Conference Coverage

HONOLULU – Sexual and gender minority (SGM) people are at increased risk for asthma severity, compared with non-SGM people, and asthma is especially exacerbated in SGM persons who use e-cigarettes compared with heterosexuals.

These findings come from a study of asthma severity among SGM people, with a special focus on the contribution of tobacco, reported Tugba Kaplan, MD, a resident in internal medicine at Luminis Health Anne Arundel Medical Center, Annapolis, Md.

“To the best of our knowledge, this is the first study assessing asthma severity among SGM people in a nationally representative longitudinal cohort study,” she said in an oral abstract session at the annual meeting of the American College of Chest Physicians (CHEST).

There has been only limited research on the health status and health needs of SGM people, and most of the studies conducted have focused on issues such as HIV/AIDS, sexual health, and substance use, not respiratory health, she said.
 

Following the PATH

Dr. Kaplan and colleagues drew on data from the Population Assessment of Tobacco and Health (PATH) Study, a nationally representative longitudinal cohort study with data on approximately 46,000 adults and adolescents in the United States.

The study uses self-reported data on tobacco use patterns; perceptions of risk and attitudes toward tobacco products; tobacco initiation, cessation, and relapse; and associated health outcomes.

The investigators combined data from three waves of the PATH Study, conducted from 2015 to 2019 on nonpregnant participants aged 18 years and older, and used mixed-effect logistic regression models to look for potential associations between sexual orientation and asthma severity.

They used standard definitions of asthma severity, based on lung function impairment measured by forced expiratory volume in 1 second and forced vital capacity, nighttime awakenings, use of a short-acting beta2-agonist for symptoms, interference with normal activity, and exacerbations requiring oral systemic corticosteroids.

The study also includes a sexual orientation question, asking participants, “do you consider yourself to be ...” with the options “straight, lesbian or gay, bisexual, something else, don’t know, or refused.”

Based on these responses, Dr. Kaplan and colleagues studied a total sample of 1,815 people who identify as SGM and 12,879 who identify as non-SGM.
 

Risks increased

In an analysis adjusted for age, sex, race/ethnicity, tobacco use, body mass index, physical activity, and asthma medication use, the authors found that, compared with non-SGM people, SGM respondents were significantly more likely to have had asthma attacks requiring steroid use in the past years (odds ratio, 1.47; 95% confidence interval, 1.01-2.15), asthma interfering with daily activities in the past month (OR, 1.33; CI, 1.10-1.61), and shortness of breath in any week over the 30 days (OR, 1.82; CI, 1.32-2.51). There was no significant difference between the groups in inhaler use over the past month, however.

They also found two interactions in the logistic regression models, one between urgent care visits and respondents who reported using both regular tobacco and e-cigarettes (dual users), and between exclusive e-cigarette use and waking up at night.

Among dual users, SGM respondents had a nearly fourfold greater risk for asthma attacks requiring urgent care visits, compared with non-SGM respondents (OR, 3.89; CI, 1.99-7.63). In contrast, among those who never used tobacco, there were no significant differences between the sexual orientation groups in regard to asthma attacks requiring urgent care visits.

Among those who reported using e-cigarettes exclusively, SGM respondents were nearly eight times more likely to report night awakening, compared with non-SGM users (OR, 7.81; CI, 2.93-20.8).

Among never users, in contrast, there was no significant difference in nighttime disturbances.
 

Possible confounders

The data suggest that “in the context of chronic illnesses like asthma, it is crucial to offer patients the knowledge and tools required to proficiently handle their conditions,” Dr. Kaplan said, adding that the differences seen between SGM and non-SGM respondents may be caused by health care disparities among SGM people that result in nonadherence to regular follow-ups.

In an interview, Jean Bourbeau, MD, MSc, who was a moderator for the session but was not involved in the study, commented that “we have to be very careful before making any conclusions, because this population could be at high risk for different reasons, and especially, do they get the same attention in terms of the care that is provided to the general population, and do they get access to the same medication?”

Nonetheless, Dr. Bourbeau continued, “I think this study is very important, because it shows us how much awareness we need to determine differences in populations, and [sexual orientation] is probably one thing that nobody had considered before, and for the first time we are now considering these potential differences in our population.”

The authors did not report a study funding source. Dr. Kaplan and Dr. Bourbeau reported having no relevant financial relationships.

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

HONOLULU – Sexual and gender minority (SGM) people are at increased risk for asthma severity, compared with non-SGM people, and asthma is especially exacerbated in SGM persons who use e-cigarettes compared with heterosexuals.

These findings come from a study of asthma severity among SGM people, with a special focus on the contribution of tobacco, reported Tugba Kaplan, MD, a resident in internal medicine at Luminis Health Anne Arundel Medical Center, Annapolis, Md.

“To the best of our knowledge, this is the first study assessing asthma severity among SGM people in a nationally representative longitudinal cohort study,” she said in an oral abstract session at the annual meeting of the American College of Chest Physicians (CHEST).

There has been only limited research on the health status and health needs of SGM people, and most of the studies conducted have focused on issues such as HIV/AIDS, sexual health, and substance use, not respiratory health, she said.
 

Following the PATH

Dr. Kaplan and colleagues drew on data from the Population Assessment of Tobacco and Health (PATH) Study, a nationally representative longitudinal cohort study with data on approximately 46,000 adults and adolescents in the United States.

The study uses self-reported data on tobacco use patterns; perceptions of risk and attitudes toward tobacco products; tobacco initiation, cessation, and relapse; and associated health outcomes.

The investigators combined data from three waves of the PATH Study, conducted from 2015 to 2019 on nonpregnant participants aged 18 years and older, and used mixed-effect logistic regression models to look for potential associations between sexual orientation and asthma severity.

They used standard definitions of asthma severity, based on lung function impairment measured by forced expiratory volume in 1 second and forced vital capacity, nighttime awakenings, use of a short-acting beta2-agonist for symptoms, interference with normal activity, and exacerbations requiring oral systemic corticosteroids.

The study also includes a sexual orientation question, asking participants, “do you consider yourself to be ...” with the options “straight, lesbian or gay, bisexual, something else, don’t know, or refused.”

Based on these responses, Dr. Kaplan and colleagues studied a total sample of 1,815 people who identify as SGM and 12,879 who identify as non-SGM.
 

Risks increased

In an analysis adjusted for age, sex, race/ethnicity, tobacco use, body mass index, physical activity, and asthma medication use, the authors found that, compared with non-SGM people, SGM respondents were significantly more likely to have had asthma attacks requiring steroid use in the past years (odds ratio, 1.47; 95% confidence interval, 1.01-2.15), asthma interfering with daily activities in the past month (OR, 1.33; CI, 1.10-1.61), and shortness of breath in any week over the 30 days (OR, 1.82; CI, 1.32-2.51). There was no significant difference between the groups in inhaler use over the past month, however.

They also found two interactions in the logistic regression models, one between urgent care visits and respondents who reported using both regular tobacco and e-cigarettes (dual users), and between exclusive e-cigarette use and waking up at night.

Among dual users, SGM respondents had a nearly fourfold greater risk for asthma attacks requiring urgent care visits, compared with non-SGM respondents (OR, 3.89; CI, 1.99-7.63). In contrast, among those who never used tobacco, there were no significant differences between the sexual orientation groups in regard to asthma attacks requiring urgent care visits.

Among those who reported using e-cigarettes exclusively, SGM respondents were nearly eight times more likely to report night awakening, compared with non-SGM users (OR, 7.81; CI, 2.93-20.8).

Among never users, in contrast, there was no significant difference in nighttime disturbances.
 

Possible confounders

The data suggest that “in the context of chronic illnesses like asthma, it is crucial to offer patients the knowledge and tools required to proficiently handle their conditions,” Dr. Kaplan said, adding that the differences seen between SGM and non-SGM respondents may be caused by health care disparities among SGM people that result in nonadherence to regular follow-ups.

In an interview, Jean Bourbeau, MD, MSc, who was a moderator for the session but was not involved in the study, commented that “we have to be very careful before making any conclusions, because this population could be at high risk for different reasons, and especially, do they get the same attention in terms of the care that is provided to the general population, and do they get access to the same medication?”

Nonetheless, Dr. Bourbeau continued, “I think this study is very important, because it shows us how much awareness we need to determine differences in populations, and [sexual orientation] is probably one thing that nobody had considered before, and for the first time we are now considering these potential differences in our population.”

The authors did not report a study funding source. Dr. Kaplan and Dr. Bourbeau reported having no relevant financial relationships.

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

HONOLULU – Sexual and gender minority (SGM) people are at increased risk for asthma severity, compared with non-SGM people, and asthma is especially exacerbated in SGM persons who use e-cigarettes compared with heterosexuals.

These findings come from a study of asthma severity among SGM people, with a special focus on the contribution of tobacco, reported Tugba Kaplan, MD, a resident in internal medicine at Luminis Health Anne Arundel Medical Center, Annapolis, Md.

“To the best of our knowledge, this is the first study assessing asthma severity among SGM people in a nationally representative longitudinal cohort study,” she said in an oral abstract session at the annual meeting of the American College of Chest Physicians (CHEST).

There has been only limited research on the health status and health needs of SGM people, and most of the studies conducted have focused on issues such as HIV/AIDS, sexual health, and substance use, not respiratory health, she said.
 

Following the PATH

Dr. Kaplan and colleagues drew on data from the Population Assessment of Tobacco and Health (PATH) Study, a nationally representative longitudinal cohort study with data on approximately 46,000 adults and adolescents in the United States.

The study uses self-reported data on tobacco use patterns; perceptions of risk and attitudes toward tobacco products; tobacco initiation, cessation, and relapse; and associated health outcomes.

The investigators combined data from three waves of the PATH Study, conducted from 2015 to 2019 on nonpregnant participants aged 18 years and older, and used mixed-effect logistic regression models to look for potential associations between sexual orientation and asthma severity.

They used standard definitions of asthma severity, based on lung function impairment measured by forced expiratory volume in 1 second and forced vital capacity, nighttime awakenings, use of a short-acting beta2-agonist for symptoms, interference with normal activity, and exacerbations requiring oral systemic corticosteroids.

The study also includes a sexual orientation question, asking participants, “do you consider yourself to be ...” with the options “straight, lesbian or gay, bisexual, something else, don’t know, or refused.”

Based on these responses, Dr. Kaplan and colleagues studied a total sample of 1,815 people who identify as SGM and 12,879 who identify as non-SGM.
 

Risks increased

In an analysis adjusted for age, sex, race/ethnicity, tobacco use, body mass index, physical activity, and asthma medication use, the authors found that, compared with non-SGM people, SGM respondents were significantly more likely to have had asthma attacks requiring steroid use in the past years (odds ratio, 1.47; 95% confidence interval, 1.01-2.15), asthma interfering with daily activities in the past month (OR, 1.33; CI, 1.10-1.61), and shortness of breath in any week over the 30 days (OR, 1.82; CI, 1.32-2.51). There was no significant difference between the groups in inhaler use over the past month, however.

They also found two interactions in the logistic regression models, one between urgent care visits and respondents who reported using both regular tobacco and e-cigarettes (dual users), and between exclusive e-cigarette use and waking up at night.

Among dual users, SGM respondents had a nearly fourfold greater risk for asthma attacks requiring urgent care visits, compared with non-SGM respondents (OR, 3.89; CI, 1.99-7.63). In contrast, among those who never used tobacco, there were no significant differences between the sexual orientation groups in regard to asthma attacks requiring urgent care visits.

Among those who reported using e-cigarettes exclusively, SGM respondents were nearly eight times more likely to report night awakening, compared with non-SGM users (OR, 7.81; CI, 2.93-20.8).

Among never users, in contrast, there was no significant difference in nighttime disturbances.
 

Possible confounders

The data suggest that “in the context of chronic illnesses like asthma, it is crucial to offer patients the knowledge and tools required to proficiently handle their conditions,” Dr. Kaplan said, adding that the differences seen between SGM and non-SGM respondents may be caused by health care disparities among SGM people that result in nonadherence to regular follow-ups.

In an interview, Jean Bourbeau, MD, MSc, who was a moderator for the session but was not involved in the study, commented that “we have to be very careful before making any conclusions, because this population could be at high risk for different reasons, and especially, do they get the same attention in terms of the care that is provided to the general population, and do they get access to the same medication?”

Nonetheless, Dr. Bourbeau continued, “I think this study is very important, because it shows us how much awareness we need to determine differences in populations, and [sexual orientation] is probably one thing that nobody had considered before, and for the first time we are now considering these potential differences in our population.”

The authors did not report a study funding source. Dr. Kaplan and Dr. Bourbeau reported having 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.

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.

HONOLULU – Patients with acute respiratory distress syndrome (ARDS) and coexisting pulmonary hypertension (PH) are significantly more likely to have longer and more costly hospital stays and to die in-hospital than patients with ARDS without PH, results of a retrospective study suggest.

Among more than 156,000 hospitalized patients with ARDS, 16.8% of whom also had a diagnosis of PH, the presence of PH was associated with about a 50% higher risk for in-hospital mortality and a 37% higher risk for longer hospital stays. In addition, the presence of PH was associated with nearly $20,000 of higher hospital expenditures, reported Kaushik Kumar, MBBS, at the annual meeting of the American College of Chest Physicians (CHEST).

“Clinicians should be vigilant in identifying and managing pulmonary hypertension in ARDS patients,” Dr. Kumar, a resident in internal medicine at Medstar Health, Baltimore, said in an oral abstract presentation.

He added that PH has the potential to serve as an indicator of disease severity for patients with ARDS.
 

National database

PH is a frequent complication of ARDS, likely related to a combination of pulmonary vasoconstriction, thromboembolism, and interstitial edema, he said.

To test their hypothesis that the presence of PH in patients with ARDS is associated with worse outcomes, Dr. Kumar and colleagues drew on the National Inpatient Sample database for information on adults aged 18 years and older who had been diagnosed with ARDS with or without PH.

They identified a total of 156,687 patients of whom 26,324 (16.8%) also had been diagnosed with PH. Among the cohort with PH, there were higher proportions of older patients, women, and patients with multiple comorbidities.

The in-hospital mortality rate was 36.8% among patients with PH, compared with 24.6% among those without. The mean length of stay was also longer among patients with PH, at 12 days versus 10 days.

In an unadjusted analysis, mean total hospital charges for patients with ARDS and PH were $210,165, versus $160,683 for patients with ARDS who did not have PH.

In an analysis in which the investigators controlled for age, sex, index admission length of stay, insurance status, and comorbidities, in-hospital mortality for patients with PH remained significantly higher, with an odds ratio of 1.52 (P < .001). PH was also significantly associated with longer length of stay (odds ratio, 1.37; P < .001) and higher total hospital costs, with a mean difference of $19,406.

Dr. Kumar said that the findings underscore the importance of a tailored approach to managing patients with ARDS, especially in the presence of PH.

The investigators plan further studies to assess the role of PH-targeted therapies, to examine the role of sepsis and right ventricular failure and to explore the long-term impact of PH among ARDS survivors, including effects with respect to pulmonary function, quality of life, and long-term morbidity.
 

Potential to inform practice

A pulmonologist who was not involved in the study said in an interview that the findings of the trial suggest that PH may have a greater influence on mortality than is currently understood and that further investigations into this association could change practice in the future.

“I think it would be very important for us to understand if that is going to change our outlook on how ARDS is managed. It’s possible that some of the interventions that we give people who don’t have pulmonary hypertension, for example, increasing the airway pressure in order to minimize oxygenation, may have a detrimental effect on the pulmonary vasculature,” said Timothy Morris, MD, medical director of the pulmonary and exercise lab and professor of medicine at the University of California, San Diego.

“I think it’s a little bit premature to say that this should guide management now, but it’s certainly an interesting question that may end up changing practice in the future,” said Dr. Morris, who was moderator of the session in which Dr. Kumar presented the data.

The study was supported by the Agency for Healthcare Research and Quality and Medstar Health Research Institute. Dr. Kumar and Dr. Morris have disclosed no relevant financial relationships.

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

HONOLULU – Patients with acute respiratory distress syndrome (ARDS) and coexisting pulmonary hypertension (PH) are significantly more likely to have longer and more costly hospital stays and to die in-hospital than patients with ARDS without PH, results of a retrospective study suggest.

Among more than 156,000 hospitalized patients with ARDS, 16.8% of whom also had a diagnosis of PH, the presence of PH was associated with about a 50% higher risk for in-hospital mortality and a 37% higher risk for longer hospital stays. In addition, the presence of PH was associated with nearly $20,000 of higher hospital expenditures, reported Kaushik Kumar, MBBS, at the annual meeting of the American College of Chest Physicians (CHEST).

“Clinicians should be vigilant in identifying and managing pulmonary hypertension in ARDS patients,” Dr. Kumar, a resident in internal medicine at Medstar Health, Baltimore, said in an oral abstract presentation.

He added that PH has the potential to serve as an indicator of disease severity for patients with ARDS.
 

National database

PH is a frequent complication of ARDS, likely related to a combination of pulmonary vasoconstriction, thromboembolism, and interstitial edema, he said.

To test their hypothesis that the presence of PH in patients with ARDS is associated with worse outcomes, Dr. Kumar and colleagues drew on the National Inpatient Sample database for information on adults aged 18 years and older who had been diagnosed with ARDS with or without PH.

They identified a total of 156,687 patients of whom 26,324 (16.8%) also had been diagnosed with PH. Among the cohort with PH, there were higher proportions of older patients, women, and patients with multiple comorbidities.

The in-hospital mortality rate was 36.8% among patients with PH, compared with 24.6% among those without. The mean length of stay was also longer among patients with PH, at 12 days versus 10 days.

In an unadjusted analysis, mean total hospital charges for patients with ARDS and PH were $210,165, versus $160,683 for patients with ARDS who did not have PH.

In an analysis in which the investigators controlled for age, sex, index admission length of stay, insurance status, and comorbidities, in-hospital mortality for patients with PH remained significantly higher, with an odds ratio of 1.52 (P < .001). PH was also significantly associated with longer length of stay (odds ratio, 1.37; P < .001) and higher total hospital costs, with a mean difference of $19,406.

Dr. Kumar said that the findings underscore the importance of a tailored approach to managing patients with ARDS, especially in the presence of PH.

The investigators plan further studies to assess the role of PH-targeted therapies, to examine the role of sepsis and right ventricular failure and to explore the long-term impact of PH among ARDS survivors, including effects with respect to pulmonary function, quality of life, and long-term morbidity.
 

Potential to inform practice

A pulmonologist who was not involved in the study said in an interview that the findings of the trial suggest that PH may have a greater influence on mortality than is currently understood and that further investigations into this association could change practice in the future.

“I think it would be very important for us to understand if that is going to change our outlook on how ARDS is managed. It’s possible that some of the interventions that we give people who don’t have pulmonary hypertension, for example, increasing the airway pressure in order to minimize oxygenation, may have a detrimental effect on the pulmonary vasculature,” said Timothy Morris, MD, medical director of the pulmonary and exercise lab and professor of medicine at the University of California, San Diego.

“I think it’s a little bit premature to say that this should guide management now, but it’s certainly an interesting question that may end up changing practice in the future,” said Dr. Morris, who was moderator of the session in which Dr. Kumar presented the data.

The study was supported by the Agency for Healthcare Research and Quality and Medstar Health Research Institute. Dr. Kumar and Dr. Morris have disclosed no relevant financial relationships.

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

HONOLULU – Patients with acute respiratory distress syndrome (ARDS) and coexisting pulmonary hypertension (PH) are significantly more likely to have longer and more costly hospital stays and to die in-hospital than patients with ARDS without PH, results of a retrospective study suggest.

Among more than 156,000 hospitalized patients with ARDS, 16.8% of whom also had a diagnosis of PH, the presence of PH was associated with about a 50% higher risk for in-hospital mortality and a 37% higher risk for longer hospital stays. In addition, the presence of PH was associated with nearly $20,000 of higher hospital expenditures, reported Kaushik Kumar, MBBS, at the annual meeting of the American College of Chest Physicians (CHEST).

“Clinicians should be vigilant in identifying and managing pulmonary hypertension in ARDS patients,” Dr. Kumar, a resident in internal medicine at Medstar Health, Baltimore, said in an oral abstract presentation.

He added that PH has the potential to serve as an indicator of disease severity for patients with ARDS.
 

National database

PH is a frequent complication of ARDS, likely related to a combination of pulmonary vasoconstriction, thromboembolism, and interstitial edema, he said.

To test their hypothesis that the presence of PH in patients with ARDS is associated with worse outcomes, Dr. Kumar and colleagues drew on the National Inpatient Sample database for information on adults aged 18 years and older who had been diagnosed with ARDS with or without PH.

They identified a total of 156,687 patients of whom 26,324 (16.8%) also had been diagnosed with PH. Among the cohort with PH, there were higher proportions of older patients, women, and patients with multiple comorbidities.

The in-hospital mortality rate was 36.8% among patients with PH, compared with 24.6% among those without. The mean length of stay was also longer among patients with PH, at 12 days versus 10 days.

In an unadjusted analysis, mean total hospital charges for patients with ARDS and PH were $210,165, versus $160,683 for patients with ARDS who did not have PH.

In an analysis in which the investigators controlled for age, sex, index admission length of stay, insurance status, and comorbidities, in-hospital mortality for patients with PH remained significantly higher, with an odds ratio of 1.52 (P < .001). PH was also significantly associated with longer length of stay (odds ratio, 1.37; P < .001) and higher total hospital costs, with a mean difference of $19,406.

Dr. Kumar said that the findings underscore the importance of a tailored approach to managing patients with ARDS, especially in the presence of PH.

The investigators plan further studies to assess the role of PH-targeted therapies, to examine the role of sepsis and right ventricular failure and to explore the long-term impact of PH among ARDS survivors, including effects with respect to pulmonary function, quality of life, and long-term morbidity.
 

Potential to inform practice

A pulmonologist who was not involved in the study said in an interview that the findings of the trial suggest that PH may have a greater influence on mortality than is currently understood and that further investigations into this association could change practice in the future.

“I think it would be very important for us to understand if that is going to change our outlook on how ARDS is managed. It’s possible that some of the interventions that we give people who don’t have pulmonary hypertension, for example, increasing the airway pressure in order to minimize oxygenation, may have a detrimental effect on the pulmonary vasculature,” said Timothy Morris, MD, medical director of the pulmonary and exercise lab and professor of medicine at the University of California, San Diego.

“I think it’s a little bit premature to say that this should guide management now, but it’s certainly an interesting question that may end up changing practice in the future,” said Dr. Morris, who was moderator of the session in which Dr. Kumar presented the data.

The study was supported by the Agency for Healthcare Research and Quality and Medstar Health Research Institute. Dr. Kumar and Dr. Morris have disclosed no relevant financial relationships.

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

MILAN – Studies are exploring hematopoietic stem cell transplantation (HSCT) as a rescue therapy in early-stage multiple sclerosis (MS), researchers told colleagues at the 9th Joint ECTRIMS-ACTRIMS meeting. But there’s no consensus over best practices.

“Is this a good alternative regarding treatment efficacy and risk? When should we switch from standard treatment? Should we switch from a low-efficacy treatment, from a previous high-efficacy treatment, or from two or more? There is no agreement on this at the moment,” said neurologist Lars Bø, MD, PhD, a professor at the University of Bergen (Norway).

However, rapid conversion to efficient treatment in the early stages of disease is turning out to be crucial, Dr. Bø said. “Early inflammatory activity has lasting effects. A delay from less than 2 years to 4-6 years has implications for disability.”

Where does HSCT fit in? According to Dr. Bø, a 2017 study found that newer treatments bring up to 50% of patients to no evidence of disease activity at 2 years compared with 70%-90% for HSCT. That study reported that “optimal candidates ... are young, ambulatory, and have inflammatory-active relapsing remitting MS.”

But other research is presenting a different picture with “data that doesn’t show such a clear-cut difference.” Dr. Bø highlighted a study published earlier this year that found that HSCT was “considerably superior” to fingolimod and “marginally superior” to natalizumab, but was not superior to ocrelizumab over shorter periods of time. As a result, “there is a need for further randomized trials comparing [HSCT] with these newer medications.”

Would it make sense to treat all younger patients with highly active MS? Research does suggest that “there’s a significant benefit in what we describe as aggressive [disease], high-disability, young age, very short disease lengths,” said neurologist Richard Nicholas, MBBS, of Imperial College London, in a separate presentation.

However, he cautioned that not everyone with highly active MS may be appropriate for HSCT. “That number could be as high as 15%, and “that’s a rather large group of people who would be treated with this therapy.” He suggested focusing on “the most important features”: “two or more relapses and also rapid accrual of disabilities.”

Dr. Nicholas also noted the findings of a study that he coauthored into HSCT versus alemtuzumab and ocrelizumab. The findings of that study were released at ECTRIMS and presented by neurologist Antonio Scalfari, MD, PhD, of Imperial College Healthcare NHS Trust.

The researchers tracked 103 patients after stem cell transplants (median, 45 months), 204 patients on alemtuzumab (median, 45 months), and 314 patients on ocrelizumab (median, 35 months). Those who received transplants had a 74% lower risk of relapse versus alemtuzumab, and a 66% lower risk of new MS activity detected via MRI. Compared with ocrelizumab, patients who received stem cell transplants had a 60% lower risk of relapse but the same risk of MS activity detected via MRI.

The researchers noted that the patients who underwent stem cell transplantation had numerous adverse effects.

What happens now? “HSCT should be available for our MS patients when standard treatment is no longer effective,” Dr. Bø said. “When treatment options are limited, it is likely to have a good effect in younger patients with a shorter disease duration and a low disability.”

He added that “there is an increasing use of high-efficacy treatment early in RRMS [relapsing-remitting MS], and this may make the subgroup with indication for HSCT as a rescue therapy smaller.”

Meanwhile, he said, “demonstrating a higher efficacy may require larger studies and a combined analysis of data from the ongoing randomized trials. Also, there is a need for follow-up longer than 2 or 3 years for the estimation of cost versus benefit for this treatment.”

Dr. Bø disclosed receiving speaker fees from Novartis and consulting fees from Viatris. Dr. Nicholas disclosed speaker advisory board relationships with Roche and Novartis.

MILAN – Studies are exploring hematopoietic stem cell transplantation (HSCT) as a rescue therapy in early-stage multiple sclerosis (MS), researchers told colleagues at the 9th Joint ECTRIMS-ACTRIMS meeting. But there’s no consensus over best practices.

“Is this a good alternative regarding treatment efficacy and risk? When should we switch from standard treatment? Should we switch from a low-efficacy treatment, from a previous high-efficacy treatment, or from two or more? There is no agreement on this at the moment,” said neurologist Lars Bø, MD, PhD, a professor at the University of Bergen (Norway).

However, rapid conversion to efficient treatment in the early stages of disease is turning out to be crucial, Dr. Bø said. “Early inflammatory activity has lasting effects. A delay from less than 2 years to 4-6 years has implications for disability.”

Where does HSCT fit in? According to Dr. Bø, a 2017 study found that newer treatments bring up to 50% of patients to no evidence of disease activity at 2 years compared with 70%-90% for HSCT. That study reported that “optimal candidates ... are young, ambulatory, and have inflammatory-active relapsing remitting MS.”

But other research is presenting a different picture with “data that doesn’t show such a clear-cut difference.” Dr. Bø highlighted a study published earlier this year that found that HSCT was “considerably superior” to fingolimod and “marginally superior” to natalizumab, but was not superior to ocrelizumab over shorter periods of time. As a result, “there is a need for further randomized trials comparing [HSCT] with these newer medications.”

Would it make sense to treat all younger patients with highly active MS? Research does suggest that “there’s a significant benefit in what we describe as aggressive [disease], high-disability, young age, very short disease lengths,” said neurologist Richard Nicholas, MBBS, of Imperial College London, in a separate presentation.

However, he cautioned that not everyone with highly active MS may be appropriate for HSCT. “That number could be as high as 15%, and “that’s a rather large group of people who would be treated with this therapy.” He suggested focusing on “the most important features”: “two or more relapses and also rapid accrual of disabilities.”

Dr. Nicholas also noted the findings of a study that he coauthored into HSCT versus alemtuzumab and ocrelizumab. The findings of that study were released at ECTRIMS and presented by neurologist Antonio Scalfari, MD, PhD, of Imperial College Healthcare NHS Trust.

The researchers tracked 103 patients after stem cell transplants (median, 45 months), 204 patients on alemtuzumab (median, 45 months), and 314 patients on ocrelizumab (median, 35 months). Those who received transplants had a 74% lower risk of relapse versus alemtuzumab, and a 66% lower risk of new MS activity detected via MRI. Compared with ocrelizumab, patients who received stem cell transplants had a 60% lower risk of relapse but the same risk of MS activity detected via MRI.

The researchers noted that the patients who underwent stem cell transplantation had numerous adverse effects.

What happens now? “HSCT should be available for our MS patients when standard treatment is no longer effective,” Dr. Bø said. “When treatment options are limited, it is likely to have a good effect in younger patients with a shorter disease duration and a low disability.”

He added that “there is an increasing use of high-efficacy treatment early in RRMS [relapsing-remitting MS], and this may make the subgroup with indication for HSCT as a rescue therapy smaller.”

Meanwhile, he said, “demonstrating a higher efficacy may require larger studies and a combined analysis of data from the ongoing randomized trials. Also, there is a need for follow-up longer than 2 or 3 years for the estimation of cost versus benefit for this treatment.”

Dr. Bø disclosed receiving speaker fees from Novartis and consulting fees from Viatris. Dr. Nicholas disclosed speaker advisory board relationships with Roche and Novartis.

MILAN – Studies are exploring hematopoietic stem cell transplantation (HSCT) as a rescue therapy in early-stage multiple sclerosis (MS), researchers told colleagues at the 9th Joint ECTRIMS-ACTRIMS meeting. But there’s no consensus over best practices.

“Is this a good alternative regarding treatment efficacy and risk? When should we switch from standard treatment? Should we switch from a low-efficacy treatment, from a previous high-efficacy treatment, or from two or more? There is no agreement on this at the moment,” said neurologist Lars Bø, MD, PhD, a professor at the University of Bergen (Norway).

However, rapid conversion to efficient treatment in the early stages of disease is turning out to be crucial, Dr. Bø said. “Early inflammatory activity has lasting effects. A delay from less than 2 years to 4-6 years has implications for disability.”

Where does HSCT fit in? According to Dr. Bø, a 2017 study found that newer treatments bring up to 50% of patients to no evidence of disease activity at 2 years compared with 70%-90% for HSCT. That study reported that “optimal candidates ... are young, ambulatory, and have inflammatory-active relapsing remitting MS.”

But other research is presenting a different picture with “data that doesn’t show such a clear-cut difference.” Dr. Bø highlighted a study published earlier this year that found that HSCT was “considerably superior” to fingolimod and “marginally superior” to natalizumab, but was not superior to ocrelizumab over shorter periods of time. As a result, “there is a need for further randomized trials comparing [HSCT] with these newer medications.”

Would it make sense to treat all younger patients with highly active MS? Research does suggest that “there’s a significant benefit in what we describe as aggressive [disease], high-disability, young age, very short disease lengths,” said neurologist Richard Nicholas, MBBS, of Imperial College London, in a separate presentation.

However, he cautioned that not everyone with highly active MS may be appropriate for HSCT. “That number could be as high as 15%, and “that’s a rather large group of people who would be treated with this therapy.” He suggested focusing on “the most important features”: “two or more relapses and also rapid accrual of disabilities.”

Dr. Nicholas also noted the findings of a study that he coauthored into HSCT versus alemtuzumab and ocrelizumab. The findings of that study were released at ECTRIMS and presented by neurologist Antonio Scalfari, MD, PhD, of Imperial College Healthcare NHS Trust.

The researchers tracked 103 patients after stem cell transplants (median, 45 months), 204 patients on alemtuzumab (median, 45 months), and 314 patients on ocrelizumab (median, 35 months). Those who received transplants had a 74% lower risk of relapse versus alemtuzumab, and a 66% lower risk of new MS activity detected via MRI. Compared with ocrelizumab, patients who received stem cell transplants had a 60% lower risk of relapse but the same risk of MS activity detected via MRI.

The researchers noted that the patients who underwent stem cell transplantation had numerous adverse effects.

What happens now? “HSCT should be available for our MS patients when standard treatment is no longer effective,” Dr. Bø said. “When treatment options are limited, it is likely to have a good effect in younger patients with a shorter disease duration and a low disability.”

He added that “there is an increasing use of high-efficacy treatment early in RRMS [relapsing-remitting MS], and this may make the subgroup with indication for HSCT as a rescue therapy smaller.”

Meanwhile, he said, “demonstrating a higher efficacy may require larger studies and a combined analysis of data from the ongoing randomized trials. Also, there is a need for follow-up longer than 2 or 3 years for the estimation of cost versus benefit for this treatment.”

Dr. Bø disclosed receiving speaker fees from Novartis and consulting fees from Viatris. Dr. Nicholas disclosed speaker advisory board relationships with Roche and Novartis.

BARCELONA – Electrodermal activity (EDA) measured via a smart bracelet/wristband may help predict and track changes in mood and more rapidly assess treatment response in patients with bipolar disorder (BD), early research suggests.

In a small observational pilot study, researchers found the E4 wristband (Empatica Inc) was able to detect fluctuations in mood.

The results highlight the potential of EDA to serve as an objective BD biomarker, noted the investigators, led by Diego Hidalgo-Mazzei, MD, PhD, Bipolar and Depressive Disorders Unit, University of Barcelona.

The findings were presented at the 36th European College of Neuropsychopharmacology (ECNP) Congress.
 

A need for objective markers

The evaluation of BD currently consists of clinical interviews, questionnaires, and scales, which largely rely on physician assessment, highlighting the need for objective biomarkers.

Previous studies show that EDA, which tracks changes in the skin due to sweat gland activity in response to psychological stimuli, is reduced in unipolar depression.

The researchers hypothesized that EDA could be a biomarker of mood changes in patients with BD. They recruited 38 patients experiencing manic (n = 12) or depressive (n = 9) episodes or who were euthymic (n = 17) and compared their responses with those of 19 healthy control persons.

Study participants were asked to wear the wristband continuously for approximately 48 hours to measure EDA, motion-based activity, blood volume pulse, and skin temperature.

The 48-hour monitoring session was determined by the battery life of the device, Dr. Hidalgo-Mazzei said in an interview.

The acute-phase patients in the study had three sessions at different time points – one during the acute state, another when the clinician determined there was a response to treatment, and again at remission. Euthymic patients and healthy control persons had a single monitoring session.

Dr. Hidalgo-Mazzei said the study’s protocol is unique because it involves unusually long sessions with the device. In this setup, each sensor collects a sample every second, resulting in highly detailed and granular data.

“At the end, it is a trade-off, as handling such an enormous amount of data for each session requires equally large preprocessing, computing power, and analysis,” he said.

Dr. Hidalgo-Mazzei characterized compliance with the device as “outstanding” for the majority of study participants.

Results showed that mean EDA was notably and significantly lower in BD patients during depressive episodes in comparison with those in other groups. Patients with depression also had significantly less frequent EDA peaks per minute (P = .001 for both).

There were also significant differences in EDA measures between baseline and after treatment in the acute BD groups.

Patients with depression had significant increases in mean EDA (P = .033), EDA peaks per minute (P = .002), and the mean amplitude of EDA peaks (P = .001) from baseline, while manic patients experienced a decrease in the mean amplitude of EDA peaks (P = .001).

It is important for the patient and doctor to know how and when mood fluctuations take place, said Dr. Hidalgo-Mazzei, because treatment for manic and depressive states differ.

“Until now, these mood swings have mostly been diagnosed subjectively, through interview with doctors or by questionnaires, and this had led to real difficulties.

“Arriving at the correct drug is difficult, with only around 30% to 40% of treated individuals having the expected response. We hope that the additional information these systems can provide will give us greater certainty in treating patients.”

However, Dr. Hidalgo-Mazzei said that is still a long way off, noting that this is an exploratory, observational study.

“We need to look at a larger sample and use machine learning to analyze all the biomarkers collected by the wearers to confirm the findings,” he said.
 

A true biomarker?

In a comment, Joseph F. Goldberg, MD, clinical professor of psychiatry at Icahn School of Medicine at Mount Sinai, New York, said the study is an “interesting use of this technology to differentiate physiological correlates of mood states.”

However, he said the findings are limited and preliminary because the sample sizes were small and the measures weren’t repeated.

In addition, medications or other factors that may influence electrophysiologic activity, such as anxiety or panic, were not considered, and Dr. Goldberg noted the researchers did not compare the results with those in patients with other diagnoses.

“So, I don’t think one could call this a biomarker in the sense of having diagnostic specificity,” he said, making the comparison with body temperature, which “goes up in an infection; but fever alone doesn’t tell us much about the nature or cause of a presumed infection. More studies are needed before generalizable conclusion can be drawn.”

Also commenting on the research, Paolo Ossola, MD, PhD, assistant professor of psychiatry, department of medicine and surgery, University of Parma, Italy, described the study as exploratory but preliminary.

He said the researchers have “laid the foundation for a new approach to diagnosing and treating bipolar disorders.

“The shift from the subjective to the biological level could also promote understanding of the underlying mechanistic dynamics of mood swings.”

The study was funded by the Instituto de Salud Carlos III and a Baszucki Brain Research Fund grant from the Milken Foundation. The authors have disclosed no relevant financial relationships.
 

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

BARCELONA – Electrodermal activity (EDA) measured via a smart bracelet/wristband may help predict and track changes in mood and more rapidly assess treatment response in patients with bipolar disorder (BD), early research suggests.

In a small observational pilot study, researchers found the E4 wristband (Empatica Inc) was able to detect fluctuations in mood.

The results highlight the potential of EDA to serve as an objective BD biomarker, noted the investigators, led by Diego Hidalgo-Mazzei, MD, PhD, Bipolar and Depressive Disorders Unit, University of Barcelona.

The findings were presented at the 36th European College of Neuropsychopharmacology (ECNP) Congress.
 

A need for objective markers

The evaluation of BD currently consists of clinical interviews, questionnaires, and scales, which largely rely on physician assessment, highlighting the need for objective biomarkers.

Previous studies show that EDA, which tracks changes in the skin due to sweat gland activity in response to psychological stimuli, is reduced in unipolar depression.

The researchers hypothesized that EDA could be a biomarker of mood changes in patients with BD. They recruited 38 patients experiencing manic (n = 12) or depressive (n = 9) episodes or who were euthymic (n = 17) and compared their responses with those of 19 healthy control persons.

Study participants were asked to wear the wristband continuously for approximately 48 hours to measure EDA, motion-based activity, blood volume pulse, and skin temperature.

The 48-hour monitoring session was determined by the battery life of the device, Dr. Hidalgo-Mazzei said in an interview.

The acute-phase patients in the study had three sessions at different time points – one during the acute state, another when the clinician determined there was a response to treatment, and again at remission. Euthymic patients and healthy control persons had a single monitoring session.

Dr. Hidalgo-Mazzei said the study’s protocol is unique because it involves unusually long sessions with the device. In this setup, each sensor collects a sample every second, resulting in highly detailed and granular data.

“At the end, it is a trade-off, as handling such an enormous amount of data for each session requires equally large preprocessing, computing power, and analysis,” he said.

Dr. Hidalgo-Mazzei characterized compliance with the device as “outstanding” for the majority of study participants.

Results showed that mean EDA was notably and significantly lower in BD patients during depressive episodes in comparison with those in other groups. Patients with depression also had significantly less frequent EDA peaks per minute (P = .001 for both).

There were also significant differences in EDA measures between baseline and after treatment in the acute BD groups.

Patients with depression had significant increases in mean EDA (P = .033), EDA peaks per minute (P = .002), and the mean amplitude of EDA peaks (P = .001) from baseline, while manic patients experienced a decrease in the mean amplitude of EDA peaks (P = .001).

It is important for the patient and doctor to know how and when mood fluctuations take place, said Dr. Hidalgo-Mazzei, because treatment for manic and depressive states differ.

“Until now, these mood swings have mostly been diagnosed subjectively, through interview with doctors or by questionnaires, and this had led to real difficulties.

“Arriving at the correct drug is difficult, with only around 30% to 40% of treated individuals having the expected response. We hope that the additional information these systems can provide will give us greater certainty in treating patients.”

However, Dr. Hidalgo-Mazzei said that is still a long way off, noting that this is an exploratory, observational study.

“We need to look at a larger sample and use machine learning to analyze all the biomarkers collected by the wearers to confirm the findings,” he said.
 

A true biomarker?

In a comment, Joseph F. Goldberg, MD, clinical professor of psychiatry at Icahn School of Medicine at Mount Sinai, New York, said the study is an “interesting use of this technology to differentiate physiological correlates of mood states.”

However, he said the findings are limited and preliminary because the sample sizes were small and the measures weren’t repeated.

In addition, medications or other factors that may influence electrophysiologic activity, such as anxiety or panic, were not considered, and Dr. Goldberg noted the researchers did not compare the results with those in patients with other diagnoses.

“So, I don’t think one could call this a biomarker in the sense of having diagnostic specificity,” he said, making the comparison with body temperature, which “goes up in an infection; but fever alone doesn’t tell us much about the nature or cause of a presumed infection. More studies are needed before generalizable conclusion can be drawn.”

Also commenting on the research, Paolo Ossola, MD, PhD, assistant professor of psychiatry, department of medicine and surgery, University of Parma, Italy, described the study as exploratory but preliminary.

He said the researchers have “laid the foundation for a new approach to diagnosing and treating bipolar disorders.

“The shift from the subjective to the biological level could also promote understanding of the underlying mechanistic dynamics of mood swings.”

The study was funded by the Instituto de Salud Carlos III and a Baszucki Brain Research Fund grant from the Milken Foundation. The authors have disclosed no relevant financial relationships.
 

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

BARCELONA – Electrodermal activity (EDA) measured via a smart bracelet/wristband may help predict and track changes in mood and more rapidly assess treatment response in patients with bipolar disorder (BD), early research suggests.

In a small observational pilot study, researchers found the E4 wristband (Empatica Inc) was able to detect fluctuations in mood.

The results highlight the potential of EDA to serve as an objective BD biomarker, noted the investigators, led by Diego Hidalgo-Mazzei, MD, PhD, Bipolar and Depressive Disorders Unit, University of Barcelona.

The findings were presented at the 36th European College of Neuropsychopharmacology (ECNP) Congress.
 

A need for objective markers

The evaluation of BD currently consists of clinical interviews, questionnaires, and scales, which largely rely on physician assessment, highlighting the need for objective biomarkers.

Previous studies show that EDA, which tracks changes in the skin due to sweat gland activity in response to psychological stimuli, is reduced in unipolar depression.

The researchers hypothesized that EDA could be a biomarker of mood changes in patients with BD. They recruited 38 patients experiencing manic (n = 12) or depressive (n = 9) episodes or who were euthymic (n = 17) and compared their responses with those of 19 healthy control persons.

Study participants were asked to wear the wristband continuously for approximately 48 hours to measure EDA, motion-based activity, blood volume pulse, and skin temperature.

The 48-hour monitoring session was determined by the battery life of the device, Dr. Hidalgo-Mazzei said in an interview.

The acute-phase patients in the study had three sessions at different time points – one during the acute state, another when the clinician determined there was a response to treatment, and again at remission. Euthymic patients and healthy control persons had a single monitoring session.

Dr. Hidalgo-Mazzei said the study’s protocol is unique because it involves unusually long sessions with the device. In this setup, each sensor collects a sample every second, resulting in highly detailed and granular data.

“At the end, it is a trade-off, as handling such an enormous amount of data for each session requires equally large preprocessing, computing power, and analysis,” he said.

Dr. Hidalgo-Mazzei characterized compliance with the device as “outstanding” for the majority of study participants.

Results showed that mean EDA was notably and significantly lower in BD patients during depressive episodes in comparison with those in other groups. Patients with depression also had significantly less frequent EDA peaks per minute (P = .001 for both).

There were also significant differences in EDA measures between baseline and after treatment in the acute BD groups.

Patients with depression had significant increases in mean EDA (P = .033), EDA peaks per minute (P = .002), and the mean amplitude of EDA peaks (P = .001) from baseline, while manic patients experienced a decrease in the mean amplitude of EDA peaks (P = .001).

It is important for the patient and doctor to know how and when mood fluctuations take place, said Dr. Hidalgo-Mazzei, because treatment for manic and depressive states differ.

“Until now, these mood swings have mostly been diagnosed subjectively, through interview with doctors or by questionnaires, and this had led to real difficulties.

“Arriving at the correct drug is difficult, with only around 30% to 40% of treated individuals having the expected response. We hope that the additional information these systems can provide will give us greater certainty in treating patients.”

However, Dr. Hidalgo-Mazzei said that is still a long way off, noting that this is an exploratory, observational study.

“We need to look at a larger sample and use machine learning to analyze all the biomarkers collected by the wearers to confirm the findings,” he said.
 

A true biomarker?

In a comment, Joseph F. Goldberg, MD, clinical professor of psychiatry at Icahn School of Medicine at Mount Sinai, New York, said the study is an “interesting use of this technology to differentiate physiological correlates of mood states.”

However, he said the findings are limited and preliminary because the sample sizes were small and the measures weren’t repeated.

In addition, medications or other factors that may influence electrophysiologic activity, such as anxiety or panic, were not considered, and Dr. Goldberg noted the researchers did not compare the results with those in patients with other diagnoses.

“So, I don’t think one could call this a biomarker in the sense of having diagnostic specificity,” he said, making the comparison with body temperature, which “goes up in an infection; but fever alone doesn’t tell us much about the nature or cause of a presumed infection. More studies are needed before generalizable conclusion can be drawn.”

Also commenting on the research, Paolo Ossola, MD, PhD, assistant professor of psychiatry, department of medicine and surgery, University of Parma, Italy, described the study as exploratory but preliminary.

He said the researchers have “laid the foundation for a new approach to diagnosing and treating bipolar disorders.

“The shift from the subjective to the biological level could also promote understanding of the underlying mechanistic dynamics of mood swings.”

The study was funded by the Instituto de Salud Carlos III and a Baszucki Brain Research Fund grant from the Milken Foundation. The authors have disclosed no relevant financial relationships.
 

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

MILAN – A weight loss intervention tailored to patients with multiple sclerosis (MS) and comorbid obesity achieved clinically meaningful weight loss, resulting in improved mobility, reduced fatigue, and better quality of life, results of a new trial show.

Seventy patients with MS and a high body mass index (BMI) were randomized to receive a multifaceted weight loss program or treatment as usual, resulting in almost two-thirds of the intervention group patients losing at least 5% of their body weight.

“Our weight loss intervention achieved clinically significant weight loss and improved mental quality of life,” said study presenter Sharon G. Lynch, MD, professor in the department of neurology at the University of Kansas Medical Center, Kansas City.

The results also showed weight loss “was associated with improved mobility, reduced fatigability, and improved physical quality of life.”

The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
 

Obesity linked to MS progression

Dr. Lynch noted that almost 40% of people with MS have comorbid obesity, and that obesity “is associated with developing MS in some studies, and also disease progression.” Moreover, MS and obesity share common chronic symptoms, particularly mobility problems, depression, fatigue, and reduced quality of life.

Despite this, no randomized controlled trials have been specifically designed to help people with MS lose weight, he noted.

The team therefore examined the efficacy of a behavioral weight loss program designed for patients with the disease, as well as the impact of weight loss on mobility and other chronic symptoms.

The participants were required to be English speaking, with access to a telephone and/or computer, and to have a confirmed diagnosis of MS. They also had to be aged 18-70 years, have a BMI of 29-50 kg/m², and have a Patient-Determined Disease Steps (PDDS) score of less than 4.

The patients were randomly assigned to receive either a weight loss intervention or brief health education and treatment as usual. They were assessed at 6 months to measure their weight loss, mobility, and self-reported quality of life and perceived fatigability.

Dr. Lynch said the intervention was “fairly time intensive,” with an hour-long telehealth group weight loss session every week for 24 weeks, as well as monthly individual sessions for 6 months.

The participants were provided with a Fitbit activity tracker, a set of Bluetooth-enabled weighing scales, and access to the Lose It! weight loss app.

Caloric restriction was encouraged, with a focus on increasing intake of fruits and vegetables, alongside a target of 150 minutes per week of moderate to vigorous physical activity, in line with Centers for Disease Control and Prevention and American Heart Association recommendations.
 

Significant loss in body weight

Seventy individuals with MS took part in the trial, of whom 83% were female and 88% were White, 9% African American, and 3% Hispanic or Latino. The mean age was 46.7 years, and the mean number of years in education was 11.8.

The vast majority (96%) of the participants had relapsing remitting MS, at a mean disease duration of 10.9 years, and 82% had a score of 0 or 1 on the PDDS.

Dr. Lynch showed that participants in the intervention group lost, over the course of the study, 8.6% of their total body weight, compared with a loss of 0.7% among controls (P < .001).

Moreover, 65% of the intervention group lost at least 5% of their body weight, whereas 41% lost at least 10% of their body weight, which again was significantly higher than that seen in the control group (P < .001).

There was also a significant increase in moderate to vigorous physical activity in the intervention group as measured by accelerometry (P < .05), although Dr. Lynch pointed out this “did not necessarily correlate with their weight loss.”

Dr. Lynch showed there were significant differences across a range of anthropometric measures from baseline to follow-up between the intervention and control groups.

The adjusted difference in weight loss between the intervention and control participants was 7.8 kg, whereas the difference in reduction of BMI was 2.7 (P = .001 for both).

There was also a significant difference in the reduction in waist-to-hip ratio between the groups, at 0.033 in favor of the intervention, as well as a difference in the reduction in fat tissue, at 3.1% (P = .001 for both).

Further analyses showed weight loss was associated with significant improvements on the 6-minute walk test, at an r value of 0.48 (P = .015), and in the 25-foot walk test (r = 0.42; P = .015). Weight loss was also linked to reductions in perceived fatigability (r = 0.48; P = .005).

Dr. Lynch also reported that a 5% reduction in body weight was associated with a “clinically meaningful” improvement of 50 meters on the 6-minute walk test.

Finally, it was found the intervention was associated with a significant improvement in mental quality of life (P = .01), whereas weight loss specifically was linked to improved physical quality of life (P = .02).

“We believe that future studies should examine weight loss in people with MS who have more advanced disability,” Dr. Lynch said, and “we should examine the effects of weight loss on the underlying disease processes.”

She added they also “need to follow the patient for longer and see if they can maintain their weight loss.”
 

Emphasizing the social side of interventions

Session cochair Brian M. Sandroff, PhD, director of the Exercise Neurorehabilitation Research Laboratory at the Kessler Foundation, East Hanover, N.J., commented that the results are “really exciting.”

He said that the improvements across the range of measures assessed in the study were not surprising, “considering the intervention was multicomponent, and so had the potential to affect a number of different physical and cognitive domains.”

One factor in managing MS that came up again and again during the discussion at the end of the session was the social aspect of interventions, with Dr. Lynch saying the group sessions in particular were appreciated by participants in her trial.

Dr. Sandroff, who was not involved in the study, said that it has been questioned whether the social side should be controlled for when assessing interventions, or “maybe it’s something we should promote within our studies.”

He explained that being social “overcomes a lot of isolation-related issues among people with MS who have comorbidities,” which can result in “reduced quality of life and differences in symptomatic manifestations.”

“Providing that group setting might have lots of outcomes besides just a biological loss of mass” because of the intervention itself, Dr. Sandroff said.

The study was supported by grants from the National MS Society. Dr. Lynch declares relationships with Biogen, Genzyme, Teva, Sanofi, Novartis, Celgene, Roche, Immunic, National Institutes of Health, National Multiple Sclerosis Society, Patient-Centered Outcomes Research Institute, Anokion, TG Therapeutics, and Actelion. Other authors also declared relationships. Dr. Sandroff declared no relevant relationships.

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

MILAN – A weight loss intervention tailored to patients with multiple sclerosis (MS) and comorbid obesity achieved clinically meaningful weight loss, resulting in improved mobility, reduced fatigue, and better quality of life, results of a new trial show.

Seventy patients with MS and a high body mass index (BMI) were randomized to receive a multifaceted weight loss program or treatment as usual, resulting in almost two-thirds of the intervention group patients losing at least 5% of their body weight.

“Our weight loss intervention achieved clinically significant weight loss and improved mental quality of life,” said study presenter Sharon G. Lynch, MD, professor in the department of neurology at the University of Kansas Medical Center, Kansas City.

The results also showed weight loss “was associated with improved mobility, reduced fatigability, and improved physical quality of life.”

The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
 

Obesity linked to MS progression

Dr. Lynch noted that almost 40% of people with MS have comorbid obesity, and that obesity “is associated with developing MS in some studies, and also disease progression.” Moreover, MS and obesity share common chronic symptoms, particularly mobility problems, depression, fatigue, and reduced quality of life.

Despite this, no randomized controlled trials have been specifically designed to help people with MS lose weight, he noted.

The team therefore examined the efficacy of a behavioral weight loss program designed for patients with the disease, as well as the impact of weight loss on mobility and other chronic symptoms.

The participants were required to be English speaking, with access to a telephone and/or computer, and to have a confirmed diagnosis of MS. They also had to be aged 18-70 years, have a BMI of 29-50 kg/m², and have a Patient-Determined Disease Steps (PDDS) score of less than 4.

The patients were randomly assigned to receive either a weight loss intervention or brief health education and treatment as usual. They were assessed at 6 months to measure their weight loss, mobility, and self-reported quality of life and perceived fatigability.

Dr. Lynch said the intervention was “fairly time intensive,” with an hour-long telehealth group weight loss session every week for 24 weeks, as well as monthly individual sessions for 6 months.

The participants were provided with a Fitbit activity tracker, a set of Bluetooth-enabled weighing scales, and access to the Lose It! weight loss app.

Caloric restriction was encouraged, with a focus on increasing intake of fruits and vegetables, alongside a target of 150 minutes per week of moderate to vigorous physical activity, in line with Centers for Disease Control and Prevention and American Heart Association recommendations.
 

Significant loss in body weight

Seventy individuals with MS took part in the trial, of whom 83% were female and 88% were White, 9% African American, and 3% Hispanic or Latino. The mean age was 46.7 years, and the mean number of years in education was 11.8.

The vast majority (96%) of the participants had relapsing remitting MS, at a mean disease duration of 10.9 years, and 82% had a score of 0 or 1 on the PDDS.

Dr. Lynch showed that participants in the intervention group lost, over the course of the study, 8.6% of their total body weight, compared with a loss of 0.7% among controls (P < .001).

Moreover, 65% of the intervention group lost at least 5% of their body weight, whereas 41% lost at least 10% of their body weight, which again was significantly higher than that seen in the control group (P < .001).

There was also a significant increase in moderate to vigorous physical activity in the intervention group as measured by accelerometry (P < .05), although Dr. Lynch pointed out this “did not necessarily correlate with their weight loss.”

Dr. Lynch showed there were significant differences across a range of anthropometric measures from baseline to follow-up between the intervention and control groups.

The adjusted difference in weight loss between the intervention and control participants was 7.8 kg, whereas the difference in reduction of BMI was 2.7 (P = .001 for both).

There was also a significant difference in the reduction in waist-to-hip ratio between the groups, at 0.033 in favor of the intervention, as well as a difference in the reduction in fat tissue, at 3.1% (P = .001 for both).

Further analyses showed weight loss was associated with significant improvements on the 6-minute walk test, at an r value of 0.48 (P = .015), and in the 25-foot walk test (r = 0.42; P = .015). Weight loss was also linked to reductions in perceived fatigability (r = 0.48; P = .005).

Dr. Lynch also reported that a 5% reduction in body weight was associated with a “clinically meaningful” improvement of 50 meters on the 6-minute walk test.

Finally, it was found the intervention was associated with a significant improvement in mental quality of life (P = .01), whereas weight loss specifically was linked to improved physical quality of life (P = .02).

“We believe that future studies should examine weight loss in people with MS who have more advanced disability,” Dr. Lynch said, and “we should examine the effects of weight loss on the underlying disease processes.”

She added they also “need to follow the patient for longer and see if they can maintain their weight loss.”
 

Emphasizing the social side of interventions

Session cochair Brian M. Sandroff, PhD, director of the Exercise Neurorehabilitation Research Laboratory at the Kessler Foundation, East Hanover, N.J., commented that the results are “really exciting.”

He said that the improvements across the range of measures assessed in the study were not surprising, “considering the intervention was multicomponent, and so had the potential to affect a number of different physical and cognitive domains.”

One factor in managing MS that came up again and again during the discussion at the end of the session was the social aspect of interventions, with Dr. Lynch saying the group sessions in particular were appreciated by participants in her trial.

Dr. Sandroff, who was not involved in the study, said that it has been questioned whether the social side should be controlled for when assessing interventions, or “maybe it’s something we should promote within our studies.”

He explained that being social “overcomes a lot of isolation-related issues among people with MS who have comorbidities,” which can result in “reduced quality of life and differences in symptomatic manifestations.”

“Providing that group setting might have lots of outcomes besides just a biological loss of mass” because of the intervention itself, Dr. Sandroff said.

The study was supported by grants from the National MS Society. Dr. Lynch declares relationships with Biogen, Genzyme, Teva, Sanofi, Novartis, Celgene, Roche, Immunic, National Institutes of Health, National Multiple Sclerosis Society, Patient-Centered Outcomes Research Institute, Anokion, TG Therapeutics, and Actelion. Other authors also declared relationships. Dr. Sandroff declared no relevant relationships.

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

MILAN – A weight loss intervention tailored to patients with multiple sclerosis (MS) and comorbid obesity achieved clinically meaningful weight loss, resulting in improved mobility, reduced fatigue, and better quality of life, results of a new trial show.

Seventy patients with MS and a high body mass index (BMI) were randomized to receive a multifaceted weight loss program or treatment as usual, resulting in almost two-thirds of the intervention group patients losing at least 5% of their body weight.

“Our weight loss intervention achieved clinically significant weight loss and improved mental quality of life,” said study presenter Sharon G. Lynch, MD, professor in the department of neurology at the University of Kansas Medical Center, Kansas City.

The results also showed weight loss “was associated with improved mobility, reduced fatigability, and improved physical quality of life.”

The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
 

Obesity linked to MS progression

Dr. Lynch noted that almost 40% of people with MS have comorbid obesity, and that obesity “is associated with developing MS in some studies, and also disease progression.” Moreover, MS and obesity share common chronic symptoms, particularly mobility problems, depression, fatigue, and reduced quality of life.

Despite this, no randomized controlled trials have been specifically designed to help people with MS lose weight, he noted.

The team therefore examined the efficacy of a behavioral weight loss program designed for patients with the disease, as well as the impact of weight loss on mobility and other chronic symptoms.

The participants were required to be English speaking, with access to a telephone and/or computer, and to have a confirmed diagnosis of MS. They also had to be aged 18-70 years, have a BMI of 29-50 kg/m², and have a Patient-Determined Disease Steps (PDDS) score of less than 4.

The patients were randomly assigned to receive either a weight loss intervention or brief health education and treatment as usual. They were assessed at 6 months to measure their weight loss, mobility, and self-reported quality of life and perceived fatigability.

Dr. Lynch said the intervention was “fairly time intensive,” with an hour-long telehealth group weight loss session every week for 24 weeks, as well as monthly individual sessions for 6 months.

The participants were provided with a Fitbit activity tracker, a set of Bluetooth-enabled weighing scales, and access to the Lose It! weight loss app.

Caloric restriction was encouraged, with a focus on increasing intake of fruits and vegetables, alongside a target of 150 minutes per week of moderate to vigorous physical activity, in line with Centers for Disease Control and Prevention and American Heart Association recommendations.
 

Significant loss in body weight

Seventy individuals with MS took part in the trial, of whom 83% were female and 88% were White, 9% African American, and 3% Hispanic or Latino. The mean age was 46.7 years, and the mean number of years in education was 11.8.

The vast majority (96%) of the participants had relapsing remitting MS, at a mean disease duration of 10.9 years, and 82% had a score of 0 or 1 on the PDDS.

Dr. Lynch showed that participants in the intervention group lost, over the course of the study, 8.6% of their total body weight, compared with a loss of 0.7% among controls (P < .001).

Moreover, 65% of the intervention group lost at least 5% of their body weight, whereas 41% lost at least 10% of their body weight, which again was significantly higher than that seen in the control group (P < .001).

There was also a significant increase in moderate to vigorous physical activity in the intervention group as measured by accelerometry (P < .05), although Dr. Lynch pointed out this “did not necessarily correlate with their weight loss.”

Dr. Lynch showed there were significant differences across a range of anthropometric measures from baseline to follow-up between the intervention and control groups.

The adjusted difference in weight loss between the intervention and control participants was 7.8 kg, whereas the difference in reduction of BMI was 2.7 (P = .001 for both).

There was also a significant difference in the reduction in waist-to-hip ratio between the groups, at 0.033 in favor of the intervention, as well as a difference in the reduction in fat tissue, at 3.1% (P = .001 for both).

Further analyses showed weight loss was associated with significant improvements on the 6-minute walk test, at an r value of 0.48 (P = .015), and in the 25-foot walk test (r = 0.42; P = .015). Weight loss was also linked to reductions in perceived fatigability (r = 0.48; P = .005).

Dr. Lynch also reported that a 5% reduction in body weight was associated with a “clinically meaningful” improvement of 50 meters on the 6-minute walk test.

Finally, it was found the intervention was associated with a significant improvement in mental quality of life (P = .01), whereas weight loss specifically was linked to improved physical quality of life (P = .02).

“We believe that future studies should examine weight loss in people with MS who have more advanced disability,” Dr. Lynch said, and “we should examine the effects of weight loss on the underlying disease processes.”

She added they also “need to follow the patient for longer and see if they can maintain their weight loss.”
 

Emphasizing the social side of interventions

Session cochair Brian M. Sandroff, PhD, director of the Exercise Neurorehabilitation Research Laboratory at the Kessler Foundation, East Hanover, N.J., commented that the results are “really exciting.”

He said that the improvements across the range of measures assessed in the study were not surprising, “considering the intervention was multicomponent, and so had the potential to affect a number of different physical and cognitive domains.”

One factor in managing MS that came up again and again during the discussion at the end of the session was the social aspect of interventions, with Dr. Lynch saying the group sessions in particular were appreciated by participants in her trial.

Dr. Sandroff, who was not involved in the study, said that it has been questioned whether the social side should be controlled for when assessing interventions, or “maybe it’s something we should promote within our studies.”

He explained that being social “overcomes a lot of isolation-related issues among people with MS who have comorbidities,” which can result in “reduced quality of life and differences in symptomatic manifestations.”

“Providing that group setting might have lots of outcomes besides just a biological loss of mass” because of the intervention itself, Dr. Sandroff said.

The study was supported by grants from the National MS Society. Dr. Lynch declares relationships with Biogen, Genzyme, Teva, Sanofi, Novartis, Celgene, Roche, Immunic, National Institutes of Health, National Multiple Sclerosis Society, Patient-Centered Outcomes Research Institute, Anokion, TG Therapeutics, and Actelion. Other authors also declared relationships. Dr. Sandroff declared no relevant 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.

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.

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.

Lack of time for self-care and rest are particularly harmful to women’s health. Various speakers at the VII National Conference of the Onda Foundation, Italy’s National Observatory for Women and Gender’s Health, focused on this topic. The conference was dedicated to the social factors that determine health within the context of gender medicine.

In our society, housework and raising a family are responsibilities placed predominantly on the shoulders of women. These responsibilities contribute significantly to women’s daily workload. The most overburdened women are working mothers (according to ISTAT, Italy’s Office for National Statistics, 2019), who are forced to combine their professional responsibilities with family life, dedicating 8 hours and 20 minutes per day to paid and unpaid work overall, compared with the 7 hours and 29 minutes spent by working fathers. Working mothers between ages 25 and 44 years have on average 2 hours and 35 minutes of free time per day.
 

Stress and sleep deprivation

“Under these conditions, the risk of chronic stress is raised, and stress leads to depression. The rate of depression in the female population is double that of the male population,” said Claudio Mencacci, MD, chair of the Italian Society of Neuropsychopharmacology and the Onda Foundation. “What’s more, stress increases the risk of cardiovascular and metabolic diseases, asthma, arthritis, and autoimmune diseases.”

The one thing that is especially damaging to physical and mental health is sleep deprivation, and working mothers get less sleep than do working fathers. “This is partially due to biological factors: hormonal changes that take place toward the end of adolescence in women during the premenstrual period are responsible for an increased rate of sleep disturbance and insomnia,” said Dr. Mencacci. “During pregnancy and the postpartum period, female sex hormones make sleep lighter, reducing time spent in the REM sleep stage. Then there’s the social aspect that plays a decisive role: by and large, it’s mothers who take care of the youngest children at night.”

According to a 2019 German study, during the first 6 years of life of the first child, a mother loses on average 44 minutes sleep per night, compared with the average time spent sleeping before pregnancy; a father loses 14 minutes.

“Another aspect to bear in mind is that, for cultural reasons, women tend to overlook the issue and not seek help, deeming sleep deprivation normal,” said Dr. Mencacci.
 

Caregivers at greatest risk

The negative effects of stress are evident in people continuously caring for a dependent older or disabled family member, so-called caregivers. This is, “A group predominantly made up of women aged between 45 and 55 years,” said Marina Petrini, PhD, of the Italian Health Institute’s Gender Medicine Center of Excellence. Dr. Petrini coordinated a study on stress and health in family caregivers.

“The results obtained reveal a high level of stress, especially among female caregivers, who are more exposed to the risk of severe symptoms of depression, physical disorders, especially those affecting the nervous and immune systems, and who tend to adopt irregular eating patterns and sedentary habits,” said Dr. Petrini.
 

Limited treatment access

Another study presented at the Onda Foundation’s conference, which shows just how much a lack of “me time” can damage your health, is the Access to Diagnostic Medicine and Treatment by Region: the Patient’s Perspective Survey, conducted by market research agency Elma Research on a sample of cancer patients requiring specialist treatment.

“Forty percent of them had to move to a different region from the one they live in to get the care they needed,” said Massimo Massagrande, CEO of Elma Research. “Of that group, 40% had to move to an area not neighboring their own. The impact of area of residence is heavy, in terms of money and logistics – so much so that a large proportion of patients interviewed were forced to turn their back on the best available treatments. For women responding to our survey, the biggest obstacle is the impossibility of reconciling the effects of a move or the prospective of a temporary transfer to another region with their responsibilities for looking after their family.”

This article was translated from Univadis Italy. A version appeared on Medscape.com.

Lack of time for self-care and rest are particularly harmful to women’s health. Various speakers at the VII National Conference of the Onda Foundation, Italy’s National Observatory for Women and Gender’s Health, focused on this topic. The conference was dedicated to the social factors that determine health within the context of gender medicine.

In our society, housework and raising a family are responsibilities placed predominantly on the shoulders of women. These responsibilities contribute significantly to women’s daily workload. The most overburdened women are working mothers (according to ISTAT, Italy’s Office for National Statistics, 2019), who are forced to combine their professional responsibilities with family life, dedicating 8 hours and 20 minutes per day to paid and unpaid work overall, compared with the 7 hours and 29 minutes spent by working fathers. Working mothers between ages 25 and 44 years have on average 2 hours and 35 minutes of free time per day.
 

Stress and sleep deprivation

“Under these conditions, the risk of chronic stress is raised, and stress leads to depression. The rate of depression in the female population is double that of the male population,” said Claudio Mencacci, MD, chair of the Italian Society of Neuropsychopharmacology and the Onda Foundation. “What’s more, stress increases the risk of cardiovascular and metabolic diseases, asthma, arthritis, and autoimmune diseases.”

The one thing that is especially damaging to physical and mental health is sleep deprivation, and working mothers get less sleep than do working fathers. “This is partially due to biological factors: hormonal changes that take place toward the end of adolescence in women during the premenstrual period are responsible for an increased rate of sleep disturbance and insomnia,” said Dr. Mencacci. “During pregnancy and the postpartum period, female sex hormones make sleep lighter, reducing time spent in the REM sleep stage. Then there’s the social aspect that plays a decisive role: by and large, it’s mothers who take care of the youngest children at night.”

According to a 2019 German study, during the first 6 years of life of the first child, a mother loses on average 44 minutes sleep per night, compared with the average time spent sleeping before pregnancy; a father loses 14 minutes.

“Another aspect to bear in mind is that, for cultural reasons, women tend to overlook the issue and not seek help, deeming sleep deprivation normal,” said Dr. Mencacci.
 

Caregivers at greatest risk

The negative effects of stress are evident in people continuously caring for a dependent older or disabled family member, so-called caregivers. This is, “A group predominantly made up of women aged between 45 and 55 years,” said Marina Petrini, PhD, of the Italian Health Institute’s Gender Medicine Center of Excellence. Dr. Petrini coordinated a study on stress and health in family caregivers.

“The results obtained reveal a high level of stress, especially among female caregivers, who are more exposed to the risk of severe symptoms of depression, physical disorders, especially those affecting the nervous and immune systems, and who tend to adopt irregular eating patterns and sedentary habits,” said Dr. Petrini.
 

Limited treatment access

Another study presented at the Onda Foundation’s conference, which shows just how much a lack of “me time” can damage your health, is the Access to Diagnostic Medicine and Treatment by Region: the Patient’s Perspective Survey, conducted by market research agency Elma Research on a sample of cancer patients requiring specialist treatment.

“Forty percent of them had to move to a different region from the one they live in to get the care they needed,” said Massimo Massagrande, CEO of Elma Research. “Of that group, 40% had to move to an area not neighboring their own. The impact of area of residence is heavy, in terms of money and logistics – so much so that a large proportion of patients interviewed were forced to turn their back on the best available treatments. For women responding to our survey, the biggest obstacle is the impossibility of reconciling the effects of a move or the prospective of a temporary transfer to another region with their responsibilities for looking after their family.”

This article was translated from Univadis Italy. A version appeared on Medscape.com.

Lack of time for self-care and rest are particularly harmful to women’s health. Various speakers at the VII National Conference of the Onda Foundation, Italy’s National Observatory for Women and Gender’s Health, focused on this topic. The conference was dedicated to the social factors that determine health within the context of gender medicine.

In our society, housework and raising a family are responsibilities placed predominantly on the shoulders of women. These responsibilities contribute significantly to women’s daily workload. The most overburdened women are working mothers (according to ISTAT, Italy’s Office for National Statistics, 2019), who are forced to combine their professional responsibilities with family life, dedicating 8 hours and 20 minutes per day to paid and unpaid work overall, compared with the 7 hours and 29 minutes spent by working fathers. Working mothers between ages 25 and 44 years have on average 2 hours and 35 minutes of free time per day.
 

Stress and sleep deprivation

“Under these conditions, the risk of chronic stress is raised, and stress leads to depression. The rate of depression in the female population is double that of the male population,” said Claudio Mencacci, MD, chair of the Italian Society of Neuropsychopharmacology and the Onda Foundation. “What’s more, stress increases the risk of cardiovascular and metabolic diseases, asthma, arthritis, and autoimmune diseases.”

The one thing that is especially damaging to physical and mental health is sleep deprivation, and working mothers get less sleep than do working fathers. “This is partially due to biological factors: hormonal changes that take place toward the end of adolescence in women during the premenstrual period are responsible for an increased rate of sleep disturbance and insomnia,” said Dr. Mencacci. “During pregnancy and the postpartum period, female sex hormones make sleep lighter, reducing time spent in the REM sleep stage. Then there’s the social aspect that plays a decisive role: by and large, it’s mothers who take care of the youngest children at night.”

According to a 2019 German study, during the first 6 years of life of the first child, a mother loses on average 44 minutes sleep per night, compared with the average time spent sleeping before pregnancy; a father loses 14 minutes.

“Another aspect to bear in mind is that, for cultural reasons, women tend to overlook the issue and not seek help, deeming sleep deprivation normal,” said Dr. Mencacci.
 

Caregivers at greatest risk

The negative effects of stress are evident in people continuously caring for a dependent older or disabled family member, so-called caregivers. This is, “A group predominantly made up of women aged between 45 and 55 years,” said Marina Petrini, PhD, of the Italian Health Institute’s Gender Medicine Center of Excellence. Dr. Petrini coordinated a study on stress and health in family caregivers.

“The results obtained reveal a high level of stress, especially among female caregivers, who are more exposed to the risk of severe symptoms of depression, physical disorders, especially those affecting the nervous and immune systems, and who tend to adopt irregular eating patterns and sedentary habits,” said Dr. Petrini.
 

Limited treatment access

Another study presented at the Onda Foundation’s conference, which shows just how much a lack of “me time” can damage your health, is the Access to Diagnostic Medicine and Treatment by Region: the Patient’s Perspective Survey, conducted by market research agency Elma Research on a sample of cancer patients requiring specialist treatment.

“Forty percent of them had to move to a different region from the one they live in to get the care they needed,” said Massimo Massagrande, CEO of Elma Research. “Of that group, 40% had to move to an area not neighboring their own. The impact of area of residence is heavy, in terms of money and logistics – so much so that a large proportion of patients interviewed were forced to turn their back on the best available treatments. For women responding to our survey, the biggest obstacle is the impossibility of reconciling the effects of a move or the prospective of a temporary transfer to another region with their responsibilities for looking after their family.”

This article was translated from Univadis Italy. A version 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.