Conference Coverage

Tirzepatide, a novel “twincretin” agent, was superior to 1-mg semaglutide treatments for reducing both hemoglobin A1c levels and body weight in patients with type 2 diabetes in a pivotal, 40-week, head-to-head trial with nearly 1,900 randomized patients, one of four positive pivotal trial results reported for tirzepatide at the annual scientific sessions of the American Diabetes Association.

“Across all four studies we see a significant and clinically meaningful decrease in A1c, and robust weight loss. The results exceeded our expectations” for both these outcomes, said Laura Fernández Landó, MD, senior medical director for tirzepatide at Lilly, the company developing the agent, and a coauthor on the semaglutide comparison study as well as on other tirzepatide reports at the meeting.

“This opens up a new avenue for results in diabetes therapy,” Jens Juul Holst, MD, remarked in a press conference.

SURPASS-2 compared three different tirzepatide doses delivered once weekly by subcutaneous injection against a 1-mg weekly, subcutaneous dose of semaglutide (Ozempic) in 1,879 adults who had been diagnosed with type 2 diabetes for an average of almost 9 years. All patients were already on metformin treatment that had proved inadequate for controlling their hyperglycemia; enrolled patients had an average A1c of 8.28%. The trial’s primary endpoint was change from baseline in A1c levels after 40 weeks.
 

Significant differences at each dose level

Patients on each of the three tirzepatide doses – 5 mg, 10 mg, or 15 mg once weekly – showed dose-dependent reductions in A1c that, for each dose, were significantly better than the reduction achieved with semaglutide. The highest tirzepatide dose reduced A1c levels by an average of 0.45% more than what semaglutide achieved, reported first author Juan P. Frias, MD; Dr. Landó; and their coauthors.

One key secondary endpoint was weight reduction, and each of the three tirzepatide doses again produced significant incremental loss beyond what semaglutide produced. The 5-mg weekly dose of tirzepatide produced an average 1.9-kg additional weight loss, compared with semaglutide, while the 15-mg dose resulted in an average 5.5-kg loss beyond what semaglutide achieved and a total average weight loss of 11.2 kg from baseline.

The study’s additional key secondary endpoints, the percentages of patients reaching an A1c of less than 7%, and less than 5.7%, also showed significantly better numbers with tirzepatide. The highest tirzepatide dose pushed 86% of patients below the 7% mark, compared with 79% on semaglutide, and the top tirzepatide dose resulted in 46% of patients getting their A1c below 5.7%, compared with 19% of patients on semaglutide.

The findings are “stunning, I must stay, and those results included that up to half of the patients treated with high doses of tirzepatide may reach A1c levels of less than 5.7%, which is really, really unheard of,” said Dr. Holst, professor of endocrinology and metabolism at the University of Copenhagen. Along with the “weight losses at the same time of up to 12% in that patient group, we are seeing some completely unexpected and really shocking and wonderful new advances in the therapy,” added Dr. Holst.

The safety profile of tirzepatide was roughly similar to semaglutide’s and to that other agents in the glucagonlike peptide-1 receptor agonist (GLP-1 RA) class. Concurrently with the report at the meeting, the results also appeared in an article published online in the New England Journal of Medicine.
 

An ‘impressive’ weight loss effect

Weight loss on tirzepatide was “impressive,” commented Katherine R. Tuttle, MD, a nephrologist affiliated with the University of Washington and executive director for research at Providence Health Care in Spokane, Wash. Another striking feature of tirzepatide’s weight-loss effect was that it did not plateau during the 40 weeks of the study, Dr. Tuttle noted in an accompanying editorial that accompanied the published report, a finding that suggests the potential for additional weight loss from continued treatment .

“The weight loss is remarkable,” commented Rodolfo J. Galindo, MD, an endocrinologist at Emory University, Atlanta. While incremental reduction of A1c on the order of less than 0.5% is helpful, incremental weight loss of more than 10 lbs on tirzepatide, compared with semaglutide “will likely be a tie-breaker” for many clinicians and patients to favor tirzepatide over semaglutide or another GLP-1 RA agent, he said in an interview. Dr. Galindo also cited other important factors that he predicted will drive decisions on using tirzepatide or a GLP-1 RA once tirzepatide reaches the U.S. market: relative cost, access, and tolerability.
 

The important issue of dose

But the edge that tirzepatide showed over semaglutide for weight loss did not occur on a completely level playing field. The 1 mg/week dose of semaglutide used as the comparator in SURPASS-2 was the maximum dose available at the time the study began, but in June 2021 the Food and Drug Administration approved a 2.4 mg/week dose (Wegovy) labeled specifically for weight loss. Dr. Tuttle cited the limitation this introduces in her editorial.

“The dose issue is important,” she wrote. The doses of tirzepatide and semaglutide compared in SURPASS-2 “were not comparable in terms of weight outcomes” given that prior evidence showed that the 2.4 mg/week semaglutide dose is more appropriate for weight loss.

Dr. Tuttle also cited other factors to consider when assessing tirzepatide compared with agents in the GLP-1 RA class.

Several GLP-1 RA agents, including semaglutide, have proven efficacy for reducing rates of atherosclerotic cardiovascular events and albuminuria, and they also slow decline in kidney function and progression of diabetic kidney disease. No details on the renal effects of tirzepatide appeared in the SURPASS-2 report. A press release from Lilly in May 2021 briefly mentioned results from a meta-analysis of several clinical studies of tirzepatide that showed a nonsignificant effect from tirzepatide on the incidence of major cardiovascular adverse events (death from cardiovascular or undetermined causes, MI, stroke, and hospitalization for unstable angina) relative to comparator groups. Results from a dedicated cardiovascular outcomes trial in high-risk patients treated with tirzepatide, SURPASS-CVOT, are not expected until 2024.

A further limitation of SURPASS-2 was the demographics of the enrolled population, which had a low (0.4%) enrollment rate of Black patients, and a high proportion (70%) of Hispanic patients, Dr. Tuttle observed.
 

Low rates of hypoglycemia

Another notable finding from SURPASS-2 was the low incidence of clinically significant hypoglycemic events (blood glucose levels less than 54 mg/dL), which occurred in 0.2%-1.7% of patients on tirzepatide, depending on their dose, and in 0.4% of patients on semaglutide. Two patients in the tirzepatide cohort had severe hypoglycemia.

These numbers are reassuring, said Dr. Galindo, and reflect the safety of tirzepatide’s dual, incretin-like mechanisms of action that make it a “twincretin.” The molecule acts as both a GLP-1 RA, and as glucose-dependent insulinotropic polypeptide, an incretin that stimulates insulin release when blood sugar is high but also increases glucagon levels when blood sugar levels are normal or low. This dual action may help explain the apparent increased potency tirzepatide showed for both A1c reduction and weight loss, compared with semaglutide, which acts only as a GLP-1 RA.

Some experts have cited the uncertainty introduced by the open-label design of SURPASS-2, a decision necessitated by the distinctly different delivery devices used for tirzepatide and semaglutide, explained Dr. Landó. But she highlighted that double blinding applied to the three different tirzepatide dosages tested in the trial. Dr. Landó said that Lilly plans to seek FDA approval for all three tested tirzepatide doses to give clinicians and patients flexibility in applying the treatment.

SURPASS-2 used a prolonged dose-escalation protocol designed to minimize gastrointestinal adverse effects that started patients on a 2.5 mg weekly dose that then increased by 2.5 mg increments every 4 weeks until patients reached their assigned target dose. This meant that patients did not begin receiving the 15-mg/week dose until halfway through the trial.
 

Several more tirzepatide trials

Reports from two other pivotal trials for tirzepatide also appeared as posters at the meeting. SURPASS-5 compared tirzepatide with placebo in 475 patients inadequately controlled with titrated insulin glargine (Lantus). SURPASS-3 randomized 1,444 patients to tirzepatide or titrated insulin degludec (Tresiba). In both studies treatment with tirzepatide led to significantly better reductions in A1c and in weight loss than the comparator treatments. Results from a third pivotal trial, SURPASS-1 which compared tirzepatide against placebo in 478 treatment-naive patients, will come in a report scheduled for the second day of the meeting.

The results from all the recent tirzepatide trials show a consistent benefit across the continuum of patients with type 2 diabetes regardless of whether it’s recent onset or well-established disease, said Dr. Landó.

The SURPASS studies were sponsored by Lilly, the company developing tirzepatide, and the reports include several authors who are Lilly employees. Dr. Landó is a Lilly employee and stockholder. Dr. Tuttle has been a consultant to Lilly and to Novo Nordisk, the company that markets semaglutide, as well as to AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, and Janssen. She has also received travel expenses from Kyokawa Hakko Kirin, and research funding from Bayer, Goldfinch Bio, and Lilly. Dr. Galindo has been a consultant to Lilly and to Novo Nordisk, as well as to Abbott Diabetes Care, Sanofi, Valeritas, and Weight Watchers, and his institution has received grant support on his behalf from Lilly, Novo Nordisk and Dexcom. Dr. Holst had no disclosures.

mzoler@mdedge.com

Tirzepatide, a novel “twincretin” agent, was superior to 1-mg semaglutide treatments for reducing both hemoglobin A1c levels and body weight in patients with type 2 diabetes in a pivotal, 40-week, head-to-head trial with nearly 1,900 randomized patients, one of four positive pivotal trial results reported for tirzepatide at the annual scientific sessions of the American Diabetes Association.

“Across all four studies we see a significant and clinically meaningful decrease in A1c, and robust weight loss. The results exceeded our expectations” for both these outcomes, said Laura Fernández Landó, MD, senior medical director for tirzepatide at Lilly, the company developing the agent, and a coauthor on the semaglutide comparison study as well as on other tirzepatide reports at the meeting.

“This opens up a new avenue for results in diabetes therapy,” Jens Juul Holst, MD, remarked in a press conference.

SURPASS-2 compared three different tirzepatide doses delivered once weekly by subcutaneous injection against a 1-mg weekly, subcutaneous dose of semaglutide (Ozempic) in 1,879 adults who had been diagnosed with type 2 diabetes for an average of almost 9 years. All patients were already on metformin treatment that had proved inadequate for controlling their hyperglycemia; enrolled patients had an average A1c of 8.28%. The trial’s primary endpoint was change from baseline in A1c levels after 40 weeks.
 

Significant differences at each dose level

Patients on each of the three tirzepatide doses – 5 mg, 10 mg, or 15 mg once weekly – showed dose-dependent reductions in A1c that, for each dose, were significantly better than the reduction achieved with semaglutide. The highest tirzepatide dose reduced A1c levels by an average of 0.45% more than what semaglutide achieved, reported first author Juan P. Frias, MD; Dr. Landó; and their coauthors.

One key secondary endpoint was weight reduction, and each of the three tirzepatide doses again produced significant incremental loss beyond what semaglutide produced. The 5-mg weekly dose of tirzepatide produced an average 1.9-kg additional weight loss, compared with semaglutide, while the 15-mg dose resulted in an average 5.5-kg loss beyond what semaglutide achieved and a total average weight loss of 11.2 kg from baseline.

The study’s additional key secondary endpoints, the percentages of patients reaching an A1c of less than 7%, and less than 5.7%, also showed significantly better numbers with tirzepatide. The highest tirzepatide dose pushed 86% of patients below the 7% mark, compared with 79% on semaglutide, and the top tirzepatide dose resulted in 46% of patients getting their A1c below 5.7%, compared with 19% of patients on semaglutide.

The findings are “stunning, I must stay, and those results included that up to half of the patients treated with high doses of tirzepatide may reach A1c levels of less than 5.7%, which is really, really unheard of,” said Dr. Holst, professor of endocrinology and metabolism at the University of Copenhagen. Along with the “weight losses at the same time of up to 12% in that patient group, we are seeing some completely unexpected and really shocking and wonderful new advances in the therapy,” added Dr. Holst.

The safety profile of tirzepatide was roughly similar to semaglutide’s and to that other agents in the glucagonlike peptide-1 receptor agonist (GLP-1 RA) class. Concurrently with the report at the meeting, the results also appeared in an article published online in the New England Journal of Medicine.
 

An ‘impressive’ weight loss effect

Weight loss on tirzepatide was “impressive,” commented Katherine R. Tuttle, MD, a nephrologist affiliated with the University of Washington and executive director for research at Providence Health Care in Spokane, Wash. Another striking feature of tirzepatide’s weight-loss effect was that it did not plateau during the 40 weeks of the study, Dr. Tuttle noted in an accompanying editorial that accompanied the published report, a finding that suggests the potential for additional weight loss from continued treatment .

“The weight loss is remarkable,” commented Rodolfo J. Galindo, MD, an endocrinologist at Emory University, Atlanta. While incremental reduction of A1c on the order of less than 0.5% is helpful, incremental weight loss of more than 10 lbs on tirzepatide, compared with semaglutide “will likely be a tie-breaker” for many clinicians and patients to favor tirzepatide over semaglutide or another GLP-1 RA agent, he said in an interview. Dr. Galindo also cited other important factors that he predicted will drive decisions on using tirzepatide or a GLP-1 RA once tirzepatide reaches the U.S. market: relative cost, access, and tolerability.
 

The important issue of dose

But the edge that tirzepatide showed over semaglutide for weight loss did not occur on a completely level playing field. The 1 mg/week dose of semaglutide used as the comparator in SURPASS-2 was the maximum dose available at the time the study began, but in June 2021 the Food and Drug Administration approved a 2.4 mg/week dose (Wegovy) labeled specifically for weight loss. Dr. Tuttle cited the limitation this introduces in her editorial.

“The dose issue is important,” she wrote. The doses of tirzepatide and semaglutide compared in SURPASS-2 “were not comparable in terms of weight outcomes” given that prior evidence showed that the 2.4 mg/week semaglutide dose is more appropriate for weight loss.

Dr. Tuttle also cited other factors to consider when assessing tirzepatide compared with agents in the GLP-1 RA class.

Several GLP-1 RA agents, including semaglutide, have proven efficacy for reducing rates of atherosclerotic cardiovascular events and albuminuria, and they also slow decline in kidney function and progression of diabetic kidney disease. No details on the renal effects of tirzepatide appeared in the SURPASS-2 report. A press release from Lilly in May 2021 briefly mentioned results from a meta-analysis of several clinical studies of tirzepatide that showed a nonsignificant effect from tirzepatide on the incidence of major cardiovascular adverse events (death from cardiovascular or undetermined causes, MI, stroke, and hospitalization for unstable angina) relative to comparator groups. Results from a dedicated cardiovascular outcomes trial in high-risk patients treated with tirzepatide, SURPASS-CVOT, are not expected until 2024.

A further limitation of SURPASS-2 was the demographics of the enrolled population, which had a low (0.4%) enrollment rate of Black patients, and a high proportion (70%) of Hispanic patients, Dr. Tuttle observed.
 

Low rates of hypoglycemia

Another notable finding from SURPASS-2 was the low incidence of clinically significant hypoglycemic events (blood glucose levels less than 54 mg/dL), which occurred in 0.2%-1.7% of patients on tirzepatide, depending on their dose, and in 0.4% of patients on semaglutide. Two patients in the tirzepatide cohort had severe hypoglycemia.

These numbers are reassuring, said Dr. Galindo, and reflect the safety of tirzepatide’s dual, incretin-like mechanisms of action that make it a “twincretin.” The molecule acts as both a GLP-1 RA, and as glucose-dependent insulinotropic polypeptide, an incretin that stimulates insulin release when blood sugar is high but also increases glucagon levels when blood sugar levels are normal or low. This dual action may help explain the apparent increased potency tirzepatide showed for both A1c reduction and weight loss, compared with semaglutide, which acts only as a GLP-1 RA.

Some experts have cited the uncertainty introduced by the open-label design of SURPASS-2, a decision necessitated by the distinctly different delivery devices used for tirzepatide and semaglutide, explained Dr. Landó. But she highlighted that double blinding applied to the three different tirzepatide dosages tested in the trial. Dr. Landó said that Lilly plans to seek FDA approval for all three tested tirzepatide doses to give clinicians and patients flexibility in applying the treatment.

SURPASS-2 used a prolonged dose-escalation protocol designed to minimize gastrointestinal adverse effects that started patients on a 2.5 mg weekly dose that then increased by 2.5 mg increments every 4 weeks until patients reached their assigned target dose. This meant that patients did not begin receiving the 15-mg/week dose until halfway through the trial.
 

Several more tirzepatide trials

Reports from two other pivotal trials for tirzepatide also appeared as posters at the meeting. SURPASS-5 compared tirzepatide with placebo in 475 patients inadequately controlled with titrated insulin glargine (Lantus). SURPASS-3 randomized 1,444 patients to tirzepatide or titrated insulin degludec (Tresiba). In both studies treatment with tirzepatide led to significantly better reductions in A1c and in weight loss than the comparator treatments. Results from a third pivotal trial, SURPASS-1 which compared tirzepatide against placebo in 478 treatment-naive patients, will come in a report scheduled for the second day of the meeting.

The results from all the recent tirzepatide trials show a consistent benefit across the continuum of patients with type 2 diabetes regardless of whether it’s recent onset or well-established disease, said Dr. Landó.

The SURPASS studies were sponsored by Lilly, the company developing tirzepatide, and the reports include several authors who are Lilly employees. Dr. Landó is a Lilly employee and stockholder. Dr. Tuttle has been a consultant to Lilly and to Novo Nordisk, the company that markets semaglutide, as well as to AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, and Janssen. She has also received travel expenses from Kyokawa Hakko Kirin, and research funding from Bayer, Goldfinch Bio, and Lilly. Dr. Galindo has been a consultant to Lilly and to Novo Nordisk, as well as to Abbott Diabetes Care, Sanofi, Valeritas, and Weight Watchers, and his institution has received grant support on his behalf from Lilly, Novo Nordisk and Dexcom. Dr. Holst had no disclosures.

mzoler@mdedge.com

Tirzepatide, a novel “twincretin” agent, was superior to 1-mg semaglutide treatments for reducing both hemoglobin A1c levels and body weight in patients with type 2 diabetes in a pivotal, 40-week, head-to-head trial with nearly 1,900 randomized patients, one of four positive pivotal trial results reported for tirzepatide at the annual scientific sessions of the American Diabetes Association.

“Across all four studies we see a significant and clinically meaningful decrease in A1c, and robust weight loss. The results exceeded our expectations” for both these outcomes, said Laura Fernández Landó, MD, senior medical director for tirzepatide at Lilly, the company developing the agent, and a coauthor on the semaglutide comparison study as well as on other tirzepatide reports at the meeting.

“This opens up a new avenue for results in diabetes therapy,” Jens Juul Holst, MD, remarked in a press conference.

SURPASS-2 compared three different tirzepatide doses delivered once weekly by subcutaneous injection against a 1-mg weekly, subcutaneous dose of semaglutide (Ozempic) in 1,879 adults who had been diagnosed with type 2 diabetes for an average of almost 9 years. All patients were already on metformin treatment that had proved inadequate for controlling their hyperglycemia; enrolled patients had an average A1c of 8.28%. The trial’s primary endpoint was change from baseline in A1c levels after 40 weeks.
 

Significant differences at each dose level

Patients on each of the three tirzepatide doses – 5 mg, 10 mg, or 15 mg once weekly – showed dose-dependent reductions in A1c that, for each dose, were significantly better than the reduction achieved with semaglutide. The highest tirzepatide dose reduced A1c levels by an average of 0.45% more than what semaglutide achieved, reported first author Juan P. Frias, MD; Dr. Landó; and their coauthors.

One key secondary endpoint was weight reduction, and each of the three tirzepatide doses again produced significant incremental loss beyond what semaglutide produced. The 5-mg weekly dose of tirzepatide produced an average 1.9-kg additional weight loss, compared with semaglutide, while the 15-mg dose resulted in an average 5.5-kg loss beyond what semaglutide achieved and a total average weight loss of 11.2 kg from baseline.

The study’s additional key secondary endpoints, the percentages of patients reaching an A1c of less than 7%, and less than 5.7%, also showed significantly better numbers with tirzepatide. The highest tirzepatide dose pushed 86% of patients below the 7% mark, compared with 79% on semaglutide, and the top tirzepatide dose resulted in 46% of patients getting their A1c below 5.7%, compared with 19% of patients on semaglutide.

The findings are “stunning, I must stay, and those results included that up to half of the patients treated with high doses of tirzepatide may reach A1c levels of less than 5.7%, which is really, really unheard of,” said Dr. Holst, professor of endocrinology and metabolism at the University of Copenhagen. Along with the “weight losses at the same time of up to 12% in that patient group, we are seeing some completely unexpected and really shocking and wonderful new advances in the therapy,” added Dr. Holst.

The safety profile of tirzepatide was roughly similar to semaglutide’s and to that other agents in the glucagonlike peptide-1 receptor agonist (GLP-1 RA) class. Concurrently with the report at the meeting, the results also appeared in an article published online in the New England Journal of Medicine.
 

An ‘impressive’ weight loss effect

Weight loss on tirzepatide was “impressive,” commented Katherine R. Tuttle, MD, a nephrologist affiliated with the University of Washington and executive director for research at Providence Health Care in Spokane, Wash. Another striking feature of tirzepatide’s weight-loss effect was that it did not plateau during the 40 weeks of the study, Dr. Tuttle noted in an accompanying editorial that accompanied the published report, a finding that suggests the potential for additional weight loss from continued treatment .

“The weight loss is remarkable,” commented Rodolfo J. Galindo, MD, an endocrinologist at Emory University, Atlanta. While incremental reduction of A1c on the order of less than 0.5% is helpful, incremental weight loss of more than 10 lbs on tirzepatide, compared with semaglutide “will likely be a tie-breaker” for many clinicians and patients to favor tirzepatide over semaglutide or another GLP-1 RA agent, he said in an interview. Dr. Galindo also cited other important factors that he predicted will drive decisions on using tirzepatide or a GLP-1 RA once tirzepatide reaches the U.S. market: relative cost, access, and tolerability.
 

The important issue of dose

But the edge that tirzepatide showed over semaglutide for weight loss did not occur on a completely level playing field. The 1 mg/week dose of semaglutide used as the comparator in SURPASS-2 was the maximum dose available at the time the study began, but in June 2021 the Food and Drug Administration approved a 2.4 mg/week dose (Wegovy) labeled specifically for weight loss. Dr. Tuttle cited the limitation this introduces in her editorial.

“The dose issue is important,” she wrote. The doses of tirzepatide and semaglutide compared in SURPASS-2 “were not comparable in terms of weight outcomes” given that prior evidence showed that the 2.4 mg/week semaglutide dose is more appropriate for weight loss.

Dr. Tuttle also cited other factors to consider when assessing tirzepatide compared with agents in the GLP-1 RA class.

Several GLP-1 RA agents, including semaglutide, have proven efficacy for reducing rates of atherosclerotic cardiovascular events and albuminuria, and they also slow decline in kidney function and progression of diabetic kidney disease. No details on the renal effects of tirzepatide appeared in the SURPASS-2 report. A press release from Lilly in May 2021 briefly mentioned results from a meta-analysis of several clinical studies of tirzepatide that showed a nonsignificant effect from tirzepatide on the incidence of major cardiovascular adverse events (death from cardiovascular or undetermined causes, MI, stroke, and hospitalization for unstable angina) relative to comparator groups. Results from a dedicated cardiovascular outcomes trial in high-risk patients treated with tirzepatide, SURPASS-CVOT, are not expected until 2024.

A further limitation of SURPASS-2 was the demographics of the enrolled population, which had a low (0.4%) enrollment rate of Black patients, and a high proportion (70%) of Hispanic patients, Dr. Tuttle observed.
 

Low rates of hypoglycemia

Another notable finding from SURPASS-2 was the low incidence of clinically significant hypoglycemic events (blood glucose levels less than 54 mg/dL), which occurred in 0.2%-1.7% of patients on tirzepatide, depending on their dose, and in 0.4% of patients on semaglutide. Two patients in the tirzepatide cohort had severe hypoglycemia.

These numbers are reassuring, said Dr. Galindo, and reflect the safety of tirzepatide’s dual, incretin-like mechanisms of action that make it a “twincretin.” The molecule acts as both a GLP-1 RA, and as glucose-dependent insulinotropic polypeptide, an incretin that stimulates insulin release when blood sugar is high but also increases glucagon levels when blood sugar levels are normal or low. This dual action may help explain the apparent increased potency tirzepatide showed for both A1c reduction and weight loss, compared with semaglutide, which acts only as a GLP-1 RA.

Some experts have cited the uncertainty introduced by the open-label design of SURPASS-2, a decision necessitated by the distinctly different delivery devices used for tirzepatide and semaglutide, explained Dr. Landó. But she highlighted that double blinding applied to the three different tirzepatide dosages tested in the trial. Dr. Landó said that Lilly plans to seek FDA approval for all three tested tirzepatide doses to give clinicians and patients flexibility in applying the treatment.

SURPASS-2 used a prolonged dose-escalation protocol designed to minimize gastrointestinal adverse effects that started patients on a 2.5 mg weekly dose that then increased by 2.5 mg increments every 4 weeks until patients reached their assigned target dose. This meant that patients did not begin receiving the 15-mg/week dose until halfway through the trial.
 

Several more tirzepatide trials

Reports from two other pivotal trials for tirzepatide also appeared as posters at the meeting. SURPASS-5 compared tirzepatide with placebo in 475 patients inadequately controlled with titrated insulin glargine (Lantus). SURPASS-3 randomized 1,444 patients to tirzepatide or titrated insulin degludec (Tresiba). In both studies treatment with tirzepatide led to significantly better reductions in A1c and in weight loss than the comparator treatments. Results from a third pivotal trial, SURPASS-1 which compared tirzepatide against placebo in 478 treatment-naive patients, will come in a report scheduled for the second day of the meeting.

The results from all the recent tirzepatide trials show a consistent benefit across the continuum of patients with type 2 diabetes regardless of whether it’s recent onset or well-established disease, said Dr. Landó.

The SURPASS studies were sponsored by Lilly, the company developing tirzepatide, and the reports include several authors who are Lilly employees. Dr. Landó is a Lilly employee and stockholder. Dr. Tuttle has been a consultant to Lilly and to Novo Nordisk, the company that markets semaglutide, as well as to AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, and Janssen. She has also received travel expenses from Kyokawa Hakko Kirin, and research funding from Bayer, Goldfinch Bio, and Lilly. Dr. Galindo has been a consultant to Lilly and to Novo Nordisk, as well as to Abbott Diabetes Care, Sanofi, Valeritas, and Weight Watchers, and his institution has received grant support on his behalf from Lilly, Novo Nordisk and Dexcom. Dr. Holst had no disclosures.

mzoler@mdedge.com

Unmanaged diabetes and high blood glucose levels are linked to more severe COVID-19 and worse rates of recovery, according to results of a retrospective study.

Patients not managing their diabetes with medication had more severe COVID-19 and length of hospitalization, compared with those who were taking medication, investigator Sudip Bajpeyi, PhD, said at the annual scientific sessions of the American Diabetes Association.

In addition, patients with higher blood glucose levels had more severe COVID-19 and longer hospital stays.

Those findings underscore the need to assess, monitor, and control blood glucose, especially in vulnerable populations, said Dr. Bajpeyi, director of the Metabolic, Nutrition, and Exercise Research Laboratory in the University of Texas, El Paso, who added that nearly 90% of the study subjects were Hispanic.

“As public health decisions are made, we think fasting blood glucose should be considered in the treatment of hospitalized COVID-19 patients,” he said in a press conference.
 

Links between diabetes and COVID-19

There are now many reports in medical literature that link diabetes to increased risk of COVID-19 severity, according to Ali Mossayebi, a master’s student who worked on the study. However, there are fewer studies that have looked specifically at the implications of poor diabetes management or acute glycemic control, the investigators said.

It’s known that poorly controlled diabetes can have severe health consequences, including higher risks for life-threatening comorbidities, they added.

Their retrospective study focused on medical records from 364 patients with COVID-19 admitted to a medical center in El Paso. Their mean age was 60 years, and their mean body mass index was 30.3 kg/m²; 87% were Hispanic.

Acute glycemic control was assessed by fasting blood glucose at the time of hospitalization, while chronic glycemic control was assessed by hemoglobin A1c, the investigators said. Severity of COVID-19 was measured with the Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA), which is based on the patient’s respiratory rate, blood pressure, and mental status.
 

Impact of unmanaged diabetes and high blood glucose

Severity of COVID-19 severity and length of hospital stay were significantly greater in patients with unmanaged diabetes, as compared with those who reported that they managed their diabetes with medication, Dr. Bajpeyi and coinvestigators found.

Among patients with unmanaged diabetes, the mean qSOFA score was 0.22, as compared with 0.44 for patients with managed diabetes. The mean length of hospital stay was 10.8 days for patients with unmanaged diabetes and 8.2 days for those with medication-managed diabetes, according to the abstract.

COVID-19 severity and hospital stay length were highest among patients with acute glycemia, the investigators further reported in an electronic poster that was part of the ADA meeting proceedings.

The mean qSOFA score was about 0.6 for patients with blood glucose levels of at least 126 mg/dL and A1c below 6.5%, and roughly 0.2 for those with normal blood glucose and normal A1c. Similarly, duration of hospital stay was significantly higher for patients with high blood glucose and A1c as compared with those with normal blood glucose and A1c.
 

Aggressive treatment needed

Findings of this study are in line with previous research showing that in-hospital hyperglycemia is a common and important marker of poor clinical outcome and mortality, with or without diabetes, according to Rodolfo J. Galindo, MD, FACE, medical chair of the hospital diabetes task force at Emory Healthcare System, Atlanta.

“These patients need aggressive treatment of hyperglycemia, regardless of the diagnosis of diabetes or A1c value,” said Dr. Galindo, who was not involved in the study. “They also need outpatient follow-up after discharge, because they may develop diabetes soon after.”

Follow-up within is important because roughly 30% of patients with stress hyperglycemia (increases in blood glucose during an acute illness) will develop diabetes within a year, according to Dr. Galindo.

“We do not know in COVID-10 patients if it is only 30%,” he said, “Our thinking in our group is that it’s probably higher.”

Dr. Bajpeyi and coauthors reported no disclosures. Dr. Galindo reported disclosures related to Abbott Diabetes, Boehringer Ingelheim International, Eli Lilly, Novo Nordisk, Sanofi US, Valeritas, and Dexcom.

Unmanaged diabetes and high blood glucose levels are linked to more severe COVID-19 and worse rates of recovery, according to results of a retrospective study.

Patients not managing their diabetes with medication had more severe COVID-19 and length of hospitalization, compared with those who were taking medication, investigator Sudip Bajpeyi, PhD, said at the annual scientific sessions of the American Diabetes Association.

In addition, patients with higher blood glucose levels had more severe COVID-19 and longer hospital stays.

Those findings underscore the need to assess, monitor, and control blood glucose, especially in vulnerable populations, said Dr. Bajpeyi, director of the Metabolic, Nutrition, and Exercise Research Laboratory in the University of Texas, El Paso, who added that nearly 90% of the study subjects were Hispanic.

“As public health decisions are made, we think fasting blood glucose should be considered in the treatment of hospitalized COVID-19 patients,” he said in a press conference.
 

Links between diabetes and COVID-19

There are now many reports in medical literature that link diabetes to increased risk of COVID-19 severity, according to Ali Mossayebi, a master’s student who worked on the study. However, there are fewer studies that have looked specifically at the implications of poor diabetes management or acute glycemic control, the investigators said.

It’s known that poorly controlled diabetes can have severe health consequences, including higher risks for life-threatening comorbidities, they added.

Their retrospective study focused on medical records from 364 patients with COVID-19 admitted to a medical center in El Paso. Their mean age was 60 years, and their mean body mass index was 30.3 kg/m²; 87% were Hispanic.

Acute glycemic control was assessed by fasting blood glucose at the time of hospitalization, while chronic glycemic control was assessed by hemoglobin A1c, the investigators said. Severity of COVID-19 was measured with the Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA), which is based on the patient’s respiratory rate, blood pressure, and mental status.
 

Impact of unmanaged diabetes and high blood glucose

Severity of COVID-19 severity and length of hospital stay were significantly greater in patients with unmanaged diabetes, as compared with those who reported that they managed their diabetes with medication, Dr. Bajpeyi and coinvestigators found.

Among patients with unmanaged diabetes, the mean qSOFA score was 0.22, as compared with 0.44 for patients with managed diabetes. The mean length of hospital stay was 10.8 days for patients with unmanaged diabetes and 8.2 days for those with medication-managed diabetes, according to the abstract.

COVID-19 severity and hospital stay length were highest among patients with acute glycemia, the investigators further reported in an electronic poster that was part of the ADA meeting proceedings.

The mean qSOFA score was about 0.6 for patients with blood glucose levels of at least 126 mg/dL and A1c below 6.5%, and roughly 0.2 for those with normal blood glucose and normal A1c. Similarly, duration of hospital stay was significantly higher for patients with high blood glucose and A1c as compared with those with normal blood glucose and A1c.
 

Aggressive treatment needed

Findings of this study are in line with previous research showing that in-hospital hyperglycemia is a common and important marker of poor clinical outcome and mortality, with or without diabetes, according to Rodolfo J. Galindo, MD, FACE, medical chair of the hospital diabetes task force at Emory Healthcare System, Atlanta.

“These patients need aggressive treatment of hyperglycemia, regardless of the diagnosis of diabetes or A1c value,” said Dr. Galindo, who was not involved in the study. “They also need outpatient follow-up after discharge, because they may develop diabetes soon after.”

Follow-up within is important because roughly 30% of patients with stress hyperglycemia (increases in blood glucose during an acute illness) will develop diabetes within a year, according to Dr. Galindo.

“We do not know in COVID-10 patients if it is only 30%,” he said, “Our thinking in our group is that it’s probably higher.”

Dr. Bajpeyi and coauthors reported no disclosures. Dr. Galindo reported disclosures related to Abbott Diabetes, Boehringer Ingelheim International, Eli Lilly, Novo Nordisk, Sanofi US, Valeritas, and Dexcom.

Unmanaged diabetes and high blood glucose levels are linked to more severe COVID-19 and worse rates of recovery, according to results of a retrospective study.

Patients not managing their diabetes with medication had more severe COVID-19 and length of hospitalization, compared with those who were taking medication, investigator Sudip Bajpeyi, PhD, said at the annual scientific sessions of the American Diabetes Association.

In addition, patients with higher blood glucose levels had more severe COVID-19 and longer hospital stays.

Those findings underscore the need to assess, monitor, and control blood glucose, especially in vulnerable populations, said Dr. Bajpeyi, director of the Metabolic, Nutrition, and Exercise Research Laboratory in the University of Texas, El Paso, who added that nearly 90% of the study subjects were Hispanic.

“As public health decisions are made, we think fasting blood glucose should be considered in the treatment of hospitalized COVID-19 patients,” he said in a press conference.
 

Links between diabetes and COVID-19

There are now many reports in medical literature that link diabetes to increased risk of COVID-19 severity, according to Ali Mossayebi, a master’s student who worked on the study. However, there are fewer studies that have looked specifically at the implications of poor diabetes management or acute glycemic control, the investigators said.

It’s known that poorly controlled diabetes can have severe health consequences, including higher risks for life-threatening comorbidities, they added.

Their retrospective study focused on medical records from 364 patients with COVID-19 admitted to a medical center in El Paso. Their mean age was 60 years, and their mean body mass index was 30.3 kg/m²; 87% were Hispanic.

Acute glycemic control was assessed by fasting blood glucose at the time of hospitalization, while chronic glycemic control was assessed by hemoglobin A1c, the investigators said. Severity of COVID-19 was measured with the Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA), which is based on the patient’s respiratory rate, blood pressure, and mental status.
 

Impact of unmanaged diabetes and high blood glucose

Severity of COVID-19 severity and length of hospital stay were significantly greater in patients with unmanaged diabetes, as compared with those who reported that they managed their diabetes with medication, Dr. Bajpeyi and coinvestigators found.

Among patients with unmanaged diabetes, the mean qSOFA score was 0.22, as compared with 0.44 for patients with managed diabetes. The mean length of hospital stay was 10.8 days for patients with unmanaged diabetes and 8.2 days for those with medication-managed diabetes, according to the abstract.

COVID-19 severity and hospital stay length were highest among patients with acute glycemia, the investigators further reported in an electronic poster that was part of the ADA meeting proceedings.

The mean qSOFA score was about 0.6 for patients with blood glucose levels of at least 126 mg/dL and A1c below 6.5%, and roughly 0.2 for those with normal blood glucose and normal A1c. Similarly, duration of hospital stay was significantly higher for patients with high blood glucose and A1c as compared with those with normal blood glucose and A1c.
 

Aggressive treatment needed

Findings of this study are in line with previous research showing that in-hospital hyperglycemia is a common and important marker of poor clinical outcome and mortality, with or without diabetes, according to Rodolfo J. Galindo, MD, FACE, medical chair of the hospital diabetes task force at Emory Healthcare System, Atlanta.

“These patients need aggressive treatment of hyperglycemia, regardless of the diagnosis of diabetes or A1c value,” said Dr. Galindo, who was not involved in the study. “They also need outpatient follow-up after discharge, because they may develop diabetes soon after.”

Follow-up within is important because roughly 30% of patients with stress hyperglycemia (increases in blood glucose during an acute illness) will develop diabetes within a year, according to Dr. Galindo.

“We do not know in COVID-10 patients if it is only 30%,” he said, “Our thinking in our group is that it’s probably higher.”

Dr. Bajpeyi and coauthors reported no disclosures. Dr. Galindo reported disclosures related to Abbott Diabetes, Boehringer Ingelheim International, Eli Lilly, Novo Nordisk, Sanofi US, Valeritas, and Dexcom.

Time-restricted eating – that is, reducing the number of hours a person is allowed to eat during the day – may produce a modest 1%-4% weight loss, even without cutting calories, early studies in humans suggest. But more research is needed to provide definitive evidence.

This type of intermittent fasting also appears to improve blood glucose, blood pressure, and oxidative stress, said Courtney M. Peterson, PhD, a researcher at the University of Alabama at Birmingham, summarizing what is known about the potential weight-loss strategy at the annual scientific sessions of the American Diabetes Association.

The best results were seen with early time-restricted eating (that is, ending the nighttime fasting early in the day) and allowing a person to eat 8-10 hours each day (for example, 8 a.m. to 4 p.m. or 8 a.m. to 6 p.m.), with fasting and only water allowed the remaining hours, she reported.

However, the 3 dozen or so studies in humans to date are mainly small, pilot, or single-arm studies lasting up to 3 months, and there are only three main randomized, controlled trials with 25 or more participants in each group.

Large trials with around 260 participants are needed, Dr. Peterson said, “before drawing definitive conclusions” about the weight-loss and cardiometabolic benefits of time-restricted eating.

Invited to comment, session chair Lisa S. Chow, MD, an associate professor of medicine in the endocrine and diabetes division at the University of Minnesota, Minneapolis, similarly said: “I think time-restricted eating is promising because of its simple message and noted weight-loss benefit, yet more data are needed.”

“Many uncertainties remain,” she added, “including the potential concern that time-restricted eating may be associated with lean [muscle] mass loss and identifying the populations most likely to benefit from time-restricted eating,” she said.
 

36 small studies, a review, a meta-analysis, 3 RCTs

There have been about three dozen small studies of time-restricted eating in humans, which examined 4- to 11-hour eating windows, Dr. Peterson explained.

A systematic review of 23 trials of time-restricted eating reported that, on average, participants lost 3% of their initial weight. And a meta-analysis of 19 trials in 475 participants found a –0.9 kg mean difference effect for weight loss.

However, those two analyses did not compare time-restricted eating with a control treatment, she stressed.

The largest randomized, controlled trial is a 12-week study in 271 adults with nonalcoholic fatty liver disease in China, Dr. Peterson said.

The researchers compared three groups:

• Alternate-day modified fasting: healthy meal provided.
• Time-restricted eating: 8-hour window, healthy meal provided.
• Control: 20% calorie reduction, no meal provided.

At 4 and 12 weeks, adults in the two treatment groups lost more weight than those in the control group, but “this was not a fair comparison” because of the lack of a provided meal in the control group, Dr. Peterson pointed out.

The next largest randomized, controlled study is the 12-week TREAT trial, published online in JAMA Internal Medicine in October 2020.

The researchers, from the University of California, San Francisco, randomized 116 adults into two groups:

• 8-hour time-restricted eating from noon to 8 p.m..
• Control: three meals/day.

Time-restricted eating did not lead to greater weight loss, compared with three structured meals a day, which was not surprising, Dr. Chow said, as “participants just reported whether they were engaged in time-restricted eating in a yes/no answer.”

Moreover, “there was no objective measure of their eating window. From our study, we showed that the extent of eating window restriction matters, not just time-restricted eating participation.”

Also, in TREAT, the eating window was noon to 8 p.m. (considered late for time-restricted eating), and the trial also allowed noncaloric beverages outside the window, whereas most studies only allow water and medications. 

Lastly, TREAT showed that time-restricted eating reduced weight, compared with baseline, but the weight loss was not significant, compared with the control group, and there was a wide spread of effects (that is, some lost a lot of weight, others didn’t lose much weight).

“That being said, the JAMA Internal Medicine paper is the largest paper to date of time-restricted eating randomized versus control, so its findings need to be acknowledged and recognized,” Dr. Chow said.

Peterson reported that her group recently completed a 14-week intervention in 90 adults with obesity divided into two groups:

• Control: Continuous energy restriction, self-selected ≥ 12-hour window.
• Early time-restricted eating: 8-hour window from 7 a.m. to 3 p.m.

The findings will provide further insight into the benefits of time-restricted eating.
 

How might time-restricted eating lead to weight loss?

Dr. Peterson concluded by presenting data suggesting how time-restricted eating may induce weight loss.

In a 4-day crossover study in 11 overweight adults, time-restricted eating did not affect energy expenditure, but it lessened swings in subjective hunger, improved appetite hormones including ghrelin, and increased fat oxidation.

Most trials have reported that time-restricted eating improves one or more cardiometabolic endpoints, she noted.

Early time-restricted eating was associated with improved insulin sensitivity and secretion, blood pressure, and oxidative stress, but not better lipid levels.

In contrast, compared with eating 3 meals/day (control), late time-restricted eating (eating 1 meal/day from 5 p.m. to 9 p.m.) was associated with worsened cardiometabolic health (glucose, insulin, blood pressure, and lipid levels) in an 8-week crossover study in 15 participants.

Dr. Peterson and Dr. Chow reported no relevant financial relationships.

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

Time-restricted eating – that is, reducing the number of hours a person is allowed to eat during the day – may produce a modest 1%-4% weight loss, even without cutting calories, early studies in humans suggest. But more research is needed to provide definitive evidence.

This type of intermittent fasting also appears to improve blood glucose, blood pressure, and oxidative stress, said Courtney M. Peterson, PhD, a researcher at the University of Alabama at Birmingham, summarizing what is known about the potential weight-loss strategy at the annual scientific sessions of the American Diabetes Association.

The best results were seen with early time-restricted eating (that is, ending the nighttime fasting early in the day) and allowing a person to eat 8-10 hours each day (for example, 8 a.m. to 4 p.m. or 8 a.m. to 6 p.m.), with fasting and only water allowed the remaining hours, she reported.

However, the 3 dozen or so studies in humans to date are mainly small, pilot, or single-arm studies lasting up to 3 months, and there are only three main randomized, controlled trials with 25 or more participants in each group.

Large trials with around 260 participants are needed, Dr. Peterson said, “before drawing definitive conclusions” about the weight-loss and cardiometabolic benefits of time-restricted eating.

Invited to comment, session chair Lisa S. Chow, MD, an associate professor of medicine in the endocrine and diabetes division at the University of Minnesota, Minneapolis, similarly said: “I think time-restricted eating is promising because of its simple message and noted weight-loss benefit, yet more data are needed.”

“Many uncertainties remain,” she added, “including the potential concern that time-restricted eating may be associated with lean [muscle] mass loss and identifying the populations most likely to benefit from time-restricted eating,” she said.
 

36 small studies, a review, a meta-analysis, 3 RCTs

There have been about three dozen small studies of time-restricted eating in humans, which examined 4- to 11-hour eating windows, Dr. Peterson explained.

A systematic review of 23 trials of time-restricted eating reported that, on average, participants lost 3% of their initial weight. And a meta-analysis of 19 trials in 475 participants found a –0.9 kg mean difference effect for weight loss.

However, those two analyses did not compare time-restricted eating with a control treatment, she stressed.

The largest randomized, controlled trial is a 12-week study in 271 adults with nonalcoholic fatty liver disease in China, Dr. Peterson said.

The researchers compared three groups:

• Alternate-day modified fasting: healthy meal provided.
• Time-restricted eating: 8-hour window, healthy meal provided.
• Control: 20% calorie reduction, no meal provided.

At 4 and 12 weeks, adults in the two treatment groups lost more weight than those in the control group, but “this was not a fair comparison” because of the lack of a provided meal in the control group, Dr. Peterson pointed out.

The next largest randomized, controlled study is the 12-week TREAT trial, published online in JAMA Internal Medicine in October 2020.

The researchers, from the University of California, San Francisco, randomized 116 adults into two groups:

• 8-hour time-restricted eating from noon to 8 p.m..
• Control: three meals/day.

Time-restricted eating did not lead to greater weight loss, compared with three structured meals a day, which was not surprising, Dr. Chow said, as “participants just reported whether they were engaged in time-restricted eating in a yes/no answer.”

Moreover, “there was no objective measure of their eating window. From our study, we showed that the extent of eating window restriction matters, not just time-restricted eating participation.”

Also, in TREAT, the eating window was noon to 8 p.m. (considered late for time-restricted eating), and the trial also allowed noncaloric beverages outside the window, whereas most studies only allow water and medications. 

Lastly, TREAT showed that time-restricted eating reduced weight, compared with baseline, but the weight loss was not significant, compared with the control group, and there was a wide spread of effects (that is, some lost a lot of weight, others didn’t lose much weight).

“That being said, the JAMA Internal Medicine paper is the largest paper to date of time-restricted eating randomized versus control, so its findings need to be acknowledged and recognized,” Dr. Chow said.

Peterson reported that her group recently completed a 14-week intervention in 90 adults with obesity divided into two groups:

• Control: Continuous energy restriction, self-selected ≥ 12-hour window.
• Early time-restricted eating: 8-hour window from 7 a.m. to 3 p.m.

The findings will provide further insight into the benefits of time-restricted eating.
 

How might time-restricted eating lead to weight loss?

Dr. Peterson concluded by presenting data suggesting how time-restricted eating may induce weight loss.

In a 4-day crossover study in 11 overweight adults, time-restricted eating did not affect energy expenditure, but it lessened swings in subjective hunger, improved appetite hormones including ghrelin, and increased fat oxidation.

Most trials have reported that time-restricted eating improves one or more cardiometabolic endpoints, she noted.

Early time-restricted eating was associated with improved insulin sensitivity and secretion, blood pressure, and oxidative stress, but not better lipid levels.

In contrast, compared with eating 3 meals/day (control), late time-restricted eating (eating 1 meal/day from 5 p.m. to 9 p.m.) was associated with worsened cardiometabolic health (glucose, insulin, blood pressure, and lipid levels) in an 8-week crossover study in 15 participants.

Dr. Peterson and Dr. Chow reported no relevant financial relationships.

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

Time-restricted eating – that is, reducing the number of hours a person is allowed to eat during the day – may produce a modest 1%-4% weight loss, even without cutting calories, early studies in humans suggest. But more research is needed to provide definitive evidence.

This type of intermittent fasting also appears to improve blood glucose, blood pressure, and oxidative stress, said Courtney M. Peterson, PhD, a researcher at the University of Alabama at Birmingham, summarizing what is known about the potential weight-loss strategy at the annual scientific sessions of the American Diabetes Association.

The best results were seen with early time-restricted eating (that is, ending the nighttime fasting early in the day) and allowing a person to eat 8-10 hours each day (for example, 8 a.m. to 4 p.m. or 8 a.m. to 6 p.m.), with fasting and only water allowed the remaining hours, she reported.

However, the 3 dozen or so studies in humans to date are mainly small, pilot, or single-arm studies lasting up to 3 months, and there are only three main randomized, controlled trials with 25 or more participants in each group.

Large trials with around 260 participants are needed, Dr. Peterson said, “before drawing definitive conclusions” about the weight-loss and cardiometabolic benefits of time-restricted eating.

Invited to comment, session chair Lisa S. Chow, MD, an associate professor of medicine in the endocrine and diabetes division at the University of Minnesota, Minneapolis, similarly said: “I think time-restricted eating is promising because of its simple message and noted weight-loss benefit, yet more data are needed.”

“Many uncertainties remain,” she added, “including the potential concern that time-restricted eating may be associated with lean [muscle] mass loss and identifying the populations most likely to benefit from time-restricted eating,” she said.
 

36 small studies, a review, a meta-analysis, 3 RCTs

There have been about three dozen small studies of time-restricted eating in humans, which examined 4- to 11-hour eating windows, Dr. Peterson explained.

A systematic review of 23 trials of time-restricted eating reported that, on average, participants lost 3% of their initial weight. And a meta-analysis of 19 trials in 475 participants found a –0.9 kg mean difference effect for weight loss.

However, those two analyses did not compare time-restricted eating with a control treatment, she stressed.

The largest randomized, controlled trial is a 12-week study in 271 adults with nonalcoholic fatty liver disease in China, Dr. Peterson said.

The researchers compared three groups:

• Alternate-day modified fasting: healthy meal provided.
• Time-restricted eating: 8-hour window, healthy meal provided.
• Control: 20% calorie reduction, no meal provided.

At 4 and 12 weeks, adults in the two treatment groups lost more weight than those in the control group, but “this was not a fair comparison” because of the lack of a provided meal in the control group, Dr. Peterson pointed out.

The next largest randomized, controlled study is the 12-week TREAT trial, published online in JAMA Internal Medicine in October 2020.

The researchers, from the University of California, San Francisco, randomized 116 adults into two groups:

• 8-hour time-restricted eating from noon to 8 p.m..
• Control: three meals/day.

Time-restricted eating did not lead to greater weight loss, compared with three structured meals a day, which was not surprising, Dr. Chow said, as “participants just reported whether they were engaged in time-restricted eating in a yes/no answer.”

Moreover, “there was no objective measure of their eating window. From our study, we showed that the extent of eating window restriction matters, not just time-restricted eating participation.”

Also, in TREAT, the eating window was noon to 8 p.m. (considered late for time-restricted eating), and the trial also allowed noncaloric beverages outside the window, whereas most studies only allow water and medications. 

Lastly, TREAT showed that time-restricted eating reduced weight, compared with baseline, but the weight loss was not significant, compared with the control group, and there was a wide spread of effects (that is, some lost a lot of weight, others didn’t lose much weight).

“That being said, the JAMA Internal Medicine paper is the largest paper to date of time-restricted eating randomized versus control, so its findings need to be acknowledged and recognized,” Dr. Chow said.

Peterson reported that her group recently completed a 14-week intervention in 90 adults with obesity divided into two groups:

• Control: Continuous energy restriction, self-selected ≥ 12-hour window.
• Early time-restricted eating: 8-hour window from 7 a.m. to 3 p.m.

The findings will provide further insight into the benefits of time-restricted eating.
 

How might time-restricted eating lead to weight loss?

Dr. Peterson concluded by presenting data suggesting how time-restricted eating may induce weight loss.

In a 4-day crossover study in 11 overweight adults, time-restricted eating did not affect energy expenditure, but it lessened swings in subjective hunger, improved appetite hormones including ghrelin, and increased fat oxidation.

Most trials have reported that time-restricted eating improves one or more cardiometabolic endpoints, she noted.

Early time-restricted eating was associated with improved insulin sensitivity and secretion, blood pressure, and oxidative stress, but not better lipid levels.

In contrast, compared with eating 3 meals/day (control), late time-restricted eating (eating 1 meal/day from 5 p.m. to 9 p.m.) was associated with worsened cardiometabolic health (glucose, insulin, blood pressure, and lipid levels) in an 8-week crossover study in 15 participants.

Dr. Peterson and Dr. Chow reported no relevant financial relationships.

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

After treatment with ruxolitinib cream for 52 weeks, between 60% and 80% of atopic dermatitis patients maintained clear or almost clear skin, with no safety signals, results from a long-term analysis of clinical trial data showed.

“The incidence of application-site reactions was low, and there were no clinically meaningful changes or trends in hematologic parameters,” Kim Papp, MD, PhD, said during the Revolutionizing Atopic Dermatitis symposium.

Ruxolitinib cream is a selective Janus kinase 1/JAK2 inhibitor being developed by Incyte for the treatment of atopic dermatitis (AD).

According to a press release from the company, the Food and Drug Administration has extended the New Drug Application review period for the agent by 3 months to September 2021. If approved, it would become first topical JAK inhibitor for use in dermatology.

In two phase 3, randomized studies of identical design involving 1,249 patients aged 12 and older with AD – TRuE-AD1 and TRuE-AD2 – ruxolitinib cream demonstrated anti-inflammatory activity, with rapid and sustained antipruritic action, compared with vehicle. To be eligible for the trials patients with an Investigator’s Global Assessment (IGA) score of 2 or 3 and 3%-20% of affected body surface area (BSA) were randomized (2:2:1) to twice-daily 0.75% ruxolitinib cream, 1.5% ruxolitinib cream, or vehicle cream for 8 continuous weeks.

A recently published report found that significantly more patients in TRuE-AD1 and TRuE-AD2 achieved IGA treatment success with 0.75% (50% vs. 39%, respectively) and 1.5% ruxolitinib cream (53.8% vs. 51.3%), compared with vehicle (15.1% vs. 7.6%; P < .0001) at week 8. In addition, significant reductions in itch, compared with vehicle, were reported within 12 hours of first applying 1.5% ruxolitinib cream (P < .05).
 

Longterm data

During the symposium, Dr. Papp presented long-term safety data of ruxolitinib cream in patients who were followed for an additional 44 weeks. Those initially randomized to vehicle were rerandomized 1:1 (blinded) to either ruxolitinib cream regimen. They were instructed to treat skin areas with active AD only and to stop treatment 3 days after clearance of lesions, and to restart treatment with ruxolitinib cream at the first sign of recurrence. Safety and tolerability were assessed by frequency and severity of adverse events, while disease control was measured by the proportion of patients with an IGA score of 0 or 1 and the affected BSA.

Dr. Papp, a dermatologist and founder of Probity Medical Research, Waterloo, Ont., reported that 543 patients from TRuE-AD1 and 530 from TRuE-AD2 entered the long-term analysis and that about 78% of these patients completed the study. From weeks 12 to 52, the proportion of patients with an IGA score of 0 or 1 with 0.75% and 1.5% ruxolitinib cream ranged from 62%-77% and 67%-77%, respectively, in TRuE-AD1 to 60%-77% and 72%-80% in TRuE-AD2.

The measured mean total affected BSA was less than 3% throughout the follow-up period in the 1.5% ruxolitinib cream arm in TRuE-AD1 and TRuE-AD2 and was less than 3% in the 0.75% ruxolitinib cream arm during most of the study period.

In a pooled safety analysis, treatment-emergent adverse events (TEAEs) were reported in 60% and 54% of patients who applied 0.75% and 1.5% ruxolitinib cream, respectively, over 44 weeks. The frequency of application-site reactions remained low. Specifically, treatment-related adverse events were reported in 5% of patients who applied 0.75% ruxolitinib cream and in 3% of patients who applied 1.5% ruxolitinib cream; none were serious. TEAEs led to discontinuation in 2% of patients in the 0.75% ruxolitinib cream group, and no patients in the 1.5% ruxolitinib cream group.

“The most common treatment adverse events were upper respiratory tract infections and nasopharyngitis,” Dr. Papp said. “When looking at exposure-adjusted adverse events, we see that there is a high degree of similarity between any of the TEAEs across all of the treatment groups in both studies. We also see that it was patients on the vehicle who experienced the greatest number of application-site reactions.”

Dr. Papp disclosed that he has received honoraria or clinical research grants as a consultant, speaker, scientific officer, advisory board member, and/or steering committee member for several pharmaceutical companies, including Incyte.

dbrunk@mdedge.com

After treatment with ruxolitinib cream for 52 weeks, between 60% and 80% of atopic dermatitis patients maintained clear or almost clear skin, with no safety signals, results from a long-term analysis of clinical trial data showed.

“The incidence of application-site reactions was low, and there were no clinically meaningful changes or trends in hematologic parameters,” Kim Papp, MD, PhD, said during the Revolutionizing Atopic Dermatitis symposium.

Ruxolitinib cream is a selective Janus kinase 1/JAK2 inhibitor being developed by Incyte for the treatment of atopic dermatitis (AD).

According to a press release from the company, the Food and Drug Administration has extended the New Drug Application review period for the agent by 3 months to September 2021. If approved, it would become first topical JAK inhibitor for use in dermatology.

In two phase 3, randomized studies of identical design involving 1,249 patients aged 12 and older with AD – TRuE-AD1 and TRuE-AD2 – ruxolitinib cream demonstrated anti-inflammatory activity, with rapid and sustained antipruritic action, compared with vehicle. To be eligible for the trials patients with an Investigator’s Global Assessment (IGA) score of 2 or 3 and 3%-20% of affected body surface area (BSA) were randomized (2:2:1) to twice-daily 0.75% ruxolitinib cream, 1.5% ruxolitinib cream, or vehicle cream for 8 continuous weeks.

A recently published report found that significantly more patients in TRuE-AD1 and TRuE-AD2 achieved IGA treatment success with 0.75% (50% vs. 39%, respectively) and 1.5% ruxolitinib cream (53.8% vs. 51.3%), compared with vehicle (15.1% vs. 7.6%; P < .0001) at week 8. In addition, significant reductions in itch, compared with vehicle, were reported within 12 hours of first applying 1.5% ruxolitinib cream (P < .05).
 

Longterm data

During the symposium, Dr. Papp presented long-term safety data of ruxolitinib cream in patients who were followed for an additional 44 weeks. Those initially randomized to vehicle were rerandomized 1:1 (blinded) to either ruxolitinib cream regimen. They were instructed to treat skin areas with active AD only and to stop treatment 3 days after clearance of lesions, and to restart treatment with ruxolitinib cream at the first sign of recurrence. Safety and tolerability were assessed by frequency and severity of adverse events, while disease control was measured by the proportion of patients with an IGA score of 0 or 1 and the affected BSA.

Dr. Papp, a dermatologist and founder of Probity Medical Research, Waterloo, Ont., reported that 543 patients from TRuE-AD1 and 530 from TRuE-AD2 entered the long-term analysis and that about 78% of these patients completed the study. From weeks 12 to 52, the proportion of patients with an IGA score of 0 or 1 with 0.75% and 1.5% ruxolitinib cream ranged from 62%-77% and 67%-77%, respectively, in TRuE-AD1 to 60%-77% and 72%-80% in TRuE-AD2.

The measured mean total affected BSA was less than 3% throughout the follow-up period in the 1.5% ruxolitinib cream arm in TRuE-AD1 and TRuE-AD2 and was less than 3% in the 0.75% ruxolitinib cream arm during most of the study period.

In a pooled safety analysis, treatment-emergent adverse events (TEAEs) were reported in 60% and 54% of patients who applied 0.75% and 1.5% ruxolitinib cream, respectively, over 44 weeks. The frequency of application-site reactions remained low. Specifically, treatment-related adverse events were reported in 5% of patients who applied 0.75% ruxolitinib cream and in 3% of patients who applied 1.5% ruxolitinib cream; none were serious. TEAEs led to discontinuation in 2% of patients in the 0.75% ruxolitinib cream group, and no patients in the 1.5% ruxolitinib cream group.

“The most common treatment adverse events were upper respiratory tract infections and nasopharyngitis,” Dr. Papp said. “When looking at exposure-adjusted adverse events, we see that there is a high degree of similarity between any of the TEAEs across all of the treatment groups in both studies. We also see that it was patients on the vehicle who experienced the greatest number of application-site reactions.”

Dr. Papp disclosed that he has received honoraria or clinical research grants as a consultant, speaker, scientific officer, advisory board member, and/or steering committee member for several pharmaceutical companies, including Incyte.

dbrunk@mdedge.com

After treatment with ruxolitinib cream for 52 weeks, between 60% and 80% of atopic dermatitis patients maintained clear or almost clear skin, with no safety signals, results from a long-term analysis of clinical trial data showed.

“The incidence of application-site reactions was low, and there were no clinically meaningful changes or trends in hematologic parameters,” Kim Papp, MD, PhD, said during the Revolutionizing Atopic Dermatitis symposium.

Ruxolitinib cream is a selective Janus kinase 1/JAK2 inhibitor being developed by Incyte for the treatment of atopic dermatitis (AD).

According to a press release from the company, the Food and Drug Administration has extended the New Drug Application review period for the agent by 3 months to September 2021. If approved, it would become first topical JAK inhibitor for use in dermatology.

In two phase 3, randomized studies of identical design involving 1,249 patients aged 12 and older with AD – TRuE-AD1 and TRuE-AD2 – ruxolitinib cream demonstrated anti-inflammatory activity, with rapid and sustained antipruritic action, compared with vehicle. To be eligible for the trials patients with an Investigator’s Global Assessment (IGA) score of 2 or 3 and 3%-20% of affected body surface area (BSA) were randomized (2:2:1) to twice-daily 0.75% ruxolitinib cream, 1.5% ruxolitinib cream, or vehicle cream for 8 continuous weeks.

A recently published report found that significantly more patients in TRuE-AD1 and TRuE-AD2 achieved IGA treatment success with 0.75% (50% vs. 39%, respectively) and 1.5% ruxolitinib cream (53.8% vs. 51.3%), compared with vehicle (15.1% vs. 7.6%; P < .0001) at week 8. In addition, significant reductions in itch, compared with vehicle, were reported within 12 hours of first applying 1.5% ruxolitinib cream (P < .05).
 

Longterm data

During the symposium, Dr. Papp presented long-term safety data of ruxolitinib cream in patients who were followed for an additional 44 weeks. Those initially randomized to vehicle were rerandomized 1:1 (blinded) to either ruxolitinib cream regimen. They were instructed to treat skin areas with active AD only and to stop treatment 3 days after clearance of lesions, and to restart treatment with ruxolitinib cream at the first sign of recurrence. Safety and tolerability were assessed by frequency and severity of adverse events, while disease control was measured by the proportion of patients with an IGA score of 0 or 1 and the affected BSA.

Dr. Papp, a dermatologist and founder of Probity Medical Research, Waterloo, Ont., reported that 543 patients from TRuE-AD1 and 530 from TRuE-AD2 entered the long-term analysis and that about 78% of these patients completed the study. From weeks 12 to 52, the proportion of patients with an IGA score of 0 or 1 with 0.75% and 1.5% ruxolitinib cream ranged from 62%-77% and 67%-77%, respectively, in TRuE-AD1 to 60%-77% and 72%-80% in TRuE-AD2.

The measured mean total affected BSA was less than 3% throughout the follow-up period in the 1.5% ruxolitinib cream arm in TRuE-AD1 and TRuE-AD2 and was less than 3% in the 0.75% ruxolitinib cream arm during most of the study period.

In a pooled safety analysis, treatment-emergent adverse events (TEAEs) were reported in 60% and 54% of patients who applied 0.75% and 1.5% ruxolitinib cream, respectively, over 44 weeks. The frequency of application-site reactions remained low. Specifically, treatment-related adverse events were reported in 5% of patients who applied 0.75% ruxolitinib cream and in 3% of patients who applied 1.5% ruxolitinib cream; none were serious. TEAEs led to discontinuation in 2% of patients in the 0.75% ruxolitinib cream group, and no patients in the 1.5% ruxolitinib cream group.

“The most common treatment adverse events were upper respiratory tract infections and nasopharyngitis,” Dr. Papp said. “When looking at exposure-adjusted adverse events, we see that there is a high degree of similarity between any of the TEAEs across all of the treatment groups in both studies. We also see that it was patients on the vehicle who experienced the greatest number of application-site reactions.”

Dr. Papp disclosed that he has received honoraria or clinical research grants as a consultant, speaker, scientific officer, advisory board member, and/or steering committee member for several pharmaceutical companies, including Incyte.

dbrunk@mdedge.com

More evidence suggests the severity of internet addiction (IA) is directly related to the severity of sleep problems in youth.

Results from a study of more than 4,000 adolescent students show IA severity was linked to less sleep and to daytime sleepiness. In addition, boys aged 12-14 years who were addicted to computer games versus social media networking were the most affected.

Sleep issues could be “easily detectable manifestations of pathological internet addiction,” investigator Sergey Tereshchenko, PhD, Scientific Research Institute for Medical Problems of the North, Krasnoyask State Medical University, Russia, told this news organization.

These sleep problems require attention and correction, Dr. Tereshchenko added.

The findings were presented at the virtual Congress of the European Academy of Neurology 2021.
 

New phenomenon

IA is a relatively new psychological phenomenon and is most prevalent in “socially vulnerable groups,” such as adolescents, Dr. Tereshchenko said.

He cited numerous studies that have “convincingly demonstrated” IA is comorbid with a broad range of psychopathologic conditions, including depression, anxiety, and attention deficit hyperactivity disorder.

There is also growing evidence, including from systematic reviews in 2014 and 2019, that IA affects a wide range of sleep parameters.

However, most studies in adolescents have used only one psychometric tool to assess addiction, revealing only the “general IA pattern” and not the type of IA, Dr. Tereshchenko noted.

Adolescents may not be addicted to the internet itself but to certain behaviors like gaming or social networking, he said.

The “undoubted advantage” of his team’s research is the use of more than one tool, making it possible to “verify the predominant content of the addiction,” he added.

The investigators previously assessed general prevalence of IA in adolescents in Siberia and found about 6.8% of participants displayed pathological IA behavior – and that gaming addiction is more common in boys whereas addiction to social networking is more common in girls.

This prevalence rate is lower than in the Philippines (21.1%), Hong Kong (16.4%), Malaysia (14.1%), China (11%), and South Korea (9.7%), but slightly higher than in Japan (6.2%).

IA prevalence among adolescents in Europe ranges from 1% to 11%, with an average of 4.4%, said Dr. Tereshchenko.
 

Siberian students’ sleep

The current study included 4,344 students aged 12-18 years (average age, about 15 years) from 10 public schools in three large cities of Central Siberia (Krasnoyarsk, Abakan, and Kyzyl). There were slightly more girls than boys in the study sample.

Participants completed the Russian language version of the Chen Internet Addiction Scale (CIAS), which covers five symptomatic criteria for addictive behavior: withdrawal symptoms, signs of tolerance, compulsive use, psychological or physical problems, and difficulty managing time.

In this questionnaire, respondents rate several statements regarding the effect of internet use, each on a 4-point Likert scale: not at all (1 point), a little bit (2 points), moderately (3 points) and extremely (4). The total score ranges from 26 to 104.

A CIAS score of 26-42 indicates adaptive internet use, 43-64 indicates maladaptive internet use, and 65 and above indicates pathological internet use (PIU), which was classified as “internet-addicted.”

The researchers also used the nine-item Social Media Disorder Scale, as well as the Pittsburgh Sleep Quality Index to assess nighttime sleep.

Among other questions, teens were asked how long it usually took them to fall asleep and when they typically went to bed and woke up on school nights.

For daytime sleepiness, investigators used the targeted Pediatric Daytime Sleepiness Scale questionnaire, making them among the few research groups to use this psychometric instrument, Dr. Tereshchenko noted.

After parental consent was given, students completed the tests at the end of the day’s lessons. Total test time was about 45 minutes.
 

Sleep disturbance

Initial study results showed that compared with the other groups, adolescents with PIU tended to go to bed later, wake up later, take longer to fall asleep, sleep less at night, have more nighttime awakenings, and have more daytime sleepiness.

Sleep quality was the most impaired in boys aged 12-14 years who are addicted to internet computer games.

“In this group, 5 of the 6 sleep assessment parameters we studied were changed,” Dr. Tereshchenko reported.

Decreased total nighttime sleep was more common in older adolescents.

On average, boys and girls aged 15-18 years got less than the recommended 8 hours of sleep per night. Boys with IA got only about 6.4 hours per night and girls with IA got about 6.6 hours.

Interestingly, IA is generally more prevalent among teen girls than boys in Russia, which is not the case in Europe and North America, Dr. Tereshchenko noted.

Mechanisms linking IA and sleep disorders are not clear, but the relationship is probably multifactorial and perhaps interrelated, creating something of a “vicious circle,” he said.

“Sleep disturbances, which reflect psychosocial problems, depression, and anxiety-phobic disorders, can precede and contribute to IA. On the other hand, sleep disturbances such as insomnia can lead to increased use of the internet in the evening and at night, further exacerbating the problem,” said Dr. Tereshchenko.

Research is lacking on useful treatments for youth with IA, but these kids would likely benefit from behavioral therapy approaches, he added.
 

No escape?

Commenting on the study for this news organization, Maurice M. Ohayon, MD, DSc, PhD, director of the Stanford Sleep Epidemiology Research Center, Stanford University, California, said the topic of youth IA is “very important.”

Previous research in this field has shown a major impact from IA not only on sleep but also on mood – with irritability, depression, and even thoughts of suicide being possible red flags, said Dr. Ohayon, who was not involved in the current study.

Interestingly, his own research has also found that young teenage boys are most at risk for gaming addiction.

Although internet gaming has some positive effects, such as fostering leadership skills and relationships, it has become increasingly violent and isolating, with more adult professional gamers preying on younger players, Dr. Ohayon said.

“The major problem is that it’s putting children in a virtual world from which it’s difficult to escape,” he added.

Dr. Ohayon also noted concern about future developmental effects in kids who play video games for hours on end without coming out of their bedroom and with no physical contact with fellow players.

Parents should intervene before this situation occurs and limit the time their children spend on the gaming console, he said.

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

More evidence suggests the severity of internet addiction (IA) is directly related to the severity of sleep problems in youth.

Results from a study of more than 4,000 adolescent students show IA severity was linked to less sleep and to daytime sleepiness. In addition, boys aged 12-14 years who were addicted to computer games versus social media networking were the most affected.

Sleep issues could be “easily detectable manifestations of pathological internet addiction,” investigator Sergey Tereshchenko, PhD, Scientific Research Institute for Medical Problems of the North, Krasnoyask State Medical University, Russia, told this news organization.

These sleep problems require attention and correction, Dr. Tereshchenko added.

The findings were presented at the virtual Congress of the European Academy of Neurology 2021.
 

New phenomenon

IA is a relatively new psychological phenomenon and is most prevalent in “socially vulnerable groups,” such as adolescents, Dr. Tereshchenko said.

He cited numerous studies that have “convincingly demonstrated” IA is comorbid with a broad range of psychopathologic conditions, including depression, anxiety, and attention deficit hyperactivity disorder.

There is also growing evidence, including from systematic reviews in 2014 and 2019, that IA affects a wide range of sleep parameters.

However, most studies in adolescents have used only one psychometric tool to assess addiction, revealing only the “general IA pattern” and not the type of IA, Dr. Tereshchenko noted.

Adolescents may not be addicted to the internet itself but to certain behaviors like gaming or social networking, he said.

The “undoubted advantage” of his team’s research is the use of more than one tool, making it possible to “verify the predominant content of the addiction,” he added.

The investigators previously assessed general prevalence of IA in adolescents in Siberia and found about 6.8% of participants displayed pathological IA behavior – and that gaming addiction is more common in boys whereas addiction to social networking is more common in girls.

This prevalence rate is lower than in the Philippines (21.1%), Hong Kong (16.4%), Malaysia (14.1%), China (11%), and South Korea (9.7%), but slightly higher than in Japan (6.2%).

IA prevalence among adolescents in Europe ranges from 1% to 11%, with an average of 4.4%, said Dr. Tereshchenko.
 

Siberian students’ sleep

The current study included 4,344 students aged 12-18 years (average age, about 15 years) from 10 public schools in three large cities of Central Siberia (Krasnoyarsk, Abakan, and Kyzyl). There were slightly more girls than boys in the study sample.

Participants completed the Russian language version of the Chen Internet Addiction Scale (CIAS), which covers five symptomatic criteria for addictive behavior: withdrawal symptoms, signs of tolerance, compulsive use, psychological or physical problems, and difficulty managing time.

In this questionnaire, respondents rate several statements regarding the effect of internet use, each on a 4-point Likert scale: not at all (1 point), a little bit (2 points), moderately (3 points) and extremely (4). The total score ranges from 26 to 104.

A CIAS score of 26-42 indicates adaptive internet use, 43-64 indicates maladaptive internet use, and 65 and above indicates pathological internet use (PIU), which was classified as “internet-addicted.”

The researchers also used the nine-item Social Media Disorder Scale, as well as the Pittsburgh Sleep Quality Index to assess nighttime sleep.

Among other questions, teens were asked how long it usually took them to fall asleep and when they typically went to bed and woke up on school nights.

For daytime sleepiness, investigators used the targeted Pediatric Daytime Sleepiness Scale questionnaire, making them among the few research groups to use this psychometric instrument, Dr. Tereshchenko noted.

After parental consent was given, students completed the tests at the end of the day’s lessons. Total test time was about 45 minutes.
 

Sleep disturbance

Initial study results showed that compared with the other groups, adolescents with PIU tended to go to bed later, wake up later, take longer to fall asleep, sleep less at night, have more nighttime awakenings, and have more daytime sleepiness.

Sleep quality was the most impaired in boys aged 12-14 years who are addicted to internet computer games.

“In this group, 5 of the 6 sleep assessment parameters we studied were changed,” Dr. Tereshchenko reported.

Decreased total nighttime sleep was more common in older adolescents.

On average, boys and girls aged 15-18 years got less than the recommended 8 hours of sleep per night. Boys with IA got only about 6.4 hours per night and girls with IA got about 6.6 hours.

Interestingly, IA is generally more prevalent among teen girls than boys in Russia, which is not the case in Europe and North America, Dr. Tereshchenko noted.

Mechanisms linking IA and sleep disorders are not clear, but the relationship is probably multifactorial and perhaps interrelated, creating something of a “vicious circle,” he said.

“Sleep disturbances, which reflect psychosocial problems, depression, and anxiety-phobic disorders, can precede and contribute to IA. On the other hand, sleep disturbances such as insomnia can lead to increased use of the internet in the evening and at night, further exacerbating the problem,” said Dr. Tereshchenko.

Research is lacking on useful treatments for youth with IA, but these kids would likely benefit from behavioral therapy approaches, he added.
 

No escape?

Commenting on the study for this news organization, Maurice M. Ohayon, MD, DSc, PhD, director of the Stanford Sleep Epidemiology Research Center, Stanford University, California, said the topic of youth IA is “very important.”

Previous research in this field has shown a major impact from IA not only on sleep but also on mood – with irritability, depression, and even thoughts of suicide being possible red flags, said Dr. Ohayon, who was not involved in the current study.

Interestingly, his own research has also found that young teenage boys are most at risk for gaming addiction.

Although internet gaming has some positive effects, such as fostering leadership skills and relationships, it has become increasingly violent and isolating, with more adult professional gamers preying on younger players, Dr. Ohayon said.

“The major problem is that it’s putting children in a virtual world from which it’s difficult to escape,” he added.

Dr. Ohayon also noted concern about future developmental effects in kids who play video games for hours on end without coming out of their bedroom and with no physical contact with fellow players.

Parents should intervene before this situation occurs and limit the time their children spend on the gaming console, he said.

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

More evidence suggests the severity of internet addiction (IA) is directly related to the severity of sleep problems in youth.

Results from a study of more than 4,000 adolescent students show IA severity was linked to less sleep and to daytime sleepiness. In addition, boys aged 12-14 years who were addicted to computer games versus social media networking were the most affected.

Sleep issues could be “easily detectable manifestations of pathological internet addiction,” investigator Sergey Tereshchenko, PhD, Scientific Research Institute for Medical Problems of the North, Krasnoyask State Medical University, Russia, told this news organization.

These sleep problems require attention and correction, Dr. Tereshchenko added.

The findings were presented at the virtual Congress of the European Academy of Neurology 2021.
 

New phenomenon

IA is a relatively new psychological phenomenon and is most prevalent in “socially vulnerable groups,” such as adolescents, Dr. Tereshchenko said.

He cited numerous studies that have “convincingly demonstrated” IA is comorbid with a broad range of psychopathologic conditions, including depression, anxiety, and attention deficit hyperactivity disorder.

There is also growing evidence, including from systematic reviews in 2014 and 2019, that IA affects a wide range of sleep parameters.

However, most studies in adolescents have used only one psychometric tool to assess addiction, revealing only the “general IA pattern” and not the type of IA, Dr. Tereshchenko noted.

Adolescents may not be addicted to the internet itself but to certain behaviors like gaming or social networking, he said.

The “undoubted advantage” of his team’s research is the use of more than one tool, making it possible to “verify the predominant content of the addiction,” he added.

The investigators previously assessed general prevalence of IA in adolescents in Siberia and found about 6.8% of participants displayed pathological IA behavior – and that gaming addiction is more common in boys whereas addiction to social networking is more common in girls.

This prevalence rate is lower than in the Philippines (21.1%), Hong Kong (16.4%), Malaysia (14.1%), China (11%), and South Korea (9.7%), but slightly higher than in Japan (6.2%).

IA prevalence among adolescents in Europe ranges from 1% to 11%, with an average of 4.4%, said Dr. Tereshchenko.
 

Siberian students’ sleep

The current study included 4,344 students aged 12-18 years (average age, about 15 years) from 10 public schools in three large cities of Central Siberia (Krasnoyarsk, Abakan, and Kyzyl). There were slightly more girls than boys in the study sample.

Participants completed the Russian language version of the Chen Internet Addiction Scale (CIAS), which covers five symptomatic criteria for addictive behavior: withdrawal symptoms, signs of tolerance, compulsive use, psychological or physical problems, and difficulty managing time.

In this questionnaire, respondents rate several statements regarding the effect of internet use, each on a 4-point Likert scale: not at all (1 point), a little bit (2 points), moderately (3 points) and extremely (4). The total score ranges from 26 to 104.

A CIAS score of 26-42 indicates adaptive internet use, 43-64 indicates maladaptive internet use, and 65 and above indicates pathological internet use (PIU), which was classified as “internet-addicted.”

The researchers also used the nine-item Social Media Disorder Scale, as well as the Pittsburgh Sleep Quality Index to assess nighttime sleep.

Among other questions, teens were asked how long it usually took them to fall asleep and when they typically went to bed and woke up on school nights.

For daytime sleepiness, investigators used the targeted Pediatric Daytime Sleepiness Scale questionnaire, making them among the few research groups to use this psychometric instrument, Dr. Tereshchenko noted.

After parental consent was given, students completed the tests at the end of the day’s lessons. Total test time was about 45 minutes.
 

Sleep disturbance

Initial study results showed that compared with the other groups, adolescents with PIU tended to go to bed later, wake up later, take longer to fall asleep, sleep less at night, have more nighttime awakenings, and have more daytime sleepiness.

Sleep quality was the most impaired in boys aged 12-14 years who are addicted to internet computer games.

“In this group, 5 of the 6 sleep assessment parameters we studied were changed,” Dr. Tereshchenko reported.

Decreased total nighttime sleep was more common in older adolescents.

On average, boys and girls aged 15-18 years got less than the recommended 8 hours of sleep per night. Boys with IA got only about 6.4 hours per night and girls with IA got about 6.6 hours.

Interestingly, IA is generally more prevalent among teen girls than boys in Russia, which is not the case in Europe and North America, Dr. Tereshchenko noted.

Mechanisms linking IA and sleep disorders are not clear, but the relationship is probably multifactorial and perhaps interrelated, creating something of a “vicious circle,” he said.

“Sleep disturbances, which reflect psychosocial problems, depression, and anxiety-phobic disorders, can precede and contribute to IA. On the other hand, sleep disturbances such as insomnia can lead to increased use of the internet in the evening and at night, further exacerbating the problem,” said Dr. Tereshchenko.

Research is lacking on useful treatments for youth with IA, but these kids would likely benefit from behavioral therapy approaches, he added.
 

No escape?

Commenting on the study for this news organization, Maurice M. Ohayon, MD, DSc, PhD, director of the Stanford Sleep Epidemiology Research Center, Stanford University, California, said the topic of youth IA is “very important.”

Previous research in this field has shown a major impact from IA not only on sleep but also on mood – with irritability, depression, and even thoughts of suicide being possible red flags, said Dr. Ohayon, who was not involved in the current study.

Interestingly, his own research has also found that young teenage boys are most at risk for gaming addiction.

Although internet gaming has some positive effects, such as fostering leadership skills and relationships, it has become increasingly violent and isolating, with more adult professional gamers preying on younger players, Dr. Ohayon said.

“The major problem is that it’s putting children in a virtual world from which it’s difficult to escape,” he added.

Dr. Ohayon also noted concern about future developmental effects in kids who play video games for hours on end without coming out of their bedroom and with no physical contact with fellow players.

Parents should intervene before this situation occurs and limit the time their children spend on the gaming console, he said.

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

Tardive dyskinesia (TD) can be reasonably managed through telemedicine, but it should be employed as part of a hybrid strategy that ideally includes an office visit at the time of diagnosis and yearly intervals thereafter, according to an expert who spoke at a meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

verbaska_studio/Getty Images

In psychiatry in general and in TD specifically, telepsychiatry is useful, but “is not a one-size-fits-all approach,” according to Rif S. El-Mallakh, MD, director of the mood disorder research program at the University of Louisville (Ky.).

Telepsychiatry was already growing as a strategy to expand psychiatric services to communities with limited resources in mental health when the COVID-19 pandemic arrived. Dependence on this type of patient care then exploded out of necessity but in advance of how it might best be applied in specific circumstances.
 

Best practices panel convened in 2020

The project to develop best practices in TD began in July 2020, when the pandemic was still limiting normal clinician-patient interactions. It was expected from the beginning that recommendations would be applicable to postpandemic circumstances.

There is no reason to expect the forces driving the growth of telepsychiatry, which include convenience of patients and efficiency for clinicians, to dissipate once the pandemic resolves, Dr. El-Mallakh said at the virtual meeting, sponsored by MedscapeLive.

The process of developing best practices for telepsychiatry in TD began with semistructured qualitative interviews of the panelists, which consisted of six neurologists, three psychiatrists, and three psychiatric nurse practitioners. The goal was to gather information about the current practice of TD diagnosis and treatment in real-world settings.

With the information on current practices providing a baseline, a virtual roundtable was then convened to develop best-practices recommendations. The deliberations were performed on the basis of expert opinion. There were no statistical methods applied to data collected from the qualitative interviews.
 

Four key points in recommendations

The panel agreed on four key points: an in-person visit is preferred for initial evaluation and diagnosis; when applied for the evaluation of TD, telepsychiatry should include video; virtual visits cannot completely replace in-person visits; and patients with TD should be evaluated in person at least once per year.

In addition, the panelists recommended specific steps aimed at maximizing the quality of the virtual visit, including confirming that patients have appropriate equipment for video and audio communication. It is also important to recognize that patients or caregivers may require instruction on how to set up the equipment.

Prior to a telemedicine visit, it is appropriate to provide patients with a checklist that includes instructions on adequate lighting and audio. In addition, patient expectations about the goals and processes in the video should be explained.

“Instructional videos prior to the visit might be helpful,” Dr. El-Mallakh said.

Immediately prior to each visit, visual and audio quality should be verified. This allows technical issues, if any, to be resolved.

For the evaluation of TD, the ability to adequately observe body movements is crucial but can pose a challenge in telepsychiatry. To capture hyperkinetic movements and functional impairments with adequate clarity, it might be necessary to engage caregivers to hold the camera or otherwise help the clinician gain an adequate view. Clinicians should consider the limitations of telepsychiatry.

In addition to the challenges of a differential diagnosis for TD that should include such entities as parkinsonism and other drug-induced movement disorders, Dr. El-Mallakh cautioned, “comorbidities add another layer of complexity to TD diagnosis.”
 

Some in-office visits recommended

It is this complexity that led to the recommendation for an in-person evaluation for new-onset TD, although the expert panel did not characterize an initial in-office visit as mandatory.

Once a diagnosis of TD is established, telepsychiatry can be an efficient strategy for education and for confirming that treatments remain effective. However, Dr. El-Mallakh pointed out that patients can and often do have more than one drug-induced movement disorder at the time of diagnosis or develop additional clinical issues over time.

According to the expert panel, telepsychiatry should not be considered an adequate strategy to manage TD by itself, but “it can be an important component” of care of these patients if used judiciously.

“We have all come to recognize the benefits of telepsychiatry and some of the limitations,” said Jonathan M. Meyer, MD, clinical professor of psychiatry, University of California, San Diego. An author or coauthor of several articles on TD, including a recent study of patient awareness of TD symptoms while on vesicular monoamine transporter 2 inhibitors, Dr. Meyer identified technical problems as among the limitations.

Doug Brunk/MDedge News

Tardive dyskinesia (TD) can be reasonably managed through telemedicine, but it should be employed as part of a hybrid strategy that ideally includes an office visit at the time of diagnosis and yearly intervals thereafter, according to an expert who spoke at a meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

verbaska_studio/Getty Images

In psychiatry in general and in TD specifically, telepsychiatry is useful, but “is not a one-size-fits-all approach,” according to Rif S. El-Mallakh, MD, director of the mood disorder research program at the University of Louisville (Ky.).

Telepsychiatry was already growing as a strategy to expand psychiatric services to communities with limited resources in mental health when the COVID-19 pandemic arrived. Dependence on this type of patient care then exploded out of necessity but in advance of how it might best be applied in specific circumstances.
 

Best practices panel convened in 2020

The project to develop best practices in TD began in July 2020, when the pandemic was still limiting normal clinician-patient interactions. It was expected from the beginning that recommendations would be applicable to postpandemic circumstances.

There is no reason to expect the forces driving the growth of telepsychiatry, which include convenience of patients and efficiency for clinicians, to dissipate once the pandemic resolves, Dr. El-Mallakh said at the virtual meeting, sponsored by MedscapeLive.

The process of developing best practices for telepsychiatry in TD began with semistructured qualitative interviews of the panelists, which consisted of six neurologists, three psychiatrists, and three psychiatric nurse practitioners. The goal was to gather information about the current practice of TD diagnosis and treatment in real-world settings.

With the information on current practices providing a baseline, a virtual roundtable was then convened to develop best-practices recommendations. The deliberations were performed on the basis of expert opinion. There were no statistical methods applied to data collected from the qualitative interviews.
 

Four key points in recommendations

The panel agreed on four key points: an in-person visit is preferred for initial evaluation and diagnosis; when applied for the evaluation of TD, telepsychiatry should include video; virtual visits cannot completely replace in-person visits; and patients with TD should be evaluated in person at least once per year.

In addition, the panelists recommended specific steps aimed at maximizing the quality of the virtual visit, including confirming that patients have appropriate equipment for video and audio communication. It is also important to recognize that patients or caregivers may require instruction on how to set up the equipment.

Prior to a telemedicine visit, it is appropriate to provide patients with a checklist that includes instructions on adequate lighting and audio. In addition, patient expectations about the goals and processes in the video should be explained.

“Instructional videos prior to the visit might be helpful,” Dr. El-Mallakh said.

Immediately prior to each visit, visual and audio quality should be verified. This allows technical issues, if any, to be resolved.

For the evaluation of TD, the ability to adequately observe body movements is crucial but can pose a challenge in telepsychiatry. To capture hyperkinetic movements and functional impairments with adequate clarity, it might be necessary to engage caregivers to hold the camera or otherwise help the clinician gain an adequate view. Clinicians should consider the limitations of telepsychiatry.

In addition to the challenges of a differential diagnosis for TD that should include such entities as parkinsonism and other drug-induced movement disorders, Dr. El-Mallakh cautioned, “comorbidities add another layer of complexity to TD diagnosis.”
 

Some in-office visits recommended

It is this complexity that led to the recommendation for an in-person evaluation for new-onset TD, although the expert panel did not characterize an initial in-office visit as mandatory.

Once a diagnosis of TD is established, telepsychiatry can be an efficient strategy for education and for confirming that treatments remain effective. However, Dr. El-Mallakh pointed out that patients can and often do have more than one drug-induced movement disorder at the time of diagnosis or develop additional clinical issues over time.

According to the expert panel, telepsychiatry should not be considered an adequate strategy to manage TD by itself, but “it can be an important component” of care of these patients if used judiciously.

“We have all come to recognize the benefits of telepsychiatry and some of the limitations,” said Jonathan M. Meyer, MD, clinical professor of psychiatry, University of California, San Diego. An author or coauthor of several articles on TD, including a recent study of patient awareness of TD symptoms while on vesicular monoamine transporter 2 inhibitors, Dr. Meyer identified technical problems as among the limitations.

Doug Brunk/MDedge News

Tardive dyskinesia (TD) can be reasonably managed through telemedicine, but it should be employed as part of a hybrid strategy that ideally includes an office visit at the time of diagnosis and yearly intervals thereafter, according to an expert who spoke at a meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

verbaska_studio/Getty Images

In psychiatry in general and in TD specifically, telepsychiatry is useful, but “is not a one-size-fits-all approach,” according to Rif S. El-Mallakh, MD, director of the mood disorder research program at the University of Louisville (Ky.).

Telepsychiatry was already growing as a strategy to expand psychiatric services to communities with limited resources in mental health when the COVID-19 pandemic arrived. Dependence on this type of patient care then exploded out of necessity but in advance of how it might best be applied in specific circumstances.
 

Best practices panel convened in 2020

The project to develop best practices in TD began in July 2020, when the pandemic was still limiting normal clinician-patient interactions. It was expected from the beginning that recommendations would be applicable to postpandemic circumstances.

There is no reason to expect the forces driving the growth of telepsychiatry, which include convenience of patients and efficiency for clinicians, to dissipate once the pandemic resolves, Dr. El-Mallakh said at the virtual meeting, sponsored by MedscapeLive.

The process of developing best practices for telepsychiatry in TD began with semistructured qualitative interviews of the panelists, which consisted of six neurologists, three psychiatrists, and three psychiatric nurse practitioners. The goal was to gather information about the current practice of TD diagnosis and treatment in real-world settings.

With the information on current practices providing a baseline, a virtual roundtable was then convened to develop best-practices recommendations. The deliberations were performed on the basis of expert opinion. There were no statistical methods applied to data collected from the qualitative interviews.
 

Four key points in recommendations

The panel agreed on four key points: an in-person visit is preferred for initial evaluation and diagnosis; when applied for the evaluation of TD, telepsychiatry should include video; virtual visits cannot completely replace in-person visits; and patients with TD should be evaluated in person at least once per year.

In addition, the panelists recommended specific steps aimed at maximizing the quality of the virtual visit, including confirming that patients have appropriate equipment for video and audio communication. It is also important to recognize that patients or caregivers may require instruction on how to set up the equipment.

Prior to a telemedicine visit, it is appropriate to provide patients with a checklist that includes instructions on adequate lighting and audio. In addition, patient expectations about the goals and processes in the video should be explained.

“Instructional videos prior to the visit might be helpful,” Dr. El-Mallakh said.

Immediately prior to each visit, visual and audio quality should be verified. This allows technical issues, if any, to be resolved.

For the evaluation of TD, the ability to adequately observe body movements is crucial but can pose a challenge in telepsychiatry. To capture hyperkinetic movements and functional impairments with adequate clarity, it might be necessary to engage caregivers to hold the camera or otherwise help the clinician gain an adequate view. Clinicians should consider the limitations of telepsychiatry.

In addition to the challenges of a differential diagnosis for TD that should include such entities as parkinsonism and other drug-induced movement disorders, Dr. El-Mallakh cautioned, “comorbidities add another layer of complexity to TD diagnosis.”
 

Some in-office visits recommended

It is this complexity that led to the recommendation for an in-person evaluation for new-onset TD, although the expert panel did not characterize an initial in-office visit as mandatory.

Once a diagnosis of TD is established, telepsychiatry can be an efficient strategy for education and for confirming that treatments remain effective. However, Dr. El-Mallakh pointed out that patients can and often do have more than one drug-induced movement disorder at the time of diagnosis or develop additional clinical issues over time.

According to the expert panel, telepsychiatry should not be considered an adequate strategy to manage TD by itself, but “it can be an important component” of care of these patients if used judiciously.

“We have all come to recognize the benefits of telepsychiatry and some of the limitations,” said Jonathan M. Meyer, MD, clinical professor of psychiatry, University of California, San Diego. An author or coauthor of several articles on TD, including a recent study of patient awareness of TD symptoms while on vesicular monoamine transporter 2 inhibitors, Dr. Meyer identified technical problems as among the limitations.

Doug Brunk/MDedge News

Listening to Mozart has a notable impact on seizure reduction in patients with epilepsy – and now researchers believe they know why.

Investigators conducting new research found that the acoustic characteristics of Mozart’s Sonata for Two Pianos in D Major (K448) suppresses brain activity in patients with epilepsy, while a piece by the 18th century classical composer Franz Joseph Haydn did not have this effect.

Listening to this Mozart sonata and perhaps other musical pieces may eventually become a treatment for preventing epileptic seizures, said study investigator Ivan Rektor, MD, CSc, Epilepsy Centre at the Hospital St. Anne and professor at the Central European Institute of Technology, Masaryk University, Brno, Czech Republic.

“This research into the impact of listening to music could lead to the development of a music-related type of palliative neurostimulation therapy,” said Dr. Rektor.

The findings were presented at the 2021 Congress of the European Academy of Neurology and published online in the European Journal of Neurology.
 

Clinically controversial?

Epilepsy affects 6 million people in Europe. Furthermore, estimates show that about 15 million Europeans have had at least one seizure at some time in their lives. In addition, about 30% of patients with epilepsy are not adequately treated with antiseizure medications.

Researchers have been studying the impact of Mozart’s music on brain-wave activity since the 1990s. Various studies report a reduction in epileptiform discharges in patients with epileptic seizures, coma, and refractory nonconvulsive status.

A 2012 meta-analysis of 12 publications involving patients with epilepsy showed an overall reduction in the number of interictal epileptic discharges (IEDs) or abnormal electrical brain waves in 84% of participants who listened to Mozart’s music. A more recent meta-analysis also showed a significant reduction in epileptic seizures and IEDs.

American researchers also found Mozart’s music regulated abnormal interictal epileptiform activity (IEA), especially in those with a high baseline rate of interictal spikes.

However, the methodological quality of some of this research “has been limited,” Dr. Rektor noted. He added that use of music therapy in clinical practice is still considered “controversial.”

The new study included 18 treatment-resistant patients with epilepsy (50% men) who ranged in age from 19 to 55 years. Participants had intracerebral electrodes implanted in the brain before undergoing surgery.

Of the total study population, 15 had temporal lobe epilepsy and three had extratemporal epilepsy. Eleven were affected on the left side, six on the right side, and one bi-temporally. Duration of epilepsy ranged from 8 to 40 years.

Patients listened to the Mozart piece intermittently on one day and to Haydn’s “Surprise” Symphony No. 94 the next day. Researchers counted the number of ED discharges before, during, and after the patients listened to the music.
 

Surprising finding

Results showed that exposure to the Mozart piece was associated with a 32% reduction in IEDs, from 28 EDs pre-exposure to 19 during exposure. However, IEDs rose to 21 post-exposure.

Overall, the Haydn piece was associated with an increase in IEDs, from 23 pre-exposure to 26 during and post-exposure.

“We saw a clear decrease in epileptic spikes while listening and after listening to Mozart, while there was an increase in spikes while listening to Haydn,” Dr. Rektor said.

He added that all 18 patients responded “more or less” to the music and that the results were statistically significant.

Dr. Rektor noted that the investigators were not surprised by the Mozart effect but were somewhat taken aback by the opposite effect from listening to Haydn.

The impact differed between men and women. The Mozart piece had a larger effect on women. In addition, the Haydn piece led to a decrease in spikes in women but led to “a clear” increase in men, Dr. Rektor reported.

In an effort to explore why the two classical pieces had such different effects, the researchers examined the acoustic properties. They worked with acoustic engineers to examine three musical properties that might influence the number of spikes: rhythm (tempo or beats per minute), dynamics (energy), and timbre (how harsh or unpleasant, how noisy, and how many “high-frequency” parts the music has).

“We observed that K448 [Mozart’s piece] has a more harmonic spectrum and its spectral content doesn’t change quickly, which probably has a positive effect on epilepsy patients,” said Dr. Rektor.

Specific features of the music had a slightly different effect on men and women. Men were more sensitive to dissonance and high-frequency parts while women were more sensitive to energy.
 

A new theory

Researchers previously hypothesized that the Mozart effect in epilepsy was connected to the emotional impact of music. The neurotransmitter dopamine, which plays a role in the brain’s reward system, is released when listening to music. However, the new research seems to challenge that theory. The majority of the participants did not express a strong preference for classical music.

“We believe emotions didn’t play an important role in these patients,” Dr. Rektor said, adding that the impact was instead mostly related to acoustic signals.

The team also found that the reduction in IEDs was larger in the lateral temporal lobe, the part of the brain involved in translating acoustic signals, rather than in the mesiotemporal limbic region, which plays an important role in the emotional response to music.

Comparing men with women, there’s an “overlap” of brain activation in most brain areas. However, some areas are more activated in men and others in women, said Dr. Rektor.

While the Mozart Sonata for two pianos in D Major has become the “gold standard” in this type of research, Dr. Rektor said “it’s very probable” that other classical compositions with similar acoustic properties have the same effect in epilepsy.

The investigators are testing other musical pieces, both classical and nonclassical. The ultimate aim is to develop individualized musical patterns based on these acoustic features.

“If it works, we would like to use it as a noninvasive neurostimulation method,” Dr. Rektor said.
 

‘Inspiring research’

Commenting on the study, session chair Marte Bjørk, MD, PhD, associate professor, department of clinical medicine, University of Bergen, Norway, called it “inspiring.” She noted that she recently had a patient whose temporal lobe seizures were consistently triggered by music played on a children’s TV program. “So I have no doubt that music can be important for some patients,” Dr. Bjørk said.

She questioned whether factors other than gender may predict response to music.

The study authors have disclosed no relevant financial relationships.

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

Listening to Mozart has a notable impact on seizure reduction in patients with epilepsy – and now researchers believe they know why.

Investigators conducting new research found that the acoustic characteristics of Mozart’s Sonata for Two Pianos in D Major (K448) suppresses brain activity in patients with epilepsy, while a piece by the 18th century classical composer Franz Joseph Haydn did not have this effect.

Listening to this Mozart sonata and perhaps other musical pieces may eventually become a treatment for preventing epileptic seizures, said study investigator Ivan Rektor, MD, CSc, Epilepsy Centre at the Hospital St. Anne and professor at the Central European Institute of Technology, Masaryk University, Brno, Czech Republic.

“This research into the impact of listening to music could lead to the development of a music-related type of palliative neurostimulation therapy,” said Dr. Rektor.

The findings were presented at the 2021 Congress of the European Academy of Neurology and published online in the European Journal of Neurology.
 

Clinically controversial?

Epilepsy affects 6 million people in Europe. Furthermore, estimates show that about 15 million Europeans have had at least one seizure at some time in their lives. In addition, about 30% of patients with epilepsy are not adequately treated with antiseizure medications.

Researchers have been studying the impact of Mozart’s music on brain-wave activity since the 1990s. Various studies report a reduction in epileptiform discharges in patients with epileptic seizures, coma, and refractory nonconvulsive status.

A 2012 meta-analysis of 12 publications involving patients with epilepsy showed an overall reduction in the number of interictal epileptic discharges (IEDs) or abnormal electrical brain waves in 84% of participants who listened to Mozart’s music. A more recent meta-analysis also showed a significant reduction in epileptic seizures and IEDs.

American researchers also found Mozart’s music regulated abnormal interictal epileptiform activity (IEA), especially in those with a high baseline rate of interictal spikes.

However, the methodological quality of some of this research “has been limited,” Dr. Rektor noted. He added that use of music therapy in clinical practice is still considered “controversial.”

The new study included 18 treatment-resistant patients with epilepsy (50% men) who ranged in age from 19 to 55 years. Participants had intracerebral electrodes implanted in the brain before undergoing surgery.

Of the total study population, 15 had temporal lobe epilepsy and three had extratemporal epilepsy. Eleven were affected on the left side, six on the right side, and one bi-temporally. Duration of epilepsy ranged from 8 to 40 years.

Patients listened to the Mozart piece intermittently on one day and to Haydn’s “Surprise” Symphony No. 94 the next day. Researchers counted the number of ED discharges before, during, and after the patients listened to the music.
 

Surprising finding

Results showed that exposure to the Mozart piece was associated with a 32% reduction in IEDs, from 28 EDs pre-exposure to 19 during exposure. However, IEDs rose to 21 post-exposure.

Overall, the Haydn piece was associated with an increase in IEDs, from 23 pre-exposure to 26 during and post-exposure.

“We saw a clear decrease in epileptic spikes while listening and after listening to Mozart, while there was an increase in spikes while listening to Haydn,” Dr. Rektor said.

He added that all 18 patients responded “more or less” to the music and that the results were statistically significant.

Dr. Rektor noted that the investigators were not surprised by the Mozart effect but were somewhat taken aback by the opposite effect from listening to Haydn.

The impact differed between men and women. The Mozart piece had a larger effect on women. In addition, the Haydn piece led to a decrease in spikes in women but led to “a clear” increase in men, Dr. Rektor reported.

In an effort to explore why the two classical pieces had such different effects, the researchers examined the acoustic properties. They worked with acoustic engineers to examine three musical properties that might influence the number of spikes: rhythm (tempo or beats per minute), dynamics (energy), and timbre (how harsh or unpleasant, how noisy, and how many “high-frequency” parts the music has).

“We observed that K448 [Mozart’s piece] has a more harmonic spectrum and its spectral content doesn’t change quickly, which probably has a positive effect on epilepsy patients,” said Dr. Rektor.

Specific features of the music had a slightly different effect on men and women. Men were more sensitive to dissonance and high-frequency parts while women were more sensitive to energy.
 

A new theory

Researchers previously hypothesized that the Mozart effect in epilepsy was connected to the emotional impact of music. The neurotransmitter dopamine, which plays a role in the brain’s reward system, is released when listening to music. However, the new research seems to challenge that theory. The majority of the participants did not express a strong preference for classical music.

“We believe emotions didn’t play an important role in these patients,” Dr. Rektor said, adding that the impact was instead mostly related to acoustic signals.

The team also found that the reduction in IEDs was larger in the lateral temporal lobe, the part of the brain involved in translating acoustic signals, rather than in the mesiotemporal limbic region, which plays an important role in the emotional response to music.

Comparing men with women, there’s an “overlap” of brain activation in most brain areas. However, some areas are more activated in men and others in women, said Dr. Rektor.

While the Mozart Sonata for two pianos in D Major has become the “gold standard” in this type of research, Dr. Rektor said “it’s very probable” that other classical compositions with similar acoustic properties have the same effect in epilepsy.

The investigators are testing other musical pieces, both classical and nonclassical. The ultimate aim is to develop individualized musical patterns based on these acoustic features.

“If it works, we would like to use it as a noninvasive neurostimulation method,” Dr. Rektor said.
 

‘Inspiring research’

Commenting on the study, session chair Marte Bjørk, MD, PhD, associate professor, department of clinical medicine, University of Bergen, Norway, called it “inspiring.” She noted that she recently had a patient whose temporal lobe seizures were consistently triggered by music played on a children’s TV program. “So I have no doubt that music can be important for some patients,” Dr. Bjørk said.

She questioned whether factors other than gender may predict response to music.

The study authors have disclosed no relevant financial relationships.

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

Listening to Mozart has a notable impact on seizure reduction in patients with epilepsy – and now researchers believe they know why.

Investigators conducting new research found that the acoustic characteristics of Mozart’s Sonata for Two Pianos in D Major (K448) suppresses brain activity in patients with epilepsy, while a piece by the 18th century classical composer Franz Joseph Haydn did not have this effect.

Listening to this Mozart sonata and perhaps other musical pieces may eventually become a treatment for preventing epileptic seizures, said study investigator Ivan Rektor, MD, CSc, Epilepsy Centre at the Hospital St. Anne and professor at the Central European Institute of Technology, Masaryk University, Brno, Czech Republic.

“This research into the impact of listening to music could lead to the development of a music-related type of palliative neurostimulation therapy,” said Dr. Rektor.

The findings were presented at the 2021 Congress of the European Academy of Neurology and published online in the European Journal of Neurology.
 

Clinically controversial?

Epilepsy affects 6 million people in Europe. Furthermore, estimates show that about 15 million Europeans have had at least one seizure at some time in their lives. In addition, about 30% of patients with epilepsy are not adequately treated with antiseizure medications.

Researchers have been studying the impact of Mozart’s music on brain-wave activity since the 1990s. Various studies report a reduction in epileptiform discharges in patients with epileptic seizures, coma, and refractory nonconvulsive status.

A 2012 meta-analysis of 12 publications involving patients with epilepsy showed an overall reduction in the number of interictal epileptic discharges (IEDs) or abnormal electrical brain waves in 84% of participants who listened to Mozart’s music. A more recent meta-analysis also showed a significant reduction in epileptic seizures and IEDs.

American researchers also found Mozart’s music regulated abnormal interictal epileptiform activity (IEA), especially in those with a high baseline rate of interictal spikes.

However, the methodological quality of some of this research “has been limited,” Dr. Rektor noted. He added that use of music therapy in clinical practice is still considered “controversial.”

The new study included 18 treatment-resistant patients with epilepsy (50% men) who ranged in age from 19 to 55 years. Participants had intracerebral electrodes implanted in the brain before undergoing surgery.

Of the total study population, 15 had temporal lobe epilepsy and three had extratemporal epilepsy. Eleven were affected on the left side, six on the right side, and one bi-temporally. Duration of epilepsy ranged from 8 to 40 years.

Patients listened to the Mozart piece intermittently on one day and to Haydn’s “Surprise” Symphony No. 94 the next day. Researchers counted the number of ED discharges before, during, and after the patients listened to the music.
 

Surprising finding

Results showed that exposure to the Mozart piece was associated with a 32% reduction in IEDs, from 28 EDs pre-exposure to 19 during exposure. However, IEDs rose to 21 post-exposure.

Overall, the Haydn piece was associated with an increase in IEDs, from 23 pre-exposure to 26 during and post-exposure.

“We saw a clear decrease in epileptic spikes while listening and after listening to Mozart, while there was an increase in spikes while listening to Haydn,” Dr. Rektor said.

He added that all 18 patients responded “more or less” to the music and that the results were statistically significant.

Dr. Rektor noted that the investigators were not surprised by the Mozart effect but were somewhat taken aback by the opposite effect from listening to Haydn.

The impact differed between men and women. The Mozart piece had a larger effect on women. In addition, the Haydn piece led to a decrease in spikes in women but led to “a clear” increase in men, Dr. Rektor reported.

In an effort to explore why the two classical pieces had such different effects, the researchers examined the acoustic properties. They worked with acoustic engineers to examine three musical properties that might influence the number of spikes: rhythm (tempo or beats per minute), dynamics (energy), and timbre (how harsh or unpleasant, how noisy, and how many “high-frequency” parts the music has).

“We observed that K448 [Mozart’s piece] has a more harmonic spectrum and its spectral content doesn’t change quickly, which probably has a positive effect on epilepsy patients,” said Dr. Rektor.

Specific features of the music had a slightly different effect on men and women. Men were more sensitive to dissonance and high-frequency parts while women were more sensitive to energy.
 

A new theory

Researchers previously hypothesized that the Mozart effect in epilepsy was connected to the emotional impact of music. The neurotransmitter dopamine, which plays a role in the brain’s reward system, is released when listening to music. However, the new research seems to challenge that theory. The majority of the participants did not express a strong preference for classical music.

“We believe emotions didn’t play an important role in these patients,” Dr. Rektor said, adding that the impact was instead mostly related to acoustic signals.

The team also found that the reduction in IEDs was larger in the lateral temporal lobe, the part of the brain involved in translating acoustic signals, rather than in the mesiotemporal limbic region, which plays an important role in the emotional response to music.

Comparing men with women, there’s an “overlap” of brain activation in most brain areas. However, some areas are more activated in men and others in women, said Dr. Rektor.

While the Mozart Sonata for two pianos in D Major has become the “gold standard” in this type of research, Dr. Rektor said “it’s very probable” that other classical compositions with similar acoustic properties have the same effect in epilepsy.

The investigators are testing other musical pieces, both classical and nonclassical. The ultimate aim is to develop individualized musical patterns based on these acoustic features.

“If it works, we would like to use it as a noninvasive neurostimulation method,” Dr. Rektor said.
 

‘Inspiring research’

Commenting on the study, session chair Marte Bjørk, MD, PhD, associate professor, department of clinical medicine, University of Bergen, Norway, called it “inspiring.” She noted that she recently had a patient whose temporal lobe seizures were consistently triggered by music played on a children’s TV program. “So I have no doubt that music can be important for some patients,” Dr. Bjørk said.

She questioned whether factors other than gender may predict response to music.

The study authors have disclosed no relevant financial relationships.

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

For adults with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ALL), frontline therapy with the chemotherapy-free combination of ponatinib (Iclusig) and blinatumomab (Blincyto) shows promise as an alternative to early hematopoietic stem cell transplantation (HSCT), investigators in a single-arm phase 2 study reported.

In an interim analysis of the combination in patients with newly diagnosed or relapsed/refractory Ph+ALL or lymphoid accelerated or blast phase chronic myeloid leukemia (CML), 20 patients who received it as frontline therapy had a rate of complete responses (CR) or complete responses with partial recovery of blood counts (CRp) of 100% and a complete molecular remission (CMR) rate of 85%, reported Nicholas Short, MD, of the University of Texas MD Anderson Cancer Center in Houston.

“This translated into an estimated 2-year overall survival of 93%, with no patients undergoing transplant in first remission, and none having relapse at last follow-up,” he said in an oral abstract presented during the European Hematology Association annual congress.

Among patients with relapsed/refractory Ph+ALL, the CR/CRp rate was 89%, the CMR rate was 88%, and the estimated 2-year overall survival rate was 53%, he said.
 

Transplants on hold

“The big selling point is the ability to avoid stem cell transplant, which is not always the first thing you do in Ph-positive ALL, but it’s always on your mind,” said Gwen Nichols, MD, chief medical officer of the Leukemia and Lymphoma Society, who was not involved in the study.

“It looks, albeit with very limited follow-up, that patients haven’t relapsed yet such that transplant would be necessary. Anything we can do to avoid people having long-term complications that go along with an allogeneic transplant is a step in the right direction,” she said in an interview.
 

One combination, three cohorts

Ph+ALL comprises about 25% of all adult ALL. The standard of care in newly diagnosed patients is chemotherapy plus a tyrosine kinase inhibitor (TKI) targeted against the BCR-ABL transcript.

Ponatinib is a pan-BCR-ABL TKI that has been shown to have activity against ALL with T315I mutations, which are present in about 75% of the cases of relapsed disease, Dr. Short said.

Blinatumomab is a bi-specific T-cell engager (BiTe) that has been shown to be effective as monotherapy against relapsed/refractory Ph+ALL as monotherapy and in combination with dasatinib.

Dr. Short and colleagues enrolled patients with newly diagnosed or relapsed/refractory Ph+ALL or lymphoid accelerated or blast phase CML. Patients in the frontline cohort could have received one or two prior lines of chemotherapy with or without a TKI.

The patients all had Eastern Cooperative Oncology Group performance status of 0-2, and adequate liver function.

Patients with clinically significant cardiovascular disease or central nervous system disease pathology were excluded, except that patients with CNS leukemia could be enrolled.

The induction phase consisted of 30 mg ponatinib daily plus blinatumomab standard dosing on a 4-week-on, 2-week-off schedule. Patients in CMR, defined for frontline patients as undetectable BCR-ABL transcripts by polymerase chain reaction, then received up to four consolidation cycles of the regimen with ponatinib at a 15-mg dose, followed by 5 years of ponatinib 15-mg maintenance. All patients also received CNS prophylaxis with 12 cycles of intrathecal chemotherapy with alternating administration of methotrexate and cytarabine.

Of the 35 patients treated to date with the combination, 20 with Ph+ALL received it as frontline therapy and 10 received it for relapsed/refractory disease; 5 patients with CML in lymphoid blast phase also were treated.
 

High CMR, CR rates

As noted before, the CMR rate, the primary endpoint among patients with newly diagnosed Ph+ALL, was 85%, with a CR/CRp rate of 100%. Six of the patients in the frontline group and one in the salvage therapy group had CRs but were positive for minimal residual disease (MRD) at study outset.

The CR/CRp rate for the entire cohort of 28 patients (excluding those with a CR at start) was 96%, with only 1 patient who had relapsed/refractory disease not having a CR. This patient had received ponatinib in a prior salvage regimen.

The CMR rate among the entire cohort was 79%, with 85% of patients in the frontline ALL cohort having a CMR, 88% in the relapsed/refractory cohort, and 40% in the CML cohort. There were no early deaths among any patients.

“After one cycle of ponatinib plus blinatumomab, 84% of frontline patients had achieved at least a major molecular response, and 58% had achieved a CMR. Among those with relapsed/refractory Ph+ALL, 75% achieved CMR after one cycle of therapy,” Dr. Short said.

Of the 20 frontline patients in CR, one patient experienced visual changes and possible stroke that were considered possibly related to the study medication. This patient was taken off study. During a later maintenance regimen this patient developed a non-ST elevation myocardial infarction and died from postprocedural bleeding and hypovolemic shock following a cardiac catheterization procedure.

The remainder of patients in the frontline cohort had ongoing responses without the need for HSCT at last follow-up. There were no relapses, with a median duration of CR of 6 months,

Among the 10 with relapsed/refractory Ph+ALL, one did not have a response, and the remaining 9 had CR/CRps.

Of the latter groups, four went on to allogeneic HSCT and three were still alive; one patient who underwent a transplant experienced a relapse and died. One additional patient was alive with relapsed disease with T315I and E255V mutations at the time of relapse, one patient in CR who went off study due to insurance issues died from an unknown cause, and the three remaining patients had ongoing responses without transplant.

Among the five patients with CML in lymphoid blast phase, two had relapses, but both are still alive and currently in remission, and three have ongoing responses without transplant.

After a median follow-up of 12 months the 1-year event-free survival (EFS) rate for the entire 35-patient group was 76%, and the 2-year EFS was 70%.

The 1-year overall survival rate was 93%, and the 2-year OS rate was 80%.

Among patients in the frontline group, the 1-year and 2-year EFS and OS rates were all 93%.

For the relapsed/refractory cohort, the estimated 2-year EFS was 41% and OS was 53%. For the CML cohort, the 2-year EFS was 60%, with all patients still alive at last follow-up.

There were no grade 4 adverse events on study. Grade 3 adverse events considered at least possibly related to study treatment were elevated lipase, fever/febrile neutropenia, increased alanine aminotransferase, cerebrovascular ischemia, hypertension, pancreatitis, deep vein thrombosis, and encephalopathy. There were no cases of grade 3 cytokine release syndrome or tremor.

The study was sponsored by MD Anderson Cancer Center with collaboration from the National Cancer Institute, Amgen, and Takeda. Dr. Short has disclosed relationships with Amgen and Takeda. Dr. Nichols reported having no conflicts of interest.

For adults with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ALL), frontline therapy with the chemotherapy-free combination of ponatinib (Iclusig) and blinatumomab (Blincyto) shows promise as an alternative to early hematopoietic stem cell transplantation (HSCT), investigators in a single-arm phase 2 study reported.

In an interim analysis of the combination in patients with newly diagnosed or relapsed/refractory Ph+ALL or lymphoid accelerated or blast phase chronic myeloid leukemia (CML), 20 patients who received it as frontline therapy had a rate of complete responses (CR) or complete responses with partial recovery of blood counts (CRp) of 100% and a complete molecular remission (CMR) rate of 85%, reported Nicholas Short, MD, of the University of Texas MD Anderson Cancer Center in Houston.

“This translated into an estimated 2-year overall survival of 93%, with no patients undergoing transplant in first remission, and none having relapse at last follow-up,” he said in an oral abstract presented during the European Hematology Association annual congress.

Among patients with relapsed/refractory Ph+ALL, the CR/CRp rate was 89%, the CMR rate was 88%, and the estimated 2-year overall survival rate was 53%, he said.
 

Transplants on hold

“The big selling point is the ability to avoid stem cell transplant, which is not always the first thing you do in Ph-positive ALL, but it’s always on your mind,” said Gwen Nichols, MD, chief medical officer of the Leukemia and Lymphoma Society, who was not involved in the study.

“It looks, albeit with very limited follow-up, that patients haven’t relapsed yet such that transplant would be necessary. Anything we can do to avoid people having long-term complications that go along with an allogeneic transplant is a step in the right direction,” she said in an interview.
 

One combination, three cohorts

Ph+ALL comprises about 25% of all adult ALL. The standard of care in newly diagnosed patients is chemotherapy plus a tyrosine kinase inhibitor (TKI) targeted against the BCR-ABL transcript.

Ponatinib is a pan-BCR-ABL TKI that has been shown to have activity against ALL with T315I mutations, which are present in about 75% of the cases of relapsed disease, Dr. Short said.

Blinatumomab is a bi-specific T-cell engager (BiTe) that has been shown to be effective as monotherapy against relapsed/refractory Ph+ALL as monotherapy and in combination with dasatinib.

Dr. Short and colleagues enrolled patients with newly diagnosed or relapsed/refractory Ph+ALL or lymphoid accelerated or blast phase CML. Patients in the frontline cohort could have received one or two prior lines of chemotherapy with or without a TKI.

The patients all had Eastern Cooperative Oncology Group performance status of 0-2, and adequate liver function.

Patients with clinically significant cardiovascular disease or central nervous system disease pathology were excluded, except that patients with CNS leukemia could be enrolled.

The induction phase consisted of 30 mg ponatinib daily plus blinatumomab standard dosing on a 4-week-on, 2-week-off schedule. Patients in CMR, defined for frontline patients as undetectable BCR-ABL transcripts by polymerase chain reaction, then received up to four consolidation cycles of the regimen with ponatinib at a 15-mg dose, followed by 5 years of ponatinib 15-mg maintenance. All patients also received CNS prophylaxis with 12 cycles of intrathecal chemotherapy with alternating administration of methotrexate and cytarabine.

Of the 35 patients treated to date with the combination, 20 with Ph+ALL received it as frontline therapy and 10 received it for relapsed/refractory disease; 5 patients with CML in lymphoid blast phase also were treated.
 

High CMR, CR rates

As noted before, the CMR rate, the primary endpoint among patients with newly diagnosed Ph+ALL, was 85%, with a CR/CRp rate of 100%. Six of the patients in the frontline group and one in the salvage therapy group had CRs but were positive for minimal residual disease (MRD) at study outset.

The CR/CRp rate for the entire cohort of 28 patients (excluding those with a CR at start) was 96%, with only 1 patient who had relapsed/refractory disease not having a CR. This patient had received ponatinib in a prior salvage regimen.

The CMR rate among the entire cohort was 79%, with 85% of patients in the frontline ALL cohort having a CMR, 88% in the relapsed/refractory cohort, and 40% in the CML cohort. There were no early deaths among any patients.

“After one cycle of ponatinib plus blinatumomab, 84% of frontline patients had achieved at least a major molecular response, and 58% had achieved a CMR. Among those with relapsed/refractory Ph+ALL, 75% achieved CMR after one cycle of therapy,” Dr. Short said.

Of the 20 frontline patients in CR, one patient experienced visual changes and possible stroke that were considered possibly related to the study medication. This patient was taken off study. During a later maintenance regimen this patient developed a non-ST elevation myocardial infarction and died from postprocedural bleeding and hypovolemic shock following a cardiac catheterization procedure.

The remainder of patients in the frontline cohort had ongoing responses without the need for HSCT at last follow-up. There were no relapses, with a median duration of CR of 6 months,

Among the 10 with relapsed/refractory Ph+ALL, one did not have a response, and the remaining 9 had CR/CRps.

Of the latter groups, four went on to allogeneic HSCT and three were still alive; one patient who underwent a transplant experienced a relapse and died. One additional patient was alive with relapsed disease with T315I and E255V mutations at the time of relapse, one patient in CR who went off study due to insurance issues died from an unknown cause, and the three remaining patients had ongoing responses without transplant.

Among the five patients with CML in lymphoid blast phase, two had relapses, but both are still alive and currently in remission, and three have ongoing responses without transplant.

After a median follow-up of 12 months the 1-year event-free survival (EFS) rate for the entire 35-patient group was 76%, and the 2-year EFS was 70%.

The 1-year overall survival rate was 93%, and the 2-year OS rate was 80%.

Among patients in the frontline group, the 1-year and 2-year EFS and OS rates were all 93%.

For the relapsed/refractory cohort, the estimated 2-year EFS was 41% and OS was 53%. For the CML cohort, the 2-year EFS was 60%, with all patients still alive at last follow-up.

There were no grade 4 adverse events on study. Grade 3 adverse events considered at least possibly related to study treatment were elevated lipase, fever/febrile neutropenia, increased alanine aminotransferase, cerebrovascular ischemia, hypertension, pancreatitis, deep vein thrombosis, and encephalopathy. There were no cases of grade 3 cytokine release syndrome or tremor.

The study was sponsored by MD Anderson Cancer Center with collaboration from the National Cancer Institute, Amgen, and Takeda. Dr. Short has disclosed relationships with Amgen and Takeda. Dr. Nichols reported having no conflicts of interest.

For adults with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ALL), frontline therapy with the chemotherapy-free combination of ponatinib (Iclusig) and blinatumomab (Blincyto) shows promise as an alternative to early hematopoietic stem cell transplantation (HSCT), investigators in a single-arm phase 2 study reported.

In an interim analysis of the combination in patients with newly diagnosed or relapsed/refractory Ph+ALL or lymphoid accelerated or blast phase chronic myeloid leukemia (CML), 20 patients who received it as frontline therapy had a rate of complete responses (CR) or complete responses with partial recovery of blood counts (CRp) of 100% and a complete molecular remission (CMR) rate of 85%, reported Nicholas Short, MD, of the University of Texas MD Anderson Cancer Center in Houston.

“This translated into an estimated 2-year overall survival of 93%, with no patients undergoing transplant in first remission, and none having relapse at last follow-up,” he said in an oral abstract presented during the European Hematology Association annual congress.

Among patients with relapsed/refractory Ph+ALL, the CR/CRp rate was 89%, the CMR rate was 88%, and the estimated 2-year overall survival rate was 53%, he said.
 

Transplants on hold

“The big selling point is the ability to avoid stem cell transplant, which is not always the first thing you do in Ph-positive ALL, but it’s always on your mind,” said Gwen Nichols, MD, chief medical officer of the Leukemia and Lymphoma Society, who was not involved in the study.

“It looks, albeit with very limited follow-up, that patients haven’t relapsed yet such that transplant would be necessary. Anything we can do to avoid people having long-term complications that go along with an allogeneic transplant is a step in the right direction,” she said in an interview.
 

One combination, three cohorts

Ph+ALL comprises about 25% of all adult ALL. The standard of care in newly diagnosed patients is chemotherapy plus a tyrosine kinase inhibitor (TKI) targeted against the BCR-ABL transcript.

Ponatinib is a pan-BCR-ABL TKI that has been shown to have activity against ALL with T315I mutations, which are present in about 75% of the cases of relapsed disease, Dr. Short said.

Blinatumomab is a bi-specific T-cell engager (BiTe) that has been shown to be effective as monotherapy against relapsed/refractory Ph+ALL as monotherapy and in combination with dasatinib.

Dr. Short and colleagues enrolled patients with newly diagnosed or relapsed/refractory Ph+ALL or lymphoid accelerated or blast phase CML. Patients in the frontline cohort could have received one or two prior lines of chemotherapy with or without a TKI.

The patients all had Eastern Cooperative Oncology Group performance status of 0-2, and adequate liver function.

Patients with clinically significant cardiovascular disease or central nervous system disease pathology were excluded, except that patients with CNS leukemia could be enrolled.

The induction phase consisted of 30 mg ponatinib daily plus blinatumomab standard dosing on a 4-week-on, 2-week-off schedule. Patients in CMR, defined for frontline patients as undetectable BCR-ABL transcripts by polymerase chain reaction, then received up to four consolidation cycles of the regimen with ponatinib at a 15-mg dose, followed by 5 years of ponatinib 15-mg maintenance. All patients also received CNS prophylaxis with 12 cycles of intrathecal chemotherapy with alternating administration of methotrexate and cytarabine.

Of the 35 patients treated to date with the combination, 20 with Ph+ALL received it as frontline therapy and 10 received it for relapsed/refractory disease; 5 patients with CML in lymphoid blast phase also were treated.
 

High CMR, CR rates

As noted before, the CMR rate, the primary endpoint among patients with newly diagnosed Ph+ALL, was 85%, with a CR/CRp rate of 100%. Six of the patients in the frontline group and one in the salvage therapy group had CRs but were positive for minimal residual disease (MRD) at study outset.

The CR/CRp rate for the entire cohort of 28 patients (excluding those with a CR at start) was 96%, with only 1 patient who had relapsed/refractory disease not having a CR. This patient had received ponatinib in a prior salvage regimen.

The CMR rate among the entire cohort was 79%, with 85% of patients in the frontline ALL cohort having a CMR, 88% in the relapsed/refractory cohort, and 40% in the CML cohort. There were no early deaths among any patients.

“After one cycle of ponatinib plus blinatumomab, 84% of frontline patients had achieved at least a major molecular response, and 58% had achieved a CMR. Among those with relapsed/refractory Ph+ALL, 75% achieved CMR after one cycle of therapy,” Dr. Short said.

Of the 20 frontline patients in CR, one patient experienced visual changes and possible stroke that were considered possibly related to the study medication. This patient was taken off study. During a later maintenance regimen this patient developed a non-ST elevation myocardial infarction and died from postprocedural bleeding and hypovolemic shock following a cardiac catheterization procedure.

The remainder of patients in the frontline cohort had ongoing responses without the need for HSCT at last follow-up. There were no relapses, with a median duration of CR of 6 months,

Among the 10 with relapsed/refractory Ph+ALL, one did not have a response, and the remaining 9 had CR/CRps.

Of the latter groups, four went on to allogeneic HSCT and three were still alive; one patient who underwent a transplant experienced a relapse and died. One additional patient was alive with relapsed disease with T315I and E255V mutations at the time of relapse, one patient in CR who went off study due to insurance issues died from an unknown cause, and the three remaining patients had ongoing responses without transplant.

Among the five patients with CML in lymphoid blast phase, two had relapses, but both are still alive and currently in remission, and three have ongoing responses without transplant.

After a median follow-up of 12 months the 1-year event-free survival (EFS) rate for the entire 35-patient group was 76%, and the 2-year EFS was 70%.

The 1-year overall survival rate was 93%, and the 2-year OS rate was 80%.

Among patients in the frontline group, the 1-year and 2-year EFS and OS rates were all 93%.

For the relapsed/refractory cohort, the estimated 2-year EFS was 41% and OS was 53%. For the CML cohort, the 2-year EFS was 60%, with all patients still alive at last follow-up.

There were no grade 4 adverse events on study. Grade 3 adverse events considered at least possibly related to study treatment were elevated lipase, fever/febrile neutropenia, increased alanine aminotransferase, cerebrovascular ischemia, hypertension, pancreatitis, deep vein thrombosis, and encephalopathy. There were no cases of grade 3 cytokine release syndrome or tremor.

The study was sponsored by MD Anderson Cancer Center with collaboration from the National Cancer Institute, Amgen, and Takeda. Dr. Short has disclosed relationships with Amgen and Takeda. Dr. Nichols reported having no conflicts of interest.

Compared with their non-Black counterparts, Black patients with atopic dermatitis (AD) are significantly more likely to be younger, have lower household incomes, live in an urban setting, and use Medicaid or state assistance. They also have significantly poorer disease control and an increased rate of comorbid skin infections.

Those are among the key findings from a 25-question survey administered to members of the National Eczema Association.

“Black individuals with AD have a unique sociodemographic and disease profile,” lead study investigator Raj Chovatiya, MD, PhD, said during the Revolutionizing Atopic Dermatitis symposium. “Out-of-pocket expenses are just one component of the real-world burden faced by this population.”

According to Dr. Chovatiya, of the department of dermatology at Northwestern University, Chicago, the clinical phenotype and burden of AD can vary across racial and ethnic groups. Black race, for example, is associated with a higher prevalence of AD, a higher burden of moderate to severe disease, increased rates of allergic comorbidities, greater AD-related impact on health-related quality of life, and more treatment-resistant AD.

“These features can make long-term AD control very difficult,” he said. “Given the variable long-term efficacy and safety of current treatments, health care providers and patients often have to combine therapies, seek new treatments, and consider adjunctive approaches – all of which can contribute to increased costs.”

AD is also associated with a considerable financial burden, he continued, including direct health care costs, lost work productivity and out-of-pocket health care expenses. “Previous population-based studies suggest that there are multifactorial increases in overall out-of-pocket health expenses in AD,” Dr. Chovatiya said. “Black race in particular is thought to be associated with increased health care utilization in AD, but little is known about the out-of-pocket health care expenses.”

To characterize the categories and impact of out-of-pocket health care expenses associated with AD management among Black individuals, he and his colleagues administered a 25-question voluntary survey to 113,502 members of the NEA between Nov. 14 and Dec. 21, 2019. They included adults with a self-reported diagnosis of AD or children, teens, or young adults who had a caregiver responding for them. In all, 1,118 respondents met inclusion criteria. Questions included those about out-of-pocket expenses for AD over the past 30 days and over the past year, as well as the disease impact on household finances.

The cohort included 75% of individuals with AD; 25% were primary caregivers of children, teens, and young adults with AD. More than three-quarters of respondents (77%) were female, 73% were White, 11% were Black, 6% were Asian, and the remainder were from other ethnic backgrounds. More than half of respondents (58%) had employer-sponsored insurance coverage and the median annual household income was between $50,000 and $75,000.

Nearly three-quarters of respondents (74%) classified their AD severity as moderate or severe, and 63% reported minimally controlled or somewhat-controlled AD. Black respondents were significantly more likely to be younger, have lower household incomes, live in an urban setting, use Medicaid or state assistance, have poor disease control, and frequent skin infections (P ≤ .02). “A numerically higher proportion of Black respondents also had increased AD severity and reported the use of step-up therapy with systemic agents, prescription polypharmacy with three or more prescriptions, and a higher monthly out-of-pocket cost,” Dr. Chovatiya said.

Compared with their non-Black counterparts, Black survey respondents reported more out-of-pocket costs for prescription medications covered by insurance (74.2% vs. 63.6%, P = .04), prescription medications not covered by insurance (65.1% vs. 46.5%, P = .0004), ED visits (22.1% vs. 11.8%, P = .005), and outpatient laboratory testing (33.3% vs. 21.8%, P = .01). Black race was associated with increased household financial impact from out-of-pocket expenses (P = .0009), and predictors of financial impact included minimally controlled AD (adjusted odds ratio, 13.88; P = .02), comorbid anxiety and/or depression (aOR, 4.34; P = .01), systemic therapy (aOR, 4.34; P = .003), out-of-pocket costs that exceeded $200 per month (aOR, 14.28; P = .0003), and Medicaid insurance (aOR, 4.02; P = .03). Blacks with Medicaid had higher odds of harmful financial impact (aOR, 3.32; P = .0002) than respondents who were Black (aOR, 1.81; P = .04) or those with Medicaid alone (aOR, 1.39; P = .04).

“I looked at some of the findings from recent studies that have talked about this burden, including an increased prevalence among Black children, a higher likelihood of moderate to severe disease, higher rates of ED visits and hospitalizations, and increased prescription medications,” Dr. Chovatiya said.“Our findings reflect these racial and socioeconomic disparities and provide another piece of evidence for increased financial burden among Black individuals with AD and support the need for targeted strategies to address these inequities.”

The study received funding support from the NEA. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for AbbVie, Incyte, and Regeneron/Sanofi-Genzyme.

dbrunk@mdedge.com

Compared with their non-Black counterparts, Black patients with atopic dermatitis (AD) are significantly more likely to be younger, have lower household incomes, live in an urban setting, and use Medicaid or state assistance. They also have significantly poorer disease control and an increased rate of comorbid skin infections.

Those are among the key findings from a 25-question survey administered to members of the National Eczema Association.

“Black individuals with AD have a unique sociodemographic and disease profile,” lead study investigator Raj Chovatiya, MD, PhD, said during the Revolutionizing Atopic Dermatitis symposium. “Out-of-pocket expenses are just one component of the real-world burden faced by this population.”

According to Dr. Chovatiya, of the department of dermatology at Northwestern University, Chicago, the clinical phenotype and burden of AD can vary across racial and ethnic groups. Black race, for example, is associated with a higher prevalence of AD, a higher burden of moderate to severe disease, increased rates of allergic comorbidities, greater AD-related impact on health-related quality of life, and more treatment-resistant AD.

“These features can make long-term AD control very difficult,” he said. “Given the variable long-term efficacy and safety of current treatments, health care providers and patients often have to combine therapies, seek new treatments, and consider adjunctive approaches – all of which can contribute to increased costs.”

AD is also associated with a considerable financial burden, he continued, including direct health care costs, lost work productivity and out-of-pocket health care expenses. “Previous population-based studies suggest that there are multifactorial increases in overall out-of-pocket health expenses in AD,” Dr. Chovatiya said. “Black race in particular is thought to be associated with increased health care utilization in AD, but little is known about the out-of-pocket health care expenses.”

To characterize the categories and impact of out-of-pocket health care expenses associated with AD management among Black individuals, he and his colleagues administered a 25-question voluntary survey to 113,502 members of the NEA between Nov. 14 and Dec. 21, 2019. They included adults with a self-reported diagnosis of AD or children, teens, or young adults who had a caregiver responding for them. In all, 1,118 respondents met inclusion criteria. Questions included those about out-of-pocket expenses for AD over the past 30 days and over the past year, as well as the disease impact on household finances.

The cohort included 75% of individuals with AD; 25% were primary caregivers of children, teens, and young adults with AD. More than three-quarters of respondents (77%) were female, 73% were White, 11% were Black, 6% were Asian, and the remainder were from other ethnic backgrounds. More than half of respondents (58%) had employer-sponsored insurance coverage and the median annual household income was between $50,000 and $75,000.

Nearly three-quarters of respondents (74%) classified their AD severity as moderate or severe, and 63% reported minimally controlled or somewhat-controlled AD. Black respondents were significantly more likely to be younger, have lower household incomes, live in an urban setting, use Medicaid or state assistance, have poor disease control, and frequent skin infections (P ≤ .02). “A numerically higher proportion of Black respondents also had increased AD severity and reported the use of step-up therapy with systemic agents, prescription polypharmacy with three or more prescriptions, and a higher monthly out-of-pocket cost,” Dr. Chovatiya said.

Compared with their non-Black counterparts, Black survey respondents reported more out-of-pocket costs for prescription medications covered by insurance (74.2% vs. 63.6%, P = .04), prescription medications not covered by insurance (65.1% vs. 46.5%, P = .0004), ED visits (22.1% vs. 11.8%, P = .005), and outpatient laboratory testing (33.3% vs. 21.8%, P = .01). Black race was associated with increased household financial impact from out-of-pocket expenses (P = .0009), and predictors of financial impact included minimally controlled AD (adjusted odds ratio, 13.88; P = .02), comorbid anxiety and/or depression (aOR, 4.34; P = .01), systemic therapy (aOR, 4.34; P = .003), out-of-pocket costs that exceeded $200 per month (aOR, 14.28; P = .0003), and Medicaid insurance (aOR, 4.02; P = .03). Blacks with Medicaid had higher odds of harmful financial impact (aOR, 3.32; P = .0002) than respondents who were Black (aOR, 1.81; P = .04) or those with Medicaid alone (aOR, 1.39; P = .04).

“I looked at some of the findings from recent studies that have talked about this burden, including an increased prevalence among Black children, a higher likelihood of moderate to severe disease, higher rates of ED visits and hospitalizations, and increased prescription medications,” Dr. Chovatiya said.“Our findings reflect these racial and socioeconomic disparities and provide another piece of evidence for increased financial burden among Black individuals with AD and support the need for targeted strategies to address these inequities.”

The study received funding support from the NEA. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for AbbVie, Incyte, and Regeneron/Sanofi-Genzyme.

dbrunk@mdedge.com

Compared with their non-Black counterparts, Black patients with atopic dermatitis (AD) are significantly more likely to be younger, have lower household incomes, live in an urban setting, and use Medicaid or state assistance. They also have significantly poorer disease control and an increased rate of comorbid skin infections.

Those are among the key findings from a 25-question survey administered to members of the National Eczema Association.

“Black individuals with AD have a unique sociodemographic and disease profile,” lead study investigator Raj Chovatiya, MD, PhD, said during the Revolutionizing Atopic Dermatitis symposium. “Out-of-pocket expenses are just one component of the real-world burden faced by this population.”

According to Dr. Chovatiya, of the department of dermatology at Northwestern University, Chicago, the clinical phenotype and burden of AD can vary across racial and ethnic groups. Black race, for example, is associated with a higher prevalence of AD, a higher burden of moderate to severe disease, increased rates of allergic comorbidities, greater AD-related impact on health-related quality of life, and more treatment-resistant AD.

“These features can make long-term AD control very difficult,” he said. “Given the variable long-term efficacy and safety of current treatments, health care providers and patients often have to combine therapies, seek new treatments, and consider adjunctive approaches – all of which can contribute to increased costs.”

AD is also associated with a considerable financial burden, he continued, including direct health care costs, lost work productivity and out-of-pocket health care expenses. “Previous population-based studies suggest that there are multifactorial increases in overall out-of-pocket health expenses in AD,” Dr. Chovatiya said. “Black race in particular is thought to be associated with increased health care utilization in AD, but little is known about the out-of-pocket health care expenses.”

To characterize the categories and impact of out-of-pocket health care expenses associated with AD management among Black individuals, he and his colleagues administered a 25-question voluntary survey to 113,502 members of the NEA between Nov. 14 and Dec. 21, 2019. They included adults with a self-reported diagnosis of AD or children, teens, or young adults who had a caregiver responding for them. In all, 1,118 respondents met inclusion criteria. Questions included those about out-of-pocket expenses for AD over the past 30 days and over the past year, as well as the disease impact on household finances.

The cohort included 75% of individuals with AD; 25% were primary caregivers of children, teens, and young adults with AD. More than three-quarters of respondents (77%) were female, 73% were White, 11% were Black, 6% were Asian, and the remainder were from other ethnic backgrounds. More than half of respondents (58%) had employer-sponsored insurance coverage and the median annual household income was between $50,000 and $75,000.

Nearly three-quarters of respondents (74%) classified their AD severity as moderate or severe, and 63% reported minimally controlled or somewhat-controlled AD. Black respondents were significantly more likely to be younger, have lower household incomes, live in an urban setting, use Medicaid or state assistance, have poor disease control, and frequent skin infections (P ≤ .02). “A numerically higher proportion of Black respondents also had increased AD severity and reported the use of step-up therapy with systemic agents, prescription polypharmacy with three or more prescriptions, and a higher monthly out-of-pocket cost,” Dr. Chovatiya said.

Compared with their non-Black counterparts, Black survey respondents reported more out-of-pocket costs for prescription medications covered by insurance (74.2% vs. 63.6%, P = .04), prescription medications not covered by insurance (65.1% vs. 46.5%, P = .0004), ED visits (22.1% vs. 11.8%, P = .005), and outpatient laboratory testing (33.3% vs. 21.8%, P = .01). Black race was associated with increased household financial impact from out-of-pocket expenses (P = .0009), and predictors of financial impact included minimally controlled AD (adjusted odds ratio, 13.88; P = .02), comorbid anxiety and/or depression (aOR, 4.34; P = .01), systemic therapy (aOR, 4.34; P = .003), out-of-pocket costs that exceeded $200 per month (aOR, 14.28; P = .0003), and Medicaid insurance (aOR, 4.02; P = .03). Blacks with Medicaid had higher odds of harmful financial impact (aOR, 3.32; P = .0002) than respondents who were Black (aOR, 1.81; P = .04) or those with Medicaid alone (aOR, 1.39; P = .04).

“I looked at some of the findings from recent studies that have talked about this burden, including an increased prevalence among Black children, a higher likelihood of moderate to severe disease, higher rates of ED visits and hospitalizations, and increased prescription medications,” Dr. Chovatiya said.“Our findings reflect these racial and socioeconomic disparities and provide another piece of evidence for increased financial burden among Black individuals with AD and support the need for targeted strategies to address these inequities.”

The study received funding support from the NEA. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for AbbVie, Incyte, and Regeneron/Sanofi-Genzyme.

dbrunk@mdedge.com

Pregnant women with a history of bariatric surgery have better cardiovascular adaptation to pregnancy compared with women who have similar early-pregnancy body mass index (BMI) but no history of weight loss surgery, new data suggest.

“Pregnant women who have had bariatric surgery demonstrate better cardiovascular adaptation through lower blood pressure, heart rate, and cardiac output, more favorable diastolic indices, and better systolic function,” reported Deesha Patel, MBBS MRCOG, specialist registrar, Chelsea and Westminster Hospital, London.

“Because the groups were matched for early pregnancy BMI, it’s unlikely that the results are due to weight loss alone but indicate that the metabolic alterations as a result of the surgery, via the enterocardiac axis, play an important role,” Dr. Patel continued.

The findings were presented at the Royal College of Obstetricians and Gynecologists 2021 Virtual World Congress.

Although obesity is known for its inflammatory and toxic effects on the cardiovascular system, it is not clear to what extent the various treatment options for obesity modify these risks in the long term, said Hutan Ashrafian, MD, clinical lecturer in surgery, Imperial College London.

“It is even less clear how anti-obesity interventions affect the cardiovascular system in pregnancy,” Dr. Ashrafian told this news organization.

“This very novel study in pregnant mothers having undergone the most successful and consistent intervention for severe obesity – bariatric or metabolic surgery – gives new clues as to the extent that bariatric procedures can alter cardiovascular risk in pregnant mothers,” continued Dr. Ashrafian, who was not involved in the study.

The results show how bariatric surgery has favorable effects on cardiac adaptation in pregnancy and in turn “might offer protection from pregnancy-related cardiovascular pathology such as preeclampsia,” explained Dr. Ashrafian. “This adds to the known effects of cardiovascular protection of bariatric surgery through the enterocardiac axis, which may explain a wider range of effects that can be translated within pregnancy and possibly following pregnancy in the postpartum era and beyond.”
 

A history of bariatric surgery versus no surgery

The prospective, longitudinal study compared 41 women who had a history of bariatric surgery with 41 women who had not undergone surgery. Patients’ characteristics were closely matched for age, BMI (34.5 kg/m2 and 34.3 kg/m2 in the surgery and bariatric surgery groups, respectively) and race. Hypertensive disorders in the post-surgery group were significantly less common compared with the no-surgery group (0% vs. 9.8%).

During the study, participants underwent cardiovascular assessment at 12-14 weeks, 20-24 weeks, and 30-32 weeks of gestation. The assessment included measurement of blood pressure and heart rate, transthoracic echocardiography, and 2D speckle tracking, performed offline to assess global longitudinal and circumferential strain.

Blood pressure readings across the three trimesters were consistently lower in the women who had undergone bariatric surgery compared with those in the no-surgery group, and all differences were statistically significant. Likewise, heart rate and cardiac output across the three trimesters were lower in the post-surgery cohort. However, there was no difference in stroke volume between the two groups.

As for diastolic function, there were more favorable indices in the post-surgery group with a higher E/A ratio, a marker of left ventricle filling (P < .001), and lower left atrial volume (P < .05), Dr. Patel reported.

With respect to systolic function, there was no difference in ejection fraction, but there was lower global longitudinal strain (P < .01) and global circumferential strain in the post-bariatric group (P = .02), suggesting better systolic function.

“Strain is a measure of differences in motion and velocity between regions of the myocardium through the cardiac cycle and can detect subclinical changes when ejection fraction is normal,” she added.

“This is a fascinating piece of work. The author should be congratulated on gathering so many [pregnant] women who had had bariatric surgery. The work gives a unique glimpse into metabolic syndrome,” said Philip Toozs-Hobson, MD, who moderated the session.

“We are increasingly recognizing the impact [of bariatric surgery] on metabolic syndrome, and the fact that this study demonstrates that there is more to it than just weight is important,” continued Dr. Toosz-Hobson, who is a consultant gynecologist at Birmingham Women’s Hospital NHS Foundation Trust, United Kingdom.
 

Cardiovascular benefits of bariatric surgery

Bariatric surgery has been associated with loss of excess body weight of up to 55% and with approximately 40% reduction in all-cause mortality in the general population. The procedure also reduces the risk for heart disease, diabetes, and cancer.

The cardiovascular benefits of bariatric surgery include reduced hypertension, remodeling of the heart with a reduction in left ventricular mass, and an improvement in diastolic and systolic function.

“Traditionally, the cardiac changes were thought to be due to weight loss and blood pressure reduction, but it is now conceivable that the metabolic components contribute to the reverse modeling via changes to the enterocardiac axis involving changes to gut hormones,” said Dr. Patel. These hormones include secretin, glucagon, and vasoactive intestinal peptide, which are known to have inotropic effects, as well as adiponectin and leptin, which are known to have cardiac effects, she added.

“Pregnancy following bariatric surgery is associated with a reduced risk of hypertensive disorders, as well as a reduced risk of gestational diabetes, large-for-gestational-age neonates, and a small increased risk of small-for-gestational-age neonates,” said Dr. Patel.

Dr. Patel and Dr. Toosz-Hobson have disclosed no relevant financial relationships.

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

Pregnant women with a history of bariatric surgery have better cardiovascular adaptation to pregnancy compared with women who have similar early-pregnancy body mass index (BMI) but no history of weight loss surgery, new data suggest.

“Pregnant women who have had bariatric surgery demonstrate better cardiovascular adaptation through lower blood pressure, heart rate, and cardiac output, more favorable diastolic indices, and better systolic function,” reported Deesha Patel, MBBS MRCOG, specialist registrar, Chelsea and Westminster Hospital, London.

“Because the groups were matched for early pregnancy BMI, it’s unlikely that the results are due to weight loss alone but indicate that the metabolic alterations as a result of the surgery, via the enterocardiac axis, play an important role,” Dr. Patel continued.

The findings were presented at the Royal College of Obstetricians and Gynecologists 2021 Virtual World Congress.

Although obesity is known for its inflammatory and toxic effects on the cardiovascular system, it is not clear to what extent the various treatment options for obesity modify these risks in the long term, said Hutan Ashrafian, MD, clinical lecturer in surgery, Imperial College London.

“It is even less clear how anti-obesity interventions affect the cardiovascular system in pregnancy,” Dr. Ashrafian told this news organization.

“This very novel study in pregnant mothers having undergone the most successful and consistent intervention for severe obesity – bariatric or metabolic surgery – gives new clues as to the extent that bariatric procedures can alter cardiovascular risk in pregnant mothers,” continued Dr. Ashrafian, who was not involved in the study.

The results show how bariatric surgery has favorable effects on cardiac adaptation in pregnancy and in turn “might offer protection from pregnancy-related cardiovascular pathology such as preeclampsia,” explained Dr. Ashrafian. “This adds to the known effects of cardiovascular protection of bariatric surgery through the enterocardiac axis, which may explain a wider range of effects that can be translated within pregnancy and possibly following pregnancy in the postpartum era and beyond.”
 

A history of bariatric surgery versus no surgery

The prospective, longitudinal study compared 41 women who had a history of bariatric surgery with 41 women who had not undergone surgery. Patients’ characteristics were closely matched for age, BMI (34.5 kg/m2 and 34.3 kg/m2 in the surgery and bariatric surgery groups, respectively) and race. Hypertensive disorders in the post-surgery group were significantly less common compared with the no-surgery group (0% vs. 9.8%).

During the study, participants underwent cardiovascular assessment at 12-14 weeks, 20-24 weeks, and 30-32 weeks of gestation. The assessment included measurement of blood pressure and heart rate, transthoracic echocardiography, and 2D speckle tracking, performed offline to assess global longitudinal and circumferential strain.

Blood pressure readings across the three trimesters were consistently lower in the women who had undergone bariatric surgery compared with those in the no-surgery group, and all differences were statistically significant. Likewise, heart rate and cardiac output across the three trimesters were lower in the post-surgery cohort. However, there was no difference in stroke volume between the two groups.

As for diastolic function, there were more favorable indices in the post-surgery group with a higher E/A ratio, a marker of left ventricle filling (P < .001), and lower left atrial volume (P < .05), Dr. Patel reported.

With respect to systolic function, there was no difference in ejection fraction, but there was lower global longitudinal strain (P < .01) and global circumferential strain in the post-bariatric group (P = .02), suggesting better systolic function.

“Strain is a measure of differences in motion and velocity between regions of the myocardium through the cardiac cycle and can detect subclinical changes when ejection fraction is normal,” she added.

“This is a fascinating piece of work. The author should be congratulated on gathering so many [pregnant] women who had had bariatric surgery. The work gives a unique glimpse into metabolic syndrome,” said Philip Toozs-Hobson, MD, who moderated the session.

“We are increasingly recognizing the impact [of bariatric surgery] on metabolic syndrome, and the fact that this study demonstrates that there is more to it than just weight is important,” continued Dr. Toosz-Hobson, who is a consultant gynecologist at Birmingham Women’s Hospital NHS Foundation Trust, United Kingdom.
 

Cardiovascular benefits of bariatric surgery

Bariatric surgery has been associated with loss of excess body weight of up to 55% and with approximately 40% reduction in all-cause mortality in the general population. The procedure also reduces the risk for heart disease, diabetes, and cancer.

The cardiovascular benefits of bariatric surgery include reduced hypertension, remodeling of the heart with a reduction in left ventricular mass, and an improvement in diastolic and systolic function.

“Traditionally, the cardiac changes were thought to be due to weight loss and blood pressure reduction, but it is now conceivable that the metabolic components contribute to the reverse modeling via changes to the enterocardiac axis involving changes to gut hormones,” said Dr. Patel. These hormones include secretin, glucagon, and vasoactive intestinal peptide, which are known to have inotropic effects, as well as adiponectin and leptin, which are known to have cardiac effects, she added.

“Pregnancy following bariatric surgery is associated with a reduced risk of hypertensive disorders, as well as a reduced risk of gestational diabetes, large-for-gestational-age neonates, and a small increased risk of small-for-gestational-age neonates,” said Dr. Patel.

Dr. Patel and Dr. Toosz-Hobson have disclosed no relevant financial relationships.

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

Pregnant women with a history of bariatric surgery have better cardiovascular adaptation to pregnancy compared with women who have similar early-pregnancy body mass index (BMI) but no history of weight loss surgery, new data suggest.

“Pregnant women who have had bariatric surgery demonstrate better cardiovascular adaptation through lower blood pressure, heart rate, and cardiac output, more favorable diastolic indices, and better systolic function,” reported Deesha Patel, MBBS MRCOG, specialist registrar, Chelsea and Westminster Hospital, London.

“Because the groups were matched for early pregnancy BMI, it’s unlikely that the results are due to weight loss alone but indicate that the metabolic alterations as a result of the surgery, via the enterocardiac axis, play an important role,” Dr. Patel continued.

The findings were presented at the Royal College of Obstetricians and Gynecologists 2021 Virtual World Congress.

Although obesity is known for its inflammatory and toxic effects on the cardiovascular system, it is not clear to what extent the various treatment options for obesity modify these risks in the long term, said Hutan Ashrafian, MD, clinical lecturer in surgery, Imperial College London.

“It is even less clear how anti-obesity interventions affect the cardiovascular system in pregnancy,” Dr. Ashrafian told this news organization.

“This very novel study in pregnant mothers having undergone the most successful and consistent intervention for severe obesity – bariatric or metabolic surgery – gives new clues as to the extent that bariatric procedures can alter cardiovascular risk in pregnant mothers,” continued Dr. Ashrafian, who was not involved in the study.

The results show how bariatric surgery has favorable effects on cardiac adaptation in pregnancy and in turn “might offer protection from pregnancy-related cardiovascular pathology such as preeclampsia,” explained Dr. Ashrafian. “This adds to the known effects of cardiovascular protection of bariatric surgery through the enterocardiac axis, which may explain a wider range of effects that can be translated within pregnancy and possibly following pregnancy in the postpartum era and beyond.”
 

A history of bariatric surgery versus no surgery

The prospective, longitudinal study compared 41 women who had a history of bariatric surgery with 41 women who had not undergone surgery. Patients’ characteristics were closely matched for age, BMI (34.5 kg/m2 and 34.3 kg/m2 in the surgery and bariatric surgery groups, respectively) and race. Hypertensive disorders in the post-surgery group were significantly less common compared with the no-surgery group (0% vs. 9.8%).

During the study, participants underwent cardiovascular assessment at 12-14 weeks, 20-24 weeks, and 30-32 weeks of gestation. The assessment included measurement of blood pressure and heart rate, transthoracic echocardiography, and 2D speckle tracking, performed offline to assess global longitudinal and circumferential strain.

Blood pressure readings across the three trimesters were consistently lower in the women who had undergone bariatric surgery compared with those in the no-surgery group, and all differences were statistically significant. Likewise, heart rate and cardiac output across the three trimesters were lower in the post-surgery cohort. However, there was no difference in stroke volume between the two groups.

As for diastolic function, there were more favorable indices in the post-surgery group with a higher E/A ratio, a marker of left ventricle filling (P < .001), and lower left atrial volume (P < .05), Dr. Patel reported.

With respect to systolic function, there was no difference in ejection fraction, but there was lower global longitudinal strain (P < .01) and global circumferential strain in the post-bariatric group (P = .02), suggesting better systolic function.

“Strain is a measure of differences in motion and velocity between regions of the myocardium through the cardiac cycle and can detect subclinical changes when ejection fraction is normal,” she added.

“This is a fascinating piece of work. The author should be congratulated on gathering so many [pregnant] women who had had bariatric surgery. The work gives a unique glimpse into metabolic syndrome,” said Philip Toozs-Hobson, MD, who moderated the session.

“We are increasingly recognizing the impact [of bariatric surgery] on metabolic syndrome, and the fact that this study demonstrates that there is more to it than just weight is important,” continued Dr. Toosz-Hobson, who is a consultant gynecologist at Birmingham Women’s Hospital NHS Foundation Trust, United Kingdom.
 

Cardiovascular benefits of bariatric surgery

Bariatric surgery has been associated with loss of excess body weight of up to 55% and with approximately 40% reduction in all-cause mortality in the general population. The procedure also reduces the risk for heart disease, diabetes, and cancer.

The cardiovascular benefits of bariatric surgery include reduced hypertension, remodeling of the heart with a reduction in left ventricular mass, and an improvement in diastolic and systolic function.

“Traditionally, the cardiac changes were thought to be due to weight loss and blood pressure reduction, but it is now conceivable that the metabolic components contribute to the reverse modeling via changes to the enterocardiac axis involving changes to gut hormones,” said Dr. Patel. These hormones include secretin, glucagon, and vasoactive intestinal peptide, which are known to have inotropic effects, as well as adiponectin and leptin, which are known to have cardiac effects, she added.

“Pregnancy following bariatric surgery is associated with a reduced risk of hypertensive disorders, as well as a reduced risk of gestational diabetes, large-for-gestational-age neonates, and a small increased risk of small-for-gestational-age neonates,” said Dr. Patel.

Dr. Patel and Dr. Toosz-Hobson have disclosed no relevant financial relationships.

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