Conference Coverage

CHARLOTTE, N.C. – Erratic sleep patterns over years or even decades, along with a patient’s age and history of depression, may be harbingers of cognitive impairment later in life, an analysis of decades of data from a large sleep study has found.

“What we were a little surprised to find in this model was that sleep duration, whether short, long or average, was not significant, but the sleep variability – the change in sleep across those time measurements—was significantly impacting the incidence of cognitive impairment,” Samantha Keil, PhD, a postdoctoral fellow at the University of Washington, Seattle, reported at the at the annual meeting of the Associated Professional Sleep Societies.

The researchers analyzed sleep and cognition data collected over decades on 1,104 adults who participated in the Seattle Longitudinal Study. Study participants ranged from age 55 to over 100, with almost 80% of the study cohort aged 65 and older.

The Seattle Longitudinal Study first started gathering data in the 1950s. Participants in the study cohort underwent an extensive cognitive battery, which was added to the study in 1984 and gathered every 5-7 years, and completed a health behavioral questionnaire (HBQ), which was added in 1993 and administered every 3-5 years, Dr. Keil said. The HBQ included a question on average nightly sleep duration.

The study used a multivariable Cox proportional hazard regression model to evaluate the overall effect of average sleep duration and changes in sleep duration over time on cognitive impairment. Covariates used in the model included apolipoprotein E4 (APOE4) genotype, gender, years of education, ethnicity, and depression.

Dr. Keil said the model found, as expected, that the  demographic variables of education, APOE status, and depression were significantly associated with cognitive impairment (hazard ratios of 1.11; 95% confidence interval [CI], 1.02-1.21; P = .01; and 2.08; 95% CI, 1.31-3.31; P < .005; and 1.08; 95% CI, 1.04-1.13; P < .005, respectively). Importantly, when evaluating the duration, change and variability of sleep, the researchers found that increased sleep variability was significantly associated with cognitive impairment (HR, 3.15; 95% CI, 1.69-5.87; P < .005).  

Under this analysis, “sleep variability over time and not median sleep duration was associated with cognitive impairment,” she said. When sleep variability was added into the model, it improved the concordance score – a value that reflects the ability of a model to predict an outcome better than random chance – from .63 to .73 (a value of .5 indicates the model is no better at predicting an outcome than a random chance model; a value of .7 or greater indicates a good model).

Identification of sleep variability as a sleep pattern of interest in longitudinal studies is important, Dr. Keil said, because simply evaluating mean or median sleep duration across time might not account for a subject’s variable sleep phenotype. Most importantly, further evaluation of sleep variability with a linear regression prediction analysis (F statistic 8.796, P < .0001, adjusted R-squared .235) found that increased age, depression, and sleep variability significantly predicted cognitive impairment 10 years downstream. “Longitudinal sleep variability is perhaps for the first time being reported as significantly associated with the development of downstream cognitive impairment,” Dr. Keil said.

What makes this study unique, Dr. Keil said in an interview, is that it used self-reported longitudinal data gathered at 3- to 5-year intervals for up to 25 years, allowing for the assessment of variation of sleep duration across this entire time frame. “If you could use that shift in sleep duration as a point of therapeutic intervention, that would be really exciting,” she said.

Future research will evaluate how sleep variability and cognitive function are impacted by other variables gathered in the Seattle Longitudinal Study over the years, including factors such as diabetes and hypertension status, diet, alcohol and tobacco use, and marital and family status. Follow-up studies will be investigating the impact of sleep variability on neuropathologic disease progression and lymphatic system impairment, Dr. Keil said.
 

A newer approach

By linking sleep variability and daytime functioning, the study employs a “newer approach,” said Joseph M. Dzierzewski, PhD, director of behavioral medicine concentration in the department of psychology at Virginia Commonwealth University in Richmond. “While some previous work has examined night-to-night fluctuation in various sleep characteristics and cognitive functioning, what differentiates the present study from these previous works is the duration of the investigation,” he said. The “richness of data” in the Seattle Longitudinal Study and how it tracks sleep and cognition over years make it “quite unique and novel.”

Future studies, he said, should be deliberate in how they evaluate sleep and neurocognitive function across years. “Disentangling short-term moment-to-moment and day-to-day fluctuation, which may be more reversible in nature, from long-term, enduring month-to-month or year-to-year fluctuation, which may be more permanent, will be important for continuing to advance our understanding of these complex phenomena,” Dr. Dzierzewski said. “An additional important area of future investigation would be to continue the hunt for a common biological factor underpinning both sleep variability and Alzheimer’s disease.” That, he said, may help identify potential intervention targets.

Dr. Keil and Dr. Dzierzewski have no relevant disclosures.

CHARLOTTE, N.C. – Erratic sleep patterns over years or even decades, along with a patient’s age and history of depression, may be harbingers of cognitive impairment later in life, an analysis of decades of data from a large sleep study has found.

“What we were a little surprised to find in this model was that sleep duration, whether short, long or average, was not significant, but the sleep variability – the change in sleep across those time measurements—was significantly impacting the incidence of cognitive impairment,” Samantha Keil, PhD, a postdoctoral fellow at the University of Washington, Seattle, reported at the at the annual meeting of the Associated Professional Sleep Societies.

The researchers analyzed sleep and cognition data collected over decades on 1,104 adults who participated in the Seattle Longitudinal Study. Study participants ranged from age 55 to over 100, with almost 80% of the study cohort aged 65 and older.

The Seattle Longitudinal Study first started gathering data in the 1950s. Participants in the study cohort underwent an extensive cognitive battery, which was added to the study in 1984 and gathered every 5-7 years, and completed a health behavioral questionnaire (HBQ), which was added in 1993 and administered every 3-5 years, Dr. Keil said. The HBQ included a question on average nightly sleep duration.

The study used a multivariable Cox proportional hazard regression model to evaluate the overall effect of average sleep duration and changes in sleep duration over time on cognitive impairment. Covariates used in the model included apolipoprotein E4 (APOE4) genotype, gender, years of education, ethnicity, and depression.

Dr. Keil said the model found, as expected, that the  demographic variables of education, APOE status, and depression were significantly associated with cognitive impairment (hazard ratios of 1.11; 95% confidence interval [CI], 1.02-1.21; P = .01; and 2.08; 95% CI, 1.31-3.31; P < .005; and 1.08; 95% CI, 1.04-1.13; P < .005, respectively). Importantly, when evaluating the duration, change and variability of sleep, the researchers found that increased sleep variability was significantly associated with cognitive impairment (HR, 3.15; 95% CI, 1.69-5.87; P < .005).  

Under this analysis, “sleep variability over time and not median sleep duration was associated with cognitive impairment,” she said. When sleep variability was added into the model, it improved the concordance score – a value that reflects the ability of a model to predict an outcome better than random chance – from .63 to .73 (a value of .5 indicates the model is no better at predicting an outcome than a random chance model; a value of .7 or greater indicates a good model).

Identification of sleep variability as a sleep pattern of interest in longitudinal studies is important, Dr. Keil said, because simply evaluating mean or median sleep duration across time might not account for a subject’s variable sleep phenotype. Most importantly, further evaluation of sleep variability with a linear regression prediction analysis (F statistic 8.796, P < .0001, adjusted R-squared .235) found that increased age, depression, and sleep variability significantly predicted cognitive impairment 10 years downstream. “Longitudinal sleep variability is perhaps for the first time being reported as significantly associated with the development of downstream cognitive impairment,” Dr. Keil said.

What makes this study unique, Dr. Keil said in an interview, is that it used self-reported longitudinal data gathered at 3- to 5-year intervals for up to 25 years, allowing for the assessment of variation of sleep duration across this entire time frame. “If you could use that shift in sleep duration as a point of therapeutic intervention, that would be really exciting,” she said.

Future research will evaluate how sleep variability and cognitive function are impacted by other variables gathered in the Seattle Longitudinal Study over the years, including factors such as diabetes and hypertension status, diet, alcohol and tobacco use, and marital and family status. Follow-up studies will be investigating the impact of sleep variability on neuropathologic disease progression and lymphatic system impairment, Dr. Keil said.
 

A newer approach

By linking sleep variability and daytime functioning, the study employs a “newer approach,” said Joseph M. Dzierzewski, PhD, director of behavioral medicine concentration in the department of psychology at Virginia Commonwealth University in Richmond. “While some previous work has examined night-to-night fluctuation in various sleep characteristics and cognitive functioning, what differentiates the present study from these previous works is the duration of the investigation,” he said. The “richness of data” in the Seattle Longitudinal Study and how it tracks sleep and cognition over years make it “quite unique and novel.”

Future studies, he said, should be deliberate in how they evaluate sleep and neurocognitive function across years. “Disentangling short-term moment-to-moment and day-to-day fluctuation, which may be more reversible in nature, from long-term, enduring month-to-month or year-to-year fluctuation, which may be more permanent, will be important for continuing to advance our understanding of these complex phenomena,” Dr. Dzierzewski said. “An additional important area of future investigation would be to continue the hunt for a common biological factor underpinning both sleep variability and Alzheimer’s disease.” That, he said, may help identify potential intervention targets.

Dr. Keil and Dr. Dzierzewski have no relevant disclosures.

CHARLOTTE, N.C. – Erratic sleep patterns over years or even decades, along with a patient’s age and history of depression, may be harbingers of cognitive impairment later in life, an analysis of decades of data from a large sleep study has found.

“What we were a little surprised to find in this model was that sleep duration, whether short, long or average, was not significant, but the sleep variability – the change in sleep across those time measurements—was significantly impacting the incidence of cognitive impairment,” Samantha Keil, PhD, a postdoctoral fellow at the University of Washington, Seattle, reported at the at the annual meeting of the Associated Professional Sleep Societies.

The researchers analyzed sleep and cognition data collected over decades on 1,104 adults who participated in the Seattle Longitudinal Study. Study participants ranged from age 55 to over 100, with almost 80% of the study cohort aged 65 and older.

The Seattle Longitudinal Study first started gathering data in the 1950s. Participants in the study cohort underwent an extensive cognitive battery, which was added to the study in 1984 and gathered every 5-7 years, and completed a health behavioral questionnaire (HBQ), which was added in 1993 and administered every 3-5 years, Dr. Keil said. The HBQ included a question on average nightly sleep duration.

The study used a multivariable Cox proportional hazard regression model to evaluate the overall effect of average sleep duration and changes in sleep duration over time on cognitive impairment. Covariates used in the model included apolipoprotein E4 (APOE4) genotype, gender, years of education, ethnicity, and depression.

Dr. Keil said the model found, as expected, that the  demographic variables of education, APOE status, and depression were significantly associated with cognitive impairment (hazard ratios of 1.11; 95% confidence interval [CI], 1.02-1.21; P = .01; and 2.08; 95% CI, 1.31-3.31; P < .005; and 1.08; 95% CI, 1.04-1.13; P < .005, respectively). Importantly, when evaluating the duration, change and variability of sleep, the researchers found that increased sleep variability was significantly associated with cognitive impairment (HR, 3.15; 95% CI, 1.69-5.87; P < .005).  

Under this analysis, “sleep variability over time and not median sleep duration was associated with cognitive impairment,” she said. When sleep variability was added into the model, it improved the concordance score – a value that reflects the ability of a model to predict an outcome better than random chance – from .63 to .73 (a value of .5 indicates the model is no better at predicting an outcome than a random chance model; a value of .7 or greater indicates a good model).

Identification of sleep variability as a sleep pattern of interest in longitudinal studies is important, Dr. Keil said, because simply evaluating mean or median sleep duration across time might not account for a subject’s variable sleep phenotype. Most importantly, further evaluation of sleep variability with a linear regression prediction analysis (F statistic 8.796, P < .0001, adjusted R-squared .235) found that increased age, depression, and sleep variability significantly predicted cognitive impairment 10 years downstream. “Longitudinal sleep variability is perhaps for the first time being reported as significantly associated with the development of downstream cognitive impairment,” Dr. Keil said.

What makes this study unique, Dr. Keil said in an interview, is that it used self-reported longitudinal data gathered at 3- to 5-year intervals for up to 25 years, allowing for the assessment of variation of sleep duration across this entire time frame. “If you could use that shift in sleep duration as a point of therapeutic intervention, that would be really exciting,” she said.

Future research will evaluate how sleep variability and cognitive function are impacted by other variables gathered in the Seattle Longitudinal Study over the years, including factors such as diabetes and hypertension status, diet, alcohol and tobacco use, and marital and family status. Follow-up studies will be investigating the impact of sleep variability on neuropathologic disease progression and lymphatic system impairment, Dr. Keil said.
 

A newer approach

By linking sleep variability and daytime functioning, the study employs a “newer approach,” said Joseph M. Dzierzewski, PhD, director of behavioral medicine concentration in the department of psychology at Virginia Commonwealth University in Richmond. “While some previous work has examined night-to-night fluctuation in various sleep characteristics and cognitive functioning, what differentiates the present study from these previous works is the duration of the investigation,” he said. The “richness of data” in the Seattle Longitudinal Study and how it tracks sleep and cognition over years make it “quite unique and novel.”

Future studies, he said, should be deliberate in how they evaluate sleep and neurocognitive function across years. “Disentangling short-term moment-to-moment and day-to-day fluctuation, which may be more reversible in nature, from long-term, enduring month-to-month or year-to-year fluctuation, which may be more permanent, will be important for continuing to advance our understanding of these complex phenomena,” Dr. Dzierzewski said. “An additional important area of future investigation would be to continue the hunt for a common biological factor underpinning both sleep variability and Alzheimer’s disease.” That, he said, may help identify potential intervention targets.

Dr. Keil and Dr. Dzierzewski have no relevant disclosures.

The development of depression after a rheumatoid arthritis diagnosis increased the risk for death “more than sixfold” when compared with having no depression at diagnosis, according to Danish researchers.

Cumulative mortality at 10 years was approximately 37% in patients with comorbid RA and depression versus around 13.5% of RA patients with no depression, Jens Kristian Pedersen, MD, PhD, of Odense (Denmark) University Hospital–Svendborg Hospital and the department of clinical research at the University of Southern Denmark, also in Odense, reported at the annual European Congress of Rheumatology.

“According to [antidepressant] exposure status, the cumulative mortality followed two clearly different paths,” Dr. Pedersen said. “The mortality curves separated early and already within the first and second year of follow-up.”
 

RA, depression, and mortality

Rates of depression in patients with RA are high, Dr. Pedersen said, and while it’s previously been reported that their coexistence can increase mortality, this is the first time that the link has been investigated in a population newly diagnosed with RA.

In this study, Dr. Pedersen and collaborators wanted to look at the association in incident RA and defined depression as the first filling of an antidepressant prescription.

“Although antidepressants are used for different indications, we have recently described that in RA the most frequent indication for filling antidepressants is depression,” he explained. Moreover, that research found that “the frequency of filling coincides with the occurrence of depressive disorder previously reported in the scientific literature.”
 

Data sourced from multiple Danish registers

To examine the mortality risk associated with newly diagnosed RA and new-onset depression, Dr. Pedersen described how five different Danish registers were used.

First, data from the DANBIO register were used to identify patients with incident RA living in Denmark over a 10-year period ending in December 2018. Although perhaps widely known as a biologics register, DANBIO is required by the Danish National Board of Health to collect information on all patients with RA, regardless of their treatment.

Next, the Danish National Prescription Register and Danish National Patient Register were consulted to obtain data on patients who had a first prescription for antidepressant treatment and information on those who developed a diagnosis of depression. Demographic, vital status, and socioeconomic data were collated from the Danish Civil Registration System and Statistics Denmark databases.

To be sure they were looking at incident cases of RA and new cases of depression, the researchers excluded anyone with an existing prescription of antidepressants or methotrexate, or who had a confirmed diagnosis of either disorder 3 years prior to the index date of Jan. 1, 2008.

This meant that, from a total population of 18,000 patients in the DANBIO database, there were just over 11,000 who could be included in the analyses.

Overall, the median age at RA diagnosis was 61 years, two-thirds were female, and two-thirds had seropositive disease.

New-onset depression in incident RA

“During follow-up, about 10% filled a prescription of antidepressants,” said Dr. Pedersen, adding that there were 671 deaths, representing around 57,000 person-years at risk.

“The majority died from natural causes,” he said, although the cause of death was unknown in 30% of cases.

Comparing those who did and did not have a prescription for antidepressants, there were some differences in the age at which death occurred, the percentage of females to males, the presence of other comorbidities, and levels of higher education and income. These were all adjusted for in the analyses.

Adjusted hazard rate ratios were calculated to look at the mortality risk in patients who had antidepressant exposure. The highest HRR for mortality with antidepressant use was seen in patients aged 55 years or younger at 6.66, with the next highest HRRs being for male gender (3.70) and seropositive RA (3.45).

But HRRs for seronegative RA, female gender, and age 55-70 years or older than 75 years were all still around 3.0.
 

Depression definition questioned

“My only concern is about the definition of depression in your analysis,” said a member of the audience at the congress.

“You used antidepressant use as a proxy of depression diagnosis, but it might be that most or many patients have taken [medication] like duloxetine for pain control, and you are just seeing higher disease activity and more aggressive RA.”

Dr. Pedersen responded: “After the EULAR 2022 submission deadline, we reanalyzed our data using two other measures of depression.

“First, we use treatment with antidepressants with a positive indication of depression, according to the prescribing physician, and secondly, we used first diagnosis with depression according to ICD-10 Code F32 – ‘depressive episode after discharge from hospital as an outpatient,’ ” he said.

“All definitions end up with a hazard rate ratio of about three. So, in my opinion, it doesn’t matter whether you focus on one measure of depression or the other.”

David Isenberg, MD, FRCP, professor of rheumatology at University College London, wanted to know more about the antecedent history of depression and whether people who had been depressed maybe a decade or 2 decades before, were more likely to get RA.

That calculation has not been done, Dr. Pedersen said, adding that the study also can’t account for people who may have had recurrent depression. Depression treatment guidelines often recommend nonpharmacologic intervention in the first instance, “so we do not necessarily get the right picture of recurrent depression if we look further back.”

Pointing out that the sixfold increase in mortality was impressive, another delegate asked about whether it was because of a higher disease activity or joint damage and if the mortality risk might be lower in patients who are in remission.

“We don’t know that yet,” Dr. Pedersen answered. “We haven’t done the calculations, but there is the issue of residual confounding if we don’t take all relevant covariates into account. So, we need to do that calculation as well.”

The study was supported by the Danish Rheumatism Association. Dr. Pedersen had no conflicts of interest to disclose.
 

The development of depression after a rheumatoid arthritis diagnosis increased the risk for death “more than sixfold” when compared with having no depression at diagnosis, according to Danish researchers.

Cumulative mortality at 10 years was approximately 37% in patients with comorbid RA and depression versus around 13.5% of RA patients with no depression, Jens Kristian Pedersen, MD, PhD, of Odense (Denmark) University Hospital–Svendborg Hospital and the department of clinical research at the University of Southern Denmark, also in Odense, reported at the annual European Congress of Rheumatology.

“According to [antidepressant] exposure status, the cumulative mortality followed two clearly different paths,” Dr. Pedersen said. “The mortality curves separated early and already within the first and second year of follow-up.”
 

RA, depression, and mortality

Rates of depression in patients with RA are high, Dr. Pedersen said, and while it’s previously been reported that their coexistence can increase mortality, this is the first time that the link has been investigated in a population newly diagnosed with RA.

In this study, Dr. Pedersen and collaborators wanted to look at the association in incident RA and defined depression as the first filling of an antidepressant prescription.

“Although antidepressants are used for different indications, we have recently described that in RA the most frequent indication for filling antidepressants is depression,” he explained. Moreover, that research found that “the frequency of filling coincides with the occurrence of depressive disorder previously reported in the scientific literature.”
 

Data sourced from multiple Danish registers

To examine the mortality risk associated with newly diagnosed RA and new-onset depression, Dr. Pedersen described how five different Danish registers were used.

First, data from the DANBIO register were used to identify patients with incident RA living in Denmark over a 10-year period ending in December 2018. Although perhaps widely known as a biologics register, DANBIO is required by the Danish National Board of Health to collect information on all patients with RA, regardless of their treatment.

Next, the Danish National Prescription Register and Danish National Patient Register were consulted to obtain data on patients who had a first prescription for antidepressant treatment and information on those who developed a diagnosis of depression. Demographic, vital status, and socioeconomic data were collated from the Danish Civil Registration System and Statistics Denmark databases.

To be sure they were looking at incident cases of RA and new cases of depression, the researchers excluded anyone with an existing prescription of antidepressants or methotrexate, or who had a confirmed diagnosis of either disorder 3 years prior to the index date of Jan. 1, 2008.

This meant that, from a total population of 18,000 patients in the DANBIO database, there were just over 11,000 who could be included in the analyses.

Overall, the median age at RA diagnosis was 61 years, two-thirds were female, and two-thirds had seropositive disease.

New-onset depression in incident RA

“During follow-up, about 10% filled a prescription of antidepressants,” said Dr. Pedersen, adding that there were 671 deaths, representing around 57,000 person-years at risk.

“The majority died from natural causes,” he said, although the cause of death was unknown in 30% of cases.

Comparing those who did and did not have a prescription for antidepressants, there were some differences in the age at which death occurred, the percentage of females to males, the presence of other comorbidities, and levels of higher education and income. These were all adjusted for in the analyses.

Adjusted hazard rate ratios were calculated to look at the mortality risk in patients who had antidepressant exposure. The highest HRR for mortality with antidepressant use was seen in patients aged 55 years or younger at 6.66, with the next highest HRRs being for male gender (3.70) and seropositive RA (3.45).

But HRRs for seronegative RA, female gender, and age 55-70 years or older than 75 years were all still around 3.0.
 

Depression definition questioned

“My only concern is about the definition of depression in your analysis,” said a member of the audience at the congress.

“You used antidepressant use as a proxy of depression diagnosis, but it might be that most or many patients have taken [medication] like duloxetine for pain control, and you are just seeing higher disease activity and more aggressive RA.”

Dr. Pedersen responded: “After the EULAR 2022 submission deadline, we reanalyzed our data using two other measures of depression.

“First, we use treatment with antidepressants with a positive indication of depression, according to the prescribing physician, and secondly, we used first diagnosis with depression according to ICD-10 Code F32 – ‘depressive episode after discharge from hospital as an outpatient,’ ” he said.

“All definitions end up with a hazard rate ratio of about three. So, in my opinion, it doesn’t matter whether you focus on one measure of depression or the other.”

David Isenberg, MD, FRCP, professor of rheumatology at University College London, wanted to know more about the antecedent history of depression and whether people who had been depressed maybe a decade or 2 decades before, were more likely to get RA.

That calculation has not been done, Dr. Pedersen said, adding that the study also can’t account for people who may have had recurrent depression. Depression treatment guidelines often recommend nonpharmacologic intervention in the first instance, “so we do not necessarily get the right picture of recurrent depression if we look further back.”

Pointing out that the sixfold increase in mortality was impressive, another delegate asked about whether it was because of a higher disease activity or joint damage and if the mortality risk might be lower in patients who are in remission.

“We don’t know that yet,” Dr. Pedersen answered. “We haven’t done the calculations, but there is the issue of residual confounding if we don’t take all relevant covariates into account. So, we need to do that calculation as well.”

The study was supported by the Danish Rheumatism Association. Dr. Pedersen had no conflicts of interest to disclose.
 

The development of depression after a rheumatoid arthritis diagnosis increased the risk for death “more than sixfold” when compared with having no depression at diagnosis, according to Danish researchers.

Cumulative mortality at 10 years was approximately 37% in patients with comorbid RA and depression versus around 13.5% of RA patients with no depression, Jens Kristian Pedersen, MD, PhD, of Odense (Denmark) University Hospital–Svendborg Hospital and the department of clinical research at the University of Southern Denmark, also in Odense, reported at the annual European Congress of Rheumatology.

“According to [antidepressant] exposure status, the cumulative mortality followed two clearly different paths,” Dr. Pedersen said. “The mortality curves separated early and already within the first and second year of follow-up.”
 

RA, depression, and mortality

Rates of depression in patients with RA are high, Dr. Pedersen said, and while it’s previously been reported that their coexistence can increase mortality, this is the first time that the link has been investigated in a population newly diagnosed with RA.

In this study, Dr. Pedersen and collaborators wanted to look at the association in incident RA and defined depression as the first filling of an antidepressant prescription.

“Although antidepressants are used for different indications, we have recently described that in RA the most frequent indication for filling antidepressants is depression,” he explained. Moreover, that research found that “the frequency of filling coincides with the occurrence of depressive disorder previously reported in the scientific literature.”
 

Data sourced from multiple Danish registers

To examine the mortality risk associated with newly diagnosed RA and new-onset depression, Dr. Pedersen described how five different Danish registers were used.

First, data from the DANBIO register were used to identify patients with incident RA living in Denmark over a 10-year period ending in December 2018. Although perhaps widely known as a biologics register, DANBIO is required by the Danish National Board of Health to collect information on all patients with RA, regardless of their treatment.

Next, the Danish National Prescription Register and Danish National Patient Register were consulted to obtain data on patients who had a first prescription for antidepressant treatment and information on those who developed a diagnosis of depression. Demographic, vital status, and socioeconomic data were collated from the Danish Civil Registration System and Statistics Denmark databases.

To be sure they were looking at incident cases of RA and new cases of depression, the researchers excluded anyone with an existing prescription of antidepressants or methotrexate, or who had a confirmed diagnosis of either disorder 3 years prior to the index date of Jan. 1, 2008.

This meant that, from a total population of 18,000 patients in the DANBIO database, there were just over 11,000 who could be included in the analyses.

Overall, the median age at RA diagnosis was 61 years, two-thirds were female, and two-thirds had seropositive disease.

New-onset depression in incident RA

“During follow-up, about 10% filled a prescription of antidepressants,” said Dr. Pedersen, adding that there were 671 deaths, representing around 57,000 person-years at risk.

“The majority died from natural causes,” he said, although the cause of death was unknown in 30% of cases.

Comparing those who did and did not have a prescription for antidepressants, there were some differences in the age at which death occurred, the percentage of females to males, the presence of other comorbidities, and levels of higher education and income. These were all adjusted for in the analyses.

Adjusted hazard rate ratios were calculated to look at the mortality risk in patients who had antidepressant exposure. The highest HRR for mortality with antidepressant use was seen in patients aged 55 years or younger at 6.66, with the next highest HRRs being for male gender (3.70) and seropositive RA (3.45).

But HRRs for seronegative RA, female gender, and age 55-70 years or older than 75 years were all still around 3.0.
 

Depression definition questioned

“My only concern is about the definition of depression in your analysis,” said a member of the audience at the congress.

“You used antidepressant use as a proxy of depression diagnosis, but it might be that most or many patients have taken [medication] like duloxetine for pain control, and you are just seeing higher disease activity and more aggressive RA.”

Dr. Pedersen responded: “After the EULAR 2022 submission deadline, we reanalyzed our data using two other measures of depression.

“First, we use treatment with antidepressants with a positive indication of depression, according to the prescribing physician, and secondly, we used first diagnosis with depression according to ICD-10 Code F32 – ‘depressive episode after discharge from hospital as an outpatient,’ ” he said.

“All definitions end up with a hazard rate ratio of about three. So, in my opinion, it doesn’t matter whether you focus on one measure of depression or the other.”

David Isenberg, MD, FRCP, professor of rheumatology at University College London, wanted to know more about the antecedent history of depression and whether people who had been depressed maybe a decade or 2 decades before, were more likely to get RA.

That calculation has not been done, Dr. Pedersen said, adding that the study also can’t account for people who may have had recurrent depression. Depression treatment guidelines often recommend nonpharmacologic intervention in the first instance, “so we do not necessarily get the right picture of recurrent depression if we look further back.”

Pointing out that the sixfold increase in mortality was impressive, another delegate asked about whether it was because of a higher disease activity or joint damage and if the mortality risk might be lower in patients who are in remission.

“We don’t know that yet,” Dr. Pedersen answered. “We haven’t done the calculations, but there is the issue of residual confounding if we don’t take all relevant covariates into account. So, we need to do that calculation as well.”

The study was supported by the Danish Rheumatism Association. Dr. Pedersen had no conflicts of interest to disclose.
 

Adding psychotherapy to pharmacologic treatment does not appear to improve treatment outcomes for patients with major depression, new research suggests.

Results of a cross-sectional, naturalistic, multicenter European study showed there were no significant differences in response rates between patients with major depressive disorder (MDD) who received combination treatment with psychotherapy and antidepressant medication in comparison with those who received antidepressant monotherapy, even when comparing different types of psychotherapy.

This “might emphasize the fundamental role of the underlying complex biological interrelationships in MDD and its treatment,” said study investigator Lucie Bartova, MD, PhD, Clinical Division of General Psychiatry, Medical University of Vienna.

However, she noted that patients who received psychotherapy in combination with antidepressants also had “beneficial sociodemographic and clinical characteristics,” which might reflect poorer access to “psychotherapeutic techniques for patients who are more severely ill and have less socioeconomic privilege.”

The resulting selection bias may cause patients with more severe illness to “fall by the wayside,” Dr. Bartova said.

Lead researcher Siegfried Kasper, MD, also from the Medical University of Vienna, agreed, saying in a press release that, by implication, “additional psychotherapy tends to be given to more highly educated and healthier patients, which may reflect the greater availability of psychotherapy to more socially and economically advantaged patients.”

The findings, some of which were previously published in the Journal of Psychiatry Research, were presented at the virtual European Psychiatric Association 2022 Congress.
 

Inconsistent guidelines

During her presentation, Dr. Bartova said that while “numerous effective antidepressant strategies are available for the treatment of MDD, many patients do not achieve a satisfactory treatment response,” which often leads to further management refinement and the use of off-label treatments.

She continued, saying that the “most obvious” approach in these situations is to try the available treatment options in a “systematic and individualized” manner, ideally by following recommended treatment algorithms.

Meta-analyses have suggested that standardized psychotherapy with fixed, regular sessions that follows an established rationale and is based on a defined school of thought is effective in MDD, “with at least moderate effects.”

Among the psychotherapy approaches, cognitive-behavioral therapy (CBT) is the “best and most investigated,” Dr. Bartova said, but international clinical practice guidelines “lack consistency” regarding recommendations for psychotherapy.

To examine the use and impact of psychotherapy for MDD patients, the researchers studied 1,410 adult inpatients and outpatients from 10 centers in eight countries who were surveyed between 2011 and 2016 by the European Group for the Study of Resistant Depression.

Participants were assessed via the Mini–International Neuropsychiatric Interview, the Montgomery-Åsberg Depression Rating Scale, and the Hamilton Depression Rating Scale.

Results showed that among 1,279 MDD patients who were included in the final analysis, 880 (68.8%) received only antidepressants, while 399 (31.2%) received some form of structured psychotherapy as part of their treatment.

These patients included 22.8% who received CBT, 3.4% who underwent psychoanalytic psychotherapy, and 1.3% who received systemic psychotherapy. The additional psychotherapy was not specified for 3.8%.

Dr. Bartova explained that the use of psychotherapy in combination pharmacologic treatment was significantly associated with younger age, higher educational attainment, and ongoing employment in comparison with antidepressant use alone (P < .001 for all).

In addition, combination therapy was associated with an earlier average age of MDD onset, lower severity of current depressive symptoms, a lower risk of suicidality, higher rates of additional melancholic features in the patients’ symptomatology, and higher rates of comorbid asthma and migraine (P < .001 for all).

There was also a significant association between the use of psychotherapy plus pharmacologic treatment and lower average daily doses of first-line antidepressant medication (P < .001), as well as more frequent administration of agomelatine (P < .001) and a trend toward greater use of vortioxetine (P = .006).

In contrast, among patients who received antidepressants alone, there was a trend toward higher rates of additional psychotic features (P = .054), and the patients were more likely to have received selective serotonin reuptake inhibitors as their first-line antidepressant medication (P < .001).

The researchers found there was no significant difference in rates of response, nonresponse, and treatment-resistant depression (TRD) between patients who received combination psychotherapy and pharmacotherapy and those who received antidepressants alone (P = .369).

Dr. Bartova showed that 25.8% of MDD patients who received combination therapy were classified as responders, compared with 23.5% of those given only antidepressants. Nonresponse was identified in 35.6% and 33.8% of patients, respectively, while 38.6% versus 42.7% had TRD.

Dr. Bartova and colleagues performed an additional analysis to determine whether there was any difference in response depending on the type of psychotherapy.

They divided patients who received combination therapy into those who had received CBT and those who had been given another form of psychotherapy.

Again, there were no significant differences in response, nonresponse, and TRD (P = .256). The response rate was 27.1% among patients given combination CBT, versus 22.4% among those who received another psychotherapy.

“Despite clinical guidelines and studies which advocate for psychotherapy and combining psychotherapy with antidepressants, this study shows that in real life, no added value can be demonstrated for psychotherapy in those already treated with antidepressants for severe depression,” Livia De Picker, MD, PhD, Collaborative Antwerp Psychiatric Research Institute, University of Antwerp, Belgium, said in the press release.

“This doesn’t necessarily mean that psychotherapy is not useful, but it is a clear sign that the way we are currently managing these depressed patients with psychotherapy is not effective and needs critical evaluation,” added Dr. De Picker, who was not involved in the research.

However, Michael E. Thase, MD, professor of psychiatry, University of Pennsylvania, Philadelphia, told this news organization that the current study “is a secondary analysis of a naturalistic study.”

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

Adding psychotherapy to pharmacologic treatment does not appear to improve treatment outcomes for patients with major depression, new research suggests.

Results of a cross-sectional, naturalistic, multicenter European study showed there were no significant differences in response rates between patients with major depressive disorder (MDD) who received combination treatment with psychotherapy and antidepressant medication in comparison with those who received antidepressant monotherapy, even when comparing different types of psychotherapy.

This “might emphasize the fundamental role of the underlying complex biological interrelationships in MDD and its treatment,” said study investigator Lucie Bartova, MD, PhD, Clinical Division of General Psychiatry, Medical University of Vienna.

However, she noted that patients who received psychotherapy in combination with antidepressants also had “beneficial sociodemographic and clinical characteristics,” which might reflect poorer access to “psychotherapeutic techniques for patients who are more severely ill and have less socioeconomic privilege.”

The resulting selection bias may cause patients with more severe illness to “fall by the wayside,” Dr. Bartova said.

Lead researcher Siegfried Kasper, MD, also from the Medical University of Vienna, agreed, saying in a press release that, by implication, “additional psychotherapy tends to be given to more highly educated and healthier patients, which may reflect the greater availability of psychotherapy to more socially and economically advantaged patients.”

The findings, some of which were previously published in the Journal of Psychiatry Research, were presented at the virtual European Psychiatric Association 2022 Congress.
 

Inconsistent guidelines

During her presentation, Dr. Bartova said that while “numerous effective antidepressant strategies are available for the treatment of MDD, many patients do not achieve a satisfactory treatment response,” which often leads to further management refinement and the use of off-label treatments.

She continued, saying that the “most obvious” approach in these situations is to try the available treatment options in a “systematic and individualized” manner, ideally by following recommended treatment algorithms.

Meta-analyses have suggested that standardized psychotherapy with fixed, regular sessions that follows an established rationale and is based on a defined school of thought is effective in MDD, “with at least moderate effects.”

Among the psychotherapy approaches, cognitive-behavioral therapy (CBT) is the “best and most investigated,” Dr. Bartova said, but international clinical practice guidelines “lack consistency” regarding recommendations for psychotherapy.

To examine the use and impact of psychotherapy for MDD patients, the researchers studied 1,410 adult inpatients and outpatients from 10 centers in eight countries who were surveyed between 2011 and 2016 by the European Group for the Study of Resistant Depression.

Participants were assessed via the Mini–International Neuropsychiatric Interview, the Montgomery-Åsberg Depression Rating Scale, and the Hamilton Depression Rating Scale.

Results showed that among 1,279 MDD patients who were included in the final analysis, 880 (68.8%) received only antidepressants, while 399 (31.2%) received some form of structured psychotherapy as part of their treatment.

These patients included 22.8% who received CBT, 3.4% who underwent psychoanalytic psychotherapy, and 1.3% who received systemic psychotherapy. The additional psychotherapy was not specified for 3.8%.

Dr. Bartova explained that the use of psychotherapy in combination pharmacologic treatment was significantly associated with younger age, higher educational attainment, and ongoing employment in comparison with antidepressant use alone (P < .001 for all).

In addition, combination therapy was associated with an earlier average age of MDD onset, lower severity of current depressive symptoms, a lower risk of suicidality, higher rates of additional melancholic features in the patients’ symptomatology, and higher rates of comorbid asthma and migraine (P < .001 for all).

There was also a significant association between the use of psychotherapy plus pharmacologic treatment and lower average daily doses of first-line antidepressant medication (P < .001), as well as more frequent administration of agomelatine (P < .001) and a trend toward greater use of vortioxetine (P = .006).

In contrast, among patients who received antidepressants alone, there was a trend toward higher rates of additional psychotic features (P = .054), and the patients were more likely to have received selective serotonin reuptake inhibitors as their first-line antidepressant medication (P < .001).

The researchers found there was no significant difference in rates of response, nonresponse, and treatment-resistant depression (TRD) between patients who received combination psychotherapy and pharmacotherapy and those who received antidepressants alone (P = .369).

Dr. Bartova showed that 25.8% of MDD patients who received combination therapy were classified as responders, compared with 23.5% of those given only antidepressants. Nonresponse was identified in 35.6% and 33.8% of patients, respectively, while 38.6% versus 42.7% had TRD.

Dr. Bartova and colleagues performed an additional analysis to determine whether there was any difference in response depending on the type of psychotherapy.

They divided patients who received combination therapy into those who had received CBT and those who had been given another form of psychotherapy.

Again, there were no significant differences in response, nonresponse, and TRD (P = .256). The response rate was 27.1% among patients given combination CBT, versus 22.4% among those who received another psychotherapy.

“Despite clinical guidelines and studies which advocate for psychotherapy and combining psychotherapy with antidepressants, this study shows that in real life, no added value can be demonstrated for psychotherapy in those already treated with antidepressants for severe depression,” Livia De Picker, MD, PhD, Collaborative Antwerp Psychiatric Research Institute, University of Antwerp, Belgium, said in the press release.

“This doesn’t necessarily mean that psychotherapy is not useful, but it is a clear sign that the way we are currently managing these depressed patients with psychotherapy is not effective and needs critical evaluation,” added Dr. De Picker, who was not involved in the research.

However, Michael E. Thase, MD, professor of psychiatry, University of Pennsylvania, Philadelphia, told this news organization that the current study “is a secondary analysis of a naturalistic study.”

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

Adding psychotherapy to pharmacologic treatment does not appear to improve treatment outcomes for patients with major depression, new research suggests.

Results of a cross-sectional, naturalistic, multicenter European study showed there were no significant differences in response rates between patients with major depressive disorder (MDD) who received combination treatment with psychotherapy and antidepressant medication in comparison with those who received antidepressant monotherapy, even when comparing different types of psychotherapy.

This “might emphasize the fundamental role of the underlying complex biological interrelationships in MDD and its treatment,” said study investigator Lucie Bartova, MD, PhD, Clinical Division of General Psychiatry, Medical University of Vienna.

However, she noted that patients who received psychotherapy in combination with antidepressants also had “beneficial sociodemographic and clinical characteristics,” which might reflect poorer access to “psychotherapeutic techniques for patients who are more severely ill and have less socioeconomic privilege.”

The resulting selection bias may cause patients with more severe illness to “fall by the wayside,” Dr. Bartova said.

Lead researcher Siegfried Kasper, MD, also from the Medical University of Vienna, agreed, saying in a press release that, by implication, “additional psychotherapy tends to be given to more highly educated and healthier patients, which may reflect the greater availability of psychotherapy to more socially and economically advantaged patients.”

The findings, some of which were previously published in the Journal of Psychiatry Research, were presented at the virtual European Psychiatric Association 2022 Congress.
 

Inconsistent guidelines

During her presentation, Dr. Bartova said that while “numerous effective antidepressant strategies are available for the treatment of MDD, many patients do not achieve a satisfactory treatment response,” which often leads to further management refinement and the use of off-label treatments.

She continued, saying that the “most obvious” approach in these situations is to try the available treatment options in a “systematic and individualized” manner, ideally by following recommended treatment algorithms.

Meta-analyses have suggested that standardized psychotherapy with fixed, regular sessions that follows an established rationale and is based on a defined school of thought is effective in MDD, “with at least moderate effects.”

Among the psychotherapy approaches, cognitive-behavioral therapy (CBT) is the “best and most investigated,” Dr. Bartova said, but international clinical practice guidelines “lack consistency” regarding recommendations for psychotherapy.

To examine the use and impact of psychotherapy for MDD patients, the researchers studied 1,410 adult inpatients and outpatients from 10 centers in eight countries who were surveyed between 2011 and 2016 by the European Group for the Study of Resistant Depression.

Participants were assessed via the Mini–International Neuropsychiatric Interview, the Montgomery-Åsberg Depression Rating Scale, and the Hamilton Depression Rating Scale.

Results showed that among 1,279 MDD patients who were included in the final analysis, 880 (68.8%) received only antidepressants, while 399 (31.2%) received some form of structured psychotherapy as part of their treatment.

These patients included 22.8% who received CBT, 3.4% who underwent psychoanalytic psychotherapy, and 1.3% who received systemic psychotherapy. The additional psychotherapy was not specified for 3.8%.

Dr. Bartova explained that the use of psychotherapy in combination pharmacologic treatment was significantly associated with younger age, higher educational attainment, and ongoing employment in comparison with antidepressant use alone (P < .001 for all).

In addition, combination therapy was associated with an earlier average age of MDD onset, lower severity of current depressive symptoms, a lower risk of suicidality, higher rates of additional melancholic features in the patients’ symptomatology, and higher rates of comorbid asthma and migraine (P < .001 for all).

There was also a significant association between the use of psychotherapy plus pharmacologic treatment and lower average daily doses of first-line antidepressant medication (P < .001), as well as more frequent administration of agomelatine (P < .001) and a trend toward greater use of vortioxetine (P = .006).

In contrast, among patients who received antidepressants alone, there was a trend toward higher rates of additional psychotic features (P = .054), and the patients were more likely to have received selective serotonin reuptake inhibitors as their first-line antidepressant medication (P < .001).

The researchers found there was no significant difference in rates of response, nonresponse, and treatment-resistant depression (TRD) between patients who received combination psychotherapy and pharmacotherapy and those who received antidepressants alone (P = .369).

Dr. Bartova showed that 25.8% of MDD patients who received combination therapy were classified as responders, compared with 23.5% of those given only antidepressants. Nonresponse was identified in 35.6% and 33.8% of patients, respectively, while 38.6% versus 42.7% had TRD.

Dr. Bartova and colleagues performed an additional analysis to determine whether there was any difference in response depending on the type of psychotherapy.

They divided patients who received combination therapy into those who had received CBT and those who had been given another form of psychotherapy.

Again, there were no significant differences in response, nonresponse, and TRD (P = .256). The response rate was 27.1% among patients given combination CBT, versus 22.4% among those who received another psychotherapy.

“Despite clinical guidelines and studies which advocate for psychotherapy and combining psychotherapy with antidepressants, this study shows that in real life, no added value can be demonstrated for psychotherapy in those already treated with antidepressants for severe depression,” Livia De Picker, MD, PhD, Collaborative Antwerp Psychiatric Research Institute, University of Antwerp, Belgium, said in the press release.

“This doesn’t necessarily mean that psychotherapy is not useful, but it is a clear sign that the way we are currently managing these depressed patients with psychotherapy is not effective and needs critical evaluation,” added Dr. De Picker, who was not involved in the research.

However, Michael E. Thase, MD, professor of psychiatry, University of Pennsylvania, Philadelphia, told this news organization that the current study “is a secondary analysis of a naturalistic study.”

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

NEW ORLEANS – Open-source automated insulin delivery systems appear to be both effective and safe in adults and children, new research finds.

Automated insulin delivery (AID) system, also known as closed-loop systems or an artificial pancreas, link an insulin pump and a continuous glucose monitor (CGM) with an algorithm that automatically adjusts insulin delivery to optimize glycemic control.

Prior to the availability of commercial AID systems, Dana Lewis, a patient with type 1 diabetes, and her partner codeveloped an algorithm that could link older versions of an insulin pump and CGM.

In 2015, they made the code and all related materials open-source, so that anyone who wanted to create their own AID system could do so. Today thousands of people worldwide with type 1 diabetes are using the systems, which are sometimes called “do-it-yourself (DIY)” AID systems although the approach has been community based.  

AID systems are not approved by any regulatory body, and despite several nonrandomized studies demonstrating their effectiveness and safety, there is still concern among some health professionals about their safety. In 2019, the U.S. Food and Drug Administration warned against the use of any nonapproved devices or algorithms. (Now, though, at least one open-source AID system algorithm is under FDA review.)

Aimed at addressing those concerns, CREATE (Community Derived Automated Insulin Delivery) is the first randomized controlled clinical trial to compare an open-source AID system to insulin pump therapy and CGM (without any communication between the two) in patients with type 1 diabetes, most of whom were naive to AID systems.

Doctors uncomfortable with open source; study provides reassurance

The findings were presented at the American Diabetes Association scientific sessions by Martin I. de Bock, PhD, a pediatric endocrinologist and senior lecturer at the University of Otago, Christchurch, New Zealand.

The study compared the most commonly used open-source AID system (using the OpenAPS algorithm from a version of AndroidAPS implemented in a smartphone with the DANA-i insulin pump and Dexcom G6 CGM) to any insulin pump plus CGM as a comparator group.

The open-source AID system led to a significant reduction in hemoglobin A1c with no major safety issues.

“The acceptance [among clinicians] of open-source systems is diverse and complicated, [with varying] personal comfort levels of seeing someone using an AID system that has no regulatory approval,” Dr. de Bock told this news organization.  

“This is one of the reasons that it was so important to conduct the CREATE trial for the many thousands of open-source AID users. Given that the trial demonstrated safety and efficacy using the most robust scientific methodology available – a long-term randomized controlled trial – it may go some way to provide assurance for providers when they are seeing people using an open-source automated system,” he said.

Asked for comment, session moderator Diana Isaacs, PharmD, CDCES, an endocrine clinical pharmacist at the Cleveland Clinic, told this news organization: “There has been concern that these systems aren’t safe, so showing the safety is important. I think people deserve choice. As long as they’re safe, patients should be able to use what they want to use, and we should support them.”

Dr. Isaacs pointed out that an advantage of open-source systems over current commercial AIDs for patients is the ability to customize glucose targets, but in CREATE, those targets were established in the protocol by the investigators.

“I think it’s nice having the data, although in the trial they had specific requirements. They had a target range and active insulin time that they were recommending. So it’s a little different than true DIY where you don’t really have those guidelines you have to follow. It is exciting, it’s very interesting, but I wouldn’t say it’s a true mirror of the real world.”
 

Open-source systems improved time-in-range, no safety issues

For the CREATE study, 100 participants were enrolled, including 50 children aged 7-15 years and 50 adults aged 16-70 years. All participants had been using insulin pumps for at least 6 months. Most of the children and about two-thirds of the adults were also using CGMs, but just 6% of the children and 18% of the adults had prior experience with AID systems.

Baseline A1c in children was 7.5% and in adults was 7.7%.

After a 4-week run-in, all patients were randomized to the open-source AID or insulin pump plus CGM for 6 months.

The final group analyzed consisted of 42 patients in the open-source AID group and 53 patients in the comparator group.

The primary outcome, the adjusted mean difference in percent time-in-range (glucose of 70-180 mg/dL) during the final 2 weeks of the 6-month trial, showed a significant difference of 14% (P < .001) with open-source AID compared with pump plus CGM only.

Time-in-range in the open-source AID group rose from 61.2% to 71.2%, while it actually dropped slightly in the comparator group, from 57.7% to 54.5%.

The proportion of patients achieving time-in-range greater than 70% with open-source AID was 60% versus just 15% with pump plus CGM.

Glycemic improvements with open-source AID were significant for adults and children and were greater for those with higher baseline A1c levels. The effect was immediate and sustained throughout the study period, “which is super-pleasing, because there was a worry that the technical burden of open source might be [leading to] dropout, but we didn’t see that. It was sustained right through to the end of the trial,” Dr. de Bock commented.

Hypoglycemic rates didn’t differ between groups, and there were no episodes of severe hypoglycemia or diabetic ketoacidosis.
 

No more waiting: What is the future of open-source AID?

When the open-source APS was first developed, users coined the motto: “We are not waiting.” But now that the “wait” is over and several commercial AIDs have been approved by regulatory bodies, with others still in the pipeline, will people still use open-source systems?

There are no current data on people moving from DIY to commercial systems. However, Dr. de Bock said, “For most who undertook an open-source option, the precision of the settings that they can use and enjoy would mean that most would likely stick to their open source.”

Dr. Isaacs agrees: “I actually don’t think it’s going to go away in the near future, because the FDA has very specific criteria for where these [formally approved] devices can be in terms of their target ranges and requirements versus with open source you can really customize. So I still think there’s going to be a subset of people who want that customization, who want the lower targets.”

Dana Lewis, the originator of the DIY system and a CREATE coauthor, told this news organization: “I don’t believe there has been a fall-off, and in fact, I think open-source AID has continued to have ongoing uptake as awareness increases about options and as more pumps and CGMs become interoperable with various open-source AID choices.”

“I think uptake increasing is also influenced by the fact that in places like Europe, Asia, and Australia there are in-warranty on-the-market pumps that are compatible and interoperable with open-source AID. I think awareness of AID overall increases uptake of commercial and open source alike,” she said.

“Clinicians, as emphasized in recent position statements, must maintain support of the person with diabetes, irrespective of the mode of treatment they are on. ... Health care providers should be encouraged to learn from the experiences of the people who have stuck with open-source AID or switched, so that they can inform themselves of the relative strengths and benefits of each system,” Dr. de Bock advised.

Ms. Lewis noted: “We are seeing increasing awareness and comfort in endocrinologists from the community perspective, and we do hope that this study helps increase conversation and awareness of the safety and efficacy of open-source AID systems as an option for people with diabetes.”

In fact, the team published an article specifically about clinicians’ experience in CREATE. “The learning curve is similar across AID technology,” she observed.  

Findings of a 6-month continuation phase of CREATE, in which all participants used the open-source AID, are scheduled to be presented in September at the European Association for the Study of Diabetes annual meeting.

The study was funded by the Health Research Council of New Zealand, with hardware support from SOOIL Developments, South Korea; Dexcom; and Vodafone New Zealand. Dr. de Bock has reported receiving honoraria and/or research funding from Novo Nordisk, Sanofi, Pfizer, Medtronic, Lilly, Ypsomed, and Dexcom. Dr. Isaacs has reported serving as a consultant for LifeScan, Lilly, and Insulet, and as a speaker for Dexcom, Medtronic, Abbott, and Novo Nordisk. Ms. Lewis has reported no relevant financial relationships.

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

NEW ORLEANS – Open-source automated insulin delivery systems appear to be both effective and safe in adults and children, new research finds.

Automated insulin delivery (AID) system, also known as closed-loop systems or an artificial pancreas, link an insulin pump and a continuous glucose monitor (CGM) with an algorithm that automatically adjusts insulin delivery to optimize glycemic control.

Prior to the availability of commercial AID systems, Dana Lewis, a patient with type 1 diabetes, and her partner codeveloped an algorithm that could link older versions of an insulin pump and CGM.

In 2015, they made the code and all related materials open-source, so that anyone who wanted to create their own AID system could do so. Today thousands of people worldwide with type 1 diabetes are using the systems, which are sometimes called “do-it-yourself (DIY)” AID systems although the approach has been community based.  

AID systems are not approved by any regulatory body, and despite several nonrandomized studies demonstrating their effectiveness and safety, there is still concern among some health professionals about their safety. In 2019, the U.S. Food and Drug Administration warned against the use of any nonapproved devices or algorithms. (Now, though, at least one open-source AID system algorithm is under FDA review.)

Aimed at addressing those concerns, CREATE (Community Derived Automated Insulin Delivery) is the first randomized controlled clinical trial to compare an open-source AID system to insulin pump therapy and CGM (without any communication between the two) in patients with type 1 diabetes, most of whom were naive to AID systems.

Doctors uncomfortable with open source; study provides reassurance

The findings were presented at the American Diabetes Association scientific sessions by Martin I. de Bock, PhD, a pediatric endocrinologist and senior lecturer at the University of Otago, Christchurch, New Zealand.

The study compared the most commonly used open-source AID system (using the OpenAPS algorithm from a version of AndroidAPS implemented in a smartphone with the DANA-i insulin pump and Dexcom G6 CGM) to any insulin pump plus CGM as a comparator group.

The open-source AID system led to a significant reduction in hemoglobin A1c with no major safety issues.

“The acceptance [among clinicians] of open-source systems is diverse and complicated, [with varying] personal comfort levels of seeing someone using an AID system that has no regulatory approval,” Dr. de Bock told this news organization.  

“This is one of the reasons that it was so important to conduct the CREATE trial for the many thousands of open-source AID users. Given that the trial demonstrated safety and efficacy using the most robust scientific methodology available – a long-term randomized controlled trial – it may go some way to provide assurance for providers when they are seeing people using an open-source automated system,” he said.

Asked for comment, session moderator Diana Isaacs, PharmD, CDCES, an endocrine clinical pharmacist at the Cleveland Clinic, told this news organization: “There has been concern that these systems aren’t safe, so showing the safety is important. I think people deserve choice. As long as they’re safe, patients should be able to use what they want to use, and we should support them.”

Dr. Isaacs pointed out that an advantage of open-source systems over current commercial AIDs for patients is the ability to customize glucose targets, but in CREATE, those targets were established in the protocol by the investigators.

“I think it’s nice having the data, although in the trial they had specific requirements. They had a target range and active insulin time that they were recommending. So it’s a little different than true DIY where you don’t really have those guidelines you have to follow. It is exciting, it’s very interesting, but I wouldn’t say it’s a true mirror of the real world.”
 

Open-source systems improved time-in-range, no safety issues

For the CREATE study, 100 participants were enrolled, including 50 children aged 7-15 years and 50 adults aged 16-70 years. All participants had been using insulin pumps for at least 6 months. Most of the children and about two-thirds of the adults were also using CGMs, but just 6% of the children and 18% of the adults had prior experience with AID systems.

Baseline A1c in children was 7.5% and in adults was 7.7%.

After a 4-week run-in, all patients were randomized to the open-source AID or insulin pump plus CGM for 6 months.

The final group analyzed consisted of 42 patients in the open-source AID group and 53 patients in the comparator group.

The primary outcome, the adjusted mean difference in percent time-in-range (glucose of 70-180 mg/dL) during the final 2 weeks of the 6-month trial, showed a significant difference of 14% (P < .001) with open-source AID compared with pump plus CGM only.

Time-in-range in the open-source AID group rose from 61.2% to 71.2%, while it actually dropped slightly in the comparator group, from 57.7% to 54.5%.

The proportion of patients achieving time-in-range greater than 70% with open-source AID was 60% versus just 15% with pump plus CGM.

Glycemic improvements with open-source AID were significant for adults and children and were greater for those with higher baseline A1c levels. The effect was immediate and sustained throughout the study period, “which is super-pleasing, because there was a worry that the technical burden of open source might be [leading to] dropout, but we didn’t see that. It was sustained right through to the end of the trial,” Dr. de Bock commented.

Hypoglycemic rates didn’t differ between groups, and there were no episodes of severe hypoglycemia or diabetic ketoacidosis.
 

No more waiting: What is the future of open-source AID?

When the open-source APS was first developed, users coined the motto: “We are not waiting.” But now that the “wait” is over and several commercial AIDs have been approved by regulatory bodies, with others still in the pipeline, will people still use open-source systems?

There are no current data on people moving from DIY to commercial systems. However, Dr. de Bock said, “For most who undertook an open-source option, the precision of the settings that they can use and enjoy would mean that most would likely stick to their open source.”

Dr. Isaacs agrees: “I actually don’t think it’s going to go away in the near future, because the FDA has very specific criteria for where these [formally approved] devices can be in terms of their target ranges and requirements versus with open source you can really customize. So I still think there’s going to be a subset of people who want that customization, who want the lower targets.”

Dana Lewis, the originator of the DIY system and a CREATE coauthor, told this news organization: “I don’t believe there has been a fall-off, and in fact, I think open-source AID has continued to have ongoing uptake as awareness increases about options and as more pumps and CGMs become interoperable with various open-source AID choices.”

“I think uptake increasing is also influenced by the fact that in places like Europe, Asia, and Australia there are in-warranty on-the-market pumps that are compatible and interoperable with open-source AID. I think awareness of AID overall increases uptake of commercial and open source alike,” she said.

“Clinicians, as emphasized in recent position statements, must maintain support of the person with diabetes, irrespective of the mode of treatment they are on. ... Health care providers should be encouraged to learn from the experiences of the people who have stuck with open-source AID or switched, so that they can inform themselves of the relative strengths and benefits of each system,” Dr. de Bock advised.

Ms. Lewis noted: “We are seeing increasing awareness and comfort in endocrinologists from the community perspective, and we do hope that this study helps increase conversation and awareness of the safety and efficacy of open-source AID systems as an option for people with diabetes.”

In fact, the team published an article specifically about clinicians’ experience in CREATE. “The learning curve is similar across AID technology,” she observed.  

Findings of a 6-month continuation phase of CREATE, in which all participants used the open-source AID, are scheduled to be presented in September at the European Association for the Study of Diabetes annual meeting.

The study was funded by the Health Research Council of New Zealand, with hardware support from SOOIL Developments, South Korea; Dexcom; and Vodafone New Zealand. Dr. de Bock has reported receiving honoraria and/or research funding from Novo Nordisk, Sanofi, Pfizer, Medtronic, Lilly, Ypsomed, and Dexcom. Dr. Isaacs has reported serving as a consultant for LifeScan, Lilly, and Insulet, and as a speaker for Dexcom, Medtronic, Abbott, and Novo Nordisk. Ms. Lewis has reported no relevant financial relationships.

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

NEW ORLEANS – Open-source automated insulin delivery systems appear to be both effective and safe in adults and children, new research finds.

Automated insulin delivery (AID) system, also known as closed-loop systems or an artificial pancreas, link an insulin pump and a continuous glucose monitor (CGM) with an algorithm that automatically adjusts insulin delivery to optimize glycemic control.

Prior to the availability of commercial AID systems, Dana Lewis, a patient with type 1 diabetes, and her partner codeveloped an algorithm that could link older versions of an insulin pump and CGM.

In 2015, they made the code and all related materials open-source, so that anyone who wanted to create their own AID system could do so. Today thousands of people worldwide with type 1 diabetes are using the systems, which are sometimes called “do-it-yourself (DIY)” AID systems although the approach has been community based.  

AID systems are not approved by any regulatory body, and despite several nonrandomized studies demonstrating their effectiveness and safety, there is still concern among some health professionals about their safety. In 2019, the U.S. Food and Drug Administration warned against the use of any nonapproved devices or algorithms. (Now, though, at least one open-source AID system algorithm is under FDA review.)

Aimed at addressing those concerns, CREATE (Community Derived Automated Insulin Delivery) is the first randomized controlled clinical trial to compare an open-source AID system to insulin pump therapy and CGM (without any communication between the two) in patients with type 1 diabetes, most of whom were naive to AID systems.

Doctors uncomfortable with open source; study provides reassurance

The findings were presented at the American Diabetes Association scientific sessions by Martin I. de Bock, PhD, a pediatric endocrinologist and senior lecturer at the University of Otago, Christchurch, New Zealand.

The study compared the most commonly used open-source AID system (using the OpenAPS algorithm from a version of AndroidAPS implemented in a smartphone with the DANA-i insulin pump and Dexcom G6 CGM) to any insulin pump plus CGM as a comparator group.

The open-source AID system led to a significant reduction in hemoglobin A1c with no major safety issues.

“The acceptance [among clinicians] of open-source systems is diverse and complicated, [with varying] personal comfort levels of seeing someone using an AID system that has no regulatory approval,” Dr. de Bock told this news organization.  

“This is one of the reasons that it was so important to conduct the CREATE trial for the many thousands of open-source AID users. Given that the trial demonstrated safety and efficacy using the most robust scientific methodology available – a long-term randomized controlled trial – it may go some way to provide assurance for providers when they are seeing people using an open-source automated system,” he said.

Asked for comment, session moderator Diana Isaacs, PharmD, CDCES, an endocrine clinical pharmacist at the Cleveland Clinic, told this news organization: “There has been concern that these systems aren’t safe, so showing the safety is important. I think people deserve choice. As long as they’re safe, patients should be able to use what they want to use, and we should support them.”

Dr. Isaacs pointed out that an advantage of open-source systems over current commercial AIDs for patients is the ability to customize glucose targets, but in CREATE, those targets were established in the protocol by the investigators.

“I think it’s nice having the data, although in the trial they had specific requirements. They had a target range and active insulin time that they were recommending. So it’s a little different than true DIY where you don’t really have those guidelines you have to follow. It is exciting, it’s very interesting, but I wouldn’t say it’s a true mirror of the real world.”
 

Open-source systems improved time-in-range, no safety issues

For the CREATE study, 100 participants were enrolled, including 50 children aged 7-15 years and 50 adults aged 16-70 years. All participants had been using insulin pumps for at least 6 months. Most of the children and about two-thirds of the adults were also using CGMs, but just 6% of the children and 18% of the adults had prior experience with AID systems.

Baseline A1c in children was 7.5% and in adults was 7.7%.

After a 4-week run-in, all patients were randomized to the open-source AID or insulin pump plus CGM for 6 months.

The final group analyzed consisted of 42 patients in the open-source AID group and 53 patients in the comparator group.

The primary outcome, the adjusted mean difference in percent time-in-range (glucose of 70-180 mg/dL) during the final 2 weeks of the 6-month trial, showed a significant difference of 14% (P < .001) with open-source AID compared with pump plus CGM only.

Time-in-range in the open-source AID group rose from 61.2% to 71.2%, while it actually dropped slightly in the comparator group, from 57.7% to 54.5%.

The proportion of patients achieving time-in-range greater than 70% with open-source AID was 60% versus just 15% with pump plus CGM.

Glycemic improvements with open-source AID were significant for adults and children and were greater for those with higher baseline A1c levels. The effect was immediate and sustained throughout the study period, “which is super-pleasing, because there was a worry that the technical burden of open source might be [leading to] dropout, but we didn’t see that. It was sustained right through to the end of the trial,” Dr. de Bock commented.

Hypoglycemic rates didn’t differ between groups, and there were no episodes of severe hypoglycemia or diabetic ketoacidosis.
 

No more waiting: What is the future of open-source AID?

When the open-source APS was first developed, users coined the motto: “We are not waiting.” But now that the “wait” is over and several commercial AIDs have been approved by regulatory bodies, with others still in the pipeline, will people still use open-source systems?

There are no current data on people moving from DIY to commercial systems. However, Dr. de Bock said, “For most who undertook an open-source option, the precision of the settings that they can use and enjoy would mean that most would likely stick to their open source.”

Dr. Isaacs agrees: “I actually don’t think it’s going to go away in the near future, because the FDA has very specific criteria for where these [formally approved] devices can be in terms of their target ranges and requirements versus with open source you can really customize. So I still think there’s going to be a subset of people who want that customization, who want the lower targets.”

Dana Lewis, the originator of the DIY system and a CREATE coauthor, told this news organization: “I don’t believe there has been a fall-off, and in fact, I think open-source AID has continued to have ongoing uptake as awareness increases about options and as more pumps and CGMs become interoperable with various open-source AID choices.”

“I think uptake increasing is also influenced by the fact that in places like Europe, Asia, and Australia there are in-warranty on-the-market pumps that are compatible and interoperable with open-source AID. I think awareness of AID overall increases uptake of commercial and open source alike,” she said.

“Clinicians, as emphasized in recent position statements, must maintain support of the person with diabetes, irrespective of the mode of treatment they are on. ... Health care providers should be encouraged to learn from the experiences of the people who have stuck with open-source AID or switched, so that they can inform themselves of the relative strengths and benefits of each system,” Dr. de Bock advised.

Ms. Lewis noted: “We are seeing increasing awareness and comfort in endocrinologists from the community perspective, and we do hope that this study helps increase conversation and awareness of the safety and efficacy of open-source AID systems as an option for people with diabetes.”

In fact, the team published an article specifically about clinicians’ experience in CREATE. “The learning curve is similar across AID technology,” she observed.  

Findings of a 6-month continuation phase of CREATE, in which all participants used the open-source AID, are scheduled to be presented in September at the European Association for the Study of Diabetes annual meeting.

The study was funded by the Health Research Council of New Zealand, with hardware support from SOOIL Developments, South Korea; Dexcom; and Vodafone New Zealand. Dr. de Bock has reported receiving honoraria and/or research funding from Novo Nordisk, Sanofi, Pfizer, Medtronic, Lilly, Ypsomed, and Dexcom. Dr. Isaacs has reported serving as a consultant for LifeScan, Lilly, and Insulet, and as a speaker for Dexcom, Medtronic, Abbott, and Novo Nordisk. Ms. Lewis has reported no relevant financial relationships.

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

MRI criteria used to diagnose axial spondyloarthritis (axSpA) may require gender-specific revision, according to research conducted at Charité Universitätsmedizin Berlin.

Although established MRI markers were detected in both sexes, their prevalence was substantially different in some cases – ankylosis and fat metaplasia were more prevalent in male than female patients, for example, while sclerosis was far more common in females.

“There’s increasing evidence in the literature and awareness in clinical practice that there are some sex differences in the clinical presentation of axSpA,” said radiologist Sevtap Tugce Ulas, MD, at the annual European Congress of Rheumatology.

She presented the first results of a study examining the diagnostic performance of MRI findings for men and women. “Men have a high risk of structural damage, while women are more likely to be affected by peripheral manifestations with a higher risk for pain, stiffness, and fatigue.”

Joint biomechanics are different in men and women, she pointed out, which might explain some of the disparities. She observed that diagnostic delay – a known problem in axSpA – was “significantly longer” in female patients.

Dr. Ulas and colleagues conducted a post hoc analysis of participants in six prospective axSpA cohorts. From a total of more than 1,100 participants, the researchers identified 684 who had both a clinical diagnosis and complete imaging data available for evaluation. The study population included 379 men and women with and 305 men and women without axSpA.

The mean age overall in all groups was 37 years, with axSpA patients more likely than controls to have elevated C-reactive protein levels; levels were also higher in men with axSpA, compared with in women with axSpA.

Men with axSpA also were more likely than women to be HLA-B27 positive (91% vs. 79%), but there were similar mean Bath Ankylosing Spondylitis Disease Activity Index scores recorded (4.4 vs. 4.6) among the subjects with axSpA.

Two experienced radiologists, blinded to the clinical diagnosis, scored the MRI images independently of each other, looking for the presence of ankylosis; erosions; sclerosis; fat metaplasia; and bone marrow edema in the ventral, mid, and dorsal regions of the sacroiliac joints. Any disagreement between the two reviewers was assessed by a third, more experienced radiologist.

Clear differences in MRI markers

“If you look in detail, we found no major sex-specific differences for erosion and bone marrow edema,” Dr. Ulas reported.

The situation was quite different for other MRI parameters examined. Indeed, more men than women had evidence of ankylosis (24.3% vs. 7.4%) and fat metaplasia (58.8% vs. 42.6%). Conversely, women were more likely than men to have evidence of sclerosis (75.0% vs. 57.6%).

“To make the performance more easily comparable, we calculated a diagnostic odds ratio, which is simply positive likelihood ratio divided by negative likelihood ratio,” Dr. Ulas said.

Doing this showed that the presence of ankylosis had “an almost 10 times stronger performance in men,” with a DOR of 40.1 versus 4.7 for women.

“Interestingly, this was not only caused by low prevalence in females, but also by high rates of false positives,” she said.

DOR for the other parameters in men and women were 18.6 and 6.3 for fat metaplasia, 2.5 and 3.0 for sclerosis, 17.6 and 11.1 for joint erosion, and 2.5 and 3.7 for bone edema.

Overall, diagnostic accuracy was improved only when middle and dorsal lesions were considered.
 

‘Remarkably different’ results

“By definition, these patients have the same disease,” said Hendrik Schulze-Koops, MD, of Ludwig Maximilian University of Munich (Germany).

EULAR

Yet these are “remarkably different” findings, Dr. Schulze-Koops said during a closing highlights session of the congress.

Current imaging practices don’t differentiate between the sexes but perhaps they might need to, he said, because these data suggest “female patients have a different MRI pattern from what we learn from the textbooks.

“[The investigators] say diagnostic performance of established imaging markers on MRI is significantly lower in female axSpA patients, and we should consider this when we are in the situation where we question the disease.”

Marta Mosca, MD, PhD, of the University of Pisa (Italy) and who cochaired the session in which Dr. Ulas had presented the findings commented: “I think is very interesting. We always talk about gender differences in treatment and in the assessment.”

However, Dr. Mosca asked if there were plans to study other patient cohorts, notably those not just referred by a rheumatologist, as that was “a big limitation.”

Dr. Ulas replied: “I think we need follow-up studies to investigate this problem, because we know that there are differences in the clinical presentation and also in the imaging, and this is an important point.”

Of course, there are other limitations, Dr. Ulas said, such as the sole use of conventional T1-weighted spin echo sequences. Although often routinely used in clinical practice, this imaging technique can lead to overestimation of structural damage. Moreover, “subtle differences might have been missed” in bone marrow edema because it wasn’t included in the semiquantitative scoring system used.

“Most importantly, the MRI images under investigation were also used in the diagnostic process, which carries the risk of circular reasoning,” Dr. Ulas said.

However, there are clearly some differences in imaging appearance between men and women, and “we show a significantly lower performance of many typical MRI findings in women,” Dr. Ulas said. “We hope that these findings might spark a critical discussion on the appropriateness of sex-blind classification criteria for axSpA, and hopefully, eventually lead to refined criteria for both sexes.”

Dr. Ulas had no conflicts of interest to disclose. Dr. Schulze-Koops and Dr. Mosca were not involved in the study and had no relevant disclosures.

MRI criteria used to diagnose axial spondyloarthritis (axSpA) may require gender-specific revision, according to research conducted at Charité Universitätsmedizin Berlin.

Although established MRI markers were detected in both sexes, their prevalence was substantially different in some cases – ankylosis and fat metaplasia were more prevalent in male than female patients, for example, while sclerosis was far more common in females.

“There’s increasing evidence in the literature and awareness in clinical practice that there are some sex differences in the clinical presentation of axSpA,” said radiologist Sevtap Tugce Ulas, MD, at the annual European Congress of Rheumatology.

She presented the first results of a study examining the diagnostic performance of MRI findings for men and women. “Men have a high risk of structural damage, while women are more likely to be affected by peripheral manifestations with a higher risk for pain, stiffness, and fatigue.”

Joint biomechanics are different in men and women, she pointed out, which might explain some of the disparities. She observed that diagnostic delay – a known problem in axSpA – was “significantly longer” in female patients.

Dr. Ulas and colleagues conducted a post hoc analysis of participants in six prospective axSpA cohorts. From a total of more than 1,100 participants, the researchers identified 684 who had both a clinical diagnosis and complete imaging data available for evaluation. The study population included 379 men and women with and 305 men and women without axSpA.

The mean age overall in all groups was 37 years, with axSpA patients more likely than controls to have elevated C-reactive protein levels; levels were also higher in men with axSpA, compared with in women with axSpA.

Men with axSpA also were more likely than women to be HLA-B27 positive (91% vs. 79%), but there were similar mean Bath Ankylosing Spondylitis Disease Activity Index scores recorded (4.4 vs. 4.6) among the subjects with axSpA.

Two experienced radiologists, blinded to the clinical diagnosis, scored the MRI images independently of each other, looking for the presence of ankylosis; erosions; sclerosis; fat metaplasia; and bone marrow edema in the ventral, mid, and dorsal regions of the sacroiliac joints. Any disagreement between the two reviewers was assessed by a third, more experienced radiologist.

Clear differences in MRI markers

“If you look in detail, we found no major sex-specific differences for erosion and bone marrow edema,” Dr. Ulas reported.

The situation was quite different for other MRI parameters examined. Indeed, more men than women had evidence of ankylosis (24.3% vs. 7.4%) and fat metaplasia (58.8% vs. 42.6%). Conversely, women were more likely than men to have evidence of sclerosis (75.0% vs. 57.6%).

“To make the performance more easily comparable, we calculated a diagnostic odds ratio, which is simply positive likelihood ratio divided by negative likelihood ratio,” Dr. Ulas said.

Doing this showed that the presence of ankylosis had “an almost 10 times stronger performance in men,” with a DOR of 40.1 versus 4.7 for women.

“Interestingly, this was not only caused by low prevalence in females, but also by high rates of false positives,” she said.

DOR for the other parameters in men and women were 18.6 and 6.3 for fat metaplasia, 2.5 and 3.0 for sclerosis, 17.6 and 11.1 for joint erosion, and 2.5 and 3.7 for bone edema.

Overall, diagnostic accuracy was improved only when middle and dorsal lesions were considered.
 

‘Remarkably different’ results

“By definition, these patients have the same disease,” said Hendrik Schulze-Koops, MD, of Ludwig Maximilian University of Munich (Germany).

EULAR

Yet these are “remarkably different” findings, Dr. Schulze-Koops said during a closing highlights session of the congress.

Current imaging practices don’t differentiate between the sexes but perhaps they might need to, he said, because these data suggest “female patients have a different MRI pattern from what we learn from the textbooks.

“[The investigators] say diagnostic performance of established imaging markers on MRI is significantly lower in female axSpA patients, and we should consider this when we are in the situation where we question the disease.”

Marta Mosca, MD, PhD, of the University of Pisa (Italy) and who cochaired the session in which Dr. Ulas had presented the findings commented: “I think is very interesting. We always talk about gender differences in treatment and in the assessment.”

However, Dr. Mosca asked if there were plans to study other patient cohorts, notably those not just referred by a rheumatologist, as that was “a big limitation.”

Dr. Ulas replied: “I think we need follow-up studies to investigate this problem, because we know that there are differences in the clinical presentation and also in the imaging, and this is an important point.”

Of course, there are other limitations, Dr. Ulas said, such as the sole use of conventional T1-weighted spin echo sequences. Although often routinely used in clinical practice, this imaging technique can lead to overestimation of structural damage. Moreover, “subtle differences might have been missed” in bone marrow edema because it wasn’t included in the semiquantitative scoring system used.

“Most importantly, the MRI images under investigation were also used in the diagnostic process, which carries the risk of circular reasoning,” Dr. Ulas said.

However, there are clearly some differences in imaging appearance between men and women, and “we show a significantly lower performance of many typical MRI findings in women,” Dr. Ulas said. “We hope that these findings might spark a critical discussion on the appropriateness of sex-blind classification criteria for axSpA, and hopefully, eventually lead to refined criteria for both sexes.”

Dr. Ulas had no conflicts of interest to disclose. Dr. Schulze-Koops and Dr. Mosca were not involved in the study and had no relevant disclosures.

MRI criteria used to diagnose axial spondyloarthritis (axSpA) may require gender-specific revision, according to research conducted at Charité Universitätsmedizin Berlin.

Although established MRI markers were detected in both sexes, their prevalence was substantially different in some cases – ankylosis and fat metaplasia were more prevalent in male than female patients, for example, while sclerosis was far more common in females.

“There’s increasing evidence in the literature and awareness in clinical practice that there are some sex differences in the clinical presentation of axSpA,” said radiologist Sevtap Tugce Ulas, MD, at the annual European Congress of Rheumatology.

She presented the first results of a study examining the diagnostic performance of MRI findings for men and women. “Men have a high risk of structural damage, while women are more likely to be affected by peripheral manifestations with a higher risk for pain, stiffness, and fatigue.”

Joint biomechanics are different in men and women, she pointed out, which might explain some of the disparities. She observed that diagnostic delay – a known problem in axSpA – was “significantly longer” in female patients.

Dr. Ulas and colleagues conducted a post hoc analysis of participants in six prospective axSpA cohorts. From a total of more than 1,100 participants, the researchers identified 684 who had both a clinical diagnosis and complete imaging data available for evaluation. The study population included 379 men and women with and 305 men and women without axSpA.

The mean age overall in all groups was 37 years, with axSpA patients more likely than controls to have elevated C-reactive protein levels; levels were also higher in men with axSpA, compared with in women with axSpA.

Men with axSpA also were more likely than women to be HLA-B27 positive (91% vs. 79%), but there were similar mean Bath Ankylosing Spondylitis Disease Activity Index scores recorded (4.4 vs. 4.6) among the subjects with axSpA.

Two experienced radiologists, blinded to the clinical diagnosis, scored the MRI images independently of each other, looking for the presence of ankylosis; erosions; sclerosis; fat metaplasia; and bone marrow edema in the ventral, mid, and dorsal regions of the sacroiliac joints. Any disagreement between the two reviewers was assessed by a third, more experienced radiologist.

Clear differences in MRI markers

“If you look in detail, we found no major sex-specific differences for erosion and bone marrow edema,” Dr. Ulas reported.

The situation was quite different for other MRI parameters examined. Indeed, more men than women had evidence of ankylosis (24.3% vs. 7.4%) and fat metaplasia (58.8% vs. 42.6%). Conversely, women were more likely than men to have evidence of sclerosis (75.0% vs. 57.6%).

“To make the performance more easily comparable, we calculated a diagnostic odds ratio, which is simply positive likelihood ratio divided by negative likelihood ratio,” Dr. Ulas said.

Doing this showed that the presence of ankylosis had “an almost 10 times stronger performance in men,” with a DOR of 40.1 versus 4.7 for women.

“Interestingly, this was not only caused by low prevalence in females, but also by high rates of false positives,” she said.

DOR for the other parameters in men and women were 18.6 and 6.3 for fat metaplasia, 2.5 and 3.0 for sclerosis, 17.6 and 11.1 for joint erosion, and 2.5 and 3.7 for bone edema.

Overall, diagnostic accuracy was improved only when middle and dorsal lesions were considered.
 

‘Remarkably different’ results

“By definition, these patients have the same disease,” said Hendrik Schulze-Koops, MD, of Ludwig Maximilian University of Munich (Germany).

EULAR

Yet these are “remarkably different” findings, Dr. Schulze-Koops said during a closing highlights session of the congress.

Current imaging practices don’t differentiate between the sexes but perhaps they might need to, he said, because these data suggest “female patients have a different MRI pattern from what we learn from the textbooks.

“[The investigators] say diagnostic performance of established imaging markers on MRI is significantly lower in female axSpA patients, and we should consider this when we are in the situation where we question the disease.”

Marta Mosca, MD, PhD, of the University of Pisa (Italy) and who cochaired the session in which Dr. Ulas had presented the findings commented: “I think is very interesting. We always talk about gender differences in treatment and in the assessment.”

However, Dr. Mosca asked if there were plans to study other patient cohorts, notably those not just referred by a rheumatologist, as that was “a big limitation.”

Dr. Ulas replied: “I think we need follow-up studies to investigate this problem, because we know that there are differences in the clinical presentation and also in the imaging, and this is an important point.”

Of course, there are other limitations, Dr. Ulas said, such as the sole use of conventional T1-weighted spin echo sequences. Although often routinely used in clinical practice, this imaging technique can lead to overestimation of structural damage. Moreover, “subtle differences might have been missed” in bone marrow edema because it wasn’t included in the semiquantitative scoring system used.

“Most importantly, the MRI images under investigation were also used in the diagnostic process, which carries the risk of circular reasoning,” Dr. Ulas said.

However, there are clearly some differences in imaging appearance between men and women, and “we show a significantly lower performance of many typical MRI findings in women,” Dr. Ulas said. “We hope that these findings might spark a critical discussion on the appropriateness of sex-blind classification criteria for axSpA, and hopefully, eventually lead to refined criteria for both sexes.”

Dr. Ulas had no conflicts of interest to disclose. Dr. Schulze-Koops and Dr. Mosca were not involved in the study and had no relevant disclosures.

CHICAGO – Comorbid autoimmune disease is associated with a greater chance of survival among women with stage IV breast cancer, according to a retrospective study presented at the annual meeting of the American Society of Clinical Oncology.

“It’s counterintuitive that, if you have two diseases instead of one, that you live longer, so then we had to scratch our heads a little bit and think about why these people are living longer,” said lead author Demitrios Dedousis, MD, University Hospitals, Case Medical Center, Cleveland.

Dr. Dedousis and colleagues conducted a retrospective analysis of patients from Surveillance, Epidemiology, and End Results–Medicare databases between 2007 and 2014 with breast cancer. The study included data from 137,324 patients diagnosed between 2007 and 2012, before the widespread use of immunotherapy. 27% of patients had an autoimmune disease, most commonly rheumatoid arthritis (23%), psoriasis (2.4%), and systemic lupus erythematosus (1.1%).

When all patients were included in the analysis, those with autoimmune disorders had slightly longer survival times, but these weren’t clinically significant. A subanalysis found a greater difference in survival.

The association appears more pronounced in metastatic cancer. Patients with stage 4 breast cancer and autoimmune disease had a longer mean overall survival (36 months vs. 30 months; hazard ratio, 1.46; P < .0001. Cancer-specific survival: HR, 1.39; P < .0001). Patients with autoimmune disease and stage 1-3 breast cancer had lower overall survival (P < .0001, P < 0.0001, and P = 0.026 respectively), compared with patients without autoimmune disease.

“What we thought was happening is that the lack of increased survival in stages 1 through 3 was hiding the increase in survival among the stage IV patients when looking at the overall cohort,” Dr. Dedousis said.

The retrospective nature of the study makes it impossible to draw any firm conclusions about causation. It could be that patients who have already been diagnosed with an autoimmune disease are more vigilant about going to health checkups. “There are other possible explanations, but the one that’s most interesting to us is that their immune system is involved in fighting the cancer. Our study certainly didn’t prove that, but it’s suggesting that’s a possibility,” Dr. Dedousis said.

He and his coauthors anticipate conducting similar studies in other cancers to see if there are similar relationships. Some preliminary work has already suggested something similar in lung cancer. “I think demonstrating this in a few kinds of cancer goes part of the way towards showing that this is a real biological phenomenon,” he said.

Another research avenue is to examine the immune systems and pathology specimens in patients with both an autoimmune disease and cancer to see if there is a greater immune response within the tumor. If so, that could suggest new immunotherapy strategies.

Another possibility is to look at the specific immune pathways within “protective” autoimmune conditions. “For the sake of argument, if we find a particular autoimmune condition is improving survival across multiple kinds of cancers, we could look at those pathways that are specifically involved in that autoimmune condition. It might help us identify a target for drug development,” Dr. Dedousis said.

Asked why a potential benefit might be more apparent in late-stage disease, he suggested that, in early-stage breast cancer, surgery and other treatments may be so effective that the immune system’s role only rarely makes a difference. It could play a larger role in late-stage disease when there are less effective therapies. It could also be that the immune system doesn’t recognize the cancer until it has spread beyond the regional lymph nodes on its way to metastasizing.

According to the National Cancer Institute, 10%-30% of people with cancer also have an autoimmune disease.

Dr. Dedousis has no relevant financial disclosures.

CHICAGO – Comorbid autoimmune disease is associated with a greater chance of survival among women with stage IV breast cancer, according to a retrospective study presented at the annual meeting of the American Society of Clinical Oncology.

“It’s counterintuitive that, if you have two diseases instead of one, that you live longer, so then we had to scratch our heads a little bit and think about why these people are living longer,” said lead author Demitrios Dedousis, MD, University Hospitals, Case Medical Center, Cleveland.

Dr. Dedousis and colleagues conducted a retrospective analysis of patients from Surveillance, Epidemiology, and End Results–Medicare databases between 2007 and 2014 with breast cancer. The study included data from 137,324 patients diagnosed between 2007 and 2012, before the widespread use of immunotherapy. 27% of patients had an autoimmune disease, most commonly rheumatoid arthritis (23%), psoriasis (2.4%), and systemic lupus erythematosus (1.1%).

When all patients were included in the analysis, those with autoimmune disorders had slightly longer survival times, but these weren’t clinically significant. A subanalysis found a greater difference in survival.

The association appears more pronounced in metastatic cancer. Patients with stage 4 breast cancer and autoimmune disease had a longer mean overall survival (36 months vs. 30 months; hazard ratio, 1.46; P < .0001. Cancer-specific survival: HR, 1.39; P < .0001). Patients with autoimmune disease and stage 1-3 breast cancer had lower overall survival (P < .0001, P < 0.0001, and P = 0.026 respectively), compared with patients without autoimmune disease.

“What we thought was happening is that the lack of increased survival in stages 1 through 3 was hiding the increase in survival among the stage IV patients when looking at the overall cohort,” Dr. Dedousis said.

The retrospective nature of the study makes it impossible to draw any firm conclusions about causation. It could be that patients who have already been diagnosed with an autoimmune disease are more vigilant about going to health checkups. “There are other possible explanations, but the one that’s most interesting to us is that their immune system is involved in fighting the cancer. Our study certainly didn’t prove that, but it’s suggesting that’s a possibility,” Dr. Dedousis said.

He and his coauthors anticipate conducting similar studies in other cancers to see if there are similar relationships. Some preliminary work has already suggested something similar in lung cancer. “I think demonstrating this in a few kinds of cancer goes part of the way towards showing that this is a real biological phenomenon,” he said.

Another research avenue is to examine the immune systems and pathology specimens in patients with both an autoimmune disease and cancer to see if there is a greater immune response within the tumor. If so, that could suggest new immunotherapy strategies.

Another possibility is to look at the specific immune pathways within “protective” autoimmune conditions. “For the sake of argument, if we find a particular autoimmune condition is improving survival across multiple kinds of cancers, we could look at those pathways that are specifically involved in that autoimmune condition. It might help us identify a target for drug development,” Dr. Dedousis said.

Asked why a potential benefit might be more apparent in late-stage disease, he suggested that, in early-stage breast cancer, surgery and other treatments may be so effective that the immune system’s role only rarely makes a difference. It could play a larger role in late-stage disease when there are less effective therapies. It could also be that the immune system doesn’t recognize the cancer until it has spread beyond the regional lymph nodes on its way to metastasizing.

According to the National Cancer Institute, 10%-30% of people with cancer also have an autoimmune disease.

Dr. Dedousis has no relevant financial disclosures.

CHICAGO – Comorbid autoimmune disease is associated with a greater chance of survival among women with stage IV breast cancer, according to a retrospective study presented at the annual meeting of the American Society of Clinical Oncology.

“It’s counterintuitive that, if you have two diseases instead of one, that you live longer, so then we had to scratch our heads a little bit and think about why these people are living longer,” said lead author Demitrios Dedousis, MD, University Hospitals, Case Medical Center, Cleveland.

Dr. Dedousis and colleagues conducted a retrospective analysis of patients from Surveillance, Epidemiology, and End Results–Medicare databases between 2007 and 2014 with breast cancer. The study included data from 137,324 patients diagnosed between 2007 and 2012, before the widespread use of immunotherapy. 27% of patients had an autoimmune disease, most commonly rheumatoid arthritis (23%), psoriasis (2.4%), and systemic lupus erythematosus (1.1%).

When all patients were included in the analysis, those with autoimmune disorders had slightly longer survival times, but these weren’t clinically significant. A subanalysis found a greater difference in survival.

The association appears more pronounced in metastatic cancer. Patients with stage 4 breast cancer and autoimmune disease had a longer mean overall survival (36 months vs. 30 months; hazard ratio, 1.46; P < .0001. Cancer-specific survival: HR, 1.39; P < .0001). Patients with autoimmune disease and stage 1-3 breast cancer had lower overall survival (P < .0001, P < 0.0001, and P = 0.026 respectively), compared with patients without autoimmune disease.

“What we thought was happening is that the lack of increased survival in stages 1 through 3 was hiding the increase in survival among the stage IV patients when looking at the overall cohort,” Dr. Dedousis said.

The retrospective nature of the study makes it impossible to draw any firm conclusions about causation. It could be that patients who have already been diagnosed with an autoimmune disease are more vigilant about going to health checkups. “There are other possible explanations, but the one that’s most interesting to us is that their immune system is involved in fighting the cancer. Our study certainly didn’t prove that, but it’s suggesting that’s a possibility,” Dr. Dedousis said.

He and his coauthors anticipate conducting similar studies in other cancers to see if there are similar relationships. Some preliminary work has already suggested something similar in lung cancer. “I think demonstrating this in a few kinds of cancer goes part of the way towards showing that this is a real biological phenomenon,” he said.

Another research avenue is to examine the immune systems and pathology specimens in patients with both an autoimmune disease and cancer to see if there is a greater immune response within the tumor. If so, that could suggest new immunotherapy strategies.

Another possibility is to look at the specific immune pathways within “protective” autoimmune conditions. “For the sake of argument, if we find a particular autoimmune condition is improving survival across multiple kinds of cancers, we could look at those pathways that are specifically involved in that autoimmune condition. It might help us identify a target for drug development,” Dr. Dedousis said.

Asked why a potential benefit might be more apparent in late-stage disease, he suggested that, in early-stage breast cancer, surgery and other treatments may be so effective that the immune system’s role only rarely makes a difference. It could play a larger role in late-stage disease when there are less effective therapies. It could also be that the immune system doesn’t recognize the cancer until it has spread beyond the regional lymph nodes on its way to metastasizing.

According to the National Cancer Institute, 10%-30% of people with cancer also have an autoimmune disease.

Dr. Dedousis has no relevant financial disclosures.

CHICAGO – Progress in breast cancer treatment over the past 2 decades has reduced expected mortality from both early-stage and metastatic disease, according to a new model that looked at 10-year distant recurrence-free survival and survival time after metastatic diagnosis, among other factors.

“There has been an accelerating influx of new treatments for breast cancer starting around 1990. We wished to ask whether and to what extent decades of metastatic treatment advances may have affected population level breast cancer mortality,” said Jennifer Lee Caswell-Jin, MD, during a presentation of the study at the annual meeting of the American Society of Clinical Oncology.

“Our models find that metastatic treatments improved population-level survival in all breast cancer subtypes since 2000 with substantial variability by subtype," said Dr. Caswell-Jin, who is a medical oncologist with Stanford (Calif.) Medicine specializing in breast cancer.

The study is based on an analysis of four models from the Cancer Intervention and Surveillance Modeling Network (CISNET). The models simulated breast cancer mortality between 2000 and 2019 factoring in the use of mammography, efficacy and dissemination of estrogen receptor (ER) and HER2-specific treatments of early-stage (stages I-III) and metastatic (stage IV or distant recurrence) disease, but also non–cancer-related mortality. The models compared overall and ER/HER2-specific breast cancer mortality rates during this period with estimated rates with no screening or treatment, and then attributed mortality reductions to screening, early-stage, or metastatic treatment.

The results were compared with three clinical trials that tested therapies in different subtypes of metastatic disease. Dr. Caswell-Jin and colleagues adjusted the analysis to reflect expected differences between clinical trial populations and the broader population by sampling simulated patients who resembled the trial population.

The investigators found that, at 71%, the biggest drop in mortality rates were for women with ER+/HER2+ breast cancer, followed by 61% for women with ER-/HER2+ breast cancer and 59% for women with ER+/HER2– breast cancer. Triple-negative breast cancer – one of the most challenging breast cancers to treat – only saw a drop of 40% during this period. About 19% of the overall reduction in breast cancer mortality were caused by treatments after metastasis.

The median survival after a diagnosis of ER+/HER2– metastatic recurrence increased from 2 years in 2000 to 3.5 years in 2019. In triple-negative breast cancer, the increase was more modest, from 1.2 years in 2000 to 1.8 years in 2019. After a diagnosis of metastatic recurrence of ER+/HER2+ breast cancer, median survival increased from 2.3 years in 2000 to 4.8 years in 2019, and for ER–/HER2+ breast cancer, from 2.2 years in 2000 to 3.9 years in 2019.

“How much metastatic treatments contributed to the overall mortality reduction varied over time depending on what therapies were entering the metastatic setting at that time and what therapies were transitioning from the metastatic to early-stage setting,” Dr. Caswell-Jin said.

The study did not include sacituzumab govitecan for metastatic triple-negative breast cancer, or trastuzumab deruxtecan and tucatinib for HER2-positive disease, which were approved after 2020. “The numbers that we cite will be better today for triple-negative breast cancer because of those two drugs. And will be even better for HER2-positive breast cancer because of those two drugs,” she said.

During the Q&A portion of the presentation, Daniel Hayes, MD, the Stuart B. Padnos Professor of Breast Cancer Research at the University of Michigan Rogel Cancer Center, Ann Arbor, asked about the potential of CISNET as an in-practice diagnostic tool.

“We’ve traditionally told patients who have metastatic disease that they will not be cured. I told two patients that on Tuesday. Can CISNET modeling let us begin to see if there is indeed now, with the improved therapies we have, a group of patients who do appear to be cured, or is that not possible?” he asked.

Perhaps, Dr. Caswell-Jin said, in a very small population of older patients with HER2-positive breast cancer that did in fact occur, but to a very small degree.

CHICAGO – Progress in breast cancer treatment over the past 2 decades has reduced expected mortality from both early-stage and metastatic disease, according to a new model that looked at 10-year distant recurrence-free survival and survival time after metastatic diagnosis, among other factors.

“There has been an accelerating influx of new treatments for breast cancer starting around 1990. We wished to ask whether and to what extent decades of metastatic treatment advances may have affected population level breast cancer mortality,” said Jennifer Lee Caswell-Jin, MD, during a presentation of the study at the annual meeting of the American Society of Clinical Oncology.

“Our models find that metastatic treatments improved population-level survival in all breast cancer subtypes since 2000 with substantial variability by subtype," said Dr. Caswell-Jin, who is a medical oncologist with Stanford (Calif.) Medicine specializing in breast cancer.

The study is based on an analysis of four models from the Cancer Intervention and Surveillance Modeling Network (CISNET). The models simulated breast cancer mortality between 2000 and 2019 factoring in the use of mammography, efficacy and dissemination of estrogen receptor (ER) and HER2-specific treatments of early-stage (stages I-III) and metastatic (stage IV or distant recurrence) disease, but also non–cancer-related mortality. The models compared overall and ER/HER2-specific breast cancer mortality rates during this period with estimated rates with no screening or treatment, and then attributed mortality reductions to screening, early-stage, or metastatic treatment.

The results were compared with three clinical trials that tested therapies in different subtypes of metastatic disease. Dr. Caswell-Jin and colleagues adjusted the analysis to reflect expected differences between clinical trial populations and the broader population by sampling simulated patients who resembled the trial population.

The investigators found that, at 71%, the biggest drop in mortality rates were for women with ER+/HER2+ breast cancer, followed by 61% for women with ER-/HER2+ breast cancer and 59% for women with ER+/HER2– breast cancer. Triple-negative breast cancer – one of the most challenging breast cancers to treat – only saw a drop of 40% during this period. About 19% of the overall reduction in breast cancer mortality were caused by treatments after metastasis.

The median survival after a diagnosis of ER+/HER2– metastatic recurrence increased from 2 years in 2000 to 3.5 years in 2019. In triple-negative breast cancer, the increase was more modest, from 1.2 years in 2000 to 1.8 years in 2019. After a diagnosis of metastatic recurrence of ER+/HER2+ breast cancer, median survival increased from 2.3 years in 2000 to 4.8 years in 2019, and for ER–/HER2+ breast cancer, from 2.2 years in 2000 to 3.9 years in 2019.

“How much metastatic treatments contributed to the overall mortality reduction varied over time depending on what therapies were entering the metastatic setting at that time and what therapies were transitioning from the metastatic to early-stage setting,” Dr. Caswell-Jin said.

The study did not include sacituzumab govitecan for metastatic triple-negative breast cancer, or trastuzumab deruxtecan and tucatinib for HER2-positive disease, which were approved after 2020. “The numbers that we cite will be better today for triple-negative breast cancer because of those two drugs. And will be even better for HER2-positive breast cancer because of those two drugs,” she said.

During the Q&A portion of the presentation, Daniel Hayes, MD, the Stuart B. Padnos Professor of Breast Cancer Research at the University of Michigan Rogel Cancer Center, Ann Arbor, asked about the potential of CISNET as an in-practice diagnostic tool.

“We’ve traditionally told patients who have metastatic disease that they will not be cured. I told two patients that on Tuesday. Can CISNET modeling let us begin to see if there is indeed now, with the improved therapies we have, a group of patients who do appear to be cured, or is that not possible?” he asked.

Perhaps, Dr. Caswell-Jin said, in a very small population of older patients with HER2-positive breast cancer that did in fact occur, but to a very small degree.

CHICAGO – Progress in breast cancer treatment over the past 2 decades has reduced expected mortality from both early-stage and metastatic disease, according to a new model that looked at 10-year distant recurrence-free survival and survival time after metastatic diagnosis, among other factors.

“There has been an accelerating influx of new treatments for breast cancer starting around 1990. We wished to ask whether and to what extent decades of metastatic treatment advances may have affected population level breast cancer mortality,” said Jennifer Lee Caswell-Jin, MD, during a presentation of the study at the annual meeting of the American Society of Clinical Oncology.

“Our models find that metastatic treatments improved population-level survival in all breast cancer subtypes since 2000 with substantial variability by subtype," said Dr. Caswell-Jin, who is a medical oncologist with Stanford (Calif.) Medicine specializing in breast cancer.

The study is based on an analysis of four models from the Cancer Intervention and Surveillance Modeling Network (CISNET). The models simulated breast cancer mortality between 2000 and 2019 factoring in the use of mammography, efficacy and dissemination of estrogen receptor (ER) and HER2-specific treatments of early-stage (stages I-III) and metastatic (stage IV or distant recurrence) disease, but also non–cancer-related mortality. The models compared overall and ER/HER2-specific breast cancer mortality rates during this period with estimated rates with no screening or treatment, and then attributed mortality reductions to screening, early-stage, or metastatic treatment.

The results were compared with three clinical trials that tested therapies in different subtypes of metastatic disease. Dr. Caswell-Jin and colleagues adjusted the analysis to reflect expected differences between clinical trial populations and the broader population by sampling simulated patients who resembled the trial population.

The investigators found that, at 71%, the biggest drop in mortality rates were for women with ER+/HER2+ breast cancer, followed by 61% for women with ER-/HER2+ breast cancer and 59% for women with ER+/HER2– breast cancer. Triple-negative breast cancer – one of the most challenging breast cancers to treat – only saw a drop of 40% during this period. About 19% of the overall reduction in breast cancer mortality were caused by treatments after metastasis.

The median survival after a diagnosis of ER+/HER2– metastatic recurrence increased from 2 years in 2000 to 3.5 years in 2019. In triple-negative breast cancer, the increase was more modest, from 1.2 years in 2000 to 1.8 years in 2019. After a diagnosis of metastatic recurrence of ER+/HER2+ breast cancer, median survival increased from 2.3 years in 2000 to 4.8 years in 2019, and for ER–/HER2+ breast cancer, from 2.2 years in 2000 to 3.9 years in 2019.

“How much metastatic treatments contributed to the overall mortality reduction varied over time depending on what therapies were entering the metastatic setting at that time and what therapies were transitioning from the metastatic to early-stage setting,” Dr. Caswell-Jin said.

The study did not include sacituzumab govitecan for metastatic triple-negative breast cancer, or trastuzumab deruxtecan and tucatinib for HER2-positive disease, which were approved after 2020. “The numbers that we cite will be better today for triple-negative breast cancer because of those two drugs. And will be even better for HER2-positive breast cancer because of those two drugs,” she said.

During the Q&A portion of the presentation, Daniel Hayes, MD, the Stuart B. Padnos Professor of Breast Cancer Research at the University of Michigan Rogel Cancer Center, Ann Arbor, asked about the potential of CISNET as an in-practice diagnostic tool.

“We’ve traditionally told patients who have metastatic disease that they will not be cured. I told two patients that on Tuesday. Can CISNET modeling let us begin to see if there is indeed now, with the improved therapies we have, a group of patients who do appear to be cured, or is that not possible?” he asked.

Perhaps, Dr. Caswell-Jin said, in a very small population of older patients with HER2-positive breast cancer that did in fact occur, but to a very small degree.

Contrary to previous analyses, women without a history of psychiatric illness who take combined hormonal contraceptives do not have an increased risk for attempted suicide but may have a reduced risk with extended use, new research suggests.

In a study of more than 800 women younger than age 50 who attempted suicide and more than 3,000 age-matched peers, results showed those who took hormonal contraceptives had a 27% reduced risk for attempted suicide.

areeya_ann/Thinkstock

Further analysis showed this was confined to women without a history of psychiatric illness and the reduction in risk rose to 43% among those who took combined hormonal contraceptives rather than progestin-only versions.

The protective effect against attempted suicide increased further to 46% if ethinyl estradiol (EE)–containing preparations were used. Moreover, the beneficial effect of contraceptive use increased over time.

The main message is the “current use of hormonal contraceptives is not associated with an increased risk of attempted suicide in our population,” study presenter Elena Toffol, MD, PhD, department of public health, University of Helsinki, told meeting attendees at the European Psychiatric Association 2022 Congress.
 

Age range differences

Dr. Toffol said there could be “several reasons” why the results are different from those in previous studies, including that the researchers included a “larger age range.” She noted it is known that “older women have a lower rate of attempted suicide and use different types of contraceptives.”

Dr. Toffol said in an interview that, although it’s “hard to estimate any causality” because this is an observational study, it is “tempting to speculate, and it is plausible, that hormones partly play a role with some, but not all, women being more sensitive to hormonal influences.”

However, the results “may also reflect life choices or a protective life status; for example, more stable relationships or more conscious and health-focused behaviors,” she said.

“It may also be that the underlying characteristics of women who are prescribed or opt for certain types of contraceptives are somehow related to their suicidal risk,” she added.

In 2019, the global age-standardized suicide rate was 9.0 per 100,000, which translates into more than 700,000 deaths every year, Dr. Toffol noted.

However, she emphasized the World Health Organization has calculated that, for every adult who dies by suicide, more than 20 people attempt suicide. In addition, data from the U.S. Centers for Disease Control and Prevention indicate that attempted suicides are three times more common among young women than in men.

“What are the reasons for this gender gap?” Dr. Toffol asked during her presentation.

“It is known that the major risk factor for suicidal behavior is a psychiatric disorder, and in particular depression and mood disorders. And depression and mood disorders are more common in women than in men,” she said.

However, there is also “growing interest into the role of biological factors” in the risk for suicide, including hormones and hormonal contraception. Some studies have also suggested that there is an increased risk for depression and “both completed and attempted suicide” after starting hormonal contraception.

Dr. Toffol added that about 70% of European women use some form of contraception and, among Finnish women, 40% choose a hormonal contraceptive.
 

Nested analysis

The researchers conducted a nested case-control analysis combining 2017 national prescription data on 587,823 women aged 15-49 years with information from general and primary healthcare registers for the years 2018 to 2019.

They were able to identify 818 cases of attempted suicide among the women. These were matched 4:1 with 3,272 age-matched healthy women who acted as the control group. Use of hormonal contraceptives in the previous 180 days was determined for the whole cohort.

Among users of hormonal contraceptives, there were 344 attempted suicides in 2017, at an incidence rate of 0.59 per 1,000 person-years. This compared with 474 attempted suicides among nonusers, at an incidence rate of 0.81 per 1000 person-years.

Kaplan-Meier analysis showed there was a significant difference in rates for attempted suicide among hormonal contraceptive users versus nonusers, at an incidence rate ratio of 0.73 (P < .0001) – and the difference increased over time.

In addition, the incidence of attempted suicide decreased with increasing age, with the highest incidence rate in women aged 15-19 years (1.62 per 1,000 person-years).

Conditional logistic regression analysis that controlled for education, marital status, chronic disease, recent psychiatric hospitalization, and current use of psychotropic medication showed hormonal contraceptive use was not linked to an increased risk of attempted suicide overall, at an odds ratio of 0.79 (95% confidence interval, 0.56-1.11).

However, when they looked specifically at women without a history of psychiatric illness, the association became significant, at an OR of 0.73 for attempted suicide among hormonal contraceptive users (95% CI, 0.58-0.91), while the relationship remained nonsignificant in women with a history of psychiatric disorders.

Further analysis suggested the significant association was confined to women taking combined hormonal contraceptives, at an OR of 0.57 for suicide attempt versus nonusers (95% CI, 0.44-0.75), and those use EE-containing preparations (OR, 0.54; 95% CI, 0.40-0.73).

There was a suggestion in the data that hormonal contraceptives containing desogestrel or drospirenone alongside EE may offer the greatest reduction in attempted suicide risk, but that did not survive multivariate analysis.

Dr. Toffol also noted that they were not able to capture data on use of intrauterine devices in their analysis.

“There is a growing number of municipalities in Finland that are providing free-of-charge contraception to young women” that is often an intrauterine device, she said. The researchers hope to include these women in a future analysis.
 

‘Age matters’

Commenting on the findings, Alexis C. Edwards, PhD, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, said the current study’s findings “made a lot of sense.” Dr. Edwards wasn’t involved with this study but conducted a previous study of 216,702 Swedish women aged 15-22 years that showed use of combination or progestin-only oral contraceptives was associated with an increased risk for suicidal behavior.

She agreed with Dr. Toffol that the “much larger age range” in the new study may have played a role in showing the opposite result.

“The trajectory that we saw if we had been able to continue following the women for longer – which we couldn’t, due to limitations of the registries – [was that] using hormonal contraceptives was going to end up being protective, so I do think that it matters what age you’re looking at,” she said.

Dr. Edwards noted the takeaway from both studies “is that, even if there is a slight increase in risk from using hormonal contraceptives, it’s short lived and it’s probably specific to young women, which is important.”

She suggested the hormonal benefit from extended contraceptive use could come from the regulation of mood, as it offers a “more stable hormonal course than what their body might be putting them through in the absence of using the pill.”

Overall, it is “really lovely to see very well-executed studies on this, providing more empirical evidence on this question, because it is something that’s relevant to anyone who’s potentially going to be using hormonal contraception,” Dr. Edwards said.
 

Clinical implications?

Andrea Fiorillo, MD, PhD, department of psychiatry, University of Campania “Luigi Vanvitelli,” Naples, Italy, said in a press release that the “striking” findings of the current study need “careful evaluation.”

They also need to be replicated in “different cohorts of women and controlled for the impact of several psychosocial stressors, such as economic upheavals, social insecurity, and uncertainty due to the COVID pandemic,” said Dr. Fiorillo, who was not involved with the research.

Nevertheless, she believes the “clinical implications of the study are obvious and may help to destigmatize the use of hormonal contraceptives.”

The study was funded by the Jane and Aatos Erkko Foundation, the Avohoidon Tsukimis äätiö (Foundation for Primary Care Research), the Yrj ö Jahnsson Foundation, and the Finnish Cultural Foundation. No relevant financial relationships were reported.

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

Contrary to previous analyses, women without a history of psychiatric illness who take combined hormonal contraceptives do not have an increased risk for attempted suicide but may have a reduced risk with extended use, new research suggests.

In a study of more than 800 women younger than age 50 who attempted suicide and more than 3,000 age-matched peers, results showed those who took hormonal contraceptives had a 27% reduced risk for attempted suicide.

areeya_ann/Thinkstock

Further analysis showed this was confined to women without a history of psychiatric illness and the reduction in risk rose to 43% among those who took combined hormonal contraceptives rather than progestin-only versions.

The protective effect against attempted suicide increased further to 46% if ethinyl estradiol (EE)–containing preparations were used. Moreover, the beneficial effect of contraceptive use increased over time.

The main message is the “current use of hormonal contraceptives is not associated with an increased risk of attempted suicide in our population,” study presenter Elena Toffol, MD, PhD, department of public health, University of Helsinki, told meeting attendees at the European Psychiatric Association 2022 Congress.
 

Age range differences

Dr. Toffol said there could be “several reasons” why the results are different from those in previous studies, including that the researchers included a “larger age range.” She noted it is known that “older women have a lower rate of attempted suicide and use different types of contraceptives.”

Dr. Toffol said in an interview that, although it’s “hard to estimate any causality” because this is an observational study, it is “tempting to speculate, and it is plausible, that hormones partly play a role with some, but not all, women being more sensitive to hormonal influences.”

However, the results “may also reflect life choices or a protective life status; for example, more stable relationships or more conscious and health-focused behaviors,” she said.

“It may also be that the underlying characteristics of women who are prescribed or opt for certain types of contraceptives are somehow related to their suicidal risk,” she added.

In 2019, the global age-standardized suicide rate was 9.0 per 100,000, which translates into more than 700,000 deaths every year, Dr. Toffol noted.

However, she emphasized the World Health Organization has calculated that, for every adult who dies by suicide, more than 20 people attempt suicide. In addition, data from the U.S. Centers for Disease Control and Prevention indicate that attempted suicides are three times more common among young women than in men.

“What are the reasons for this gender gap?” Dr. Toffol asked during her presentation.

“It is known that the major risk factor for suicidal behavior is a psychiatric disorder, and in particular depression and mood disorders. And depression and mood disorders are more common in women than in men,” she said.

However, there is also “growing interest into the role of biological factors” in the risk for suicide, including hormones and hormonal contraception. Some studies have also suggested that there is an increased risk for depression and “both completed and attempted suicide” after starting hormonal contraception.

Dr. Toffol added that about 70% of European women use some form of contraception and, among Finnish women, 40% choose a hormonal contraceptive.
 

Nested analysis

The researchers conducted a nested case-control analysis combining 2017 national prescription data on 587,823 women aged 15-49 years with information from general and primary healthcare registers for the years 2018 to 2019.

They were able to identify 818 cases of attempted suicide among the women. These were matched 4:1 with 3,272 age-matched healthy women who acted as the control group. Use of hormonal contraceptives in the previous 180 days was determined for the whole cohort.

Among users of hormonal contraceptives, there were 344 attempted suicides in 2017, at an incidence rate of 0.59 per 1,000 person-years. This compared with 474 attempted suicides among nonusers, at an incidence rate of 0.81 per 1000 person-years.

Kaplan-Meier analysis showed there was a significant difference in rates for attempted suicide among hormonal contraceptive users versus nonusers, at an incidence rate ratio of 0.73 (P < .0001) – and the difference increased over time.

In addition, the incidence of attempted suicide decreased with increasing age, with the highest incidence rate in women aged 15-19 years (1.62 per 1,000 person-years).

Conditional logistic regression analysis that controlled for education, marital status, chronic disease, recent psychiatric hospitalization, and current use of psychotropic medication showed hormonal contraceptive use was not linked to an increased risk of attempted suicide overall, at an odds ratio of 0.79 (95% confidence interval, 0.56-1.11).

However, when they looked specifically at women without a history of psychiatric illness, the association became significant, at an OR of 0.73 for attempted suicide among hormonal contraceptive users (95% CI, 0.58-0.91), while the relationship remained nonsignificant in women with a history of psychiatric disorders.

Further analysis suggested the significant association was confined to women taking combined hormonal contraceptives, at an OR of 0.57 for suicide attempt versus nonusers (95% CI, 0.44-0.75), and those use EE-containing preparations (OR, 0.54; 95% CI, 0.40-0.73).

There was a suggestion in the data that hormonal contraceptives containing desogestrel or drospirenone alongside EE may offer the greatest reduction in attempted suicide risk, but that did not survive multivariate analysis.

Dr. Toffol also noted that they were not able to capture data on use of intrauterine devices in their analysis.

“There is a growing number of municipalities in Finland that are providing free-of-charge contraception to young women” that is often an intrauterine device, she said. The researchers hope to include these women in a future analysis.
 

‘Age matters’

Commenting on the findings, Alexis C. Edwards, PhD, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, said the current study’s findings “made a lot of sense.” Dr. Edwards wasn’t involved with this study but conducted a previous study of 216,702 Swedish women aged 15-22 years that showed use of combination or progestin-only oral contraceptives was associated with an increased risk for suicidal behavior.

She agreed with Dr. Toffol that the “much larger age range” in the new study may have played a role in showing the opposite result.

“The trajectory that we saw if we had been able to continue following the women for longer – which we couldn’t, due to limitations of the registries – [was that] using hormonal contraceptives was going to end up being protective, so I do think that it matters what age you’re looking at,” she said.

Dr. Edwards noted the takeaway from both studies “is that, even if there is a slight increase in risk from using hormonal contraceptives, it’s short lived and it’s probably specific to young women, which is important.”

She suggested the hormonal benefit from extended contraceptive use could come from the regulation of mood, as it offers a “more stable hormonal course than what their body might be putting them through in the absence of using the pill.”

Overall, it is “really lovely to see very well-executed studies on this, providing more empirical evidence on this question, because it is something that’s relevant to anyone who’s potentially going to be using hormonal contraception,” Dr. Edwards said.
 

Clinical implications?

Andrea Fiorillo, MD, PhD, department of psychiatry, University of Campania “Luigi Vanvitelli,” Naples, Italy, said in a press release that the “striking” findings of the current study need “careful evaluation.”

They also need to be replicated in “different cohorts of women and controlled for the impact of several psychosocial stressors, such as economic upheavals, social insecurity, and uncertainty due to the COVID pandemic,” said Dr. Fiorillo, who was not involved with the research.

Nevertheless, she believes the “clinical implications of the study are obvious and may help to destigmatize the use of hormonal contraceptives.”

The study was funded by the Jane and Aatos Erkko Foundation, the Avohoidon Tsukimis äätiö (Foundation for Primary Care Research), the Yrj ö Jahnsson Foundation, and the Finnish Cultural Foundation. No relevant financial relationships were reported.

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

Contrary to previous analyses, women without a history of psychiatric illness who take combined hormonal contraceptives do not have an increased risk for attempted suicide but may have a reduced risk with extended use, new research suggests.

In a study of more than 800 women younger than age 50 who attempted suicide and more than 3,000 age-matched peers, results showed those who took hormonal contraceptives had a 27% reduced risk for attempted suicide.

areeya_ann/Thinkstock

Further analysis showed this was confined to women without a history of psychiatric illness and the reduction in risk rose to 43% among those who took combined hormonal contraceptives rather than progestin-only versions.

The protective effect against attempted suicide increased further to 46% if ethinyl estradiol (EE)–containing preparations were used. Moreover, the beneficial effect of contraceptive use increased over time.

The main message is the “current use of hormonal contraceptives is not associated with an increased risk of attempted suicide in our population,” study presenter Elena Toffol, MD, PhD, department of public health, University of Helsinki, told meeting attendees at the European Psychiatric Association 2022 Congress.
 

Age range differences

Dr. Toffol said there could be “several reasons” why the results are different from those in previous studies, including that the researchers included a “larger age range.” She noted it is known that “older women have a lower rate of attempted suicide and use different types of contraceptives.”

Dr. Toffol said in an interview that, although it’s “hard to estimate any causality” because this is an observational study, it is “tempting to speculate, and it is plausible, that hormones partly play a role with some, but not all, women being more sensitive to hormonal influences.”

However, the results “may also reflect life choices or a protective life status; for example, more stable relationships or more conscious and health-focused behaviors,” she said.

“It may also be that the underlying characteristics of women who are prescribed or opt for certain types of contraceptives are somehow related to their suicidal risk,” she added.

In 2019, the global age-standardized suicide rate was 9.0 per 100,000, which translates into more than 700,000 deaths every year, Dr. Toffol noted.

However, she emphasized the World Health Organization has calculated that, for every adult who dies by suicide, more than 20 people attempt suicide. In addition, data from the U.S. Centers for Disease Control and Prevention indicate that attempted suicides are three times more common among young women than in men.

“What are the reasons for this gender gap?” Dr. Toffol asked during her presentation.

“It is known that the major risk factor for suicidal behavior is a psychiatric disorder, and in particular depression and mood disorders. And depression and mood disorders are more common in women than in men,” she said.

However, there is also “growing interest into the role of biological factors” in the risk for suicide, including hormones and hormonal contraception. Some studies have also suggested that there is an increased risk for depression and “both completed and attempted suicide” after starting hormonal contraception.

Dr. Toffol added that about 70% of European women use some form of contraception and, among Finnish women, 40% choose a hormonal contraceptive.
 

Nested analysis

The researchers conducted a nested case-control analysis combining 2017 national prescription data on 587,823 women aged 15-49 years with information from general and primary healthcare registers for the years 2018 to 2019.

They were able to identify 818 cases of attempted suicide among the women. These were matched 4:1 with 3,272 age-matched healthy women who acted as the control group. Use of hormonal contraceptives in the previous 180 days was determined for the whole cohort.

Among users of hormonal contraceptives, there were 344 attempted suicides in 2017, at an incidence rate of 0.59 per 1,000 person-years. This compared with 474 attempted suicides among nonusers, at an incidence rate of 0.81 per 1000 person-years.

Kaplan-Meier analysis showed there was a significant difference in rates for attempted suicide among hormonal contraceptive users versus nonusers, at an incidence rate ratio of 0.73 (P < .0001) – and the difference increased over time.

In addition, the incidence of attempted suicide decreased with increasing age, with the highest incidence rate in women aged 15-19 years (1.62 per 1,000 person-years).

Conditional logistic regression analysis that controlled for education, marital status, chronic disease, recent psychiatric hospitalization, and current use of psychotropic medication showed hormonal contraceptive use was not linked to an increased risk of attempted suicide overall, at an odds ratio of 0.79 (95% confidence interval, 0.56-1.11).

However, when they looked specifically at women without a history of psychiatric illness, the association became significant, at an OR of 0.73 for attempted suicide among hormonal contraceptive users (95% CI, 0.58-0.91), while the relationship remained nonsignificant in women with a history of psychiatric disorders.

Further analysis suggested the significant association was confined to women taking combined hormonal contraceptives, at an OR of 0.57 for suicide attempt versus nonusers (95% CI, 0.44-0.75), and those use EE-containing preparations (OR, 0.54; 95% CI, 0.40-0.73).

There was a suggestion in the data that hormonal contraceptives containing desogestrel or drospirenone alongside EE may offer the greatest reduction in attempted suicide risk, but that did not survive multivariate analysis.

Dr. Toffol also noted that they were not able to capture data on use of intrauterine devices in their analysis.

“There is a growing number of municipalities in Finland that are providing free-of-charge contraception to young women” that is often an intrauterine device, she said. The researchers hope to include these women in a future analysis.
 

‘Age matters’

Commenting on the findings, Alexis C. Edwards, PhD, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, said the current study’s findings “made a lot of sense.” Dr. Edwards wasn’t involved with this study but conducted a previous study of 216,702 Swedish women aged 15-22 years that showed use of combination or progestin-only oral contraceptives was associated with an increased risk for suicidal behavior.

She agreed with Dr. Toffol that the “much larger age range” in the new study may have played a role in showing the opposite result.

“The trajectory that we saw if we had been able to continue following the women for longer – which we couldn’t, due to limitations of the registries – [was that] using hormonal contraceptives was going to end up being protective, so I do think that it matters what age you’re looking at,” she said.

Dr. Edwards noted the takeaway from both studies “is that, even if there is a slight increase in risk from using hormonal contraceptives, it’s short lived and it’s probably specific to young women, which is important.”

She suggested the hormonal benefit from extended contraceptive use could come from the regulation of mood, as it offers a “more stable hormonal course than what their body might be putting them through in the absence of using the pill.”

Overall, it is “really lovely to see very well-executed studies on this, providing more empirical evidence on this question, because it is something that’s relevant to anyone who’s potentially going to be using hormonal contraception,” Dr. Edwards said.
 

Clinical implications?

Andrea Fiorillo, MD, PhD, department of psychiatry, University of Campania “Luigi Vanvitelli,” Naples, Italy, said in a press release that the “striking” findings of the current study need “careful evaluation.”

They also need to be replicated in “different cohorts of women and controlled for the impact of several psychosocial stressors, such as economic upheavals, social insecurity, and uncertainty due to the COVID pandemic,” said Dr. Fiorillo, who was not involved with the research.

Nevertheless, she believes the “clinical implications of the study are obvious and may help to destigmatize the use of hormonal contraceptives.”

The study was funded by the Jane and Aatos Erkko Foundation, the Avohoidon Tsukimis äätiö (Foundation for Primary Care Research), the Yrj ö Jahnsson Foundation, and the Finnish Cultural Foundation. No relevant financial relationships were reported.

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

Prediabetes is not only a predictor of diabetes and the cardiovascular complications that ensue, but it is also a risk factor by itself for myocardial infarction, according to data drawn from almost 1.8 million patients hospitalized for MI.

“Our study serves as a wakeup call for clinicians and patients to shift the focus to preventing prediabetes, and not just diabetes, said Geethika Thota, MD, at the annual meeting of the Endocrine Society.

There are plenty of data suggesting that prediabetes places patients on a trajectory toward cardiovascular disease. In a meta-analysis of 129 studies published 2 years ago, prediabetes was not only associated with a statistically significant 16% increase in coronary heart disease, but also a 13% increased risk of all-cause mortality relative to those with normoglycemia.
 

Data drawn from 1.8 million patients

In this study, 1,794,149 weighted patient hospitalizations for MI were drawn from the National Inpatient Sample database. Excluding patients who eventually developed diabetes, roughly 1% of these patients had a history of prediabetes in the past, according to a search of ICD-10 codes.

Before adjustment for other risk factors, prediabetes was linked to a greater than 40% increased odds of MI (odds ratio, 1.41; P < .01). After adjustment for a large array of known MI risk factors – including prior history of MI, dyslipidemia, hypertension, nicotine dependence, and obesity – prediabetes remained an independent risk factor, corresponding with a 25% increased risk of MI (OR, 1.25; P < .01).

A history of prediabetes was also an independent risk factor for percutaneous intervention and coronary artery bypass grafting, with increased risk of 45% and 95%, respectively.

As a retrospective study looking at prediabetes as a risk factor in those who already had a MI, it is possible that not all patients with prediabetes were properly coded, but Dr. Thota said that was unlikely to have been an issue of sufficient magnitude to have affected the major conclusions.
 

Relevance seen for community care

Although the study was drawn from hospitalized patients, its relevance is for the community setting, where screening and intervention for prediabetes has the potential to alter the risk, according to Dr. Thota.

Most clinicians are likely aware of the value of screening for prediabetes, which was defined in this study as a hemoglobin A1c of 5.7%-6.4%, but Dr. Thota suggested that many might not fully grasp the full scope of goals. Early detection and prevention will prevent diabetes and, by extension, cardiovascular disease, but her data suggest that control of prediabetes with lower cardiovascular risk by a more direct route.

“Despite mounting evidence, many clinicians are unaware that prediabetes is also a major risk factor for atherosclerotic cardiovascular disease,” said Dr. Thota, an internal medicine resident at Saint Peter’s University Hospital, New Brunswick, N.J.

Like diabetes, the prevalence of prediabetes is growing rapidly, according to data from the Centers for Disease Control that Dr. Thota cited. In 2020, the Centers for Disease Control and Prevention estimated that 38% of the adult population have prediabetes. By 2030, one model predicts a further 25% growth.

Screening for hyperglycemia is part of routine patient evaluations at Dr. Thota’s center. In an interview, she said that once a diagnosis of prediabetes is entered in the electronic medical record, the history is carried forward so that changes in status are continually monitored.
 

Worsening prediabetes should be addressed

“Prediabetes is not treated with medication, at least initially,” Dr. Thota explained. Rather, patients are educated about important lifestyle changes, such as diet and physical activity, that can reverse the diagnosis. However, patients who remain on a path of worsening hyperglycemia are candidates for more intensive lifestyle intervention and might be considered selectively for metformin.

“Early recognition of prediabetes through screening is important,” Dr. Thota emphasized. The benefit for preventing patients from progressing to diabetes is well recognized, but these data provide the basis for incentivizing lifestyle changes in patients with prediabetes by telling them that it can reduce their risk for MI.

These data have an important message, but they are not surprising, according to Deepak L. Bhatt, MD, executive director, interventional cardiovascular programs, Brigham and Women’s Hospital Heart & Vascular Center, Boston.

“In fact, in daily practice we see a substantial percentage of patients with MI who have prediabetes that had not been previously recognized or formally diagnosed,” Dr. Bhatt said in an interview.

“Identifying these patients – preferably prior to coming in with cardiovascular complications – is important both to reduce cardiovascular risk but also to try and prevent progression at diabetes,” he added.

Dr. Bhatt went on to say that this large analysis, confirming that prediabetes is independently associated with MI, should prompt clinicians to screen patients rigorously for this condition.

“At a minimum, such patients would be candidates for intensive lifestyle modification aimed at weight loss and treatment of frequent coexistent conditions, such as hypertension and dyslipidemia,” Dr. Bhatt said.

Dr. Thota reports no potential conflicts of interest. Dr. Bhatt has financial relationships with more than 30 pharmaceutical companies, many of which make products relevant to the management of diabetes and cardiovascular disease.

Prediabetes is not only a predictor of diabetes and the cardiovascular complications that ensue, but it is also a risk factor by itself for myocardial infarction, according to data drawn from almost 1.8 million patients hospitalized for MI.

“Our study serves as a wakeup call for clinicians and patients to shift the focus to preventing prediabetes, and not just diabetes, said Geethika Thota, MD, at the annual meeting of the Endocrine Society.

There are plenty of data suggesting that prediabetes places patients on a trajectory toward cardiovascular disease. In a meta-analysis of 129 studies published 2 years ago, prediabetes was not only associated with a statistically significant 16% increase in coronary heart disease, but also a 13% increased risk of all-cause mortality relative to those with normoglycemia.
 

Data drawn from 1.8 million patients

In this study, 1,794,149 weighted patient hospitalizations for MI were drawn from the National Inpatient Sample database. Excluding patients who eventually developed diabetes, roughly 1% of these patients had a history of prediabetes in the past, according to a search of ICD-10 codes.

Before adjustment for other risk factors, prediabetes was linked to a greater than 40% increased odds of MI (odds ratio, 1.41; P < .01). After adjustment for a large array of known MI risk factors – including prior history of MI, dyslipidemia, hypertension, nicotine dependence, and obesity – prediabetes remained an independent risk factor, corresponding with a 25% increased risk of MI (OR, 1.25; P < .01).

A history of prediabetes was also an independent risk factor for percutaneous intervention and coronary artery bypass grafting, with increased risk of 45% and 95%, respectively.

As a retrospective study looking at prediabetes as a risk factor in those who already had a MI, it is possible that not all patients with prediabetes were properly coded, but Dr. Thota said that was unlikely to have been an issue of sufficient magnitude to have affected the major conclusions.
 

Relevance seen for community care

Although the study was drawn from hospitalized patients, its relevance is for the community setting, where screening and intervention for prediabetes has the potential to alter the risk, according to Dr. Thota.

Most clinicians are likely aware of the value of screening for prediabetes, which was defined in this study as a hemoglobin A1c of 5.7%-6.4%, but Dr. Thota suggested that many might not fully grasp the full scope of goals. Early detection and prevention will prevent diabetes and, by extension, cardiovascular disease, but her data suggest that control of prediabetes with lower cardiovascular risk by a more direct route.

“Despite mounting evidence, many clinicians are unaware that prediabetes is also a major risk factor for atherosclerotic cardiovascular disease,” said Dr. Thota, an internal medicine resident at Saint Peter’s University Hospital, New Brunswick, N.J.

Like diabetes, the prevalence of prediabetes is growing rapidly, according to data from the Centers for Disease Control that Dr. Thota cited. In 2020, the Centers for Disease Control and Prevention estimated that 38% of the adult population have prediabetes. By 2030, one model predicts a further 25% growth.

Screening for hyperglycemia is part of routine patient evaluations at Dr. Thota’s center. In an interview, she said that once a diagnosis of prediabetes is entered in the electronic medical record, the history is carried forward so that changes in status are continually monitored.
 

Worsening prediabetes should be addressed

“Prediabetes is not treated with medication, at least initially,” Dr. Thota explained. Rather, patients are educated about important lifestyle changes, such as diet and physical activity, that can reverse the diagnosis. However, patients who remain on a path of worsening hyperglycemia are candidates for more intensive lifestyle intervention and might be considered selectively for metformin.

“Early recognition of prediabetes through screening is important,” Dr. Thota emphasized. The benefit for preventing patients from progressing to diabetes is well recognized, but these data provide the basis for incentivizing lifestyle changes in patients with prediabetes by telling them that it can reduce their risk for MI.

These data have an important message, but they are not surprising, according to Deepak L. Bhatt, MD, executive director, interventional cardiovascular programs, Brigham and Women’s Hospital Heart & Vascular Center, Boston.

“In fact, in daily practice we see a substantial percentage of patients with MI who have prediabetes that had not been previously recognized or formally diagnosed,” Dr. Bhatt said in an interview.

“Identifying these patients – preferably prior to coming in with cardiovascular complications – is important both to reduce cardiovascular risk but also to try and prevent progression at diabetes,” he added.

Dr. Bhatt went on to say that this large analysis, confirming that prediabetes is independently associated with MI, should prompt clinicians to screen patients rigorously for this condition.

“At a minimum, such patients would be candidates for intensive lifestyle modification aimed at weight loss and treatment of frequent coexistent conditions, such as hypertension and dyslipidemia,” Dr. Bhatt said.

Dr. Thota reports no potential conflicts of interest. Dr. Bhatt has financial relationships with more than 30 pharmaceutical companies, many of which make products relevant to the management of diabetes and cardiovascular disease.

Prediabetes is not only a predictor of diabetes and the cardiovascular complications that ensue, but it is also a risk factor by itself for myocardial infarction, according to data drawn from almost 1.8 million patients hospitalized for MI.

“Our study serves as a wakeup call for clinicians and patients to shift the focus to preventing prediabetes, and not just diabetes, said Geethika Thota, MD, at the annual meeting of the Endocrine Society.

There are plenty of data suggesting that prediabetes places patients on a trajectory toward cardiovascular disease. In a meta-analysis of 129 studies published 2 years ago, prediabetes was not only associated with a statistically significant 16% increase in coronary heart disease, but also a 13% increased risk of all-cause mortality relative to those with normoglycemia.
 

Data drawn from 1.8 million patients

In this study, 1,794,149 weighted patient hospitalizations for MI were drawn from the National Inpatient Sample database. Excluding patients who eventually developed diabetes, roughly 1% of these patients had a history of prediabetes in the past, according to a search of ICD-10 codes.

Before adjustment for other risk factors, prediabetes was linked to a greater than 40% increased odds of MI (odds ratio, 1.41; P < .01). After adjustment for a large array of known MI risk factors – including prior history of MI, dyslipidemia, hypertension, nicotine dependence, and obesity – prediabetes remained an independent risk factor, corresponding with a 25% increased risk of MI (OR, 1.25; P < .01).

A history of prediabetes was also an independent risk factor for percutaneous intervention and coronary artery bypass grafting, with increased risk of 45% and 95%, respectively.

As a retrospective study looking at prediabetes as a risk factor in those who already had a MI, it is possible that not all patients with prediabetes were properly coded, but Dr. Thota said that was unlikely to have been an issue of sufficient magnitude to have affected the major conclusions.
 

Relevance seen for community care

Although the study was drawn from hospitalized patients, its relevance is for the community setting, where screening and intervention for prediabetes has the potential to alter the risk, according to Dr. Thota.

Most clinicians are likely aware of the value of screening for prediabetes, which was defined in this study as a hemoglobin A1c of 5.7%-6.4%, but Dr. Thota suggested that many might not fully grasp the full scope of goals. Early detection and prevention will prevent diabetes and, by extension, cardiovascular disease, but her data suggest that control of prediabetes with lower cardiovascular risk by a more direct route.

“Despite mounting evidence, many clinicians are unaware that prediabetes is also a major risk factor for atherosclerotic cardiovascular disease,” said Dr. Thota, an internal medicine resident at Saint Peter’s University Hospital, New Brunswick, N.J.

Like diabetes, the prevalence of prediabetes is growing rapidly, according to data from the Centers for Disease Control that Dr. Thota cited. In 2020, the Centers for Disease Control and Prevention estimated that 38% of the adult population have prediabetes. By 2030, one model predicts a further 25% growth.

Screening for hyperglycemia is part of routine patient evaluations at Dr. Thota’s center. In an interview, she said that once a diagnosis of prediabetes is entered in the electronic medical record, the history is carried forward so that changes in status are continually monitored.
 

Worsening prediabetes should be addressed

“Prediabetes is not treated with medication, at least initially,” Dr. Thota explained. Rather, patients are educated about important lifestyle changes, such as diet and physical activity, that can reverse the diagnosis. However, patients who remain on a path of worsening hyperglycemia are candidates for more intensive lifestyle intervention and might be considered selectively for metformin.

“Early recognition of prediabetes through screening is important,” Dr. Thota emphasized. The benefit for preventing patients from progressing to diabetes is well recognized, but these data provide the basis for incentivizing lifestyle changes in patients with prediabetes by telling them that it can reduce their risk for MI.

These data have an important message, but they are not surprising, according to Deepak L. Bhatt, MD, executive director, interventional cardiovascular programs, Brigham and Women’s Hospital Heart & Vascular Center, Boston.

“In fact, in daily practice we see a substantial percentage of patients with MI who have prediabetes that had not been previously recognized or formally diagnosed,” Dr. Bhatt said in an interview.

“Identifying these patients – preferably prior to coming in with cardiovascular complications – is important both to reduce cardiovascular risk but also to try and prevent progression at diabetes,” he added.

Dr. Bhatt went on to say that this large analysis, confirming that prediabetes is independently associated with MI, should prompt clinicians to screen patients rigorously for this condition.

“At a minimum, such patients would be candidates for intensive lifestyle modification aimed at weight loss and treatment of frequent coexistent conditions, such as hypertension and dyslipidemia,” Dr. Bhatt said.

Dr. Thota reports no potential conflicts of interest. Dr. Bhatt has financial relationships with more than 30 pharmaceutical companies, many of which make products relevant to the management of diabetes and cardiovascular disease.

Avexitide (Eiger Biopharmaceuticals), a first-in-class glucagonlike peptide (GLP)–1 receptor blocker, significantly reduced hypoglycemia in patients with refractory postbariatric hypoglycemia, new research finds.  

Postbariatric hypoglycemia is a complication of bariatric surgery that is estimated to occur in about 29%-34% of people who undergo Roux-en-Y gastric bypass and in 11%-23% of those who undergo vertical sleeve gastrectomy. It typically manifests about 1-3 hours after meals and can lead to severe neuroglycopenic symptoms including blurred vision, confusion, drowsiness, and incoordination.

In addition, more than one-third (37%) with the condition have hypoglycemic unawareness. This can lead to seizures in about 59%, loss of consciousness and hospitalization in 50%, motor vehicle accidents, and even death. More than 90% with the condition consider themselves disabled, and 41% report being unable to work.

There are no currently approved medical treatments for postbariatric hypoglycemia. The standard of care is medical nutrition therapy involving a low-carbohydrate diet with carb restriction and small, frequent mixed meals. If this doesn’t work, off-label stepped pharmacotherapy has been tried, including acarbose (Precose), octreotide (Sandostatin), and diazoxide (Proglycem).

But “these are limited by efficacy and tolerability,” said Marilyn Tan, MD, who presented the findings from the phase 2 trial of avexitide at the annual meeting of the Endocrine Society.

In very severe cases, gastrostomy tubes or bypass reversal are options but those lead to weight regain and incomplete efficacy. “Safe, effective, and targeted therapies are needed urgently for postbariatric hypoglycemia,” said Dr. Tan, of the department of endocrinology at Stanford (Calif.) University.

The pathophysiology isn’t fully understood, but there appears to be an exaggerated GLP-1 response that leads to abnormal insulin secretion and symptomatic hyperinsulinemic hypoglycemia. Avexitide (formerly exendin 9-39), blocks the GLP-1 receptor and mitigates the excessive GLP-1 response, she explained.

Asked to comment, session moderator Michelle Van Name, MD, told this news organization, “This is a problem and it’s important for us to understand more about it and to identify different treatment options so these patients can continue to live their full, healthy lives post bariatric surgery.”

And, avexitide also holds potential for treating congenital hyperinsulinism, “which is a very challenging disease to treat in babies,” noted Dr. Van Name, a pediatric endocrinologist at Yale University, New Haven, Conn.
 

Drug reduced all levels of hypoglycemia, across surgery types

The study enrolled 14 women and 2 men with severe refractory postbariatric surgery hypoglycemia despite medical nutrition therapy. A majority (9) had undergone Roux-en-Y gastric bypass, 4 had vertical sleeve gastrectomy, 2 gastrectomy, and 1 had Nissen fundoplication. Seven patients (43.7%) had experienced loss of consciousness from hyperinsulinemic hypoglycemia. None had diabetes.

They were randomly assigned to either subcutaneous 45 mg of avexitide twice daily or 90 mg once daily for 14 days each, with a 2-day washout period followed by a switch to the other dose.

Both doses resulted in significant reductions in hypoglycemia as measured by self–blood glucose monitoring. The once-daily dose reduced level 1 hypoglycemia (glucose < 70 mg/dL) by 67.5% and it reduced level 2 (< 54 mg/dL) by 53.3% (P = .0043).

Even greater reductions were seen in severe hypoglycemia (that is, altered mental status/requiring assistance) – by 67.5% for the twice-daily dose (P = .0003) and by 66.1% with the once-daily dose (P = .0003). 

“This is consistent with what we’ve seen in prior avexitide trials,” Dr. Tan noted.

More hypoglycemic events were captured using blinded continuous glucose monitoring (CGM), since it picked up episodes of which the patient was unaware. There were significant reductions in percentage time spent in level 1 and level 2 hypoglycemia, as well as in absolute number of hypoglycemic events over 14 days.

Here, the effect was greater with the once-daily 90 mg dose, with reductions of up to 65% in time spent and number of events, but results for the twice-daily dose were also significant, Dr. Tan said.

The drug was effective across all surgical subtypes. Patients who underwent vertical sleeve gastrectomy/gastrectomy had greater rates of hypoglycemia at baseline and “robust responses to avexitide subcutaneous injections. This supports the critical role of GLP-1,” Dr. Tan said.

There were no severe adverse events. The most commonly reported adverse events were diarrhea, headache, bloating, and injection-site reaction/bruising. All were mild and self-limited and resolved without treatment. No participants withdrew from the study.

Eiger Biopharmaceuticals is currently working with the U.S. Food and Drug Administration and the European Medicines Agency to design a phase 3 trial.

The study is an investor-initiated trial with funding from Eiger Biopharmaceuticals. Dr. Tan receives research support from Eiger Biopharmaceuticals as a site investigator. Dr. Van Name is an investigator for a trial sponsored by Provention Bio.

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

Avexitide (Eiger Biopharmaceuticals), a first-in-class glucagonlike peptide (GLP)–1 receptor blocker, significantly reduced hypoglycemia in patients with refractory postbariatric hypoglycemia, new research finds.  

Postbariatric hypoglycemia is a complication of bariatric surgery that is estimated to occur in about 29%-34% of people who undergo Roux-en-Y gastric bypass and in 11%-23% of those who undergo vertical sleeve gastrectomy. It typically manifests about 1-3 hours after meals and can lead to severe neuroglycopenic symptoms including blurred vision, confusion, drowsiness, and incoordination.

In addition, more than one-third (37%) with the condition have hypoglycemic unawareness. This can lead to seizures in about 59%, loss of consciousness and hospitalization in 50%, motor vehicle accidents, and even death. More than 90% with the condition consider themselves disabled, and 41% report being unable to work.

There are no currently approved medical treatments for postbariatric hypoglycemia. The standard of care is medical nutrition therapy involving a low-carbohydrate diet with carb restriction and small, frequent mixed meals. If this doesn’t work, off-label stepped pharmacotherapy has been tried, including acarbose (Precose), octreotide (Sandostatin), and diazoxide (Proglycem).

But “these are limited by efficacy and tolerability,” said Marilyn Tan, MD, who presented the findings from the phase 2 trial of avexitide at the annual meeting of the Endocrine Society.

In very severe cases, gastrostomy tubes or bypass reversal are options but those lead to weight regain and incomplete efficacy. “Safe, effective, and targeted therapies are needed urgently for postbariatric hypoglycemia,” said Dr. Tan, of the department of endocrinology at Stanford (Calif.) University.

The pathophysiology isn’t fully understood, but there appears to be an exaggerated GLP-1 response that leads to abnormal insulin secretion and symptomatic hyperinsulinemic hypoglycemia. Avexitide (formerly exendin 9-39), blocks the GLP-1 receptor and mitigates the excessive GLP-1 response, she explained.

Asked to comment, session moderator Michelle Van Name, MD, told this news organization, “This is a problem and it’s important for us to understand more about it and to identify different treatment options so these patients can continue to live their full, healthy lives post bariatric surgery.”

And, avexitide also holds potential for treating congenital hyperinsulinism, “which is a very challenging disease to treat in babies,” noted Dr. Van Name, a pediatric endocrinologist at Yale University, New Haven, Conn.
 

Drug reduced all levels of hypoglycemia, across surgery types

The study enrolled 14 women and 2 men with severe refractory postbariatric surgery hypoglycemia despite medical nutrition therapy. A majority (9) had undergone Roux-en-Y gastric bypass, 4 had vertical sleeve gastrectomy, 2 gastrectomy, and 1 had Nissen fundoplication. Seven patients (43.7%) had experienced loss of consciousness from hyperinsulinemic hypoglycemia. None had diabetes.

They were randomly assigned to either subcutaneous 45 mg of avexitide twice daily or 90 mg once daily for 14 days each, with a 2-day washout period followed by a switch to the other dose.

Both doses resulted in significant reductions in hypoglycemia as measured by self–blood glucose monitoring. The once-daily dose reduced level 1 hypoglycemia (glucose < 70 mg/dL) by 67.5% and it reduced level 2 (< 54 mg/dL) by 53.3% (P = .0043).

Even greater reductions were seen in severe hypoglycemia (that is, altered mental status/requiring assistance) – by 67.5% for the twice-daily dose (P = .0003) and by 66.1% with the once-daily dose (P = .0003). 

“This is consistent with what we’ve seen in prior avexitide trials,” Dr. Tan noted.

More hypoglycemic events were captured using blinded continuous glucose monitoring (CGM), since it picked up episodes of which the patient was unaware. There were significant reductions in percentage time spent in level 1 and level 2 hypoglycemia, as well as in absolute number of hypoglycemic events over 14 days.

Here, the effect was greater with the once-daily 90 mg dose, with reductions of up to 65% in time spent and number of events, but results for the twice-daily dose were also significant, Dr. Tan said.

The drug was effective across all surgical subtypes. Patients who underwent vertical sleeve gastrectomy/gastrectomy had greater rates of hypoglycemia at baseline and “robust responses to avexitide subcutaneous injections. This supports the critical role of GLP-1,” Dr. Tan said.

There were no severe adverse events. The most commonly reported adverse events were diarrhea, headache, bloating, and injection-site reaction/bruising. All were mild and self-limited and resolved without treatment. No participants withdrew from the study.

Eiger Biopharmaceuticals is currently working with the U.S. Food and Drug Administration and the European Medicines Agency to design a phase 3 trial.

The study is an investor-initiated trial with funding from Eiger Biopharmaceuticals. Dr. Tan receives research support from Eiger Biopharmaceuticals as a site investigator. Dr. Van Name is an investigator for a trial sponsored by Provention Bio.

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

Avexitide (Eiger Biopharmaceuticals), a first-in-class glucagonlike peptide (GLP)–1 receptor blocker, significantly reduced hypoglycemia in patients with refractory postbariatric hypoglycemia, new research finds.  

Postbariatric hypoglycemia is a complication of bariatric surgery that is estimated to occur in about 29%-34% of people who undergo Roux-en-Y gastric bypass and in 11%-23% of those who undergo vertical sleeve gastrectomy. It typically manifests about 1-3 hours after meals and can lead to severe neuroglycopenic symptoms including blurred vision, confusion, drowsiness, and incoordination.

In addition, more than one-third (37%) with the condition have hypoglycemic unawareness. This can lead to seizures in about 59%, loss of consciousness and hospitalization in 50%, motor vehicle accidents, and even death. More than 90% with the condition consider themselves disabled, and 41% report being unable to work.

There are no currently approved medical treatments for postbariatric hypoglycemia. The standard of care is medical nutrition therapy involving a low-carbohydrate diet with carb restriction and small, frequent mixed meals. If this doesn’t work, off-label stepped pharmacotherapy has been tried, including acarbose (Precose), octreotide (Sandostatin), and diazoxide (Proglycem).

But “these are limited by efficacy and tolerability,” said Marilyn Tan, MD, who presented the findings from the phase 2 trial of avexitide at the annual meeting of the Endocrine Society.

In very severe cases, gastrostomy tubes or bypass reversal are options but those lead to weight regain and incomplete efficacy. “Safe, effective, and targeted therapies are needed urgently for postbariatric hypoglycemia,” said Dr. Tan, of the department of endocrinology at Stanford (Calif.) University.

The pathophysiology isn’t fully understood, but there appears to be an exaggerated GLP-1 response that leads to abnormal insulin secretion and symptomatic hyperinsulinemic hypoglycemia. Avexitide (formerly exendin 9-39), blocks the GLP-1 receptor and mitigates the excessive GLP-1 response, she explained.

Asked to comment, session moderator Michelle Van Name, MD, told this news organization, “This is a problem and it’s important for us to understand more about it and to identify different treatment options so these patients can continue to live their full, healthy lives post bariatric surgery.”

And, avexitide also holds potential for treating congenital hyperinsulinism, “which is a very challenging disease to treat in babies,” noted Dr. Van Name, a pediatric endocrinologist at Yale University, New Haven, Conn.
 

Drug reduced all levels of hypoglycemia, across surgery types

The study enrolled 14 women and 2 men with severe refractory postbariatric surgery hypoglycemia despite medical nutrition therapy. A majority (9) had undergone Roux-en-Y gastric bypass, 4 had vertical sleeve gastrectomy, 2 gastrectomy, and 1 had Nissen fundoplication. Seven patients (43.7%) had experienced loss of consciousness from hyperinsulinemic hypoglycemia. None had diabetes.

They were randomly assigned to either subcutaneous 45 mg of avexitide twice daily or 90 mg once daily for 14 days each, with a 2-day washout period followed by a switch to the other dose.

Both doses resulted in significant reductions in hypoglycemia as measured by self–blood glucose monitoring. The once-daily dose reduced level 1 hypoglycemia (glucose < 70 mg/dL) by 67.5% and it reduced level 2 (< 54 mg/dL) by 53.3% (P = .0043).

Even greater reductions were seen in severe hypoglycemia (that is, altered mental status/requiring assistance) – by 67.5% for the twice-daily dose (P = .0003) and by 66.1% with the once-daily dose (P = .0003). 

“This is consistent with what we’ve seen in prior avexitide trials,” Dr. Tan noted.

More hypoglycemic events were captured using blinded continuous glucose monitoring (CGM), since it picked up episodes of which the patient was unaware. There were significant reductions in percentage time spent in level 1 and level 2 hypoglycemia, as well as in absolute number of hypoglycemic events over 14 days.

Here, the effect was greater with the once-daily 90 mg dose, with reductions of up to 65% in time spent and number of events, but results for the twice-daily dose were also significant, Dr. Tan said.

The drug was effective across all surgical subtypes. Patients who underwent vertical sleeve gastrectomy/gastrectomy had greater rates of hypoglycemia at baseline and “robust responses to avexitide subcutaneous injections. This supports the critical role of GLP-1,” Dr. Tan said.

There were no severe adverse events. The most commonly reported adverse events were diarrhea, headache, bloating, and injection-site reaction/bruising. All were mild and self-limited and resolved without treatment. No participants withdrew from the study.

Eiger Biopharmaceuticals is currently working with the U.S. Food and Drug Administration and the European Medicines Agency to design a phase 3 trial.

The study is an investor-initiated trial with funding from Eiger Biopharmaceuticals. Dr. Tan receives research support from Eiger Biopharmaceuticals as a site investigator. Dr. Van Name is an investigator for a trial sponsored by Provention Bio.

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