple days of the week,” they concluded.
 

Proceed with caution

The current study findings should be interpreted cautiously in light of the potential unmeasured confounding factors and selection bias that often occur in studies of physical activity, James Sawalla Guseh, MD, of Massachusetts General Hospital, and Jose F. Figueroa, MD, of Harvard T.H. Chan School of Public Health, Boston, wrote in an accompanying editorial.

The results support previous studies showing some longevity benefits with “weekend warrior” patterns of intense physical activity for only a couple of days; however, “the body of evidence for sporadic activity is not as robust as the evidence for sustained and regular aerobic activity,” the authors emphasized.

The editorial authors also highlighted the limitations of the current study, including the observational design and significant differences in demographics and comorbidities between the 1- to 2-days of 8,000 steps exercise group and the 0-day group, as well as the reliance on only a week’s worth of data to infer 10 years’ mortality.

Although the data are consistent with previous observations that increased exercise volume reduces mortality, more research is needed, as the current study findings may not reflect other dimensions of health, including neurological health, they said.

Despite the need for cautious interpretation of the results, the current study “supports the emerging and popular idea that step counting, which does not require consideration of exercise duration or intensity, can offer guidance toward robust and favorable health outcomes,” and may inform step-based activity goals to improve public health, the editorialists wrote.

The study was supported by the Japan Agency for Medical Research and Development, the Japan Society for the Promotion of Science, the Japan Endocrine Society, and the Meiji Yasuda Life Foundation of Health and Welfare. Dr. Inoue also was supported by the Program for the Development of Next-Generation Leading Scientists With Global Insight sponsored by the Ministry of Education, Culture, Sports, Science and Technology, Japan. The other researchers had no relevant financial conflicts to disclose. The editorial authors had no financial conflicts to disclose.

Taking 8,000 steps or more for just 1 or 2 days a week was linked to a significant reduction in all-cause and cardiovascular mortality, according to a study of about 3,000 adults.

Previous research has shown lower mortality rates among individuals who walk consistently, especially those who log at least 8,000 steps daily, but the benefit of intense walking just once or twice a week on long-term health outcomes has not been examined, wrote Kosuke Inoue, MD, of Kyoto University, Japan, and colleagues.

iStock/thinkstockphotos

In a study published in JAMA Network Open, the researchers reviewed 10-year follow-up data for 3,101 adults aged 20 years and older who were part of the 2005 and 2006 National Health and Nutrition Examination Survey (NHANES).

The participants were asked to wear accelerometers to track their steps for 7 consecutive days. The researchers assessed the dose-response relationship between days of taking 8,000 steps or more (about 4 miles) during 1 week, and the primary outcome of all-cause mortality risk after 10 years. Cardiovascular mortality risk after 10 years was a secondary outcome.

The mean age of the participants was 50.5 years and 51% were women. The breakdown by ethnicity was 51% White, 21% Black, 24% Hispanic, and 4% other races/ethnicities. A total of 632 individuals took 8,000 steps or more 0 days a week, 532 took at least 8,000 steps 1-2 days per week, and 1,937 took at least 8,000 steps 3-7 days a week.

During the 10-year follow-up period, overall all-cause mortality was 14.2% and cardiovascular mortality was 5.3% across all step groups.

In an adjusted analysis, individuals who took at least 8,000 steps 1-2 days a week had a 14.9% lower all-cause mortality risk compared with those who never reached 8,000 daily steps. This difference was similar to the 16.5% reduced mortality risk for those who took at least 8,000 steps 3-7 days a week.

Similarly, compared with the group with no days of at least 8,000 steps, cardiovascular mortality risk was 8.1% lower for those who took 8,000 steps 1-2 days per week and 8.4% lower for those who took at least 8,000 steps 3-7 days per week. The decreased mortality risk plateaued at 3-4 days.

These patterns in reduced all-cause mortality risk persisted in a stratified analysis by age (younger than 65 years and 65 years and older) and sex. Similar patterns in reduced mortality also emerged when the researchers used different thresholds of daily steps, such as a minimum of 10,000 steps instead of 8,000. The adjusted all-cause mortality for groups who took at least 10,000 steps 1-2 days a week, 3-7 days a week, and no days a week were 8.1%, 7.3%, and 16.7%, respectively, with corresponding cardiovascular mortality risks of 2.4%, 2.3%, and 7.0%, respectively.

“Given the simplicity and ease of counting daily steps, our findings indicate that the recommended number of steps taken on as few as 1 to 2 days per week may be a feasible option for individuals who are striving to achieve some health benefits through adhering to a recommended daily step count but are unable to accomplish this on a daily basis,” the researchers wrote in their discussion.

The findings were limited by several factors including the use daily step measures for 1 week only at baseline, with no data on how physical activity changes might impact mortality risk, the researchers noted. Other limitations included possible accelerometer error and misclassification of activity, possible selection bias, and lack of data on cause-specific mortality outside of cardiovascular death, they said.

However, the results were strengthened by the use of accelerometers as objective measures of activity and by the availability of 10-year follow-up data for nearly 100% of the participants, they said.

“Although our findings might suffer from residual confounding that should be addressed in future research, they suggest that people may receive substantial health benefits even if a sufficient number of steps are taken on only a couple days of the week,” they concluded.
 

Proceed with caution

The current study findings should be interpreted cautiously in light of the potential unmeasured confounding factors and selection bias that often occur in studies of physical activity, James Sawalla Guseh, MD, of Massachusetts General Hospital, and Jose F. Figueroa, MD, of Harvard T.H. Chan School of Public Health, Boston, wrote in an accompanying editorial.

The results support previous studies showing some longevity benefits with “weekend warrior” patterns of intense physical activity for only a couple of days; however, “the body of evidence for sporadic activity is not as robust as the evidence for sustained and regular aerobic activity,” the authors emphasized.

The editorial authors also highlighted the limitations of the current study, including the observational design and significant differences in demographics and comorbidities between the 1- to 2-days of 8,000 steps exercise group and the 0-day group, as well as the reliance on only a week’s worth of data to infer 10 years’ mortality.

Although the data are consistent with previous observations that increased exercise volume reduces mortality, more research is needed, as the current study findings may not reflect other dimensions of health, including neurological health, they said.

Despite the need for cautious interpretation of the results, the current study “supports the emerging and popular idea that step counting, which does not require consideration of exercise duration or intensity, can offer guidance toward robust and favorable health outcomes,” and may inform step-based activity goals to improve public health, the editorialists wrote.

The study was supported by the Japan Agency for Medical Research and Development, the Japan Society for the Promotion of Science, the Japan Endocrine Society, and the Meiji Yasuda Life Foundation of Health and Welfare. Dr. Inoue also was supported by the Program for the Development of Next-Generation Leading Scientists With Global Insight sponsored by the Ministry of Education, Culture, Sports, Science and Technology, Japan. The other researchers had no relevant financial conflicts to disclose. The editorial authors had no financial conflicts to disclose.

Taking 8,000 steps or more for just 1 or 2 days a week was linked to a significant reduction in all-cause and cardiovascular mortality, according to a study of about 3,000 adults.

Previous research has shown lower mortality rates among individuals who walk consistently, especially those who log at least 8,000 steps daily, but the benefit of intense walking just once or twice a week on long-term health outcomes has not been examined, wrote Kosuke Inoue, MD, of Kyoto University, Japan, and colleagues.

iStock/thinkstockphotos

In a study published in JAMA Network Open, the researchers reviewed 10-year follow-up data for 3,101 adults aged 20 years and older who were part of the 2005 and 2006 National Health and Nutrition Examination Survey (NHANES).

The participants were asked to wear accelerometers to track their steps for 7 consecutive days. The researchers assessed the dose-response relationship between days of taking 8,000 steps or more (about 4 miles) during 1 week, and the primary outcome of all-cause mortality risk after 10 years. Cardiovascular mortality risk after 10 years was a secondary outcome.

The mean age of the participants was 50.5 years and 51% were women. The breakdown by ethnicity was 51% White, 21% Black, 24% Hispanic, and 4% other races/ethnicities. A total of 632 individuals took 8,000 steps or more 0 days a week, 532 took at least 8,000 steps 1-2 days per week, and 1,937 took at least 8,000 steps 3-7 days a week.

During the 10-year follow-up period, overall all-cause mortality was 14.2% and cardiovascular mortality was 5.3% across all step groups.

In an adjusted analysis, individuals who took at least 8,000 steps 1-2 days a week had a 14.9% lower all-cause mortality risk compared with those who never reached 8,000 daily steps. This difference was similar to the 16.5% reduced mortality risk for those who took at least 8,000 steps 3-7 days a week.

Similarly, compared with the group with no days of at least 8,000 steps, cardiovascular mortality risk was 8.1% lower for those who took 8,000 steps 1-2 days per week and 8.4% lower for those who took at least 8,000 steps 3-7 days per week. The decreased mortality risk plateaued at 3-4 days.

These patterns in reduced all-cause mortality risk persisted in a stratified analysis by age (younger than 65 years and 65 years and older) and sex. Similar patterns in reduced mortality also emerged when the researchers used different thresholds of daily steps, such as a minimum of 10,000 steps instead of 8,000. The adjusted all-cause mortality for groups who took at least 10,000 steps 1-2 days a week, 3-7 days a week, and no days a week were 8.1%, 7.3%, and 16.7%, respectively, with corresponding cardiovascular mortality risks of 2.4%, 2.3%, and 7.0%, respectively.

“Given the simplicity and ease of counting daily steps, our findings indicate that the recommended number of steps taken on as few as 1 to 2 days per week may be a feasible option for individuals who are striving to achieve some health benefits through adhering to a recommended daily step count but are unable to accomplish this on a daily basis,” the researchers wrote in their discussion.

The findings were limited by several factors including the use daily step measures for 1 week only at baseline, with no data on how physical activity changes might impact mortality risk, the researchers noted. Other limitations included possible accelerometer error and misclassification of activity, possible selection bias, and lack of data on cause-specific mortality outside of cardiovascular death, they said.

However, the results were strengthened by the use of accelerometers as objective measures of activity and by the availability of 10-year follow-up data for nearly 100% of the participants, they said.

“Although our findings might suffer from residual confounding that should be addressed in future research, they suggest that people may receive substantial health benefits even if a sufficient number of steps are taken on only a couple days of the week,” they concluded.
 

Proceed with caution

The current study findings should be interpreted cautiously in light of the potential unmeasured confounding factors and selection bias that often occur in studies of physical activity, James Sawalla Guseh, MD, of Massachusetts General Hospital, and Jose F. Figueroa, MD, of Harvard T.H. Chan School of Public Health, Boston, wrote in an accompanying editorial.

The results support previous studies showing some longevity benefits with “weekend warrior” patterns of intense physical activity for only a couple of days; however, “the body of evidence for sporadic activity is not as robust as the evidence for sustained and regular aerobic activity,” the authors emphasized.

The editorial authors also highlighted the limitations of the current study, including the observational design and significant differences in demographics and comorbidities between the 1- to 2-days of 8,000 steps exercise group and the 0-day group, as well as the reliance on only a week’s worth of data to infer 10 years’ mortality.

Although the data are consistent with previous observations that increased exercise volume reduces mortality, more research is needed, as the current study findings may not reflect other dimensions of health, including neurological health, they said.

Despite the need for cautious interpretation of the results, the current study “supports the emerging and popular idea that step counting, which does not require consideration of exercise duration or intensity, can offer guidance toward robust and favorable health outcomes,” and may inform step-based activity goals to improve public health, the editorialists wrote.

The study was supported by the Japan Agency for Medical Research and Development, the Japan Society for the Promotion of Science, the Japan Endocrine Society, and the Meiji Yasuda Life Foundation of Health and Welfare. Dr. Inoue also was supported by the Program for the Development of Next-Generation Leading Scientists With Global Insight sponsored by the Ministry of Education, Culture, Sports, Science and Technology, Japan. The other researchers had no relevant financial conflicts to disclose. The editorial authors had no financial conflicts to disclose.

Plasma exchange successfully improved symptoms of immunoglobulin A vasculitis in an adult female patient who developed the condition after infection with COVID-19, according to a case report published in Cureus.

Immunoglobulin A (IgA) vasculitis can affect all ages, but is relatively rare in adults, and the etiology remains unclear, wrote Hassan Alwafi, MD, of Umm Al-Qura University, Makkah, Saudi Arabia, and colleagues.

COVID-19 has been associated with pulmonary and extrapulmonary complications, but COVID-19–induced IgA vasculitis has previously been described mainly in pediatric and older adult populations, the authors wrote.

The authors described a case of a 41-year-old otherwise healthy Saudi Arabian woman who presented with an ascending rash on both lower extremities, along with arthralgia. Blood tests showed high blood urea nitrogen, creatinine, and inflammatory markers, and a negative immune panel. The patient had been infected with COVID-19 approximately 2 weeks before the onset of symptoms, but she was treated with supportive care and required no antiviral therapy of dexamethasone.

In addition, the patient’s urinalysis showed proteinuria and hematuria. After a kidney biopsy revealed additional abnormalities, the patient was started on intravenous methylprednisolone pulse therapy.

A few days after the initiation of therapy, the patient experienced nosebleeds and coughing up blood. After a chest x-ray showed bilateral pleural effusion, the patient was transferred to the ICU. The patient was started on intravenous piperacillin-tazobactam, and received two doses of intravenous immunoglobulin and plasma exchange after consultation with a nephrologist. Ultimately, the initial rash and other clinical symptoms improved, and the patient was discharged with a tapering schedule of oral prednisolone.

In this case, COVID-19 may have played a role in the development of IgA vasculitis, the authors said.

The authors also listed 21 cases of IgA vasculitis following COVID-19 infection, including 14 children and 7 adults. Of these, three cases had combined kidney and lung involvement, the two pediatric cases died from respiratory failure, while the adult case was successfully treated with steroid monotherapy.

“As COVID-19 is a novel disease and its pathogenic mechanism of causing IgA vasculitis is not well understood, every patient who is infected with or recently recovered from COVID-19 and presents with a skin rash or arthralgia should have baseline blood and urine tests done and should be treated promptly to avoid the emergence of irreversible consequences,” the authors wrote in their discussion.

Although case reports cannot prove a cause-and-effect link, the data from the cases in the current review suggest that COVID-19 infection may be an indirect trigger for IgA vasculitis, including cases associated with pulmonary renal syndrome, they said. However, more research is needed, especially on the efficacy of treatments in adults, they concluded.

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

Plasma exchange successfully improved symptoms of immunoglobulin A vasculitis in an adult female patient who developed the condition after infection with COVID-19, according to a case report published in Cureus.

Immunoglobulin A (IgA) vasculitis can affect all ages, but is relatively rare in adults, and the etiology remains unclear, wrote Hassan Alwafi, MD, of Umm Al-Qura University, Makkah, Saudi Arabia, and colleagues.

COVID-19 has been associated with pulmonary and extrapulmonary complications, but COVID-19–induced IgA vasculitis has previously been described mainly in pediatric and older adult populations, the authors wrote.

The authors described a case of a 41-year-old otherwise healthy Saudi Arabian woman who presented with an ascending rash on both lower extremities, along with arthralgia. Blood tests showed high blood urea nitrogen, creatinine, and inflammatory markers, and a negative immune panel. The patient had been infected with COVID-19 approximately 2 weeks before the onset of symptoms, but she was treated with supportive care and required no antiviral therapy of dexamethasone.

In addition, the patient’s urinalysis showed proteinuria and hematuria. After a kidney biopsy revealed additional abnormalities, the patient was started on intravenous methylprednisolone pulse therapy.

A few days after the initiation of therapy, the patient experienced nosebleeds and coughing up blood. After a chest x-ray showed bilateral pleural effusion, the patient was transferred to the ICU. The patient was started on intravenous piperacillin-tazobactam, and received two doses of intravenous immunoglobulin and plasma exchange after consultation with a nephrologist. Ultimately, the initial rash and other clinical symptoms improved, and the patient was discharged with a tapering schedule of oral prednisolone.

In this case, COVID-19 may have played a role in the development of IgA vasculitis, the authors said.

The authors also listed 21 cases of IgA vasculitis following COVID-19 infection, including 14 children and 7 adults. Of these, three cases had combined kidney and lung involvement, the two pediatric cases died from respiratory failure, while the adult case was successfully treated with steroid monotherapy.

“As COVID-19 is a novel disease and its pathogenic mechanism of causing IgA vasculitis is not well understood, every patient who is infected with or recently recovered from COVID-19 and presents with a skin rash or arthralgia should have baseline blood and urine tests done and should be treated promptly to avoid the emergence of irreversible consequences,” the authors wrote in their discussion.

Although case reports cannot prove a cause-and-effect link, the data from the cases in the current review suggest that COVID-19 infection may be an indirect trigger for IgA vasculitis, including cases associated with pulmonary renal syndrome, they said. However, more research is needed, especially on the efficacy of treatments in adults, they concluded.

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

Plasma exchange successfully improved symptoms of immunoglobulin A vasculitis in an adult female patient who developed the condition after infection with COVID-19, according to a case report published in Cureus.

Immunoglobulin A (IgA) vasculitis can affect all ages, but is relatively rare in adults, and the etiology remains unclear, wrote Hassan Alwafi, MD, of Umm Al-Qura University, Makkah, Saudi Arabia, and colleagues.

COVID-19 has been associated with pulmonary and extrapulmonary complications, but COVID-19–induced IgA vasculitis has previously been described mainly in pediatric and older adult populations, the authors wrote.

The authors described a case of a 41-year-old otherwise healthy Saudi Arabian woman who presented with an ascending rash on both lower extremities, along with arthralgia. Blood tests showed high blood urea nitrogen, creatinine, and inflammatory markers, and a negative immune panel. The patient had been infected with COVID-19 approximately 2 weeks before the onset of symptoms, but she was treated with supportive care and required no antiviral therapy of dexamethasone.

In addition, the patient’s urinalysis showed proteinuria and hematuria. After a kidney biopsy revealed additional abnormalities, the patient was started on intravenous methylprednisolone pulse therapy.

A few days after the initiation of therapy, the patient experienced nosebleeds and coughing up blood. After a chest x-ray showed bilateral pleural effusion, the patient was transferred to the ICU. The patient was started on intravenous piperacillin-tazobactam, and received two doses of intravenous immunoglobulin and plasma exchange after consultation with a nephrologist. Ultimately, the initial rash and other clinical symptoms improved, and the patient was discharged with a tapering schedule of oral prednisolone.

In this case, COVID-19 may have played a role in the development of IgA vasculitis, the authors said.

The authors also listed 21 cases of IgA vasculitis following COVID-19 infection, including 14 children and 7 adults. Of these, three cases had combined kidney and lung involvement, the two pediatric cases died from respiratory failure, while the adult case was successfully treated with steroid monotherapy.

“As COVID-19 is a novel disease and its pathogenic mechanism of causing IgA vasculitis is not well understood, every patient who is infected with or recently recovered from COVID-19 and presents with a skin rash or arthralgia should have baseline blood and urine tests done and should be treated promptly to avoid the emergence of irreversible consequences,” the authors wrote in their discussion.

Although case reports cannot prove a cause-and-effect link, the data from the cases in the current review suggest that COVID-19 infection may be an indirect trigger for IgA vasculitis, including cases associated with pulmonary renal syndrome, they said. However, more research is needed, especially on the efficacy of treatments in adults, they concluded.

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

Dupilumab, a fully human monoclonal antibody, significantly improved quality of life and respiratory symptoms compared with placebo in a phase 3 trial of more than 900 adults with uncontrolled chronic obstructive pulmonary disease.

In the study, known as the BOREAS trial, dupilumab met its primary and secondary endpoints, with a significant reduction compared with placebo in exacerbations for adults with chronic obstructive pulmonary disease (COPD) that was uncontrolled despite use of the maximal standard-of-care inhaled therapy (triple therapy), according to a press release from manufacturers Regeneron and Sanofi.

Dupilumab, which inhibits the signaling of the interleukin-4 (IL-4) and interleukin-13 (IL-13) pathways, is currently approved in multiple countries for certain patients with conditions including atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, or prurigo nodularis in different age groups. The drug is not an immunosuppressant, and would be the first biologic approved for COPD, according to the manufacturers.

In the BOREAS trial, 468 adults with COPD who were current or former smokers aged 40-80 years were randomized to dupilumab and 471 to placebo; both groups continued to receive maximal standard of care.

Over 52 weeks, patients in the dupilumab group experienced a 30% reduction in moderate to severe COPD exacerbations compared with placebo (P = .0005).

In addition, patients treated with dupilumab met the key secondary endpoints of significant improvement in lung function from baseline to 12 weeks compared with placebo (160 mL vs. 77 mL, P < .0001); this difference persisted at 52 weeks (P = .0003).

Dupilumab also met endpoints for improvement in patient-reported health-related quality of life based on the St. George’s Respiratory Questionnaire (SGRQ) and reduction in the severity of respiratory symptoms of COPD based on the Evaluation Respiratory Symptoms: COPD (E-RS: COPD) Scale, according to the companies’ statement.

The results represent a previously unreported magnitude of improvement for COPD patients treated with a biologic, principal investigator George D. Yancopoulos, MD, said in the statement. “These results also validate the role type 2 inflammation plays in driving COPD in these patients, advancing the scientific community’s understanding of the underlying biology of this disease,” he added.

The safety results in the BOREAS trial were generally consistent with the known safety profile of Dupixent in its approved indications. Overall adverse event rates were similar for dupilumab and placebo patients (77% and 76%, respectively) and the overall safety profiles were consistent with the currently approved dupilumab indications, according to the manufacturers.

The adverse events that were more common in dupilumab patients compared with placebo patients were headache (8.1% vs. 6.8%), diarrhea (5.3% vs. 3.6%), and back pain (5.1% vs. 3.4%).

Adverse events leading to deaths were similar between the groups (1.7% in placebo patients and 1.5% in dupilumab patients).

Complete safety and efficacy results from the BOREAS trial are scheduled to be presented in a future scientific forum, and a second phase 3 trial of dupilumab for COPD, known as NOTUS, is ongoing, with data expected in 2024, according to the manufacturers.

The Boreas trial was sponsored by Sanofi and Regeneron Pharmaceuticals.

Dupilumab, a fully human monoclonal antibody, significantly improved quality of life and respiratory symptoms compared with placebo in a phase 3 trial of more than 900 adults with uncontrolled chronic obstructive pulmonary disease.

In the study, known as the BOREAS trial, dupilumab met its primary and secondary endpoints, with a significant reduction compared with placebo in exacerbations for adults with chronic obstructive pulmonary disease (COPD) that was uncontrolled despite use of the maximal standard-of-care inhaled therapy (triple therapy), according to a press release from manufacturers Regeneron and Sanofi.

Dupilumab, which inhibits the signaling of the interleukin-4 (IL-4) and interleukin-13 (IL-13) pathways, is currently approved in multiple countries for certain patients with conditions including atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, or prurigo nodularis in different age groups. The drug is not an immunosuppressant, and would be the first biologic approved for COPD, according to the manufacturers.

In the BOREAS trial, 468 adults with COPD who were current or former smokers aged 40-80 years were randomized to dupilumab and 471 to placebo; both groups continued to receive maximal standard of care.

Over 52 weeks, patients in the dupilumab group experienced a 30% reduction in moderate to severe COPD exacerbations compared with placebo (P = .0005).

In addition, patients treated with dupilumab met the key secondary endpoints of significant improvement in lung function from baseline to 12 weeks compared with placebo (160 mL vs. 77 mL, P < .0001); this difference persisted at 52 weeks (P = .0003).

Dupilumab also met endpoints for improvement in patient-reported health-related quality of life based on the St. George’s Respiratory Questionnaire (SGRQ) and reduction in the severity of respiratory symptoms of COPD based on the Evaluation Respiratory Symptoms: COPD (E-RS: COPD) Scale, according to the companies’ statement.

The results represent a previously unreported magnitude of improvement for COPD patients treated with a biologic, principal investigator George D. Yancopoulos, MD, said in the statement. “These results also validate the role type 2 inflammation plays in driving COPD in these patients, advancing the scientific community’s understanding of the underlying biology of this disease,” he added.

The safety results in the BOREAS trial were generally consistent with the known safety profile of Dupixent in its approved indications. Overall adverse event rates were similar for dupilumab and placebo patients (77% and 76%, respectively) and the overall safety profiles were consistent with the currently approved dupilumab indications, according to the manufacturers.

The adverse events that were more common in dupilumab patients compared with placebo patients were headache (8.1% vs. 6.8%), diarrhea (5.3% vs. 3.6%), and back pain (5.1% vs. 3.4%).

Adverse events leading to deaths were similar between the groups (1.7% in placebo patients and 1.5% in dupilumab patients).

Complete safety and efficacy results from the BOREAS trial are scheduled to be presented in a future scientific forum, and a second phase 3 trial of dupilumab for COPD, known as NOTUS, is ongoing, with data expected in 2024, according to the manufacturers.

The Boreas trial was sponsored by Sanofi and Regeneron Pharmaceuticals.

Dupilumab, a fully human monoclonal antibody, significantly improved quality of life and respiratory symptoms compared with placebo in a phase 3 trial of more than 900 adults with uncontrolled chronic obstructive pulmonary disease.

In the study, known as the BOREAS trial, dupilumab met its primary and secondary endpoints, with a significant reduction compared with placebo in exacerbations for adults with chronic obstructive pulmonary disease (COPD) that was uncontrolled despite use of the maximal standard-of-care inhaled therapy (triple therapy), according to a press release from manufacturers Regeneron and Sanofi.

Dupilumab, which inhibits the signaling of the interleukin-4 (IL-4) and interleukin-13 (IL-13) pathways, is currently approved in multiple countries for certain patients with conditions including atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, or prurigo nodularis in different age groups. The drug is not an immunosuppressant, and would be the first biologic approved for COPD, according to the manufacturers.

In the BOREAS trial, 468 adults with COPD who were current or former smokers aged 40-80 years were randomized to dupilumab and 471 to placebo; both groups continued to receive maximal standard of care.

Over 52 weeks, patients in the dupilumab group experienced a 30% reduction in moderate to severe COPD exacerbations compared with placebo (P = .0005).

In addition, patients treated with dupilumab met the key secondary endpoints of significant improvement in lung function from baseline to 12 weeks compared with placebo (160 mL vs. 77 mL, P < .0001); this difference persisted at 52 weeks (P = .0003).

Dupilumab also met endpoints for improvement in patient-reported health-related quality of life based on the St. George’s Respiratory Questionnaire (SGRQ) and reduction in the severity of respiratory symptoms of COPD based on the Evaluation Respiratory Symptoms: COPD (E-RS: COPD) Scale, according to the companies’ statement.

The results represent a previously unreported magnitude of improvement for COPD patients treated with a biologic, principal investigator George D. Yancopoulos, MD, said in the statement. “These results also validate the role type 2 inflammation plays in driving COPD in these patients, advancing the scientific community’s understanding of the underlying biology of this disease,” he added.

The safety results in the BOREAS trial were generally consistent with the known safety profile of Dupixent in its approved indications. Overall adverse event rates were similar for dupilumab and placebo patients (77% and 76%, respectively) and the overall safety profiles were consistent with the currently approved dupilumab indications, according to the manufacturers.

The adverse events that were more common in dupilumab patients compared with placebo patients were headache (8.1% vs. 6.8%), diarrhea (5.3% vs. 3.6%), and back pain (5.1% vs. 3.4%).

Adverse events leading to deaths were similar between the groups (1.7% in placebo patients and 1.5% in dupilumab patients).

Complete safety and efficacy results from the BOREAS trial are scheduled to be presented in a future scientific forum, and a second phase 3 trial of dupilumab for COPD, known as NOTUS, is ongoing, with data expected in 2024, according to the manufacturers.

The Boreas trial was sponsored by Sanofi and Regeneron Pharmaceuticals.

The Food and Drug Administration has approved a citrate-free, 100 mg/mL formulation of the biosimilar adalimumab-adaz (Hyrimoz), according to a statement from manufacturer Sandoz.

Hyrimoz, a tumor necrosis factor (TNF) blocker that is biosimilar to its reference product Humira, was approved by the FDA in 2018 at a concentration of 50 mg/mL for rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and plaque psoriasis. The high-concentration formula is indicated for these same conditions.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Sandoz said that it intends to launch the citrate-free formulation in the United States on July 1. It will be one of up to nine other adalimumab biosimilars that are expected to launch in July. On January 31, Amjevita (adalimumab-atto) became the first adalimumab biosimilar to launch in the United States.

The current label for Hyrimoz contains a black box warning emphasizing certain risks, notably the increased risk for serious infections, such as tuberculosis or sepsis, and an increased risk of malignancy, particularly lymphomas.

Adverse effects associated with Hyrimoz with an incidence greater than 10% include upper respiratory infections and sinusitis, injection-site reactions, headache, and rash.

The approval for the high-concentration formulation was based on data from a phase 1 pharmacokinetics bridging study that compared Hyrimoz 50 mg/mL and citrate-free Hyrimoz 100 mg/mL.

“This study met all of the primary objectives, demonstrating comparable pharmacokinetics and showing similar safety and immunogenicity of the Hyrimoz 50 mg/mL and Hyrimoz [100 mg/mL],” according to Sandoz, a division of Novartis.

The approval for Hyrimoz 50 mg/mL in 2018 was based on preclinical and clinical research comparing Hyrimoz and Humira. In a phase 3 trial published in the British Journal of Dermatology, which included adults with clinically stable but active moderate to severe chronic plaque psoriasis, Hyrimoz and Humira showed a similar percentage of patients met the primary endpoint of a 75% reduction or more in Psoriasis Area and Severity Index (PASI 75) score at 16 weeks, compared with baseline (66.8% and 65%, respectively).

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

The Food and Drug Administration has approved a citrate-free, 100 mg/mL formulation of the biosimilar adalimumab-adaz (Hyrimoz), according to a statement from manufacturer Sandoz.

Hyrimoz, a tumor necrosis factor (TNF) blocker that is biosimilar to its reference product Humira, was approved by the FDA in 2018 at a concentration of 50 mg/mL for rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and plaque psoriasis. The high-concentration formula is indicated for these same conditions.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Sandoz said that it intends to launch the citrate-free formulation in the United States on July 1. It will be one of up to nine other adalimumab biosimilars that are expected to launch in July. On January 31, Amjevita (adalimumab-atto) became the first adalimumab biosimilar to launch in the United States.

The current label for Hyrimoz contains a black box warning emphasizing certain risks, notably the increased risk for serious infections, such as tuberculosis or sepsis, and an increased risk of malignancy, particularly lymphomas.

Adverse effects associated with Hyrimoz with an incidence greater than 10% include upper respiratory infections and sinusitis, injection-site reactions, headache, and rash.

The approval for the high-concentration formulation was based on data from a phase 1 pharmacokinetics bridging study that compared Hyrimoz 50 mg/mL and citrate-free Hyrimoz 100 mg/mL.

“This study met all of the primary objectives, demonstrating comparable pharmacokinetics and showing similar safety and immunogenicity of the Hyrimoz 50 mg/mL and Hyrimoz [100 mg/mL],” according to Sandoz, a division of Novartis.

The approval for Hyrimoz 50 mg/mL in 2018 was based on preclinical and clinical research comparing Hyrimoz and Humira. In a phase 3 trial published in the British Journal of Dermatology, which included adults with clinically stable but active moderate to severe chronic plaque psoriasis, Hyrimoz and Humira showed a similar percentage of patients met the primary endpoint of a 75% reduction or more in Psoriasis Area and Severity Index (PASI 75) score at 16 weeks, compared with baseline (66.8% and 65%, respectively).

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

The Food and Drug Administration has approved a citrate-free, 100 mg/mL formulation of the biosimilar adalimumab-adaz (Hyrimoz), according to a statement from manufacturer Sandoz.

Hyrimoz, a tumor necrosis factor (TNF) blocker that is biosimilar to its reference product Humira, was approved by the FDA in 2018 at a concentration of 50 mg/mL for rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and plaque psoriasis. The high-concentration formula is indicated for these same conditions.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Sandoz said that it intends to launch the citrate-free formulation in the United States on July 1. It will be one of up to nine other adalimumab biosimilars that are expected to launch in July. On January 31, Amjevita (adalimumab-atto) became the first adalimumab biosimilar to launch in the United States.

The current label for Hyrimoz contains a black box warning emphasizing certain risks, notably the increased risk for serious infections, such as tuberculosis or sepsis, and an increased risk of malignancy, particularly lymphomas.

Adverse effects associated with Hyrimoz with an incidence greater than 10% include upper respiratory infections and sinusitis, injection-site reactions, headache, and rash.

The approval for the high-concentration formulation was based on data from a phase 1 pharmacokinetics bridging study that compared Hyrimoz 50 mg/mL and citrate-free Hyrimoz 100 mg/mL.

“This study met all of the primary objectives, demonstrating comparable pharmacokinetics and showing similar safety and immunogenicity of the Hyrimoz 50 mg/mL and Hyrimoz [100 mg/mL],” according to Sandoz, a division of Novartis.

The approval for Hyrimoz 50 mg/mL in 2018 was based on preclinical and clinical research comparing Hyrimoz and Humira. In a phase 3 trial published in the British Journal of Dermatology, which included adults with clinically stable but active moderate to severe chronic plaque psoriasis, Hyrimoz and Humira showed a similar percentage of patients met the primary endpoint of a 75% reduction or more in Psoriasis Area and Severity Index (PASI 75) score at 16 weeks, compared with baseline (66.8% and 65%, respectively).

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

An electronic nose effectively detected Staphylococcus aureus in children with cystic fibrosis, based on data from 100 individuals.

Staphylococcus aureus is the most common pathogen found in children with cystic fibrosis (CF), but current detection strategies are based on microbiology cultures, wrote Johann-Christoph Licht, a medical student at the University of Toronto, and colleagues.

Noninvasive tools are needed to screen children with CF early for respiratory infections, the researchers said.

The electronic Nose (eNose) is a technology that detects volatile organic compounds (VOCs). Although exhaled breath can be used to create distinct profiles, the ability of eNose to identify S. aureus (SA) in the breath of children with CF remains unclear, they wrote.

In a study published in the Journal of Cystic Fibrosis, the researchers analyzed breath profiles data from 100 children with CF. The study population included children aged 5-18 years with clinically stable CF who were recruited from CF clinics during routine visits. Patients with a CF pulmonary exacerbation were excluded.

The children’s median predicted FEV₁ was 91%. The researchers collected sputum from 67 patients and throat cultures for 33 patients. A group of 25 age-matched healthy controls served for comparison.

Eighty patients were positive for CF pathogens. Of these, 67 were positive for SA (44 with SA only and 23 with SA and at least one other pathogen).

Overall, patients with any CF pathogen on airway cultures were identified compared to airway cultures with no CF pathogens with an area under the curve accuracy of 79.0%.

Previous studies have shown a high rate of accuracy using eNose to detect Pseudomonas aeruginosa (PA). In the current study, the area under the curve accuracy for PA infection compared to no CF pathogens was 78%. Both SA-specific and PA-specific signatures were driven by different sensors in the eNose, which suggests pathogen-specific breath signatures, the researchers wrote.

The study findings were limited by several factors including the small number of patients with positive airway cultures for PA and the lack of data on variability of measures over time or treatment-induced changes, the researchers noted.

However, the results confirm the value of the eNose in real-time point-of-care detection of airway infection in children with CF, and this is the first study known to suggest the potential of an eNose to detect SA infection in particular in a routine clinical setting, the researchers wrote in their discussion.

Other points in favor of eNose compared to current practice include “low cost, ease of use and portability to the point-of-care,” they said. The eNose provides an opportunity for early detection of pathogens that challenges conventional microbiology testing, they concluded.

The study received no outside funding. Two coauthors disclosed fees and/or an interest in the company Breathomix BV.

An electronic nose effectively detected Staphylococcus aureus in children with cystic fibrosis, based on data from 100 individuals.

Staphylococcus aureus is the most common pathogen found in children with cystic fibrosis (CF), but current detection strategies are based on microbiology cultures, wrote Johann-Christoph Licht, a medical student at the University of Toronto, and colleagues.

Noninvasive tools are needed to screen children with CF early for respiratory infections, the researchers said.

The electronic Nose (eNose) is a technology that detects volatile organic compounds (VOCs). Although exhaled breath can be used to create distinct profiles, the ability of eNose to identify S. aureus (SA) in the breath of children with CF remains unclear, they wrote.

In a study published in the Journal of Cystic Fibrosis, the researchers analyzed breath profiles data from 100 children with CF. The study population included children aged 5-18 years with clinically stable CF who were recruited from CF clinics during routine visits. Patients with a CF pulmonary exacerbation were excluded.

The children’s median predicted FEV₁ was 91%. The researchers collected sputum from 67 patients and throat cultures for 33 patients. A group of 25 age-matched healthy controls served for comparison.

Eighty patients were positive for CF pathogens. Of these, 67 were positive for SA (44 with SA only and 23 with SA and at least one other pathogen).

Overall, patients with any CF pathogen on airway cultures were identified compared to airway cultures with no CF pathogens with an area under the curve accuracy of 79.0%.

Previous studies have shown a high rate of accuracy using eNose to detect Pseudomonas aeruginosa (PA). In the current study, the area under the curve accuracy for PA infection compared to no CF pathogens was 78%. Both SA-specific and PA-specific signatures were driven by different sensors in the eNose, which suggests pathogen-specific breath signatures, the researchers wrote.

The study findings were limited by several factors including the small number of patients with positive airway cultures for PA and the lack of data on variability of measures over time or treatment-induced changes, the researchers noted.

However, the results confirm the value of the eNose in real-time point-of-care detection of airway infection in children with CF, and this is the first study known to suggest the potential of an eNose to detect SA infection in particular in a routine clinical setting, the researchers wrote in their discussion.

Other points in favor of eNose compared to current practice include “low cost, ease of use and portability to the point-of-care,” they said. The eNose provides an opportunity for early detection of pathogens that challenges conventional microbiology testing, they concluded.

The study received no outside funding. Two coauthors disclosed fees and/or an interest in the company Breathomix BV.

An electronic nose effectively detected Staphylococcus aureus in children with cystic fibrosis, based on data from 100 individuals.

Staphylococcus aureus is the most common pathogen found in children with cystic fibrosis (CF), but current detection strategies are based on microbiology cultures, wrote Johann-Christoph Licht, a medical student at the University of Toronto, and colleagues.

Noninvasive tools are needed to screen children with CF early for respiratory infections, the researchers said.

The electronic Nose (eNose) is a technology that detects volatile organic compounds (VOCs). Although exhaled breath can be used to create distinct profiles, the ability of eNose to identify S. aureus (SA) in the breath of children with CF remains unclear, they wrote.

In a study published in the Journal of Cystic Fibrosis, the researchers analyzed breath profiles data from 100 children with CF. The study population included children aged 5-18 years with clinically stable CF who were recruited from CF clinics during routine visits. Patients with a CF pulmonary exacerbation were excluded.

The children’s median predicted FEV₁ was 91%. The researchers collected sputum from 67 patients and throat cultures for 33 patients. A group of 25 age-matched healthy controls served for comparison.

Eighty patients were positive for CF pathogens. Of these, 67 were positive for SA (44 with SA only and 23 with SA and at least one other pathogen).

Overall, patients with any CF pathogen on airway cultures were identified compared to airway cultures with no CF pathogens with an area under the curve accuracy of 79.0%.

Previous studies have shown a high rate of accuracy using eNose to detect Pseudomonas aeruginosa (PA). In the current study, the area under the curve accuracy for PA infection compared to no CF pathogens was 78%. Both SA-specific and PA-specific signatures were driven by different sensors in the eNose, which suggests pathogen-specific breath signatures, the researchers wrote.

The study findings were limited by several factors including the small number of patients with positive airway cultures for PA and the lack of data on variability of measures over time or treatment-induced changes, the researchers noted.

However, the results confirm the value of the eNose in real-time point-of-care detection of airway infection in children with CF, and this is the first study known to suggest the potential of an eNose to detect SA infection in particular in a routine clinical setting, the researchers wrote in their discussion.

Other points in favor of eNose compared to current practice include “low cost, ease of use and portability to the point-of-care,” they said. The eNose provides an opportunity for early detection of pathogens that challenges conventional microbiology testing, they concluded.

The study received no outside funding. Two coauthors disclosed fees and/or an interest in the company Breathomix BV.

Five different nonreceptor tyrosine kinase inhibitors were effective against viral replication of pandemic viruses and seasonal influenza viruses in an ex vivo lung model.

Influenza viruses remain a high cause of morbidity and mortality worldwide as viral mutations outwit vaccine efficacy, Robert Meineke, PhD, of the University of Veterinary Medicine in Hannover, Germany, and colleagues wrote.

“As with previous influenza pandemics and the current SARS-CoV-2 pandemic, effective vaccines are not readily available at early stages of a pandemic,” they noted. To help manage the limitations of timing and effectiveness of current vaccines, the researchers proposed repurposing nonreceptor tyrosine kinase inhibitors (NRTKIs) to block seasonal flu and COVID-19 viral replication.

In a study published in iScience, the researchers identified six NRTKIs currently approved by the U.S. Food and Drug Administration that showed in vitro inhibition of both pandemic viruses (H1N1) and seasonal influenza viruses (H3N2). These included defactinib, acalabrutinib, saracatinib, and bosutinib, all of which reduced hPCLS infectivity by approximately 50%. In addition, ibrutinib and bosutinib had the largest impact on viral titers. The antiviral effects of NRTKIs appeared to be independent of multiplicity of infection.

The researchers then tested the NRIKIs on an ex vivo model of human precision-cut lung slices to validate the effects of NRTKIs as antivirals against influenza A viruses (IAVs).

In this model, the highest peak titers were achieved at 48 hpi following infection with virus strains NL09 and NL11. The hPCLS models also showed consistent tolerability to 1x concentrations. “Our cytotoxicity cut-off was 20% of the positive control treatment; none of the NRTKIs surpassed this cutoff at [1x] max,” the researchers wrote.

Five of the six identified NRTKIs were validated in the ex vivo setting. All five reduced viral titers by at least 10-fold to more than 1,000-fold. Of these, ibrutinib, bosutinib, and bosutinib showed a significant effect at all concentrations, while treatments with acalabrutinib and defactinib were significant at 24 hpi and 48 hpi. The NRTKs also showed a high genetic barrier against emerging resistant virus mutations.

The study demonstrates the ability of NRTKIs to target kinases required for replication of IAV, the researchers wrote, and that NRTKIs “represent promising drugs for the development of the next generation of antivirals.”

More research is needed to determine the therapeutic window given that NRTKIs are targeting host factors versus virus-targeted antivirals, but the advantages of NRTKIs include localized delivery that can limit possible cytotoxic effects, and their safety and bioavailability are well established, they said.

The findings were limited by several factors including the use of lung tissue mainly from older donors with lung cancer, the researchers noted. However, this population could be considered at increased risk for IAVs and therefore the data are more clinically applicable.

In addition, “because many viruses utilize the same (or related) host kinases to facilitate replication and transmission, our studies have broader implications for the potential use of these SMKIs to treat infections by other viruses,” they concluded.

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

Five different nonreceptor tyrosine kinase inhibitors were effective against viral replication of pandemic viruses and seasonal influenza viruses in an ex vivo lung model.

Influenza viruses remain a high cause of morbidity and mortality worldwide as viral mutations outwit vaccine efficacy, Robert Meineke, PhD, of the University of Veterinary Medicine in Hannover, Germany, and colleagues wrote.

“As with previous influenza pandemics and the current SARS-CoV-2 pandemic, effective vaccines are not readily available at early stages of a pandemic,” they noted. To help manage the limitations of timing and effectiveness of current vaccines, the researchers proposed repurposing nonreceptor tyrosine kinase inhibitors (NRTKIs) to block seasonal flu and COVID-19 viral replication.

In a study published in iScience, the researchers identified six NRTKIs currently approved by the U.S. Food and Drug Administration that showed in vitro inhibition of both pandemic viruses (H1N1) and seasonal influenza viruses (H3N2). These included defactinib, acalabrutinib, saracatinib, and bosutinib, all of which reduced hPCLS infectivity by approximately 50%. In addition, ibrutinib and bosutinib had the largest impact on viral titers. The antiviral effects of NRTKIs appeared to be independent of multiplicity of infection.

The researchers then tested the NRIKIs on an ex vivo model of human precision-cut lung slices to validate the effects of NRTKIs as antivirals against influenza A viruses (IAVs).

In this model, the highest peak titers were achieved at 48 hpi following infection with virus strains NL09 and NL11. The hPCLS models also showed consistent tolerability to 1x concentrations. “Our cytotoxicity cut-off was 20% of the positive control treatment; none of the NRTKIs surpassed this cutoff at [1x] max,” the researchers wrote.

Five of the six identified NRTKIs were validated in the ex vivo setting. All five reduced viral titers by at least 10-fold to more than 1,000-fold. Of these, ibrutinib, bosutinib, and bosutinib showed a significant effect at all concentrations, while treatments with acalabrutinib and defactinib were significant at 24 hpi and 48 hpi. The NRTKs also showed a high genetic barrier against emerging resistant virus mutations.

The study demonstrates the ability of NRTKIs to target kinases required for replication of IAV, the researchers wrote, and that NRTKIs “represent promising drugs for the development of the next generation of antivirals.”

More research is needed to determine the therapeutic window given that NRTKIs are targeting host factors versus virus-targeted antivirals, but the advantages of NRTKIs include localized delivery that can limit possible cytotoxic effects, and their safety and bioavailability are well established, they said.

The findings were limited by several factors including the use of lung tissue mainly from older donors with lung cancer, the researchers noted. However, this population could be considered at increased risk for IAVs and therefore the data are more clinically applicable.

In addition, “because many viruses utilize the same (or related) host kinases to facilitate replication and transmission, our studies have broader implications for the potential use of these SMKIs to treat infections by other viruses,” they concluded.

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

Five different nonreceptor tyrosine kinase inhibitors were effective against viral replication of pandemic viruses and seasonal influenza viruses in an ex vivo lung model.

Influenza viruses remain a high cause of morbidity and mortality worldwide as viral mutations outwit vaccine efficacy, Robert Meineke, PhD, of the University of Veterinary Medicine in Hannover, Germany, and colleagues wrote.

“As with previous influenza pandemics and the current SARS-CoV-2 pandemic, effective vaccines are not readily available at early stages of a pandemic,” they noted. To help manage the limitations of timing and effectiveness of current vaccines, the researchers proposed repurposing nonreceptor tyrosine kinase inhibitors (NRTKIs) to block seasonal flu and COVID-19 viral replication.

In a study published in iScience, the researchers identified six NRTKIs currently approved by the U.S. Food and Drug Administration that showed in vitro inhibition of both pandemic viruses (H1N1) and seasonal influenza viruses (H3N2). These included defactinib, acalabrutinib, saracatinib, and bosutinib, all of which reduced hPCLS infectivity by approximately 50%. In addition, ibrutinib and bosutinib had the largest impact on viral titers. The antiviral effects of NRTKIs appeared to be independent of multiplicity of infection.

The researchers then tested the NRIKIs on an ex vivo model of human precision-cut lung slices to validate the effects of NRTKIs as antivirals against influenza A viruses (IAVs).

In this model, the highest peak titers were achieved at 48 hpi following infection with virus strains NL09 and NL11. The hPCLS models also showed consistent tolerability to 1x concentrations. “Our cytotoxicity cut-off was 20% of the positive control treatment; none of the NRTKIs surpassed this cutoff at [1x] max,” the researchers wrote.

Five of the six identified NRTKIs were validated in the ex vivo setting. All five reduced viral titers by at least 10-fold to more than 1,000-fold. Of these, ibrutinib, bosutinib, and bosutinib showed a significant effect at all concentrations, while treatments with acalabrutinib and defactinib were significant at 24 hpi and 48 hpi. The NRTKs also showed a high genetic barrier against emerging resistant virus mutations.

The study demonstrates the ability of NRTKIs to target kinases required for replication of IAV, the researchers wrote, and that NRTKIs “represent promising drugs for the development of the next generation of antivirals.”

More research is needed to determine the therapeutic window given that NRTKIs are targeting host factors versus virus-targeted antivirals, but the advantages of NRTKIs include localized delivery that can limit possible cytotoxic effects, and their safety and bioavailability are well established, they said.

The findings were limited by several factors including the use of lung tissue mainly from older donors with lung cancer, the researchers noted. However, this population could be considered at increased risk for IAVs and therefore the data are more clinically applicable.

In addition, “because many viruses utilize the same (or related) host kinases to facilitate replication and transmission, our studies have broader implications for the potential use of these SMKIs to treat infections by other viruses,” they concluded.

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

Women with psoriatic arthritis (PsA) presented with more severe disease at baseline and were less likely to achieve favorable outcomes after 12 months of treatment with either ustekinumab (Stelara) or a tumor necrosis factor (TNF) inhibitor, compared with men, according to a post hoc analysis of data from nearly 1,000 individuals.

Although data suggest that the overall prevalence of PsA is similar across genders, recent studies have identified differences in various aspects of PsA between men and women, wrote Arno W.R. Van Kuijk, MD, of Amsterdam Rheumatology and Immunology Center, and colleagues wrote in a study published in Rheumatology.

“Accumulating evidence in multiple rheumatic diseases indicates that gender may influence the likelihood of achieving the desired outcome with treatment,” but studies of differences in treatment response according to gender are limited, they said.

The researchers conducted a post hoc analysis of women and men with PsA who were part of PsABio, a noninterventional European study of patients with PsA. All participants were starting first-, second-, or third-line treatment with ustekinumab or a TNF inhibitor. The primary outcome was response to treatment at 12 months. Disease activity was assessed using the clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA), the Health Assessment Questionnaire–Disability Index (HAQ-DI), and total score on the 12-item Psoriatic Arthritis Impact of Disease (PsAID-12) questionnaire.

Baseline available data for 512 women and 417 men showed the mean duration of disease was similar between genders (6.7 years for females and 6.9 years for males); body mass index was similar, as was the proportion of male and female patients receiving concomitant conventional synthetic disease-modifying antirheumatic drugs (DMARDs). Females scored significantly worse than males on disease activity assessments at baseline with mean cDAPSA scores of 32.3 and 26.8, respectively.

The final analysis of 895 patients with baseline data and a postbaseline assessment included 439 who started ustekinumab (247 females, 192 males), and 456 who started a TNF inhibitor (248 females, 208 males).

At 12 months, females showed smaller degrees of improvement than males; 57.8% and 80.3%, respectively, achieved low disease activity based on cDAPSA scores, while 33.7% and 55.5% of females and males, respectively, achieved minimal disease activity. Measures of disability were higher in females than males, with HAQ-DI scores of 0.85 versus 0.50. PsAID-12 scores also were higher for females, compared with males (3.5 vs. 2.4).

A total of 81.7% of patients were on their initial biologic DMARD after 12 months, but more females than males who were taking ustekinumab or a TNF inhibitor changed or discontinued treatment.

Treatment persistence was significantly lower in females than males (P = .01), and lack of effectiveness was the main reason for discontinuation regardless of gender.

“The analysis of gender subgroup results of the PsABio study has expanded previously published observations that men and women with PsA have different experiences with the disease activity, clinical manifestations, impact on health-related quality of life, response to [biologic] DMARDs, and drug persistence,” the researchers wrote.

The lack of a medication protocol in the PsABio study limited the conclusions that could be drawn from the post hoc analysis, but the results were strengthened by the relatively large and diverse sample size and the inclusion of responses to more than one medication, the researchers noted.

The study was supported by Janssen. Dr. Van Kuijk disclosed serving as a consultant and receiving grant support from Janssen and other companies; several coauthors also disclosed relationships with Janssen.

Women with psoriatic arthritis (PsA) presented with more severe disease at baseline and were less likely to achieve favorable outcomes after 12 months of treatment with either ustekinumab (Stelara) or a tumor necrosis factor (TNF) inhibitor, compared with men, according to a post hoc analysis of data from nearly 1,000 individuals.

Although data suggest that the overall prevalence of PsA is similar across genders, recent studies have identified differences in various aspects of PsA between men and women, wrote Arno W.R. Van Kuijk, MD, of Amsterdam Rheumatology and Immunology Center, and colleagues wrote in a study published in Rheumatology.

“Accumulating evidence in multiple rheumatic diseases indicates that gender may influence the likelihood of achieving the desired outcome with treatment,” but studies of differences in treatment response according to gender are limited, they said.

The researchers conducted a post hoc analysis of women and men with PsA who were part of PsABio, a noninterventional European study of patients with PsA. All participants were starting first-, second-, or third-line treatment with ustekinumab or a TNF inhibitor. The primary outcome was response to treatment at 12 months. Disease activity was assessed using the clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA), the Health Assessment Questionnaire–Disability Index (HAQ-DI), and total score on the 12-item Psoriatic Arthritis Impact of Disease (PsAID-12) questionnaire.

Baseline available data for 512 women and 417 men showed the mean duration of disease was similar between genders (6.7 years for females and 6.9 years for males); body mass index was similar, as was the proportion of male and female patients receiving concomitant conventional synthetic disease-modifying antirheumatic drugs (DMARDs). Females scored significantly worse than males on disease activity assessments at baseline with mean cDAPSA scores of 32.3 and 26.8, respectively.

The final analysis of 895 patients with baseline data and a postbaseline assessment included 439 who started ustekinumab (247 females, 192 males), and 456 who started a TNF inhibitor (248 females, 208 males).

At 12 months, females showed smaller degrees of improvement than males; 57.8% and 80.3%, respectively, achieved low disease activity based on cDAPSA scores, while 33.7% and 55.5% of females and males, respectively, achieved minimal disease activity. Measures of disability were higher in females than males, with HAQ-DI scores of 0.85 versus 0.50. PsAID-12 scores also were higher for females, compared with males (3.5 vs. 2.4).

A total of 81.7% of patients were on their initial biologic DMARD after 12 months, but more females than males who were taking ustekinumab or a TNF inhibitor changed or discontinued treatment.

Treatment persistence was significantly lower in females than males (P = .01), and lack of effectiveness was the main reason for discontinuation regardless of gender.

“The analysis of gender subgroup results of the PsABio study has expanded previously published observations that men and women with PsA have different experiences with the disease activity, clinical manifestations, impact on health-related quality of life, response to [biologic] DMARDs, and drug persistence,” the researchers wrote.

The lack of a medication protocol in the PsABio study limited the conclusions that could be drawn from the post hoc analysis, but the results were strengthened by the relatively large and diverse sample size and the inclusion of responses to more than one medication, the researchers noted.

The study was supported by Janssen. Dr. Van Kuijk disclosed serving as a consultant and receiving grant support from Janssen and other companies; several coauthors also disclosed relationships with Janssen.

Women with psoriatic arthritis (PsA) presented with more severe disease at baseline and were less likely to achieve favorable outcomes after 12 months of treatment with either ustekinumab (Stelara) or a tumor necrosis factor (TNF) inhibitor, compared with men, according to a post hoc analysis of data from nearly 1,000 individuals.

Although data suggest that the overall prevalence of PsA is similar across genders, recent studies have identified differences in various aspects of PsA between men and women, wrote Arno W.R. Van Kuijk, MD, of Amsterdam Rheumatology and Immunology Center, and colleagues wrote in a study published in Rheumatology.

“Accumulating evidence in multiple rheumatic diseases indicates that gender may influence the likelihood of achieving the desired outcome with treatment,” but studies of differences in treatment response according to gender are limited, they said.

The researchers conducted a post hoc analysis of women and men with PsA who were part of PsABio, a noninterventional European study of patients with PsA. All participants were starting first-, second-, or third-line treatment with ustekinumab or a TNF inhibitor. The primary outcome was response to treatment at 12 months. Disease activity was assessed using the clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA), the Health Assessment Questionnaire–Disability Index (HAQ-DI), and total score on the 12-item Psoriatic Arthritis Impact of Disease (PsAID-12) questionnaire.

Baseline available data for 512 women and 417 men showed the mean duration of disease was similar between genders (6.7 years for females and 6.9 years for males); body mass index was similar, as was the proportion of male and female patients receiving concomitant conventional synthetic disease-modifying antirheumatic drugs (DMARDs). Females scored significantly worse than males on disease activity assessments at baseline with mean cDAPSA scores of 32.3 and 26.8, respectively.

The final analysis of 895 patients with baseline data and a postbaseline assessment included 439 who started ustekinumab (247 females, 192 males), and 456 who started a TNF inhibitor (248 females, 208 males).

At 12 months, females showed smaller degrees of improvement than males; 57.8% and 80.3%, respectively, achieved low disease activity based on cDAPSA scores, while 33.7% and 55.5% of females and males, respectively, achieved minimal disease activity. Measures of disability were higher in females than males, with HAQ-DI scores of 0.85 versus 0.50. PsAID-12 scores also were higher for females, compared with males (3.5 vs. 2.4).

A total of 81.7% of patients were on their initial biologic DMARD after 12 months, but more females than males who were taking ustekinumab or a TNF inhibitor changed or discontinued treatment.

Treatment persistence was significantly lower in females than males (P = .01), and lack of effectiveness was the main reason for discontinuation regardless of gender.

“The analysis of gender subgroup results of the PsABio study has expanded previously published observations that men and women with PsA have different experiences with the disease activity, clinical manifestations, impact on health-related quality of life, response to [biologic] DMARDs, and drug persistence,” the researchers wrote.

The lack of a medication protocol in the PsABio study limited the conclusions that could be drawn from the post hoc analysis, but the results were strengthened by the relatively large and diverse sample size and the inclusion of responses to more than one medication, the researchers noted.

The study was supported by Janssen. Dr. Van Kuijk disclosed serving as a consultant and receiving grant support from Janssen and other companies; several coauthors also disclosed relationships with Janssen.