Federal Practitioner

TOPLINE:

Adoption of doublet therapy – androgen deprivation therapy (ADT) combined with either docetaxel or an androgen receptor pathway inhibitor – has led to a clinically meaningful increase in long-term survival in men with de novo metastatic castration-sensitive prostate cancer, Swedish registry data show.

METHODOLOGY:

• The use of doublet therapy has increased significantly in Sweden in recent years given the growing body of evidence demonstrating that doublet therapy improves survival in individuals with de novo metastatic castration-sensitive prostate cancer.
• Investigators wanted to see whether the increasing use of doublet therapy in this patient population has improved survival when taking various other factors into consideration.
• The analysis, which included 11,382 men diagnosed with metastatic castration-sensitive prostate cancer in Sweden from 2008-2020 and registered in the country’s National Prostate Cancer Register, explored the use of doublet therapy over time and its association with survival, adjusting for age, comorbidities, and cancer characteristics.
• The researchers estimated average 5-year and 10-year survival over time using a survival model.

TAKEAWAY:

• During the study period, patients exhibited a shift toward less advanced prostate cancer, with median prostate-specific antigen (PSA) levels at diagnosis decreasing from 145 to 107 ng/mL in men with metastatic disease.
• Upfront treatment with doublet therapy in these men simultaneously increased from 1% in 2016 to 44% in 2020.
• Adjusted 5-year overall survival increased from 26% between 2008-2012 to 35% in the period 2017-2020; in the 5 years following diagnosis, patients’ mean survival increased by about 6 months between 2008-2012 and 2017-2020.
• The percentage of patients still alive at 10 years doubled from 9% in 2008 to 18% in 2020. Improvements were greater in men younger than 80 years old.

IN PRACTICE:

“A clinically meaningful increase in long-term survival was observed in men diagnosed with de novo [metastatic castration-sensitive prostate cancer] between 2008 and 2020 in Sweden. We argue that the main reason for this improvement was the increased upfront use of doublet therapy,” the authors concluded.

SOURCE:

The study, with first author Christian Corsini, MD, of Uppsala (Sweden) University, was published online in JAMA Network Open.

LIMITATIONS:

Although there were no substantial changes in the diagnostic workup, unmeasured and unknown changes over the years may have affected survival.  The researchers lacked information on PSA levels during follow-up, and therefore could not assess progression-free survival. Some upfront docetaxel use was not captured before 2017.

DISCLOSURES:

The study received funding from the Swedish Cancer Society and Region Uppsala. The authors reported no relevant financial relationships.

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

TOPLINE:

Adoption of doublet therapy – androgen deprivation therapy (ADT) combined with either docetaxel or an androgen receptor pathway inhibitor – has led to a clinically meaningful increase in long-term survival in men with de novo metastatic castration-sensitive prostate cancer, Swedish registry data show.

METHODOLOGY:

• The use of doublet therapy has increased significantly in Sweden in recent years given the growing body of evidence demonstrating that doublet therapy improves survival in individuals with de novo metastatic castration-sensitive prostate cancer.
• Investigators wanted to see whether the increasing use of doublet therapy in this patient population has improved survival when taking various other factors into consideration.
• The analysis, which included 11,382 men diagnosed with metastatic castration-sensitive prostate cancer in Sweden from 2008-2020 and registered in the country’s National Prostate Cancer Register, explored the use of doublet therapy over time and its association with survival, adjusting for age, comorbidities, and cancer characteristics.
• The researchers estimated average 5-year and 10-year survival over time using a survival model.

TAKEAWAY:

• During the study period, patients exhibited a shift toward less advanced prostate cancer, with median prostate-specific antigen (PSA) levels at diagnosis decreasing from 145 to 107 ng/mL in men with metastatic disease.
• Upfront treatment with doublet therapy in these men simultaneously increased from 1% in 2016 to 44% in 2020.
• Adjusted 5-year overall survival increased from 26% between 2008-2012 to 35% in the period 2017-2020; in the 5 years following diagnosis, patients’ mean survival increased by about 6 months between 2008-2012 and 2017-2020.
• The percentage of patients still alive at 10 years doubled from 9% in 2008 to 18% in 2020. Improvements were greater in men younger than 80 years old.

IN PRACTICE:

“A clinically meaningful increase in long-term survival was observed in men diagnosed with de novo [metastatic castration-sensitive prostate cancer] between 2008 and 2020 in Sweden. We argue that the main reason for this improvement was the increased upfront use of doublet therapy,” the authors concluded.

SOURCE:

The study, with first author Christian Corsini, MD, of Uppsala (Sweden) University, was published online in JAMA Network Open.

LIMITATIONS:

Although there were no substantial changes in the diagnostic workup, unmeasured and unknown changes over the years may have affected survival.  The researchers lacked information on PSA levels during follow-up, and therefore could not assess progression-free survival. Some upfront docetaxel use was not captured before 2017.

DISCLOSURES:

The study received funding from the Swedish Cancer Society and Region Uppsala. The authors reported no relevant financial relationships.

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

TOPLINE:

Adoption of doublet therapy – androgen deprivation therapy (ADT) combined with either docetaxel or an androgen receptor pathway inhibitor – has led to a clinically meaningful increase in long-term survival in men with de novo metastatic castration-sensitive prostate cancer, Swedish registry data show.

METHODOLOGY:

• The use of doublet therapy has increased significantly in Sweden in recent years given the growing body of evidence demonstrating that doublet therapy improves survival in individuals with de novo metastatic castration-sensitive prostate cancer.
• Investigators wanted to see whether the increasing use of doublet therapy in this patient population has improved survival when taking various other factors into consideration.
• The analysis, which included 11,382 men diagnosed with metastatic castration-sensitive prostate cancer in Sweden from 2008-2020 and registered in the country’s National Prostate Cancer Register, explored the use of doublet therapy over time and its association with survival, adjusting for age, comorbidities, and cancer characteristics.
• The researchers estimated average 5-year and 10-year survival over time using a survival model.

TAKEAWAY:

• During the study period, patients exhibited a shift toward less advanced prostate cancer, with median prostate-specific antigen (PSA) levels at diagnosis decreasing from 145 to 107 ng/mL in men with metastatic disease.
• Upfront treatment with doublet therapy in these men simultaneously increased from 1% in 2016 to 44% in 2020.
• Adjusted 5-year overall survival increased from 26% between 2008-2012 to 35% in the period 2017-2020; in the 5 years following diagnosis, patients’ mean survival increased by about 6 months between 2008-2012 and 2017-2020.
• The percentage of patients still alive at 10 years doubled from 9% in 2008 to 18% in 2020. Improvements were greater in men younger than 80 years old.

IN PRACTICE:

“A clinically meaningful increase in long-term survival was observed in men diagnosed with de novo [metastatic castration-sensitive prostate cancer] between 2008 and 2020 in Sweden. We argue that the main reason for this improvement was the increased upfront use of doublet therapy,” the authors concluded.

SOURCE:

The study, with first author Christian Corsini, MD, of Uppsala (Sweden) University, was published online in JAMA Network Open.

LIMITATIONS:

Although there were no substantial changes in the diagnostic workup, unmeasured and unknown changes over the years may have affected survival.  The researchers lacked information on PSA levels during follow-up, and therefore could not assess progression-free survival. Some upfront docetaxel use was not captured before 2017.

DISCLOSURES:

The study received funding from the Swedish Cancer Society and Region Uppsala. The authors reported no relevant financial relationships.

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

HAMBURG, GERMANY – The investigational incretin receptor agonist pemvidutide produced significant weight loss and other cardiometabolic benefits in a phase 2 randomized trial, adding a different type of “twincretin” to a growing mix of incretin-based weight-loss drugs in development that also offer additional benefits.

Pemvidutide (Altimmune Inc) is a long-acting “balanced” dual agonist of both glucagon-like peptide 1 (GLP-1) and glucagon that is in development for the treatment of obesity and nonalcoholic steatohepatitis (NASH) but not type 2 diabetes, as its effect on glucose is neutral. Phase 1 data for pemvidutide’s liver effect were presented in 2022.

In contrast, the dual GLP-1-glucose-dependent insulinotropic polypeptide (GIP) agonist tirzepatide (Mounjaro, Lilly) has been approved for the treatment of type 2 diabetes. It awaits an indication for obesity.

“When you look [at] the results for any given agent, think about obesity as a series of problems. Some overlap, and some don’t. While about 20%-25% of people with obesity also have type 2 diabetes, not everybody does. So the compounds that don’t lower glucose ... those will be great for others who have [fatty liver disease] or hyperlipidemia. ... It’s not going to be one compound for everybody,” said Louis J. Aronne, MD, director of the center for weight management and metabolic clinical research, Weill Cornell Medicine, New York.

Results of a new 24-week interim analysis of data from the phase 2 pemvidutide trial, called MOMENTUM, were presented at the annual meeting of the European Association for the Study of Diabetes by Dr. Aronne.

Included in that session were encore presentations of data for another GLP-1-glucagon dual agonist, survodutide, as well as data for Eli Lilly’s GLP-1-GIP-glucagon “triagonist,” retatrutide. Retatrutide is in development to induce weight loss, while survodutide (Boehringer Ingelheim and Zealand Pharma), like pemvidutide, is in development to induce weight loss and treat fatty liver disease.

Added Dr. Aronne, “As good as [the triple agonist] retatrutide looks, I doubt that every single person with obesity in the world will be treated with it. ... Think about this as a field, the way you treat diabetes and every other chronic illness.”

Asked to comment, session moderator Rajna Golubic, PhD, of the Oxford (England) Centre for Diabetes, Endocrinology and Metabolism, told this news organization, “We need to think in terms of treating beyond weight loss. ... We need to look at the person holistically and at other aspects of cardiometabolic health and treat in a personalized way and choose treatments according to the comorbidities people have.”

Regarding the dual GLP-1-glucagon agonists, including pemvidutide, Dr. Golubic pointed out that the glucagon agonism does the opposite of glucose-lowering agents but that the compound is “balanced for greater affinity for the GLP-1 receptor vs. glucagon, so that the beneficial effects outweigh the effect for glucose but it still harnesses the benefits of glucagon on liver with a decrease in liver fat, with positive effects on heart, positive effects on kidneys, and other beneficial metabolic effects.”
 

Pemvidutide lowers weight, LDL cholesterol, triglycerides, and blood pressure

Dr. Aronne began his presentation by noting that dyslipidemia, fatty liver disease, and hypertension are the most significant comorbidities of obesity, occurring in 66%-70%, 58%-75%, and 45%-55% of patients, respectively, while type 2 diabetes is less common, at 19%-23%.

Pemvidutide’s GLP-1 receptor agonism reduces appetite, inflammation, and gastric emptying, while glucagon agonism increases lipolysis, mobilizes fat, and increases energy expenditure, Dr. Aronne explained.

The 48-week phase 2 MOMENTUM trial randomly assigned 320 participants with overweight or obesity and at least one obesity-related comorbidity but not diabetes to receive weekly doses of 1.2 mg, 1.8 mg, or 2.4 mg of pemvidutide or placebo. The two lower pemvidutide doses were initiated immediately without titration, while the 2.4-mg dose was titrated rapidly over 4 weeks.

In a prespecified interim analysis of 160 participants, the percent body weight loss at 24 weeks was 10.7%, 9.4%, and 7.3% with the 2.4-mg, 1.8-mg, and 1.2-mg doses, respectively (P < .001). All weight loss values were significant; weight loss with placebo was a nonsignificant 1%.

The proportions of patients who lost at least 5% of their body weight were 84.6%, 66.7%, and 66.7%, respectively, vs. 25% with placebo. Half of the patients who received the 2.4-mg and 1.8-mg doses lost at least 10% of their body weight. Reductions in waist circumference followed suit; the patients who received the 2.4-mg dose lost an average of 10.2 cm, or “in the U.S., about 4 inches or 4 belt loops. That’s pretty good, you need a new belt,” Dr. Aronne commented.

Significant reductions in total cholesterol and triglyceride levels were also seen at week 24 by 16.5% and 25.0%, respectively, with the 2.4-mg dose. Low-density lipoprotein cholesterol levels also dropped, although not significantly; high-density lipoprotein levels dropped significantly.

Systolic blood pressure dropped by 5.5 mm Hg, and diastolic blood pressure dropped by 1.8 mm Hg in the 2.4-mg group and by lesser degrees among the patients who received lower doses. There were no significant changes in heart rate, Dr. Aronne noted.

Glucose homeostasis was preserved in all groups throughout the 24 weeks.

As with all drugs in the incretin class, gastrointestinal adverse events were common. Severe vomiting occurred in one person in the 1.8-mg group and in four with 2.4 mg. Efforts will be made to reduce that in subsequent trials, Dr. Aronne said.

“We have learned over time that going more gradually in titrating up these agents is a better strategy, allowing dose reduction may be a better strategy, and allowing antiemetics temporarily as we increase the dose is a lesson that many have learned doing these trials and of course in our clinical practices,” he commented.

Dr. Golubic told this news organization that the recent emergence of potent incretin-based weight loss drugs is “a huge paradigm shift. The prevalence of obesity will be 35% or higher by 2035. Bariatric surgery isn’t feasible for everyone, and it’s very expensive, so we need drugs to provide benefits in terms of lowering weight, glucose, and other cardiometabolic risk factors.”

The full 48-week data for MOMENTUM will be announced in the fourth quarter of 2023.

Dr. Aronne has received consulting fees from and serves on advisory boards for Allurion, Altimmune, Atria, Gelesis, Jamieson Wellness, Janssen Pharmaceuticals, Jazz Pharmaceuticals, Novo Nordisk, Pfizer, Optum, Eli Lilly, Senda Biosciences, and Versanis; has received research funding from Allurion, AstraZeneca, Gelesis, Janssen Pharmaceuticals, Novo Nordisk, and Eli Lilly; has equity interests in Allurion, ERX Pharmaceuticals, Gelesis, Intellihealth, Jamieson Wellness, and Myos Corp; and serves on a board of directors for ERX Pharmaceuticals, Intellihealth, and Jamieson Wellness. Dr. Golubic has received research support from AstraZeneca.

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

HAMBURG, GERMANY – The investigational incretin receptor agonist pemvidutide produced significant weight loss and other cardiometabolic benefits in a phase 2 randomized trial, adding a different type of “twincretin” to a growing mix of incretin-based weight-loss drugs in development that also offer additional benefits.

Pemvidutide (Altimmune Inc) is a long-acting “balanced” dual agonist of both glucagon-like peptide 1 (GLP-1) and glucagon that is in development for the treatment of obesity and nonalcoholic steatohepatitis (NASH) but not type 2 diabetes, as its effect on glucose is neutral. Phase 1 data for pemvidutide’s liver effect were presented in 2022.

In contrast, the dual GLP-1-glucose-dependent insulinotropic polypeptide (GIP) agonist tirzepatide (Mounjaro, Lilly) has been approved for the treatment of type 2 diabetes. It awaits an indication for obesity.

“When you look [at] the results for any given agent, think about obesity as a series of problems. Some overlap, and some don’t. While about 20%-25% of people with obesity also have type 2 diabetes, not everybody does. So the compounds that don’t lower glucose ... those will be great for others who have [fatty liver disease] or hyperlipidemia. ... It’s not going to be one compound for everybody,” said Louis J. Aronne, MD, director of the center for weight management and metabolic clinical research, Weill Cornell Medicine, New York.

Results of a new 24-week interim analysis of data from the phase 2 pemvidutide trial, called MOMENTUM, were presented at the annual meeting of the European Association for the Study of Diabetes by Dr. Aronne.

Included in that session were encore presentations of data for another GLP-1-glucagon dual agonist, survodutide, as well as data for Eli Lilly’s GLP-1-GIP-glucagon “triagonist,” retatrutide. Retatrutide is in development to induce weight loss, while survodutide (Boehringer Ingelheim and Zealand Pharma), like pemvidutide, is in development to induce weight loss and treat fatty liver disease.

Added Dr. Aronne, “As good as [the triple agonist] retatrutide looks, I doubt that every single person with obesity in the world will be treated with it. ... Think about this as a field, the way you treat diabetes and every other chronic illness.”

Asked to comment, session moderator Rajna Golubic, PhD, of the Oxford (England) Centre for Diabetes, Endocrinology and Metabolism, told this news organization, “We need to think in terms of treating beyond weight loss. ... We need to look at the person holistically and at other aspects of cardiometabolic health and treat in a personalized way and choose treatments according to the comorbidities people have.”

Regarding the dual GLP-1-glucagon agonists, including pemvidutide, Dr. Golubic pointed out that the glucagon agonism does the opposite of glucose-lowering agents but that the compound is “balanced for greater affinity for the GLP-1 receptor vs. glucagon, so that the beneficial effects outweigh the effect for glucose but it still harnesses the benefits of glucagon on liver with a decrease in liver fat, with positive effects on heart, positive effects on kidneys, and other beneficial metabolic effects.”
 

Pemvidutide lowers weight, LDL cholesterol, triglycerides, and blood pressure

Dr. Aronne began his presentation by noting that dyslipidemia, fatty liver disease, and hypertension are the most significant comorbidities of obesity, occurring in 66%-70%, 58%-75%, and 45%-55% of patients, respectively, while type 2 diabetes is less common, at 19%-23%.

Pemvidutide’s GLP-1 receptor agonism reduces appetite, inflammation, and gastric emptying, while glucagon agonism increases lipolysis, mobilizes fat, and increases energy expenditure, Dr. Aronne explained.

The 48-week phase 2 MOMENTUM trial randomly assigned 320 participants with overweight or obesity and at least one obesity-related comorbidity but not diabetes to receive weekly doses of 1.2 mg, 1.8 mg, or 2.4 mg of pemvidutide or placebo. The two lower pemvidutide doses were initiated immediately without titration, while the 2.4-mg dose was titrated rapidly over 4 weeks.

In a prespecified interim analysis of 160 participants, the percent body weight loss at 24 weeks was 10.7%, 9.4%, and 7.3% with the 2.4-mg, 1.8-mg, and 1.2-mg doses, respectively (P < .001). All weight loss values were significant; weight loss with placebo was a nonsignificant 1%.

The proportions of patients who lost at least 5% of their body weight were 84.6%, 66.7%, and 66.7%, respectively, vs. 25% with placebo. Half of the patients who received the 2.4-mg and 1.8-mg doses lost at least 10% of their body weight. Reductions in waist circumference followed suit; the patients who received the 2.4-mg dose lost an average of 10.2 cm, or “in the U.S., about 4 inches or 4 belt loops. That’s pretty good, you need a new belt,” Dr. Aronne commented.

Significant reductions in total cholesterol and triglyceride levels were also seen at week 24 by 16.5% and 25.0%, respectively, with the 2.4-mg dose. Low-density lipoprotein cholesterol levels also dropped, although not significantly; high-density lipoprotein levels dropped significantly.

Systolic blood pressure dropped by 5.5 mm Hg, and diastolic blood pressure dropped by 1.8 mm Hg in the 2.4-mg group and by lesser degrees among the patients who received lower doses. There were no significant changes in heart rate, Dr. Aronne noted.

Glucose homeostasis was preserved in all groups throughout the 24 weeks.

As with all drugs in the incretin class, gastrointestinal adverse events were common. Severe vomiting occurred in one person in the 1.8-mg group and in four with 2.4 mg. Efforts will be made to reduce that in subsequent trials, Dr. Aronne said.

“We have learned over time that going more gradually in titrating up these agents is a better strategy, allowing dose reduction may be a better strategy, and allowing antiemetics temporarily as we increase the dose is a lesson that many have learned doing these trials and of course in our clinical practices,” he commented.

Dr. Golubic told this news organization that the recent emergence of potent incretin-based weight loss drugs is “a huge paradigm shift. The prevalence of obesity will be 35% or higher by 2035. Bariatric surgery isn’t feasible for everyone, and it’s very expensive, so we need drugs to provide benefits in terms of lowering weight, glucose, and other cardiometabolic risk factors.”

The full 48-week data for MOMENTUM will be announced in the fourth quarter of 2023.

Dr. Aronne has received consulting fees from and serves on advisory boards for Allurion, Altimmune, Atria, Gelesis, Jamieson Wellness, Janssen Pharmaceuticals, Jazz Pharmaceuticals, Novo Nordisk, Pfizer, Optum, Eli Lilly, Senda Biosciences, and Versanis; has received research funding from Allurion, AstraZeneca, Gelesis, Janssen Pharmaceuticals, Novo Nordisk, and Eli Lilly; has equity interests in Allurion, ERX Pharmaceuticals, Gelesis, Intellihealth, Jamieson Wellness, and Myos Corp; and serves on a board of directors for ERX Pharmaceuticals, Intellihealth, and Jamieson Wellness. Dr. Golubic has received research support from AstraZeneca.

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

HAMBURG, GERMANY – The investigational incretin receptor agonist pemvidutide produced significant weight loss and other cardiometabolic benefits in a phase 2 randomized trial, adding a different type of “twincretin” to a growing mix of incretin-based weight-loss drugs in development that also offer additional benefits.

Pemvidutide (Altimmune Inc) is a long-acting “balanced” dual agonist of both glucagon-like peptide 1 (GLP-1) and glucagon that is in development for the treatment of obesity and nonalcoholic steatohepatitis (NASH) but not type 2 diabetes, as its effect on glucose is neutral. Phase 1 data for pemvidutide’s liver effect were presented in 2022.

In contrast, the dual GLP-1-glucose-dependent insulinotropic polypeptide (GIP) agonist tirzepatide (Mounjaro, Lilly) has been approved for the treatment of type 2 diabetes. It awaits an indication for obesity.

“When you look [at] the results for any given agent, think about obesity as a series of problems. Some overlap, and some don’t. While about 20%-25% of people with obesity also have type 2 diabetes, not everybody does. So the compounds that don’t lower glucose ... those will be great for others who have [fatty liver disease] or hyperlipidemia. ... It’s not going to be one compound for everybody,” said Louis J. Aronne, MD, director of the center for weight management and metabolic clinical research, Weill Cornell Medicine, New York.

Results of a new 24-week interim analysis of data from the phase 2 pemvidutide trial, called MOMENTUM, were presented at the annual meeting of the European Association for the Study of Diabetes by Dr. Aronne.

Included in that session were encore presentations of data for another GLP-1-glucagon dual agonist, survodutide, as well as data for Eli Lilly’s GLP-1-GIP-glucagon “triagonist,” retatrutide. Retatrutide is in development to induce weight loss, while survodutide (Boehringer Ingelheim and Zealand Pharma), like pemvidutide, is in development to induce weight loss and treat fatty liver disease.

Added Dr. Aronne, “As good as [the triple agonist] retatrutide looks, I doubt that every single person with obesity in the world will be treated with it. ... Think about this as a field, the way you treat diabetes and every other chronic illness.”

Asked to comment, session moderator Rajna Golubic, PhD, of the Oxford (England) Centre for Diabetes, Endocrinology and Metabolism, told this news organization, “We need to think in terms of treating beyond weight loss. ... We need to look at the person holistically and at other aspects of cardiometabolic health and treat in a personalized way and choose treatments according to the comorbidities people have.”

Regarding the dual GLP-1-glucagon agonists, including pemvidutide, Dr. Golubic pointed out that the glucagon agonism does the opposite of glucose-lowering agents but that the compound is “balanced for greater affinity for the GLP-1 receptor vs. glucagon, so that the beneficial effects outweigh the effect for glucose but it still harnesses the benefits of glucagon on liver with a decrease in liver fat, with positive effects on heart, positive effects on kidneys, and other beneficial metabolic effects.”
 

Pemvidutide lowers weight, LDL cholesterol, triglycerides, and blood pressure

Dr. Aronne began his presentation by noting that dyslipidemia, fatty liver disease, and hypertension are the most significant comorbidities of obesity, occurring in 66%-70%, 58%-75%, and 45%-55% of patients, respectively, while type 2 diabetes is less common, at 19%-23%.

Pemvidutide’s GLP-1 receptor agonism reduces appetite, inflammation, and gastric emptying, while glucagon agonism increases lipolysis, mobilizes fat, and increases energy expenditure, Dr. Aronne explained.

The 48-week phase 2 MOMENTUM trial randomly assigned 320 participants with overweight or obesity and at least one obesity-related comorbidity but not diabetes to receive weekly doses of 1.2 mg, 1.8 mg, or 2.4 mg of pemvidutide or placebo. The two lower pemvidutide doses were initiated immediately without titration, while the 2.4-mg dose was titrated rapidly over 4 weeks.

In a prespecified interim analysis of 160 participants, the percent body weight loss at 24 weeks was 10.7%, 9.4%, and 7.3% with the 2.4-mg, 1.8-mg, and 1.2-mg doses, respectively (P < .001). All weight loss values were significant; weight loss with placebo was a nonsignificant 1%.

The proportions of patients who lost at least 5% of their body weight were 84.6%, 66.7%, and 66.7%, respectively, vs. 25% with placebo. Half of the patients who received the 2.4-mg and 1.8-mg doses lost at least 10% of their body weight. Reductions in waist circumference followed suit; the patients who received the 2.4-mg dose lost an average of 10.2 cm, or “in the U.S., about 4 inches or 4 belt loops. That’s pretty good, you need a new belt,” Dr. Aronne commented.

Significant reductions in total cholesterol and triglyceride levels were also seen at week 24 by 16.5% and 25.0%, respectively, with the 2.4-mg dose. Low-density lipoprotein cholesterol levels also dropped, although not significantly; high-density lipoprotein levels dropped significantly.

Systolic blood pressure dropped by 5.5 mm Hg, and diastolic blood pressure dropped by 1.8 mm Hg in the 2.4-mg group and by lesser degrees among the patients who received lower doses. There were no significant changes in heart rate, Dr. Aronne noted.

Glucose homeostasis was preserved in all groups throughout the 24 weeks.

As with all drugs in the incretin class, gastrointestinal adverse events were common. Severe vomiting occurred in one person in the 1.8-mg group and in four with 2.4 mg. Efforts will be made to reduce that in subsequent trials, Dr. Aronne said.

“We have learned over time that going more gradually in titrating up these agents is a better strategy, allowing dose reduction may be a better strategy, and allowing antiemetics temporarily as we increase the dose is a lesson that many have learned doing these trials and of course in our clinical practices,” he commented.

Dr. Golubic told this news organization that the recent emergence of potent incretin-based weight loss drugs is “a huge paradigm shift. The prevalence of obesity will be 35% or higher by 2035. Bariatric surgery isn’t feasible for everyone, and it’s very expensive, so we need drugs to provide benefits in terms of lowering weight, glucose, and other cardiometabolic risk factors.”

The full 48-week data for MOMENTUM will be announced in the fourth quarter of 2023.

Dr. Aronne has received consulting fees from and serves on advisory boards for Allurion, Altimmune, Atria, Gelesis, Jamieson Wellness, Janssen Pharmaceuticals, Jazz Pharmaceuticals, Novo Nordisk, Pfizer, Optum, Eli Lilly, Senda Biosciences, and Versanis; has received research funding from Allurion, AstraZeneca, Gelesis, Janssen Pharmaceuticals, Novo Nordisk, and Eli Lilly; has equity interests in Allurion, ERX Pharmaceuticals, Gelesis, Intellihealth, Jamieson Wellness, and Myos Corp; and serves on a board of directors for ERX Pharmaceuticals, Intellihealth, and Jamieson Wellness. Dr. Golubic has received research support from AstraZeneca.

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

PHILADELPHIA – Treatment of vasomotor symptoms with estetrol (E4) led to improvements in postmenopausal patients’ lipid profiles and blood glucose, according to findings of a phase 3 clinical trial presented at the annual meeting of the Menopause Society (formerly The North American Menopause Society).

Participants taking estetrol experienced a decrease in hemoglobin A1c, fasting plasma glucose, total cholesterol, LDL and lipoprotein as well as an increase in HDL cholesterol, according to the findings presented by Wolf Utian, MD, PhD, DSC, a professor emeritus of reproductive biology at Case Western Reserve University, Cleveland, and medical director emeritus of the Menopause Society.

A separate poster at the conference from the same trial also reported significant improvements from estetrol in quality of life, including that related to vasomotor symptoms, and several psychosocial and sexual functioning areas.

Mayo Clinic

E4 is already available as combination oral contraception and is now being considered for treating vasomotor symptoms, explained Chrisandra Shufelt, MD, professor and chair of general internal of medicine and associate director of the Women’s Health Research Center at Mayo Clinic Florida, who was not involved in the study.
 

Background on estetrol

E4 is a human fetal liver estrogen produced during pregnancy that’s synthesized from plants for pharmaceutical use, including as the oral contraceptive drospirenone, Dr. Utian told attendees. It’s classified as a native estrogen with selective tissue activity (NEST), he said.

“E4 is a completely different native estrogen with oral administration mimicking the benefits of transdermals and hence safe and effective,” Dr. Utian said in an interview. “It would be a significant new addition to the pharmaceutical armamentarium.”

Two phase 3 trials presented by Dr. Utian at the same conference last year found estetrol reduced the frequency and severity of moderate to severe vasomotor symptoms, and a previous phase 2 trial finding vasomotor and genitourinary symptom benefits suggested it had potential benefits for lipids, carbohydrate metabolism, and bone turnover.

“In summary, E4 at a daily dose of 15 mg exhibited estrogenic effects in the vagina, leading to improved vaginal health and reduced signs of atrophy, emerging as a promising treatment option not only for vasomotor symptoms but also for other significant menopausal symptoms,” Dr. Utian said. “E4 could offer comprehensive relief for women experiencing a range of menopause-related discomforts.”

Dr. Utian also referenced a 2017 trial in which estetrol positively impacted lipid profiles, “lowering low-density lipoprotein cholesterol, increasing high-density lipoprotein cholesterol, and showing minimal influence on triglycerides,” he said. “Importantly, estetrol was associated with a significant decrease in osteocalcin levels in the higher dose groups, suggesting a potential preventive effect on bone loss,” he added. A recent review of the overall evidence on estetrol suggests its use is “promising,” Dr. Utian noted.
 

Current trial

His current randomized controlled phase 3 trial included postmenopausal women ages 40-65 from 151 sites in 14 countries in Europe, Latin America, and North America, and Russia. Among the 640 participants in the trial, 213 women randomly received 15 mg of estetrol, 213 women received 20 mg of estetrol, and 214 women received a placebo every day for 3 months. All women without hysterectomies also received 200 mg of progesterone once daily for two weeks after completing the estetrol treatment to protect the endometrium.

Researchers took blood samples from the participants at baseline and week 12 to assess total cholesterol, LDL, HDL, the total cholesterol/HDL ratio, triglycerides, lipoprotein A, fasting plasma glucose, insulin, and A1c.

Compared with women in the placebo group, women in both the 15 mg and 20 mg groups saw a statistically significant decrease in lipoprotein A and in the ratio of total cholesterol to HDL, and a statistically significant increase in HDL. Only the women in the 15 mg group saw a statistically significant decrease in LDL and increase in triglycerides; an increase in triglycerides in the 20 mg group did not reach statistical significance.

Statistically significant decreases in fasting plasma glucose and A1c also occurred in both treatment groups, but a decrease in insulin levels and in the homeostasis model-assessment-estimated insulin resistance (HOMA-IR) seen in both treatment arms did not reach significance.

“While the mean changes after 12 weeks from baseline overall were small changes to the cholesterol and blood sugar profiles, they are clinically meaningful because it suggests that E4 does not have any adverse effects to these measures,” Dr. Shufelt said in an interview. “An advantage is that this gives us another hormone option for vasomotor symptoms since it is a native estrogen with selective tissue.”

It’s too early, however, to determine whether estetrol offers benefits in terms of its safety profile, compared with currently available therapies, Dr. Shufelt said.

”These findings of E4 are similar to how oral estradiol changes lipids, which finds an increase in high-density lipoprotein cholesterol, and decreases plasma concentrations of total and low-density lipoprotein cholesterol. an increase in HDL-C and triglycerides and decrease in LDL-C,” she said.
 

Poster findings also promising

For the findings reported in the poster, researchers assessed quality of life and the clinical meaningfulness of vasomotor symptoms’ reduction at baseline and 12 weeks using the Menopause-Specific Quality of Life (MENQOL) questionnaire and the Clinical Global Impression questionnaire, respectively. They also assessed women’s self-reported genitourinary symptoms, including vaginal dryness, pain during urination, vaginal pain and bleeding related to sex, and vaginal or vulvar irritation or itching. Most of these findings primarily confirmed previous positive effects from E4 in other trials.

Women in both the 15 mg and 20 mg estetrol groups reported a statistically significant improvement at 12 weeks, compared with placebo, in their total MENQOL score and in the vasomotor, psychosocial, and sexual functioning domain scores (P < .05). Those in the 20 mg group also had a statistically significant improvement in their physical domain score (P < .05).

Although numerical improvements in genitourinary symptoms occurred at 12 weeks across all three groups, the only statistically significant difference from baseline occurred in patients taking 15 mg of estetrol, who experienced a decrease in vaginal dryness and vaginal pain during sex (P = .0142 and P = .003, respectively).

The Clinical Global Impression questionnaire asked women at 4 and 12 weeks to rate on a seven-item Likert scale their response to this question: “Rate the total improvement, whether or not in your judgment it is due entirely to drug treatment. Compared to your condition at admission to the study, how much has it changed?” Responses of “very much improved” and “much improved” counted as a clinically meaningful difference.

Compared with 27.9% of patients in the placebo group, 52.9% of patients in the 15 mg group and 59.8% of patients in the 20 mg group rated the weekly frequency of moderate to severe vasomotor symptoms as “much improved” or “very much improved” at 4 weeks (P < .0001). At 12 weeks, those numbers rose to 47% in the placebo group, 73.3% in the 15 mg group and 77.8% in the 20 mg group (P < .0001).

The trial’s primary limitation at this point is having only a 12-week follow-up, Dr. Shufelt said, though a few other questions remain.

“Because the two phase 3 RCTs included hysterectomized and nonhysterectomized women, it was unclear how many women in the study had E4 alone versus E4 with progesterone, as that might play a role in both cholesterol and carbohydrate metabolism,” Dr. Shufelt said. “While baseline data was not presented, it would also be important to know baseline values for the women and confirm that none were on lipid-lowering medications.”

The research was funded by Estetra SRL, an affiliate of Mithra Pharmaceuticals. Dr. Utian is a member of the Mithra and Elektra Scientific Advisory Boards. Dr. Shufelt has no disclosures.
 

PHILADELPHIA – Treatment of vasomotor symptoms with estetrol (E4) led to improvements in postmenopausal patients’ lipid profiles and blood glucose, according to findings of a phase 3 clinical trial presented at the annual meeting of the Menopause Society (formerly The North American Menopause Society).

Participants taking estetrol experienced a decrease in hemoglobin A1c, fasting plasma glucose, total cholesterol, LDL and lipoprotein as well as an increase in HDL cholesterol, according to the findings presented by Wolf Utian, MD, PhD, DSC, a professor emeritus of reproductive biology at Case Western Reserve University, Cleveland, and medical director emeritus of the Menopause Society.

A separate poster at the conference from the same trial also reported significant improvements from estetrol in quality of life, including that related to vasomotor symptoms, and several psychosocial and sexual functioning areas.

Mayo Clinic

E4 is already available as combination oral contraception and is now being considered for treating vasomotor symptoms, explained Chrisandra Shufelt, MD, professor and chair of general internal of medicine and associate director of the Women’s Health Research Center at Mayo Clinic Florida, who was not involved in the study.
 

Background on estetrol

E4 is a human fetal liver estrogen produced during pregnancy that’s synthesized from plants for pharmaceutical use, including as the oral contraceptive drospirenone, Dr. Utian told attendees. It’s classified as a native estrogen with selective tissue activity (NEST), he said.

“E4 is a completely different native estrogen with oral administration mimicking the benefits of transdermals and hence safe and effective,” Dr. Utian said in an interview. “It would be a significant new addition to the pharmaceutical armamentarium.”

Two phase 3 trials presented by Dr. Utian at the same conference last year found estetrol reduced the frequency and severity of moderate to severe vasomotor symptoms, and a previous phase 2 trial finding vasomotor and genitourinary symptom benefits suggested it had potential benefits for lipids, carbohydrate metabolism, and bone turnover.

“In summary, E4 at a daily dose of 15 mg exhibited estrogenic effects in the vagina, leading to improved vaginal health and reduced signs of atrophy, emerging as a promising treatment option not only for vasomotor symptoms but also for other significant menopausal symptoms,” Dr. Utian said. “E4 could offer comprehensive relief for women experiencing a range of menopause-related discomforts.”

Dr. Utian also referenced a 2017 trial in which estetrol positively impacted lipid profiles, “lowering low-density lipoprotein cholesterol, increasing high-density lipoprotein cholesterol, and showing minimal influence on triglycerides,” he said. “Importantly, estetrol was associated with a significant decrease in osteocalcin levels in the higher dose groups, suggesting a potential preventive effect on bone loss,” he added. A recent review of the overall evidence on estetrol suggests its use is “promising,” Dr. Utian noted.
 

Current trial

His current randomized controlled phase 3 trial included postmenopausal women ages 40-65 from 151 sites in 14 countries in Europe, Latin America, and North America, and Russia. Among the 640 participants in the trial, 213 women randomly received 15 mg of estetrol, 213 women received 20 mg of estetrol, and 214 women received a placebo every day for 3 months. All women without hysterectomies also received 200 mg of progesterone once daily for two weeks after completing the estetrol treatment to protect the endometrium.

Researchers took blood samples from the participants at baseline and week 12 to assess total cholesterol, LDL, HDL, the total cholesterol/HDL ratio, triglycerides, lipoprotein A, fasting plasma glucose, insulin, and A1c.

Compared with women in the placebo group, women in both the 15 mg and 20 mg groups saw a statistically significant decrease in lipoprotein A and in the ratio of total cholesterol to HDL, and a statistically significant increase in HDL. Only the women in the 15 mg group saw a statistically significant decrease in LDL and increase in triglycerides; an increase in triglycerides in the 20 mg group did not reach statistical significance.

Statistically significant decreases in fasting plasma glucose and A1c also occurred in both treatment groups, but a decrease in insulin levels and in the homeostasis model-assessment-estimated insulin resistance (HOMA-IR) seen in both treatment arms did not reach significance.

“While the mean changes after 12 weeks from baseline overall were small changes to the cholesterol and blood sugar profiles, they are clinically meaningful because it suggests that E4 does not have any adverse effects to these measures,” Dr. Shufelt said in an interview. “An advantage is that this gives us another hormone option for vasomotor symptoms since it is a native estrogen with selective tissue.”

It’s too early, however, to determine whether estetrol offers benefits in terms of its safety profile, compared with currently available therapies, Dr. Shufelt said.

”These findings of E4 are similar to how oral estradiol changes lipids, which finds an increase in high-density lipoprotein cholesterol, and decreases plasma concentrations of total and low-density lipoprotein cholesterol. an increase in HDL-C and triglycerides and decrease in LDL-C,” she said.
 

Poster findings also promising

For the findings reported in the poster, researchers assessed quality of life and the clinical meaningfulness of vasomotor symptoms’ reduction at baseline and 12 weeks using the Menopause-Specific Quality of Life (MENQOL) questionnaire and the Clinical Global Impression questionnaire, respectively. They also assessed women’s self-reported genitourinary symptoms, including vaginal dryness, pain during urination, vaginal pain and bleeding related to sex, and vaginal or vulvar irritation or itching. Most of these findings primarily confirmed previous positive effects from E4 in other trials.

Women in both the 15 mg and 20 mg estetrol groups reported a statistically significant improvement at 12 weeks, compared with placebo, in their total MENQOL score and in the vasomotor, psychosocial, and sexual functioning domain scores (P < .05). Those in the 20 mg group also had a statistically significant improvement in their physical domain score (P < .05).

Although numerical improvements in genitourinary symptoms occurred at 12 weeks across all three groups, the only statistically significant difference from baseline occurred in patients taking 15 mg of estetrol, who experienced a decrease in vaginal dryness and vaginal pain during sex (P = .0142 and P = .003, respectively).

The Clinical Global Impression questionnaire asked women at 4 and 12 weeks to rate on a seven-item Likert scale their response to this question: “Rate the total improvement, whether or not in your judgment it is due entirely to drug treatment. Compared to your condition at admission to the study, how much has it changed?” Responses of “very much improved” and “much improved” counted as a clinically meaningful difference.

Compared with 27.9% of patients in the placebo group, 52.9% of patients in the 15 mg group and 59.8% of patients in the 20 mg group rated the weekly frequency of moderate to severe vasomotor symptoms as “much improved” or “very much improved” at 4 weeks (P < .0001). At 12 weeks, those numbers rose to 47% in the placebo group, 73.3% in the 15 mg group and 77.8% in the 20 mg group (P < .0001).

The trial’s primary limitation at this point is having only a 12-week follow-up, Dr. Shufelt said, though a few other questions remain.

“Because the two phase 3 RCTs included hysterectomized and nonhysterectomized women, it was unclear how many women in the study had E4 alone versus E4 with progesterone, as that might play a role in both cholesterol and carbohydrate metabolism,” Dr. Shufelt said. “While baseline data was not presented, it would also be important to know baseline values for the women and confirm that none were on lipid-lowering medications.”

The research was funded by Estetra SRL, an affiliate of Mithra Pharmaceuticals. Dr. Utian is a member of the Mithra and Elektra Scientific Advisory Boards. Dr. Shufelt has no disclosures.
 

PHILADELPHIA – Treatment of vasomotor symptoms with estetrol (E4) led to improvements in postmenopausal patients’ lipid profiles and blood glucose, according to findings of a phase 3 clinical trial presented at the annual meeting of the Menopause Society (formerly The North American Menopause Society).

Participants taking estetrol experienced a decrease in hemoglobin A1c, fasting plasma glucose, total cholesterol, LDL and lipoprotein as well as an increase in HDL cholesterol, according to the findings presented by Wolf Utian, MD, PhD, DSC, a professor emeritus of reproductive biology at Case Western Reserve University, Cleveland, and medical director emeritus of the Menopause Society.

A separate poster at the conference from the same trial also reported significant improvements from estetrol in quality of life, including that related to vasomotor symptoms, and several psychosocial and sexual functioning areas.

Mayo Clinic

E4 is already available as combination oral contraception and is now being considered for treating vasomotor symptoms, explained Chrisandra Shufelt, MD, professor and chair of general internal of medicine and associate director of the Women’s Health Research Center at Mayo Clinic Florida, who was not involved in the study.
 

Background on estetrol

E4 is a human fetal liver estrogen produced during pregnancy that’s synthesized from plants for pharmaceutical use, including as the oral contraceptive drospirenone, Dr. Utian told attendees. It’s classified as a native estrogen with selective tissue activity (NEST), he said.

“E4 is a completely different native estrogen with oral administration mimicking the benefits of transdermals and hence safe and effective,” Dr. Utian said in an interview. “It would be a significant new addition to the pharmaceutical armamentarium.”

Two phase 3 trials presented by Dr. Utian at the same conference last year found estetrol reduced the frequency and severity of moderate to severe vasomotor symptoms, and a previous phase 2 trial finding vasomotor and genitourinary symptom benefits suggested it had potential benefits for lipids, carbohydrate metabolism, and bone turnover.

“In summary, E4 at a daily dose of 15 mg exhibited estrogenic effects in the vagina, leading to improved vaginal health and reduced signs of atrophy, emerging as a promising treatment option not only for vasomotor symptoms but also for other significant menopausal symptoms,” Dr. Utian said. “E4 could offer comprehensive relief for women experiencing a range of menopause-related discomforts.”

Dr. Utian also referenced a 2017 trial in which estetrol positively impacted lipid profiles, “lowering low-density lipoprotein cholesterol, increasing high-density lipoprotein cholesterol, and showing minimal influence on triglycerides,” he said. “Importantly, estetrol was associated with a significant decrease in osteocalcin levels in the higher dose groups, suggesting a potential preventive effect on bone loss,” he added. A recent review of the overall evidence on estetrol suggests its use is “promising,” Dr. Utian noted.
 

Current trial

His current randomized controlled phase 3 trial included postmenopausal women ages 40-65 from 151 sites in 14 countries in Europe, Latin America, and North America, and Russia. Among the 640 participants in the trial, 213 women randomly received 15 mg of estetrol, 213 women received 20 mg of estetrol, and 214 women received a placebo every day for 3 months. All women without hysterectomies also received 200 mg of progesterone once daily for two weeks after completing the estetrol treatment to protect the endometrium.

Researchers took blood samples from the participants at baseline and week 12 to assess total cholesterol, LDL, HDL, the total cholesterol/HDL ratio, triglycerides, lipoprotein A, fasting plasma glucose, insulin, and A1c.

Compared with women in the placebo group, women in both the 15 mg and 20 mg groups saw a statistically significant decrease in lipoprotein A and in the ratio of total cholesterol to HDL, and a statistically significant increase in HDL. Only the women in the 15 mg group saw a statistically significant decrease in LDL and increase in triglycerides; an increase in triglycerides in the 20 mg group did not reach statistical significance.

Statistically significant decreases in fasting plasma glucose and A1c also occurred in both treatment groups, but a decrease in insulin levels and in the homeostasis model-assessment-estimated insulin resistance (HOMA-IR) seen in both treatment arms did not reach significance.

“While the mean changes after 12 weeks from baseline overall were small changes to the cholesterol and blood sugar profiles, they are clinically meaningful because it suggests that E4 does not have any adverse effects to these measures,” Dr. Shufelt said in an interview. “An advantage is that this gives us another hormone option for vasomotor symptoms since it is a native estrogen with selective tissue.”

It’s too early, however, to determine whether estetrol offers benefits in terms of its safety profile, compared with currently available therapies, Dr. Shufelt said.

”These findings of E4 are similar to how oral estradiol changes lipids, which finds an increase in high-density lipoprotein cholesterol, and decreases plasma concentrations of total and low-density lipoprotein cholesterol. an increase in HDL-C and triglycerides and decrease in LDL-C,” she said.
 

Poster findings also promising

For the findings reported in the poster, researchers assessed quality of life and the clinical meaningfulness of vasomotor symptoms’ reduction at baseline and 12 weeks using the Menopause-Specific Quality of Life (MENQOL) questionnaire and the Clinical Global Impression questionnaire, respectively. They also assessed women’s self-reported genitourinary symptoms, including vaginal dryness, pain during urination, vaginal pain and bleeding related to sex, and vaginal or vulvar irritation or itching. Most of these findings primarily confirmed previous positive effects from E4 in other trials.

Women in both the 15 mg and 20 mg estetrol groups reported a statistically significant improvement at 12 weeks, compared with placebo, in their total MENQOL score and in the vasomotor, psychosocial, and sexual functioning domain scores (P < .05). Those in the 20 mg group also had a statistically significant improvement in their physical domain score (P < .05).

Although numerical improvements in genitourinary symptoms occurred at 12 weeks across all three groups, the only statistically significant difference from baseline occurred in patients taking 15 mg of estetrol, who experienced a decrease in vaginal dryness and vaginal pain during sex (P = .0142 and P = .003, respectively).

The Clinical Global Impression questionnaire asked women at 4 and 12 weeks to rate on a seven-item Likert scale their response to this question: “Rate the total improvement, whether or not in your judgment it is due entirely to drug treatment. Compared to your condition at admission to the study, how much has it changed?” Responses of “very much improved” and “much improved” counted as a clinically meaningful difference.

Compared with 27.9% of patients in the placebo group, 52.9% of patients in the 15 mg group and 59.8% of patients in the 20 mg group rated the weekly frequency of moderate to severe vasomotor symptoms as “much improved” or “very much improved” at 4 weeks (P < .0001). At 12 weeks, those numbers rose to 47% in the placebo group, 73.3% in the 15 mg group and 77.8% in the 20 mg group (P < .0001).

The trial’s primary limitation at this point is having only a 12-week follow-up, Dr. Shufelt said, though a few other questions remain.

“Because the two phase 3 RCTs included hysterectomized and nonhysterectomized women, it was unclear how many women in the study had E4 alone versus E4 with progesterone, as that might play a role in both cholesterol and carbohydrate metabolism,” Dr. Shufelt said. “While baseline data was not presented, it would also be important to know baseline values for the women and confirm that none were on lipid-lowering medications.”

The research was funded by Estetra SRL, an affiliate of Mithra Pharmaceuticals. Dr. Utian is a member of the Mithra and Elektra Scientific Advisory Boards. Dr. Shufelt has no disclosures.
 

CLEVELAND – Patients with heart failure (HF) who are started on sacubitril-valsartan (Entresto) in the hospital or soon after discharge will see a sharp drop in clinical risk whether their ejection fraction is “reduced” or merely “below normal,” suggests a combined analysis of two major studies.

Short-term risk for cardiovascular (CV) death or HF hospitalization fell 30% for such patients put on the angiotensin-receptor/neprilysin inhibitor (ARNI) at that early stage, compared with those assigned to receive an ACE inhibitor or angiotensin receptor blocker (ARB).

Of note, the risk-reduction benefit reached 41% among the overwhelming majority of patients with a left ventricular ejection fraction (LVEF) of 60% or lower across the two trials, PIONEER-HF and PARAGLIDE-HF. No such significant benefit was seen in patients with higher LVEF.

The prespecified analysis of 1,347 patients medically stabilized after a “worsening-HF event” was reported by Robert J. Mentz, MD, Duke Clinical Research Institute, Durham, N.C., at the annual scientific meeting of the Heart Failure Society of America.

Across both studies, levels of the prognostically telling biomarker NT-proBNP dropped further in the ARNI group, by almost a fourth, compared with those getting an ACE inhibitor or ARB. The difference emerged within a week and was “similar and consistent” throughout at least 8 weeks of follow-up, Dr. Mentz said.

Sacubitril-valsartan is approved in the United States for chronic HF, broadly but with labeling suggesting clearer efficacy at lower LVEF levels, based on the PARADIGM-HF and PARAGON-HF trials.

The PIONEER-HF and PARAGLIDE-HF trials lending patients to the current analysis demonstrated superiority for the drug vs. an ACE inhibitor or ARB when started in hospital in stabilized patients with HF.
 

Cautions about starting sacubitril-valsartan

In the pooled analysis, patients on sacubitril-valsartan were more likely to experience symptomatic hypotension, with a relative risk for drug’s known potential side effect reaching 1.35 (95% confidence interval, 1.05-1.72), compared with ACE inhibitor or ARB recipients.

But the hypotension risk when starting the drug is manageable to some extent, observed Dr. Mentz. “We can safely start sacubitril-valsartan in the hospital or early post discharge, but we need to make sure their volume status is okay” and keep track of their blood pressure trajectory, he told this news organization.

Those with initially low BP, unsurprisingly, seem more susceptible to the problem, Dr. Mentz said. In such patients “on antihypertensives or other therapies that aren’t going to give them a clinical outcome benefit,” those meds can be withdrawn or their dosages reduced before sacubitril-valsartan is added.

Such cautions are an “important take-home message” of the analysis, observed invited discussant Carolyn S. P. Lam, MBBS, PhD, National Heart Centre, Singapore, after the Dr. Mentz presentation.

Sacubitril-valsartan should be started only in stabilized patients, she emphasized. It should be delayed in those “with ongoing adjustments of antihypertensives, diuretics, and so on,” in whom premature initiation of the drug may promote symptomatic hypotension. Should that happen, Dr. Lam cautioned, there’s a risk that such patients would be “mislabeled as intolerant” of the ARNI and so wouldn’t be started on it later.

The pooled PIONEER-HF and PARAGLIDE-HF analysis, Dr. Lam proposed, might also help overcome the “clinical inertia and fear” that is slowing the uptake of early guideline-directed drug therapy initiation in patients hospitalized with HF.
 

LVEF spectrum across two studies

As Dr. Mentz reported, the analysis included 881 and 466 patients from PIONEER-HF and PARAGLIDE-HF, respectively. Of the total, 673 were assigned to receive valsartan and 674 to receive either enalapril or valsartan. Overall, 36% of the population were women.

Patients in PIONEER-HF, with an LVEF 40% or lower, were started on their assigned drug during an acute-HF hospitalization and followed a median of 8 weeks. PARAGLIDE-HF patients, with LVEF higher than 40%, started therapy either in hospital (in 70% of cases) or within 30 days of their HF event; they were followed a median of 6 months.

Hazard ratios for outcomes in the sacubitril-valsartan group vs. those on ACE inhibitors or ARBs were 0.76; 95% CI, 0.69-0.83; P < .0001 for change in NT-proBNP levels. For the composite of CV death or HF hospitalization, HRs were as follows:

• 0.70 (95% CI, 0.54-0.91; P = .0077) overall.
• 0.59 (95% CI, 0.44-0.79) for LVEF < 60%.
• 1.53 (95% CI, 0.80-2.91) for LVEF > 60%.

Current guidelines, Dr. Mentz noted, recommend that sacubitril-valsartan “be initiated de novo” predischarge in patients without contraindications who are hospitalized with acute HF with reduced LVEF. The combined analysis of PIONEER-HF and PARAGLIDE-HF, he said, potentially extends the recommendation “across the ejection fraction spectrum.”

Dr. Mentz has received research support and honoraria from Abbott, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Fast BioMedical, Gilead, Innolife, Eli Lilly, Medtronic, Medable, Merck, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Relypsa, Respicardia, Roche, Sanofi, Vifor, Windtree Therapeutics, and Zoll. Dr. Lam has reported financial relationships “with more than 25 pharmaceutical or device manufacturers, many of which produce therapies for heart failure,” as well as with Medscape/WebMD Global LLC.

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

CLEVELAND – Patients with heart failure (HF) who are started on sacubitril-valsartan (Entresto) in the hospital or soon after discharge will see a sharp drop in clinical risk whether their ejection fraction is “reduced” or merely “below normal,” suggests a combined analysis of two major studies.

Short-term risk for cardiovascular (CV) death or HF hospitalization fell 30% for such patients put on the angiotensin-receptor/neprilysin inhibitor (ARNI) at that early stage, compared with those assigned to receive an ACE inhibitor or angiotensin receptor blocker (ARB).

Of note, the risk-reduction benefit reached 41% among the overwhelming majority of patients with a left ventricular ejection fraction (LVEF) of 60% or lower across the two trials, PIONEER-HF and PARAGLIDE-HF. No such significant benefit was seen in patients with higher LVEF.

The prespecified analysis of 1,347 patients medically stabilized after a “worsening-HF event” was reported by Robert J. Mentz, MD, Duke Clinical Research Institute, Durham, N.C., at the annual scientific meeting of the Heart Failure Society of America.

Across both studies, levels of the prognostically telling biomarker NT-proBNP dropped further in the ARNI group, by almost a fourth, compared with those getting an ACE inhibitor or ARB. The difference emerged within a week and was “similar and consistent” throughout at least 8 weeks of follow-up, Dr. Mentz said.

Sacubitril-valsartan is approved in the United States for chronic HF, broadly but with labeling suggesting clearer efficacy at lower LVEF levels, based on the PARADIGM-HF and PARAGON-HF trials.

The PIONEER-HF and PARAGLIDE-HF trials lending patients to the current analysis demonstrated superiority for the drug vs. an ACE inhibitor or ARB when started in hospital in stabilized patients with HF.
 

Cautions about starting sacubitril-valsartan

In the pooled analysis, patients on sacubitril-valsartan were more likely to experience symptomatic hypotension, with a relative risk for drug’s known potential side effect reaching 1.35 (95% confidence interval, 1.05-1.72), compared with ACE inhibitor or ARB recipients.

But the hypotension risk when starting the drug is manageable to some extent, observed Dr. Mentz. “We can safely start sacubitril-valsartan in the hospital or early post discharge, but we need to make sure their volume status is okay” and keep track of their blood pressure trajectory, he told this news organization.

Those with initially low BP, unsurprisingly, seem more susceptible to the problem, Dr. Mentz said. In such patients “on antihypertensives or other therapies that aren’t going to give them a clinical outcome benefit,” those meds can be withdrawn or their dosages reduced before sacubitril-valsartan is added.

Such cautions are an “important take-home message” of the analysis, observed invited discussant Carolyn S. P. Lam, MBBS, PhD, National Heart Centre, Singapore, after the Dr. Mentz presentation.

Sacubitril-valsartan should be started only in stabilized patients, she emphasized. It should be delayed in those “with ongoing adjustments of antihypertensives, diuretics, and so on,” in whom premature initiation of the drug may promote symptomatic hypotension. Should that happen, Dr. Lam cautioned, there’s a risk that such patients would be “mislabeled as intolerant” of the ARNI and so wouldn’t be started on it later.

The pooled PIONEER-HF and PARAGLIDE-HF analysis, Dr. Lam proposed, might also help overcome the “clinical inertia and fear” that is slowing the uptake of early guideline-directed drug therapy initiation in patients hospitalized with HF.
 

LVEF spectrum across two studies

As Dr. Mentz reported, the analysis included 881 and 466 patients from PIONEER-HF and PARAGLIDE-HF, respectively. Of the total, 673 were assigned to receive valsartan and 674 to receive either enalapril or valsartan. Overall, 36% of the population were women.

Patients in PIONEER-HF, with an LVEF 40% or lower, were started on their assigned drug during an acute-HF hospitalization and followed a median of 8 weeks. PARAGLIDE-HF patients, with LVEF higher than 40%, started therapy either in hospital (in 70% of cases) or within 30 days of their HF event; they were followed a median of 6 months.

Hazard ratios for outcomes in the sacubitril-valsartan group vs. those on ACE inhibitors or ARBs were 0.76; 95% CI, 0.69-0.83; P < .0001 for change in NT-proBNP levels. For the composite of CV death or HF hospitalization, HRs were as follows:

• 0.70 (95% CI, 0.54-0.91; P = .0077) overall.
• 0.59 (95% CI, 0.44-0.79) for LVEF < 60%.
• 1.53 (95% CI, 0.80-2.91) for LVEF > 60%.

Current guidelines, Dr. Mentz noted, recommend that sacubitril-valsartan “be initiated de novo” predischarge in patients without contraindications who are hospitalized with acute HF with reduced LVEF. The combined analysis of PIONEER-HF and PARAGLIDE-HF, he said, potentially extends the recommendation “across the ejection fraction spectrum.”

Dr. Mentz has received research support and honoraria from Abbott, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Fast BioMedical, Gilead, Innolife, Eli Lilly, Medtronic, Medable, Merck, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Relypsa, Respicardia, Roche, Sanofi, Vifor, Windtree Therapeutics, and Zoll. Dr. Lam has reported financial relationships “with more than 25 pharmaceutical or device manufacturers, many of which produce therapies for heart failure,” as well as with Medscape/WebMD Global LLC.

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

CLEVELAND – Patients with heart failure (HF) who are started on sacubitril-valsartan (Entresto) in the hospital or soon after discharge will see a sharp drop in clinical risk whether their ejection fraction is “reduced” or merely “below normal,” suggests a combined analysis of two major studies.

Short-term risk for cardiovascular (CV) death or HF hospitalization fell 30% for such patients put on the angiotensin-receptor/neprilysin inhibitor (ARNI) at that early stage, compared with those assigned to receive an ACE inhibitor or angiotensin receptor blocker (ARB).

Of note, the risk-reduction benefit reached 41% among the overwhelming majority of patients with a left ventricular ejection fraction (LVEF) of 60% or lower across the two trials, PIONEER-HF and PARAGLIDE-HF. No such significant benefit was seen in patients with higher LVEF.

The prespecified analysis of 1,347 patients medically stabilized after a “worsening-HF event” was reported by Robert J. Mentz, MD, Duke Clinical Research Institute, Durham, N.C., at the annual scientific meeting of the Heart Failure Society of America.

Across both studies, levels of the prognostically telling biomarker NT-proBNP dropped further in the ARNI group, by almost a fourth, compared with those getting an ACE inhibitor or ARB. The difference emerged within a week and was “similar and consistent” throughout at least 8 weeks of follow-up, Dr. Mentz said.

Sacubitril-valsartan is approved in the United States for chronic HF, broadly but with labeling suggesting clearer efficacy at lower LVEF levels, based on the PARADIGM-HF and PARAGON-HF trials.

The PIONEER-HF and PARAGLIDE-HF trials lending patients to the current analysis demonstrated superiority for the drug vs. an ACE inhibitor or ARB when started in hospital in stabilized patients with HF.
 

Cautions about starting sacubitril-valsartan

In the pooled analysis, patients on sacubitril-valsartan were more likely to experience symptomatic hypotension, with a relative risk for drug’s known potential side effect reaching 1.35 (95% confidence interval, 1.05-1.72), compared with ACE inhibitor or ARB recipients.

But the hypotension risk when starting the drug is manageable to some extent, observed Dr. Mentz. “We can safely start sacubitril-valsartan in the hospital or early post discharge, but we need to make sure their volume status is okay” and keep track of their blood pressure trajectory, he told this news organization.

Those with initially low BP, unsurprisingly, seem more susceptible to the problem, Dr. Mentz said. In such patients “on antihypertensives or other therapies that aren’t going to give them a clinical outcome benefit,” those meds can be withdrawn or their dosages reduced before sacubitril-valsartan is added.

Such cautions are an “important take-home message” of the analysis, observed invited discussant Carolyn S. P. Lam, MBBS, PhD, National Heart Centre, Singapore, after the Dr. Mentz presentation.

Sacubitril-valsartan should be started only in stabilized patients, she emphasized. It should be delayed in those “with ongoing adjustments of antihypertensives, diuretics, and so on,” in whom premature initiation of the drug may promote symptomatic hypotension. Should that happen, Dr. Lam cautioned, there’s a risk that such patients would be “mislabeled as intolerant” of the ARNI and so wouldn’t be started on it later.

The pooled PIONEER-HF and PARAGLIDE-HF analysis, Dr. Lam proposed, might also help overcome the “clinical inertia and fear” that is slowing the uptake of early guideline-directed drug therapy initiation in patients hospitalized with HF.
 

LVEF spectrum across two studies

As Dr. Mentz reported, the analysis included 881 and 466 patients from PIONEER-HF and PARAGLIDE-HF, respectively. Of the total, 673 were assigned to receive valsartan and 674 to receive either enalapril or valsartan. Overall, 36% of the population were women.

Patients in PIONEER-HF, with an LVEF 40% or lower, were started on their assigned drug during an acute-HF hospitalization and followed a median of 8 weeks. PARAGLIDE-HF patients, with LVEF higher than 40%, started therapy either in hospital (in 70% of cases) or within 30 days of their HF event; they were followed a median of 6 months.

Hazard ratios for outcomes in the sacubitril-valsartan group vs. those on ACE inhibitors or ARBs were 0.76; 95% CI, 0.69-0.83; P < .0001 for change in NT-proBNP levels. For the composite of CV death or HF hospitalization, HRs were as follows:

• 0.70 (95% CI, 0.54-0.91; P = .0077) overall.
• 0.59 (95% CI, 0.44-0.79) for LVEF < 60%.
• 1.53 (95% CI, 0.80-2.91) for LVEF > 60%.

Current guidelines, Dr. Mentz noted, recommend that sacubitril-valsartan “be initiated de novo” predischarge in patients without contraindications who are hospitalized with acute HF with reduced LVEF. The combined analysis of PIONEER-HF and PARAGLIDE-HF, he said, potentially extends the recommendation “across the ejection fraction spectrum.”

Dr. Mentz has received research support and honoraria from Abbott, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Fast BioMedical, Gilead, Innolife, Eli Lilly, Medtronic, Medable, Merck, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Relypsa, Respicardia, Roche, Sanofi, Vifor, Windtree Therapeutics, and Zoll. Dr. Lam has reported financial relationships “with more than 25 pharmaceutical or device manufacturers, many of which produce therapies for heart failure,” as well as with Medscape/WebMD Global LLC.

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

CHICAGO—The VA could save nearly $10,000 annually per patient in the Mountain West region referral area by administering lower-level hematology/oncology care within the system instead of in the community, according to a new analysis.

The findings reflect that the community care encouraged by the MISSION Act is more expensive than US Department of Veterans Affairs (VA) care, said report lead author Alyson Clough, PharmD, a clinical pharmacy specialist with the George E. Wahlen Veterans Affairs Medical Center (VAMC) in Salt Lake City, Utah, in an interview. Clough and colleagues presented the poster at the 2023 annual meeting of the Association of VA Hematology/Oncology.

The 2018 MISSION Act expanded the eligibility for non-VA community services within the VA. “If a veteran requires care that a VA cannot provide in-house, lives in a state/territory without a full-service VAMC, and/or lives further than a certain distance/time from a VA Medical Center, then the veteran may be eligible to receive care in the community,” Clough said.

For the new analysis, the researchers focused on the Salt Lake City VAMC referral area, which spans about 125,000 square miles in Utah, Idaho, and Nevada. “While the MISSION Act helped give those veterans more options for specialty care—including hematology/oncology—many veterans are still driving several hours on a routine basis for chemotherapy treatment and injection therapies, even in the community setting,” Clough explained.

The researchers looked at the costs of “low-risk cancer care,” which Clough said consists of “chemotherapy or immunotherapy that is less likely to cause significant side effects during the infusion, is typically nonhazardous, and/or can be administered via a short infusion [30 minutes or less] or an injection.”

In fiscal year 2022, the VA paid more than $5.7 million for community care services for 380 veterans in the referral area, about $15,060 each, according to the analysis. In contrast, the average cost for 1774 veterans within the VA system was $5424. “By retaining or re-establishing hematology/oncology veteran care within VA, we estimate cost savings of approximately $9636 per unique veteran.”

Specifically, the researchers wrote that the average care costs were $5297 per veteran in the community vs $1143 at the VA, and average drug costs were $9763 per veteran in the community vs $4281 in the VA. These amount to total costs of $15,060 per veteran in the community vs $5424 in the VA.

Low-risk services “are ideal to bring to more isolated regions,” Clough noted. “Traveling and/or finding accommodations for pets can be very difficult for veterans during chemotherapy treatments. Bringing care to the veteran increases veteran convenience, reduces need for transportation, reduces out-of-pocket cost to the veteran, and can improve care coordination.”

It’s not clear why VA care is cheaper than community care, she said, “but it may be related to the [higher] patient volumes we see in our VA facilities.” Lower overhead costs and government pricing contracts for chemotherapies/injectables could also be factors, Clough explained. In an interview, Todd Wagner, PhD, Stanford University Professor in the Department of Surgery and Director of the Health Economics Research Center at the VA, said the analysis needs risk adjustment for cancer severity and other illnesses and comorbidities that could affect cancer treatment. “In our work, sicker veterans get care in VA, and healthier veterans are choosing VA-purchased care [in the community].”

He noted that in the new analysis, the VA care looks much cheaper. “I'm struggling with that result: It flies in the face of our past work,” he said. He added that an analysis should also look at surgery and radiation. “VA has a tradition of providing high-value medications at a lower cost. But VA’s costs of surgery and radiation tend to be more expensive.”

Clough does not plan more research in this area. For now, she said, her site is working to expand to include infusion clinics at local VA community-based outpatient clinics as part of the Close to Me program. The program, launched by the VA in 2022, aims to provide cancer services at community-based outpatient clinics, mobile infusion units, and patient homes.

“As part of this service, we are looking to maximize video-based and phone visits between our existing oncology staff and veterans living in more isolated areas, coordinate labs/imaging locally, and deliver infusion and/or injectable therapies to the veteran,” Clough said.

In addition, she said, “We currently have a dedicated hematology/oncology trained pharmacist and 2 infusion nurses working to expand the service and deliver veteran care in these remote areas.”

There was no funding for this study, and the authors have no disclosures. Wagner discloses grant funding to his institutions from the VA, the National Institutes of Health, the Agency for Healthcare Research and Quality, the Robert Wood Johnson Foundation, and the Heinz Foundation. 

CHICAGO—The VA could save nearly $10,000 annually per patient in the Mountain West region referral area by administering lower-level hematology/oncology care within the system instead of in the community, according to a new analysis.

The findings reflect that the community care encouraged by the MISSION Act is more expensive than US Department of Veterans Affairs (VA) care, said report lead author Alyson Clough, PharmD, a clinical pharmacy specialist with the George E. Wahlen Veterans Affairs Medical Center (VAMC) in Salt Lake City, Utah, in an interview. Clough and colleagues presented the poster at the 2023 annual meeting of the Association of VA Hematology/Oncology.

The 2018 MISSION Act expanded the eligibility for non-VA community services within the VA. “If a veteran requires care that a VA cannot provide in-house, lives in a state/territory without a full-service VAMC, and/or lives further than a certain distance/time from a VA Medical Center, then the veteran may be eligible to receive care in the community,” Clough said.

For the new analysis, the researchers focused on the Salt Lake City VAMC referral area, which spans about 125,000 square miles in Utah, Idaho, and Nevada. “While the MISSION Act helped give those veterans more options for specialty care—including hematology/oncology—many veterans are still driving several hours on a routine basis for chemotherapy treatment and injection therapies, even in the community setting,” Clough explained.

The researchers looked at the costs of “low-risk cancer care,” which Clough said consists of “chemotherapy or immunotherapy that is less likely to cause significant side effects during the infusion, is typically nonhazardous, and/or can be administered via a short infusion [30 minutes or less] or an injection.”

In fiscal year 2022, the VA paid more than $5.7 million for community care services for 380 veterans in the referral area, about $15,060 each, according to the analysis. In contrast, the average cost for 1774 veterans within the VA system was $5424. “By retaining or re-establishing hematology/oncology veteran care within VA, we estimate cost savings of approximately $9636 per unique veteran.”

Specifically, the researchers wrote that the average care costs were $5297 per veteran in the community vs $1143 at the VA, and average drug costs were $9763 per veteran in the community vs $4281 in the VA. These amount to total costs of $15,060 per veteran in the community vs $5424 in the VA.

Low-risk services “are ideal to bring to more isolated regions,” Clough noted. “Traveling and/or finding accommodations for pets can be very difficult for veterans during chemotherapy treatments. Bringing care to the veteran increases veteran convenience, reduces need for transportation, reduces out-of-pocket cost to the veteran, and can improve care coordination.”

It’s not clear why VA care is cheaper than community care, she said, “but it may be related to the [higher] patient volumes we see in our VA facilities.” Lower overhead costs and government pricing contracts for chemotherapies/injectables could also be factors, Clough explained. In an interview, Todd Wagner, PhD, Stanford University Professor in the Department of Surgery and Director of the Health Economics Research Center at the VA, said the analysis needs risk adjustment for cancer severity and other illnesses and comorbidities that could affect cancer treatment. “In our work, sicker veterans get care in VA, and healthier veterans are choosing VA-purchased care [in the community].”

He noted that in the new analysis, the VA care looks much cheaper. “I'm struggling with that result: It flies in the face of our past work,” he said. He added that an analysis should also look at surgery and radiation. “VA has a tradition of providing high-value medications at a lower cost. But VA’s costs of surgery and radiation tend to be more expensive.”

Clough does not plan more research in this area. For now, she said, her site is working to expand to include infusion clinics at local VA community-based outpatient clinics as part of the Close to Me program. The program, launched by the VA in 2022, aims to provide cancer services at community-based outpatient clinics, mobile infusion units, and patient homes.

“As part of this service, we are looking to maximize video-based and phone visits between our existing oncology staff and veterans living in more isolated areas, coordinate labs/imaging locally, and deliver infusion and/or injectable therapies to the veteran,” Clough said.

In addition, she said, “We currently have a dedicated hematology/oncology trained pharmacist and 2 infusion nurses working to expand the service and deliver veteran care in these remote areas.”

There was no funding for this study, and the authors have no disclosures. Wagner discloses grant funding to his institutions from the VA, the National Institutes of Health, the Agency for Healthcare Research and Quality, the Robert Wood Johnson Foundation, and the Heinz Foundation. 

CHICAGO—The VA could save nearly $10,000 annually per patient in the Mountain West region referral area by administering lower-level hematology/oncology care within the system instead of in the community, according to a new analysis.

The findings reflect that the community care encouraged by the MISSION Act is more expensive than US Department of Veterans Affairs (VA) care, said report lead author Alyson Clough, PharmD, a clinical pharmacy specialist with the George E. Wahlen Veterans Affairs Medical Center (VAMC) in Salt Lake City, Utah, in an interview. Clough and colleagues presented the poster at the 2023 annual meeting of the Association of VA Hematology/Oncology.

The 2018 MISSION Act expanded the eligibility for non-VA community services within the VA. “If a veteran requires care that a VA cannot provide in-house, lives in a state/territory without a full-service VAMC, and/or lives further than a certain distance/time from a VA Medical Center, then the veteran may be eligible to receive care in the community,” Clough said.

For the new analysis, the researchers focused on the Salt Lake City VAMC referral area, which spans about 125,000 square miles in Utah, Idaho, and Nevada. “While the MISSION Act helped give those veterans more options for specialty care—including hematology/oncology—many veterans are still driving several hours on a routine basis for chemotherapy treatment and injection therapies, even in the community setting,” Clough explained.

The researchers looked at the costs of “low-risk cancer care,” which Clough said consists of “chemotherapy or immunotherapy that is less likely to cause significant side effects during the infusion, is typically nonhazardous, and/or can be administered via a short infusion [30 minutes or less] or an injection.”

In fiscal year 2022, the VA paid more than $5.7 million for community care services for 380 veterans in the referral area, about $15,060 each, according to the analysis. In contrast, the average cost for 1774 veterans within the VA system was $5424. “By retaining or re-establishing hematology/oncology veteran care within VA, we estimate cost savings of approximately $9636 per unique veteran.”

Specifically, the researchers wrote that the average care costs were $5297 per veteran in the community vs $1143 at the VA, and average drug costs were $9763 per veteran in the community vs $4281 in the VA. These amount to total costs of $15,060 per veteran in the community vs $5424 in the VA.

Low-risk services “are ideal to bring to more isolated regions,” Clough noted. “Traveling and/or finding accommodations for pets can be very difficult for veterans during chemotherapy treatments. Bringing care to the veteran increases veteran convenience, reduces need for transportation, reduces out-of-pocket cost to the veteran, and can improve care coordination.”

It’s not clear why VA care is cheaper than community care, she said, “but it may be related to the [higher] patient volumes we see in our VA facilities.” Lower overhead costs and government pricing contracts for chemotherapies/injectables could also be factors, Clough explained. In an interview, Todd Wagner, PhD, Stanford University Professor in the Department of Surgery and Director of the Health Economics Research Center at the VA, said the analysis needs risk adjustment for cancer severity and other illnesses and comorbidities that could affect cancer treatment. “In our work, sicker veterans get care in VA, and healthier veterans are choosing VA-purchased care [in the community].”

He noted that in the new analysis, the VA care looks much cheaper. “I'm struggling with that result: It flies in the face of our past work,” he said. He added that an analysis should also look at surgery and radiation. “VA has a tradition of providing high-value medications at a lower cost. But VA’s costs of surgery and radiation tend to be more expensive.”

Clough does not plan more research in this area. For now, she said, her site is working to expand to include infusion clinics at local VA community-based outpatient clinics as part of the Close to Me program. The program, launched by the VA in 2022, aims to provide cancer services at community-based outpatient clinics, mobile infusion units, and patient homes.

“As part of this service, we are looking to maximize video-based and phone visits between our existing oncology staff and veterans living in more isolated areas, coordinate labs/imaging locally, and deliver infusion and/or injectable therapies to the veteran,” Clough said.

In addition, she said, “We currently have a dedicated hematology/oncology trained pharmacist and 2 infusion nurses working to expand the service and deliver veteran care in these remote areas.”

There was no funding for this study, and the authors have no disclosures. Wagner discloses grant funding to his institutions from the VA, the National Institutes of Health, the Agency for Healthcare Research and Quality, the Robert Wood Johnson Foundation, and the Heinz Foundation. 

The US Department of Veterans Affairs (VA) provides health care to about 600,000 women veterans—half are of child-bearing age. Pregnancies in women veterans using VA care have increased by more than 80% since 2014, from 6950 in 2014 to 12,524 in 2022.

Until recently, VA maternity care coordinators would help women navigate health care from the beginning of pregnancy to 8 weeks postpartum. But “[e]vidence shows that new mothers often need support and care coordination long after 8 weeks postpartum, which is why VA is taking action to support veteran mothers for much longer after they give birth,” said Under Secretary for Health Shereef Elnahal, MD. As of October 1, 2023, the maternity support is now extended to 12 months postpartum.

The full range of maternity care services includes primary care, examinations, tests, ultrasounds, newborn care, and screening for social determinants of health, mental health risk factors, and relationship health and safety. Maternity care coordinators also connect veterans with care after delivery and ensure access to follow-up screenings.

The VA says expanding access to maternity care coordinators is part of the work it’s doing to implement the White House Blueprint for Addressing the Maternal Health Crisis, released last year. The US maternal mortality rate is the highest of any developed nation in the world and more than double the rate of peer countries, the report says. According to the Centers for Disease Control and Prevention (CDC), from 2018 to 2021, the maternal death rate in the US increased from 17.4 to 32.9 per 100,000 live births.

Moreover, “[t]housands of women experience unexpected outcomes of labor and delivery that result in significant short- or long-term consequences to their health,” the White House report says, “such as heart issues, the need for blood transfusions, eclampsia, and blood infections.” Disturbingly, more than 80% of pregnancy-related deaths are preventable. Black and American Indian/Alaska Native women, regardless of income or education, are most likely to experience poor outcomes. Women who live in rural America—where there are many maternal care “deserts”—are about 60% more likely to die, the White House report says.

Quality care requires “care organized for and provided to all women in a manner that maintains their dignity, privacy, and confidentiality, ensures freedom from harm and mistreatment, and enables informed choice and con­tinuous support during labor and childbirth,” say CDC researchers who surveyed 2407 women about their maternity care experiences. One in 5 respondents reported instances of mistreatment. Roughly one-third of Black, Hispanic, and multiracial women reported, for instance, receiving no response to requests for help, being shouted at or scolded, not having their physical privacy protected, and being threatened with withholding treatment or made to accept unwanted treatment.

The White House Blueprint delineates several goals. One is to ”ensure those giving birth are heard and are decisionmakers in accountable systems of care…to improve quality of care, hold providers accountable, and prioritize patient needs and their experience before, during, and after pregnancy.”

The Blueprint advises, for instance, expanding the Hear Her campaign to include culturally relevant materials to raise awareness of urgent maternal warning signs and improve communication between patients and clinicians. It also urges addressing social determinants of maternal health, supporting projects to expand maternal mental health access, increasing access to digital tools, and expanding models that train maternal health care practitoners and students on how to address implicit bias and racism and screen for social determinants of health.

Answering its question of “how we get there,” the Blueprint says, “In working toward this vision, the Biden-Harris Administration has developed, for the first time, a national, whole-of-government strategy to address our maternal health crisis. This strategy starts with the recognition that a concerted national effort to solve the crisis must begin with clear leadership and action from across the federal government. Addressing the maternal health crisis is not limited to a single health care policy or federal agency but should include experts across the government, including: the US Departments of Health and Human Services, Agriculture, Defense, Housing and Urban Development, Labor, Justice, Environmental Protection Agency, Office of Personnel Management, as well as the VA.

“The Biden-Harris Administration believes that only through this whole-of-government approach—one that considers the entirety of a person’s health and experiences over the course of their full life—will we finally be able to make real progress in tackling this longstanding challenge.”

The US Department of Veterans Affairs (VA) provides health care to about 600,000 women veterans—half are of child-bearing age. Pregnancies in women veterans using VA care have increased by more than 80% since 2014, from 6950 in 2014 to 12,524 in 2022.

Until recently, VA maternity care coordinators would help women navigate health care from the beginning of pregnancy to 8 weeks postpartum. But “[e]vidence shows that new mothers often need support and care coordination long after 8 weeks postpartum, which is why VA is taking action to support veteran mothers for much longer after they give birth,” said Under Secretary for Health Shereef Elnahal, MD. As of October 1, 2023, the maternity support is now extended to 12 months postpartum.

The full range of maternity care services includes primary care, examinations, tests, ultrasounds, newborn care, and screening for social determinants of health, mental health risk factors, and relationship health and safety. Maternity care coordinators also connect veterans with care after delivery and ensure access to follow-up screenings.

The VA says expanding access to maternity care coordinators is part of the work it’s doing to implement the White House Blueprint for Addressing the Maternal Health Crisis, released last year. The US maternal mortality rate is the highest of any developed nation in the world and more than double the rate of peer countries, the report says. According to the Centers for Disease Control and Prevention (CDC), from 2018 to 2021, the maternal death rate in the US increased from 17.4 to 32.9 per 100,000 live births.

Moreover, “[t]housands of women experience unexpected outcomes of labor and delivery that result in significant short- or long-term consequences to their health,” the White House report says, “such as heart issues, the need for blood transfusions, eclampsia, and blood infections.” Disturbingly, more than 80% of pregnancy-related deaths are preventable. Black and American Indian/Alaska Native women, regardless of income or education, are most likely to experience poor outcomes. Women who live in rural America—where there are many maternal care “deserts”—are about 60% more likely to die, the White House report says.

Quality care requires “care organized for and provided to all women in a manner that maintains their dignity, privacy, and confidentiality, ensures freedom from harm and mistreatment, and enables informed choice and con­tinuous support during labor and childbirth,” say CDC researchers who surveyed 2407 women about their maternity care experiences. One in 5 respondents reported instances of mistreatment. Roughly one-third of Black, Hispanic, and multiracial women reported, for instance, receiving no response to requests for help, being shouted at or scolded, not having their physical privacy protected, and being threatened with withholding treatment or made to accept unwanted treatment.

The White House Blueprint delineates several goals. One is to ”ensure those giving birth are heard and are decisionmakers in accountable systems of care…to improve quality of care, hold providers accountable, and prioritize patient needs and their experience before, during, and after pregnancy.”

The Blueprint advises, for instance, expanding the Hear Her campaign to include culturally relevant materials to raise awareness of urgent maternal warning signs and improve communication between patients and clinicians. It also urges addressing social determinants of maternal health, supporting projects to expand maternal mental health access, increasing access to digital tools, and expanding models that train maternal health care practitoners and students on how to address implicit bias and racism and screen for social determinants of health.

Answering its question of “how we get there,” the Blueprint says, “In working toward this vision, the Biden-Harris Administration has developed, for the first time, a national, whole-of-government strategy to address our maternal health crisis. This strategy starts with the recognition that a concerted national effort to solve the crisis must begin with clear leadership and action from across the federal government. Addressing the maternal health crisis is not limited to a single health care policy or federal agency but should include experts across the government, including: the US Departments of Health and Human Services, Agriculture, Defense, Housing and Urban Development, Labor, Justice, Environmental Protection Agency, Office of Personnel Management, as well as the VA.

“The Biden-Harris Administration believes that only through this whole-of-government approach—one that considers the entirety of a person’s health and experiences over the course of their full life—will we finally be able to make real progress in tackling this longstanding challenge.”

The US Department of Veterans Affairs (VA) provides health care to about 600,000 women veterans—half are of child-bearing age. Pregnancies in women veterans using VA care have increased by more than 80% since 2014, from 6950 in 2014 to 12,524 in 2022.

Until recently, VA maternity care coordinators would help women navigate health care from the beginning of pregnancy to 8 weeks postpartum. But “[e]vidence shows that new mothers often need support and care coordination long after 8 weeks postpartum, which is why VA is taking action to support veteran mothers for much longer after they give birth,” said Under Secretary for Health Shereef Elnahal, MD. As of October 1, 2023, the maternity support is now extended to 12 months postpartum.

The full range of maternity care services includes primary care, examinations, tests, ultrasounds, newborn care, and screening for social determinants of health, mental health risk factors, and relationship health and safety. Maternity care coordinators also connect veterans with care after delivery and ensure access to follow-up screenings.

The VA says expanding access to maternity care coordinators is part of the work it’s doing to implement the White House Blueprint for Addressing the Maternal Health Crisis, released last year. The US maternal mortality rate is the highest of any developed nation in the world and more than double the rate of peer countries, the report says. According to the Centers for Disease Control and Prevention (CDC), from 2018 to 2021, the maternal death rate in the US increased from 17.4 to 32.9 per 100,000 live births.

Moreover, “[t]housands of women experience unexpected outcomes of labor and delivery that result in significant short- or long-term consequences to their health,” the White House report says, “such as heart issues, the need for blood transfusions, eclampsia, and blood infections.” Disturbingly, more than 80% of pregnancy-related deaths are preventable. Black and American Indian/Alaska Native women, regardless of income or education, are most likely to experience poor outcomes. Women who live in rural America—where there are many maternal care “deserts”—are about 60% more likely to die, the White House report says.

Quality care requires “care organized for and provided to all women in a manner that maintains their dignity, privacy, and confidentiality, ensures freedom from harm and mistreatment, and enables informed choice and con­tinuous support during labor and childbirth,” say CDC researchers who surveyed 2407 women about their maternity care experiences. One in 5 respondents reported instances of mistreatment. Roughly one-third of Black, Hispanic, and multiracial women reported, for instance, receiving no response to requests for help, being shouted at or scolded, not having their physical privacy protected, and being threatened with withholding treatment or made to accept unwanted treatment.

The White House Blueprint delineates several goals. One is to ”ensure those giving birth are heard and are decisionmakers in accountable systems of care…to improve quality of care, hold providers accountable, and prioritize patient needs and their experience before, during, and after pregnancy.”

The Blueprint advises, for instance, expanding the Hear Her campaign to include culturally relevant materials to raise awareness of urgent maternal warning signs and improve communication between patients and clinicians. It also urges addressing social determinants of maternal health, supporting projects to expand maternal mental health access, increasing access to digital tools, and expanding models that train maternal health care practitoners and students on how to address implicit bias and racism and screen for social determinants of health.

Answering its question of “how we get there,” the Blueprint says, “In working toward this vision, the Biden-Harris Administration has developed, for the first time, a national, whole-of-government strategy to address our maternal health crisis. This strategy starts with the recognition that a concerted national effort to solve the crisis must begin with clear leadership and action from across the federal government. Addressing the maternal health crisis is not limited to a single health care policy or federal agency but should include experts across the government, including: the US Departments of Health and Human Services, Agriculture, Defense, Housing and Urban Development, Labor, Justice, Environmental Protection Agency, Office of Personnel Management, as well as the VA.

“The Biden-Harris Administration believes that only through this whole-of-government approach—one that considers the entirety of a person’s health and experiences over the course of their full life—will we finally be able to make real progress in tackling this longstanding challenge.”

BERLIN – Further findings from the PSORRO study suggest that oral roflumilast may be an option for treating patients with moderate to severe plaque psoriasis, particularly if they have a high body mass index (BMI).

Reporting secondary outcomes from the investigator-led trial at the annual congress of the European Academy of Dermatology and Venereology, Alexander Egeberg, MD, PhD, DMSc, noted that “clinically significant weight loss” was seen among patients who were treated with oral roflumilast, 500 mcg once daily, versus those receiving placebo.

Indeed, after 12 weeks of therapy, one in three patients treated with oral roflumilast experienced at least a 5% drop in their baseline body weight vs no patients who received placebo (35% vs. 0%; P < .05).

Additionally, a respective 17% versus 0% of patients lost 10% or more of their body weight, and 4% versus 0% lost 15% or more of their baseline body weight at 12 weeks.

After 24 weeks’ treatment, a substantial percentage of patients still had greater than or equal to 5%, greater than or equal to 10%, or greater than or equal to 15% weight loss, at 30%, 17%, and 13% for oral roflumilast, compared with 9%, 0%, and 0% for placebo, respectively.

“We saw that the higher baseline weight correlated with the proportion of weight loss, so that the more heavy patients at baseline also were the ones who experienced the greatest weight loss,” said Dr. Egeberg, who is professor of dermatology at the University of Copenhagen and a senior consultant at the department of dermatology at Bispebjerg Hospital, Copenhagen.
 

A beneficial side effect in psoriasis?

“You may have heard in psoriasis about topical roflumilast, but oral roflumilast is actually also shown to be effective in treating psoriasis,” said Egeberg.

Topical roflumilast is approved in the United States and Canada for treating plaque psoriasis.

Efficacy results from the PSORRO study were published earlier this year and showed a significantly greater improvement in Psoriasis Area and Severity Index (PASI) 75 with oral roflumilast vs. placebo at 12 weeks (35% vs. 0%), with a sustained effect seen at 24 weeks (44% vs. 40%).

Weight loss was among the most common side effects seen, leading Dr. Egeberg and fellow PSORRO investigators to wonder whether this may actually be a beneficial effect in patients with psoriasis.

“Oral roflumilast is actually a drug that has been on the market for quite a number of years,” Dr. Egeberg said.

Although only currently licensed for chronic obstructive pulmonary disease (COPD) in the United States, oral roflumilast, a phosphodiesterase (PDE) 4 inhibitor, is available as a generic, “which also means that it is extremely affordable,” suggested Dr. Edeberg.

Weight loss may be a problem in patients with COPD, he acknowledged; these patients tend to be underweight as a result of their poor state of health caused by the lung condition. Weight loss could be an advantage in patients with psoriasis who are overweight or living with obesity and have poor cardiometabolic parameters.

The psoriasis treatment with oral roflumilast study

The PSORRO study was a phase 2, multicenter, placebo-controlled, randomized trial performed between 2021 and 2022. A total of 46 adults with plaque psoriasis participated; half were initially treated with oral roflumilast and half with placebo.

Treatment was double-blind for the first 12 weeks, with all patients then receiving open-label treatment with roflumilast for 12 weeks.

The primary endpoint was the proportion of patients achieving at least 75% reduction from baseline PASI (PASI75). A host of secondary endpoints were studied, including weight and cardiometabolic parameters, which Dr. Egeberg reported at the EADV meeting.

Looking at the baseline characteristics of the oral roflumilast and placebo groups, the mean age was a respective 38 and 39 years, 65% and 83% were men, and the mean starting body weight was 102 kg and 105.1 kg.

After 12 weeks of treatment, body weight fell by a mean of 5.4 kg in the oral roflumilast group, with a further decrease of 1.4 kg by 24 weeks, bringing the total average weight loss to 6.8 kg. By comparison, weight loss among those in the placebo group was 0 kg at 12 weeks and around 2 kg at 24 weeks.

The majority of participants in both groups had high baseline BMIs; 70% of those who received oral roflumilast and 61% of those who received placebo had a BMI of 30 or higher.

“We wanted to investigate the impact of body weight, [so] we didn’t allow patients to be underweight when they were included,” Dr. Egeberg explained. Thus, for inclusion, patients had to have a BMI of 20 or higher.

An “extraordinary” finding was how some patients’ weight status based on their BMI changed throughout the study.

“We could see people that went from obese class 3, all the way to obese class 1. And we could see people going from being overweight to normal weight, which is really extraordinary for patients with psoriasis,” Dr. Egeberg said.

“But most importantly,” he added, “we didn’t have any patients who became underweight, suggesting that it actually is safe to use also in normal-weight patients.”
 

Reduced appetite behind benefit?

Trying to see why the weight loss occurred, Dr. Egeberg noted that it looked like it could be a result of a reduced appetite.

In common with other PDE-4 inhibitors, oral roflumilast treatment was associated with gastrointestinal symptoms – nausea, diarrhea, and abdominal pain – but all of these “decrease to placebo levels again, quite quickly,” he said.

“This really suggests that it’s not because of diarrhea, it’s not because of nausea and abdominal pain; it is because of a reduced appetite that patients actually lose weight when treated with roflumilast,” Dr. Egeberg said. It’s a potential bonus for the drug’s effects on the skin and could afford clinicians an opportunity to help motivate patients to eat well when they do eat, he observed.

Other cardiometabolic parameters assessed included blood pressure, glycated hemoglobin, total cholesterol and other key lipids, creatinine, alanine aminotransferase, and high-sensitivity C-reactive protein, but there were no noteworthy differences between the groups.

Roflumilast is an inexpensive drug because it is generic, Dr. Egeberg observed, but that also means that its use is likely to be off-label.

“It will be up to the treating physician to decide if this is an optimal therapy for their patients,” he suggested.
 

Cardiometabolic comorbidities important to target

Obesity is a cardiometabolic comorbidity that is important to consider when treating your patients with psoriasis, Paolo Gisondi, MD, of the University of Verona (Italy), said at a separate presentation at the EADV meeting.

While not directly commenting on the roflumilast study, he noted that moderate to severe psoriasis was “frequently associated” with metabolic disorders that put people at additional risk for cardiovascular and fatty liver diseases.

The PSORRO study was an investigator-initiated and investigator-led study and received no commercial funding. Research funding came from the Danish Psoriasis Foundation, Herlev and Gentofte Hospital, and several charitable and humanitarian organizations. Dr. Egeberg acknowledged acting as the principal investigator, speaker, and/or consultant to multiple pharma companies, all of which were unrelated to the study he presented. Dr. Gisondi’s comments were from a separate presentation, and he was not involved in the study.

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

BERLIN – Further findings from the PSORRO study suggest that oral roflumilast may be an option for treating patients with moderate to severe plaque psoriasis, particularly if they have a high body mass index (BMI).

Reporting secondary outcomes from the investigator-led trial at the annual congress of the European Academy of Dermatology and Venereology, Alexander Egeberg, MD, PhD, DMSc, noted that “clinically significant weight loss” was seen among patients who were treated with oral roflumilast, 500 mcg once daily, versus those receiving placebo.

Indeed, after 12 weeks of therapy, one in three patients treated with oral roflumilast experienced at least a 5% drop in their baseline body weight vs no patients who received placebo (35% vs. 0%; P < .05).

Additionally, a respective 17% versus 0% of patients lost 10% or more of their body weight, and 4% versus 0% lost 15% or more of their baseline body weight at 12 weeks.

After 24 weeks’ treatment, a substantial percentage of patients still had greater than or equal to 5%, greater than or equal to 10%, or greater than or equal to 15% weight loss, at 30%, 17%, and 13% for oral roflumilast, compared with 9%, 0%, and 0% for placebo, respectively.

“We saw that the higher baseline weight correlated with the proportion of weight loss, so that the more heavy patients at baseline also were the ones who experienced the greatest weight loss,” said Dr. Egeberg, who is professor of dermatology at the University of Copenhagen and a senior consultant at the department of dermatology at Bispebjerg Hospital, Copenhagen.
 

A beneficial side effect in psoriasis?

“You may have heard in psoriasis about topical roflumilast, but oral roflumilast is actually also shown to be effective in treating psoriasis,” said Egeberg.

Topical roflumilast is approved in the United States and Canada for treating plaque psoriasis.

Efficacy results from the PSORRO study were published earlier this year and showed a significantly greater improvement in Psoriasis Area and Severity Index (PASI) 75 with oral roflumilast vs. placebo at 12 weeks (35% vs. 0%), with a sustained effect seen at 24 weeks (44% vs. 40%).

Weight loss was among the most common side effects seen, leading Dr. Egeberg and fellow PSORRO investigators to wonder whether this may actually be a beneficial effect in patients with psoriasis.

“Oral roflumilast is actually a drug that has been on the market for quite a number of years,” Dr. Egeberg said.

Although only currently licensed for chronic obstructive pulmonary disease (COPD) in the United States, oral roflumilast, a phosphodiesterase (PDE) 4 inhibitor, is available as a generic, “which also means that it is extremely affordable,” suggested Dr. Edeberg.

Weight loss may be a problem in patients with COPD, he acknowledged; these patients tend to be underweight as a result of their poor state of health caused by the lung condition. Weight loss could be an advantage in patients with psoriasis who are overweight or living with obesity and have poor cardiometabolic parameters.

The psoriasis treatment with oral roflumilast study

The PSORRO study was a phase 2, multicenter, placebo-controlled, randomized trial performed between 2021 and 2022. A total of 46 adults with plaque psoriasis participated; half were initially treated with oral roflumilast and half with placebo.

Treatment was double-blind for the first 12 weeks, with all patients then receiving open-label treatment with roflumilast for 12 weeks.

The primary endpoint was the proportion of patients achieving at least 75% reduction from baseline PASI (PASI75). A host of secondary endpoints were studied, including weight and cardiometabolic parameters, which Dr. Egeberg reported at the EADV meeting.

Looking at the baseline characteristics of the oral roflumilast and placebo groups, the mean age was a respective 38 and 39 years, 65% and 83% were men, and the mean starting body weight was 102 kg and 105.1 kg.

After 12 weeks of treatment, body weight fell by a mean of 5.4 kg in the oral roflumilast group, with a further decrease of 1.4 kg by 24 weeks, bringing the total average weight loss to 6.8 kg. By comparison, weight loss among those in the placebo group was 0 kg at 12 weeks and around 2 kg at 24 weeks.

The majority of participants in both groups had high baseline BMIs; 70% of those who received oral roflumilast and 61% of those who received placebo had a BMI of 30 or higher.

“We wanted to investigate the impact of body weight, [so] we didn’t allow patients to be underweight when they were included,” Dr. Egeberg explained. Thus, for inclusion, patients had to have a BMI of 20 or higher.

An “extraordinary” finding was how some patients’ weight status based on their BMI changed throughout the study.

“We could see people that went from obese class 3, all the way to obese class 1. And we could see people going from being overweight to normal weight, which is really extraordinary for patients with psoriasis,” Dr. Egeberg said.

“But most importantly,” he added, “we didn’t have any patients who became underweight, suggesting that it actually is safe to use also in normal-weight patients.”
 

Reduced appetite behind benefit?

Trying to see why the weight loss occurred, Dr. Egeberg noted that it looked like it could be a result of a reduced appetite.

In common with other PDE-4 inhibitors, oral roflumilast treatment was associated with gastrointestinal symptoms – nausea, diarrhea, and abdominal pain – but all of these “decrease to placebo levels again, quite quickly,” he said.

“This really suggests that it’s not because of diarrhea, it’s not because of nausea and abdominal pain; it is because of a reduced appetite that patients actually lose weight when treated with roflumilast,” Dr. Egeberg said. It’s a potential bonus for the drug’s effects on the skin and could afford clinicians an opportunity to help motivate patients to eat well when they do eat, he observed.

Other cardiometabolic parameters assessed included blood pressure, glycated hemoglobin, total cholesterol and other key lipids, creatinine, alanine aminotransferase, and high-sensitivity C-reactive protein, but there were no noteworthy differences between the groups.

Roflumilast is an inexpensive drug because it is generic, Dr. Egeberg observed, but that also means that its use is likely to be off-label.

“It will be up to the treating physician to decide if this is an optimal therapy for their patients,” he suggested.
 

Cardiometabolic comorbidities important to target

Obesity is a cardiometabolic comorbidity that is important to consider when treating your patients with psoriasis, Paolo Gisondi, MD, of the University of Verona (Italy), said at a separate presentation at the EADV meeting.

While not directly commenting on the roflumilast study, he noted that moderate to severe psoriasis was “frequently associated” with metabolic disorders that put people at additional risk for cardiovascular and fatty liver diseases.

The PSORRO study was an investigator-initiated and investigator-led study and received no commercial funding. Research funding came from the Danish Psoriasis Foundation, Herlev and Gentofte Hospital, and several charitable and humanitarian organizations. Dr. Egeberg acknowledged acting as the principal investigator, speaker, and/or consultant to multiple pharma companies, all of which were unrelated to the study he presented. Dr. Gisondi’s comments were from a separate presentation, and he was not involved in the study.

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

BERLIN – Further findings from the PSORRO study suggest that oral roflumilast may be an option for treating patients with moderate to severe plaque psoriasis, particularly if they have a high body mass index (BMI).

Reporting secondary outcomes from the investigator-led trial at the annual congress of the European Academy of Dermatology and Venereology, Alexander Egeberg, MD, PhD, DMSc, noted that “clinically significant weight loss” was seen among patients who were treated with oral roflumilast, 500 mcg once daily, versus those receiving placebo.

Indeed, after 12 weeks of therapy, one in three patients treated with oral roflumilast experienced at least a 5% drop in their baseline body weight vs no patients who received placebo (35% vs. 0%; P < .05).

Additionally, a respective 17% versus 0% of patients lost 10% or more of their body weight, and 4% versus 0% lost 15% or more of their baseline body weight at 12 weeks.

After 24 weeks’ treatment, a substantial percentage of patients still had greater than or equal to 5%, greater than or equal to 10%, or greater than or equal to 15% weight loss, at 30%, 17%, and 13% for oral roflumilast, compared with 9%, 0%, and 0% for placebo, respectively.

“We saw that the higher baseline weight correlated with the proportion of weight loss, so that the more heavy patients at baseline also were the ones who experienced the greatest weight loss,” said Dr. Egeberg, who is professor of dermatology at the University of Copenhagen and a senior consultant at the department of dermatology at Bispebjerg Hospital, Copenhagen.
 

A beneficial side effect in psoriasis?

“You may have heard in psoriasis about topical roflumilast, but oral roflumilast is actually also shown to be effective in treating psoriasis,” said Egeberg.

Topical roflumilast is approved in the United States and Canada for treating plaque psoriasis.

Efficacy results from the PSORRO study were published earlier this year and showed a significantly greater improvement in Psoriasis Area and Severity Index (PASI) 75 with oral roflumilast vs. placebo at 12 weeks (35% vs. 0%), with a sustained effect seen at 24 weeks (44% vs. 40%).

Weight loss was among the most common side effects seen, leading Dr. Egeberg and fellow PSORRO investigators to wonder whether this may actually be a beneficial effect in patients with psoriasis.

“Oral roflumilast is actually a drug that has been on the market for quite a number of years,” Dr. Egeberg said.

Although only currently licensed for chronic obstructive pulmonary disease (COPD) in the United States, oral roflumilast, a phosphodiesterase (PDE) 4 inhibitor, is available as a generic, “which also means that it is extremely affordable,” suggested Dr. Edeberg.

Weight loss may be a problem in patients with COPD, he acknowledged; these patients tend to be underweight as a result of their poor state of health caused by the lung condition. Weight loss could be an advantage in patients with psoriasis who are overweight or living with obesity and have poor cardiometabolic parameters.

The psoriasis treatment with oral roflumilast study

The PSORRO study was a phase 2, multicenter, placebo-controlled, randomized trial performed between 2021 and 2022. A total of 46 adults with plaque psoriasis participated; half were initially treated with oral roflumilast and half with placebo.

Treatment was double-blind for the first 12 weeks, with all patients then receiving open-label treatment with roflumilast for 12 weeks.

The primary endpoint was the proportion of patients achieving at least 75% reduction from baseline PASI (PASI75). A host of secondary endpoints were studied, including weight and cardiometabolic parameters, which Dr. Egeberg reported at the EADV meeting.

Looking at the baseline characteristics of the oral roflumilast and placebo groups, the mean age was a respective 38 and 39 years, 65% and 83% were men, and the mean starting body weight was 102 kg and 105.1 kg.

After 12 weeks of treatment, body weight fell by a mean of 5.4 kg in the oral roflumilast group, with a further decrease of 1.4 kg by 24 weeks, bringing the total average weight loss to 6.8 kg. By comparison, weight loss among those in the placebo group was 0 kg at 12 weeks and around 2 kg at 24 weeks.

The majority of participants in both groups had high baseline BMIs; 70% of those who received oral roflumilast and 61% of those who received placebo had a BMI of 30 or higher.

“We wanted to investigate the impact of body weight, [so] we didn’t allow patients to be underweight when they were included,” Dr. Egeberg explained. Thus, for inclusion, patients had to have a BMI of 20 or higher.

An “extraordinary” finding was how some patients’ weight status based on their BMI changed throughout the study.

“We could see people that went from obese class 3, all the way to obese class 1. And we could see people going from being overweight to normal weight, which is really extraordinary for patients with psoriasis,” Dr. Egeberg said.

“But most importantly,” he added, “we didn’t have any patients who became underweight, suggesting that it actually is safe to use also in normal-weight patients.”
 

Reduced appetite behind benefit?

Trying to see why the weight loss occurred, Dr. Egeberg noted that it looked like it could be a result of a reduced appetite.

In common with other PDE-4 inhibitors, oral roflumilast treatment was associated with gastrointestinal symptoms – nausea, diarrhea, and abdominal pain – but all of these “decrease to placebo levels again, quite quickly,” he said.

“This really suggests that it’s not because of diarrhea, it’s not because of nausea and abdominal pain; it is because of a reduced appetite that patients actually lose weight when treated with roflumilast,” Dr. Egeberg said. It’s a potential bonus for the drug’s effects on the skin and could afford clinicians an opportunity to help motivate patients to eat well when they do eat, he observed.

Other cardiometabolic parameters assessed included blood pressure, glycated hemoglobin, total cholesterol and other key lipids, creatinine, alanine aminotransferase, and high-sensitivity C-reactive protein, but there were no noteworthy differences between the groups.

Roflumilast is an inexpensive drug because it is generic, Dr. Egeberg observed, but that also means that its use is likely to be off-label.

“It will be up to the treating physician to decide if this is an optimal therapy for their patients,” he suggested.
 

Cardiometabolic comorbidities important to target

Obesity is a cardiometabolic comorbidity that is important to consider when treating your patients with psoriasis, Paolo Gisondi, MD, of the University of Verona (Italy), said at a separate presentation at the EADV meeting.

While not directly commenting on the roflumilast study, he noted that moderate to severe psoriasis was “frequently associated” with metabolic disorders that put people at additional risk for cardiovascular and fatty liver diseases.

The PSORRO study was an investigator-initiated and investigator-led study and received no commercial funding. Research funding came from the Danish Psoriasis Foundation, Herlev and Gentofte Hospital, and several charitable and humanitarian organizations. Dr. Egeberg acknowledged acting as the principal investigator, speaker, and/or consultant to multiple pharma companies, all of which were unrelated to the study he presented. Dr. Gisondi’s comments were from a separate presentation, and he was not involved in the study.

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

TOPLINE:

A topical fixed-dose combination of three approved acne treatments significantly improves moderate to severe acne with a strong safety profile.

METHODOLOGY:

• The two multicenter studies included 363 individuals aged 9 years and older with moderate to severe acne from 30 centers, including 15 in North America.
• Moderate to severe acne was defined as having 30-100 inflammatory lesions (papules, pustules, or nodules), 35-150 noninflammatory lesions (open or closed comedones), and at least two nodules.
• Participants were randomly assigned to receive treatment with a combination gel containing  phosphate 1.2%,  0.15%, and  3.1% (known as IDP-126) or a vehicle gel for once-daily application for 12 weeks.
• Treatment success was defined as a reduction of at least two grades from baseline on the Evaluator’s Global Severity Score (EGSS) and lesion counts of clear (0) or almost clear (1) at weeks 2, 4, 8, and 12.

TAKEAWAY:

• Treatment success occurred in 49.6% of the IDP-126 group, vs 24.9% of the vehicle group in study 1, and in 50.5% of the IDP-126 group, vs 20.5% of the vehicle group in study 2. Overall treatment compliance was 93.7% and 91.3% for studies 1 and 2, respectively (P < .01 for both).
• Patients in the IDP-126 groups for both studies 1 and 2 had significantly greater absolute mean reductions in both inflammatory and noninflammatory lesions from baseline to week 12 compared to the vehicle patients (P ≤ .001 for all).
• Significantly more patients in the IDP-126 group achieved a grade reduction of 2 or more in EGSS compared with those who received the vehicle, with treatment differences of approximately 32% in both studies. Changes in lesion reductions between the treatment and the vehicle groups were significantly greater as early as week 4.
• The most common treatment-related adverse events among patients treated with IDP-126 were erythema, application-site pain, dryness, irritation, and exfoliation. Discontinuation of the study drug as a result of adverse events occurred in 2.5% and 3.3% of these patients in studies 1 and 2, respectively.

IN PRACTICE:

“With its simple treatment regimen containing 3 recommended acne treatments (benzoyl peroxide, a topical retinoid, and a topical antibiotic), IDP-126 is a potential new treatment option for acne,” the researchers concluded.

SOURCE:

The study was led by Linda Stein Gold, MD, of Henry Ford Hospital, Detroit. The study was published online in the Journal of the American Academy of Dermatology.

LIMITATIONS:

In both studies, treatment duration was short, and the studies may not reflect patients’ real-world experiences. The results may be affected by interobserver bias or variation in assessment of acne severity.

DISCLOSURES:

Gold has served as investigator/consultant or speaker for Ortho Dermatologics, LEO Pharma, Dermavant, Incyte, Novartis, AbbVie, Pfizer, Sun Pharma, UCB, Arcutis, and Lilly. Other study coauthors have relationships with multiple companies, including Ortho Dermatologics, which provided medical writing support for the study.

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

TOPLINE:

A topical fixed-dose combination of three approved acne treatments significantly improves moderate to severe acne with a strong safety profile.

METHODOLOGY:

• The two multicenter studies included 363 individuals aged 9 years and older with moderate to severe acne from 30 centers, including 15 in North America.
• Moderate to severe acne was defined as having 30-100 inflammatory lesions (papules, pustules, or nodules), 35-150 noninflammatory lesions (open or closed comedones), and at least two nodules.
• Participants were randomly assigned to receive treatment with a combination gel containing  phosphate 1.2%,  0.15%, and  3.1% (known as IDP-126) or a vehicle gel for once-daily application for 12 weeks.
• Treatment success was defined as a reduction of at least two grades from baseline on the Evaluator’s Global Severity Score (EGSS) and lesion counts of clear (0) or almost clear (1) at weeks 2, 4, 8, and 12.

TAKEAWAY:

• Treatment success occurred in 49.6% of the IDP-126 group, vs 24.9% of the vehicle group in study 1, and in 50.5% of the IDP-126 group, vs 20.5% of the vehicle group in study 2. Overall treatment compliance was 93.7% and 91.3% for studies 1 and 2, respectively (P < .01 for both).
• Patients in the IDP-126 groups for both studies 1 and 2 had significantly greater absolute mean reductions in both inflammatory and noninflammatory lesions from baseline to week 12 compared to the vehicle patients (P ≤ .001 for all).
• Significantly more patients in the IDP-126 group achieved a grade reduction of 2 or more in EGSS compared with those who received the vehicle, with treatment differences of approximately 32% in both studies. Changes in lesion reductions between the treatment and the vehicle groups were significantly greater as early as week 4.
• The most common treatment-related adverse events among patients treated with IDP-126 were erythema, application-site pain, dryness, irritation, and exfoliation. Discontinuation of the study drug as a result of adverse events occurred in 2.5% and 3.3% of these patients in studies 1 and 2, respectively.

IN PRACTICE:

“With its simple treatment regimen containing 3 recommended acne treatments (benzoyl peroxide, a topical retinoid, and a topical antibiotic), IDP-126 is a potential new treatment option for acne,” the researchers concluded.

SOURCE:

The study was led by Linda Stein Gold, MD, of Henry Ford Hospital, Detroit. The study was published online in the Journal of the American Academy of Dermatology.

LIMITATIONS:

In both studies, treatment duration was short, and the studies may not reflect patients’ real-world experiences. The results may be affected by interobserver bias or variation in assessment of acne severity.

DISCLOSURES:

Gold has served as investigator/consultant or speaker for Ortho Dermatologics, LEO Pharma, Dermavant, Incyte, Novartis, AbbVie, Pfizer, Sun Pharma, UCB, Arcutis, and Lilly. Other study coauthors have relationships with multiple companies, including Ortho Dermatologics, which provided medical writing support for the study.

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

TOPLINE:

A topical fixed-dose combination of three approved acne treatments significantly improves moderate to severe acne with a strong safety profile.

METHODOLOGY:

• The two multicenter studies included 363 individuals aged 9 years and older with moderate to severe acne from 30 centers, including 15 in North America.
• Moderate to severe acne was defined as having 30-100 inflammatory lesions (papules, pustules, or nodules), 35-150 noninflammatory lesions (open or closed comedones), and at least two nodules.
• Participants were randomly assigned to receive treatment with a combination gel containing  phosphate 1.2%,  0.15%, and  3.1% (known as IDP-126) or a vehicle gel for once-daily application for 12 weeks.
• Treatment success was defined as a reduction of at least two grades from baseline on the Evaluator’s Global Severity Score (EGSS) and lesion counts of clear (0) or almost clear (1) at weeks 2, 4, 8, and 12.

TAKEAWAY:

• Treatment success occurred in 49.6% of the IDP-126 group, vs 24.9% of the vehicle group in study 1, and in 50.5% of the IDP-126 group, vs 20.5% of the vehicle group in study 2. Overall treatment compliance was 93.7% and 91.3% for studies 1 and 2, respectively (P < .01 for both).
• Patients in the IDP-126 groups for both studies 1 and 2 had significantly greater absolute mean reductions in both inflammatory and noninflammatory lesions from baseline to week 12 compared to the vehicle patients (P ≤ .001 for all).
• Significantly more patients in the IDP-126 group achieved a grade reduction of 2 or more in EGSS compared with those who received the vehicle, with treatment differences of approximately 32% in both studies. Changes in lesion reductions between the treatment and the vehicle groups were significantly greater as early as week 4.
• The most common treatment-related adverse events among patients treated with IDP-126 were erythema, application-site pain, dryness, irritation, and exfoliation. Discontinuation of the study drug as a result of adverse events occurred in 2.5% and 3.3% of these patients in studies 1 and 2, respectively.

IN PRACTICE:

“With its simple treatment regimen containing 3 recommended acne treatments (benzoyl peroxide, a topical retinoid, and a topical antibiotic), IDP-126 is a potential new treatment option for acne,” the researchers concluded.

SOURCE:

The study was led by Linda Stein Gold, MD, of Henry Ford Hospital, Detroit. The study was published online in the Journal of the American Academy of Dermatology.

LIMITATIONS:

In both studies, treatment duration was short, and the studies may not reflect patients’ real-world experiences. The results may be affected by interobserver bias or variation in assessment of acne severity.

DISCLOSURES:

Gold has served as investigator/consultant or speaker for Ortho Dermatologics, LEO Pharma, Dermavant, Incyte, Novartis, AbbVie, Pfizer, Sun Pharma, UCB, Arcutis, and Lilly. Other study coauthors have relationships with multiple companies, including Ortho Dermatologics, which provided medical writing support for the study.

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

Personal beliefs and health care system barriers contribute to inappropriate antibiotic use by patients, report researchers presenting results at an annual scientific meeting on infectious diseases.

Nonprescription antibiotic use includes accessing medication left over from a prior prescribed course, obtained from social networks, and purchased over-the-counter in other countries or illegally in stores and markets in the United States.

Overuse and misuse of antibiotics contributes to a growing threat of antimicrobial resistance, and it is tough to say how common it is, Lindsey A. Laytner, PhD, MPH, with Baylor College of Medicine, Houston, pointed out in her presentation.

“This is an understudied area. We don’t routinely collect these data, so we don’t actually know what the true prevalence is. The factors that contribute to this unsafe practice in the U.S. are also underexplored,” Dr. Laytner said.

To investigate, the researchers conducted in-depth interviews with 86 adults (median age, 49 years; 62% women) to identify patients’ motivations to use antibiotics without a prescription. All of them answered “yes” when asked in a previous survey whether they would use antibiotics without contacting a doctor, nurse, dentist, or clinic.

Dr. Laytner said several prominent themes emerged.

Nearly all interviewees reported nonprescription antibiotic use for symptoms that mostly do not warrant antibiotics. These included symptoms of COVID-19, influenza, and the common cold, as well as for pain management, allergies, and even wounds.
 

Ineffectively treating symptoms

Many felt they “knew their body, knew what they had, and knew how to treat themselves” without a health care provider, Dr. Laytner said.

They also felt the over-the-counter medicines “don’t always work and that antibiotics are like gold or this cure-all and because they are difficult to get a prescription for, they should be kept on hand,” she explained.

A variety of health care system barriers also contribute to inappropriate antibiotic use, including long wait times to schedule appointments and to see the doctor while at their appointments; high costs for clinic visits and prescriptions; and transportation issues.

Many patients opted to use nonprescription antibiotics out of “convenience,” Laytner added.

She explains that the findings could help inform community-level education efforts on inappropriate use of antibiotics and help shape policies to promote antibiotic stewardship.
 

Access to care, education

Commenting on the study, Emily Sydnor Spivak, MD, associate professor of medicine at University of Utah, Salt Lake City, said she “wasn’t totally surprised by the results, but found it very interesting how there was a theme of autonomy, or ‘I know my body,’ that seemed to drive patients to get antibiotics for relief of symptoms.”

“There is patient education that needs to happen about the role of antibiotics, how they act, and how they don’t actually provide symptom relief and have downsides and side effects,” said Dr. Spivak, who is also medical director of antimicrobial stewardship programs at University of Utah Health and VA Salt Lake City Health Care System.

“Given the lack of access to health care as a reason some patients use nonprescription antibiotics, we need to think about access to the health care system and process changes and policy changes to allow better access. Without better access or interaction with the health care system, we can’t educate patients,” Dr. Spivak said.

The study had no commercial funding. Dr. Laytner and Dr. Spivak report no relevant financial disclosures.

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

Personal beliefs and health care system barriers contribute to inappropriate antibiotic use by patients, report researchers presenting results at an annual scientific meeting on infectious diseases.

Nonprescription antibiotic use includes accessing medication left over from a prior prescribed course, obtained from social networks, and purchased over-the-counter in other countries or illegally in stores and markets in the United States.

Overuse and misuse of antibiotics contributes to a growing threat of antimicrobial resistance, and it is tough to say how common it is, Lindsey A. Laytner, PhD, MPH, with Baylor College of Medicine, Houston, pointed out in her presentation.

“This is an understudied area. We don’t routinely collect these data, so we don’t actually know what the true prevalence is. The factors that contribute to this unsafe practice in the U.S. are also underexplored,” Dr. Laytner said.

To investigate, the researchers conducted in-depth interviews with 86 adults (median age, 49 years; 62% women) to identify patients’ motivations to use antibiotics without a prescription. All of them answered “yes” when asked in a previous survey whether they would use antibiotics without contacting a doctor, nurse, dentist, or clinic.

Dr. Laytner said several prominent themes emerged.

Nearly all interviewees reported nonprescription antibiotic use for symptoms that mostly do not warrant antibiotics. These included symptoms of COVID-19, influenza, and the common cold, as well as for pain management, allergies, and even wounds.
 

Ineffectively treating symptoms

Many felt they “knew their body, knew what they had, and knew how to treat themselves” without a health care provider, Dr. Laytner said.

They also felt the over-the-counter medicines “don’t always work and that antibiotics are like gold or this cure-all and because they are difficult to get a prescription for, they should be kept on hand,” she explained.

A variety of health care system barriers also contribute to inappropriate antibiotic use, including long wait times to schedule appointments and to see the doctor while at their appointments; high costs for clinic visits and prescriptions; and transportation issues.

Many patients opted to use nonprescription antibiotics out of “convenience,” Laytner added.

She explains that the findings could help inform community-level education efforts on inappropriate use of antibiotics and help shape policies to promote antibiotic stewardship.
 

Access to care, education

Commenting on the study, Emily Sydnor Spivak, MD, associate professor of medicine at University of Utah, Salt Lake City, said she “wasn’t totally surprised by the results, but found it very interesting how there was a theme of autonomy, or ‘I know my body,’ that seemed to drive patients to get antibiotics for relief of symptoms.”

“There is patient education that needs to happen about the role of antibiotics, how they act, and how they don’t actually provide symptom relief and have downsides and side effects,” said Dr. Spivak, who is also medical director of antimicrobial stewardship programs at University of Utah Health and VA Salt Lake City Health Care System.

“Given the lack of access to health care as a reason some patients use nonprescription antibiotics, we need to think about access to the health care system and process changes and policy changes to allow better access. Without better access or interaction with the health care system, we can’t educate patients,” Dr. Spivak said.

The study had no commercial funding. Dr. Laytner and Dr. Spivak report no relevant financial disclosures.

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

Personal beliefs and health care system barriers contribute to inappropriate antibiotic use by patients, report researchers presenting results at an annual scientific meeting on infectious diseases.

Nonprescription antibiotic use includes accessing medication left over from a prior prescribed course, obtained from social networks, and purchased over-the-counter in other countries or illegally in stores and markets in the United States.

Overuse and misuse of antibiotics contributes to a growing threat of antimicrobial resistance, and it is tough to say how common it is, Lindsey A. Laytner, PhD, MPH, with Baylor College of Medicine, Houston, pointed out in her presentation.

“This is an understudied area. We don’t routinely collect these data, so we don’t actually know what the true prevalence is. The factors that contribute to this unsafe practice in the U.S. are also underexplored,” Dr. Laytner said.

To investigate, the researchers conducted in-depth interviews with 86 adults (median age, 49 years; 62% women) to identify patients’ motivations to use antibiotics without a prescription. All of them answered “yes” when asked in a previous survey whether they would use antibiotics without contacting a doctor, nurse, dentist, or clinic.

Dr. Laytner said several prominent themes emerged.

Nearly all interviewees reported nonprescription antibiotic use for symptoms that mostly do not warrant antibiotics. These included symptoms of COVID-19, influenza, and the common cold, as well as for pain management, allergies, and even wounds.
 

Ineffectively treating symptoms

Many felt they “knew their body, knew what they had, and knew how to treat themselves” without a health care provider, Dr. Laytner said.

They also felt the over-the-counter medicines “don’t always work and that antibiotics are like gold or this cure-all and because they are difficult to get a prescription for, they should be kept on hand,” she explained.

A variety of health care system barriers also contribute to inappropriate antibiotic use, including long wait times to schedule appointments and to see the doctor while at their appointments; high costs for clinic visits and prescriptions; and transportation issues.

Many patients opted to use nonprescription antibiotics out of “convenience,” Laytner added.

She explains that the findings could help inform community-level education efforts on inappropriate use of antibiotics and help shape policies to promote antibiotic stewardship.
 

Access to care, education

Commenting on the study, Emily Sydnor Spivak, MD, associate professor of medicine at University of Utah, Salt Lake City, said she “wasn’t totally surprised by the results, but found it very interesting how there was a theme of autonomy, or ‘I know my body,’ that seemed to drive patients to get antibiotics for relief of symptoms.”

“There is patient education that needs to happen about the role of antibiotics, how they act, and how they don’t actually provide symptom relief and have downsides and side effects,” said Dr. Spivak, who is also medical director of antimicrobial stewardship programs at University of Utah Health and VA Salt Lake City Health Care System.

“Given the lack of access to health care as a reason some patients use nonprescription antibiotics, we need to think about access to the health care system and process changes and policy changes to allow better access. Without better access or interaction with the health care system, we can’t educate patients,” Dr. Spivak said.

The study had no commercial funding. Dr. Laytner and Dr. Spivak report no relevant financial disclosures.

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