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HAMBURG, GERMANY – Testosterone replacement therapy was associated with significant reductions in hemoglobin A1c at 1 and 2 years among men with type 2 diabetes, a multinational audit shows.

“If you have a patient with type 2 diabetes, sexual dysfunction, or fatigue, please consider checking their testosterone level. And if they fulfill criteria for testosterone deficiency and have had their [prostate-specific antigen] checked, consider a trial of treatment and follow them,” study lead author T. Hugh Jones, MD, consultant physician and endocrinologist at Barnsley (England) Hospital NHS Foundation Trust advised, speaking with this news organization.

Dr. Jones also urges clinicians worldwide to enter their patients’ data into the ABCD Testosterone Audit, which aims to identify long-term outcomes and predictors of response to testosterone replacement therapy.

Dr. Jones, who is also professor of andrology at the University of Sheffield, presented the preliminary data analysis at the annual meeting of the European Association for the Study of Diabetes.

Thus far, a total of 428 men with type 2 diabetes and hypogonadism are entered into the audit, from 34 centers in eight countries: the United Kingdom, Germany, Canada, Brazil, South Africa, New Zealand, Malaysia, and Vietnam. Among 121 of the men at 12 months, there was a drop in A1c from a baseline level of 71.27 mmol/mol (8.7%) to 61.26 mmol/mol (7.8%). Among 104 men at 24 months, the drop was from 71.4 mmol/mol (8.7%) to 55.97 mmol/mol (7.3%). Both decreases were significant (P < .001).

Prior data from Dr. Jones’ group showed that about 40% of men with type 2 diabetes have symptomatic testosterone deficiency. Testosterone deficiency is also associated with adverse effects on cardiovascular risk factors, bone health, muscle strength, sexual function, and psychological well-being, yet it is often overlooked, Dr. Jones noted.

“It’s not typically measured in routine clinical practice. ... Deficiency is very common, but a lot of practitioners don’t treat it and don’t ask about it. But in fact, treatment has very significant benefits for patients. ... We know from sildenafil (Viagra) studies that 60%of people who didn’t respond were testosterone deficient. After being given testosterone, they converted to Viagra responders,” he noted.

Regarding safety concerns, the recent findings from the TRAVERSE study, in which about 70% of participants had type 2 diabetes, demonstrated no increased cardiovascular risk. There was also no association with prostate cancer, although it’s important to monitor prostate-specific antigen in patients for the first year on testosterone replacement, Dr. Jones said.

Asked to comment, endocrinologist Bradley D. Anawalt, MD, chief of medicine at the University of Washington Medical Center, Seattle, told this news organization, “This ‘worldwide survey’ confirms many studies from around the world over the past 20 years. ... [T]he association is due to ‘reverse causation,’ in that diabetes type 2 and obesity lower testosterone concentrations. Weight loss of 5%-10% may raise testosterone concentrations in men with high body mass indices, large waist circumferences, and low blood testosterone concentrations.”

At the same time, Dr. Anawalt pointed to data suggesting that “[t]reatment of androgen deficiency may facilitate lifestyle measures in men with high [body mass indexes] and high risk of type 2 diabetes to prevent, or more likely delay, the development of type 2 diabetes.”

However, both Dr. Jones and Dr. Anawalt emphasized that testosterone therapy would not be expected to affect blood glucose levels or any other cardiometabolic parameters in men who are not testosterone deficient, regardless of diabetes status.

“It’s important when you give testosterone to replace it to the normal level. Adequate treatment gives the greatest benefit,”Dr. Jones said.

As more centers contribute data to the ABCD audit, Jones anticipates collecting clinical practice data on a variety of clinical parameters, including complications, total insulin dose, kidney function, and eventually cardiovascular outcomes.

In the meantime, he said, giving testosterone replacement to men with deficiency can be very rewarding for many reasons. “People feel better. Individual patients come back and say ‘thank you doctor, you’ve given me my life back.’ It’s not often you get that. And the compliance is excellent.”

Dr. Jones is a speaker for, advisory board member for, and/or travel grant recipient of Besins Healthcare, Grantss, Grunenthal, and Simple Pharma. Dr. Anawalt has no disclosures.

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

HAMBURG, GERMANY – Testosterone replacement therapy was associated with significant reductions in hemoglobin A1c at 1 and 2 years among men with type 2 diabetes, a multinational audit shows.

“If you have a patient with type 2 diabetes, sexual dysfunction, or fatigue, please consider checking their testosterone level. And if they fulfill criteria for testosterone deficiency and have had their [prostate-specific antigen] checked, consider a trial of treatment and follow them,” study lead author T. Hugh Jones, MD, consultant physician and endocrinologist at Barnsley (England) Hospital NHS Foundation Trust advised, speaking with this news organization.

Dr. Jones also urges clinicians worldwide to enter their patients’ data into the ABCD Testosterone Audit, which aims to identify long-term outcomes and predictors of response to testosterone replacement therapy.

Dr. Jones, who is also professor of andrology at the University of Sheffield, presented the preliminary data analysis at the annual meeting of the European Association for the Study of Diabetes.

Thus far, a total of 428 men with type 2 diabetes and hypogonadism are entered into the audit, from 34 centers in eight countries: the United Kingdom, Germany, Canada, Brazil, South Africa, New Zealand, Malaysia, and Vietnam. Among 121 of the men at 12 months, there was a drop in A1c from a baseline level of 71.27 mmol/mol (8.7%) to 61.26 mmol/mol (7.8%). Among 104 men at 24 months, the drop was from 71.4 mmol/mol (8.7%) to 55.97 mmol/mol (7.3%). Both decreases were significant (P < .001).

Prior data from Dr. Jones’ group showed that about 40% of men with type 2 diabetes have symptomatic testosterone deficiency. Testosterone deficiency is also associated with adverse effects on cardiovascular risk factors, bone health, muscle strength, sexual function, and psychological well-being, yet it is often overlooked, Dr. Jones noted.

“It’s not typically measured in routine clinical practice. ... Deficiency is very common, but a lot of practitioners don’t treat it and don’t ask about it. But in fact, treatment has very significant benefits for patients. ... We know from sildenafil (Viagra) studies that 60%of people who didn’t respond were testosterone deficient. After being given testosterone, they converted to Viagra responders,” he noted.

Regarding safety concerns, the recent findings from the TRAVERSE study, in which about 70% of participants had type 2 diabetes, demonstrated no increased cardiovascular risk. There was also no association with prostate cancer, although it’s important to monitor prostate-specific antigen in patients for the first year on testosterone replacement, Dr. Jones said.

Asked to comment, endocrinologist Bradley D. Anawalt, MD, chief of medicine at the University of Washington Medical Center, Seattle, told this news organization, “This ‘worldwide survey’ confirms many studies from around the world over the past 20 years. ... [T]he association is due to ‘reverse causation,’ in that diabetes type 2 and obesity lower testosterone concentrations. Weight loss of 5%-10% may raise testosterone concentrations in men with high body mass indices, large waist circumferences, and low blood testosterone concentrations.”

At the same time, Dr. Anawalt pointed to data suggesting that “[t]reatment of androgen deficiency may facilitate lifestyle measures in men with high [body mass indexes] and high risk of type 2 diabetes to prevent, or more likely delay, the development of type 2 diabetes.”

However, both Dr. Jones and Dr. Anawalt emphasized that testosterone therapy would not be expected to affect blood glucose levels or any other cardiometabolic parameters in men who are not testosterone deficient, regardless of diabetes status.

“It’s important when you give testosterone to replace it to the normal level. Adequate treatment gives the greatest benefit,”Dr. Jones said.

As more centers contribute data to the ABCD audit, Jones anticipates collecting clinical practice data on a variety of clinical parameters, including complications, total insulin dose, kidney function, and eventually cardiovascular outcomes.

In the meantime, he said, giving testosterone replacement to men with deficiency can be very rewarding for many reasons. “People feel better. Individual patients come back and say ‘thank you doctor, you’ve given me my life back.’ It’s not often you get that. And the compliance is excellent.”

Dr. Jones is a speaker for, advisory board member for, and/or travel grant recipient of Besins Healthcare, Grantss, Grunenthal, and Simple Pharma. Dr. Anawalt has no disclosures.

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

HAMBURG, GERMANY – Testosterone replacement therapy was associated with significant reductions in hemoglobin A1c at 1 and 2 years among men with type 2 diabetes, a multinational audit shows.

“If you have a patient with type 2 diabetes, sexual dysfunction, or fatigue, please consider checking their testosterone level. And if they fulfill criteria for testosterone deficiency and have had their [prostate-specific antigen] checked, consider a trial of treatment and follow them,” study lead author T. Hugh Jones, MD, consultant physician and endocrinologist at Barnsley (England) Hospital NHS Foundation Trust advised, speaking with this news organization.

Dr. Jones also urges clinicians worldwide to enter their patients’ data into the ABCD Testosterone Audit, which aims to identify long-term outcomes and predictors of response to testosterone replacement therapy.

Dr. Jones, who is also professor of andrology at the University of Sheffield, presented the preliminary data analysis at the annual meeting of the European Association for the Study of Diabetes.

Thus far, a total of 428 men with type 2 diabetes and hypogonadism are entered into the audit, from 34 centers in eight countries: the United Kingdom, Germany, Canada, Brazil, South Africa, New Zealand, Malaysia, and Vietnam. Among 121 of the men at 12 months, there was a drop in A1c from a baseline level of 71.27 mmol/mol (8.7%) to 61.26 mmol/mol (7.8%). Among 104 men at 24 months, the drop was from 71.4 mmol/mol (8.7%) to 55.97 mmol/mol (7.3%). Both decreases were significant (P < .001).

Prior data from Dr. Jones’ group showed that about 40% of men with type 2 diabetes have symptomatic testosterone deficiency. Testosterone deficiency is also associated with adverse effects on cardiovascular risk factors, bone health, muscle strength, sexual function, and psychological well-being, yet it is often overlooked, Dr. Jones noted.

“It’s not typically measured in routine clinical practice. ... Deficiency is very common, but a lot of practitioners don’t treat it and don’t ask about it. But in fact, treatment has very significant benefits for patients. ... We know from sildenafil (Viagra) studies that 60%of people who didn’t respond were testosterone deficient. After being given testosterone, they converted to Viagra responders,” he noted.

Regarding safety concerns, the recent findings from the TRAVERSE study, in which about 70% of participants had type 2 diabetes, demonstrated no increased cardiovascular risk. There was also no association with prostate cancer, although it’s important to monitor prostate-specific antigen in patients for the first year on testosterone replacement, Dr. Jones said.

Asked to comment, endocrinologist Bradley D. Anawalt, MD, chief of medicine at the University of Washington Medical Center, Seattle, told this news organization, “This ‘worldwide survey’ confirms many studies from around the world over the past 20 years. ... [T]he association is due to ‘reverse causation,’ in that diabetes type 2 and obesity lower testosterone concentrations. Weight loss of 5%-10% may raise testosterone concentrations in men with high body mass indices, large waist circumferences, and low blood testosterone concentrations.”

At the same time, Dr. Anawalt pointed to data suggesting that “[t]reatment of androgen deficiency may facilitate lifestyle measures in men with high [body mass indexes] and high risk of type 2 diabetes to prevent, or more likely delay, the development of type 2 diabetes.”

However, both Dr. Jones and Dr. Anawalt emphasized that testosterone therapy would not be expected to affect blood glucose levels or any other cardiometabolic parameters in men who are not testosterone deficient, regardless of diabetes status.

“It’s important when you give testosterone to replace it to the normal level. Adequate treatment gives the greatest benefit,”Dr. Jones said.

As more centers contribute data to the ABCD audit, Jones anticipates collecting clinical practice data on a variety of clinical parameters, including complications, total insulin dose, kidney function, and eventually cardiovascular outcomes.

In the meantime, he said, giving testosterone replacement to men with deficiency can be very rewarding for many reasons. “People feel better. Individual patients come back and say ‘thank you doctor, you’ve given me my life back.’ It’s not often you get that. And the compliance is excellent.”

Dr. Jones is a speaker for, advisory board member for, and/or travel grant recipient of Besins Healthcare, Grantss, Grunenthal, and Simple Pharma. Dr. Anawalt has no disclosures.

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

VANCOUVER – The occurrence of a fracture predicts future fracture risk, but the increase in risk is the same no matter what the age of the patient, according to a new population-based study drawn from the Manitoba BMD Registry.

The work expands previous studies that focused mostly on fracture risk prediction after a first fracture among individuals aged 45-50 and older. Other limitations of prior studies include large age categories (such as “premenopausal”), reliance on self-reporting, and small sample sizes.

As a result, some guidelines recommend considering fracture history only for patients older than a certain age when assessing for future risk, such as with the Fracture Risk Assessment Tool (FRAX). The new study suggests a potential need to reconsider that stance.

“The [percentage] of increased risk from having had prevalent fractures in the past, no matter what your age, is about the same. I think that it’s really paradigm shifting because [when] most of us think [of] young people who fracture, we’re not thinking of osteoporosis or future fracture risk. We’re not saying, ‘Oh, I had a fracture when I was 25. When I’m 70, I should be thinking about osteoporosis.’ So, I think this study is quite eye-opening that way,” Carrie Ye, MD, who presented the study at the annual meeting of the American Society for Bone and Mineral Research, said in an interview.

Participants of younger age who are referred for dual-energy x-ray absorptiometry (DXA) likely represent a population at increased risk of osteoporosis, according to Dr. Ye. “Maybe they have Crohn’s disease or maybe they’re on a bunch of steroids, and so a clinician has flagged them,” said Dr. Ye, who is an assistant professor and rheumatologist at the University of Alberta, Edmonton.

The researchers limited the analysis to nontraumatic fractures, but session moderator Nicholas Harvey, MD, PhD, wondered if a similar finding would occur with traumatic fractures. In an interview, he noted that researchers led by William Leslie, MD, at the University of Manitoba, Winnipeg, found that prior traumatic fracture also predicted future low bone-mineral density (BMD) and osteoporotic fracture. “I think that would have been one interesting question,” said Dr. Harvey, director of the Medical Research Council Lifecourse Epidemiology Centre at the University of Southampton, England.

Dr. Ye’s study included 88,696 individuals who underwent a first DXA scan between 1996 and 2018, which researchers then linked to provincial administrative health data collected between 1979 and 2018. The mean age at first DXA was 64.6 years, and 90.3% were women. Their mean body mass index was 27.4 kg/m². Current smokers made up 10.1% of the cohort, 5.5% had a history of prolonged glucocorticoid use, 3.1% had rheumatoid arthritis, and among 14.9% of patients, there was a secondary cause of osteoporosis. Over a median 25.1 years of observation prior to DXA, clinical fracture occurred in 23.8% of participants.

The mean age of the patients at the time of their first prior fracture was 57.7 years. Over a mean 9.0 years of follow-up, 14.6% of participants experienced a fracture of any kind, 14.0% had osteoporotic fractures, 10.6% had a major osteoporotic fracture (nonankle), and 3.5% had a hip fracture. Among persons aged 20-29 years to 80 years or older, the adjusted hazard ratios for future fractures were similar, ranging from 1.51 to 2.12 (P for trend = .120).

The results were similar when age groups were analyzed with regard to all fractures, osteoporotic fractures, major osteoporotic fractures, or hip fractures.

Going forward, Dr. Ye hopes to expand the research into childhood fractures. “They can break their bones pretty easily, especially as they’re going through growth spurts and things like that,” she said.

Asked what her advice to physicians would be, Dr. Ye responded: “Don’t ignore prior fractures, even if they occurred at an early age. I think if someone’s had a fracture, they bought themselves a fracture risk assessment, and that doesn’t mean necessarily a DXA scan. It means you go through their other risk factors: What medications are they on? Do they have a family history? Are they super low BMI? Look at other reasons why you should be worried about their bones, and if you should be worried about their bones, certainly [measure their] BMD and see what’s going on.”

Dr. Ye and Dr. Harvey have disclosed no relevant financial relationships.

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

VANCOUVER – The occurrence of a fracture predicts future fracture risk, but the increase in risk is the same no matter what the age of the patient, according to a new population-based study drawn from the Manitoba BMD Registry.

The work expands previous studies that focused mostly on fracture risk prediction after a first fracture among individuals aged 45-50 and older. Other limitations of prior studies include large age categories (such as “premenopausal”), reliance on self-reporting, and small sample sizes.

As a result, some guidelines recommend considering fracture history only for patients older than a certain age when assessing for future risk, such as with the Fracture Risk Assessment Tool (FRAX). The new study suggests a potential need to reconsider that stance.

“The [percentage] of increased risk from having had prevalent fractures in the past, no matter what your age, is about the same. I think that it’s really paradigm shifting because [when] most of us think [of] young people who fracture, we’re not thinking of osteoporosis or future fracture risk. We’re not saying, ‘Oh, I had a fracture when I was 25. When I’m 70, I should be thinking about osteoporosis.’ So, I think this study is quite eye-opening that way,” Carrie Ye, MD, who presented the study at the annual meeting of the American Society for Bone and Mineral Research, said in an interview.

Participants of younger age who are referred for dual-energy x-ray absorptiometry (DXA) likely represent a population at increased risk of osteoporosis, according to Dr. Ye. “Maybe they have Crohn’s disease or maybe they’re on a bunch of steroids, and so a clinician has flagged them,” said Dr. Ye, who is an assistant professor and rheumatologist at the University of Alberta, Edmonton.

The researchers limited the analysis to nontraumatic fractures, but session moderator Nicholas Harvey, MD, PhD, wondered if a similar finding would occur with traumatic fractures. In an interview, he noted that researchers led by William Leslie, MD, at the University of Manitoba, Winnipeg, found that prior traumatic fracture also predicted future low bone-mineral density (BMD) and osteoporotic fracture. “I think that would have been one interesting question,” said Dr. Harvey, director of the Medical Research Council Lifecourse Epidemiology Centre at the University of Southampton, England.

Dr. Ye’s study included 88,696 individuals who underwent a first DXA scan between 1996 and 2018, which researchers then linked to provincial administrative health data collected between 1979 and 2018. The mean age at first DXA was 64.6 years, and 90.3% were women. Their mean body mass index was 27.4 kg/m². Current smokers made up 10.1% of the cohort, 5.5% had a history of prolonged glucocorticoid use, 3.1% had rheumatoid arthritis, and among 14.9% of patients, there was a secondary cause of osteoporosis. Over a median 25.1 years of observation prior to DXA, clinical fracture occurred in 23.8% of participants.

The mean age of the patients at the time of their first prior fracture was 57.7 years. Over a mean 9.0 years of follow-up, 14.6% of participants experienced a fracture of any kind, 14.0% had osteoporotic fractures, 10.6% had a major osteoporotic fracture (nonankle), and 3.5% had a hip fracture. Among persons aged 20-29 years to 80 years or older, the adjusted hazard ratios for future fractures were similar, ranging from 1.51 to 2.12 (P for trend = .120).

The results were similar when age groups were analyzed with regard to all fractures, osteoporotic fractures, major osteoporotic fractures, or hip fractures.

Going forward, Dr. Ye hopes to expand the research into childhood fractures. “They can break their bones pretty easily, especially as they’re going through growth spurts and things like that,” she said.

Asked what her advice to physicians would be, Dr. Ye responded: “Don’t ignore prior fractures, even if they occurred at an early age. I think if someone’s had a fracture, they bought themselves a fracture risk assessment, and that doesn’t mean necessarily a DXA scan. It means you go through their other risk factors: What medications are they on? Do they have a family history? Are they super low BMI? Look at other reasons why you should be worried about their bones, and if you should be worried about their bones, certainly [measure their] BMD and see what’s going on.”

Dr. Ye and Dr. Harvey have disclosed no relevant financial relationships.

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

VANCOUVER – The occurrence of a fracture predicts future fracture risk, but the increase in risk is the same no matter what the age of the patient, according to a new population-based study drawn from the Manitoba BMD Registry.

The work expands previous studies that focused mostly on fracture risk prediction after a first fracture among individuals aged 45-50 and older. Other limitations of prior studies include large age categories (such as “premenopausal”), reliance on self-reporting, and small sample sizes.

As a result, some guidelines recommend considering fracture history only for patients older than a certain age when assessing for future risk, such as with the Fracture Risk Assessment Tool (FRAX). The new study suggests a potential need to reconsider that stance.

“The [percentage] of increased risk from having had prevalent fractures in the past, no matter what your age, is about the same. I think that it’s really paradigm shifting because [when] most of us think [of] young people who fracture, we’re not thinking of osteoporosis or future fracture risk. We’re not saying, ‘Oh, I had a fracture when I was 25. When I’m 70, I should be thinking about osteoporosis.’ So, I think this study is quite eye-opening that way,” Carrie Ye, MD, who presented the study at the annual meeting of the American Society for Bone and Mineral Research, said in an interview.

Participants of younger age who are referred for dual-energy x-ray absorptiometry (DXA) likely represent a population at increased risk of osteoporosis, according to Dr. Ye. “Maybe they have Crohn’s disease or maybe they’re on a bunch of steroids, and so a clinician has flagged them,” said Dr. Ye, who is an assistant professor and rheumatologist at the University of Alberta, Edmonton.

The researchers limited the analysis to nontraumatic fractures, but session moderator Nicholas Harvey, MD, PhD, wondered if a similar finding would occur with traumatic fractures. In an interview, he noted that researchers led by William Leslie, MD, at the University of Manitoba, Winnipeg, found that prior traumatic fracture also predicted future low bone-mineral density (BMD) and osteoporotic fracture. “I think that would have been one interesting question,” said Dr. Harvey, director of the Medical Research Council Lifecourse Epidemiology Centre at the University of Southampton, England.

Dr. Ye’s study included 88,696 individuals who underwent a first DXA scan between 1996 and 2018, which researchers then linked to provincial administrative health data collected between 1979 and 2018. The mean age at first DXA was 64.6 years, and 90.3% were women. Their mean body mass index was 27.4 kg/m². Current smokers made up 10.1% of the cohort, 5.5% had a history of prolonged glucocorticoid use, 3.1% had rheumatoid arthritis, and among 14.9% of patients, there was a secondary cause of osteoporosis. Over a median 25.1 years of observation prior to DXA, clinical fracture occurred in 23.8% of participants.

The mean age of the patients at the time of their first prior fracture was 57.7 years. Over a mean 9.0 years of follow-up, 14.6% of participants experienced a fracture of any kind, 14.0% had osteoporotic fractures, 10.6% had a major osteoporotic fracture (nonankle), and 3.5% had a hip fracture. Among persons aged 20-29 years to 80 years or older, the adjusted hazard ratios for future fractures were similar, ranging from 1.51 to 2.12 (P for trend = .120).

The results were similar when age groups were analyzed with regard to all fractures, osteoporotic fractures, major osteoporotic fractures, or hip fractures.

Going forward, Dr. Ye hopes to expand the research into childhood fractures. “They can break their bones pretty easily, especially as they’re going through growth spurts and things like that,” she said.

Asked what her advice to physicians would be, Dr. Ye responded: “Don’t ignore prior fractures, even if they occurred at an early age. I think if someone’s had a fracture, they bought themselves a fracture risk assessment, and that doesn’t mean necessarily a DXA scan. It means you go through their other risk factors: What medications are they on? Do they have a family history? Are they super low BMI? Look at other reasons why you should be worried about their bones, and if you should be worried about their bones, certainly [measure their] BMD and see what’s going on.”

Dr. Ye and Dr. Harvey have disclosed no relevant financial relationships.

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

TOPLINE:

In combination with methotrexate, both abatacept (Orencia) and certolizumab pegol (Cimzia), but not tocilizumab (Actemra), showed superiority over different combinations of active conventional disease-modifying antirheumatic drugs (DMARDs) for promoting remission in patients with early, untreated rheumatoid arthritis.

METHODOLOGY:

The study population included 812 adults from sites in six European countries who had treatment-naive early RA (less than 24 months’ duration) and moderate to severe disease.

Participants were randomly assigned to open-label treatment with methotrexate plus one of four treatments:

• Active conventional therapy (oral , tapered quickly and discontinued after 9 months, or , hydroxychloroquine, and intra-articular glucocorticoid injections in swollen joints).
• Certolizumab pegol.
• Abatacept.
• Tocilizumab.

In all the biologic-treated groups, intra-articular glucocorticoid injections were allowed on demand up to week 12; thereafter, up to 40 mg were allowed every 12 weeks. In all groups, intra-articular glucocorticoids were prohibited in weeks 20-24 and weeks 44-48 to minimize their influence on week 24 and week 48 outcomes.

TAKEAWAY:

• Clinical remission rates at week 48 based on Clinical Disease Activity Index scores of 2.8 or less were 59.3% with abatacept and 52.3% with certolizumab, which were significantly greater than the rate of 39.2% seen with active conventional therapy. The 51.9% rate seen with tocilizumab was not superior to active conventional therapy.
• The co–primary outcome of change in van der Heijde-modified Sharp Score from baseline to week 48 was relatively low across all groups: 0.45 for active conventional therapy, and 0.62, 0.47, and 0.50 for abatacept, certolizumab pegol, and tocilizumab, respectively.
• No new safety signals appeared, nor did any significantly increased risk associated with glucocorticoid use; at least one adverse event was reported in 88.3%, 89.6%, 85.8%, and 96.7% of patients taking conventional therapy, certolizumab pegol, abatacept, and tocilizumab, respectively.

IN PRACTICE:

The results suggest that both abatacept and certolizumab pegol yield higher remission rates than optimized conventional therapy, and “should be considered when the management of patients with newly diagnosed RA is decided, both in clinical practice and in treatment recommendations,” the authors write.

SOURCE:

The lead author on the study was Mikkel Østergaard, MD, PhD, of the Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen. The study was published online in Annals of the Rheumatic Disease.  

LIMITATIONS:

The open-label study design could influence some subjective outcomes, and conventional therapy included two slightly different strategies based on national recommendations for the individual countries.

DISCLOSURES:

The study was funded by multiple public sources to centers from countries participating in the study, as well as the Icelandic Society for Rheumatology, the Swedish Rheumatism Association, and the Research Fund of University Hospital, Reykjavik, Iceland. UCB and Bristol-Myers Squibb provided certolizumab pegol and abatacept, respectively, at no cost, but were not otherwise involved in the study. Many authors, including Dr. Østergaard, report financial relationships with multiple pharmaceutical companies. The full list can be found with the original article.

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

TOPLINE:

In combination with methotrexate, both abatacept (Orencia) and certolizumab pegol (Cimzia), but not tocilizumab (Actemra), showed superiority over different combinations of active conventional disease-modifying antirheumatic drugs (DMARDs) for promoting remission in patients with early, untreated rheumatoid arthritis.

METHODOLOGY:

The study population included 812 adults from sites in six European countries who had treatment-naive early RA (less than 24 months’ duration) and moderate to severe disease.

Participants were randomly assigned to open-label treatment with methotrexate plus one of four treatments:

• Active conventional therapy (oral , tapered quickly and discontinued after 9 months, or , hydroxychloroquine, and intra-articular glucocorticoid injections in swollen joints).
• Certolizumab pegol.
• Abatacept.
• Tocilizumab.

In all the biologic-treated groups, intra-articular glucocorticoid injections were allowed on demand up to week 12; thereafter, up to 40 mg were allowed every 12 weeks. In all groups, intra-articular glucocorticoids were prohibited in weeks 20-24 and weeks 44-48 to minimize their influence on week 24 and week 48 outcomes.

TAKEAWAY:

• Clinical remission rates at week 48 based on Clinical Disease Activity Index scores of 2.8 or less were 59.3% with abatacept and 52.3% with certolizumab, which were significantly greater than the rate of 39.2% seen with active conventional therapy. The 51.9% rate seen with tocilizumab was not superior to active conventional therapy.
• The co–primary outcome of change in van der Heijde-modified Sharp Score from baseline to week 48 was relatively low across all groups: 0.45 for active conventional therapy, and 0.62, 0.47, and 0.50 for abatacept, certolizumab pegol, and tocilizumab, respectively.
• No new safety signals appeared, nor did any significantly increased risk associated with glucocorticoid use; at least one adverse event was reported in 88.3%, 89.6%, 85.8%, and 96.7% of patients taking conventional therapy, certolizumab pegol, abatacept, and tocilizumab, respectively.

IN PRACTICE:

The results suggest that both abatacept and certolizumab pegol yield higher remission rates than optimized conventional therapy, and “should be considered when the management of patients with newly diagnosed RA is decided, both in clinical practice and in treatment recommendations,” the authors write.

SOURCE:

The lead author on the study was Mikkel Østergaard, MD, PhD, of the Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen. The study was published online in Annals of the Rheumatic Disease.  

LIMITATIONS:

The open-label study design could influence some subjective outcomes, and conventional therapy included two slightly different strategies based on national recommendations for the individual countries.

DISCLOSURES:

The study was funded by multiple public sources to centers from countries participating in the study, as well as the Icelandic Society for Rheumatology, the Swedish Rheumatism Association, and the Research Fund of University Hospital, Reykjavik, Iceland. UCB and Bristol-Myers Squibb provided certolizumab pegol and abatacept, respectively, at no cost, but were not otherwise involved in the study. Many authors, including Dr. Østergaard, report financial relationships with multiple pharmaceutical companies. The full list can be found with the original article.

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

TOPLINE:

In combination with methotrexate, both abatacept (Orencia) and certolizumab pegol (Cimzia), but not tocilizumab (Actemra), showed superiority over different combinations of active conventional disease-modifying antirheumatic drugs (DMARDs) for promoting remission in patients with early, untreated rheumatoid arthritis.

METHODOLOGY:

The study population included 812 adults from sites in six European countries who had treatment-naive early RA (less than 24 months’ duration) and moderate to severe disease.

Participants were randomly assigned to open-label treatment with methotrexate plus one of four treatments:

• Active conventional therapy (oral , tapered quickly and discontinued after 9 months, or , hydroxychloroquine, and intra-articular glucocorticoid injections in swollen joints).
• Certolizumab pegol.
• Abatacept.
• Tocilizumab.

In all the biologic-treated groups, intra-articular glucocorticoid injections were allowed on demand up to week 12; thereafter, up to 40 mg were allowed every 12 weeks. In all groups, intra-articular glucocorticoids were prohibited in weeks 20-24 and weeks 44-48 to minimize their influence on week 24 and week 48 outcomes.

TAKEAWAY:

• Clinical remission rates at week 48 based on Clinical Disease Activity Index scores of 2.8 or less were 59.3% with abatacept and 52.3% with certolizumab, which were significantly greater than the rate of 39.2% seen with active conventional therapy. The 51.9% rate seen with tocilizumab was not superior to active conventional therapy.
• The co–primary outcome of change in van der Heijde-modified Sharp Score from baseline to week 48 was relatively low across all groups: 0.45 for active conventional therapy, and 0.62, 0.47, and 0.50 for abatacept, certolizumab pegol, and tocilizumab, respectively.
• No new safety signals appeared, nor did any significantly increased risk associated with glucocorticoid use; at least one adverse event was reported in 88.3%, 89.6%, 85.8%, and 96.7% of patients taking conventional therapy, certolizumab pegol, abatacept, and tocilizumab, respectively.

IN PRACTICE:

The results suggest that both abatacept and certolizumab pegol yield higher remission rates than optimized conventional therapy, and “should be considered when the management of patients with newly diagnosed RA is decided, both in clinical practice and in treatment recommendations,” the authors write.

SOURCE:

The lead author on the study was Mikkel Østergaard, MD, PhD, of the Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen. The study was published online in Annals of the Rheumatic Disease.  

LIMITATIONS:

The open-label study design could influence some subjective outcomes, and conventional therapy included two slightly different strategies based on national recommendations for the individual countries.

DISCLOSURES:

The study was funded by multiple public sources to centers from countries participating in the study, as well as the Icelandic Society for Rheumatology, the Swedish Rheumatism Association, and the Research Fund of University Hospital, Reykjavik, Iceland. UCB and Bristol-Myers Squibb provided certolizumab pegol and abatacept, respectively, at no cost, but were not otherwise involved in the study. Many authors, including Dr. Østergaard, report financial relationships with multiple pharmaceutical companies. The full list can be found with the original article.

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

TOPLINE:

Solriamfetol – a medication approved for excessive daytime sleepiness caused by narcolepsy or obstructive sleep apnea – significantly improved symptoms of attention-deficit/hyperactivity disorder (ADHD) and clinical impression of ADHD severity in a pilot study of adults with ADHD.

METHODOLOGY:

• Solriamfetol is a dopamine and norepinephrine reuptake inhibitor that shares some of the properties of current ADHD medications.
• Researchers conducted a randomized, double-blind, placebo-controlled, dose-optimization trial of 75- or 150-mg solriamfetol in 60 adults with ADHD. For nearly all of the individuals who received solriamfetol, doses increased to 150 mg after the first week.
• The primary outcome was change in scores on the Adult ADHD Investigator Symptom Rating Scale (AISRS).
• Secondary outcomes included scores on the Clinical Global Impressions (CGI) scale and standard measures of executive function, behavior, and sleep.

TAKEAWAY:

• By week 6, total AISRS score improved 25% for 52% of individuals to took solriamfetol, vs. 17% of those who received placebo. Total AISRS score improved 50% by week 6 in 28% of those who took solriamfetol, vs. 3.4% of those who received placebo.
• By week 6, CGI ratings of “much improved” or “very much improved” occurred in significantly more individuals who received solriamfetol than those who took placebo (45% vs. 7%).
• Significantly more individuals who received solriamfetol than placebo self-reported improvements in executive function (69% vs. 34%). Improvement in wakefulness was noted with solriamfetol, but that did not moderate the change in ADHD symptom burden.
• Solriamfetol was well tolerated, with no significant effect on sleep quality or blood pressure. Adverse effects that occurred at a higher rate in the treatment group than in the placebo group were typical for solriamfetol and sympathomimetic agents used for ADHD.

IN PRACTICE:

Massachusetts General Hospital

“Solriamfetol may be a safe and effective treatment for ADHD in adults. Larger studies replicating these findings could confirm the strong evidence of benefit and the tolerability of this agent as a treatment,” lead author Craig B.H. Surman, MD, director of the clinical and research program in adult ADHD, Massachusetts General Hospital, Boston, said in a statement.

SOURCE:

The study was published online in The Journal of Clinical Psychiatry.

LIMITATIONS:

Limitations include the small sample size and short 6-week duration. More women than men received solriamfetol; it’s unclear how this could have affected the results.

DISCLOSURES:

The study was an investigator-initiated trial supported by Jazz Pharmaceuticals and Axsome Therapeutics. Dr. Surman has received consultant fees, research support, and royalties from multiple companies.

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

TOPLINE:

Solriamfetol – a medication approved for excessive daytime sleepiness caused by narcolepsy or obstructive sleep apnea – significantly improved symptoms of attention-deficit/hyperactivity disorder (ADHD) and clinical impression of ADHD severity in a pilot study of adults with ADHD.

METHODOLOGY:

• Solriamfetol is a dopamine and norepinephrine reuptake inhibitor that shares some of the properties of current ADHD medications.
• Researchers conducted a randomized, double-blind, placebo-controlled, dose-optimization trial of 75- or 150-mg solriamfetol in 60 adults with ADHD. For nearly all of the individuals who received solriamfetol, doses increased to 150 mg after the first week.
• The primary outcome was change in scores on the Adult ADHD Investigator Symptom Rating Scale (AISRS).
• Secondary outcomes included scores on the Clinical Global Impressions (CGI) scale and standard measures of executive function, behavior, and sleep.

TAKEAWAY:

• By week 6, total AISRS score improved 25% for 52% of individuals to took solriamfetol, vs. 17% of those who received placebo. Total AISRS score improved 50% by week 6 in 28% of those who took solriamfetol, vs. 3.4% of those who received placebo.
• By week 6, CGI ratings of “much improved” or “very much improved” occurred in significantly more individuals who received solriamfetol than those who took placebo (45% vs. 7%).
• Significantly more individuals who received solriamfetol than placebo self-reported improvements in executive function (69% vs. 34%). Improvement in wakefulness was noted with solriamfetol, but that did not moderate the change in ADHD symptom burden.
• Solriamfetol was well tolerated, with no significant effect on sleep quality or blood pressure. Adverse effects that occurred at a higher rate in the treatment group than in the placebo group were typical for solriamfetol and sympathomimetic agents used for ADHD.

IN PRACTICE:

Massachusetts General Hospital

“Solriamfetol may be a safe and effective treatment for ADHD in adults. Larger studies replicating these findings could confirm the strong evidence of benefit and the tolerability of this agent as a treatment,” lead author Craig B.H. Surman, MD, director of the clinical and research program in adult ADHD, Massachusetts General Hospital, Boston, said in a statement.

SOURCE:

The study was published online in The Journal of Clinical Psychiatry.

LIMITATIONS:

Limitations include the small sample size and short 6-week duration. More women than men received solriamfetol; it’s unclear how this could have affected the results.

DISCLOSURES:

The study was an investigator-initiated trial supported by Jazz Pharmaceuticals and Axsome Therapeutics. Dr. Surman has received consultant fees, research support, and royalties from multiple companies.

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

TOPLINE:

Solriamfetol – a medication approved for excessive daytime sleepiness caused by narcolepsy or obstructive sleep apnea – significantly improved symptoms of attention-deficit/hyperactivity disorder (ADHD) and clinical impression of ADHD severity in a pilot study of adults with ADHD.

METHODOLOGY:

• Solriamfetol is a dopamine and norepinephrine reuptake inhibitor that shares some of the properties of current ADHD medications.
• Researchers conducted a randomized, double-blind, placebo-controlled, dose-optimization trial of 75- or 150-mg solriamfetol in 60 adults with ADHD. For nearly all of the individuals who received solriamfetol, doses increased to 150 mg after the first week.
• The primary outcome was change in scores on the Adult ADHD Investigator Symptom Rating Scale (AISRS).
• Secondary outcomes included scores on the Clinical Global Impressions (CGI) scale and standard measures of executive function, behavior, and sleep.

TAKEAWAY:

• By week 6, total AISRS score improved 25% for 52% of individuals to took solriamfetol, vs. 17% of those who received placebo. Total AISRS score improved 50% by week 6 in 28% of those who took solriamfetol, vs. 3.4% of those who received placebo.
• By week 6, CGI ratings of “much improved” or “very much improved” occurred in significantly more individuals who received solriamfetol than those who took placebo (45% vs. 7%).
• Significantly more individuals who received solriamfetol than placebo self-reported improvements in executive function (69% vs. 34%). Improvement in wakefulness was noted with solriamfetol, but that did not moderate the change in ADHD symptom burden.
• Solriamfetol was well tolerated, with no significant effect on sleep quality or blood pressure. Adverse effects that occurred at a higher rate in the treatment group than in the placebo group were typical for solriamfetol and sympathomimetic agents used for ADHD.

IN PRACTICE:

Massachusetts General Hospital

“Solriamfetol may be a safe and effective treatment for ADHD in adults. Larger studies replicating these findings could confirm the strong evidence of benefit and the tolerability of this agent as a treatment,” lead author Craig B.H. Surman, MD, director of the clinical and research program in adult ADHD, Massachusetts General Hospital, Boston, said in a statement.

SOURCE:

The study was published online in The Journal of Clinical Psychiatry.

LIMITATIONS:

Limitations include the small sample size and short 6-week duration. More women than men received solriamfetol; it’s unclear how this could have affected the results.

DISCLOSURES:

The study was an investigator-initiated trial supported by Jazz Pharmaceuticals and Axsome Therapeutics. Dr. Surman has received consultant fees, research support, and royalties from multiple companies.

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

VANCOUVER – A highly controlled retrospective analysis suggests that denosumab (Prolia) leads to greater reduction in fracture risk than does zoledronic acid (Reclast) among treatment-naive postmenopausal women with osteoporosis.

A previous head-to-head comparison showed that denosumab increased bone mineral density at key skeletal sites compared with zoledronic acid, but only a single, small observational study has examined fracture risk, and it found no difference.

The new study, presented at the annual meeting of the American Society for Bone and Mineral Research, used a relatively new method of real-world comparative effectiveness analysis called negative control outcome (NCO) to analyze Medicare fee-for-service data.

NCO analysis takes extra pains to remove bias through data that might be linked to potential confounders but could not reasonably be attributed to a drug. For example, people who have greater contact with the health care system may be more likely to get one drug or another. The researchers used the frequency of receiving a flu or pneumonia vaccine as a proxy for this. If the two comparison groups had a significant difference in a proxy, it suggested a hidden bias and forced the researchers to abandon those groupings. Another example used car accidents as a proxy for cognitive impairment.

“If you find meaningful differences between the two groups, and you can say there’s no way a bone drug could account for these differences, then we shouldn’t do this analysis because these groups just aren’t comparable. They probably differ by that confounding factor we couldn’t measure,” said Jeffrey Curtis, MD, who presented the study. He is a professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham.

The study strongly suggests superiority for denosumab. “There was a significant difference in multiple different groupings of fractures – beginning at year 2, extending to year 3 and even out to year 5 – that showed that there is a significant reduction in fracture risk if you get treated with denosumab [that was greater] than if you get treated with zoledronic acid,” Dr. Curtis said.

The researchers weighed 118 covariates and ultimately identified a population of 90,805 women taking denosumab and 37,328 taking zoledronic acid that was equally balanced in all patient characteristics. The mean age was about 75 years in the denosumab group and 74 in the zoledronic acid group.

The researchers found a 34% lower risk for hip fracture in the denosumab group by 5 years (relative risk, 0.66; 95% confidence interval, 0.43-0.90).

Similar patterns in fracture risk reduction were observed at 5 years for nonvertebral fracture (RR, 0.67; 95% CI, 0.52-0.82), nonhip nonvertebral fracture (RR, 0.69; 95% CI, 0.50-0.88), and major osteoporotic fracture (RR, 0.74; 95% CI, 0.59-0.89).

During the Q&A session after the talk, one audience member commented that the study was limited because the researchers only followed patients who received zoledronic acid for 60 days, which could have missed potential long-term benefits of the drug, especially since bisphosphonates have a lengthy skeletal retention time. Dr. Curtis acknowledged the point but said, “Usually, that’s not something we do, but these are different enough mechanisms of action that it may be warranted at least as a sensitivity analysis,” he said.

The study and its methodology were impressive, according to Yumie Rhee, MD, who comoderated the session where the study was presented. “I think they did a really good job by doing the negative control analysis. We’re not going to have a head-to-head clinical trial, so we don’t know the real fracture reduction differences [between denosumab and zoledronic acid]. [The NCO analysis] is more than the propensity matching score that we do usually,” said Dr. Rhee, who is a professor of endocrinology at Yonsei University College of Medicine in Seoul, South Korea.

In particular, the study showed a significantly greater reduction in hip fractures with denosumab. “Even in the RCTs, it was really hard to see the reduction in hip fracture, so I think this is showing much stronger data for denosumab. Especially in patients who have more [general fracture] risk and patients with higher hip fracture risk, I would go with denosumab,” Dr. Rhee said.

Her comoderator, Maria Zanchetta, MD, agreed. “It can have clinical implication, because we think denosumab is better than [zoledronic acid] for higher-risk patients, but we didn’t have the evidence. So at least we have a new [study] to look at, and I think it’s very important for our practice,” said Dr. Zanchetta, who is a professor of osteology at the Institute of Diagnostics and Metabolic Research, Universidad del Salvador, Buenos Aires.

The study was funded by Amgen, which markets denosumab. Dr. Curtis has consulted for Amgen. Dr. Rhee and Dr. Zanchetta report no relevant financial relationships.

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

VANCOUVER – A highly controlled retrospective analysis suggests that denosumab (Prolia) leads to greater reduction in fracture risk than does zoledronic acid (Reclast) among treatment-naive postmenopausal women with osteoporosis.

A previous head-to-head comparison showed that denosumab increased bone mineral density at key skeletal sites compared with zoledronic acid, but only a single, small observational study has examined fracture risk, and it found no difference.

The new study, presented at the annual meeting of the American Society for Bone and Mineral Research, used a relatively new method of real-world comparative effectiveness analysis called negative control outcome (NCO) to analyze Medicare fee-for-service data.

NCO analysis takes extra pains to remove bias through data that might be linked to potential confounders but could not reasonably be attributed to a drug. For example, people who have greater contact with the health care system may be more likely to get one drug or another. The researchers used the frequency of receiving a flu or pneumonia vaccine as a proxy for this. If the two comparison groups had a significant difference in a proxy, it suggested a hidden bias and forced the researchers to abandon those groupings. Another example used car accidents as a proxy for cognitive impairment.

“If you find meaningful differences between the two groups, and you can say there’s no way a bone drug could account for these differences, then we shouldn’t do this analysis because these groups just aren’t comparable. They probably differ by that confounding factor we couldn’t measure,” said Jeffrey Curtis, MD, who presented the study. He is a professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham.

The study strongly suggests superiority for denosumab. “There was a significant difference in multiple different groupings of fractures – beginning at year 2, extending to year 3 and even out to year 5 – that showed that there is a significant reduction in fracture risk if you get treated with denosumab [that was greater] than if you get treated with zoledronic acid,” Dr. Curtis said.

The researchers weighed 118 covariates and ultimately identified a population of 90,805 women taking denosumab and 37,328 taking zoledronic acid that was equally balanced in all patient characteristics. The mean age was about 75 years in the denosumab group and 74 in the zoledronic acid group.

The researchers found a 34% lower risk for hip fracture in the denosumab group by 5 years (relative risk, 0.66; 95% confidence interval, 0.43-0.90).

Similar patterns in fracture risk reduction were observed at 5 years for nonvertebral fracture (RR, 0.67; 95% CI, 0.52-0.82), nonhip nonvertebral fracture (RR, 0.69; 95% CI, 0.50-0.88), and major osteoporotic fracture (RR, 0.74; 95% CI, 0.59-0.89).

During the Q&A session after the talk, one audience member commented that the study was limited because the researchers only followed patients who received zoledronic acid for 60 days, which could have missed potential long-term benefits of the drug, especially since bisphosphonates have a lengthy skeletal retention time. Dr. Curtis acknowledged the point but said, “Usually, that’s not something we do, but these are different enough mechanisms of action that it may be warranted at least as a sensitivity analysis,” he said.

The study and its methodology were impressive, according to Yumie Rhee, MD, who comoderated the session where the study was presented. “I think they did a really good job by doing the negative control analysis. We’re not going to have a head-to-head clinical trial, so we don’t know the real fracture reduction differences [between denosumab and zoledronic acid]. [The NCO analysis] is more than the propensity matching score that we do usually,” said Dr. Rhee, who is a professor of endocrinology at Yonsei University College of Medicine in Seoul, South Korea.

In particular, the study showed a significantly greater reduction in hip fractures with denosumab. “Even in the RCTs, it was really hard to see the reduction in hip fracture, so I think this is showing much stronger data for denosumab. Especially in patients who have more [general fracture] risk and patients with higher hip fracture risk, I would go with denosumab,” Dr. Rhee said.

Her comoderator, Maria Zanchetta, MD, agreed. “It can have clinical implication, because we think denosumab is better than [zoledronic acid] for higher-risk patients, but we didn’t have the evidence. So at least we have a new [study] to look at, and I think it’s very important for our practice,” said Dr. Zanchetta, who is a professor of osteology at the Institute of Diagnostics and Metabolic Research, Universidad del Salvador, Buenos Aires.

The study was funded by Amgen, which markets denosumab. Dr. Curtis has consulted for Amgen. Dr. Rhee and Dr. Zanchetta report no relevant financial relationships.

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

VANCOUVER – A highly controlled retrospective analysis suggests that denosumab (Prolia) leads to greater reduction in fracture risk than does zoledronic acid (Reclast) among treatment-naive postmenopausal women with osteoporosis.

A previous head-to-head comparison showed that denosumab increased bone mineral density at key skeletal sites compared with zoledronic acid, but only a single, small observational study has examined fracture risk, and it found no difference.

The new study, presented at the annual meeting of the American Society for Bone and Mineral Research, used a relatively new method of real-world comparative effectiveness analysis called negative control outcome (NCO) to analyze Medicare fee-for-service data.

NCO analysis takes extra pains to remove bias through data that might be linked to potential confounders but could not reasonably be attributed to a drug. For example, people who have greater contact with the health care system may be more likely to get one drug or another. The researchers used the frequency of receiving a flu or pneumonia vaccine as a proxy for this. If the two comparison groups had a significant difference in a proxy, it suggested a hidden bias and forced the researchers to abandon those groupings. Another example used car accidents as a proxy for cognitive impairment.

“If you find meaningful differences between the two groups, and you can say there’s no way a bone drug could account for these differences, then we shouldn’t do this analysis because these groups just aren’t comparable. They probably differ by that confounding factor we couldn’t measure,” said Jeffrey Curtis, MD, who presented the study. He is a professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham.

The study strongly suggests superiority for denosumab. “There was a significant difference in multiple different groupings of fractures – beginning at year 2, extending to year 3 and even out to year 5 – that showed that there is a significant reduction in fracture risk if you get treated with denosumab [that was greater] than if you get treated with zoledronic acid,” Dr. Curtis said.

The researchers weighed 118 covariates and ultimately identified a population of 90,805 women taking denosumab and 37,328 taking zoledronic acid that was equally balanced in all patient characteristics. The mean age was about 75 years in the denosumab group and 74 in the zoledronic acid group.

The researchers found a 34% lower risk for hip fracture in the denosumab group by 5 years (relative risk, 0.66; 95% confidence interval, 0.43-0.90).

Similar patterns in fracture risk reduction were observed at 5 years for nonvertebral fracture (RR, 0.67; 95% CI, 0.52-0.82), nonhip nonvertebral fracture (RR, 0.69; 95% CI, 0.50-0.88), and major osteoporotic fracture (RR, 0.74; 95% CI, 0.59-0.89).

During the Q&A session after the talk, one audience member commented that the study was limited because the researchers only followed patients who received zoledronic acid for 60 days, which could have missed potential long-term benefits of the drug, especially since bisphosphonates have a lengthy skeletal retention time. Dr. Curtis acknowledged the point but said, “Usually, that’s not something we do, but these are different enough mechanisms of action that it may be warranted at least as a sensitivity analysis,” he said.

The study and its methodology were impressive, according to Yumie Rhee, MD, who comoderated the session where the study was presented. “I think they did a really good job by doing the negative control analysis. We’re not going to have a head-to-head clinical trial, so we don’t know the real fracture reduction differences [between denosumab and zoledronic acid]. [The NCO analysis] is more than the propensity matching score that we do usually,” said Dr. Rhee, who is a professor of endocrinology at Yonsei University College of Medicine in Seoul, South Korea.

In particular, the study showed a significantly greater reduction in hip fractures with denosumab. “Even in the RCTs, it was really hard to see the reduction in hip fracture, so I think this is showing much stronger data for denosumab. Especially in patients who have more [general fracture] risk and patients with higher hip fracture risk, I would go with denosumab,” Dr. Rhee said.

Her comoderator, Maria Zanchetta, MD, agreed. “It can have clinical implication, because we think denosumab is better than [zoledronic acid] for higher-risk patients, but we didn’t have the evidence. So at least we have a new [study] to look at, and I think it’s very important for our practice,” said Dr. Zanchetta, who is a professor of osteology at the Institute of Diagnostics and Metabolic Research, Universidad del Salvador, Buenos Aires.

The study was funded by Amgen, which markets denosumab. Dr. Curtis has consulted for Amgen. Dr. Rhee and Dr. Zanchetta report 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.

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.