Middle-aged White women who had higher levels of some breakdown products of phthalates – a class of endocrine disrupting chemicals (EDCs), or “forever chemicals,” that act as plasticizers – had a significantly greater risk of developing type 2 diabetes over a 6-year period compared with other similar women.

However, this association was not seen among Black or Asian middle-aged women.

These findings from the Study of Women’s Health Across the Nation – Multipollutant Study (SWAN-MPS), by Mia Q. Peng, PhD, MPH, and colleagues, have been published online in the Journal of Clinical Endocrinology & Metabolism.

“Overall, our study has added some evidence to support the potential diabetogenic effects of phthalates, but it also highlights that much is still unknown about the metabolic effects of these chemicals,” the group noted.

“The apparent racial/ethnic differences in the associations between phthalates and incident diabetes should be investigated in future studies,” they cautioned.

Recruiting younger participants and observing them longer, they suggested, “will also help us understand the effects of phthalates on different stages of the diabetogenic process, including whether body fat gain is an important mediator.”
 

Phthalates are all around us

Low-molecular-weight phthalates are frequently added to personal care products, such as fragrance, nail polish, and some feminine hygiene products, as solvents, plasticizers, and fixatives, the researchers explained.

And high-molecular-weight phthalates are frequently added to polyvinyl chloride plastic products, such as plastic food packaging, clothing, and vinyl flooring, as plasticizers.

Phthalates have been hypothesized to contribute to the development of diabetes, but longitudinal evidence in humans was limited.

“Given widespread exposure to phthalates and the enormous costs of diabetes to individuals and societies, ongoing investments in the research on phthalates’ metabolic effects are warranted,” the researchers concluded.
 

Racial differences in phthalates and incident diabetes

“A new finding is that we observed some phthalates are associated with a higher risk of diabetes development, especially in White women [that] were not seen in Black or Asian women,” senior author Sung Kyun Park, ScD, MPH, of the University of Michigan, Ann Arbor, told this news organization.

“We were surprised to see the racial/ethnic differences,” added Dr. Peng, formerly of the University of Michigan and now at Lifecourse Epidemiology of Adiposity and Diabetes Center, University of Colorado Anschutz Medical Campus.

A possible explanation is that “compared to White women, Black women develop diabetes at a younger age and are exposed to higher levels of several phthalates,” and this study excluded women who already had diabetes by midlife, she noted.

“Although our study was conducted in a cohort of women,” Dr. Park stressed, “we hope that our findings are not interpreted that only women should be concerned of phthalates. Our findings add to the current literature that phthalates may be a potential risk factor for type 2 diabetes.

“Certain phthalates are prohibited in children’s toys and child care articles,” Dr. Peng noted, as explained by the U.S. Consumer Product Safety Commission. In addition, a bill has been introduced in Congress to ban phthalates in food contact substances.

“If phthalates are removed from plastics and other consumer products,” she cautioned, “we do have to be careful in the process to avoid replacing them with some other potentially harmful chemicals.”

A well-known example of this type of “regrettable substitution,” Dr. Park added, “is ‘BPA-free’ plastics that replaced bisphenol A with other bisphenols such as bisphenol-F (BPF) or bisphenol-S (BPS). The product has a label of ‘BPA-free’, but those replaced chemicals turned out to be equally toxic. Science is slow to determine if a new chemical introduced to the market is safe and can replace a regulated chemical.”

And studies have shown that a diet rich in meat, fat, and ultraprocessed foods is associated with increased exposures to some phthalates, especially when the foods are obtained away from home, such as fast foods, Dr. Peng observed. In addition, some phthalates are added to personal care products such as fragrance.

“As a first step,” she said, “I think reducing consumption of ultraprocessed foods packaged in plastics may help reduce phthalate exposure.”

A 2020 report from the Endocrine Society and the International Pollutants Elimination Network (IPEN), titled, “Plastics, EDCs, and Health,” summarizes research on bisphenol A, per- and polyfluoroalkyl substances (PFAS), phthalates, and other EDCs that leach from plastics. The Endocrine Society website also has a link to a 2-page summary.  
 

Levels of 12 phthalate metabolites

Previously, the researchers reported how another class of “forever chemicals,” PFAS, were associated with risk of hypertension in a 17-year follow-up of middle-aged women in the SWAN study.

In the current study, they analyzed data from 1,308 women in SWAN-MPS who had been recruited at five study sites (Oakland, Calif; Los Angeles; Detroit; Pittsburgh; and Boston).

The women were between ages 42 and 52 years in 1996-1997 and self-identified as White, Black, Chinese, or Japanese.

They did not have diabetes in 1999-2000 and had sufficient urine samples for phthalate assessment then and midway through a 6-year follow-up.

The women were a median age of 49 years in 1999-2000. About half were White, 20% were Black, 13% were Chinese, and 15% were Japanese.

Researchers analyzed levels of 12 metabolites, chosen because their parent phthalates have been widely used in industry and commerce, and exposure to these phthalates is a national biomonitoring priority.

The measured phthalates were:

Three metabolites of low-molecular-weight phthalates:

• mono-ethyl phthalate (MEP)
• mono-n-butyl phthalate (MnBP)
• mono-isobutyl phthalate (MiBP)

Four metabolites of the high-molecular-weight phthalate di(2-ethylhexyl) phthalate (DEHP), which is of particular public health interest:

• mono(2-ethylhexyl) phthalate (MEHP)
• mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP)
• mono(2-ethyl-5-oxohexyl) phthalate (MEOHP)
• mono(2-ethyl-5-carboxypentyl) phthalate (MECPP)

Five metabolites of other high-molecular-weight phthalates:

• monobenzyl phthalate (MBzP)
• monoisononyl phthalate (MiNP)
• mono-carboxyoctyl phthalate (MCOP)
• mono-carboxy-isononyl phthalate (MCNP)
• mono(3-carboxypropyl) phthalate (MCPP)

The researchers excluded MiNP from all analyses because it was detected in less than 1% of urine samples.

The different phthalate metabolites were detected in 84.8% of samples (MEHP) to 100% of samples (MnBP and MECPP).

Women who were younger, Black, current smokers, or obese generally had higher concentrations of phthalate metabolites.

Over 6 years, 61 women developed diabetes (an incidence rate of 8.1 per 1000 person-years).

Compared with other women, those with incident diabetes had significantly higher concentrations of all phthalate metabolites except DEHP metabolites and MCPP. 

Phthalates were not associated with incident diabetes in Black or Asian women.

However, among White women, each doubling of the concentrations of MiBP, MBzP, MCOP, MCNP, and MCCP was associated with a 30% to 63% higher incidence of diabetes (HR 1.30 for MCNP; HR 1.63 for MiBP).

The SWAN study was supported by the National Institutes of Health, Department of Health & Human Services, National Institute on Aging, National Institute of Nursing Research, NIH Office of Research on Women’s Health, and SWAN Repository. The current study was supported by the National Center for Research Resources, National Center for Advancing Translational Sciences, NIH, National Institute of Environmental Health, and Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health. Dr. Peng was supported by an Interdisciplinary Research Training on Health and Aging grant from the NIA. The authors have reported no relevant financial relationships.

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

Middle-aged White women who had higher levels of some breakdown products of phthalates – a class of endocrine disrupting chemicals (EDCs), or “forever chemicals,” that act as plasticizers – had a significantly greater risk of developing type 2 diabetes over a 6-year period compared with other similar women.

However, this association was not seen among Black or Asian middle-aged women.

These findings from the Study of Women’s Health Across the Nation – Multipollutant Study (SWAN-MPS), by Mia Q. Peng, PhD, MPH, and colleagues, have been published online in the Journal of Clinical Endocrinology & Metabolism.

“Overall, our study has added some evidence to support the potential diabetogenic effects of phthalates, but it also highlights that much is still unknown about the metabolic effects of these chemicals,” the group noted.

“The apparent racial/ethnic differences in the associations between phthalates and incident diabetes should be investigated in future studies,” they cautioned.

Recruiting younger participants and observing them longer, they suggested, “will also help us understand the effects of phthalates on different stages of the diabetogenic process, including whether body fat gain is an important mediator.”
 

Phthalates are all around us

Low-molecular-weight phthalates are frequently added to personal care products, such as fragrance, nail polish, and some feminine hygiene products, as solvents, plasticizers, and fixatives, the researchers explained.

And high-molecular-weight phthalates are frequently added to polyvinyl chloride plastic products, such as plastic food packaging, clothing, and vinyl flooring, as plasticizers.

Phthalates have been hypothesized to contribute to the development of diabetes, but longitudinal evidence in humans was limited.

“Given widespread exposure to phthalates and the enormous costs of diabetes to individuals and societies, ongoing investments in the research on phthalates’ metabolic effects are warranted,” the researchers concluded.
 

Racial differences in phthalates and incident diabetes

“A new finding is that we observed some phthalates are associated with a higher risk of diabetes development, especially in White women [that] were not seen in Black or Asian women,” senior author Sung Kyun Park, ScD, MPH, of the University of Michigan, Ann Arbor, told this news organization.

“We were surprised to see the racial/ethnic differences,” added Dr. Peng, formerly of the University of Michigan and now at Lifecourse Epidemiology of Adiposity and Diabetes Center, University of Colorado Anschutz Medical Campus.

A possible explanation is that “compared to White women, Black women develop diabetes at a younger age and are exposed to higher levels of several phthalates,” and this study excluded women who already had diabetes by midlife, she noted.

“Although our study was conducted in a cohort of women,” Dr. Park stressed, “we hope that our findings are not interpreted that only women should be concerned of phthalates. Our findings add to the current literature that phthalates may be a potential risk factor for type 2 diabetes.

“Certain phthalates are prohibited in children’s toys and child care articles,” Dr. Peng noted, as explained by the U.S. Consumer Product Safety Commission. In addition, a bill has been introduced in Congress to ban phthalates in food contact substances.

“If phthalates are removed from plastics and other consumer products,” she cautioned, “we do have to be careful in the process to avoid replacing them with some other potentially harmful chemicals.”

A well-known example of this type of “regrettable substitution,” Dr. Park added, “is ‘BPA-free’ plastics that replaced bisphenol A with other bisphenols such as bisphenol-F (BPF) or bisphenol-S (BPS). The product has a label of ‘BPA-free’, but those replaced chemicals turned out to be equally toxic. Science is slow to determine if a new chemical introduced to the market is safe and can replace a regulated chemical.”

And studies have shown that a diet rich in meat, fat, and ultraprocessed foods is associated with increased exposures to some phthalates, especially when the foods are obtained away from home, such as fast foods, Dr. Peng observed. In addition, some phthalates are added to personal care products such as fragrance.

“As a first step,” she said, “I think reducing consumption of ultraprocessed foods packaged in plastics may help reduce phthalate exposure.”

A 2020 report from the Endocrine Society and the International Pollutants Elimination Network (IPEN), titled, “Plastics, EDCs, and Health,” summarizes research on bisphenol A, per- and polyfluoroalkyl substances (PFAS), phthalates, and other EDCs that leach from plastics. The Endocrine Society website also has a link to a 2-page summary.  
 

Levels of 12 phthalate metabolites

Previously, the researchers reported how another class of “forever chemicals,” PFAS, were associated with risk of hypertension in a 17-year follow-up of middle-aged women in the SWAN study.

In the current study, they analyzed data from 1,308 women in SWAN-MPS who had been recruited at five study sites (Oakland, Calif; Los Angeles; Detroit; Pittsburgh; and Boston).

The women were between ages 42 and 52 years in 1996-1997 and self-identified as White, Black, Chinese, or Japanese.

They did not have diabetes in 1999-2000 and had sufficient urine samples for phthalate assessment then and midway through a 6-year follow-up.

The women were a median age of 49 years in 1999-2000. About half were White, 20% were Black, 13% were Chinese, and 15% were Japanese.

Researchers analyzed levels of 12 metabolites, chosen because their parent phthalates have been widely used in industry and commerce, and exposure to these phthalates is a national biomonitoring priority.

The measured phthalates were:

Three metabolites of low-molecular-weight phthalates:

• mono-ethyl phthalate (MEP)
• mono-n-butyl phthalate (MnBP)
• mono-isobutyl phthalate (MiBP)

Four metabolites of the high-molecular-weight phthalate di(2-ethylhexyl) phthalate (DEHP), which is of particular public health interest:

• mono(2-ethylhexyl) phthalate (MEHP)
• mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP)
• mono(2-ethyl-5-oxohexyl) phthalate (MEOHP)
• mono(2-ethyl-5-carboxypentyl) phthalate (MECPP)

Five metabolites of other high-molecular-weight phthalates:

• monobenzyl phthalate (MBzP)
• monoisononyl phthalate (MiNP)
• mono-carboxyoctyl phthalate (MCOP)
• mono-carboxy-isononyl phthalate (MCNP)
• mono(3-carboxypropyl) phthalate (MCPP)

The researchers excluded MiNP from all analyses because it was detected in less than 1% of urine samples.

The different phthalate metabolites were detected in 84.8% of samples (MEHP) to 100% of samples (MnBP and MECPP).

Women who were younger, Black, current smokers, or obese generally had higher concentrations of phthalate metabolites.

Over 6 years, 61 women developed diabetes (an incidence rate of 8.1 per 1000 person-years).

Compared with other women, those with incident diabetes had significantly higher concentrations of all phthalate metabolites except DEHP metabolites and MCPP. 

Phthalates were not associated with incident diabetes in Black or Asian women.

However, among White women, each doubling of the concentrations of MiBP, MBzP, MCOP, MCNP, and MCCP was associated with a 30% to 63% higher incidence of diabetes (HR 1.30 for MCNP; HR 1.63 for MiBP).

The SWAN study was supported by the National Institutes of Health, Department of Health & Human Services, National Institute on Aging, National Institute of Nursing Research, NIH Office of Research on Women’s Health, and SWAN Repository. The current study was supported by the National Center for Research Resources, National Center for Advancing Translational Sciences, NIH, National Institute of Environmental Health, and Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health. Dr. Peng was supported by an Interdisciplinary Research Training on Health and Aging grant from the NIA. The authors have reported no relevant financial relationships.

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

Middle-aged White women who had higher levels of some breakdown products of phthalates – a class of endocrine disrupting chemicals (EDCs), or “forever chemicals,” that act as plasticizers – had a significantly greater risk of developing type 2 diabetes over a 6-year period compared with other similar women.

However, this association was not seen among Black or Asian middle-aged women.

These findings from the Study of Women’s Health Across the Nation – Multipollutant Study (SWAN-MPS), by Mia Q. Peng, PhD, MPH, and colleagues, have been published online in the Journal of Clinical Endocrinology & Metabolism.

“Overall, our study has added some evidence to support the potential diabetogenic effects of phthalates, but it also highlights that much is still unknown about the metabolic effects of these chemicals,” the group noted.

“The apparent racial/ethnic differences in the associations between phthalates and incident diabetes should be investigated in future studies,” they cautioned.

Recruiting younger participants and observing them longer, they suggested, “will also help us understand the effects of phthalates on different stages of the diabetogenic process, including whether body fat gain is an important mediator.”
 

Phthalates are all around us

Low-molecular-weight phthalates are frequently added to personal care products, such as fragrance, nail polish, and some feminine hygiene products, as solvents, plasticizers, and fixatives, the researchers explained.

And high-molecular-weight phthalates are frequently added to polyvinyl chloride plastic products, such as plastic food packaging, clothing, and vinyl flooring, as plasticizers.

Phthalates have been hypothesized to contribute to the development of diabetes, but longitudinal evidence in humans was limited.

“Given widespread exposure to phthalates and the enormous costs of diabetes to individuals and societies, ongoing investments in the research on phthalates’ metabolic effects are warranted,” the researchers concluded.
 

Racial differences in phthalates and incident diabetes

“A new finding is that we observed some phthalates are associated with a higher risk of diabetes development, especially in White women [that] were not seen in Black or Asian women,” senior author Sung Kyun Park, ScD, MPH, of the University of Michigan, Ann Arbor, told this news organization.

“We were surprised to see the racial/ethnic differences,” added Dr. Peng, formerly of the University of Michigan and now at Lifecourse Epidemiology of Adiposity and Diabetes Center, University of Colorado Anschutz Medical Campus.

A possible explanation is that “compared to White women, Black women develop diabetes at a younger age and are exposed to higher levels of several phthalates,” and this study excluded women who already had diabetes by midlife, she noted.

“Although our study was conducted in a cohort of women,” Dr. Park stressed, “we hope that our findings are not interpreted that only women should be concerned of phthalates. Our findings add to the current literature that phthalates may be a potential risk factor for type 2 diabetes.

“Certain phthalates are prohibited in children’s toys and child care articles,” Dr. Peng noted, as explained by the U.S. Consumer Product Safety Commission. In addition, a bill has been introduced in Congress to ban phthalates in food contact substances.

“If phthalates are removed from plastics and other consumer products,” she cautioned, “we do have to be careful in the process to avoid replacing them with some other potentially harmful chemicals.”

A well-known example of this type of “regrettable substitution,” Dr. Park added, “is ‘BPA-free’ plastics that replaced bisphenol A with other bisphenols such as bisphenol-F (BPF) or bisphenol-S (BPS). The product has a label of ‘BPA-free’, but those replaced chemicals turned out to be equally toxic. Science is slow to determine if a new chemical introduced to the market is safe and can replace a regulated chemical.”

And studies have shown that a diet rich in meat, fat, and ultraprocessed foods is associated with increased exposures to some phthalates, especially when the foods are obtained away from home, such as fast foods, Dr. Peng observed. In addition, some phthalates are added to personal care products such as fragrance.

“As a first step,” she said, “I think reducing consumption of ultraprocessed foods packaged in plastics may help reduce phthalate exposure.”

A 2020 report from the Endocrine Society and the International Pollutants Elimination Network (IPEN), titled, “Plastics, EDCs, and Health,” summarizes research on bisphenol A, per- and polyfluoroalkyl substances (PFAS), phthalates, and other EDCs that leach from plastics. The Endocrine Society website also has a link to a 2-page summary.  
 

Levels of 12 phthalate metabolites

Previously, the researchers reported how another class of “forever chemicals,” PFAS, were associated with risk of hypertension in a 17-year follow-up of middle-aged women in the SWAN study.

In the current study, they analyzed data from 1,308 women in SWAN-MPS who had been recruited at five study sites (Oakland, Calif; Los Angeles; Detroit; Pittsburgh; and Boston).

The women were between ages 42 and 52 years in 1996-1997 and self-identified as White, Black, Chinese, or Japanese.

They did not have diabetes in 1999-2000 and had sufficient urine samples for phthalate assessment then and midway through a 6-year follow-up.

The women were a median age of 49 years in 1999-2000. About half were White, 20% were Black, 13% were Chinese, and 15% were Japanese.

Researchers analyzed levels of 12 metabolites, chosen because their parent phthalates have been widely used in industry and commerce, and exposure to these phthalates is a national biomonitoring priority.

The measured phthalates were:

Three metabolites of low-molecular-weight phthalates:

• mono-ethyl phthalate (MEP)
• mono-n-butyl phthalate (MnBP)
• mono-isobutyl phthalate (MiBP)

Four metabolites of the high-molecular-weight phthalate di(2-ethylhexyl) phthalate (DEHP), which is of particular public health interest:

• mono(2-ethylhexyl) phthalate (MEHP)
• mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP)
• mono(2-ethyl-5-oxohexyl) phthalate (MEOHP)
• mono(2-ethyl-5-carboxypentyl) phthalate (MECPP)

Five metabolites of other high-molecular-weight phthalates:

• monobenzyl phthalate (MBzP)
• monoisononyl phthalate (MiNP)
• mono-carboxyoctyl phthalate (MCOP)
• mono-carboxy-isononyl phthalate (MCNP)
• mono(3-carboxypropyl) phthalate (MCPP)

The researchers excluded MiNP from all analyses because it was detected in less than 1% of urine samples.

The different phthalate metabolites were detected in 84.8% of samples (MEHP) to 100% of samples (MnBP and MECPP).

Women who were younger, Black, current smokers, or obese generally had higher concentrations of phthalate metabolites.

Over 6 years, 61 women developed diabetes (an incidence rate of 8.1 per 1000 person-years).

Compared with other women, those with incident diabetes had significantly higher concentrations of all phthalate metabolites except DEHP metabolites and MCPP. 

Phthalates were not associated with incident diabetes in Black or Asian women.

However, among White women, each doubling of the concentrations of MiBP, MBzP, MCOP, MCNP, and MCCP was associated with a 30% to 63% higher incidence of diabetes (HR 1.30 for MCNP; HR 1.63 for MiBP).

The SWAN study was supported by the National Institutes of Health, Department of Health & Human Services, National Institute on Aging, National Institute of Nursing Research, NIH Office of Research on Women’s Health, and SWAN Repository. The current study was supported by the National Center for Research Resources, National Center for Advancing Translational Sciences, NIH, National Institute of Environmental Health, and Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health. Dr. Peng was supported by an Interdisciplinary Research Training on Health and Aging grant from the NIA. The authors have reported no relevant financial relationships.

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

In the STROKE AF study, among patients who had a stroke presumably caused by atherosclerosis, the rate of atrial fibrillation (AFib) was almost 22% at 3 years, as detected by continuous monitoring.

The 3-year results from the study were presented by Lee H. Schwamm, MD, of Massachusetts General Hospital, Boston, at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

Dr. Schwamm said the high rate of AFib detection in this study suggests that continuous monitoring for AFib should be considered for a larger population of stroke patients, rather than just those with cryptogenic stroke.

“We found a much higher rate of AF[ib] than we expected in this population of patients who have had an atherosclerotic stroke,” Dr. Schwamm said in an interview.

“These AF[ib] occurrences were found by a device, so they are known as ‘device-documented AF[ib].’ The patient is not generally aware of symptoms, but 67% of the AF[ib] episodes lasted for more than 1 hour, showing that this is not trivial AF[ib]. This is meaningful AF[ib],” he said.

Dr. Schwamm said the major question is whether these cases of AFib that are detected with a device warrant treatment with anticoagulation. He noted that, in this study, clinicians decided to provide anticoagulation to 70%-80% of patients in whom AFib was detected.

“If we think it deserves treatment, then we have to look for it. And if we care about finding AF[ib], we have no choice but to monitor continuously,” he said.

“If this data doesn’t convince you that AF[ib] is present in this population, I don’t think any data will. Because it is consistent, it accumulates over time and looks remarkably similar to a set of data that we have all become very comfortable with – the CRYSTAL-AF study in patients with cryptogenic stroke,” he stated.

Dr. Schwamm noted that the STROKE AF trial was not based on the cause of the index stroke; rather, it was asking whether there are risk factors that could contribute to the 25% stroke recurrence rate in this population that are not covered in current guidelines.

“I’m really trying to move away from the anchor that I was trained in, which is to figure out the cause of the last stroke to help decide how to prevent the next stroke, towards more of a probabilistic model – of what is all the information I have at my disposal and how do I act on it to prevent the next stroke? We have to start thinking differently about building models for future stroke risk and determining therapy based on that,” he commented.
 

Changing practice

ISC 2023 program chair Tudor Jovin, MD, Cooper Neurological Institute, Cherry Hill, N.J., and moderator of the session at which the results were presented, discussed the STROKE AF results in a highlights presentation.

“To me as clinician, these results are even more relevant than those at 12 months,” Dr. Jovin said. “The lesson I took is that AF[ib] is even more prevalent than we thought. The burden of AF[ib] is significant in these patients, and it doesn’t seem to be limited to a particular time. These are very thought-provoking results which are going to change clinical practice. I think the threshold for long-term monitoring will be lower.”

Comoderator Lauren Sansing, MD, Yale University, New Haven, Conn., added: “This study shows that the longer we monitor, the more patients with AF[ib] we are likely to pick up. And because in two-thirds of patients with AF[ib], it lasted longer than 1 hour, I do believe this was clinically relevant AF[ib]. The question now is, do we monitor everyone? I think it puts the burden on us to search for AF[ib] in our patients.”

In his presentation, Dr. Schwamm explained that, on the basis of the CRYSTAL-AF study, insertable cardiac monitoring devices are frequently used to identify poststroke AFib in patients with cryptogenic stroke. In the device-monitored arm of that study, AFib was detected in 12.4% of patients over 12 months versus 2.0% in the control arm.

“However, we don’t know how often AF[ib] is detected in other presumed stroke types – largely those due to atherosclerosis,” he said.

He pointed out that, at present, long-term monitoring post stroke for the detection of AFib is not currently recommended for patients with ischemic stroke, owing to presumed small-vessel occlusion or large-artery atherosclerosis.

“In these patients, we are not suspecting AF[ib] because we believe the cause of the stroke was not embolic. But we wanted to investigate what the AF[ib] risk is in these patients, who often have multiple stroke risk factors,” he said.

The trial enrolled 496 patients at 33 centers in the United States. Eligible patients were aged 60 years or older or aged 50-59 years with at least one additional stroke risk factor and had an index stroke that was attributed to large-artery or small-vessel disease. Patients were randomly assigned either to continuous monitoring with the Reveal LINQ device (Medtronic) or to the control arm following site-specific standard of care for AFib detection.

Dr. Schwamm noted that usual care for these patients normally involves monitoring for just a few days while in hospital, but this picks up less than 5% of AFib occurrences.

Baseline characteristics of patients in the STROKE AF study showed that the enrolled population was at high risk for stroke, with a CHADSVASC score of 5. But the index strokes were generally small; the median National Institutes of Health Stroke Scale score was 2.

Results at 12 months, reported 2 years ago, showed a 12.5% incidence of AFib with continuous monitoring versus 1.8% with standard of care (hazard ratio, 7.7; P < .001), rates similar to that found in the CRYSTAL-AF study.

By 3 years, the rate of detected AFib had risen to 21.7% in the continuous monitoring arm versus 2.4% in the control arm (HR, 10.0; P < .001).

“At 12 months, we were seven times more likely to detect AF[ib] with continuous monitoring in these patients, and by 3 years, it was 10 times more likely that AF would be detected with continuous monitoring. I think we’ve settled the question of the best way to find AF[ib] in these patients – it is with an inserted device,” Dr. Schwamm said.

“We have also shown that this is not a transient rise in AFib after the stroke which then diminishes over the next few years. It is a continuous and progressive detection of AF[ib].”

Dr. Schwamm pointed out that 88% of the recorded AFib episodes were asymptomatic. “So relying on patients self-reporting symptoms when deciding who to monitor is unreliable and not a sensible strategy.”

The median time to the first adjudicated AFib episode at 12-month follow-up was 99 days; at the 3-year follow-up, it was 284 days.

“This shows that 30 days of monitoring with an external patch is not sufficient to exclude the presence of AF[ib]. And this really argues for a strategy of immediate insertion of cardiac monitor placement if your goal is to look for AF[ib],” Dr. Schwamm commented.
 

Is this clinically relevant AFib?

Dr. Schwamm acknowledged that there is a question of whether device-detected AFib should be thought about in the same way as clinically detected AFib with respect to future stroke risk.

He noted that, in this study, 67.4% of patients for whom AFib was detected by continuous monitoring (31 of 46 patients) had at least one episode of AFib that lasted more than 1 hour.

“This is not a trivial little squiggle of something on an EKG which then goes away. This is of significant duration that the cardiologist who adjudicated these rhythm strips felt confident was AF[ib].”

He added: “AF[ib] lasting more than 1 hour crosses the threshold for most practitioners I know to feel confident in treating the patient with anticoagulation. If it was symptomatic AF, this wouldn’t even be a question.”

Dr. Schwamm made the point that device-detected A AFib F has been accepted as worthy of treatment in patients after cryptogenic stroke.

“If we are honest with ourselves and if we have no hesitation in starting anticoagulation in a patient with cryptogenic stroke who has had device-detected AF 6 months later, should we decide that if the patient has had a lacunar stroke, we can ignore that same device-detected fibrillation?”

He put forward the idea that, at some level, all stroke is cryptogenic. “We never know for sure what the cause was. We have hypotheses, we have associations, but we don’t really know. So how much should we weigh that presumptive etiology in terms of how we interpret a rhythm disturbance of fibrillation?”

When looking for predictors of AFib in this study, the investigators found that patients were more likely to have an episode of AFib detected if they had one of the four following risk factors: congestive heart failure, left atrial enlargement, obesity, or QRS prolongation.

“In patients with any one of those four factors, 30% of those had device-detected AF[ib]. These are same predictors of AF[ib] that we are all accustomed to,” Dr. Schwamm said.
 

Shared decision-making

Dr. Schwamm said in an interview that, in his practice, for these patients, the decision as to whether to use continuous monitoring is made with the patient through shared decision-making.

“We discuss the chance that they could have AF[ib], and I suggest that it might be worth looking for it, but there are factors to be considered. There is a cost to the device, and reimbursement may depend on insurance coverage. Also, some patients may have strong feelings about having the chip implanted in their body.”

He says implanting the chip is easy. “It takes longer to check in at the front desk than to put the device in. It is injected under the skin. It just needs two stitches and a Band-Aid.” The device connects with a smartphone, and the results are interpreted by a cardiologist.

Dr. Schwamm pointed out that the optimal antithrombotic regimen for these patients in whom AFib is detected remains uncertain and should be the focus of future research.

“Do we just stick to antiplatelet therapy or advance to anticoagulation? In moving to an anticoagulant, are we providing less effective prevention for the atherosclerotic stroke risk at the expense of reducing the AF[ib]-related stroke risk? That may be a reasonable trade-off because we know the disability from AF[ib]-associated stroke is much higher.

“Or perhaps the optimal therapy is aspirin plus low-dose anticoagulant? Or left atrial appendage closure and an antiplatelet for patients at a higher risk of bleeding?” he said. “These are the really important questions we need to start asking.”

He added that he hopes a future study will address these questions, but he noted that it would have to be a large study, that it would have to first identify these patients and then randomly assign them to anticoagulation or to no treatment. “That is quite a major undertaking.”

In the highlights presentation, Dr. Jovin said he was uncertain of which of these patients in whom AFib is detected would benefit from anticoagulation. He said he would also like to see a randomized trial on this. But he added: “This would be challenging, as there is the issue of whether there would be equipoise to allow us to randomize to a placebo.”

Dr. Sansing agreed. “I think it would be a hard sell. I would have to think carefully about randomizing a patient to anticoagulation therapy or no therapy who has been found to have AF[ib].”

Dr. Schwamm noted that the current STROKE-AF study was not designed or powered to detect differences in stroke recurrence rates and that there was no difference in stroke recurrence rates between the two arms. There was also no randomization with regard to treatment; choice of medication was left to the discretion of the treating physician.

But he noted that only for 3 of the 34 patients with recurrent stroke in the continuous-monitor arm was AFib detected prior to the recurrent stroke, and only one of those three was receiving anticoagulation at the time of the recurrent stroke.

“These strokes were occurring in patients who did not have device-detected AF[ib],” Dr. Schwamm said. “This is because the population in this study were loaded with stroke risk factors and are at risk of recurrent stroke, but we don’t have the opportunity in this study to really understand the significance of the recurrent strokes.”

The STROKE AF trial was funded by Medtronic. Dr. Schwamm is a consultant to Medtronic.

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

In the STROKE AF study, among patients who had a stroke presumably caused by atherosclerosis, the rate of atrial fibrillation (AFib) was almost 22% at 3 years, as detected by continuous monitoring.

The 3-year results from the study were presented by Lee H. Schwamm, MD, of Massachusetts General Hospital, Boston, at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

Dr. Schwamm said the high rate of AFib detection in this study suggests that continuous monitoring for AFib should be considered for a larger population of stroke patients, rather than just those with cryptogenic stroke.

“We found a much higher rate of AF[ib] than we expected in this population of patients who have had an atherosclerotic stroke,” Dr. Schwamm said in an interview.

“These AF[ib] occurrences were found by a device, so they are known as ‘device-documented AF[ib].’ The patient is not generally aware of symptoms, but 67% of the AF[ib] episodes lasted for more than 1 hour, showing that this is not trivial AF[ib]. This is meaningful AF[ib],” he said.

Dr. Schwamm said the major question is whether these cases of AFib that are detected with a device warrant treatment with anticoagulation. He noted that, in this study, clinicians decided to provide anticoagulation to 70%-80% of patients in whom AFib was detected.

“If we think it deserves treatment, then we have to look for it. And if we care about finding AF[ib], we have no choice but to monitor continuously,” he said.

“If this data doesn’t convince you that AF[ib] is present in this population, I don’t think any data will. Because it is consistent, it accumulates over time and looks remarkably similar to a set of data that we have all become very comfortable with – the CRYSTAL-AF study in patients with cryptogenic stroke,” he stated.

Dr. Schwamm noted that the STROKE AF trial was not based on the cause of the index stroke; rather, it was asking whether there are risk factors that could contribute to the 25% stroke recurrence rate in this population that are not covered in current guidelines.

“I’m really trying to move away from the anchor that I was trained in, which is to figure out the cause of the last stroke to help decide how to prevent the next stroke, towards more of a probabilistic model – of what is all the information I have at my disposal and how do I act on it to prevent the next stroke? We have to start thinking differently about building models for future stroke risk and determining therapy based on that,” he commented.
 

Changing practice

ISC 2023 program chair Tudor Jovin, MD, Cooper Neurological Institute, Cherry Hill, N.J., and moderator of the session at which the results were presented, discussed the STROKE AF results in a highlights presentation.

“To me as clinician, these results are even more relevant than those at 12 months,” Dr. Jovin said. “The lesson I took is that AF[ib] is even more prevalent than we thought. The burden of AF[ib] is significant in these patients, and it doesn’t seem to be limited to a particular time. These are very thought-provoking results which are going to change clinical practice. I think the threshold for long-term monitoring will be lower.”

Comoderator Lauren Sansing, MD, Yale University, New Haven, Conn., added: “This study shows that the longer we monitor, the more patients with AF[ib] we are likely to pick up. And because in two-thirds of patients with AF[ib], it lasted longer than 1 hour, I do believe this was clinically relevant AF[ib]. The question now is, do we monitor everyone? I think it puts the burden on us to search for AF[ib] in our patients.”

In his presentation, Dr. Schwamm explained that, on the basis of the CRYSTAL-AF study, insertable cardiac monitoring devices are frequently used to identify poststroke AFib in patients with cryptogenic stroke. In the device-monitored arm of that study, AFib was detected in 12.4% of patients over 12 months versus 2.0% in the control arm.

“However, we don’t know how often AF[ib] is detected in other presumed stroke types – largely those due to atherosclerosis,” he said.

He pointed out that, at present, long-term monitoring post stroke for the detection of AFib is not currently recommended for patients with ischemic stroke, owing to presumed small-vessel occlusion or large-artery atherosclerosis.

“In these patients, we are not suspecting AF[ib] because we believe the cause of the stroke was not embolic. But we wanted to investigate what the AF[ib] risk is in these patients, who often have multiple stroke risk factors,” he said.

The trial enrolled 496 patients at 33 centers in the United States. Eligible patients were aged 60 years or older or aged 50-59 years with at least one additional stroke risk factor and had an index stroke that was attributed to large-artery or small-vessel disease. Patients were randomly assigned either to continuous monitoring with the Reveal LINQ device (Medtronic) or to the control arm following site-specific standard of care for AFib detection.

Dr. Schwamm noted that usual care for these patients normally involves monitoring for just a few days while in hospital, but this picks up less than 5% of AFib occurrences.

Baseline characteristics of patients in the STROKE AF study showed that the enrolled population was at high risk for stroke, with a CHADSVASC score of 5. But the index strokes were generally small; the median National Institutes of Health Stroke Scale score was 2.

Results at 12 months, reported 2 years ago, showed a 12.5% incidence of AFib with continuous monitoring versus 1.8% with standard of care (hazard ratio, 7.7; P < .001), rates similar to that found in the CRYSTAL-AF study.

By 3 years, the rate of detected AFib had risen to 21.7% in the continuous monitoring arm versus 2.4% in the control arm (HR, 10.0; P < .001).

“At 12 months, we were seven times more likely to detect AF[ib] with continuous monitoring in these patients, and by 3 years, it was 10 times more likely that AF would be detected with continuous monitoring. I think we’ve settled the question of the best way to find AF[ib] in these patients – it is with an inserted device,” Dr. Schwamm said.

“We have also shown that this is not a transient rise in AFib after the stroke which then diminishes over the next few years. It is a continuous and progressive detection of AF[ib].”

Dr. Schwamm pointed out that 88% of the recorded AFib episodes were asymptomatic. “So relying on patients self-reporting symptoms when deciding who to monitor is unreliable and not a sensible strategy.”

The median time to the first adjudicated AFib episode at 12-month follow-up was 99 days; at the 3-year follow-up, it was 284 days.

“This shows that 30 days of monitoring with an external patch is not sufficient to exclude the presence of AF[ib]. And this really argues for a strategy of immediate insertion of cardiac monitor placement if your goal is to look for AF[ib],” Dr. Schwamm commented.
 

Is this clinically relevant AFib?

Dr. Schwamm acknowledged that there is a question of whether device-detected AFib should be thought about in the same way as clinically detected AFib with respect to future stroke risk.

He noted that, in this study, 67.4% of patients for whom AFib was detected by continuous monitoring (31 of 46 patients) had at least one episode of AFib that lasted more than 1 hour.

“This is not a trivial little squiggle of something on an EKG which then goes away. This is of significant duration that the cardiologist who adjudicated these rhythm strips felt confident was AF[ib].”

He added: “AF[ib] lasting more than 1 hour crosses the threshold for most practitioners I know to feel confident in treating the patient with anticoagulation. If it was symptomatic AF, this wouldn’t even be a question.”

Dr. Schwamm made the point that device-detected A AFib F has been accepted as worthy of treatment in patients after cryptogenic stroke.

“If we are honest with ourselves and if we have no hesitation in starting anticoagulation in a patient with cryptogenic stroke who has had device-detected AF 6 months later, should we decide that if the patient has had a lacunar stroke, we can ignore that same device-detected fibrillation?”

He put forward the idea that, at some level, all stroke is cryptogenic. “We never know for sure what the cause was. We have hypotheses, we have associations, but we don’t really know. So how much should we weigh that presumptive etiology in terms of how we interpret a rhythm disturbance of fibrillation?”

When looking for predictors of AFib in this study, the investigators found that patients were more likely to have an episode of AFib detected if they had one of the four following risk factors: congestive heart failure, left atrial enlargement, obesity, or QRS prolongation.

“In patients with any one of those four factors, 30% of those had device-detected AF[ib]. These are same predictors of AF[ib] that we are all accustomed to,” Dr. Schwamm said.
 

Shared decision-making

Dr. Schwamm said in an interview that, in his practice, for these patients, the decision as to whether to use continuous monitoring is made with the patient through shared decision-making.

“We discuss the chance that they could have AF[ib], and I suggest that it might be worth looking for it, but there are factors to be considered. There is a cost to the device, and reimbursement may depend on insurance coverage. Also, some patients may have strong feelings about having the chip implanted in their body.”

He says implanting the chip is easy. “It takes longer to check in at the front desk than to put the device in. It is injected under the skin. It just needs two stitches and a Band-Aid.” The device connects with a smartphone, and the results are interpreted by a cardiologist.

Dr. Schwamm pointed out that the optimal antithrombotic regimen for these patients in whom AFib is detected remains uncertain and should be the focus of future research.

“Do we just stick to antiplatelet therapy or advance to anticoagulation? In moving to an anticoagulant, are we providing less effective prevention for the atherosclerotic stroke risk at the expense of reducing the AF[ib]-related stroke risk? That may be a reasonable trade-off because we know the disability from AF[ib]-associated stroke is much higher.

“Or perhaps the optimal therapy is aspirin plus low-dose anticoagulant? Or left atrial appendage closure and an antiplatelet for patients at a higher risk of bleeding?” he said. “These are the really important questions we need to start asking.”

He added that he hopes a future study will address these questions, but he noted that it would have to be a large study, that it would have to first identify these patients and then randomly assign them to anticoagulation or to no treatment. “That is quite a major undertaking.”

In the highlights presentation, Dr. Jovin said he was uncertain of which of these patients in whom AFib is detected would benefit from anticoagulation. He said he would also like to see a randomized trial on this. But he added: “This would be challenging, as there is the issue of whether there would be equipoise to allow us to randomize to a placebo.”

Dr. Sansing agreed. “I think it would be a hard sell. I would have to think carefully about randomizing a patient to anticoagulation therapy or no therapy who has been found to have AF[ib].”

Dr. Schwamm noted that the current STROKE-AF study was not designed or powered to detect differences in stroke recurrence rates and that there was no difference in stroke recurrence rates between the two arms. There was also no randomization with regard to treatment; choice of medication was left to the discretion of the treating physician.

But he noted that only for 3 of the 34 patients with recurrent stroke in the continuous-monitor arm was AFib detected prior to the recurrent stroke, and only one of those three was receiving anticoagulation at the time of the recurrent stroke.

“These strokes were occurring in patients who did not have device-detected AF[ib],” Dr. Schwamm said. “This is because the population in this study were loaded with stroke risk factors and are at risk of recurrent stroke, but we don’t have the opportunity in this study to really understand the significance of the recurrent strokes.”

The STROKE AF trial was funded by Medtronic. Dr. Schwamm is a consultant to Medtronic.

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

In the STROKE AF study, among patients who had a stroke presumably caused by atherosclerosis, the rate of atrial fibrillation (AFib) was almost 22% at 3 years, as detected by continuous monitoring.

The 3-year results from the study were presented by Lee H. Schwamm, MD, of Massachusetts General Hospital, Boston, at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

Dr. Schwamm said the high rate of AFib detection in this study suggests that continuous monitoring for AFib should be considered for a larger population of stroke patients, rather than just those with cryptogenic stroke.

“We found a much higher rate of AF[ib] than we expected in this population of patients who have had an atherosclerotic stroke,” Dr. Schwamm said in an interview.

“These AF[ib] occurrences were found by a device, so they are known as ‘device-documented AF[ib].’ The patient is not generally aware of symptoms, but 67% of the AF[ib] episodes lasted for more than 1 hour, showing that this is not trivial AF[ib]. This is meaningful AF[ib],” he said.

Dr. Schwamm said the major question is whether these cases of AFib that are detected with a device warrant treatment with anticoagulation. He noted that, in this study, clinicians decided to provide anticoagulation to 70%-80% of patients in whom AFib was detected.

“If we think it deserves treatment, then we have to look for it. And if we care about finding AF[ib], we have no choice but to monitor continuously,” he said.

“If this data doesn’t convince you that AF[ib] is present in this population, I don’t think any data will. Because it is consistent, it accumulates over time and looks remarkably similar to a set of data that we have all become very comfortable with – the CRYSTAL-AF study in patients with cryptogenic stroke,” he stated.

Dr. Schwamm noted that the STROKE AF trial was not based on the cause of the index stroke; rather, it was asking whether there are risk factors that could contribute to the 25% stroke recurrence rate in this population that are not covered in current guidelines.

“I’m really trying to move away from the anchor that I was trained in, which is to figure out the cause of the last stroke to help decide how to prevent the next stroke, towards more of a probabilistic model – of what is all the information I have at my disposal and how do I act on it to prevent the next stroke? We have to start thinking differently about building models for future stroke risk and determining therapy based on that,” he commented.
 

Changing practice

ISC 2023 program chair Tudor Jovin, MD, Cooper Neurological Institute, Cherry Hill, N.J., and moderator of the session at which the results were presented, discussed the STROKE AF results in a highlights presentation.

“To me as clinician, these results are even more relevant than those at 12 months,” Dr. Jovin said. “The lesson I took is that AF[ib] is even more prevalent than we thought. The burden of AF[ib] is significant in these patients, and it doesn’t seem to be limited to a particular time. These are very thought-provoking results which are going to change clinical practice. I think the threshold for long-term monitoring will be lower.”

Comoderator Lauren Sansing, MD, Yale University, New Haven, Conn., added: “This study shows that the longer we monitor, the more patients with AF[ib] we are likely to pick up. And because in two-thirds of patients with AF[ib], it lasted longer than 1 hour, I do believe this was clinically relevant AF[ib]. The question now is, do we monitor everyone? I think it puts the burden on us to search for AF[ib] in our patients.”

In his presentation, Dr. Schwamm explained that, on the basis of the CRYSTAL-AF study, insertable cardiac monitoring devices are frequently used to identify poststroke AFib in patients with cryptogenic stroke. In the device-monitored arm of that study, AFib was detected in 12.4% of patients over 12 months versus 2.0% in the control arm.

“However, we don’t know how often AF[ib] is detected in other presumed stroke types – largely those due to atherosclerosis,” he said.

He pointed out that, at present, long-term monitoring post stroke for the detection of AFib is not currently recommended for patients with ischemic stroke, owing to presumed small-vessel occlusion or large-artery atherosclerosis.

“In these patients, we are not suspecting AF[ib] because we believe the cause of the stroke was not embolic. But we wanted to investigate what the AF[ib] risk is in these patients, who often have multiple stroke risk factors,” he said.

The trial enrolled 496 patients at 33 centers in the United States. Eligible patients were aged 60 years or older or aged 50-59 years with at least one additional stroke risk factor and had an index stroke that was attributed to large-artery or small-vessel disease. Patients were randomly assigned either to continuous monitoring with the Reveal LINQ device (Medtronic) or to the control arm following site-specific standard of care for AFib detection.

Dr. Schwamm noted that usual care for these patients normally involves monitoring for just a few days while in hospital, but this picks up less than 5% of AFib occurrences.

Baseline characteristics of patients in the STROKE AF study showed that the enrolled population was at high risk for stroke, with a CHADSVASC score of 5. But the index strokes were generally small; the median National Institutes of Health Stroke Scale score was 2.

Results at 12 months, reported 2 years ago, showed a 12.5% incidence of AFib with continuous monitoring versus 1.8% with standard of care (hazard ratio, 7.7; P < .001), rates similar to that found in the CRYSTAL-AF study.

By 3 years, the rate of detected AFib had risen to 21.7% in the continuous monitoring arm versus 2.4% in the control arm (HR, 10.0; P < .001).

“At 12 months, we were seven times more likely to detect AF[ib] with continuous monitoring in these patients, and by 3 years, it was 10 times more likely that AF would be detected with continuous monitoring. I think we’ve settled the question of the best way to find AF[ib] in these patients – it is with an inserted device,” Dr. Schwamm said.

“We have also shown that this is not a transient rise in AFib after the stroke which then diminishes over the next few years. It is a continuous and progressive detection of AF[ib].”

Dr. Schwamm pointed out that 88% of the recorded AFib episodes were asymptomatic. “So relying on patients self-reporting symptoms when deciding who to monitor is unreliable and not a sensible strategy.”

The median time to the first adjudicated AFib episode at 12-month follow-up was 99 days; at the 3-year follow-up, it was 284 days.

“This shows that 30 days of monitoring with an external patch is not sufficient to exclude the presence of AF[ib]. And this really argues for a strategy of immediate insertion of cardiac monitor placement if your goal is to look for AF[ib],” Dr. Schwamm commented.
 

Is this clinically relevant AFib?

Dr. Schwamm acknowledged that there is a question of whether device-detected AFib should be thought about in the same way as clinically detected AFib with respect to future stroke risk.

He noted that, in this study, 67.4% of patients for whom AFib was detected by continuous monitoring (31 of 46 patients) had at least one episode of AFib that lasted more than 1 hour.

“This is not a trivial little squiggle of something on an EKG which then goes away. This is of significant duration that the cardiologist who adjudicated these rhythm strips felt confident was AF[ib].”

He added: “AF[ib] lasting more than 1 hour crosses the threshold for most practitioners I know to feel confident in treating the patient with anticoagulation. If it was symptomatic AF, this wouldn’t even be a question.”

Dr. Schwamm made the point that device-detected A AFib F has been accepted as worthy of treatment in patients after cryptogenic stroke.

“If we are honest with ourselves and if we have no hesitation in starting anticoagulation in a patient with cryptogenic stroke who has had device-detected AF 6 months later, should we decide that if the patient has had a lacunar stroke, we can ignore that same device-detected fibrillation?”

He put forward the idea that, at some level, all stroke is cryptogenic. “We never know for sure what the cause was. We have hypotheses, we have associations, but we don’t really know. So how much should we weigh that presumptive etiology in terms of how we interpret a rhythm disturbance of fibrillation?”

When looking for predictors of AFib in this study, the investigators found that patients were more likely to have an episode of AFib detected if they had one of the four following risk factors: congestive heart failure, left atrial enlargement, obesity, or QRS prolongation.

“In patients with any one of those four factors, 30% of those had device-detected AF[ib]. These are same predictors of AF[ib] that we are all accustomed to,” Dr. Schwamm said.
 

Shared decision-making

Dr. Schwamm said in an interview that, in his practice, for these patients, the decision as to whether to use continuous monitoring is made with the patient through shared decision-making.

“We discuss the chance that they could have AF[ib], and I suggest that it might be worth looking for it, but there are factors to be considered. There is a cost to the device, and reimbursement may depend on insurance coverage. Also, some patients may have strong feelings about having the chip implanted in their body.”

He says implanting the chip is easy. “It takes longer to check in at the front desk than to put the device in. It is injected under the skin. It just needs two stitches and a Band-Aid.” The device connects with a smartphone, and the results are interpreted by a cardiologist.

Dr. Schwamm pointed out that the optimal antithrombotic regimen for these patients in whom AFib is detected remains uncertain and should be the focus of future research.

“Do we just stick to antiplatelet therapy or advance to anticoagulation? In moving to an anticoagulant, are we providing less effective prevention for the atherosclerotic stroke risk at the expense of reducing the AF[ib]-related stroke risk? That may be a reasonable trade-off because we know the disability from AF[ib]-associated stroke is much higher.

“Or perhaps the optimal therapy is aspirin plus low-dose anticoagulant? Or left atrial appendage closure and an antiplatelet for patients at a higher risk of bleeding?” he said. “These are the really important questions we need to start asking.”

He added that he hopes a future study will address these questions, but he noted that it would have to be a large study, that it would have to first identify these patients and then randomly assign them to anticoagulation or to no treatment. “That is quite a major undertaking.”

In the highlights presentation, Dr. Jovin said he was uncertain of which of these patients in whom AFib is detected would benefit from anticoagulation. He said he would also like to see a randomized trial on this. But he added: “This would be challenging, as there is the issue of whether there would be equipoise to allow us to randomize to a placebo.”

Dr. Sansing agreed. “I think it would be a hard sell. I would have to think carefully about randomizing a patient to anticoagulation therapy or no therapy who has been found to have AF[ib].”

Dr. Schwamm noted that the current STROKE-AF study was not designed or powered to detect differences in stroke recurrence rates and that there was no difference in stroke recurrence rates between the two arms. There was also no randomization with regard to treatment; choice of medication was left to the discretion of the treating physician.

But he noted that only for 3 of the 34 patients with recurrent stroke in the continuous-monitor arm was AFib detected prior to the recurrent stroke, and only one of those three was receiving anticoagulation at the time of the recurrent stroke.

“These strokes were occurring in patients who did not have device-detected AF[ib],” Dr. Schwamm said. “This is because the population in this study were loaded with stroke risk factors and are at risk of recurrent stroke, but we don’t have the opportunity in this study to really understand the significance of the recurrent strokes.”

The STROKE AF trial was funded by Medtronic. Dr. Schwamm is a consultant to Medtronic.

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

PEMAZYRE® (pemigatinib) is indicated for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s)¹. 

PEMAZYRE can cause serious adverse reactions including Ocular Toxicity (Retinal Pigment Epithelial Detachment [RPED] and Dry Eye), Hyperphosphatemia and Soft Tissue Mineralization, and Embryo-Fetal Toxicity. See Additional Important Safety Information Below¹.

Cholangiocarcinoma, or CCA, is a rare cancer formed in the bile duct. It is difficult to diagnose due to generalized symptoms patients often experience². As with any serious disease, the initial diagnosis can be an incredibly overwhelming experience for patients and their families. For people living with CCA specifically, the diagnosis process can be very long and arduous, which often means a patient’s condition can reach an advanced stage where the prognosis is poor by the time he or she is diagnosed³.

Scientific advancements, such as biomarker testing, or genomic analysis of a patient’s tissue, have made it possible to better understand a person’s specific cancer. Understanding patients’ tumors at the molecular level may help health care professionals individualize a treatment plan that is specific to each patient. 

As the genomic profile of CCA has become clearer, actionable alterations in the DNA that are amenable to treatment with either existing agents or those in development have come into focus. Certain actionable genomic alterations have been identified in up to 2/3 of patients with the intrahepatic subtype of CCA, although this percentage may vary in actual practice⁴. Specifically, research has found that fibroblast growth factor receptor 2 (FGFR2) alterations, which play an important role in the development of cancers like CCA, especially the intrahepatic subtype, is on the rise³. This has prompted recognition of comprehensive genomic testing. Due to the rapid advances in precision medicine for CCA, the NCCN guidelines recommend the use of biomarker testing for advanced CCA⁵. 

The First Targeted Treatment Option for CCA

Though an incredibly useful tool, there is a need for further education about the importance of early biomarker testing amongst the medical community. In one large community-based hospital in California, the implementation of a precision medicine program allowed oncologists and pathologists to standardize all tumor biomarker testing, resulting in an increase in testing⁵. However, there is still much improvement needed. What’s more, scientific advancements in recent years have opened the door to targeted treatment options including Pemazyre® (pemigatinib). Pemazyre was approved by the U.S. Food and Drug Administration (FDA) under accelerated approval in 2020 as the first targeted treatment for adults with previously treated, unresectable locally advanced or metastatic CCA with a FGFR2 fusion or other rearrangement as detected by an FDA-approved test.

“The FDA approval of Pemazyre was and continues to be an encouraging milestone for the CCA community, as patients historically had limited options after first-line chemotherapy or surgery, after which relapse rates were high,” said Dr. Sahai.

Pemazyre works by helping to stop the activity of the abnormal FGFR2 protein, which may help reduce the size of CCA tumors or cause them to disappear. Pemazyre’s approval was based on the results of the multicenter, open-label, single arm FIGHT-202 study in 146 previously treated patients with locally advanced or metastatic CCA1. 

• The efficacy population consisted of 107 patients with disease that had progressed on or after at least 1 prior therapy and who had an FGFR2 fusion or non-fusion rearrangement, as determined by a clinical trial assay (FoundationOne® CDx) performed at a central laboratory.
• The major efficacy outcome measures were overall response rate (ORR) and duration of response (DoR). The study found an ORR of 36%, and median DoR of 9.1 months. 
• The most common adverse reactions (incidence ≥20%) in all patients were hyperphosphatemia, alopecia, diarrhea, nail toxicity, fatigue, dysgeusia, nausea, constipation, stomatitis, dry eye, dry mouth, decreased appetite, vomiting, arthralgia, abdominal pain, hypophosphatemia, back pain, and dry skin.

Meet Fred, Battling CCA

Meet Fred – a man living with CCA. After noticing an unusual amount of blood following what he thought was a normal kidney stone, Fred contacted his doctor right away. Unfortunately, it was not clear from his initial symptoms what the problem was. A computed tomography (CT or CAT) scan revealed Fred did indeed have a kidney stone, but it also showed a large mass had formed on his liver, leading to more testing. After several tests, Fred was diagnosed with CCA. Because of the nonspecific symptoms he had been experiencing, his cancer unfortunately had time to grow. Upon advice from his doctor, Fred met with a CCA specialist who quickly ordered biomarker testing, revealing that he had FGFR2-driven CCA. With a molecular understanding of Fred’s specific CCA, his health care team was able to prescribe him Pemazyre. 

“I’m grateful I was able to start receiving treatment for my condition following chemotherapy and continue to see improvements in my condition,” noted Fred. “Though I fight side effects such as great fatigue, dry eye, dry skin, and fingernail discoloration, these innovations in science that lead to treatments like Pemazyre are what continue to give my family and I hope.”

Through his own experience, Fred has become an advocate for encouraging others living with CCA to educate themselves about the disease and the importance of early biomarker testing. “My advice is to be your own health advocate. Take charge of how your diagnosis and treatment plan is formed with your doctor, and don’t be afraid to speak openly with your doctor about the tools, like biomarker testing, that are available,” said Fred. “I feel fortunate that my health care team initiated biomarker testing quickly after my diagnosis, which enabled me to find an appropriate treatment option for my specific condition. I know that’s not always the case for my fellow CCA warriors, so I urge those in the community to take charge of their health conversations.” 

Leverage The Leading Tools at Hand 

Fred’s story, like that of so many other CCA patients, was a long and winding road to an accurate diagnosis; however, once he was diagnosed, biomarker testing allowed for Fred’s health care team to fully understand his condition, which led to a tailored treatment plan with Pemazyre. While the regular use of biomarker testing is on the rise, it’s critical that health care providers continue to institute early biomarker testing as standard practice, as it may provide the opportunity to quickly and accurately determine the best path forward for their patients. 

For more information about treatment with Pemazyre, visit Pemzayre.com and Full Prescribing Information.  

###

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

PEMAZYRE^® is indicated for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test.

This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

IMPORTANT SAFETY INFORMATION

Ocular Toxicity
Retinal Pigment Epithelial Detachment (RPED): PEMAZYRE can cause RPED, which may cause symptoms such as blurred vision, visual floaters, or photopsia. Clinical trials of PEMAZYRE did not conduct routine monitoring including optical coherence tomography (OCT) to detect asymptomatic RPED; therefore, the incidence of asymptomatic RPED with PEMAZYRE is unknown.

Among 635 patients who received a starting dose of PEMAZYRE 13.5 mg across clinical trials, RPED occurred in 11% of patients, including Grade 3-4 RPED in 1.3%. The median time to first onset of RPED was 56 days. RPED led to dose interruption of PEMAZYRE in 3.1% of patients, and dose reduction and permanent discontinuation in 1.3% and in 0.2% of patients, respectively. RPED resolved or improved to Grade 1 levels in 76% of patients who required dosage modification of PEMAZYRE for RPED.

Perform a comprehensive ophthalmological examination including OCT prior to initiation of PEMAZYRE and every 2 months for the first 6 months and every 3 months thereafter during treatment. For onset of visual symptoms, refer patients for ophthalmologic evaluation urgently, with follow-up every 3 weeks until resolution or discontinuation of PEMAZYRE. Modify the dose or permanently discontinue PEMAZYRE as recommended in the prescribing information for PEMAZYRE. 

Dry Eye:  Among 635 patients who received a starting dose of PEMAZYRE 13.5 mg across clinical trials, dry eye occurred in 31% of patients, including Grade 3-4 in 1.6% of patients. Treat patients with ocular demulcents as needed.

Hyperphosphatemia and Soft Tissue Mineralization
PEMAZYRE can cause hyperphosphatemia leading to soft tissue mineralization, cutaneous calcification, calcinosis, and non-uremic calciphylaxis. Increases in phosphate levels are a pharmacodynamic effect of PEMAZYRE. Among 635 patients who received a starting dose of PEMAZYRE 13.5 mg across clinical trials, hyperphosphatemia was reported in 93% of patients based on laboratory values above the upper limit of normal. The median time to onset of hyperphosphatemia was 8 days (range 1-169). Phosphate lowering therapy was required in 33% of patients receiving PEMAZYRE.

Monitor for hyperphosphatemia and initiate a low phosphate diet when serum phosphate level is >5.5 mg/dL. For serum phosphate levels >7 mg/dL, initiate phosphate lowering therapy and withhold, reduce the dose, or permanently discontinue PEMAZYRE based on duration and severity of hyperphosphatemia as recommended in the prescribing information.

Embryo-Fetal Toxicity
Based on findings in an animal study and its mechanism of action, PEMAZYRE can cause fetal harm when administered to a pregnant woman. Oral administration of pemigatinib to pregnant rats during the period of organogenesis caused fetal malformations, fetal growth retardation, and embryo-fetal death at maternal exposures lower than the human exposure based on area under the curve (AUC) at the clinical dose of 13.5 mg.

Advise pregnant women of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during treatment with PEMAZYRE and for 1 week after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with PEMAZYRE and for 1 week after the last dose.

Adverse Reactions:  Cholangiocarcinoma
Serious adverse reactions occurred in 45% of patients receiving PEMAZYRE (n=146). Serious adverse reactions in ≥2% of patients who received PEMAZYRE included abdominal pain, pyrexia, cholangitis, pleural effusion, acute kidney injury, cholangitis infective, failure to thrive, hypercalcemia, hyponatremia, small intestinal obstruction, and urinary tract infection. Fatal adverse reactions occurred in 4.1% of patients, including failure to thrive, bile duct obstruction, cholangitis, sepsis, and pleural effusion.

Permanent discontinuation due to an adverse reaction occurred in 9% of patients who received PEMAZYRE. Adverse reactions requiring permanent discontinuation in ≥1% of patients included intestinal obstruction and acute kidney injury.

Dosage interruptions due to an adverse reaction occurred in 43% of patients who received PEMAZYRE.  Adverse reactions requiring dosage interruption in ≥1% of patients included stomatitis, palmar-plantar erythrodysesthesia syndrome, arthralgia, fatigue, abdominal pain, AST increased, asthenia, pyrexia, ALT increased, cholangitis, small intestinal obstruction, alkaline phosphatase increased, diarrhea, hyperbilirubinemia, electrocardiogram QT prolonged, decreased appetite, dehydration, hypercalcemia, hyperphosphatemia, hypophosphatemia, back pain, pain in extremity, syncope, acute kidney injury, onychomadesis, and hypotension.

Dose reductions due to an adverse reaction occurred in 14% of patients who received PEMAZYRE.  Adverse reactions requiring dosage reductions in ≥1% of patients who received PEMAZYRE included stomatitis, arthralgia, palmar-plantar erythrodysesthesia syndrome, asthenia, and onychomadesis.

Clinically relevant adverse reactions occurring in ≤10% of patients included fractures (2.1%). In all patients treated with pemigatinib, 0.5% experienced pathologic fractures (which included patients with and without cholangiocarcinoma [N = 635]). Soft tissue mineralization, including cutaneous calcification, calcinosis, and non-uremic calciphylaxis associated with hyperphosphatemia were observed with PEMAZYRE treatment.

Within the first 21-day cycle of PEMAZYRE dosing, serum creatinine increased (mean increase of 0.2 mg/dL) and reached steady state by Day 8, and then decreased during the 7 days off therapy. Consider alternative markers of renal function if persistent elevations in serum creatinine are observed.

In cholangiocarcinoma (n=146) the most common adverse reactions (incidence ≥20%) were hyperphosphatemia (60%), alopecia (49%), diarrhea (47%), nail toxicity (43%), fatigue (42%), dysgeusia (40%), nausea (40%), constipation (35%), stomatitis (35%), dry eye (35%), dry mouth (34%), decreased appetite (33%), vomiting (27%), arthralgia (25%), abdominal pain (23%), hypophosphatemia (23%), back pain (20%), and dry skin (20%).

Drug Interactions
Avoid concomitant use of strong and moderate CYP3A inhibitors with PEMAZYRE. Reduce the dose of PEMAZYRE if concomitant use with a strong or moderate CYP3A inhibitor cannot be avoided. Avoid concomitant use of strong and moderate CYP3A inducers with PEMAZYRE.  
Special Populations
Advise lactating women not to breastfeed during treatment with PEMAZYRE and for 1 week after the last dose.

Reduce the recommended dose of PEMAZYRE for patients with severe renal impairment as described in the prescribing information.

Reduce the recommended dose of PEMAZYRE for patients with severe hepatic impairment as described in the prescribing information. 

Please see Full Prescribing Information for PEMAZYRE.

Incyte and the Incyte logo are registered trademarks of Incyte.
PEMAZYRE  and the PEMAZYRE logo are registered trademarks of Incyte.
All other trademarks are the property of their respective owners.
© 2022, Incyte. MAT-PEM-00414  10/22

^{References:
1.    Pemazyre. Prescribing Information. Incyte Corporation. Accessed August 22, 2022.https://www.pemazyre.com/pdf/prescribing-information.pdf.
2.    Signs and Symptoms of Bile Duct Cancer. American Cancer Society. Updated January 27, 2021. Accessed June 16, 2022. https://www.cancer.org/cancer/bile-duct-cancer/detection-diagnosis-staging/survival-by-stage.html.
3.    Banales JM, Cardinale V, Carpino G, et al. Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the study of cholangiocarcinoma. Nat Rev Gastroenterol Hepatol. 2016;13(5):261-280.
4.    Ross JS, Wang K, Gay L, et al. New routes to targeted therapy of intrahepatic cholangiocarcinomas revealed by next-generation sequencing. Oncol. 2014;19(3):235-242. 
5.    Cho M, Gholami S, Gui D, et al. Optimizing the diagnosis and biomarker testing for patients with intrahepatic cholangiocarcinoma: a multidisciplinary approach. National Library of Medicine. 2022;13(1).} 
 

PEMAZYRE® (pemigatinib) is indicated for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s)¹. 

PEMAZYRE can cause serious adverse reactions including Ocular Toxicity (Retinal Pigment Epithelial Detachment [RPED] and Dry Eye), Hyperphosphatemia and Soft Tissue Mineralization, and Embryo-Fetal Toxicity. See Additional Important Safety Information Below¹.

Cholangiocarcinoma, or CCA, is a rare cancer formed in the bile duct. It is difficult to diagnose due to generalized symptoms patients often experience². As with any serious disease, the initial diagnosis can be an incredibly overwhelming experience for patients and their families. For people living with CCA specifically, the diagnosis process can be very long and arduous, which often means a patient’s condition can reach an advanced stage where the prognosis is poor by the time he or she is diagnosed³.

Scientific advancements, such as biomarker testing, or genomic analysis of a patient’s tissue, have made it possible to better understand a person’s specific cancer. Understanding patients’ tumors at the molecular level may help health care professionals individualize a treatment plan that is specific to each patient. 

As the genomic profile of CCA has become clearer, actionable alterations in the DNA that are amenable to treatment with either existing agents or those in development have come into focus. Certain actionable genomic alterations have been identified in up to 2/3 of patients with the intrahepatic subtype of CCA, although this percentage may vary in actual practice⁴. Specifically, research has found that fibroblast growth factor receptor 2 (FGFR2) alterations, which play an important role in the development of cancers like CCA, especially the intrahepatic subtype, is on the rise³. This has prompted recognition of comprehensive genomic testing. Due to the rapid advances in precision medicine for CCA, the NCCN guidelines recommend the use of biomarker testing for advanced CCA⁵. 

The First Targeted Treatment Option for CCA

Though an incredibly useful tool, there is a need for further education about the importance of early biomarker testing amongst the medical community. In one large community-based hospital in California, the implementation of a precision medicine program allowed oncologists and pathologists to standardize all tumor biomarker testing, resulting in an increase in testing⁵. However, there is still much improvement needed. What’s more, scientific advancements in recent years have opened the door to targeted treatment options including Pemazyre® (pemigatinib). Pemazyre was approved by the U.S. Food and Drug Administration (FDA) under accelerated approval in 2020 as the first targeted treatment for adults with previously treated, unresectable locally advanced or metastatic CCA with a FGFR2 fusion or other rearrangement as detected by an FDA-approved test.

“The FDA approval of Pemazyre was and continues to be an encouraging milestone for the CCA community, as patients historically had limited options after first-line chemotherapy or surgery, after which relapse rates were high,” said Dr. Sahai.

Pemazyre works by helping to stop the activity of the abnormal FGFR2 protein, which may help reduce the size of CCA tumors or cause them to disappear. Pemazyre’s approval was based on the results of the multicenter, open-label, single arm FIGHT-202 study in 146 previously treated patients with locally advanced or metastatic CCA1. 

• The efficacy population consisted of 107 patients with disease that had progressed on or after at least 1 prior therapy and who had an FGFR2 fusion or non-fusion rearrangement, as determined by a clinical trial assay (FoundationOne® CDx) performed at a central laboratory.
• The major efficacy outcome measures were overall response rate (ORR) and duration of response (DoR). The study found an ORR of 36%, and median DoR of 9.1 months. 
• The most common adverse reactions (incidence ≥20%) in all patients were hyperphosphatemia, alopecia, diarrhea, nail toxicity, fatigue, dysgeusia, nausea, constipation, stomatitis, dry eye, dry mouth, decreased appetite, vomiting, arthralgia, abdominal pain, hypophosphatemia, back pain, and dry skin.

Meet Fred, Battling CCA

Meet Fred – a man living with CCA. After noticing an unusual amount of blood following what he thought was a normal kidney stone, Fred contacted his doctor right away. Unfortunately, it was not clear from his initial symptoms what the problem was. A computed tomography (CT or CAT) scan revealed Fred did indeed have a kidney stone, but it also showed a large mass had formed on his liver, leading to more testing. After several tests, Fred was diagnosed with CCA. Because of the nonspecific symptoms he had been experiencing, his cancer unfortunately had time to grow. Upon advice from his doctor, Fred met with a CCA specialist who quickly ordered biomarker testing, revealing that he had FGFR2-driven CCA. With a molecular understanding of Fred’s specific CCA, his health care team was able to prescribe him Pemazyre. 

“I’m grateful I was able to start receiving treatment for my condition following chemotherapy and continue to see improvements in my condition,” noted Fred. “Though I fight side effects such as great fatigue, dry eye, dry skin, and fingernail discoloration, these innovations in science that lead to treatments like Pemazyre are what continue to give my family and I hope.”

Through his own experience, Fred has become an advocate for encouraging others living with CCA to educate themselves about the disease and the importance of early biomarker testing. “My advice is to be your own health advocate. Take charge of how your diagnosis and treatment plan is formed with your doctor, and don’t be afraid to speak openly with your doctor about the tools, like biomarker testing, that are available,” said Fred. “I feel fortunate that my health care team initiated biomarker testing quickly after my diagnosis, which enabled me to find an appropriate treatment option for my specific condition. I know that’s not always the case for my fellow CCA warriors, so I urge those in the community to take charge of their health conversations.” 

Leverage The Leading Tools at Hand 

Fred’s story, like that of so many other CCA patients, was a long and winding road to an accurate diagnosis; however, once he was diagnosed, biomarker testing allowed for Fred’s health care team to fully understand his condition, which led to a tailored treatment plan with Pemazyre. While the regular use of biomarker testing is on the rise, it’s critical that health care providers continue to institute early biomarker testing as standard practice, as it may provide the opportunity to quickly and accurately determine the best path forward for their patients. 

For more information about treatment with Pemazyre, visit Pemzayre.com and Full Prescribing Information.  

###

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

PEMAZYRE^® is indicated for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test.

This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

IMPORTANT SAFETY INFORMATION

Ocular Toxicity
Retinal Pigment Epithelial Detachment (RPED): PEMAZYRE can cause RPED, which may cause symptoms such as blurred vision, visual floaters, or photopsia. Clinical trials of PEMAZYRE did not conduct routine monitoring including optical coherence tomography (OCT) to detect asymptomatic RPED; therefore, the incidence of asymptomatic RPED with PEMAZYRE is unknown.

Among 635 patients who received a starting dose of PEMAZYRE 13.5 mg across clinical trials, RPED occurred in 11% of patients, including Grade 3-4 RPED in 1.3%. The median time to first onset of RPED was 56 days. RPED led to dose interruption of PEMAZYRE in 3.1% of patients, and dose reduction and permanent discontinuation in 1.3% and in 0.2% of patients, respectively. RPED resolved or improved to Grade 1 levels in 76% of patients who required dosage modification of PEMAZYRE for RPED.

Perform a comprehensive ophthalmological examination including OCT prior to initiation of PEMAZYRE and every 2 months for the first 6 months and every 3 months thereafter during treatment. For onset of visual symptoms, refer patients for ophthalmologic evaluation urgently, with follow-up every 3 weeks until resolution or discontinuation of PEMAZYRE. Modify the dose or permanently discontinue PEMAZYRE as recommended in the prescribing information for PEMAZYRE. 

Dry Eye:  Among 635 patients who received a starting dose of PEMAZYRE 13.5 mg across clinical trials, dry eye occurred in 31% of patients, including Grade 3-4 in 1.6% of patients. Treat patients with ocular demulcents as needed.

Hyperphosphatemia and Soft Tissue Mineralization
PEMAZYRE can cause hyperphosphatemia leading to soft tissue mineralization, cutaneous calcification, calcinosis, and non-uremic calciphylaxis. Increases in phosphate levels are a pharmacodynamic effect of PEMAZYRE. Among 635 patients who received a starting dose of PEMAZYRE 13.5 mg across clinical trials, hyperphosphatemia was reported in 93% of patients based on laboratory values above the upper limit of normal. The median time to onset of hyperphosphatemia was 8 days (range 1-169). Phosphate lowering therapy was required in 33% of patients receiving PEMAZYRE.

Monitor for hyperphosphatemia and initiate a low phosphate diet when serum phosphate level is >5.5 mg/dL. For serum phosphate levels >7 mg/dL, initiate phosphate lowering therapy and withhold, reduce the dose, or permanently discontinue PEMAZYRE based on duration and severity of hyperphosphatemia as recommended in the prescribing information.

Embryo-Fetal Toxicity
Based on findings in an animal study and its mechanism of action, PEMAZYRE can cause fetal harm when administered to a pregnant woman. Oral administration of pemigatinib to pregnant rats during the period of organogenesis caused fetal malformations, fetal growth retardation, and embryo-fetal death at maternal exposures lower than the human exposure based on area under the curve (AUC) at the clinical dose of 13.5 mg.

Advise pregnant women of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during treatment with PEMAZYRE and for 1 week after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with PEMAZYRE and for 1 week after the last dose.

Adverse Reactions:  Cholangiocarcinoma
Serious adverse reactions occurred in 45% of patients receiving PEMAZYRE (n=146). Serious adverse reactions in ≥2% of patients who received PEMAZYRE included abdominal pain, pyrexia, cholangitis, pleural effusion, acute kidney injury, cholangitis infective, failure to thrive, hypercalcemia, hyponatremia, small intestinal obstruction, and urinary tract infection. Fatal adverse reactions occurred in 4.1% of patients, including failure to thrive, bile duct obstruction, cholangitis, sepsis, and pleural effusion.

Permanent discontinuation due to an adverse reaction occurred in 9% of patients who received PEMAZYRE. Adverse reactions requiring permanent discontinuation in ≥1% of patients included intestinal obstruction and acute kidney injury.

Dosage interruptions due to an adverse reaction occurred in 43% of patients who received PEMAZYRE.  Adverse reactions requiring dosage interruption in ≥1% of patients included stomatitis, palmar-plantar erythrodysesthesia syndrome, arthralgia, fatigue, abdominal pain, AST increased, asthenia, pyrexia, ALT increased, cholangitis, small intestinal obstruction, alkaline phosphatase increased, diarrhea, hyperbilirubinemia, electrocardiogram QT prolonged, decreased appetite, dehydration, hypercalcemia, hyperphosphatemia, hypophosphatemia, back pain, pain in extremity, syncope, acute kidney injury, onychomadesis, and hypotension.

Dose reductions due to an adverse reaction occurred in 14% of patients who received PEMAZYRE.  Adverse reactions requiring dosage reductions in ≥1% of patients who received PEMAZYRE included stomatitis, arthralgia, palmar-plantar erythrodysesthesia syndrome, asthenia, and onychomadesis.

Clinically relevant adverse reactions occurring in ≤10% of patients included fractures (2.1%). In all patients treated with pemigatinib, 0.5% experienced pathologic fractures (which included patients with and without cholangiocarcinoma [N = 635]). Soft tissue mineralization, including cutaneous calcification, calcinosis, and non-uremic calciphylaxis associated with hyperphosphatemia were observed with PEMAZYRE treatment.

Within the first 21-day cycle of PEMAZYRE dosing, serum creatinine increased (mean increase of 0.2 mg/dL) and reached steady state by Day 8, and then decreased during the 7 days off therapy. Consider alternative markers of renal function if persistent elevations in serum creatinine are observed.

In cholangiocarcinoma (n=146) the most common adverse reactions (incidence ≥20%) were hyperphosphatemia (60%), alopecia (49%), diarrhea (47%), nail toxicity (43%), fatigue (42%), dysgeusia (40%), nausea (40%), constipation (35%), stomatitis (35%), dry eye (35%), dry mouth (34%), decreased appetite (33%), vomiting (27%), arthralgia (25%), abdominal pain (23%), hypophosphatemia (23%), back pain (20%), and dry skin (20%).

Drug Interactions
Avoid concomitant use of strong and moderate CYP3A inhibitors with PEMAZYRE. Reduce the dose of PEMAZYRE if concomitant use with a strong or moderate CYP3A inhibitor cannot be avoided. Avoid concomitant use of strong and moderate CYP3A inducers with PEMAZYRE.  
Special Populations
Advise lactating women not to breastfeed during treatment with PEMAZYRE and for 1 week after the last dose.

Reduce the recommended dose of PEMAZYRE for patients with severe renal impairment as described in the prescribing information.

Reduce the recommended dose of PEMAZYRE for patients with severe hepatic impairment as described in the prescribing information. 

Please see Full Prescribing Information for PEMAZYRE.

Incyte and the Incyte logo are registered trademarks of Incyte.
PEMAZYRE  and the PEMAZYRE logo are registered trademarks of Incyte.
All other trademarks are the property of their respective owners.
© 2022, Incyte. MAT-PEM-00414  10/22

^{References:
1.    Pemazyre. Prescribing Information. Incyte Corporation. Accessed August 22, 2022.https://www.pemazyre.com/pdf/prescribing-information.pdf.
2.    Signs and Symptoms of Bile Duct Cancer. American Cancer Society. Updated January 27, 2021. Accessed June 16, 2022. https://www.cancer.org/cancer/bile-duct-cancer/detection-diagnosis-staging/survival-by-stage.html.
3.    Banales JM, Cardinale V, Carpino G, et al. Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the study of cholangiocarcinoma. Nat Rev Gastroenterol Hepatol. 2016;13(5):261-280.
4.    Ross JS, Wang K, Gay L, et al. New routes to targeted therapy of intrahepatic cholangiocarcinomas revealed by next-generation sequencing. Oncol. 2014;19(3):235-242. 
5.    Cho M, Gholami S, Gui D, et al. Optimizing the diagnosis and biomarker testing for patients with intrahepatic cholangiocarcinoma: a multidisciplinary approach. National Library of Medicine. 2022;13(1).} 
 

PEMAZYRE® (pemigatinib) is indicated for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s)¹. 

PEMAZYRE can cause serious adverse reactions including Ocular Toxicity (Retinal Pigment Epithelial Detachment [RPED] and Dry Eye), Hyperphosphatemia and Soft Tissue Mineralization, and Embryo-Fetal Toxicity. See Additional Important Safety Information Below¹.

Cholangiocarcinoma, or CCA, is a rare cancer formed in the bile duct. It is difficult to diagnose due to generalized symptoms patients often experience². As with any serious disease, the initial diagnosis can be an incredibly overwhelming experience for patients and their families. For people living with CCA specifically, the diagnosis process can be very long and arduous, which often means a patient’s condition can reach an advanced stage where the prognosis is poor by the time he or she is diagnosed³.

Scientific advancements, such as biomarker testing, or genomic analysis of a patient’s tissue, have made it possible to better understand a person’s specific cancer. Understanding patients’ tumors at the molecular level may help health care professionals individualize a treatment plan that is specific to each patient. 

As the genomic profile of CCA has become clearer, actionable alterations in the DNA that are amenable to treatment with either existing agents or those in development have come into focus. Certain actionable genomic alterations have been identified in up to 2/3 of patients with the intrahepatic subtype of CCA, although this percentage may vary in actual practice⁴. Specifically, research has found that fibroblast growth factor receptor 2 (FGFR2) alterations, which play an important role in the development of cancers like CCA, especially the intrahepatic subtype, is on the rise³. This has prompted recognition of comprehensive genomic testing. Due to the rapid advances in precision medicine for CCA, the NCCN guidelines recommend the use of biomarker testing for advanced CCA⁵. 

The First Targeted Treatment Option for CCA

Though an incredibly useful tool, there is a need for further education about the importance of early biomarker testing amongst the medical community. In one large community-based hospital in California, the implementation of a precision medicine program allowed oncologists and pathologists to standardize all tumor biomarker testing, resulting in an increase in testing⁵. However, there is still much improvement needed. What’s more, scientific advancements in recent years have opened the door to targeted treatment options including Pemazyre® (pemigatinib). Pemazyre was approved by the U.S. Food and Drug Administration (FDA) under accelerated approval in 2020 as the first targeted treatment for adults with previously treated, unresectable locally advanced or metastatic CCA with a FGFR2 fusion or other rearrangement as detected by an FDA-approved test.

“The FDA approval of Pemazyre was and continues to be an encouraging milestone for the CCA community, as patients historically had limited options after first-line chemotherapy or surgery, after which relapse rates were high,” said Dr. Sahai.

Pemazyre works by helping to stop the activity of the abnormal FGFR2 protein, which may help reduce the size of CCA tumors or cause them to disappear. Pemazyre’s approval was based on the results of the multicenter, open-label, single arm FIGHT-202 study in 146 previously treated patients with locally advanced or metastatic CCA1. 

• The efficacy population consisted of 107 patients with disease that had progressed on or after at least 1 prior therapy and who had an FGFR2 fusion or non-fusion rearrangement, as determined by a clinical trial assay (FoundationOne® CDx) performed at a central laboratory.
• The major efficacy outcome measures were overall response rate (ORR) and duration of response (DoR). The study found an ORR of 36%, and median DoR of 9.1 months. 
• The most common adverse reactions (incidence ≥20%) in all patients were hyperphosphatemia, alopecia, diarrhea, nail toxicity, fatigue, dysgeusia, nausea, constipation, stomatitis, dry eye, dry mouth, decreased appetite, vomiting, arthralgia, abdominal pain, hypophosphatemia, back pain, and dry skin.

Meet Fred, Battling CCA

Meet Fred – a man living with CCA. After noticing an unusual amount of blood following what he thought was a normal kidney stone, Fred contacted his doctor right away. Unfortunately, it was not clear from his initial symptoms what the problem was. A computed tomography (CT or CAT) scan revealed Fred did indeed have a kidney stone, but it also showed a large mass had formed on his liver, leading to more testing. After several tests, Fred was diagnosed with CCA. Because of the nonspecific symptoms he had been experiencing, his cancer unfortunately had time to grow. Upon advice from his doctor, Fred met with a CCA specialist who quickly ordered biomarker testing, revealing that he had FGFR2-driven CCA. With a molecular understanding of Fred’s specific CCA, his health care team was able to prescribe him Pemazyre. 

“I’m grateful I was able to start receiving treatment for my condition following chemotherapy and continue to see improvements in my condition,” noted Fred. “Though I fight side effects such as great fatigue, dry eye, dry skin, and fingernail discoloration, these innovations in science that lead to treatments like Pemazyre are what continue to give my family and I hope.”

Through his own experience, Fred has become an advocate for encouraging others living with CCA to educate themselves about the disease and the importance of early biomarker testing. “My advice is to be your own health advocate. Take charge of how your diagnosis and treatment plan is formed with your doctor, and don’t be afraid to speak openly with your doctor about the tools, like biomarker testing, that are available,” said Fred. “I feel fortunate that my health care team initiated biomarker testing quickly after my diagnosis, which enabled me to find an appropriate treatment option for my specific condition. I know that’s not always the case for my fellow CCA warriors, so I urge those in the community to take charge of their health conversations.” 

Leverage The Leading Tools at Hand 

Fred’s story, like that of so many other CCA patients, was a long and winding road to an accurate diagnosis; however, once he was diagnosed, biomarker testing allowed for Fred’s health care team to fully understand his condition, which led to a tailored treatment plan with Pemazyre. While the regular use of biomarker testing is on the rise, it’s critical that health care providers continue to institute early biomarker testing as standard practice, as it may provide the opportunity to quickly and accurately determine the best path forward for their patients. 

For more information about treatment with Pemazyre, visit Pemzayre.com and Full Prescribing Information.  

###

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

PEMAZYRE^® is indicated for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test.

This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

IMPORTANT SAFETY INFORMATION

Ocular Toxicity
Retinal Pigment Epithelial Detachment (RPED): PEMAZYRE can cause RPED, which may cause symptoms such as blurred vision, visual floaters, or photopsia. Clinical trials of PEMAZYRE did not conduct routine monitoring including optical coherence tomography (OCT) to detect asymptomatic RPED; therefore, the incidence of asymptomatic RPED with PEMAZYRE is unknown.

Among 635 patients who received a starting dose of PEMAZYRE 13.5 mg across clinical trials, RPED occurred in 11% of patients, including Grade 3-4 RPED in 1.3%. The median time to first onset of RPED was 56 days. RPED led to dose interruption of PEMAZYRE in 3.1% of patients, and dose reduction and permanent discontinuation in 1.3% and in 0.2% of patients, respectively. RPED resolved or improved to Grade 1 levels in 76% of patients who required dosage modification of PEMAZYRE for RPED.

Perform a comprehensive ophthalmological examination including OCT prior to initiation of PEMAZYRE and every 2 months for the first 6 months and every 3 months thereafter during treatment. For onset of visual symptoms, refer patients for ophthalmologic evaluation urgently, with follow-up every 3 weeks until resolution or discontinuation of PEMAZYRE. Modify the dose or permanently discontinue PEMAZYRE as recommended in the prescribing information for PEMAZYRE. 

Dry Eye:  Among 635 patients who received a starting dose of PEMAZYRE 13.5 mg across clinical trials, dry eye occurred in 31% of patients, including Grade 3-4 in 1.6% of patients. Treat patients with ocular demulcents as needed.

Hyperphosphatemia and Soft Tissue Mineralization
PEMAZYRE can cause hyperphosphatemia leading to soft tissue mineralization, cutaneous calcification, calcinosis, and non-uremic calciphylaxis. Increases in phosphate levels are a pharmacodynamic effect of PEMAZYRE. Among 635 patients who received a starting dose of PEMAZYRE 13.5 mg across clinical trials, hyperphosphatemia was reported in 93% of patients based on laboratory values above the upper limit of normal. The median time to onset of hyperphosphatemia was 8 days (range 1-169). Phosphate lowering therapy was required in 33% of patients receiving PEMAZYRE.

Monitor for hyperphosphatemia and initiate a low phosphate diet when serum phosphate level is >5.5 mg/dL. For serum phosphate levels >7 mg/dL, initiate phosphate lowering therapy and withhold, reduce the dose, or permanently discontinue PEMAZYRE based on duration and severity of hyperphosphatemia as recommended in the prescribing information.

Embryo-Fetal Toxicity
Based on findings in an animal study and its mechanism of action, PEMAZYRE can cause fetal harm when administered to a pregnant woman. Oral administration of pemigatinib to pregnant rats during the period of organogenesis caused fetal malformations, fetal growth retardation, and embryo-fetal death at maternal exposures lower than the human exposure based on area under the curve (AUC) at the clinical dose of 13.5 mg.

Advise pregnant women of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during treatment with PEMAZYRE and for 1 week after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with PEMAZYRE and for 1 week after the last dose.

Adverse Reactions:  Cholangiocarcinoma
Serious adverse reactions occurred in 45% of patients receiving PEMAZYRE (n=146). Serious adverse reactions in ≥2% of patients who received PEMAZYRE included abdominal pain, pyrexia, cholangitis, pleural effusion, acute kidney injury, cholangitis infective, failure to thrive, hypercalcemia, hyponatremia, small intestinal obstruction, and urinary tract infection. Fatal adverse reactions occurred in 4.1% of patients, including failure to thrive, bile duct obstruction, cholangitis, sepsis, and pleural effusion.

Permanent discontinuation due to an adverse reaction occurred in 9% of patients who received PEMAZYRE. Adverse reactions requiring permanent discontinuation in ≥1% of patients included intestinal obstruction and acute kidney injury.

Dosage interruptions due to an adverse reaction occurred in 43% of patients who received PEMAZYRE.  Adverse reactions requiring dosage interruption in ≥1% of patients included stomatitis, palmar-plantar erythrodysesthesia syndrome, arthralgia, fatigue, abdominal pain, AST increased, asthenia, pyrexia, ALT increased, cholangitis, small intestinal obstruction, alkaline phosphatase increased, diarrhea, hyperbilirubinemia, electrocardiogram QT prolonged, decreased appetite, dehydration, hypercalcemia, hyperphosphatemia, hypophosphatemia, back pain, pain in extremity, syncope, acute kidney injury, onychomadesis, and hypotension.

Dose reductions due to an adverse reaction occurred in 14% of patients who received PEMAZYRE.  Adverse reactions requiring dosage reductions in ≥1% of patients who received PEMAZYRE included stomatitis, arthralgia, palmar-plantar erythrodysesthesia syndrome, asthenia, and onychomadesis.

Clinically relevant adverse reactions occurring in ≤10% of patients included fractures (2.1%). In all patients treated with pemigatinib, 0.5% experienced pathologic fractures (which included patients with and without cholangiocarcinoma [N = 635]). Soft tissue mineralization, including cutaneous calcification, calcinosis, and non-uremic calciphylaxis associated with hyperphosphatemia were observed with PEMAZYRE treatment.

Within the first 21-day cycle of PEMAZYRE dosing, serum creatinine increased (mean increase of 0.2 mg/dL) and reached steady state by Day 8, and then decreased during the 7 days off therapy. Consider alternative markers of renal function if persistent elevations in serum creatinine are observed.

In cholangiocarcinoma (n=146) the most common adverse reactions (incidence ≥20%) were hyperphosphatemia (60%), alopecia (49%), diarrhea (47%), nail toxicity (43%), fatigue (42%), dysgeusia (40%), nausea (40%), constipation (35%), stomatitis (35%), dry eye (35%), dry mouth (34%), decreased appetite (33%), vomiting (27%), arthralgia (25%), abdominal pain (23%), hypophosphatemia (23%), back pain (20%), and dry skin (20%).

Drug Interactions
Avoid concomitant use of strong and moderate CYP3A inhibitors with PEMAZYRE. Reduce the dose of PEMAZYRE if concomitant use with a strong or moderate CYP3A inhibitor cannot be avoided. Avoid concomitant use of strong and moderate CYP3A inducers with PEMAZYRE.  
Special Populations
Advise lactating women not to breastfeed during treatment with PEMAZYRE and for 1 week after the last dose.

Reduce the recommended dose of PEMAZYRE for patients with severe renal impairment as described in the prescribing information.

Reduce the recommended dose of PEMAZYRE for patients with severe hepatic impairment as described in the prescribing information. 

Please see Full Prescribing Information for PEMAZYRE.

Incyte and the Incyte logo are registered trademarks of Incyte.
PEMAZYRE  and the PEMAZYRE logo are registered trademarks of Incyte.
All other trademarks are the property of their respective owners.
© 2022, Incyte. MAT-PEM-00414  10/22

^{References:
1.    Pemazyre. Prescribing Information. Incyte Corporation. Accessed August 22, 2022.https://www.pemazyre.com/pdf/prescribing-information.pdf.
2.    Signs and Symptoms of Bile Duct Cancer. American Cancer Society. Updated January 27, 2021. Accessed June 16, 2022. https://www.cancer.org/cancer/bile-duct-cancer/detection-diagnosis-staging/survival-by-stage.html.
3.    Banales JM, Cardinale V, Carpino G, et al. Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the study of cholangiocarcinoma. Nat Rev Gastroenterol Hepatol. 2016;13(5):261-280.
4.    Ross JS, Wang K, Gay L, et al. New routes to targeted therapy of intrahepatic cholangiocarcinomas revealed by next-generation sequencing. Oncol. 2014;19(3):235-242. 
5.    Cho M, Gholami S, Gui D, et al. Optimizing the diagnosis and biomarker testing for patients with intrahepatic cholangiocarcinoma: a multidisciplinary approach. National Library of Medicine. 2022;13(1).} 
 

The U.S. Food and Drug Administration today expanded the indication for Pfizer’s oral Janus kinase (JAK) inhibitor for atopic dermatitis (AD), abrocitinib (Cibinqo), to include adolescents aged 12 through 17 years.

Abrocitinib, taken once daily, previously was approved only for treating adults aged 18 and older.

It joins upadacitinib (Rinvoq), previously the only oral JAK inhibitor to be approved for use by adolescents aged 12 through 17 with refractory moderate to severe AD.

The indication has been expanded for teens whose disease is not adequately controlled with other systemic drugs, including biologics, or those for whom use of those drugs is not advised.

Prescribing information was updated to reflect data from JADE TEEN, a phase 3, randomized, placebo-controlled trial that supported the indication for adolescents. That trial evaluated both the 100-mg and 200-mg doses of abrocitinib in comparison with placebo in 285 adolescents aged 12-18 who had moderate to severe AD and who were also receiving background therapy with topical medications.

The most common toxicities that were reported in at least 1% of patients treated with abrocitinib for up to 16 weeks included nasopharyngitis, nausea, and headache.

Efficacy measures included improvements in itch, skin clearance, and disease severity using the Investigator Global Assessment (IGA), the Peak Pruritus Numerical Rating Scale (PP-NRS), and the Eczema Area and Severity Index (EASI), according to the Pfizer statement announcing the expanded approval.

Select JADE TEEN findings include the following:

• IGA response rate of 0 or 1 at week 12: 39% with abrocitinib 100 mg; 46% with abrocitinib 200 mg; and 24% with placebo.
• EASI-75 response rate at week 12: 64%, 71%, and 41%, respectively.
• Proportion of participants achieving PP-NRS with at least a 4-point decrease from baseline at week 2: 13%, 25%, and 8%, respectively.

Data included in the prescribing information now encompass five randomized, placebo-controlled clinical trials and a long-term extension study with more than 1,600 patients treated with abrocitinib, according to the statement from Pfizer.

In a 2021 story, when JADE TEEN trial results were presented, Lawrence Eichenfield, MD, professor of dermatology and pediatrics, University of California, San Diego, and Rady Children’s Hospital, San Diego, told this news organization that he welcomed oral JAKs as a weapon against atopic dermatitis.

He noted that moderate to severe AD can have a tremendous impact on adolescents. “Traditionally, we have treated it with intermittent topical corticosteroids, but this has left a significant percentage of patients without long-term disease control,” he said.

Abrocitinib is not recommended for use with other JAK inhibitors, biologic immunomodulators, or other immunosuppressants.

AD, one of the most common inflammatory skin diseases, affects approximately 5%-10% of adults in the United States and approximately 11% of children. About one in three adults and one in three children and adolescents aged 17 and younger with AD have moderate to severe disease.

JAK inhibition is thought to modulate multiple cytokines involved in AD, including interleukin (IL)–4, IL-13, IL-31, IL-22, and thymic stromal lymphopoietin.

Prescribing information includes a warning that use of abrocitinib should be avoided by patients with an active, serious infection, including localized infections. A boxed warning is included in the labels of JAK inhibitors regarding the risk of serious infections, mortality, major cardiovascular events, and thrombosis.

Treatment risks and benefits should be carefully considered for patients with chronic or recurrent infections or those who have lived in or traveled in areas of endemic tuberculosis or endemic mycoses, the information states.

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

The U.S. Food and Drug Administration today expanded the indication for Pfizer’s oral Janus kinase (JAK) inhibitor for atopic dermatitis (AD), abrocitinib (Cibinqo), to include adolescents aged 12 through 17 years.

Abrocitinib, taken once daily, previously was approved only for treating adults aged 18 and older.

It joins upadacitinib (Rinvoq), previously the only oral JAK inhibitor to be approved for use by adolescents aged 12 through 17 with refractory moderate to severe AD.

The indication has been expanded for teens whose disease is not adequately controlled with other systemic drugs, including biologics, or those for whom use of those drugs is not advised.

Prescribing information was updated to reflect data from JADE TEEN, a phase 3, randomized, placebo-controlled trial that supported the indication for adolescents. That trial evaluated both the 100-mg and 200-mg doses of abrocitinib in comparison with placebo in 285 adolescents aged 12-18 who had moderate to severe AD and who were also receiving background therapy with topical medications.

The most common toxicities that were reported in at least 1% of patients treated with abrocitinib for up to 16 weeks included nasopharyngitis, nausea, and headache.

Efficacy measures included improvements in itch, skin clearance, and disease severity using the Investigator Global Assessment (IGA), the Peak Pruritus Numerical Rating Scale (PP-NRS), and the Eczema Area and Severity Index (EASI), according to the Pfizer statement announcing the expanded approval.

Select JADE TEEN findings include the following:

• IGA response rate of 0 or 1 at week 12: 39% with abrocitinib 100 mg; 46% with abrocitinib 200 mg; and 24% with placebo.
• EASI-75 response rate at week 12: 64%, 71%, and 41%, respectively.
• Proportion of participants achieving PP-NRS with at least a 4-point decrease from baseline at week 2: 13%, 25%, and 8%, respectively.

Data included in the prescribing information now encompass five randomized, placebo-controlled clinical trials and a long-term extension study with more than 1,600 patients treated with abrocitinib, according to the statement from Pfizer.

In a 2021 story, when JADE TEEN trial results were presented, Lawrence Eichenfield, MD, professor of dermatology and pediatrics, University of California, San Diego, and Rady Children’s Hospital, San Diego, told this news organization that he welcomed oral JAKs as a weapon against atopic dermatitis.

He noted that moderate to severe AD can have a tremendous impact on adolescents. “Traditionally, we have treated it with intermittent topical corticosteroids, but this has left a significant percentage of patients without long-term disease control,” he said.

Abrocitinib is not recommended for use with other JAK inhibitors, biologic immunomodulators, or other immunosuppressants.

AD, one of the most common inflammatory skin diseases, affects approximately 5%-10% of adults in the United States and approximately 11% of children. About one in three adults and one in three children and adolescents aged 17 and younger with AD have moderate to severe disease.

JAK inhibition is thought to modulate multiple cytokines involved in AD, including interleukin (IL)–4, IL-13, IL-31, IL-22, and thymic stromal lymphopoietin.

Prescribing information includes a warning that use of abrocitinib should be avoided by patients with an active, serious infection, including localized infections. A boxed warning is included in the labels of JAK inhibitors regarding the risk of serious infections, mortality, major cardiovascular events, and thrombosis.

Treatment risks and benefits should be carefully considered for patients with chronic or recurrent infections or those who have lived in or traveled in areas of endemic tuberculosis or endemic mycoses, the information states.

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

The U.S. Food and Drug Administration today expanded the indication for Pfizer’s oral Janus kinase (JAK) inhibitor for atopic dermatitis (AD), abrocitinib (Cibinqo), to include adolescents aged 12 through 17 years.

Abrocitinib, taken once daily, previously was approved only for treating adults aged 18 and older.

It joins upadacitinib (Rinvoq), previously the only oral JAK inhibitor to be approved for use by adolescents aged 12 through 17 with refractory moderate to severe AD.

The indication has been expanded for teens whose disease is not adequately controlled with other systemic drugs, including biologics, or those for whom use of those drugs is not advised.

Prescribing information was updated to reflect data from JADE TEEN, a phase 3, randomized, placebo-controlled trial that supported the indication for adolescents. That trial evaluated both the 100-mg and 200-mg doses of abrocitinib in comparison with placebo in 285 adolescents aged 12-18 who had moderate to severe AD and who were also receiving background therapy with topical medications.

The most common toxicities that were reported in at least 1% of patients treated with abrocitinib for up to 16 weeks included nasopharyngitis, nausea, and headache.

Efficacy measures included improvements in itch, skin clearance, and disease severity using the Investigator Global Assessment (IGA), the Peak Pruritus Numerical Rating Scale (PP-NRS), and the Eczema Area and Severity Index (EASI), according to the Pfizer statement announcing the expanded approval.

Select JADE TEEN findings include the following:

• IGA response rate of 0 or 1 at week 12: 39% with abrocitinib 100 mg; 46% with abrocitinib 200 mg; and 24% with placebo.
• EASI-75 response rate at week 12: 64%, 71%, and 41%, respectively.
• Proportion of participants achieving PP-NRS with at least a 4-point decrease from baseline at week 2: 13%, 25%, and 8%, respectively.

Data included in the prescribing information now encompass five randomized, placebo-controlled clinical trials and a long-term extension study with more than 1,600 patients treated with abrocitinib, according to the statement from Pfizer.

In a 2021 story, when JADE TEEN trial results were presented, Lawrence Eichenfield, MD, professor of dermatology and pediatrics, University of California, San Diego, and Rady Children’s Hospital, San Diego, told this news organization that he welcomed oral JAKs as a weapon against atopic dermatitis.

He noted that moderate to severe AD can have a tremendous impact on adolescents. “Traditionally, we have treated it with intermittent topical corticosteroids, but this has left a significant percentage of patients without long-term disease control,” he said.

Abrocitinib is not recommended for use with other JAK inhibitors, biologic immunomodulators, or other immunosuppressants.

AD, one of the most common inflammatory skin diseases, affects approximately 5%-10% of adults in the United States and approximately 11% of children. About one in three adults and one in three children and adolescents aged 17 and younger with AD have moderate to severe disease.

JAK inhibition is thought to modulate multiple cytokines involved in AD, including interleukin (IL)–4, IL-13, IL-31, IL-22, and thymic stromal lymphopoietin.

Prescribing information includes a warning that use of abrocitinib should be avoided by patients with an active, serious infection, including localized infections. A boxed warning is included in the labels of JAK inhibitors regarding the risk of serious infections, mortality, major cardiovascular events, and thrombosis.

Treatment risks and benefits should be carefully considered for patients with chronic or recurrent infections or those who have lived in or traveled in areas of endemic tuberculosis or endemic mycoses, the information states.

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

Adherence to the Seattle biopsy protocol and recommended endoscopic surveillance intervals – two established quality indicators (QIs) in Barrett esophagus (BE) – varies widely by individual endoscopist and center, an analysis of U.S. registry data shows.

“As the GI Quality Improvement Consortium (GIQuIC) registry represents the ‘best-case scenario’ for adherence, since sites and endoscopists enrolled in this quality registry are aware that their practices are being monitored, these results indicate that there is still room for improvement and better consistency,” the researchers write.

The study was published online in The American Journal of Gastroenterology.

Quality care in BE, which is a precursor to esophageal adenocarcinoma (EAC), includes adherence to the Seattle biopsy protocol for sampling the BE segment (four-quadrant biopsies every 2 cm) and to a surveillance interval of 3-5 years for patients with nondysplastic BE (NDBE).

Previous studies have found poor adherence to these two QIs, but those studies only provided overall estimates, and individual endoscopists or different sites were not taken into consideration.

Jennifer Kolb, MD, with the University of California, Los Angeles, and colleagues say their study is the first to highlight variation in adherence to these measures at the center and endoscopist levels.

The study is also the first U.S. population–based study to report the dysplasia detection rate (DDR), which is a proposed quality indicator. The findings on this metric also demonstrate marked variability across endoscopists and sites.
 

Study details

Using the nationwide GIQuIC registry, the researchers evaluated endoscopist and site-based adherence to the Seattle protocol and surveillance interval advice from January 2018 to May 2021.

Among 255 practices with 1,195 endoscopists who performed 20,155 upper endoscopies for suspected or established BE, overall adherence to the Seattle protocol was 86%, which is considerably higher than the 51% reported in a study conducted from 2002 to 2007, Dr. Kolb and colleagues note.

When researchers looked specifically at 572 endoscopists for whom there were at least 10 endoscopy records in the registry, they found high variability in adherence to the Seattle protocol (median, 93.8%; interquartile range, 18.9%).

Adherence to the Seattle protocol was also variable among 153 practices for which there were at least 20 endoscopy records (median, 90%; IQR, 20.1%).

Of the 12,100 upper endoscopies with documented NDBE, 8,517 (70.4%) had a guideline-concordant–recommended surveillance interval of 3-5 years, with variability at both the endoscopist (median, 82.4%; IQR, 36.3%) and site level (median, 77.2%; IQR, 28.9%).

Endoscopist and site adherence to the Seattle protocol and surveillance guidance generally rose along with volume of upper endoscopies performed.

The overall DDR was 3.1%; it varied among endoscopists and sites (mean, 3.3% for both).

The investigators note that the 95% confidence intervals for each provider for DDR were “highly variable” and ranged from –20% to 119.3%. Notably, increasing upper endoscopy volume had an inconsistent effect on adherence rates and DDR by endoscopists and sites.

The investigators saw no correlation between overall DDR and Seattle protocol adherence among sites and only weak but statistically significant negative correlation between DDR and Seattle protocol adherence among individual endoscopists.
 

Practical approaches to improvement

The researchers say their observations from the GIQuIC database “most accurately represent the real-world experience in Barrett’s endoscopy.”

The results can serve as a “benchmark for quality initiatives and intervention trials aimed at improving outcomes for patients with BE,” they say.

Improving adherence to key QI measures and ensuring more consistent clinical behavior across practice groups and endoscopists are “critical first steps” to ensure high-quality BE care, Dr. Kolb and colleagues say.

To that end, they encourage professional societies to emphasize these metrics to their members and to streamline the reporting systems for QIs within the electronic health records used across various practice settings.

Avenues to improve examination quality may include educational interventions, such as online learning platforms that teach dysplasia detection or that highlight best practices, they add. These educational tools should be easy to use and should emphasize quality improvement measures.

“Future efforts are warranted to identify and extinguish predictors of this variability and to determine whether these interventions can improve DDR and adherence rates to QIs among endoscopists doing these examinations with the goal to improve EAC outcomes,” they conclude.

The study had no financial support. The authors have disclosed no relevant financial relationships.

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

Adherence to the Seattle biopsy protocol and recommended endoscopic surveillance intervals – two established quality indicators (QIs) in Barrett esophagus (BE) – varies widely by individual endoscopist and center, an analysis of U.S. registry data shows.

“As the GI Quality Improvement Consortium (GIQuIC) registry represents the ‘best-case scenario’ for adherence, since sites and endoscopists enrolled in this quality registry are aware that their practices are being monitored, these results indicate that there is still room for improvement and better consistency,” the researchers write.

The study was published online in The American Journal of Gastroenterology.

Quality care in BE, which is a precursor to esophageal adenocarcinoma (EAC), includes adherence to the Seattle biopsy protocol for sampling the BE segment (four-quadrant biopsies every 2 cm) and to a surveillance interval of 3-5 years for patients with nondysplastic BE (NDBE).

Previous studies have found poor adherence to these two QIs, but those studies only provided overall estimates, and individual endoscopists or different sites were not taken into consideration.

Jennifer Kolb, MD, with the University of California, Los Angeles, and colleagues say their study is the first to highlight variation in adherence to these measures at the center and endoscopist levels.

The study is also the first U.S. population–based study to report the dysplasia detection rate (DDR), which is a proposed quality indicator. The findings on this metric also demonstrate marked variability across endoscopists and sites.
 

Study details

Using the nationwide GIQuIC registry, the researchers evaluated endoscopist and site-based adherence to the Seattle protocol and surveillance interval advice from January 2018 to May 2021.

Among 255 practices with 1,195 endoscopists who performed 20,155 upper endoscopies for suspected or established BE, overall adherence to the Seattle protocol was 86%, which is considerably higher than the 51% reported in a study conducted from 2002 to 2007, Dr. Kolb and colleagues note.

When researchers looked specifically at 572 endoscopists for whom there were at least 10 endoscopy records in the registry, they found high variability in adherence to the Seattle protocol (median, 93.8%; interquartile range, 18.9%).

Adherence to the Seattle protocol was also variable among 153 practices for which there were at least 20 endoscopy records (median, 90%; IQR, 20.1%).

Of the 12,100 upper endoscopies with documented NDBE, 8,517 (70.4%) had a guideline-concordant–recommended surveillance interval of 3-5 years, with variability at both the endoscopist (median, 82.4%; IQR, 36.3%) and site level (median, 77.2%; IQR, 28.9%).

Endoscopist and site adherence to the Seattle protocol and surveillance guidance generally rose along with volume of upper endoscopies performed.

The overall DDR was 3.1%; it varied among endoscopists and sites (mean, 3.3% for both).

The investigators note that the 95% confidence intervals for each provider for DDR were “highly variable” and ranged from –20% to 119.3%. Notably, increasing upper endoscopy volume had an inconsistent effect on adherence rates and DDR by endoscopists and sites.

The investigators saw no correlation between overall DDR and Seattle protocol adherence among sites and only weak but statistically significant negative correlation between DDR and Seattle protocol adherence among individual endoscopists.
 

Practical approaches to improvement

The researchers say their observations from the GIQuIC database “most accurately represent the real-world experience in Barrett’s endoscopy.”

The results can serve as a “benchmark for quality initiatives and intervention trials aimed at improving outcomes for patients with BE,” they say.

Improving adherence to key QI measures and ensuring more consistent clinical behavior across practice groups and endoscopists are “critical first steps” to ensure high-quality BE care, Dr. Kolb and colleagues say.

To that end, they encourage professional societies to emphasize these metrics to their members and to streamline the reporting systems for QIs within the electronic health records used across various practice settings.

Avenues to improve examination quality may include educational interventions, such as online learning platforms that teach dysplasia detection or that highlight best practices, they add. These educational tools should be easy to use and should emphasize quality improvement measures.

“Future efforts are warranted to identify and extinguish predictors of this variability and to determine whether these interventions can improve DDR and adherence rates to QIs among endoscopists doing these examinations with the goal to improve EAC outcomes,” they conclude.

The study had no financial support. The authors have disclosed no relevant financial relationships.

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

Adherence to the Seattle biopsy protocol and recommended endoscopic surveillance intervals – two established quality indicators (QIs) in Barrett esophagus (BE) – varies widely by individual endoscopist and center, an analysis of U.S. registry data shows.

“As the GI Quality Improvement Consortium (GIQuIC) registry represents the ‘best-case scenario’ for adherence, since sites and endoscopists enrolled in this quality registry are aware that their practices are being monitored, these results indicate that there is still room for improvement and better consistency,” the researchers write.

The study was published online in The American Journal of Gastroenterology.

Quality care in BE, which is a precursor to esophageal adenocarcinoma (EAC), includes adherence to the Seattle biopsy protocol for sampling the BE segment (four-quadrant biopsies every 2 cm) and to a surveillance interval of 3-5 years for patients with nondysplastic BE (NDBE).

Previous studies have found poor adherence to these two QIs, but those studies only provided overall estimates, and individual endoscopists or different sites were not taken into consideration.

Jennifer Kolb, MD, with the University of California, Los Angeles, and colleagues say their study is the first to highlight variation in adherence to these measures at the center and endoscopist levels.

The study is also the first U.S. population–based study to report the dysplasia detection rate (DDR), which is a proposed quality indicator. The findings on this metric also demonstrate marked variability across endoscopists and sites.
 

Study details

Using the nationwide GIQuIC registry, the researchers evaluated endoscopist and site-based adherence to the Seattle protocol and surveillance interval advice from January 2018 to May 2021.

Among 255 practices with 1,195 endoscopists who performed 20,155 upper endoscopies for suspected or established BE, overall adherence to the Seattle protocol was 86%, which is considerably higher than the 51% reported in a study conducted from 2002 to 2007, Dr. Kolb and colleagues note.

When researchers looked specifically at 572 endoscopists for whom there were at least 10 endoscopy records in the registry, they found high variability in adherence to the Seattle protocol (median, 93.8%; interquartile range, 18.9%).

Adherence to the Seattle protocol was also variable among 153 practices for which there were at least 20 endoscopy records (median, 90%; IQR, 20.1%).

Of the 12,100 upper endoscopies with documented NDBE, 8,517 (70.4%) had a guideline-concordant–recommended surveillance interval of 3-5 years, with variability at both the endoscopist (median, 82.4%; IQR, 36.3%) and site level (median, 77.2%; IQR, 28.9%).

Endoscopist and site adherence to the Seattle protocol and surveillance guidance generally rose along with volume of upper endoscopies performed.

The overall DDR was 3.1%; it varied among endoscopists and sites (mean, 3.3% for both).

The investigators note that the 95% confidence intervals for each provider for DDR were “highly variable” and ranged from –20% to 119.3%. Notably, increasing upper endoscopy volume had an inconsistent effect on adherence rates and DDR by endoscopists and sites.

The investigators saw no correlation between overall DDR and Seattle protocol adherence among sites and only weak but statistically significant negative correlation between DDR and Seattle protocol adherence among individual endoscopists.
 

Practical approaches to improvement

The researchers say their observations from the GIQuIC database “most accurately represent the real-world experience in Barrett’s endoscopy.”

The results can serve as a “benchmark for quality initiatives and intervention trials aimed at improving outcomes for patients with BE,” they say.

Improving adherence to key QI measures and ensuring more consistent clinical behavior across practice groups and endoscopists are “critical first steps” to ensure high-quality BE care, Dr. Kolb and colleagues say.

To that end, they encourage professional societies to emphasize these metrics to their members and to streamline the reporting systems for QIs within the electronic health records used across various practice settings.

Avenues to improve examination quality may include educational interventions, such as online learning platforms that teach dysplasia detection or that highlight best practices, they add. These educational tools should be easy to use and should emphasize quality improvement measures.

“Future efforts are warranted to identify and extinguish predictors of this variability and to determine whether these interventions can improve DDR and adherence rates to QIs among endoscopists doing these examinations with the goal to improve EAC outcomes,” they conclude.

The study had no financial support. The authors have disclosed no relevant financial relationships.

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

Brain volume disparities among young children of different races may be attributable to adverse childhood experiences related to socioeconomic conditions and structural racism, new research suggests.

Investigators from the Belmont, Mass.–based McLean Hospital, an affiliate of Mass General Brigham, found that 9- and 10-year-old children of different racial and socioeconomic backgrounds have subtle neurobiological differences in gray matter volume in certain brain regions associated with trauma and stress.

Lead investigator Nathaniel Harnett, PhD, of the department of psychiatry at Harvard Medical School, Boston, believes this research shows evidence that “structural racism” – broad socioeconomic disadvantages that lead to poverty and emotional trauma – may affect brain structures and growth and ultimately may lead to psychiatric illness.

“For clinicians, I think the take-home message is that we really need to be more aware about the ways in which the disproportionate burden of stress might impact some groups,” Dr. Harnett told this news organization.

“This in turn can affect the way they respond either to later stress or maybe even treatment outcomes.” He added that other brain regions and compensatory mechanisms are likely to be involved, and more work needs to explore these connections.

The study was published online in the American Journal of Psychiatry.
 

‘Toxic stressor’

Dr. Harnett and colleagues used MRI and survey data from the 2019 Adolescent Brain Cognitive Development (ABCD) study involving over 12,000 children from 21 sites across the United States.

Participating children provided information about emotional and physical conflicts in the household. The ABCD study also surveyed the parents about their race and ethnicity, parental education, employment, and family income. Another factor in the analysis was neighborhood disadvantage, based on the Area Deprivation Index utilizing 17 socioeconomic indicators from the U.S. Census, including poverty and housing.

Comparing brain MRI findings from approximately 7,300 White children and 1,800 Black children in the ABCD study, Dr. Harnett’s group found that Black children had lower gray matter volume in the amygdala, hippocampus, and other subregions of the prefrontal cortex.

Experience of adversity was the “sole factor” explaining brain volume differences, with household income being the predominant factor.

Compared with White children, Black children were three times less likely to have parents who were currently employed. In addition, White parents were more likely than Black parents to have higher education at 75.2% versus 40.6%. Black families had significantly lower household income than White families and experienced more family conflict, material hardship, neighborhood disadvantage, and traumatic events.

The researchers analyzed race-related differences in posttraumatic stress disorder symptoms and the relationship with adversity and found that Black children had significantly greater PTSD symptom severity, and that symptom severity was “further predicted by adversity.”

“Taken together, early-life adversity may act as a toxic stressor that disproportionately impacts Black children as a result of their significantly greater exposure to adversity and contributes to differential neural development of key threat-processing regions,” the investigators write.

“These parts of the brain are involved in what we typically call threat learning,” Dr. Harnett explained. “Threat learning is basically learning to recognize potential dangers in our environment and selecting behaviors to keep us safe, whether we’re going to run away from a danger or face it head on. When you have chronic exposure to things that can be dangerous or can make you feel unsafe, that might have an impact on how these brain regions develop, with potential implications for how these regions function later on in life.”
 

A consequence of toxic stress

This study is part of a growing body of work on the influence of “toxic stress” and other forms of PTSD on brain architecture. The authors note that prolonged exposure to adverse experiences leads to excessive activation of stress-response systems and accumulation of stress hormones. This disrupts immune and metabolic regulatory systems that influence the developing structures of the brain.

The study helps to contradict the “pseudoscientific falsehood” of biologic race-related differences in brain volume, instead emphasizing the role of adversity brought on by structural racism, the authors add.

In an accompanying editor’s note, the publication’s Editor-in-Chief Ned H. Kalin, MD, called childhood adversity, maltreatment, and stress, “significant risk factors for the development of psychopathology.”

These findings are “critically important, as they speak to the need for psychiatry as a field to be outspoken about the detrimental psychological impacts of race-related disparities in childhood adversity, to call out the fact that these disparities stem from structural racism, and to vigorously support rectifying efforts by pursuing policy changes,” he stated in a news release.
 

Social construct?

Joan Luby, MD, coauthor of an accompanying editorial, said she and her coauthor “really appreciate the study and think the findings are overall very consistent with the emerging literature, increasing the confidence [in the findings].”

Dr. Luby, a professor of child psychiatry and director of the Early Emotional Development Program, Washington University, St. Louis, noted that she “takes issue” with the fact that the study “makes inferences regarding race, when we think those inferences aren’t well justified, are misinterpretations, and could be misleading.”

Race is a “social construct” and there are many sources of adversity that the authors didn’t measure in the study and are likely the source of any remaining variance they found, including experiences of structural racism and discrimination,” said Dr. Luby, who was not involved in the study.

“How people look doesn’t have any bearing on their inherent biological characteristics, and more [needs to be studied] on how they experience the psychosocial environment and how the psychosocial environment rejects or reacts to them.”

These psychosocial issues “have to be taken into account and measured in a very comprehensive way,” she added.

The ABCD study was supported by the National Institutes of Health and additional federal partners. Dr. Harnett reports no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. Luby receives royalties from Guilford Press. Her coauthor reports no relevant financial relationships.

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

Brain volume disparities among young children of different races may be attributable to adverse childhood experiences related to socioeconomic conditions and structural racism, new research suggests.

Investigators from the Belmont, Mass.–based McLean Hospital, an affiliate of Mass General Brigham, found that 9- and 10-year-old children of different racial and socioeconomic backgrounds have subtle neurobiological differences in gray matter volume in certain brain regions associated with trauma and stress.

Lead investigator Nathaniel Harnett, PhD, of the department of psychiatry at Harvard Medical School, Boston, believes this research shows evidence that “structural racism” – broad socioeconomic disadvantages that lead to poverty and emotional trauma – may affect brain structures and growth and ultimately may lead to psychiatric illness.

“For clinicians, I think the take-home message is that we really need to be more aware about the ways in which the disproportionate burden of stress might impact some groups,” Dr. Harnett told this news organization.

“This in turn can affect the way they respond either to later stress or maybe even treatment outcomes.” He added that other brain regions and compensatory mechanisms are likely to be involved, and more work needs to explore these connections.

The study was published online in the American Journal of Psychiatry.
 

‘Toxic stressor’

Dr. Harnett and colleagues used MRI and survey data from the 2019 Adolescent Brain Cognitive Development (ABCD) study involving over 12,000 children from 21 sites across the United States.

Participating children provided information about emotional and physical conflicts in the household. The ABCD study also surveyed the parents about their race and ethnicity, parental education, employment, and family income. Another factor in the analysis was neighborhood disadvantage, based on the Area Deprivation Index utilizing 17 socioeconomic indicators from the U.S. Census, including poverty and housing.

Comparing brain MRI findings from approximately 7,300 White children and 1,800 Black children in the ABCD study, Dr. Harnett’s group found that Black children had lower gray matter volume in the amygdala, hippocampus, and other subregions of the prefrontal cortex.

Experience of adversity was the “sole factor” explaining brain volume differences, with household income being the predominant factor.

Compared with White children, Black children were three times less likely to have parents who were currently employed. In addition, White parents were more likely than Black parents to have higher education at 75.2% versus 40.6%. Black families had significantly lower household income than White families and experienced more family conflict, material hardship, neighborhood disadvantage, and traumatic events.

The researchers analyzed race-related differences in posttraumatic stress disorder symptoms and the relationship with adversity and found that Black children had significantly greater PTSD symptom severity, and that symptom severity was “further predicted by adversity.”

“Taken together, early-life adversity may act as a toxic stressor that disproportionately impacts Black children as a result of their significantly greater exposure to adversity and contributes to differential neural development of key threat-processing regions,” the investigators write.

“These parts of the brain are involved in what we typically call threat learning,” Dr. Harnett explained. “Threat learning is basically learning to recognize potential dangers in our environment and selecting behaviors to keep us safe, whether we’re going to run away from a danger or face it head on. When you have chronic exposure to things that can be dangerous or can make you feel unsafe, that might have an impact on how these brain regions develop, with potential implications for how these regions function later on in life.”
 

A consequence of toxic stress

This study is part of a growing body of work on the influence of “toxic stress” and other forms of PTSD on brain architecture. The authors note that prolonged exposure to adverse experiences leads to excessive activation of stress-response systems and accumulation of stress hormones. This disrupts immune and metabolic regulatory systems that influence the developing structures of the brain.

The study helps to contradict the “pseudoscientific falsehood” of biologic race-related differences in brain volume, instead emphasizing the role of adversity brought on by structural racism, the authors add.

In an accompanying editor’s note, the publication’s Editor-in-Chief Ned H. Kalin, MD, called childhood adversity, maltreatment, and stress, “significant risk factors for the development of psychopathology.”

These findings are “critically important, as they speak to the need for psychiatry as a field to be outspoken about the detrimental psychological impacts of race-related disparities in childhood adversity, to call out the fact that these disparities stem from structural racism, and to vigorously support rectifying efforts by pursuing policy changes,” he stated in a news release.
 

Social construct?

Joan Luby, MD, coauthor of an accompanying editorial, said she and her coauthor “really appreciate the study and think the findings are overall very consistent with the emerging literature, increasing the confidence [in the findings].”

Dr. Luby, a professor of child psychiatry and director of the Early Emotional Development Program, Washington University, St. Louis, noted that she “takes issue” with the fact that the study “makes inferences regarding race, when we think those inferences aren’t well justified, are misinterpretations, and could be misleading.”

Race is a “social construct” and there are many sources of adversity that the authors didn’t measure in the study and are likely the source of any remaining variance they found, including experiences of structural racism and discrimination,” said Dr. Luby, who was not involved in the study.

“How people look doesn’t have any bearing on their inherent biological characteristics, and more [needs to be studied] on how they experience the psychosocial environment and how the psychosocial environment rejects or reacts to them.”

These psychosocial issues “have to be taken into account and measured in a very comprehensive way,” she added.

The ABCD study was supported by the National Institutes of Health and additional federal partners. Dr. Harnett reports no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. Luby receives royalties from Guilford Press. Her coauthor reports no relevant financial relationships.

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

Brain volume disparities among young children of different races may be attributable to adverse childhood experiences related to socioeconomic conditions and structural racism, new research suggests.

Investigators from the Belmont, Mass.–based McLean Hospital, an affiliate of Mass General Brigham, found that 9- and 10-year-old children of different racial and socioeconomic backgrounds have subtle neurobiological differences in gray matter volume in certain brain regions associated with trauma and stress.

Lead investigator Nathaniel Harnett, PhD, of the department of psychiatry at Harvard Medical School, Boston, believes this research shows evidence that “structural racism” – broad socioeconomic disadvantages that lead to poverty and emotional trauma – may affect brain structures and growth and ultimately may lead to psychiatric illness.

“For clinicians, I think the take-home message is that we really need to be more aware about the ways in which the disproportionate burden of stress might impact some groups,” Dr. Harnett told this news organization.

“This in turn can affect the way they respond either to later stress or maybe even treatment outcomes.” He added that other brain regions and compensatory mechanisms are likely to be involved, and more work needs to explore these connections.

The study was published online in the American Journal of Psychiatry.
 

‘Toxic stressor’

Dr. Harnett and colleagues used MRI and survey data from the 2019 Adolescent Brain Cognitive Development (ABCD) study involving over 12,000 children from 21 sites across the United States.

Participating children provided information about emotional and physical conflicts in the household. The ABCD study also surveyed the parents about their race and ethnicity, parental education, employment, and family income. Another factor in the analysis was neighborhood disadvantage, based on the Area Deprivation Index utilizing 17 socioeconomic indicators from the U.S. Census, including poverty and housing.

Comparing brain MRI findings from approximately 7,300 White children and 1,800 Black children in the ABCD study, Dr. Harnett’s group found that Black children had lower gray matter volume in the amygdala, hippocampus, and other subregions of the prefrontal cortex.

Experience of adversity was the “sole factor” explaining brain volume differences, with household income being the predominant factor.

Compared with White children, Black children were three times less likely to have parents who were currently employed. In addition, White parents were more likely than Black parents to have higher education at 75.2% versus 40.6%. Black families had significantly lower household income than White families and experienced more family conflict, material hardship, neighborhood disadvantage, and traumatic events.

The researchers analyzed race-related differences in posttraumatic stress disorder symptoms and the relationship with adversity and found that Black children had significantly greater PTSD symptom severity, and that symptom severity was “further predicted by adversity.”

“Taken together, early-life adversity may act as a toxic stressor that disproportionately impacts Black children as a result of their significantly greater exposure to adversity and contributes to differential neural development of key threat-processing regions,” the investigators write.

“These parts of the brain are involved in what we typically call threat learning,” Dr. Harnett explained. “Threat learning is basically learning to recognize potential dangers in our environment and selecting behaviors to keep us safe, whether we’re going to run away from a danger or face it head on. When you have chronic exposure to things that can be dangerous or can make you feel unsafe, that might have an impact on how these brain regions develop, with potential implications for how these regions function later on in life.”
 

A consequence of toxic stress

This study is part of a growing body of work on the influence of “toxic stress” and other forms of PTSD on brain architecture. The authors note that prolonged exposure to adverse experiences leads to excessive activation of stress-response systems and accumulation of stress hormones. This disrupts immune and metabolic regulatory systems that influence the developing structures of the brain.

The study helps to contradict the “pseudoscientific falsehood” of biologic race-related differences in brain volume, instead emphasizing the role of adversity brought on by structural racism, the authors add.

In an accompanying editor’s note, the publication’s Editor-in-Chief Ned H. Kalin, MD, called childhood adversity, maltreatment, and stress, “significant risk factors for the development of psychopathology.”

These findings are “critically important, as they speak to the need for psychiatry as a field to be outspoken about the detrimental psychological impacts of race-related disparities in childhood adversity, to call out the fact that these disparities stem from structural racism, and to vigorously support rectifying efforts by pursuing policy changes,” he stated in a news release.
 

Social construct?

Joan Luby, MD, coauthor of an accompanying editorial, said she and her coauthor “really appreciate the study and think the findings are overall very consistent with the emerging literature, increasing the confidence [in the findings].”

Dr. Luby, a professor of child psychiatry and director of the Early Emotional Development Program, Washington University, St. Louis, noted that she “takes issue” with the fact that the study “makes inferences regarding race, when we think those inferences aren’t well justified, are misinterpretations, and could be misleading.”

Race is a “social construct” and there are many sources of adversity that the authors didn’t measure in the study and are likely the source of any remaining variance they found, including experiences of structural racism and discrimination,” said Dr. Luby, who was not involved in the study.

“How people look doesn’t have any bearing on their inherent biological characteristics, and more [needs to be studied] on how they experience the psychosocial environment and how the psychosocial environment rejects or reacts to them.”

These psychosocial issues “have to be taken into account and measured in a very comprehensive way,” she added.

The ABCD study was supported by the National Institutes of Health and additional federal partners. Dr. Harnett reports no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. Luby receives royalties from Guilford Press. Her coauthor reports no relevant financial relationships.

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

Dementia frequently coexists with hepatic encephalopathy (HE) in patients with cirrhosis but doesn’t correlate with other decompensating events, according to a new study involving U.S. veterans.

The overlap between dementia and HE was also independent of alcohol use, brain injury, age, and other metabolic risk factors.

“The aging of patients with cirrhosis leads us to encounter several individuals who may be prone to both of these diseases,” senior author Jasmohan Bajaj, MD, a professor of gastroenterology, hepatology, and nutrition at Virginia Commonwealth University Medical Center and GI section of the Central Virginia Veterans Healthcare System in Richmond, said in an interview.

“Given the epidemic of metabolic syndrome and alcohol, consider excluding cirrhosis in your patient [for] whom the presumptive diagnosis is dementia, since they could have concomitant HE,” he said.

“On the flip side, in those with HE who have predominant long-term memory issues and persistent cognitive changes, consider consulting a neuropsychiatrist or neurologist to ensure there is a resolution of the underlying disease process,” Dr. Bajaj added.

The study was published online in The American Journal of Gastroenterology.
 

Analyzing associations

HE is a common decompensating event in patients with cirrhosis. Because of the aging population of patients with cirrhosis, however, it’s important to differentiate HE from nonhepatic etiologies of cognitive impairment, such as dementia, the authors note.

Using data from the VA Corporate Data Warehouse, Dr. Bajaj and colleagues identified veterans with cirrhosis who received VA care between October 2019 and September 2021 and compared baseline characteristics between the cohorts based on the presence or absence of dementia. The research team then evaluated factors associated with having a diagnosis of dementia, adjusting for demographics, comorbid illnesses, cirrhosis etiology, and cirrhosis complications.

Investigators identified 71,522 veterans with diagnostic codes for cirrhosis who were engaged in VA care in 2019. They were mostly men (96.2%) and had a median age of 66. The most common etiologies of cirrhosis were alcohol and hepatitis C, followed by nonalcoholic steatohepatitis (NASH). The group also included veterans with predominantly compensated cirrhosis and a median MELD-Na score of 9. The MELD-Na score gauges the severity of chronic liver disease using values such as serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time and sodium to predict survival.

Among those with cirrhosis, 5,647 (7.9%) also had dementia diagnosis codes. This rate is higher than the prevalence of dementia in the general population and equivalent to the rate of dementia in veterans without cirrhosis who are older than 65, the authors note.

In general, veterans with dementia tended to be older, to be White, to live in an urban area, and to have higher MELD-Na scores, and they were more frequently diagnosed with alcohol-related cirrhosis, alcohol and tobacco use disorder, diabetes, chronic kidney disease, chronic heart failure, brain trauma, and cerebrovascular disease.

In a multivariable analysis, the presence of any decompensating event was significantly associated with dementia. In subsequent analyses of individual decompensating events, however, the strongest association was with HE, while ascites or variceal bleeding did not add to the risk.

When HE was defined as patients who filled prescriptions for lactulose or rifaximin, the frequency of patients with HE decreased from 13.7% to 10.9%. In an analysis with HE as the decompensating event, the association between HE and dementia remained significant compared to when HE was defined by diagnostic codes alone.

“We were surprised by the high proportion of patients with dementia who also had cirrhosis, and given the genuine difficulty that clinicians have with defining HE vs. dementia, we were not very surprised at that overlap,” Dr. Bajaj said.

“We were also surprised at the specificity of this overlap only with HE and not with other decompensating events, which was also independent of head injury, alcohol use, and PTSD,” he added.
 

Additional research needed

Future research should look at the characteristics of HE, including the number of episodes or breakthrough episodes, and should focus on objective biomarkers to differentiate dementia and HE, the study authors write.

“The distinction and study of potential overlapping features among HE and dementia is important because HE is often treatable with medications and reverses after liver transplant, while this does not occur with dementia,” they add.

Dr. Bajaj and colleagues call for a greater awareness of disease processes and complications in older patients with cirrhosis, particularly since diagnostic imprecision can lead to patient and family confusion, distrust, and ineffective treatment.

The study will help physicians better understand the important overlap between dementia and HE, said Eric Orman, MD, an associate professor of medicine at Indiana University, Indianapolis.

Dr. Orman, who wasn’t involved with this study, has researched recent trends in the characteristics and outcomes of patients with newly diagnosed cirrhosis and has found that the proportion of older adults has increased, as well as those with alcoholic cirrhosis and NASH, which has implications for future patient care.

“It is important to recognize that both dementia and HE can occur either separately or concurrently in individuals with cirrhosis,” Dr. Orman told this news organization. “When seeing patients with cognitive impairment, having a high index of suspicion for both conditions is critical to ensure appropriate diagnosis and treatment.”

The study’s findings “represent the tip of the iceberg,” Neal Parikh, MD, an assistant professor of neurology and neuroscience at Weill Cornell Medicine in New York, said in an interview. “There is a tremendous amount left to be discovered regarding the role of the liver in brain health.”

Dr. Parikh, who wasn’t associated with this study, has researched the impact of chronic liver conditions on cognitive impairment and dementia. He is working on a project that addresses HE in detail.

“There is growing recognition of a so-called ‘liver-brain axis,’ with several researchers, including my group, showing that a range of chronic liver conditions may detrimentally impact cognitive function and increase the risk of dementia,” he said. “Studying the specific contributions of cirrhosis is critical for understanding the role of hepatic encephalopathy in age-related cognitive decline.”

The study received no financial support. The authors reported no potential competing interests.

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

Dementia frequently coexists with hepatic encephalopathy (HE) in patients with cirrhosis but doesn’t correlate with other decompensating events, according to a new study involving U.S. veterans.

The overlap between dementia and HE was also independent of alcohol use, brain injury, age, and other metabolic risk factors.

“The aging of patients with cirrhosis leads us to encounter several individuals who may be prone to both of these diseases,” senior author Jasmohan Bajaj, MD, a professor of gastroenterology, hepatology, and nutrition at Virginia Commonwealth University Medical Center and GI section of the Central Virginia Veterans Healthcare System in Richmond, said in an interview.

“Given the epidemic of metabolic syndrome and alcohol, consider excluding cirrhosis in your patient [for] whom the presumptive diagnosis is dementia, since they could have concomitant HE,” he said.

“On the flip side, in those with HE who have predominant long-term memory issues and persistent cognitive changes, consider consulting a neuropsychiatrist or neurologist to ensure there is a resolution of the underlying disease process,” Dr. Bajaj added.

The study was published online in The American Journal of Gastroenterology.
 

Analyzing associations

HE is a common decompensating event in patients with cirrhosis. Because of the aging population of patients with cirrhosis, however, it’s important to differentiate HE from nonhepatic etiologies of cognitive impairment, such as dementia, the authors note.

Using data from the VA Corporate Data Warehouse, Dr. Bajaj and colleagues identified veterans with cirrhosis who received VA care between October 2019 and September 2021 and compared baseline characteristics between the cohorts based on the presence or absence of dementia. The research team then evaluated factors associated with having a diagnosis of dementia, adjusting for demographics, comorbid illnesses, cirrhosis etiology, and cirrhosis complications.

Investigators identified 71,522 veterans with diagnostic codes for cirrhosis who were engaged in VA care in 2019. They were mostly men (96.2%) and had a median age of 66. The most common etiologies of cirrhosis were alcohol and hepatitis C, followed by nonalcoholic steatohepatitis (NASH). The group also included veterans with predominantly compensated cirrhosis and a median MELD-Na score of 9. The MELD-Na score gauges the severity of chronic liver disease using values such as serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time and sodium to predict survival.

Among those with cirrhosis, 5,647 (7.9%) also had dementia diagnosis codes. This rate is higher than the prevalence of dementia in the general population and equivalent to the rate of dementia in veterans without cirrhosis who are older than 65, the authors note.

In general, veterans with dementia tended to be older, to be White, to live in an urban area, and to have higher MELD-Na scores, and they were more frequently diagnosed with alcohol-related cirrhosis, alcohol and tobacco use disorder, diabetes, chronic kidney disease, chronic heart failure, brain trauma, and cerebrovascular disease.

In a multivariable analysis, the presence of any decompensating event was significantly associated with dementia. In subsequent analyses of individual decompensating events, however, the strongest association was with HE, while ascites or variceal bleeding did not add to the risk.

When HE was defined as patients who filled prescriptions for lactulose or rifaximin, the frequency of patients with HE decreased from 13.7% to 10.9%. In an analysis with HE as the decompensating event, the association between HE and dementia remained significant compared to when HE was defined by diagnostic codes alone.

“We were surprised by the high proportion of patients with dementia who also had cirrhosis, and given the genuine difficulty that clinicians have with defining HE vs. dementia, we were not very surprised at that overlap,” Dr. Bajaj said.

“We were also surprised at the specificity of this overlap only with HE and not with other decompensating events, which was also independent of head injury, alcohol use, and PTSD,” he added.
 

Additional research needed

Future research should look at the characteristics of HE, including the number of episodes or breakthrough episodes, and should focus on objective biomarkers to differentiate dementia and HE, the study authors write.

“The distinction and study of potential overlapping features among HE and dementia is important because HE is often treatable with medications and reverses after liver transplant, while this does not occur with dementia,” they add.

Dr. Bajaj and colleagues call for a greater awareness of disease processes and complications in older patients with cirrhosis, particularly since diagnostic imprecision can lead to patient and family confusion, distrust, and ineffective treatment.

The study will help physicians better understand the important overlap between dementia and HE, said Eric Orman, MD, an associate professor of medicine at Indiana University, Indianapolis.

Dr. Orman, who wasn’t involved with this study, has researched recent trends in the characteristics and outcomes of patients with newly diagnosed cirrhosis and has found that the proportion of older adults has increased, as well as those with alcoholic cirrhosis and NASH, which has implications for future patient care.

“It is important to recognize that both dementia and HE can occur either separately or concurrently in individuals with cirrhosis,” Dr. Orman told this news organization. “When seeing patients with cognitive impairment, having a high index of suspicion for both conditions is critical to ensure appropriate diagnosis and treatment.”

The study’s findings “represent the tip of the iceberg,” Neal Parikh, MD, an assistant professor of neurology and neuroscience at Weill Cornell Medicine in New York, said in an interview. “There is a tremendous amount left to be discovered regarding the role of the liver in brain health.”

Dr. Parikh, who wasn’t associated with this study, has researched the impact of chronic liver conditions on cognitive impairment and dementia. He is working on a project that addresses HE in detail.

“There is growing recognition of a so-called ‘liver-brain axis,’ with several researchers, including my group, showing that a range of chronic liver conditions may detrimentally impact cognitive function and increase the risk of dementia,” he said. “Studying the specific contributions of cirrhosis is critical for understanding the role of hepatic encephalopathy in age-related cognitive decline.”

The study received no financial support. The authors reported no potential competing interests.

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

Dementia frequently coexists with hepatic encephalopathy (HE) in patients with cirrhosis but doesn’t correlate with other decompensating events, according to a new study involving U.S. veterans.

The overlap between dementia and HE was also independent of alcohol use, brain injury, age, and other metabolic risk factors.

“The aging of patients with cirrhosis leads us to encounter several individuals who may be prone to both of these diseases,” senior author Jasmohan Bajaj, MD, a professor of gastroenterology, hepatology, and nutrition at Virginia Commonwealth University Medical Center and GI section of the Central Virginia Veterans Healthcare System in Richmond, said in an interview.

“Given the epidemic of metabolic syndrome and alcohol, consider excluding cirrhosis in your patient [for] whom the presumptive diagnosis is dementia, since they could have concomitant HE,” he said.

“On the flip side, in those with HE who have predominant long-term memory issues and persistent cognitive changes, consider consulting a neuropsychiatrist or neurologist to ensure there is a resolution of the underlying disease process,” Dr. Bajaj added.

The study was published online in The American Journal of Gastroenterology.
 

Analyzing associations

HE is a common decompensating event in patients with cirrhosis. Because of the aging population of patients with cirrhosis, however, it’s important to differentiate HE from nonhepatic etiologies of cognitive impairment, such as dementia, the authors note.

Using data from the VA Corporate Data Warehouse, Dr. Bajaj and colleagues identified veterans with cirrhosis who received VA care between October 2019 and September 2021 and compared baseline characteristics between the cohorts based on the presence or absence of dementia. The research team then evaluated factors associated with having a diagnosis of dementia, adjusting for demographics, comorbid illnesses, cirrhosis etiology, and cirrhosis complications.

Investigators identified 71,522 veterans with diagnostic codes for cirrhosis who were engaged in VA care in 2019. They were mostly men (96.2%) and had a median age of 66. The most common etiologies of cirrhosis were alcohol and hepatitis C, followed by nonalcoholic steatohepatitis (NASH). The group also included veterans with predominantly compensated cirrhosis and a median MELD-Na score of 9. The MELD-Na score gauges the severity of chronic liver disease using values such as serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time and sodium to predict survival.

Among those with cirrhosis, 5,647 (7.9%) also had dementia diagnosis codes. This rate is higher than the prevalence of dementia in the general population and equivalent to the rate of dementia in veterans without cirrhosis who are older than 65, the authors note.

In general, veterans with dementia tended to be older, to be White, to live in an urban area, and to have higher MELD-Na scores, and they were more frequently diagnosed with alcohol-related cirrhosis, alcohol and tobacco use disorder, diabetes, chronic kidney disease, chronic heart failure, brain trauma, and cerebrovascular disease.

In a multivariable analysis, the presence of any decompensating event was significantly associated with dementia. In subsequent analyses of individual decompensating events, however, the strongest association was with HE, while ascites or variceal bleeding did not add to the risk.

When HE was defined as patients who filled prescriptions for lactulose or rifaximin, the frequency of patients with HE decreased from 13.7% to 10.9%. In an analysis with HE as the decompensating event, the association between HE and dementia remained significant compared to when HE was defined by diagnostic codes alone.

“We were surprised by the high proportion of patients with dementia who also had cirrhosis, and given the genuine difficulty that clinicians have with defining HE vs. dementia, we were not very surprised at that overlap,” Dr. Bajaj said.

“We were also surprised at the specificity of this overlap only with HE and not with other decompensating events, which was also independent of head injury, alcohol use, and PTSD,” he added.
 

Additional research needed

Future research should look at the characteristics of HE, including the number of episodes or breakthrough episodes, and should focus on objective biomarkers to differentiate dementia and HE, the study authors write.

“The distinction and study of potential overlapping features among HE and dementia is important because HE is often treatable with medications and reverses after liver transplant, while this does not occur with dementia,” they add.

Dr. Bajaj and colleagues call for a greater awareness of disease processes and complications in older patients with cirrhosis, particularly since diagnostic imprecision can lead to patient and family confusion, distrust, and ineffective treatment.

The study will help physicians better understand the important overlap between dementia and HE, said Eric Orman, MD, an associate professor of medicine at Indiana University, Indianapolis.

Dr. Orman, who wasn’t involved with this study, has researched recent trends in the characteristics and outcomes of patients with newly diagnosed cirrhosis and has found that the proportion of older adults has increased, as well as those with alcoholic cirrhosis and NASH, which has implications for future patient care.

“It is important to recognize that both dementia and HE can occur either separately or concurrently in individuals with cirrhosis,” Dr. Orman told this news organization. “When seeing patients with cognitive impairment, having a high index of suspicion for both conditions is critical to ensure appropriate diagnosis and treatment.”

The study’s findings “represent the tip of the iceberg,” Neal Parikh, MD, an assistant professor of neurology and neuroscience at Weill Cornell Medicine in New York, said in an interview. “There is a tremendous amount left to be discovered regarding the role of the liver in brain health.”

Dr. Parikh, who wasn’t associated with this study, has researched the impact of chronic liver conditions on cognitive impairment and dementia. He is working on a project that addresses HE in detail.

“There is growing recognition of a so-called ‘liver-brain axis,’ with several researchers, including my group, showing that a range of chronic liver conditions may detrimentally impact cognitive function and increase the risk of dementia,” he said. “Studying the specific contributions of cirrhosis is critical for understanding the role of hepatic encephalopathy in age-related cognitive decline.”

The study received no financial support. The authors reported no potential competing interests.

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

Autism can be detected in children almost from birth using an algorithm to review their health records, a study from Duke University, Durham, N.C., says.

“We can use the first 30 days of a child’s health care experience to say, ‘This child is really at risk,’ ” said David Mandell, DSc, a professor of psychiatry at the University of Pennsylvania, Philadelphia, in USA Today. He was not involved in the research.

Researchers analyzed electronic medical records of 45,000 children treated in the Duke University Health System as infants between 2006 and 2020. They created an algorithm that could predict which babies later developed autism. These babies were more likely to have been to an ophthalmologist or neurologist; had stomach or gastrointestinal issues; or received physical therapy.

“A huge number of factors across the infant’s entire health profile” went into the models, said study coauthor Matthew Engelhard, MD, an assistant professor of biostatistics and bioinformatics at Duke University. “Each one of those factors contributes incrementally.”

USA Today said the team “paid particular attention to how the model performed in groups of children who are often overlooked by traditional screening methods and, therefore, miss the advantages of early diagnosis, including girls, children of color, and children with combined diagnoses of autism and ADHD,” according to Dr. Engelhard.

The study could lead to the algorithm being used with other tools to diagnose and help children earlier, said study author Geraldine Dawson, PhD, who directs the Duke Center for Autism and Brain Development.

“We need to be thinking about autism as not only a behavioral health condition but also a condition that involves physical health,” she said. “This is one way to take advantage of that information: in doing a better job at early detection.”

Autism is a complicated condition that includes communication and behavior challenges involving a range of symptoms and skills. It can be minor or a disability that requires full-time care.

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

Autism can be detected in children almost from birth using an algorithm to review their health records, a study from Duke University, Durham, N.C., says.

“We can use the first 30 days of a child’s health care experience to say, ‘This child is really at risk,’ ” said David Mandell, DSc, a professor of psychiatry at the University of Pennsylvania, Philadelphia, in USA Today. He was not involved in the research.

Researchers analyzed electronic medical records of 45,000 children treated in the Duke University Health System as infants between 2006 and 2020. They created an algorithm that could predict which babies later developed autism. These babies were more likely to have been to an ophthalmologist or neurologist; had stomach or gastrointestinal issues; or received physical therapy.

“A huge number of factors across the infant’s entire health profile” went into the models, said study coauthor Matthew Engelhard, MD, an assistant professor of biostatistics and bioinformatics at Duke University. “Each one of those factors contributes incrementally.”

USA Today said the team “paid particular attention to how the model performed in groups of children who are often overlooked by traditional screening methods and, therefore, miss the advantages of early diagnosis, including girls, children of color, and children with combined diagnoses of autism and ADHD,” according to Dr. Engelhard.

The study could lead to the algorithm being used with other tools to diagnose and help children earlier, said study author Geraldine Dawson, PhD, who directs the Duke Center for Autism and Brain Development.

“We need to be thinking about autism as not only a behavioral health condition but also a condition that involves physical health,” she said. “This is one way to take advantage of that information: in doing a better job at early detection.”

Autism is a complicated condition that includes communication and behavior challenges involving a range of symptoms and skills. It can be minor or a disability that requires full-time care.

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

Autism can be detected in children almost from birth using an algorithm to review their health records, a study from Duke University, Durham, N.C., says.

“We can use the first 30 days of a child’s health care experience to say, ‘This child is really at risk,’ ” said David Mandell, DSc, a professor of psychiatry at the University of Pennsylvania, Philadelphia, in USA Today. He was not involved in the research.

Researchers analyzed electronic medical records of 45,000 children treated in the Duke University Health System as infants between 2006 and 2020. They created an algorithm that could predict which babies later developed autism. These babies were more likely to have been to an ophthalmologist or neurologist; had stomach or gastrointestinal issues; or received physical therapy.

“A huge number of factors across the infant’s entire health profile” went into the models, said study coauthor Matthew Engelhard, MD, an assistant professor of biostatistics and bioinformatics at Duke University. “Each one of those factors contributes incrementally.”

USA Today said the team “paid particular attention to how the model performed in groups of children who are often overlooked by traditional screening methods and, therefore, miss the advantages of early diagnosis, including girls, children of color, and children with combined diagnoses of autism and ADHD,” according to Dr. Engelhard.

The study could lead to the algorithm being used with other tools to diagnose and help children earlier, said study author Geraldine Dawson, PhD, who directs the Duke Center for Autism and Brain Development.

“We need to be thinking about autism as not only a behavioral health condition but also a condition that involves physical health,” she said. “This is one way to take advantage of that information: in doing a better job at early detection.”

Autism is a complicated condition that includes communication and behavior challenges involving a range of symptoms and skills. It can be minor or a disability that requires full-time care.

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

Among pediatric patients with psoriasis who began treatment with ustekinumab, etanercept, or methotrexate, the rate of serious infections at 6 months was low, with an incidence ranging between 14.9 and 25.6 per 1,000 person-years.

Those are key findings from what is believed to be the largest cohort study of its kind to estimate the 6-month rate of infections among children with psoriasis who started treatment with ustekinumab, etanercept, or methotrexate.

“Clinical trials have demonstrated high efficacy of new immunomodulatory agents in treating children with psoriasis,” lead author Maria C. Schneeweiss, MD, of the division of pharmacoepidemiology in the departments of medicine and dermatology at Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues wrote in the article, which was published online in JAMA Dermatology. “However, the risk of infections in clinical practice has not been fully characterized by comparing these medications against each other in pairwise comparisons.”

Drawing from two large U.S. insurance claims databases, the researchers identified 2,338 patients aged 17 years and younger who were receiving treatment with a topical medication for psoriasis and started new treatment with ustekinumab, etanercept, or methotrexate. They stratified their analysis by the time before pediatric labeling (2009-2015) and after pediatric approval (2016-2021), and their follow-up of patients started 1 day after initiating treatment and ended at 6 months.

Of the 2,338 patients, 1,368 (58%) were girls. From 2009 through 2021, 379 patients began treatment with ustekinumab, 779 patients began treatment with etanercept, and 1,180 patients began treatment with methotrexate. The propensity score–adjusted incidence rate of serious infection was 18.4 per 1,000 person-years (3 events) for those who used ustekinumab, 25.6 per 1,000 person-years (9 events) for those who used etanercept, and 14.9 per 1,000 person-years (8 events) for those who used methotrexate. The adjusted rate of outpatient infections was 254.9 per 1,000 person-years (39 events) for those who used ustekinumab, 435.7 per 1,000 person-years (139 events) for those who used etanercept, and 433.6 per 1,000 person-years (209 events) for those who used methotrexate. Meanwhile, the adjusted rate ratio of outpatient infections was 0.58 for ustekinumab vs. etanercept, 0.66 for ustekinumab vs. methotrexate, and 0.95 for etanercept vs. methotrexate. The researchers found that ratios were similar during the off-label use era and after pediatric labeling.

Anna L. Grossberg, MD, director of pediatric dermatology at the Johns Hopkins Children’s Center, Baltimore, who was asked to comment on the work, told this news organization that the data on outpatient infections in ustekinumab users “demonstrated that they may have a decreased risk of infection compared to pediatric psoriasis patients treated with methotrexate or the TNF-alpha inhibitor etanercept. This is previously unreported and reflects my personal experience with this medication in my own pediatric psoriasis patients.” She added the study’s overall findings lend further support to the safety of biologic medications and nonbiologic systemic immunomodulatory treatments for management of psoriasis. “This study will help guide pediatric dermatologists in counseling patients and their families about these risks [of infection], and in general providing reassurance that these risks appear to be quite low,” Dr. Grossberg said. “In particular, ustekinumab, a newer biologic medication that was recently FDA-approved for children 6 years and older for pediatric psoriasis, was not associated with higher infection rates than the other agents analyzed in this study, and in fact appears to carry a reduced risk compared to both etanercept and methotrexate.”

She noted certain limitations of the study, including its reliance on insurance claims data, “which can be limiting because information on possible confounding variables may not be known,” she said. “For example, the authors point out that environmental and behavioral risk factors for serious infection could not be evaluated or adjusted for, nor could the severity of the patients’ psoriasis. Additionally, this study only reported on outpatient infections that resulted in an antibiotic or other medications being prescribed and filled. It therefore may have missed children who presented with certain viral infections (examples could include the common cold and uncomplicated ear infections), which often will not require a prescription medication. Furthermore, it would fail to capture those who may have been seen for an infection but failed to fill the intended prescription.”

Dr. Schneeweiss reported receiving grants from AbbVie and UCB to Brigham and Women’s Hospital unrelated to the topic of this study and outside the submitted work. The study was supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Grossberg reported having no financial disclosures.

Among pediatric patients with psoriasis who began treatment with ustekinumab, etanercept, or methotrexate, the rate of serious infections at 6 months was low, with an incidence ranging between 14.9 and 25.6 per 1,000 person-years.

Those are key findings from what is believed to be the largest cohort study of its kind to estimate the 6-month rate of infections among children with psoriasis who started treatment with ustekinumab, etanercept, or methotrexate.

“Clinical trials have demonstrated high efficacy of new immunomodulatory agents in treating children with psoriasis,” lead author Maria C. Schneeweiss, MD, of the division of pharmacoepidemiology in the departments of medicine and dermatology at Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues wrote in the article, which was published online in JAMA Dermatology. “However, the risk of infections in clinical practice has not been fully characterized by comparing these medications against each other in pairwise comparisons.”

Drawing from two large U.S. insurance claims databases, the researchers identified 2,338 patients aged 17 years and younger who were receiving treatment with a topical medication for psoriasis and started new treatment with ustekinumab, etanercept, or methotrexate. They stratified their analysis by the time before pediatric labeling (2009-2015) and after pediatric approval (2016-2021), and their follow-up of patients started 1 day after initiating treatment and ended at 6 months.

Of the 2,338 patients, 1,368 (58%) were girls. From 2009 through 2021, 379 patients began treatment with ustekinumab, 779 patients began treatment with etanercept, and 1,180 patients began treatment with methotrexate. The propensity score–adjusted incidence rate of serious infection was 18.4 per 1,000 person-years (3 events) for those who used ustekinumab, 25.6 per 1,000 person-years (9 events) for those who used etanercept, and 14.9 per 1,000 person-years (8 events) for those who used methotrexate. The adjusted rate of outpatient infections was 254.9 per 1,000 person-years (39 events) for those who used ustekinumab, 435.7 per 1,000 person-years (139 events) for those who used etanercept, and 433.6 per 1,000 person-years (209 events) for those who used methotrexate. Meanwhile, the adjusted rate ratio of outpatient infections was 0.58 for ustekinumab vs. etanercept, 0.66 for ustekinumab vs. methotrexate, and 0.95 for etanercept vs. methotrexate. The researchers found that ratios were similar during the off-label use era and after pediatric labeling.

Anna L. Grossberg, MD, director of pediatric dermatology at the Johns Hopkins Children’s Center, Baltimore, who was asked to comment on the work, told this news organization that the data on outpatient infections in ustekinumab users “demonstrated that they may have a decreased risk of infection compared to pediatric psoriasis patients treated with methotrexate or the TNF-alpha inhibitor etanercept. This is previously unreported and reflects my personal experience with this medication in my own pediatric psoriasis patients.” She added the study’s overall findings lend further support to the safety of biologic medications and nonbiologic systemic immunomodulatory treatments for management of psoriasis. “This study will help guide pediatric dermatologists in counseling patients and their families about these risks [of infection], and in general providing reassurance that these risks appear to be quite low,” Dr. Grossberg said. “In particular, ustekinumab, a newer biologic medication that was recently FDA-approved for children 6 years and older for pediatric psoriasis, was not associated with higher infection rates than the other agents analyzed in this study, and in fact appears to carry a reduced risk compared to both etanercept and methotrexate.”

She noted certain limitations of the study, including its reliance on insurance claims data, “which can be limiting because information on possible confounding variables may not be known,” she said. “For example, the authors point out that environmental and behavioral risk factors for serious infection could not be evaluated or adjusted for, nor could the severity of the patients’ psoriasis. Additionally, this study only reported on outpatient infections that resulted in an antibiotic or other medications being prescribed and filled. It therefore may have missed children who presented with certain viral infections (examples could include the common cold and uncomplicated ear infections), which often will not require a prescription medication. Furthermore, it would fail to capture those who may have been seen for an infection but failed to fill the intended prescription.”

Dr. Schneeweiss reported receiving grants from AbbVie and UCB to Brigham and Women’s Hospital unrelated to the topic of this study and outside the submitted work. The study was supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Grossberg reported having no financial disclosures.

Among pediatric patients with psoriasis who began treatment with ustekinumab, etanercept, or methotrexate, the rate of serious infections at 6 months was low, with an incidence ranging between 14.9 and 25.6 per 1,000 person-years.

Those are key findings from what is believed to be the largest cohort study of its kind to estimate the 6-month rate of infections among children with psoriasis who started treatment with ustekinumab, etanercept, or methotrexate.

“Clinical trials have demonstrated high efficacy of new immunomodulatory agents in treating children with psoriasis,” lead author Maria C. Schneeweiss, MD, of the division of pharmacoepidemiology in the departments of medicine and dermatology at Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues wrote in the article, which was published online in JAMA Dermatology. “However, the risk of infections in clinical practice has not been fully characterized by comparing these medications against each other in pairwise comparisons.”

Drawing from two large U.S. insurance claims databases, the researchers identified 2,338 patients aged 17 years and younger who were receiving treatment with a topical medication for psoriasis and started new treatment with ustekinumab, etanercept, or methotrexate. They stratified their analysis by the time before pediatric labeling (2009-2015) and after pediatric approval (2016-2021), and their follow-up of patients started 1 day after initiating treatment and ended at 6 months.

Of the 2,338 patients, 1,368 (58%) were girls. From 2009 through 2021, 379 patients began treatment with ustekinumab, 779 patients began treatment with etanercept, and 1,180 patients began treatment with methotrexate. The propensity score–adjusted incidence rate of serious infection was 18.4 per 1,000 person-years (3 events) for those who used ustekinumab, 25.6 per 1,000 person-years (9 events) for those who used etanercept, and 14.9 per 1,000 person-years (8 events) for those who used methotrexate. The adjusted rate of outpatient infections was 254.9 per 1,000 person-years (39 events) for those who used ustekinumab, 435.7 per 1,000 person-years (139 events) for those who used etanercept, and 433.6 per 1,000 person-years (209 events) for those who used methotrexate. Meanwhile, the adjusted rate ratio of outpatient infections was 0.58 for ustekinumab vs. etanercept, 0.66 for ustekinumab vs. methotrexate, and 0.95 for etanercept vs. methotrexate. The researchers found that ratios were similar during the off-label use era and after pediatric labeling.

Anna L. Grossberg, MD, director of pediatric dermatology at the Johns Hopkins Children’s Center, Baltimore, who was asked to comment on the work, told this news organization that the data on outpatient infections in ustekinumab users “demonstrated that they may have a decreased risk of infection compared to pediatric psoriasis patients treated with methotrexate or the TNF-alpha inhibitor etanercept. This is previously unreported and reflects my personal experience with this medication in my own pediatric psoriasis patients.” She added the study’s overall findings lend further support to the safety of biologic medications and nonbiologic systemic immunomodulatory treatments for management of psoriasis. “This study will help guide pediatric dermatologists in counseling patients and their families about these risks [of infection], and in general providing reassurance that these risks appear to be quite low,” Dr. Grossberg said. “In particular, ustekinumab, a newer biologic medication that was recently FDA-approved for children 6 years and older for pediatric psoriasis, was not associated with higher infection rates than the other agents analyzed in this study, and in fact appears to carry a reduced risk compared to both etanercept and methotrexate.”

She noted certain limitations of the study, including its reliance on insurance claims data, “which can be limiting because information on possible confounding variables may not be known,” she said. “For example, the authors point out that environmental and behavioral risk factors for serious infection could not be evaluated or adjusted for, nor could the severity of the patients’ psoriasis. Additionally, this study only reported on outpatient infections that resulted in an antibiotic or other medications being prescribed and filled. It therefore may have missed children who presented with certain viral infections (examples could include the common cold and uncomplicated ear infections), which often will not require a prescription medication. Furthermore, it would fail to capture those who may have been seen for an infection but failed to fill the intended prescription.”

Dr. Schneeweiss reported receiving grants from AbbVie and UCB to Brigham and Women’s Hospital unrelated to the topic of this study and outside the submitted work. The study was supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Grossberg reported having no financial disclosures.

Bright light therapy significantly improved depressive symptoms in approximately half of adults with bipolar depression in a pilot study of 41 individuals.

Both depression and bipolar disorder are leading causes of disability worldwide, and data show that only 50%-60% of these patients respond to first-line antidepressants, wrote Alessandro Cuomo, MD, of the University of Siena Medical Center, Italy, and colleagues.

Bright light therapy (BLT) was originally introduced as a treatment for seasonal affective disorder, but its use has been expanded to treat nonseasonal depression and bipolar disorder, they said. However, the impact of BLT on depressive symptoms in bipolar depression in particular has not been examined, they noted.

In a study published in the Journal of Affective Disorders, the researchers identified 18 men and 23 women aged 18 years and older with bipolar depression based on DSM-5 criteria who had already been treated with antidepressants. The participants were randomized to antidepressants combined with BLT or antidepressants combined with red light exposure (controls). The participants were positioned at 30-80 cm from the 10,000-lux light source for 30 minutes daily. The mean age of the participants was 49.1 years.

The primary outcome was scores on the Montgomery-Åsberg Depression Scale (MADRS), Hamilton Depression Rating Scale (HAMD-17), and CGI-Severity of illness (CGI-S), Fatigue Severity Scale (FSS), and Quality of Life Scale (QOLS) after the 8 weeks of treatment.

After 4 weeks, MADRS scores and HAMD-17 scores were significantly lower in the treatment group, compared with the controls (20 and 18 vs. 27.5 and 24.9, respectively; P < .001). Quality of life scores increased in the treatment group, compared with controls, with median scores of 39 vs. 29.50, respectively.

After 8 weeks, the treatment group continued to show significant improvement, compared with the control group, with scores on the MADRS, HAMD-17, CGI-S, and QOLS of 14.0, 9.0, 1.0, and 62.0 vs. 16.0, 15.5, 2.0, and 40.0, respectively. No side effects were reported.

“From our findings, BLT [proved] particularly effective in bipolar patients without triggering any manic switch, as evidenced instead in some similar studies,” the researchers wrote in their discussion.

Although the mechanism of action for BLT remains unclear, the current study findings confirm the existing knowledge of BLT, they noted. The positive effect of BLT on quality of life “might be attributable to the ability of BLT to reduce the latency times of antidepressants and increase the production of serotonin and melatonin,” as shown in previous work, they said.

The study findings were limited by several factors including the small sample size, which prevents definitive conclusions about the effectiveness of BLT in combination with different antidepressants, and the heterogeneity of the antidepressant treatments, the researchers noted. Larger, prospective studies and randomized, controlled trials are needed, as are studies of special populations such as older adults or those with degenerative diseases, they said.

However, the results suggest BLT has value as a safe and effective treatment and a way to boost therapeutic response and reduce the impact of long-lasting therapies, they concluded.

The study received no outside funding. Dr. Cuomo disclosed serving as a consultant and/or a speaker for Angelini, Glaxo Smith Kline, Lundbeck, Janssen, Otsuka, Pfizer, and Recordati.

Bright light therapy significantly improved depressive symptoms in approximately half of adults with bipolar depression in a pilot study of 41 individuals.

Both depression and bipolar disorder are leading causes of disability worldwide, and data show that only 50%-60% of these patients respond to first-line antidepressants, wrote Alessandro Cuomo, MD, of the University of Siena Medical Center, Italy, and colleagues.

Bright light therapy (BLT) was originally introduced as a treatment for seasonal affective disorder, but its use has been expanded to treat nonseasonal depression and bipolar disorder, they said. However, the impact of BLT on depressive symptoms in bipolar depression in particular has not been examined, they noted.

In a study published in the Journal of Affective Disorders, the researchers identified 18 men and 23 women aged 18 years and older with bipolar depression based on DSM-5 criteria who had already been treated with antidepressants. The participants were randomized to antidepressants combined with BLT or antidepressants combined with red light exposure (controls). The participants were positioned at 30-80 cm from the 10,000-lux light source for 30 minutes daily. The mean age of the participants was 49.1 years.

The primary outcome was scores on the Montgomery-Åsberg Depression Scale (MADRS), Hamilton Depression Rating Scale (HAMD-17), and CGI-Severity of illness (CGI-S), Fatigue Severity Scale (FSS), and Quality of Life Scale (QOLS) after the 8 weeks of treatment.

After 4 weeks, MADRS scores and HAMD-17 scores were significantly lower in the treatment group, compared with the controls (20 and 18 vs. 27.5 and 24.9, respectively; P < .001). Quality of life scores increased in the treatment group, compared with controls, with median scores of 39 vs. 29.50, respectively.

After 8 weeks, the treatment group continued to show significant improvement, compared with the control group, with scores on the MADRS, HAMD-17, CGI-S, and QOLS of 14.0, 9.0, 1.0, and 62.0 vs. 16.0, 15.5, 2.0, and 40.0, respectively. No side effects were reported.

“From our findings, BLT [proved] particularly effective in bipolar patients without triggering any manic switch, as evidenced instead in some similar studies,” the researchers wrote in their discussion.

Although the mechanism of action for BLT remains unclear, the current study findings confirm the existing knowledge of BLT, they noted. The positive effect of BLT on quality of life “might be attributable to the ability of BLT to reduce the latency times of antidepressants and increase the production of serotonin and melatonin,” as shown in previous work, they said.

The study findings were limited by several factors including the small sample size, which prevents definitive conclusions about the effectiveness of BLT in combination with different antidepressants, and the heterogeneity of the antidepressant treatments, the researchers noted. Larger, prospective studies and randomized, controlled trials are needed, as are studies of special populations such as older adults or those with degenerative diseases, they said.

However, the results suggest BLT has value as a safe and effective treatment and a way to boost therapeutic response and reduce the impact of long-lasting therapies, they concluded.

The study received no outside funding. Dr. Cuomo disclosed serving as a consultant and/or a speaker for Angelini, Glaxo Smith Kline, Lundbeck, Janssen, Otsuka, Pfizer, and Recordati.

Bright light therapy significantly improved depressive symptoms in approximately half of adults with bipolar depression in a pilot study of 41 individuals.

Both depression and bipolar disorder are leading causes of disability worldwide, and data show that only 50%-60% of these patients respond to first-line antidepressants, wrote Alessandro Cuomo, MD, of the University of Siena Medical Center, Italy, and colleagues.

Bright light therapy (BLT) was originally introduced as a treatment for seasonal affective disorder, but its use has been expanded to treat nonseasonal depression and bipolar disorder, they said. However, the impact of BLT on depressive symptoms in bipolar depression in particular has not been examined, they noted.

In a study published in the Journal of Affective Disorders, the researchers identified 18 men and 23 women aged 18 years and older with bipolar depression based on DSM-5 criteria who had already been treated with antidepressants. The participants were randomized to antidepressants combined with BLT or antidepressants combined with red light exposure (controls). The participants were positioned at 30-80 cm from the 10,000-lux light source for 30 minutes daily. The mean age of the participants was 49.1 years.

The primary outcome was scores on the Montgomery-Åsberg Depression Scale (MADRS), Hamilton Depression Rating Scale (HAMD-17), and CGI-Severity of illness (CGI-S), Fatigue Severity Scale (FSS), and Quality of Life Scale (QOLS) after the 8 weeks of treatment.

After 4 weeks, MADRS scores and HAMD-17 scores were significantly lower in the treatment group, compared with the controls (20 and 18 vs. 27.5 and 24.9, respectively; P < .001). Quality of life scores increased in the treatment group, compared with controls, with median scores of 39 vs. 29.50, respectively.

After 8 weeks, the treatment group continued to show significant improvement, compared with the control group, with scores on the MADRS, HAMD-17, CGI-S, and QOLS of 14.0, 9.0, 1.0, and 62.0 vs. 16.0, 15.5, 2.0, and 40.0, respectively. No side effects were reported.

“From our findings, BLT [proved] particularly effective in bipolar patients without triggering any manic switch, as evidenced instead in some similar studies,” the researchers wrote in their discussion.

Although the mechanism of action for BLT remains unclear, the current study findings confirm the existing knowledge of BLT, they noted. The positive effect of BLT on quality of life “might be attributable to the ability of BLT to reduce the latency times of antidepressants and increase the production of serotonin and melatonin,” as shown in previous work, they said.

The study findings were limited by several factors including the small sample size, which prevents definitive conclusions about the effectiveness of BLT in combination with different antidepressants, and the heterogeneity of the antidepressant treatments, the researchers noted. Larger, prospective studies and randomized, controlled trials are needed, as are studies of special populations such as older adults or those with degenerative diseases, they said.

However, the results suggest BLT has value as a safe and effective treatment and a way to boost therapeutic response and reduce the impact of long-lasting therapies, they concluded.

The study received no outside funding. Dr. Cuomo disclosed serving as a consultant and/or a speaker for Angelini, Glaxo Smith Kline, Lundbeck, Janssen, Otsuka, Pfizer, and Recordati.