Conference Coverage

MADRID — Airplane travel consistently causes insulin pumps to over-deliver a little over half a unit on takeoff and under-deliver a bit less on landing, new research found.

This phenomenon is due to air bubble formation and reabsorption in the insulin caused by ambient pressure changes in the airplane’s cabin. It has nothing to do with the pump itself and happens with all insulin pumps, including those in hybrid closed-loop systems, Bruce King, MD, said at the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting.

The extent to which this affects people with diabetes who use insulin pumps depends on their dose and insulin sensitivity among other factors, but all who fly should be aware of the possibility and take precautions, particularly with children, Dr. King, a pediatric endocrinologist at John Hunter Children’s Hospital, Newcastle, Australia, told this news organization.

“Basically, the pumps are very safe in flight, but they deliver a little bit of extra insulin when you go up and stop delivery when you come back down again. There are a couple of simple steps that people can take to make sure that they don’t have problems during the flight,” he said.

Specifically, he advised that for pumps with tubing, wearers can disconnect just prior to takeoff and reconnect when the plane reaches cruising altitude, about 20 minutes into the flight. The insulin will still come out, but it won’t be delivered to the person, Dr. King said.

On descent, they can disconnect after landing and prime the line to remove the insulin deficit.

With the Omnipod, which can’t be disconnected, the only solution is to eat a small snack on takeoff. And on landing, eat another small snack such as a banana, and give a bolus for it to overcome the blockage of insulin delivery.

In any case, Dr. King said, “One of the most important things is informing people with diabetes about this effect so they’re aware of it and can act appropriately when they fly.”

Asked to comment, Nicholas B. Argento, MD, a practicing endocrinologist in Columbia, Maryland, and author of the American Diabetes Association’s book, “Putting Your Patients on the Pump,” called the issue a “minor effect,” adding, “While I think it would be reasonable to make those changes ... it seems like a lot of effort for a difference of 0.6 units extra on ascent and 0.5 units less on descent.”

He noted there is a risk that the individual might forget to reattach the pump after 20 minutes, leading to hyperglycemia and even diabetic ketoacidosis. Instead, “one could put the pump on suspend for 1 hour on ascent. That would not stop the extra insulin but would net less insulin during that time period.”

And after descent, “you have to walk a lot in most cases, so I don’t think they need to take this into consideration. So many other factors change in air travel that I don’t think this is a significant enough effect to make the effort.”
 

A Known Phenomenon, the Manufacturers Are Aware

This phenomenon has been described previously, including by Dr. King in a 2011 Diabetes Care paper. The new research is among a series of experiments funded by the European Union Aviation Safety Agency in collaboration with the pump manufacturers Medtronic (MiniMed), Tandem (t:slim), and Insulet (Omnipod), primarily aimed at establishing safety parameters for airline pilots with insulin-treated diabetes.

Both the Omnipod DASH and Omnipod 5 User Guides include warnings about unintended insulin delivery during flight, and both advise users to check their blood glucose levels frequently while flying.

In a statement, Jordan Pinsker, MD, Chief Medical Officer at Tandem Diabetes Care, told this news organization, “While it has long been known that routine air travel pressure changes can cause minor fluctuations in insulin pump delivery, the impact of these variations have been found to be generally minor as it relates to glycemic control.”

Dr. Pinsker added that the Tandem Mobi user manual includes a warning related to significant pressure changes in specific air travel situations and offers guidance to disconnect. However, “the t:slim X2 pump’s microdelivery technology limits how much extra insulin can get delivered from air pressure changes due to a mechanism between the tubing and the contents of the bag inside the cartridge.”

Medtronic’s user guide says that the 780G system has not been tested at altitudes higher than 10,150 feet.
 

Hypobaric Chamber Used to Simulate Flight

The study was conducted in vitro, in a hypobaric chamber designed to mimic atmospheric changes during commercial flight. A total of 10 Medtronic MiniMed 780G, 10 Tandem t:slim X2, and six Insulet Omnipod DASH pumps were tested.

The hypobaric chamber was depressurized to 550 mm Hg over a 20-minute ascent, maintained at a 30-minute cruise, followed by a 20-minute descent to ground (750 mm Hg). During the simulated flights, insulin infusion was set at 0.6 units per hour, a rate typical for both adults and children, to allow accurate measurements with multiple flights.

Insulin delivery rates and bubble formation were recorded by attaching infusion sets to open-ended 100 µL capillary tubes against 1-mm grid paper.

Full cartridges — Medtronic: 3 mL, t:slim: 3 mL, and Omnipod: 2 mL — all over-delivered 0.60 units of insulin over a 20-minute ascent compared with delivery at ground level. And during descent, the cartridges under-delivered 0.51 units of insulin.
 

But if There’s Rapid Decompression…

In a separate protocol, insulin infusion sets without pumps were tested in a simulation of rapid decompression. Insulin delivery during both ascent and descent showed statistically significant differences compared with delivery at ground level (both P < .001). In this scenario, fluid delivery was equivalent to 5.6 units of excess insulin.

Dr. King pointed out that while these are rare events, about 40-50 occur annually. One was the widely publicized Alaska Airlines flight in January 2024 when the door fell off in midair.

Dr. Argento said, “The catastrophic decompression is of note, and I would want patients to be aware of this, but it is asking a lot for someone thinking they are going to die to remember to disconnect as it starts.”

The researchers are investigating this phenomenon further in people, including airline pilots.

Dr. King’s research group has been involved in research with Medtronic, Tandem, and Insulet. Dr. Argento has consulted or been on advisory boards for Eli Lilly Diabetes, Dexcom, Diabeloop, Convatec, and Senseonics and served on the speakers’ bureaus for Boehringer Ingelheim, Dexcom, Eli Lilly Diabetes, MannKind, Novo Nordisk, Xeris, and Zealand Pharma.
 

A version of this article appeared on Medscape.com.

MADRID — Airplane travel consistently causes insulin pumps to over-deliver a little over half a unit on takeoff and under-deliver a bit less on landing, new research found.

This phenomenon is due to air bubble formation and reabsorption in the insulin caused by ambient pressure changes in the airplane’s cabin. It has nothing to do with the pump itself and happens with all insulin pumps, including those in hybrid closed-loop systems, Bruce King, MD, said at the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting.

The extent to which this affects people with diabetes who use insulin pumps depends on their dose and insulin sensitivity among other factors, but all who fly should be aware of the possibility and take precautions, particularly with children, Dr. King, a pediatric endocrinologist at John Hunter Children’s Hospital, Newcastle, Australia, told this news organization.

“Basically, the pumps are very safe in flight, but they deliver a little bit of extra insulin when you go up and stop delivery when you come back down again. There are a couple of simple steps that people can take to make sure that they don’t have problems during the flight,” he said.

Specifically, he advised that for pumps with tubing, wearers can disconnect just prior to takeoff and reconnect when the plane reaches cruising altitude, about 20 minutes into the flight. The insulin will still come out, but it won’t be delivered to the person, Dr. King said.

On descent, they can disconnect after landing and prime the line to remove the insulin deficit.

With the Omnipod, which can’t be disconnected, the only solution is to eat a small snack on takeoff. And on landing, eat another small snack such as a banana, and give a bolus for it to overcome the blockage of insulin delivery.

In any case, Dr. King said, “One of the most important things is informing people with diabetes about this effect so they’re aware of it and can act appropriately when they fly.”

Asked to comment, Nicholas B. Argento, MD, a practicing endocrinologist in Columbia, Maryland, and author of the American Diabetes Association’s book, “Putting Your Patients on the Pump,” called the issue a “minor effect,” adding, “While I think it would be reasonable to make those changes ... it seems like a lot of effort for a difference of 0.6 units extra on ascent and 0.5 units less on descent.”

He noted there is a risk that the individual might forget to reattach the pump after 20 minutes, leading to hyperglycemia and even diabetic ketoacidosis. Instead, “one could put the pump on suspend for 1 hour on ascent. That would not stop the extra insulin but would net less insulin during that time period.”

And after descent, “you have to walk a lot in most cases, so I don’t think they need to take this into consideration. So many other factors change in air travel that I don’t think this is a significant enough effect to make the effort.”
 

A Known Phenomenon, the Manufacturers Are Aware

This phenomenon has been described previously, including by Dr. King in a 2011 Diabetes Care paper. The new research is among a series of experiments funded by the European Union Aviation Safety Agency in collaboration with the pump manufacturers Medtronic (MiniMed), Tandem (t:slim), and Insulet (Omnipod), primarily aimed at establishing safety parameters for airline pilots with insulin-treated diabetes.

Both the Omnipod DASH and Omnipod 5 User Guides include warnings about unintended insulin delivery during flight, and both advise users to check their blood glucose levels frequently while flying.

In a statement, Jordan Pinsker, MD, Chief Medical Officer at Tandem Diabetes Care, told this news organization, “While it has long been known that routine air travel pressure changes can cause minor fluctuations in insulin pump delivery, the impact of these variations have been found to be generally minor as it relates to glycemic control.”

Dr. Pinsker added that the Tandem Mobi user manual includes a warning related to significant pressure changes in specific air travel situations and offers guidance to disconnect. However, “the t:slim X2 pump’s microdelivery technology limits how much extra insulin can get delivered from air pressure changes due to a mechanism between the tubing and the contents of the bag inside the cartridge.”

Medtronic’s user guide says that the 780G system has not been tested at altitudes higher than 10,150 feet.
 

Hypobaric Chamber Used to Simulate Flight

The study was conducted in vitro, in a hypobaric chamber designed to mimic atmospheric changes during commercial flight. A total of 10 Medtronic MiniMed 780G, 10 Tandem t:slim X2, and six Insulet Omnipod DASH pumps were tested.

The hypobaric chamber was depressurized to 550 mm Hg over a 20-minute ascent, maintained at a 30-minute cruise, followed by a 20-minute descent to ground (750 mm Hg). During the simulated flights, insulin infusion was set at 0.6 units per hour, a rate typical for both adults and children, to allow accurate measurements with multiple flights.

Insulin delivery rates and bubble formation were recorded by attaching infusion sets to open-ended 100 µL capillary tubes against 1-mm grid paper.

Full cartridges — Medtronic: 3 mL, t:slim: 3 mL, and Omnipod: 2 mL — all over-delivered 0.60 units of insulin over a 20-minute ascent compared with delivery at ground level. And during descent, the cartridges under-delivered 0.51 units of insulin.
 

But if There’s Rapid Decompression…

In a separate protocol, insulin infusion sets without pumps were tested in a simulation of rapid decompression. Insulin delivery during both ascent and descent showed statistically significant differences compared with delivery at ground level (both P < .001). In this scenario, fluid delivery was equivalent to 5.6 units of excess insulin.

Dr. King pointed out that while these are rare events, about 40-50 occur annually. One was the widely publicized Alaska Airlines flight in January 2024 when the door fell off in midair.

Dr. Argento said, “The catastrophic decompression is of note, and I would want patients to be aware of this, but it is asking a lot for someone thinking they are going to die to remember to disconnect as it starts.”

The researchers are investigating this phenomenon further in people, including airline pilots.

Dr. King’s research group has been involved in research with Medtronic, Tandem, and Insulet. Dr. Argento has consulted or been on advisory boards for Eli Lilly Diabetes, Dexcom, Diabeloop, Convatec, and Senseonics and served on the speakers’ bureaus for Boehringer Ingelheim, Dexcom, Eli Lilly Diabetes, MannKind, Novo Nordisk, Xeris, and Zealand Pharma.
 

A version of this article appeared on Medscape.com.

MADRID — Airplane travel consistently causes insulin pumps to over-deliver a little over half a unit on takeoff and under-deliver a bit less on landing, new research found.

This phenomenon is due to air bubble formation and reabsorption in the insulin caused by ambient pressure changes in the airplane’s cabin. It has nothing to do with the pump itself and happens with all insulin pumps, including those in hybrid closed-loop systems, Bruce King, MD, said at the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting.

The extent to which this affects people with diabetes who use insulin pumps depends on their dose and insulin sensitivity among other factors, but all who fly should be aware of the possibility and take precautions, particularly with children, Dr. King, a pediatric endocrinologist at John Hunter Children’s Hospital, Newcastle, Australia, told this news organization.

“Basically, the pumps are very safe in flight, but they deliver a little bit of extra insulin when you go up and stop delivery when you come back down again. There are a couple of simple steps that people can take to make sure that they don’t have problems during the flight,” he said.

Specifically, he advised that for pumps with tubing, wearers can disconnect just prior to takeoff and reconnect when the plane reaches cruising altitude, about 20 minutes into the flight. The insulin will still come out, but it won’t be delivered to the person, Dr. King said.

On descent, they can disconnect after landing and prime the line to remove the insulin deficit.

With the Omnipod, which can’t be disconnected, the only solution is to eat a small snack on takeoff. And on landing, eat another small snack such as a banana, and give a bolus for it to overcome the blockage of insulin delivery.

In any case, Dr. King said, “One of the most important things is informing people with diabetes about this effect so they’re aware of it and can act appropriately when they fly.”

Asked to comment, Nicholas B. Argento, MD, a practicing endocrinologist in Columbia, Maryland, and author of the American Diabetes Association’s book, “Putting Your Patients on the Pump,” called the issue a “minor effect,” adding, “While I think it would be reasonable to make those changes ... it seems like a lot of effort for a difference of 0.6 units extra on ascent and 0.5 units less on descent.”

He noted there is a risk that the individual might forget to reattach the pump after 20 minutes, leading to hyperglycemia and even diabetic ketoacidosis. Instead, “one could put the pump on suspend for 1 hour on ascent. That would not stop the extra insulin but would net less insulin during that time period.”

And after descent, “you have to walk a lot in most cases, so I don’t think they need to take this into consideration. So many other factors change in air travel that I don’t think this is a significant enough effect to make the effort.”
 

A Known Phenomenon, the Manufacturers Are Aware

This phenomenon has been described previously, including by Dr. King in a 2011 Diabetes Care paper. The new research is among a series of experiments funded by the European Union Aviation Safety Agency in collaboration with the pump manufacturers Medtronic (MiniMed), Tandem (t:slim), and Insulet (Omnipod), primarily aimed at establishing safety parameters for airline pilots with insulin-treated diabetes.

Both the Omnipod DASH and Omnipod 5 User Guides include warnings about unintended insulin delivery during flight, and both advise users to check their blood glucose levels frequently while flying.

In a statement, Jordan Pinsker, MD, Chief Medical Officer at Tandem Diabetes Care, told this news organization, “While it has long been known that routine air travel pressure changes can cause minor fluctuations in insulin pump delivery, the impact of these variations have been found to be generally minor as it relates to glycemic control.”

Dr. Pinsker added that the Tandem Mobi user manual includes a warning related to significant pressure changes in specific air travel situations and offers guidance to disconnect. However, “the t:slim X2 pump’s microdelivery technology limits how much extra insulin can get delivered from air pressure changes due to a mechanism between the tubing and the contents of the bag inside the cartridge.”

Medtronic’s user guide says that the 780G system has not been tested at altitudes higher than 10,150 feet.
 

Hypobaric Chamber Used to Simulate Flight

The study was conducted in vitro, in a hypobaric chamber designed to mimic atmospheric changes during commercial flight. A total of 10 Medtronic MiniMed 780G, 10 Tandem t:slim X2, and six Insulet Omnipod DASH pumps were tested.

The hypobaric chamber was depressurized to 550 mm Hg over a 20-minute ascent, maintained at a 30-minute cruise, followed by a 20-minute descent to ground (750 mm Hg). During the simulated flights, insulin infusion was set at 0.6 units per hour, a rate typical for both adults and children, to allow accurate measurements with multiple flights.

Insulin delivery rates and bubble formation were recorded by attaching infusion sets to open-ended 100 µL capillary tubes against 1-mm grid paper.

Full cartridges — Medtronic: 3 mL, t:slim: 3 mL, and Omnipod: 2 mL — all over-delivered 0.60 units of insulin over a 20-minute ascent compared with delivery at ground level. And during descent, the cartridges under-delivered 0.51 units of insulin.
 

But if There’s Rapid Decompression…

In a separate protocol, insulin infusion sets without pumps were tested in a simulation of rapid decompression. Insulin delivery during both ascent and descent showed statistically significant differences compared with delivery at ground level (both P < .001). In this scenario, fluid delivery was equivalent to 5.6 units of excess insulin.

Dr. King pointed out that while these are rare events, about 40-50 occur annually. One was the widely publicized Alaska Airlines flight in January 2024 when the door fell off in midair.

Dr. Argento said, “The catastrophic decompression is of note, and I would want patients to be aware of this, but it is asking a lot for someone thinking they are going to die to remember to disconnect as it starts.”

The researchers are investigating this phenomenon further in people, including airline pilots.

Dr. King’s research group has been involved in research with Medtronic, Tandem, and Insulet. Dr. Argento has consulted or been on advisory boards for Eli Lilly Diabetes, Dexcom, Diabeloop, Convatec, and Senseonics and served on the speakers’ bureaus for Boehringer Ingelheim, Dexcom, Eli Lilly Diabetes, MannKind, Novo Nordisk, Xeris, and Zealand Pharma.
 

A version of this article appeared on Medscape.com.

MADRID — Emerging data points to the urgent need for cardiovascular risk reduction in all adults with type 1 diabetes (T1D), including those who are young and those diagnosed in adulthood.

At the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting, two entire oral abstract sessions were devoted to research examining cardiovascular risk specifically in people with T1D. There is increasing evidence that as with type 2 diabetes (T2D), clinical visits need to focus on other cardiovascular risk factors and glucose.

Findings included the evidence of severe coronary artery disease (CAD) in asymptomatic adults with T1D, increased risks for mortality and cardiac events in people diagnosed with T1D in adulthood, and a greater cardiovascular risk for those with overweight/obesity and among those with more cumulative exposure to both hyperglycemia and dyslipidemia.

One speaker, Dr. Rebecka Johanna Bergdal, of the Folkhälsan Research Center and the University of Helsinki, Finland, issued a “call to action,” saying, “We call on healthcare professionals to continue supporting and encouraging individuals with T1D towards better management of diabetes, including both glucose and lipid management.”

Session Moderator Krzysztof Strojek, MD, PhD, head of the Department of Internal Medicine, Diabetology and Cardiometabolic Diseases at the Medical University of Silesia, Katowice, Poland, told this news organization that all the data point in the same direction for T1D management, to “look not only at A1c and blood glucose control but also lipids, hypertension, smoking status, all these risk factors recognized in type 2 ... are also important in T1D.”
 

The ‘Alarming’ Finding of CAD in Asymptomatic Patients

Michal Dubsky, MD, PhD, of the Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic, presented findings from 62 asymptomatic patients with T1D for > 10 years (mean, 36 years), with a mean A1c of 7.5% (58 mmol/mol), and no prior history of cardiovascular disease (CVD). They had slightly elevated CVD biomarkers, including a mean low-density lipoprotein (LDL) cholesterol level of 2.33 mmol/L, lipoprotein (a) level of 15 nmol/L, and N-terminal pro-B-type natriuretic peptide level of 125.3 ng/L. 

All underwent a noninvasive carotid ultrasound and coronary artery calcium (CAC) scoring. Of those, 12 patients had a CAC score > 400 and/or presence of two or more carotid plaques identified as high-risk.

Those 12 patients underwent coronary angiography and had a total of 29 vessels examined by optical coherence tomography (OCT), “an invasive intravascular method for assessing coronary atherosclerosis that is far more sensitive than standard coronary angiography, especially for the detection of high-risk vulnerable plaques without a hemodynamically significant stenosis,” Dr. Dubsky explained.

Coronary angiography showed obstructive CAD in 5 of the 12 patients. Their mean calcium score was 950 and mean number of carotid plaques was 2.8. Features associated with plaque vulnerability included microphage accumulation in 24 vessels, lipid-rich plaques in 23, spotty calcium in 19, and neovascularizations in 13.

Thin-cap fibroatheroma, a strong predictor of plaque rupture, was present in 7 of the 12 patients (58.3%), and four had features of very high-risk plaques, defined as thin-cap fibroatheroma with a minimal lumen area < 3.5 mm², a lipid arch > 180 degrees, and macrophages. 

“Our study showed that asymptomatic T1D patients with high CAC score and carotid plaques had very severe OCT findings. We observed a significant proportion of high-risk lesions potentially associated with plaque rupture and risk of CV death. Therefore, we believe these patients should be treated as very high-risk with target LDL below 1.4 mmol/L (55 mg/dL), even though they are completely asymptomatic,” Dr. Dubsky concluded.

He added that because OCT is invasive and costly, the CAC score can be used to guide the decision for statin use, with any score above 100 considered elevated risk. 

Study coauthor Martin Haluzik, MD, professor of internal medicine in the Charles University, Prague, Czech Republic, told this news organization, “I think it’s very alarming because some of these are basically very healthy-looking young people, so you don’t really expect them to have significant cardiovascular complications already or significant plaques. I think it shows that we should be more proactive in looking into the risk of cardiovascular complications and in looking into the early cardiovascular changes.”
 

Later Diagnosis Doesn’t Always Protect: Risk Seen in Adult-Onset T1D

Yuxia Wei, a PhD student at the Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, presented an analysis of data from Sweden’s national health databases comparing cardiovascular outcomes between 10,184 people diagnosed with T1D at ages 18-29 years, 30-39 years, and ≥ 40 years; another 375,523 people diagnosed with T2D at those ages; and 509,172 population controls matched for age, sex, and county.

Those diagnosed after age 40 years had higher A1c levels and were less likely to be using insulin pumps than those diagnosed at younger adult ages. 

Compared with population controls, at a median of about 7 years of follow-up, people with T1D had significantly higher all-cause mortality at all diagnosis age groups, with a hazard ratio of 1.71. This rose to 2.78 for those diagnosed at age 30-39 years.

Compared with those with T2D, the mortality risks weren’t significantly different at any age, but the risks for non-cardiovascular death, including from cancer and infection, were significantly higher among those diagnosed after age 40 years (1.31 overall). Those diagnosed with T1D at any adult age had lower risks for major cardiovascular events than those diagnosed with T2D. Hazard ratios ranged from 0.27 for those diagnosed at age 18-29 years to 0.78 for those diagnosed after the age of 40 years.

Smoking and A1c above target were the greatest contributors to mortality. Those two factors, along with body mass index (BMI), were the strongest contributors to major adverse cardiovascular events (MACE).

“Adult-onset T1D carries excess risk of death and cardiovascular disease, without obvious attenuation over age at diagnosis…Smoking, A1c, and BMI are the key factors to be managed to improve prognosis in adult-onset T1D,” Ms. Wei concluded.
 

BMI: Often Overlooked in T1D, but a Major CVD Risk Factor

Two studies examined the link between overweight/obesity and cardiovascular risk in T1D. One, by Laurence Salle, MCU PH, of the Endocrinology, Diabetes and Metabolic Diseases Department at CHU Limoges, France, was a prospective, longitudinal cohort study of 2367 people with T1D at 68 centers in France who didn’t have a cardiovascular history at baseline.

Of those, 51% had normal BMI (18.5-24.9), 31% had overweight (25-29.9), and 18% had obesity (≥ 30). Cardiovascular risk factors, including LDL cholesterol, triglycerides, and hypertension increased with an increasing BMI. The 10-year CVD risk was significantly higher for those with overweight (9.61%) and obesity (9.93%) than for those with normal weight (7.24%), in both men and women. 

However, BMI was found to be an independent predictor of 10-year high cardiovascular risk in men but not women, while waist:height ratio independently predicted risk in both men and women, Dr. Salle reported.

The second BMI study, from Enrique Soto-Pedre, MBBS, of the Division of Population Health and Genomics at the University of Dundee, Scotland, presented data on a retrospective follow-up from 1995 to 2019 of 1973 people with T1D aged > 18 years at diagnosis (42% women; mean age, 34.2 years; 18.9% had obesity.

After 10 years of follow-up, those with overweight and obesity had significantly higher odds of developing arterial hypertension, even among those taking angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, with statistically significant adjusted hazard ratios of 1.73 and 3.37 for the obese and overweight groups, respectively. 

MACE were significantly more common among those with obesity, with an adjusted hazard ratio of 2.95, as was acute myocardial infarction, 3.33. 

“These results emphasize the importance of incorporating weight management into the overall management of individuals with T1D. No one has doubts about weight management in T2D, but in type 1, it’s not so clear. One of the main [concerns] would be safety [in terms of hypoglycemia],” Dr. Soto-Pedre concluded. 
 

Call for Action: Cumulative Glucose and Lipid Exposures Increase Risk

Dr. Bergdal presented data on the effects of cumulative glycemia and lipids on the risk for CAD in 3495 adults with T1D who had been diagnosed prior to the age of 40 years. The history of CAD or stroke was exclusion criteria. There were a total of 534 CAD events within a median follow-up of 19.4 years.

Cumulative glycemia, LDL cholesterol, triglycerides, and non–high-density lipoprotein cholesterol exposures were all significantly associated with CAD risk (P < .001 for all). With an adjustment for confounders, the highest tertile of glycemia was associated with a twofold increased risk for CAD. Both hyperglycemia and dyslipidemia were independently associated with CAD risk, Dr. Bergdal reported. 

“It’s important to minimize the time spent above A1c 7%, and lipid management in T1D must not be forgotten,” she said, prior to issuing her call for action.

Dr. Haluzik reported receiving honoraria for talks and/or consultancy and/or research funding from Eli Lilly, Novo Nordisk, Sanofi, AstraZeneca, Mundipharma, Bristol Myers Squibb, Amgen, Boehringer Ingelheim, Janssen, Ypsomed, and Johnson & Johnson. The presenters had no disclosures.
 

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

MADRID — Emerging data points to the urgent need for cardiovascular risk reduction in all adults with type 1 diabetes (T1D), including those who are young and those diagnosed in adulthood.

At the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting, two entire oral abstract sessions were devoted to research examining cardiovascular risk specifically in people with T1D. There is increasing evidence that as with type 2 diabetes (T2D), clinical visits need to focus on other cardiovascular risk factors and glucose.

Findings included the evidence of severe coronary artery disease (CAD) in asymptomatic adults with T1D, increased risks for mortality and cardiac events in people diagnosed with T1D in adulthood, and a greater cardiovascular risk for those with overweight/obesity and among those with more cumulative exposure to both hyperglycemia and dyslipidemia.

One speaker, Dr. Rebecka Johanna Bergdal, of the Folkhälsan Research Center and the University of Helsinki, Finland, issued a “call to action,” saying, “We call on healthcare professionals to continue supporting and encouraging individuals with T1D towards better management of diabetes, including both glucose and lipid management.”

Session Moderator Krzysztof Strojek, MD, PhD, head of the Department of Internal Medicine, Diabetology and Cardiometabolic Diseases at the Medical University of Silesia, Katowice, Poland, told this news organization that all the data point in the same direction for T1D management, to “look not only at A1c and blood glucose control but also lipids, hypertension, smoking status, all these risk factors recognized in type 2 ... are also important in T1D.”
 

The ‘Alarming’ Finding of CAD in Asymptomatic Patients

Michal Dubsky, MD, PhD, of the Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic, presented findings from 62 asymptomatic patients with T1D for > 10 years (mean, 36 years), with a mean A1c of 7.5% (58 mmol/mol), and no prior history of cardiovascular disease (CVD). They had slightly elevated CVD biomarkers, including a mean low-density lipoprotein (LDL) cholesterol level of 2.33 mmol/L, lipoprotein (a) level of 15 nmol/L, and N-terminal pro-B-type natriuretic peptide level of 125.3 ng/L. 

All underwent a noninvasive carotid ultrasound and coronary artery calcium (CAC) scoring. Of those, 12 patients had a CAC score > 400 and/or presence of two or more carotid plaques identified as high-risk.

Those 12 patients underwent coronary angiography and had a total of 29 vessels examined by optical coherence tomography (OCT), “an invasive intravascular method for assessing coronary atherosclerosis that is far more sensitive than standard coronary angiography, especially for the detection of high-risk vulnerable plaques without a hemodynamically significant stenosis,” Dr. Dubsky explained.

Coronary angiography showed obstructive CAD in 5 of the 12 patients. Their mean calcium score was 950 and mean number of carotid plaques was 2.8. Features associated with plaque vulnerability included microphage accumulation in 24 vessels, lipid-rich plaques in 23, spotty calcium in 19, and neovascularizations in 13.

Thin-cap fibroatheroma, a strong predictor of plaque rupture, was present in 7 of the 12 patients (58.3%), and four had features of very high-risk plaques, defined as thin-cap fibroatheroma with a minimal lumen area < 3.5 mm², a lipid arch > 180 degrees, and macrophages. 

“Our study showed that asymptomatic T1D patients with high CAC score and carotid plaques had very severe OCT findings. We observed a significant proportion of high-risk lesions potentially associated with plaque rupture and risk of CV death. Therefore, we believe these patients should be treated as very high-risk with target LDL below 1.4 mmol/L (55 mg/dL), even though they are completely asymptomatic,” Dr. Dubsky concluded.

He added that because OCT is invasive and costly, the CAC score can be used to guide the decision for statin use, with any score above 100 considered elevated risk. 

Study coauthor Martin Haluzik, MD, professor of internal medicine in the Charles University, Prague, Czech Republic, told this news organization, “I think it’s very alarming because some of these are basically very healthy-looking young people, so you don’t really expect them to have significant cardiovascular complications already or significant plaques. I think it shows that we should be more proactive in looking into the risk of cardiovascular complications and in looking into the early cardiovascular changes.”
 

Later Diagnosis Doesn’t Always Protect: Risk Seen in Adult-Onset T1D

Yuxia Wei, a PhD student at the Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, presented an analysis of data from Sweden’s national health databases comparing cardiovascular outcomes between 10,184 people diagnosed with T1D at ages 18-29 years, 30-39 years, and ≥ 40 years; another 375,523 people diagnosed with T2D at those ages; and 509,172 population controls matched for age, sex, and county.

Those diagnosed after age 40 years had higher A1c levels and were less likely to be using insulin pumps than those diagnosed at younger adult ages. 

Compared with population controls, at a median of about 7 years of follow-up, people with T1D had significantly higher all-cause mortality at all diagnosis age groups, with a hazard ratio of 1.71. This rose to 2.78 for those diagnosed at age 30-39 years.

Compared with those with T2D, the mortality risks weren’t significantly different at any age, but the risks for non-cardiovascular death, including from cancer and infection, were significantly higher among those diagnosed after age 40 years (1.31 overall). Those diagnosed with T1D at any adult age had lower risks for major cardiovascular events than those diagnosed with T2D. Hazard ratios ranged from 0.27 for those diagnosed at age 18-29 years to 0.78 for those diagnosed after the age of 40 years.

Smoking and A1c above target were the greatest contributors to mortality. Those two factors, along with body mass index (BMI), were the strongest contributors to major adverse cardiovascular events (MACE).

“Adult-onset T1D carries excess risk of death and cardiovascular disease, without obvious attenuation over age at diagnosis…Smoking, A1c, and BMI are the key factors to be managed to improve prognosis in adult-onset T1D,” Ms. Wei concluded.
 

BMI: Often Overlooked in T1D, but a Major CVD Risk Factor

Two studies examined the link between overweight/obesity and cardiovascular risk in T1D. One, by Laurence Salle, MCU PH, of the Endocrinology, Diabetes and Metabolic Diseases Department at CHU Limoges, France, was a prospective, longitudinal cohort study of 2367 people with T1D at 68 centers in France who didn’t have a cardiovascular history at baseline.

Of those, 51% had normal BMI (18.5-24.9), 31% had overweight (25-29.9), and 18% had obesity (≥ 30). Cardiovascular risk factors, including LDL cholesterol, triglycerides, and hypertension increased with an increasing BMI. The 10-year CVD risk was significantly higher for those with overweight (9.61%) and obesity (9.93%) than for those with normal weight (7.24%), in both men and women. 

However, BMI was found to be an independent predictor of 10-year high cardiovascular risk in men but not women, while waist:height ratio independently predicted risk in both men and women, Dr. Salle reported.

The second BMI study, from Enrique Soto-Pedre, MBBS, of the Division of Population Health and Genomics at the University of Dundee, Scotland, presented data on a retrospective follow-up from 1995 to 2019 of 1973 people with T1D aged > 18 years at diagnosis (42% women; mean age, 34.2 years; 18.9% had obesity.

After 10 years of follow-up, those with overweight and obesity had significantly higher odds of developing arterial hypertension, even among those taking angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, with statistically significant adjusted hazard ratios of 1.73 and 3.37 for the obese and overweight groups, respectively. 

MACE were significantly more common among those with obesity, with an adjusted hazard ratio of 2.95, as was acute myocardial infarction, 3.33. 

“These results emphasize the importance of incorporating weight management into the overall management of individuals with T1D. No one has doubts about weight management in T2D, but in type 1, it’s not so clear. One of the main [concerns] would be safety [in terms of hypoglycemia],” Dr. Soto-Pedre concluded. 
 

Call for Action: Cumulative Glucose and Lipid Exposures Increase Risk

Dr. Bergdal presented data on the effects of cumulative glycemia and lipids on the risk for CAD in 3495 adults with T1D who had been diagnosed prior to the age of 40 years. The history of CAD or stroke was exclusion criteria. There were a total of 534 CAD events within a median follow-up of 19.4 years.

Cumulative glycemia, LDL cholesterol, triglycerides, and non–high-density lipoprotein cholesterol exposures were all significantly associated with CAD risk (P < .001 for all). With an adjustment for confounders, the highest tertile of glycemia was associated with a twofold increased risk for CAD. Both hyperglycemia and dyslipidemia were independently associated with CAD risk, Dr. Bergdal reported. 

“It’s important to minimize the time spent above A1c 7%, and lipid management in T1D must not be forgotten,” she said, prior to issuing her call for action.

Dr. Haluzik reported receiving honoraria for talks and/or consultancy and/or research funding from Eli Lilly, Novo Nordisk, Sanofi, AstraZeneca, Mundipharma, Bristol Myers Squibb, Amgen, Boehringer Ingelheim, Janssen, Ypsomed, and Johnson & Johnson. The presenters had no disclosures.
 

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

MADRID — Emerging data points to the urgent need for cardiovascular risk reduction in all adults with type 1 diabetes (T1D), including those who are young and those diagnosed in adulthood.

At the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting, two entire oral abstract sessions were devoted to research examining cardiovascular risk specifically in people with T1D. There is increasing evidence that as with type 2 diabetes (T2D), clinical visits need to focus on other cardiovascular risk factors and glucose.

Findings included the evidence of severe coronary artery disease (CAD) in asymptomatic adults with T1D, increased risks for mortality and cardiac events in people diagnosed with T1D in adulthood, and a greater cardiovascular risk for those with overweight/obesity and among those with more cumulative exposure to both hyperglycemia and dyslipidemia.

One speaker, Dr. Rebecka Johanna Bergdal, of the Folkhälsan Research Center and the University of Helsinki, Finland, issued a “call to action,” saying, “We call on healthcare professionals to continue supporting and encouraging individuals with T1D towards better management of diabetes, including both glucose and lipid management.”

Session Moderator Krzysztof Strojek, MD, PhD, head of the Department of Internal Medicine, Diabetology and Cardiometabolic Diseases at the Medical University of Silesia, Katowice, Poland, told this news organization that all the data point in the same direction for T1D management, to “look not only at A1c and blood glucose control but also lipids, hypertension, smoking status, all these risk factors recognized in type 2 ... are also important in T1D.”
 

The ‘Alarming’ Finding of CAD in Asymptomatic Patients

Michal Dubsky, MD, PhD, of the Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic, presented findings from 62 asymptomatic patients with T1D for > 10 years (mean, 36 years), with a mean A1c of 7.5% (58 mmol/mol), and no prior history of cardiovascular disease (CVD). They had slightly elevated CVD biomarkers, including a mean low-density lipoprotein (LDL) cholesterol level of 2.33 mmol/L, lipoprotein (a) level of 15 nmol/L, and N-terminal pro-B-type natriuretic peptide level of 125.3 ng/L. 

All underwent a noninvasive carotid ultrasound and coronary artery calcium (CAC) scoring. Of those, 12 patients had a CAC score > 400 and/or presence of two or more carotid plaques identified as high-risk.

Those 12 patients underwent coronary angiography and had a total of 29 vessels examined by optical coherence tomography (OCT), “an invasive intravascular method for assessing coronary atherosclerosis that is far more sensitive than standard coronary angiography, especially for the detection of high-risk vulnerable plaques without a hemodynamically significant stenosis,” Dr. Dubsky explained.

Coronary angiography showed obstructive CAD in 5 of the 12 patients. Their mean calcium score was 950 and mean number of carotid plaques was 2.8. Features associated with plaque vulnerability included microphage accumulation in 24 vessels, lipid-rich plaques in 23, spotty calcium in 19, and neovascularizations in 13.

Thin-cap fibroatheroma, a strong predictor of plaque rupture, was present in 7 of the 12 patients (58.3%), and four had features of very high-risk plaques, defined as thin-cap fibroatheroma with a minimal lumen area < 3.5 mm², a lipid arch > 180 degrees, and macrophages. 

“Our study showed that asymptomatic T1D patients with high CAC score and carotid plaques had very severe OCT findings. We observed a significant proportion of high-risk lesions potentially associated with plaque rupture and risk of CV death. Therefore, we believe these patients should be treated as very high-risk with target LDL below 1.4 mmol/L (55 mg/dL), even though they are completely asymptomatic,” Dr. Dubsky concluded.

He added that because OCT is invasive and costly, the CAC score can be used to guide the decision for statin use, with any score above 100 considered elevated risk. 

Study coauthor Martin Haluzik, MD, professor of internal medicine in the Charles University, Prague, Czech Republic, told this news organization, “I think it’s very alarming because some of these are basically very healthy-looking young people, so you don’t really expect them to have significant cardiovascular complications already or significant plaques. I think it shows that we should be more proactive in looking into the risk of cardiovascular complications and in looking into the early cardiovascular changes.”
 

Later Diagnosis Doesn’t Always Protect: Risk Seen in Adult-Onset T1D

Yuxia Wei, a PhD student at the Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, presented an analysis of data from Sweden’s national health databases comparing cardiovascular outcomes between 10,184 people diagnosed with T1D at ages 18-29 years, 30-39 years, and ≥ 40 years; another 375,523 people diagnosed with T2D at those ages; and 509,172 population controls matched for age, sex, and county.

Those diagnosed after age 40 years had higher A1c levels and were less likely to be using insulin pumps than those diagnosed at younger adult ages. 

Compared with population controls, at a median of about 7 years of follow-up, people with T1D had significantly higher all-cause mortality at all diagnosis age groups, with a hazard ratio of 1.71. This rose to 2.78 for those diagnosed at age 30-39 years.

Compared with those with T2D, the mortality risks weren’t significantly different at any age, but the risks for non-cardiovascular death, including from cancer and infection, were significantly higher among those diagnosed after age 40 years (1.31 overall). Those diagnosed with T1D at any adult age had lower risks for major cardiovascular events than those diagnosed with T2D. Hazard ratios ranged from 0.27 for those diagnosed at age 18-29 years to 0.78 for those diagnosed after the age of 40 years.

Smoking and A1c above target were the greatest contributors to mortality. Those two factors, along with body mass index (BMI), were the strongest contributors to major adverse cardiovascular events (MACE).

“Adult-onset T1D carries excess risk of death and cardiovascular disease, without obvious attenuation over age at diagnosis…Smoking, A1c, and BMI are the key factors to be managed to improve prognosis in adult-onset T1D,” Ms. Wei concluded.
 

BMI: Often Overlooked in T1D, but a Major CVD Risk Factor

Two studies examined the link between overweight/obesity and cardiovascular risk in T1D. One, by Laurence Salle, MCU PH, of the Endocrinology, Diabetes and Metabolic Diseases Department at CHU Limoges, France, was a prospective, longitudinal cohort study of 2367 people with T1D at 68 centers in France who didn’t have a cardiovascular history at baseline.

Of those, 51% had normal BMI (18.5-24.9), 31% had overweight (25-29.9), and 18% had obesity (≥ 30). Cardiovascular risk factors, including LDL cholesterol, triglycerides, and hypertension increased with an increasing BMI. The 10-year CVD risk was significantly higher for those with overweight (9.61%) and obesity (9.93%) than for those with normal weight (7.24%), in both men and women. 

However, BMI was found to be an independent predictor of 10-year high cardiovascular risk in men but not women, while waist:height ratio independently predicted risk in both men and women, Dr. Salle reported.

The second BMI study, from Enrique Soto-Pedre, MBBS, of the Division of Population Health and Genomics at the University of Dundee, Scotland, presented data on a retrospective follow-up from 1995 to 2019 of 1973 people with T1D aged > 18 years at diagnosis (42% women; mean age, 34.2 years; 18.9% had obesity.

After 10 years of follow-up, those with overweight and obesity had significantly higher odds of developing arterial hypertension, even among those taking angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, with statistically significant adjusted hazard ratios of 1.73 and 3.37 for the obese and overweight groups, respectively. 

MACE were significantly more common among those with obesity, with an adjusted hazard ratio of 2.95, as was acute myocardial infarction, 3.33. 

“These results emphasize the importance of incorporating weight management into the overall management of individuals with T1D. No one has doubts about weight management in T2D, but in type 1, it’s not so clear. One of the main [concerns] would be safety [in terms of hypoglycemia],” Dr. Soto-Pedre concluded. 
 

Call for Action: Cumulative Glucose and Lipid Exposures Increase Risk

Dr. Bergdal presented data on the effects of cumulative glycemia and lipids on the risk for CAD in 3495 adults with T1D who had been diagnosed prior to the age of 40 years. The history of CAD or stroke was exclusion criteria. There were a total of 534 CAD events within a median follow-up of 19.4 years.

Cumulative glycemia, LDL cholesterol, triglycerides, and non–high-density lipoprotein cholesterol exposures were all significantly associated with CAD risk (P < .001 for all). With an adjustment for confounders, the highest tertile of glycemia was associated with a twofold increased risk for CAD. Both hyperglycemia and dyslipidemia were independently associated with CAD risk, Dr. Bergdal reported. 

“It’s important to minimize the time spent above A1c 7%, and lipid management in T1D must not be forgotten,” she said, prior to issuing her call for action.

Dr. Haluzik reported receiving honoraria for talks and/or consultancy and/or research funding from Eli Lilly, Novo Nordisk, Sanofi, AstraZeneca, Mundipharma, Bristol Myers Squibb, Amgen, Boehringer Ingelheim, Janssen, Ypsomed, and Johnson & Johnson. The presenters had no disclosures.
 

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

AMSTERDAM — There is a mountain of evidence that atopic dermatitis (AD) exerts a large negative impact on quality of life, but a unique study with data from more than 30,000 individuals showed that adults whose AD started in childhood carry a far greater psychological and social burden throughout their life relative to AD starting after childhood.

These data, drawn from the ambitious Scars of Life (SOL) project, “suggest that childhood AD persisting into adulthood is its own phenotype,” reported Jonathan I. Silverberg, MD, PhD, director of clinical research, Department of Dermatology, George Washington University, Washington, DC.

Dr. Silverberg

One reasonable message from these data is that the failure to achieve adequate control of AD in children, whether by a late start of systemic agents or other reasons, results in a greater lifetime burden of disease when the burden beyond physical symptoms is measured, according to Dr. Silverberg.
 

More Than 30,000 From Five Continents Participated

In the SOL project, which was designed to analyze how the age of AD onset affects the severity of symptoms and quality of life, completed questionnaires were collected from 30,801 individuals in 27 countries on five continents. The questions, which elicited data to measure the burden of AD, were developed in association with several professional and patient associations with an interest in AD, including the National Eczema Association.

The SOL project has produced an enormous amount of data in four distinct groups, but Dr. Silverberg, speaking in a late-breaking news session at the annual congress of the European Academy of Dermatology and Venereology, focused on a comparison between the 2875 participants who had AD in childhood that has persisted into adulthood and the 7383 adults with adult-onset AD. Data from the other two subsets in SOL — AD in childhood but not in adulthood and no AD in either phase of life — are expected to fuel an extended series of publications.

In the two groups, baseline characteristics were similar with about 60% reporting moderate to severe symptoms and a median age of about 37 years. The proportion of women was 61% in both groups.

Using the PUSH-D questionnaire, which Dr. Silverberg described as a validated tool for gauging a sense of stigmatization, the greater burden of AD was remarkably consistent for those with childhood-onset AD vs adult-onset AD. With higher scores representing a greater sense of stigmatization, the differences in the overall score (23.0 vs 18.1; P < .0001) were highly significant as was every other domain evaluated.

For all five social behavior domains, such as avoiding contact in public and wariness of approaching people spontaneously, having AD onset in childhood persisting into adulthood produced significantly higher scores than having AD onset in adulthood, with no exceptions (P < .001 for all).
 

AD From Childhood Consistently Results in Worse Outcomes

Providing examples for some of the other 12 domains, Dr. Silverberg maintained that feelings of shame and psychological discomfort were always greater in adults with AD persistent since childhood vs AD starting in adulthood. The P values for these outcomes, such as experiencing bias at work or reporting a sense that others avoided them, were typically highly significant (P < .001).

Compared with those whose AD started in adulthood, “adults with atopic eczema that started during childhood have significantly more difficulties in their life, including occupational relationships, daily life, personal life, and partner or family relationships,” Dr. Silverberg reported.

He said that the data were controlled for multiple confounders, particularly greater severity of AD. He acknowledged that childhood onset might be considered a surrogate for more severe disease, but the data were controlled for this possibility.

Despite the fact that there are “thousands of studies across all age groups showing the burden of AD,” Dr. Silverberg considers these data to be unique by emphasizing the burden of chronicity rather than the impact of AD in any single moment in time.

For those with chronic AD from childhood, “the effect is not just on physical health but a deep negative influence on psychological and social aspects of life,” Dr. Silverberg said, suggesting that the independent effects of chronicity might be worth studying across other dermatologic diseases.

“Regulatory agencies focus on what you can do in that moment of time, losing the bigger picture of how patients are affected chronically,” he said, adding that this is an area of clinical research that should be further explored.

What the data further suggest “is that the earlier we intervene, the more likely patients will do better long term,” he said.
 

Data Provide Evidence of Systemic Therapy in Kids

For Gudrun Ratzinger, MD, of the Department of Dermatology and Venerology at the Medical University of Innsbruck in Austria, these are valuable data.

“When I prescribe systemic therapies to children, I often get resistance from the healthcare system and even other colleagues,” said Dr. Ratzinger, who was asked to comment on the results. “We are at a teaching hospital, but I often find that when patients return to their home physician, the systemic therapies are stopped.”

In her own practice, she believes the most effective therapies should be introduced in children and adults when complete control is not achieved on first-line drugs. “These data are very helpful for me in explaining to others the importance of effective treatment of atopic dermatitis in children,” she said.

Dr. Silverberg reported financial relationships with more than 40 pharmaceutical companies, including those that make drugs for AD. Dr. Ratzinger reported financial relationships with AbbVie, Almirall, Boehringer Ingelheim, Eli Lilly, Janssen, Leo Pharma, Novartis, Pelpharma, Pfizer, and UCB.

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

AMSTERDAM — There is a mountain of evidence that atopic dermatitis (AD) exerts a large negative impact on quality of life, but a unique study with data from more than 30,000 individuals showed that adults whose AD started in childhood carry a far greater psychological and social burden throughout their life relative to AD starting after childhood.

These data, drawn from the ambitious Scars of Life (SOL) project, “suggest that childhood AD persisting into adulthood is its own phenotype,” reported Jonathan I. Silverberg, MD, PhD, director of clinical research, Department of Dermatology, George Washington University, Washington, DC.

Dr. Silverberg

One reasonable message from these data is that the failure to achieve adequate control of AD in children, whether by a late start of systemic agents or other reasons, results in a greater lifetime burden of disease when the burden beyond physical symptoms is measured, according to Dr. Silverberg.
 

More Than 30,000 From Five Continents Participated

In the SOL project, which was designed to analyze how the age of AD onset affects the severity of symptoms and quality of life, completed questionnaires were collected from 30,801 individuals in 27 countries on five continents. The questions, which elicited data to measure the burden of AD, were developed in association with several professional and patient associations with an interest in AD, including the National Eczema Association.

The SOL project has produced an enormous amount of data in four distinct groups, but Dr. Silverberg, speaking in a late-breaking news session at the annual congress of the European Academy of Dermatology and Venereology, focused on a comparison between the 2875 participants who had AD in childhood that has persisted into adulthood and the 7383 adults with adult-onset AD. Data from the other two subsets in SOL — AD in childhood but not in adulthood and no AD in either phase of life — are expected to fuel an extended series of publications.

In the two groups, baseline characteristics were similar with about 60% reporting moderate to severe symptoms and a median age of about 37 years. The proportion of women was 61% in both groups.

Using the PUSH-D questionnaire, which Dr. Silverberg described as a validated tool for gauging a sense of stigmatization, the greater burden of AD was remarkably consistent for those with childhood-onset AD vs adult-onset AD. With higher scores representing a greater sense of stigmatization, the differences in the overall score (23.0 vs 18.1; P < .0001) were highly significant as was every other domain evaluated.

For all five social behavior domains, such as avoiding contact in public and wariness of approaching people spontaneously, having AD onset in childhood persisting into adulthood produced significantly higher scores than having AD onset in adulthood, with no exceptions (P < .001 for all).
 

AD From Childhood Consistently Results in Worse Outcomes

Providing examples for some of the other 12 domains, Dr. Silverberg maintained that feelings of shame and psychological discomfort were always greater in adults with AD persistent since childhood vs AD starting in adulthood. The P values for these outcomes, such as experiencing bias at work or reporting a sense that others avoided them, were typically highly significant (P < .001).

Compared with those whose AD started in adulthood, “adults with atopic eczema that started during childhood have significantly more difficulties in their life, including occupational relationships, daily life, personal life, and partner or family relationships,” Dr. Silverberg reported.

He said that the data were controlled for multiple confounders, particularly greater severity of AD. He acknowledged that childhood onset might be considered a surrogate for more severe disease, but the data were controlled for this possibility.

Despite the fact that there are “thousands of studies across all age groups showing the burden of AD,” Dr. Silverberg considers these data to be unique by emphasizing the burden of chronicity rather than the impact of AD in any single moment in time.

For those with chronic AD from childhood, “the effect is not just on physical health but a deep negative influence on psychological and social aspects of life,” Dr. Silverberg said, suggesting that the independent effects of chronicity might be worth studying across other dermatologic diseases.

“Regulatory agencies focus on what you can do in that moment of time, losing the bigger picture of how patients are affected chronically,” he said, adding that this is an area of clinical research that should be further explored.

What the data further suggest “is that the earlier we intervene, the more likely patients will do better long term,” he said.
 

Data Provide Evidence of Systemic Therapy in Kids

For Gudrun Ratzinger, MD, of the Department of Dermatology and Venerology at the Medical University of Innsbruck in Austria, these are valuable data.

“When I prescribe systemic therapies to children, I often get resistance from the healthcare system and even other colleagues,” said Dr. Ratzinger, who was asked to comment on the results. “We are at a teaching hospital, but I often find that when patients return to their home physician, the systemic therapies are stopped.”

In her own practice, she believes the most effective therapies should be introduced in children and adults when complete control is not achieved on first-line drugs. “These data are very helpful for me in explaining to others the importance of effective treatment of atopic dermatitis in children,” she said.

Dr. Silverberg reported financial relationships with more than 40 pharmaceutical companies, including those that make drugs for AD. Dr. Ratzinger reported financial relationships with AbbVie, Almirall, Boehringer Ingelheim, Eli Lilly, Janssen, Leo Pharma, Novartis, Pelpharma, Pfizer, and UCB.

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

AMSTERDAM — There is a mountain of evidence that atopic dermatitis (AD) exerts a large negative impact on quality of life, but a unique study with data from more than 30,000 individuals showed that adults whose AD started in childhood carry a far greater psychological and social burden throughout their life relative to AD starting after childhood.

These data, drawn from the ambitious Scars of Life (SOL) project, “suggest that childhood AD persisting into adulthood is its own phenotype,” reported Jonathan I. Silverberg, MD, PhD, director of clinical research, Department of Dermatology, George Washington University, Washington, DC.

Dr. Silverberg

One reasonable message from these data is that the failure to achieve adequate control of AD in children, whether by a late start of systemic agents or other reasons, results in a greater lifetime burden of disease when the burden beyond physical symptoms is measured, according to Dr. Silverberg.
 

More Than 30,000 From Five Continents Participated

In the SOL project, which was designed to analyze how the age of AD onset affects the severity of symptoms and quality of life, completed questionnaires were collected from 30,801 individuals in 27 countries on five continents. The questions, which elicited data to measure the burden of AD, were developed in association with several professional and patient associations with an interest in AD, including the National Eczema Association.

The SOL project has produced an enormous amount of data in four distinct groups, but Dr. Silverberg, speaking in a late-breaking news session at the annual congress of the European Academy of Dermatology and Venereology, focused on a comparison between the 2875 participants who had AD in childhood that has persisted into adulthood and the 7383 adults with adult-onset AD. Data from the other two subsets in SOL — AD in childhood but not in adulthood and no AD in either phase of life — are expected to fuel an extended series of publications.

In the two groups, baseline characteristics were similar with about 60% reporting moderate to severe symptoms and a median age of about 37 years. The proportion of women was 61% in both groups.

Using the PUSH-D questionnaire, which Dr. Silverberg described as a validated tool for gauging a sense of stigmatization, the greater burden of AD was remarkably consistent for those with childhood-onset AD vs adult-onset AD. With higher scores representing a greater sense of stigmatization, the differences in the overall score (23.0 vs 18.1; P < .0001) were highly significant as was every other domain evaluated.

For all five social behavior domains, such as avoiding contact in public and wariness of approaching people spontaneously, having AD onset in childhood persisting into adulthood produced significantly higher scores than having AD onset in adulthood, with no exceptions (P < .001 for all).
 

AD From Childhood Consistently Results in Worse Outcomes

Providing examples for some of the other 12 domains, Dr. Silverberg maintained that feelings of shame and psychological discomfort were always greater in adults with AD persistent since childhood vs AD starting in adulthood. The P values for these outcomes, such as experiencing bias at work or reporting a sense that others avoided them, were typically highly significant (P < .001).

Compared with those whose AD started in adulthood, “adults with atopic eczema that started during childhood have significantly more difficulties in their life, including occupational relationships, daily life, personal life, and partner or family relationships,” Dr. Silverberg reported.

He said that the data were controlled for multiple confounders, particularly greater severity of AD. He acknowledged that childhood onset might be considered a surrogate for more severe disease, but the data were controlled for this possibility.

Despite the fact that there are “thousands of studies across all age groups showing the burden of AD,” Dr. Silverberg considers these data to be unique by emphasizing the burden of chronicity rather than the impact of AD in any single moment in time.

For those with chronic AD from childhood, “the effect is not just on physical health but a deep negative influence on psychological and social aspects of life,” Dr. Silverberg said, suggesting that the independent effects of chronicity might be worth studying across other dermatologic diseases.

“Regulatory agencies focus on what you can do in that moment of time, losing the bigger picture of how patients are affected chronically,” he said, adding that this is an area of clinical research that should be further explored.

What the data further suggest “is that the earlier we intervene, the more likely patients will do better long term,” he said.
 

Data Provide Evidence of Systemic Therapy in Kids

For Gudrun Ratzinger, MD, of the Department of Dermatology and Venerology at the Medical University of Innsbruck in Austria, these are valuable data.

“When I prescribe systemic therapies to children, I often get resistance from the healthcare system and even other colleagues,” said Dr. Ratzinger, who was asked to comment on the results. “We are at a teaching hospital, but I often find that when patients return to their home physician, the systemic therapies are stopped.”

In her own practice, she believes the most effective therapies should be introduced in children and adults when complete control is not achieved on first-line drugs. “These data are very helpful for me in explaining to others the importance of effective treatment of atopic dermatitis in children,” she said.

Dr. Silverberg reported financial relationships with more than 40 pharmaceutical companies, including those that make drugs for AD. Dr. Ratzinger reported financial relationships with AbbVie, Almirall, Boehringer Ingelheim, Eli Lilly, Janssen, Leo Pharma, Novartis, Pelpharma, Pfizer, and UCB.

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

BARCELONA, SPAIN — Not all patients with colorectal cancer are the same, and more research is needed to examine differences between patients according to their sex, gender, and even menopause status, according to experts speaking here at the European Society for Medical Oncology (ESMO) Annual Meeting 2024.

“The concepts of gender and sex are not at all new in oncology, but what is needed is a renewed focus on them and the prospective collection of data in this regard,” said Kathrin Heinrich, MD, of University Hospital LMU Munich, Germany.
 

Sex and Gender: What’s New? 

Speaking at the conference, Dr. Heinrich cited a 2020 study published in The Lancet that stated, “Sex and gender are the foundation of precision medicine, and their differences should guide decision-making processes to promote gender equity.”

Sex differences have clear biological and pathophysiological consequences in oncology. Available data show differences between men and women in terms of gene expression, epigenetics, metabolomics, tumor microenvironment, immune system, and microbiome. These are all critical for understanding tumor biology and identifying new treatments.

Colorectal cancer provides an excellent example of how sex differences can influence treatment outcomes.

From an incidence perspective, the numbers reported by the large epidemiological GLOBOCAN study are quite similar between the two sexes, with men accounting for 56% of patients and women for 44%.

However, there are noticeable differences in tumor characteristics, with women more frequently presenting with right-sided colon tumors and BRAF mutations; both features associated with a worse prognosis.

Sex also affects body composition, influencing the percentage of metabolically active body mass, which can alter the effectiveness and distribution of a drug and the necessary dose to achieve the desired effect.

“Despite this evidence, clinical practice often overlooks differences between the sexes when planning therapies,” Dr. Heinrich said, also recalling how in many cases the side effects of treatments — from chemotherapy to immunotherapy — differ in intensity and type between men and women.
 

Toward a More Targeted and Inclusive Approach

Sex is a well-defined concept from a biological standpoint and, consequently, the differences between the sexes are easy to identify. Analyzing gender differences is much more complex.

“It is not enough to tick the male or female box on a questionnaire. It is necessary to consider more complex aspects to measure, such as identity, role, and gender relations,” Dr. Heinrich said, also presenting a list of specific questionnaires to assess these components.

In today’s oncology, however, such questionnaires are mainly used to analyze secondary outcomes such as quality of life, while examples from other areas of medicine, particularly cardiology, show how questionnaires on gender can predict some clinical outcomes better than those on sex alone and that studies considering sex and gender are feasible.

Gender identity influences many aspects of health, such as attitudes toward prevention, the seeking of information and medical care, and risk behaviors. “The new approach to discussing sex and gender in oncology is to consider these factors in therapeutic decisions,” Dr. Heinrich said. “I hope that within a few years this will be fully achievable, thanks to the inclusion in our studies of gender scores, ad hoc patient-reported outcomes, and information related, for example, to menopausal status or the number of pregnancies,” she added.

To harness the differences between sex and gender in favor of the patient, however, it is also necessary to change the approach to clinical studies. Currently, data on these aspects are typically collected retrospectively. However, they should be integrated prospectively from the study’s beginning.

“We look at increasingly smaller subgroups of patients, at mutations affecting 1%-2% of our patients, but we do not collect data on sex or menopausal status, which are actually extremely simple to record,” Dr. Heinrich said, calling for more inclusive studies, especially involving the LGBTQI+ community, traditionally excluded from clinical trials and many services.

“Fortunately, we live in an era in which sensitivity towards this community is continuously increasing. We must gather information on this population, which fully belongs to what we scientifically define as the ‘real-world’ approach.”

Dr. Heinrich declared honoraria, consulting and advisory roles, and travel support from several companies, including Amgen, BMS, Merck, MSD, Roche-Janssen, Taiho, Servier, and Streamed Up.

This story was translated from Univadis Italy using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

BARCELONA, SPAIN — Not all patients with colorectal cancer are the same, and more research is needed to examine differences between patients according to their sex, gender, and even menopause status, according to experts speaking here at the European Society for Medical Oncology (ESMO) Annual Meeting 2024.

“The concepts of gender and sex are not at all new in oncology, but what is needed is a renewed focus on them and the prospective collection of data in this regard,” said Kathrin Heinrich, MD, of University Hospital LMU Munich, Germany.
 

Sex and Gender: What’s New? 

Speaking at the conference, Dr. Heinrich cited a 2020 study published in The Lancet that stated, “Sex and gender are the foundation of precision medicine, and their differences should guide decision-making processes to promote gender equity.”

Sex differences have clear biological and pathophysiological consequences in oncology. Available data show differences between men and women in terms of gene expression, epigenetics, metabolomics, tumor microenvironment, immune system, and microbiome. These are all critical for understanding tumor biology and identifying new treatments.

Colorectal cancer provides an excellent example of how sex differences can influence treatment outcomes.

From an incidence perspective, the numbers reported by the large epidemiological GLOBOCAN study are quite similar between the two sexes, with men accounting for 56% of patients and women for 44%.

However, there are noticeable differences in tumor characteristics, with women more frequently presenting with right-sided colon tumors and BRAF mutations; both features associated with a worse prognosis.

Sex also affects body composition, influencing the percentage of metabolically active body mass, which can alter the effectiveness and distribution of a drug and the necessary dose to achieve the desired effect.

“Despite this evidence, clinical practice often overlooks differences between the sexes when planning therapies,” Dr. Heinrich said, also recalling how in many cases the side effects of treatments — from chemotherapy to immunotherapy — differ in intensity and type between men and women.
 

Toward a More Targeted and Inclusive Approach

Sex is a well-defined concept from a biological standpoint and, consequently, the differences between the sexes are easy to identify. Analyzing gender differences is much more complex.

“It is not enough to tick the male or female box on a questionnaire. It is necessary to consider more complex aspects to measure, such as identity, role, and gender relations,” Dr. Heinrich said, also presenting a list of specific questionnaires to assess these components.

In today’s oncology, however, such questionnaires are mainly used to analyze secondary outcomes such as quality of life, while examples from other areas of medicine, particularly cardiology, show how questionnaires on gender can predict some clinical outcomes better than those on sex alone and that studies considering sex and gender are feasible.

Gender identity influences many aspects of health, such as attitudes toward prevention, the seeking of information and medical care, and risk behaviors. “The new approach to discussing sex and gender in oncology is to consider these factors in therapeutic decisions,” Dr. Heinrich said. “I hope that within a few years this will be fully achievable, thanks to the inclusion in our studies of gender scores, ad hoc patient-reported outcomes, and information related, for example, to menopausal status or the number of pregnancies,” she added.

To harness the differences between sex and gender in favor of the patient, however, it is also necessary to change the approach to clinical studies. Currently, data on these aspects are typically collected retrospectively. However, they should be integrated prospectively from the study’s beginning.

“We look at increasingly smaller subgroups of patients, at mutations affecting 1%-2% of our patients, but we do not collect data on sex or menopausal status, which are actually extremely simple to record,” Dr. Heinrich said, calling for more inclusive studies, especially involving the LGBTQI+ community, traditionally excluded from clinical trials and many services.

“Fortunately, we live in an era in which sensitivity towards this community is continuously increasing. We must gather information on this population, which fully belongs to what we scientifically define as the ‘real-world’ approach.”

Dr. Heinrich declared honoraria, consulting and advisory roles, and travel support from several companies, including Amgen, BMS, Merck, MSD, Roche-Janssen, Taiho, Servier, and Streamed Up.

This story was translated from Univadis Italy using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

BARCELONA, SPAIN — Not all patients with colorectal cancer are the same, and more research is needed to examine differences between patients according to their sex, gender, and even menopause status, according to experts speaking here at the European Society for Medical Oncology (ESMO) Annual Meeting 2024.

“The concepts of gender and sex are not at all new in oncology, but what is needed is a renewed focus on them and the prospective collection of data in this regard,” said Kathrin Heinrich, MD, of University Hospital LMU Munich, Germany.
 

Sex and Gender: What’s New? 

Speaking at the conference, Dr. Heinrich cited a 2020 study published in The Lancet that stated, “Sex and gender are the foundation of precision medicine, and their differences should guide decision-making processes to promote gender equity.”

Sex differences have clear biological and pathophysiological consequences in oncology. Available data show differences between men and women in terms of gene expression, epigenetics, metabolomics, tumor microenvironment, immune system, and microbiome. These are all critical for understanding tumor biology and identifying new treatments.

Colorectal cancer provides an excellent example of how sex differences can influence treatment outcomes.

From an incidence perspective, the numbers reported by the large epidemiological GLOBOCAN study are quite similar between the two sexes, with men accounting for 56% of patients and women for 44%.

However, there are noticeable differences in tumor characteristics, with women more frequently presenting with right-sided colon tumors and BRAF mutations; both features associated with a worse prognosis.

Sex also affects body composition, influencing the percentage of metabolically active body mass, which can alter the effectiveness and distribution of a drug and the necessary dose to achieve the desired effect.

“Despite this evidence, clinical practice often overlooks differences between the sexes when planning therapies,” Dr. Heinrich said, also recalling how in many cases the side effects of treatments — from chemotherapy to immunotherapy — differ in intensity and type between men and women.
 

Toward a More Targeted and Inclusive Approach

Sex is a well-defined concept from a biological standpoint and, consequently, the differences between the sexes are easy to identify. Analyzing gender differences is much more complex.

“It is not enough to tick the male or female box on a questionnaire. It is necessary to consider more complex aspects to measure, such as identity, role, and gender relations,” Dr. Heinrich said, also presenting a list of specific questionnaires to assess these components.

In today’s oncology, however, such questionnaires are mainly used to analyze secondary outcomes such as quality of life, while examples from other areas of medicine, particularly cardiology, show how questionnaires on gender can predict some clinical outcomes better than those on sex alone and that studies considering sex and gender are feasible.

Gender identity influences many aspects of health, such as attitudes toward prevention, the seeking of information and medical care, and risk behaviors. “The new approach to discussing sex and gender in oncology is to consider these factors in therapeutic decisions,” Dr. Heinrich said. “I hope that within a few years this will be fully achievable, thanks to the inclusion in our studies of gender scores, ad hoc patient-reported outcomes, and information related, for example, to menopausal status or the number of pregnancies,” she added.

To harness the differences between sex and gender in favor of the patient, however, it is also necessary to change the approach to clinical studies. Currently, data on these aspects are typically collected retrospectively. However, they should be integrated prospectively from the study’s beginning.

“We look at increasingly smaller subgroups of patients, at mutations affecting 1%-2% of our patients, but we do not collect data on sex or menopausal status, which are actually extremely simple to record,” Dr. Heinrich said, calling for more inclusive studies, especially involving the LGBTQI+ community, traditionally excluded from clinical trials and many services.

“Fortunately, we live in an era in which sensitivity towards this community is continuously increasing. We must gather information on this population, which fully belongs to what we scientifically define as the ‘real-world’ approach.”

Dr. Heinrich declared honoraria, consulting and advisory roles, and travel support from several companies, including Amgen, BMS, Merck, MSD, Roche-Janssen, Taiho, Servier, and Streamed Up.

This story was translated from Univadis Italy using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

COPENHAGEN — Multiple Sclerosis (MS) experts are recommending updates to the 2017 McDonald diagnostic criteria in order to make diagnosis easier, faster, and more accurate.

Among its recommendations, the expert panel advises incorporating optic nerve imaging for diagnosis and applying stricter criteria for older patients. In addition, it proposes that radiologically isolated syndrome (RIS) may be diagnosed as MS in certain cases and that disease dissemination in time (DIT) should no longer be required. 

The proposed criteria changes were presented at the 2024 ECTRIMS annual meeting.

Committee member Xavier Montalban, MD, PhD, from the Department of Neurology and the MS Centre of Catalonia at Vall d’Hebron University Hospital in Barcelona, Spain, told conference attendees that MS is a diagnosis of exclusion.

Brain and spinal cord MRI remains the most useful paraclinical test to diagnose the disease, he said, and an abnormal MRI showing typical lesions is required.

Dr. Montalban noted that optic neuritis is the first manifestation of MS in 25%-35% of cases with clinically isolated syndrome (CIS) — one of the four MS disease courses.

Therefore, he said, the panel is recommending that the optic nerve serve as the “fifth topography” or a fifth anatomical location to demonstrate dissemination in space (DIS) if there’s no better explanation for optic nerve pathology, he said. 

Considerable evidence supports the minimal threshold of at least one lesion in at least two of the five topographies after including the optic nerve, he added.
 

DIS Alone Sufficient?

The panel also concluded that demonstrating DIS alone, without the need for DIT or positive cerebrospinal fluid (CSF), may be sufficient for an MS diagnosis. Currently, both DIS and DIT are required.

The committee broached the topic of RIS, which is identified by the incidental discovery of central nervous system (CNS) white matter T2-weighted hyperintense foci on MRI. These hyperintense foci demonstrate morphological and spatial characteristics highly typical of MS but without clinical symptomatology related to inflammatory demyelination.

Dr. Montalban noted that most patients with RIS will develop MS within 10 years. For these individuals, the panel concluded that the following criteria are sufficient for an MS diagnosis: fulfilling both DIS and DIT; fulfilling DIS and the presence of oligoclonal bands (OCBs) in the cerebrospinal fluid; or fulfilling DIS along with six or more central vein signs (CVS).

The panel proposes the addition of CVS and paramagnetic rim lesions, which are MRI markers of chronic active lesions, as optional tools for MS diagnosis in certain situations. Demonstration of CVS by MRI can increase specificity, said Dr. Montalban.

Evidence also suggests that kappa free light chains (KFLCs) could serve as a valid, simpler, and rater-independent alternative to detecting OCBs, he added. Because KFLCs are interchangeable with OCBs, they can be used in place of OCBs for diagnosing MS through CSF analysis.
 

Stricter Criteria

The panel is also calling for stricter criteria for confirming an MS diagnosis in those over age 50 or individuals with headache or vascular disorders. In such patients, they strongly recommend additional features such as a spinal cord lesion, positive CSF, and CVS select 6 (six positive lesions).

The panel is also recommending laboratory tests (MOG-IgG Ab) to confirm a diagnosis in children and adolescents. Dr. Montalban noted the presence of CVS in about 50% of T2 lesions strongly suggests MS in this population.

Primary progressive MS (PPMS) requires evidence of clinical progression over at least 12 months. The committee determined that the same criteria for relapsing-remitting MS could be used for PPMS. 

Having a single, unified framework of diagnostic criteria will be “very useful,” said Dr. Montalban.

During the same meeting session, Marcello Moccia, MD, PhD, University College London (UCL) Queen Square Institute of Neurology, Faculty of Brain Sciences, London, England, presented examples of patients for whom the revised criteria could be beneficial. 

These examples help illustrate how using the new criteria, for example optic nerve imaging, could lead to earlier diagnoses, and, in some cases, easier diagnoses, possibly with less CSF, he said. It could also lead to fewer misdiagnoses, he added, thanks to high-specificity tools.

Implementing the new criteria could offer greater flexibility and reduce complexity, Dr. Moccia concluded, adding that not every patient with suspected MS requires exhaustive testing.

The committee’s next steps will include consulting with the wider MS community and preparing the information for publication, said Dr. Montalban.

Commenting on the proposals, Bruce Bebo, executive vice president of research, National MS Society, agreed the proposed changes to the McDonald Criteria will make diagnosing MS “faster and easier.”

“Importantly, we are providing guidance that is inclusive — how to confirm diagnoses in children, or in people over the age of 50,” said Dr. Bebo. “We’re bringing the latest research and imaging technology to the forefront, to help people with MS get treatment faster, so they can live their best lives.”

Dr. Montalban’s institution has received compensation for lecture honoraria and travel expenses, participation in scientific meetings, clinical trial steering committee membership, or clinical advisory board participation in recent years from AbbVie, Actelion, Alexion, Bial PD, Biogen, Bristol Myers Squibb/Celgene, EMD Serona, Genzyme, Hoffmann-La Roche, Immunic Therapeutics, Janssen Pharmaceuticals, MedDay, Merck, Mylan, Nervgen, Neuraxpharm, Novartis, PeerVoice, Samsung-Biosys Sandoz Sanofi-Genzyme, Teva Pharmaceuticals, TG Therapeutics, EXCEMED, ECTRIMS, MSIF, and NMSS or any of their affiliates. Dr. Moccia reports receiving a salary from University of Naples, Policlinico University Hospital (Naples) and Neurology (US); research grants from MUR PNRR Extended Partnership, ECTRIMS-MAGNIMS, UK MS Society, and Merck; honoraria from AbbVie, Biogen, BMS Celgene, Ipsen, Jansen, Merck, Novartis, Roche, and Sanofi-Genzyme. 

A version of this article appeared on Medscape.com.

COPENHAGEN — Multiple Sclerosis (MS) experts are recommending updates to the 2017 McDonald diagnostic criteria in order to make diagnosis easier, faster, and more accurate.

Among its recommendations, the expert panel advises incorporating optic nerve imaging for diagnosis and applying stricter criteria for older patients. In addition, it proposes that radiologically isolated syndrome (RIS) may be diagnosed as MS in certain cases and that disease dissemination in time (DIT) should no longer be required. 

The proposed criteria changes were presented at the 2024 ECTRIMS annual meeting.

Committee member Xavier Montalban, MD, PhD, from the Department of Neurology and the MS Centre of Catalonia at Vall d’Hebron University Hospital in Barcelona, Spain, told conference attendees that MS is a diagnosis of exclusion.

Brain and spinal cord MRI remains the most useful paraclinical test to diagnose the disease, he said, and an abnormal MRI showing typical lesions is required.

Dr. Montalban noted that optic neuritis is the first manifestation of MS in 25%-35% of cases with clinically isolated syndrome (CIS) — one of the four MS disease courses.

Therefore, he said, the panel is recommending that the optic nerve serve as the “fifth topography” or a fifth anatomical location to demonstrate dissemination in space (DIS) if there’s no better explanation for optic nerve pathology, he said. 

Considerable evidence supports the minimal threshold of at least one lesion in at least two of the five topographies after including the optic nerve, he added.
 

DIS Alone Sufficient?

The panel also concluded that demonstrating DIS alone, without the need for DIT or positive cerebrospinal fluid (CSF), may be sufficient for an MS diagnosis. Currently, both DIS and DIT are required.

The committee broached the topic of RIS, which is identified by the incidental discovery of central nervous system (CNS) white matter T2-weighted hyperintense foci on MRI. These hyperintense foci demonstrate morphological and spatial characteristics highly typical of MS but without clinical symptomatology related to inflammatory demyelination.

Dr. Montalban noted that most patients with RIS will develop MS within 10 years. For these individuals, the panel concluded that the following criteria are sufficient for an MS diagnosis: fulfilling both DIS and DIT; fulfilling DIS and the presence of oligoclonal bands (OCBs) in the cerebrospinal fluid; or fulfilling DIS along with six or more central vein signs (CVS).

The panel proposes the addition of CVS and paramagnetic rim lesions, which are MRI markers of chronic active lesions, as optional tools for MS diagnosis in certain situations. Demonstration of CVS by MRI can increase specificity, said Dr. Montalban.

Evidence also suggests that kappa free light chains (KFLCs) could serve as a valid, simpler, and rater-independent alternative to detecting OCBs, he added. Because KFLCs are interchangeable with OCBs, they can be used in place of OCBs for diagnosing MS through CSF analysis.
 

Stricter Criteria

The panel is also calling for stricter criteria for confirming an MS diagnosis in those over age 50 or individuals with headache or vascular disorders. In such patients, they strongly recommend additional features such as a spinal cord lesion, positive CSF, and CVS select 6 (six positive lesions).

The panel is also recommending laboratory tests (MOG-IgG Ab) to confirm a diagnosis in children and adolescents. Dr. Montalban noted the presence of CVS in about 50% of T2 lesions strongly suggests MS in this population.

Primary progressive MS (PPMS) requires evidence of clinical progression over at least 12 months. The committee determined that the same criteria for relapsing-remitting MS could be used for PPMS. 

Having a single, unified framework of diagnostic criteria will be “very useful,” said Dr. Montalban.

During the same meeting session, Marcello Moccia, MD, PhD, University College London (UCL) Queen Square Institute of Neurology, Faculty of Brain Sciences, London, England, presented examples of patients for whom the revised criteria could be beneficial. 

These examples help illustrate how using the new criteria, for example optic nerve imaging, could lead to earlier diagnoses, and, in some cases, easier diagnoses, possibly with less CSF, he said. It could also lead to fewer misdiagnoses, he added, thanks to high-specificity tools.

Implementing the new criteria could offer greater flexibility and reduce complexity, Dr. Moccia concluded, adding that not every patient with suspected MS requires exhaustive testing.

The committee’s next steps will include consulting with the wider MS community and preparing the information for publication, said Dr. Montalban.

Commenting on the proposals, Bruce Bebo, executive vice president of research, National MS Society, agreed the proposed changes to the McDonald Criteria will make diagnosing MS “faster and easier.”

“Importantly, we are providing guidance that is inclusive — how to confirm diagnoses in children, or in people over the age of 50,” said Dr. Bebo. “We’re bringing the latest research and imaging technology to the forefront, to help people with MS get treatment faster, so they can live their best lives.”

Dr. Montalban’s institution has received compensation for lecture honoraria and travel expenses, participation in scientific meetings, clinical trial steering committee membership, or clinical advisory board participation in recent years from AbbVie, Actelion, Alexion, Bial PD, Biogen, Bristol Myers Squibb/Celgene, EMD Serona, Genzyme, Hoffmann-La Roche, Immunic Therapeutics, Janssen Pharmaceuticals, MedDay, Merck, Mylan, Nervgen, Neuraxpharm, Novartis, PeerVoice, Samsung-Biosys Sandoz Sanofi-Genzyme, Teva Pharmaceuticals, TG Therapeutics, EXCEMED, ECTRIMS, MSIF, and NMSS or any of their affiliates. Dr. Moccia reports receiving a salary from University of Naples, Policlinico University Hospital (Naples) and Neurology (US); research grants from MUR PNRR Extended Partnership, ECTRIMS-MAGNIMS, UK MS Society, and Merck; honoraria from AbbVie, Biogen, BMS Celgene, Ipsen, Jansen, Merck, Novartis, Roche, and Sanofi-Genzyme. 

A version of this article appeared on Medscape.com.

COPENHAGEN — Multiple Sclerosis (MS) experts are recommending updates to the 2017 McDonald diagnostic criteria in order to make diagnosis easier, faster, and more accurate.

Among its recommendations, the expert panel advises incorporating optic nerve imaging for diagnosis and applying stricter criteria for older patients. In addition, it proposes that radiologically isolated syndrome (RIS) may be diagnosed as MS in certain cases and that disease dissemination in time (DIT) should no longer be required. 

The proposed criteria changes were presented at the 2024 ECTRIMS annual meeting.

Committee member Xavier Montalban, MD, PhD, from the Department of Neurology and the MS Centre of Catalonia at Vall d’Hebron University Hospital in Barcelona, Spain, told conference attendees that MS is a diagnosis of exclusion.

Brain and spinal cord MRI remains the most useful paraclinical test to diagnose the disease, he said, and an abnormal MRI showing typical lesions is required.

Dr. Montalban noted that optic neuritis is the first manifestation of MS in 25%-35% of cases with clinically isolated syndrome (CIS) — one of the four MS disease courses.

Therefore, he said, the panel is recommending that the optic nerve serve as the “fifth topography” or a fifth anatomical location to demonstrate dissemination in space (DIS) if there’s no better explanation for optic nerve pathology, he said. 

Considerable evidence supports the minimal threshold of at least one lesion in at least two of the five topographies after including the optic nerve, he added.
 

DIS Alone Sufficient?

The panel also concluded that demonstrating DIS alone, without the need for DIT or positive cerebrospinal fluid (CSF), may be sufficient for an MS diagnosis. Currently, both DIS and DIT are required.

The committee broached the topic of RIS, which is identified by the incidental discovery of central nervous system (CNS) white matter T2-weighted hyperintense foci on MRI. These hyperintense foci demonstrate morphological and spatial characteristics highly typical of MS but without clinical symptomatology related to inflammatory demyelination.

Dr. Montalban noted that most patients with RIS will develop MS within 10 years. For these individuals, the panel concluded that the following criteria are sufficient for an MS diagnosis: fulfilling both DIS and DIT; fulfilling DIS and the presence of oligoclonal bands (OCBs) in the cerebrospinal fluid; or fulfilling DIS along with six or more central vein signs (CVS).

The panel proposes the addition of CVS and paramagnetic rim lesions, which are MRI markers of chronic active lesions, as optional tools for MS diagnosis in certain situations. Demonstration of CVS by MRI can increase specificity, said Dr. Montalban.

Evidence also suggests that kappa free light chains (KFLCs) could serve as a valid, simpler, and rater-independent alternative to detecting OCBs, he added. Because KFLCs are interchangeable with OCBs, they can be used in place of OCBs for diagnosing MS through CSF analysis.
 

Stricter Criteria

The panel is also calling for stricter criteria for confirming an MS diagnosis in those over age 50 or individuals with headache or vascular disorders. In such patients, they strongly recommend additional features such as a spinal cord lesion, positive CSF, and CVS select 6 (six positive lesions).

The panel is also recommending laboratory tests (MOG-IgG Ab) to confirm a diagnosis in children and adolescents. Dr. Montalban noted the presence of CVS in about 50% of T2 lesions strongly suggests MS in this population.

Primary progressive MS (PPMS) requires evidence of clinical progression over at least 12 months. The committee determined that the same criteria for relapsing-remitting MS could be used for PPMS. 

Having a single, unified framework of diagnostic criteria will be “very useful,” said Dr. Montalban.

During the same meeting session, Marcello Moccia, MD, PhD, University College London (UCL) Queen Square Institute of Neurology, Faculty of Brain Sciences, London, England, presented examples of patients for whom the revised criteria could be beneficial. 

These examples help illustrate how using the new criteria, for example optic nerve imaging, could lead to earlier diagnoses, and, in some cases, easier diagnoses, possibly with less CSF, he said. It could also lead to fewer misdiagnoses, he added, thanks to high-specificity tools.

Implementing the new criteria could offer greater flexibility and reduce complexity, Dr. Moccia concluded, adding that not every patient with suspected MS requires exhaustive testing.

The committee’s next steps will include consulting with the wider MS community and preparing the information for publication, said Dr. Montalban.

Commenting on the proposals, Bruce Bebo, executive vice president of research, National MS Society, agreed the proposed changes to the McDonald Criteria will make diagnosing MS “faster and easier.”

“Importantly, we are providing guidance that is inclusive — how to confirm diagnoses in children, or in people over the age of 50,” said Dr. Bebo. “We’re bringing the latest research and imaging technology to the forefront, to help people with MS get treatment faster, so they can live their best lives.”

Dr. Montalban’s institution has received compensation for lecture honoraria and travel expenses, participation in scientific meetings, clinical trial steering committee membership, or clinical advisory board participation in recent years from AbbVie, Actelion, Alexion, Bial PD, Biogen, Bristol Myers Squibb/Celgene, EMD Serona, Genzyme, Hoffmann-La Roche, Immunic Therapeutics, Janssen Pharmaceuticals, MedDay, Merck, Mylan, Nervgen, Neuraxpharm, Novartis, PeerVoice, Samsung-Biosys Sandoz Sanofi-Genzyme, Teva Pharmaceuticals, TG Therapeutics, EXCEMED, ECTRIMS, MSIF, and NMSS or any of their affiliates. Dr. Moccia reports receiving a salary from University of Naples, Policlinico University Hospital (Naples) and Neurology (US); research grants from MUR PNRR Extended Partnership, ECTRIMS-MAGNIMS, UK MS Society, and Merck; honoraria from AbbVie, Biogen, BMS Celgene, Ipsen, Jansen, Merck, Novartis, Roche, and Sanofi-Genzyme. 

A version of this article appeared on Medscape.com.

COPENHAGEN — A higher cumulative genetic burden for depression is associated with an increased risk for relapse and worsening disability in people with multiple sclerosis (MS), early results of a new study showed.

Unlike the previous research, the current analysis used polygenic risk scores for depression, which summarize the estimated effect of genetic variants to determine the potential association with MS disease activity, so results are less likely to be explained by reverse causality.

This study increases awareness of the link between depression and MS, said study investigator Kaarina Kowalec, PhD, assistant professor, College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada. “We’re starting to understand how depression affects relapses and disability progression in MS,” she said.

The findings were presented at the 2024 ECTRIMS annual meeting.
 

Common Comorbidity

Depression is a common comorbidity in patients with MS and is associated with increased relapse and disability progression. Depression risk is partly polygenic in nature, involving numerous common genetic variants, said Dr. Kowalec.

The case-control study included 3420 relapsing-onset MS cases of European ancestry from four existing cohorts in three countries.

The Canadian cohort included those enrolled in a prospective longitudinal study of psychiatric comorbidity in chronic immune-mediated inflammatory disease (IMID), including MS; the Swedish cohort was an MS registry (SSReg) that encompasses 64 MS clinics (the cohort was split into two groups); and the US cohort was enrolled in a clinical trial of combined therapy with interferon and glatiramer acetate (CombiRx) in patients with MS.

The median follow-up in these cohorts ranged from 3 to 5 years.

Not surprisingly, most participants were women (from 71% in one of the Swedish cohorts to 83% in the Canadian cohort), and the age at MS onset ranged from 29 years in the Canadian cohort to 35 years in one of the Swedish cohorts.

The median baseline Expanded Disability Status Scale (EDSS) score was higher in the Canadian cohort (3.5) than in the Swedish (1.5) and US (2.0) cohorts, “reflective of the Canadian cohort being slightly more progressed,” said Dr. Kowalec.
 

Inherited Variants

To measure depression heritability, researchers generated a polygenic risk score in whole-genome imputed genotypes. The score reflects the number of inherited common genetic variants, weighted by effect sizes.

Researchers investigated the association between depression polygenic risk scores (top 20% vs. bottom 80%) with annualized relapse rate and worsening disability in MS measured by the rate of change in EDSS score. In the US cohort, they also explored the association between depression polygenic risk scores and time to relapse and confirmed EDSS worsening.

Covariates included use of disease-modifying therapy, age, sex, and the first five genetic ancestry principal components. The latter was done to capture residual stratification by genetic ancestry, although Dr. Kowalec stressed analyses were done only in those of European ancestry.

Investigators found a higher depression polygenic risk score was associated with relapse risk (incident rate ratio, 1.23; 95% CI, 1.01-1.49).

“Essentially, for every one standard deviation increase in the depression polygenic score, we found a significant increased hazard of 23% for experiencing a relapse over the follow-up period,” said Dr. Kowalec, who is also affiliated with the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

She noted the Canadian cohort did not have many relapses, while the US and Swedish cohorts “had an increased rate.”

Other analyses examined the risk of having a relapse or worsening disability. Every one SD increase in the depression polygenic risk score was significantly associated with a 2.2 greater risk of experiencing relapse (hazard ratio [HR], 2.20; 95% CI, 1.35-3.60) and a 51% increased risk for confirmed EDSS progression (HR, 1.51; 95% CI, 1.03-2.22).
 

‘An Ideal Marker’

Use of polygenetic risk scores reduces the possibility of reverse causation, noted Dr. Kowalec. “These markers are fixed at birth and don’t change over your lifespan, so they’re really an ideal marker.”

The results suggest polygenetic risk scores represent a potential biomarker for risk stratification in people with MS, said Dr. Kowalec. Although depression polygenic risk scores are not currently available in clinical practice, “I would hope this would change in the next 3-4 years,” she said.

Asked by a delegate if confounding by a third variable is possible, Dr. Kowalec said because genetic markers don’t change over time, there is a hint that the direction is causal and that depression is driving the outcome. However, she added, further confirmation is needed.

Dr. Kowalec noted that there were no data on antidepressant use but noted that about half of the Canadian and US cohorts — and likely the same number in the Swedish cohorts — self-reported depression.

A limitation of the study was that it included only participants of European ancestry.
 

Clinical Implications Unclear

Commenting on the research, Lauren Gluck, MD, program director, Montefiore Multiple Sclerosis Center, Bronx, New York, described the study as “fascinating” but noted that it’s unclear how to use this new information in clinical practice.

“Clinicians frequently ask people with MS about mood symptoms and offer interventions like antidepressants and referrals to therapists. However, genetic testing is not routine, so we don’t yet know who to target based on these data.”

Preexisting depression or more severe depression could be viewed as a “red flag” for risk for more disease activity in the future, she said.

“This could encourage clinicians to use more highly effective therapy in these patients, similar to our strategies for people with MS with frequent attacks and more disease burden on MRIs.”

The study received support from the Consortium of Multiple Sclerosis Centers and the Congressionally Directed Medical Research Programs, Department of Defense.

Dr. Kowalec reported no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

COPENHAGEN — A higher cumulative genetic burden for depression is associated with an increased risk for relapse and worsening disability in people with multiple sclerosis (MS), early results of a new study showed.

Unlike the previous research, the current analysis used polygenic risk scores for depression, which summarize the estimated effect of genetic variants to determine the potential association with MS disease activity, so results are less likely to be explained by reverse causality.

This study increases awareness of the link between depression and MS, said study investigator Kaarina Kowalec, PhD, assistant professor, College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada. “We’re starting to understand how depression affects relapses and disability progression in MS,” she said.

The findings were presented at the 2024 ECTRIMS annual meeting.
 

Common Comorbidity

Depression is a common comorbidity in patients with MS and is associated with increased relapse and disability progression. Depression risk is partly polygenic in nature, involving numerous common genetic variants, said Dr. Kowalec.

The case-control study included 3420 relapsing-onset MS cases of European ancestry from four existing cohorts in three countries.

The Canadian cohort included those enrolled in a prospective longitudinal study of psychiatric comorbidity in chronic immune-mediated inflammatory disease (IMID), including MS; the Swedish cohort was an MS registry (SSReg) that encompasses 64 MS clinics (the cohort was split into two groups); and the US cohort was enrolled in a clinical trial of combined therapy with interferon and glatiramer acetate (CombiRx) in patients with MS.

The median follow-up in these cohorts ranged from 3 to 5 years.

Not surprisingly, most participants were women (from 71% in one of the Swedish cohorts to 83% in the Canadian cohort), and the age at MS onset ranged from 29 years in the Canadian cohort to 35 years in one of the Swedish cohorts.

The median baseline Expanded Disability Status Scale (EDSS) score was higher in the Canadian cohort (3.5) than in the Swedish (1.5) and US (2.0) cohorts, “reflective of the Canadian cohort being slightly more progressed,” said Dr. Kowalec.
 

Inherited Variants

To measure depression heritability, researchers generated a polygenic risk score in whole-genome imputed genotypes. The score reflects the number of inherited common genetic variants, weighted by effect sizes.

Researchers investigated the association between depression polygenic risk scores (top 20% vs. bottom 80%) with annualized relapse rate and worsening disability in MS measured by the rate of change in EDSS score. In the US cohort, they also explored the association between depression polygenic risk scores and time to relapse and confirmed EDSS worsening.

Covariates included use of disease-modifying therapy, age, sex, and the first five genetic ancestry principal components. The latter was done to capture residual stratification by genetic ancestry, although Dr. Kowalec stressed analyses were done only in those of European ancestry.

Investigators found a higher depression polygenic risk score was associated with relapse risk (incident rate ratio, 1.23; 95% CI, 1.01-1.49).

“Essentially, for every one standard deviation increase in the depression polygenic score, we found a significant increased hazard of 23% for experiencing a relapse over the follow-up period,” said Dr. Kowalec, who is also affiliated with the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

She noted the Canadian cohort did not have many relapses, while the US and Swedish cohorts “had an increased rate.”

Other analyses examined the risk of having a relapse or worsening disability. Every one SD increase in the depression polygenic risk score was significantly associated with a 2.2 greater risk of experiencing relapse (hazard ratio [HR], 2.20; 95% CI, 1.35-3.60) and a 51% increased risk for confirmed EDSS progression (HR, 1.51; 95% CI, 1.03-2.22).
 

‘An Ideal Marker’

Use of polygenetic risk scores reduces the possibility of reverse causation, noted Dr. Kowalec. “These markers are fixed at birth and don’t change over your lifespan, so they’re really an ideal marker.”

The results suggest polygenetic risk scores represent a potential biomarker for risk stratification in people with MS, said Dr. Kowalec. Although depression polygenic risk scores are not currently available in clinical practice, “I would hope this would change in the next 3-4 years,” she said.

Asked by a delegate if confounding by a third variable is possible, Dr. Kowalec said because genetic markers don’t change over time, there is a hint that the direction is causal and that depression is driving the outcome. However, she added, further confirmation is needed.

Dr. Kowalec noted that there were no data on antidepressant use but noted that about half of the Canadian and US cohorts — and likely the same number in the Swedish cohorts — self-reported depression.

A limitation of the study was that it included only participants of European ancestry.
 

Clinical Implications Unclear

Commenting on the research, Lauren Gluck, MD, program director, Montefiore Multiple Sclerosis Center, Bronx, New York, described the study as “fascinating” but noted that it’s unclear how to use this new information in clinical practice.

“Clinicians frequently ask people with MS about mood symptoms and offer interventions like antidepressants and referrals to therapists. However, genetic testing is not routine, so we don’t yet know who to target based on these data.”

Preexisting depression or more severe depression could be viewed as a “red flag” for risk for more disease activity in the future, she said.

“This could encourage clinicians to use more highly effective therapy in these patients, similar to our strategies for people with MS with frequent attacks and more disease burden on MRIs.”

The study received support from the Consortium of Multiple Sclerosis Centers and the Congressionally Directed Medical Research Programs, Department of Defense.

Dr. Kowalec reported no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

COPENHAGEN — A higher cumulative genetic burden for depression is associated with an increased risk for relapse and worsening disability in people with multiple sclerosis (MS), early results of a new study showed.

Unlike the previous research, the current analysis used polygenic risk scores for depression, which summarize the estimated effect of genetic variants to determine the potential association with MS disease activity, so results are less likely to be explained by reverse causality.

This study increases awareness of the link between depression and MS, said study investigator Kaarina Kowalec, PhD, assistant professor, College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada. “We’re starting to understand how depression affects relapses and disability progression in MS,” she said.

The findings were presented at the 2024 ECTRIMS annual meeting.
 

Common Comorbidity

Depression is a common comorbidity in patients with MS and is associated with increased relapse and disability progression. Depression risk is partly polygenic in nature, involving numerous common genetic variants, said Dr. Kowalec.

The case-control study included 3420 relapsing-onset MS cases of European ancestry from four existing cohorts in three countries.

The Canadian cohort included those enrolled in a prospective longitudinal study of psychiatric comorbidity in chronic immune-mediated inflammatory disease (IMID), including MS; the Swedish cohort was an MS registry (SSReg) that encompasses 64 MS clinics (the cohort was split into two groups); and the US cohort was enrolled in a clinical trial of combined therapy with interferon and glatiramer acetate (CombiRx) in patients with MS.

The median follow-up in these cohorts ranged from 3 to 5 years.

Not surprisingly, most participants were women (from 71% in one of the Swedish cohorts to 83% in the Canadian cohort), and the age at MS onset ranged from 29 years in the Canadian cohort to 35 years in one of the Swedish cohorts.

The median baseline Expanded Disability Status Scale (EDSS) score was higher in the Canadian cohort (3.5) than in the Swedish (1.5) and US (2.0) cohorts, “reflective of the Canadian cohort being slightly more progressed,” said Dr. Kowalec.
 

Inherited Variants

To measure depression heritability, researchers generated a polygenic risk score in whole-genome imputed genotypes. The score reflects the number of inherited common genetic variants, weighted by effect sizes.

Researchers investigated the association between depression polygenic risk scores (top 20% vs. bottom 80%) with annualized relapse rate and worsening disability in MS measured by the rate of change in EDSS score. In the US cohort, they also explored the association between depression polygenic risk scores and time to relapse and confirmed EDSS worsening.

Covariates included use of disease-modifying therapy, age, sex, and the first five genetic ancestry principal components. The latter was done to capture residual stratification by genetic ancestry, although Dr. Kowalec stressed analyses were done only in those of European ancestry.

Investigators found a higher depression polygenic risk score was associated with relapse risk (incident rate ratio, 1.23; 95% CI, 1.01-1.49).

“Essentially, for every one standard deviation increase in the depression polygenic score, we found a significant increased hazard of 23% for experiencing a relapse over the follow-up period,” said Dr. Kowalec, who is also affiliated with the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

She noted the Canadian cohort did not have many relapses, while the US and Swedish cohorts “had an increased rate.”

Other analyses examined the risk of having a relapse or worsening disability. Every one SD increase in the depression polygenic risk score was significantly associated with a 2.2 greater risk of experiencing relapse (hazard ratio [HR], 2.20; 95% CI, 1.35-3.60) and a 51% increased risk for confirmed EDSS progression (HR, 1.51; 95% CI, 1.03-2.22).
 

‘An Ideal Marker’

Use of polygenetic risk scores reduces the possibility of reverse causation, noted Dr. Kowalec. “These markers are fixed at birth and don’t change over your lifespan, so they’re really an ideal marker.”

The results suggest polygenetic risk scores represent a potential biomarker for risk stratification in people with MS, said Dr. Kowalec. Although depression polygenic risk scores are not currently available in clinical practice, “I would hope this would change in the next 3-4 years,” she said.

Asked by a delegate if confounding by a third variable is possible, Dr. Kowalec said because genetic markers don’t change over time, there is a hint that the direction is causal and that depression is driving the outcome. However, she added, further confirmation is needed.

Dr. Kowalec noted that there were no data on antidepressant use but noted that about half of the Canadian and US cohorts — and likely the same number in the Swedish cohorts — self-reported depression.

A limitation of the study was that it included only participants of European ancestry.
 

Clinical Implications Unclear

Commenting on the research, Lauren Gluck, MD, program director, Montefiore Multiple Sclerosis Center, Bronx, New York, described the study as “fascinating” but noted that it’s unclear how to use this new information in clinical practice.

“Clinicians frequently ask people with MS about mood symptoms and offer interventions like antidepressants and referrals to therapists. However, genetic testing is not routine, so we don’t yet know who to target based on these data.”

Preexisting depression or more severe depression could be viewed as a “red flag” for risk for more disease activity in the future, she said.

“This could encourage clinicians to use more highly effective therapy in these patients, similar to our strategies for people with MS with frequent attacks and more disease burden on MRIs.”

The study received support from the Consortium of Multiple Sclerosis Centers and the Congressionally Directed Medical Research Programs, Department of Defense.

Dr. Kowalec reported no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

COPENHAGEN — Relative to starting on an immunomodulator and then switching to a more potent anti-CD20 monoclonal antibody, the likelihood of long-term accumulation of disability in patients with multiple sclerosis (MS) is significantly lower if the more potent drug is started first, according to extension data out to 6 years.

By the most recent analysis of a phase 3 extension study, there were “fewer disability worsening events and greater likelihood of being progression free among those started on ofatumumab than those started on teriflunomide and switched,” reported Amit Bar-Or, MD, director of the Center of Neuroinflammation and Neurotherapeutics, University of Pennsylvania, Philadelphia.

Stated differently, if ofatumumab is delayed, it never fully compensates for the advantage of better early MS control in treatment-naïve patients, according to Dr. Bar-Or, who presented these data at the 2024 ECTRIMS annual meeting.
 

Anti-CD20 Disability Protection Already Seen in Pivotal Trial

In two phase 3 trials called ASCLEPIOS I and II that were published together several years ago in The New England Journal of Medicine, the anti-CD20 monoclonal antibody ofatumumab reduced the annualized relapse rate (ARR) by half (0.11 vs. 0.22). While ARR was the primary endpoint, ofatumumab was also associated with a 34% reduction (P = .002) in risk of confirmed disability worsening at 3 months (3mCDW) at a medium follow-up of 1.6 years.

After the completion of ASCLEPIOS I and II, the majority of both arms of the study were enrolled in the ALITHIOS extension study. Patients in ofatumumab arm have remained on their initially assigned drug. Patients in the teriflunomide group were switched. Characterized as the delayed ofatumumab group, they have been receiving the same 20-mg, once-monthly subcutaneous (SQ) dose of ofatumumab as those initially assigned to this drug. ALITHIOS will continue to follow both groups until 2028.

Patients have now been followed for up to 6 years. In the latest results presented at ECTRIMS, data were available for 690 patients on continuous treatment and 677 switch patients. Baseline characteristics of the two groups were similar. About half of each group were treatment naive when enrolled in the ASCLEPIOS trials.

Whether compared for 6-month confirmed disability worsening (6mCDW), 6-month progression independent of relapse activity (6mPIRA) or 6-month relapse-associated worsening (6mRAW), disease progression was consistently worse for those with delayed ofatumumab. The differences were most pronounced in those who were treatment naive when started on therapy.
 

Anti-CD20 MAB sustains Disability Protection for up to Years

For those who were treatment naive, the rates of 6mCDW at the most recent follow-up were 16.61% vs 23.74% (P = .033) for continuous and delayed ofatumumab, respectively. For the entire study, these rates were 21.09% versus 24.77%, respectively, which represented a strong trend (P = .063).

The relative rates for 6mPIRA (11.12% vs 16.75%) and 6mRAW (4.26% vs 4.82%) in treatment-naive patients also favored continuous over delayed ofatumumab, and the numerical advantage was also seen with up to 6 years of follow-up in the overall study population for 6mPIRA (15.45% vs 16.56%) and 6mRAW (5.24% vs 5.81%).

Translating these into freedom from disability, Dr. Bar-Or reported that more than 80% (83.4%) of patients on continuous ofatumumab were progression free for up to 6 years, a figure that exceeded the 76.3% free of progression in the delayed ofatumumab group.

On the basis of 6mPIRA, that absence of disability progression neared 90% (88.9%) on continuous ofatumumab relative to 83.3% for delayed ofatumumab.

An advantage for a reduction in disability accumulation for ofatumumab relative to teriflunomide was established at the end of the ASCLEPIOS I and II trial, but the latest follow-up shows that it is “sustained out to 6 years.” The advantage is achieved with no greater cost in adverse events during the early treatment period, according to Dr. Bar-Or, who noted that ofatumumab and teriflunomide were similarly well tolerated in ASCLEPIOS I and II.
 

No New Gd T1 Lesions Observed Over 12 Months

Although other anti-CD20 monoclonal antibodies have also been shown to be highly effective and often more effective than immunomodulators in the first- and second-line treatment of relapsing remitting MS (RRMS), another set of data presented at ECTRIMS 2024 looked specifically at transitioning from intravenous (IV) anti-CD20 drugs to SQ ofatumumab.

In this study, called OLIKOS, 102 RRMS patients who had received either IV ocrelizumab or IV rituximab were followed after transitioning to ofatumumab administered SQ with an autoinjector pen. The primary endpoint was the proportion of patients with no change or a reduction gadolinium-enhancing (Gd) T1 lesions over 12 months of follow-up.

“At month 12, 84 of 84 evaluable patients with evaluable MRI assessments met the primary endpoint,” reported the principal investigator Le Hua, MD, director of the Multiple Sclerosis Program, Cleveland Clinic in Ohio.

At 12 months, there were also no new or enlarging T2 lesions in 98% of patients receiving SQ ofatumumab following the transition from one of the other anti-CD20 IV drugs, but Dr. Hua characterized this as an exploratory endpoint.

The safety and tolerability data during the OLIKOS study was also reassuring with no new or unexpected safety signals for SQ ofatumumab, which has been well tolerated in the phase 3 development program. IgM and IgG levels remained stable over the course of follow-up.

High-efficacy anti-CD20 drugs were once reserved for RRMS patients with highly active disease, but long-term data, such as those generated by the ALITHIOS extension study, suggest greater efficacy with acceptable safety of these agents relative to conventional first-line RRMS therapies. Based on ALITHIOS data, Dr. Bar-Or suggested that early use of the most effective therapy appears to lead to better long-term protection from increased cumulative disability.

Dr. Bar-Or reported financial relationships with Accure, Atara, Biogen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Gossamer, Janssen/Actelion, Medimmune, Merck/EMD Serono, Novartis, Roche/Genentech, and Sanofi-Genzyme. Dr. Hua reported financial relationships with Alexion, EMD Serono, Genentech, Horizon, Novartis, and TG Therapeutics.

COPENHAGEN — Relative to starting on an immunomodulator and then switching to a more potent anti-CD20 monoclonal antibody, the likelihood of long-term accumulation of disability in patients with multiple sclerosis (MS) is significantly lower if the more potent drug is started first, according to extension data out to 6 years.

By the most recent analysis of a phase 3 extension study, there were “fewer disability worsening events and greater likelihood of being progression free among those started on ofatumumab than those started on teriflunomide and switched,” reported Amit Bar-Or, MD, director of the Center of Neuroinflammation and Neurotherapeutics, University of Pennsylvania, Philadelphia.

Stated differently, if ofatumumab is delayed, it never fully compensates for the advantage of better early MS control in treatment-naïve patients, according to Dr. Bar-Or, who presented these data at the 2024 ECTRIMS annual meeting.
 

Anti-CD20 Disability Protection Already Seen in Pivotal Trial

In two phase 3 trials called ASCLEPIOS I and II that were published together several years ago in The New England Journal of Medicine, the anti-CD20 monoclonal antibody ofatumumab reduced the annualized relapse rate (ARR) by half (0.11 vs. 0.22). While ARR was the primary endpoint, ofatumumab was also associated with a 34% reduction (P = .002) in risk of confirmed disability worsening at 3 months (3mCDW) at a medium follow-up of 1.6 years.

After the completion of ASCLEPIOS I and II, the majority of both arms of the study were enrolled in the ALITHIOS extension study. Patients in ofatumumab arm have remained on their initially assigned drug. Patients in the teriflunomide group were switched. Characterized as the delayed ofatumumab group, they have been receiving the same 20-mg, once-monthly subcutaneous (SQ) dose of ofatumumab as those initially assigned to this drug. ALITHIOS will continue to follow both groups until 2028.

Patients have now been followed for up to 6 years. In the latest results presented at ECTRIMS, data were available for 690 patients on continuous treatment and 677 switch patients. Baseline characteristics of the two groups were similar. About half of each group were treatment naive when enrolled in the ASCLEPIOS trials.

Whether compared for 6-month confirmed disability worsening (6mCDW), 6-month progression independent of relapse activity (6mPIRA) or 6-month relapse-associated worsening (6mRAW), disease progression was consistently worse for those with delayed ofatumumab. The differences were most pronounced in those who were treatment naive when started on therapy.
 

Anti-CD20 MAB sustains Disability Protection for up to Years

For those who were treatment naive, the rates of 6mCDW at the most recent follow-up were 16.61% vs 23.74% (P = .033) for continuous and delayed ofatumumab, respectively. For the entire study, these rates were 21.09% versus 24.77%, respectively, which represented a strong trend (P = .063).

The relative rates for 6mPIRA (11.12% vs 16.75%) and 6mRAW (4.26% vs 4.82%) in treatment-naive patients also favored continuous over delayed ofatumumab, and the numerical advantage was also seen with up to 6 years of follow-up in the overall study population for 6mPIRA (15.45% vs 16.56%) and 6mRAW (5.24% vs 5.81%).

Translating these into freedom from disability, Dr. Bar-Or reported that more than 80% (83.4%) of patients on continuous ofatumumab were progression free for up to 6 years, a figure that exceeded the 76.3% free of progression in the delayed ofatumumab group.

On the basis of 6mPIRA, that absence of disability progression neared 90% (88.9%) on continuous ofatumumab relative to 83.3% for delayed ofatumumab.

An advantage for a reduction in disability accumulation for ofatumumab relative to teriflunomide was established at the end of the ASCLEPIOS I and II trial, but the latest follow-up shows that it is “sustained out to 6 years.” The advantage is achieved with no greater cost in adverse events during the early treatment period, according to Dr. Bar-Or, who noted that ofatumumab and teriflunomide were similarly well tolerated in ASCLEPIOS I and II.
 

No New Gd T1 Lesions Observed Over 12 Months

Although other anti-CD20 monoclonal antibodies have also been shown to be highly effective and often more effective than immunomodulators in the first- and second-line treatment of relapsing remitting MS (RRMS), another set of data presented at ECTRIMS 2024 looked specifically at transitioning from intravenous (IV) anti-CD20 drugs to SQ ofatumumab.

In this study, called OLIKOS, 102 RRMS patients who had received either IV ocrelizumab or IV rituximab were followed after transitioning to ofatumumab administered SQ with an autoinjector pen. The primary endpoint was the proportion of patients with no change or a reduction gadolinium-enhancing (Gd) T1 lesions over 12 months of follow-up.

“At month 12, 84 of 84 evaluable patients with evaluable MRI assessments met the primary endpoint,” reported the principal investigator Le Hua, MD, director of the Multiple Sclerosis Program, Cleveland Clinic in Ohio.

At 12 months, there were also no new or enlarging T2 lesions in 98% of patients receiving SQ ofatumumab following the transition from one of the other anti-CD20 IV drugs, but Dr. Hua characterized this as an exploratory endpoint.

The safety and tolerability data during the OLIKOS study was also reassuring with no new or unexpected safety signals for SQ ofatumumab, which has been well tolerated in the phase 3 development program. IgM and IgG levels remained stable over the course of follow-up.

High-efficacy anti-CD20 drugs were once reserved for RRMS patients with highly active disease, but long-term data, such as those generated by the ALITHIOS extension study, suggest greater efficacy with acceptable safety of these agents relative to conventional first-line RRMS therapies. Based on ALITHIOS data, Dr. Bar-Or suggested that early use of the most effective therapy appears to lead to better long-term protection from increased cumulative disability.

Dr. Bar-Or reported financial relationships with Accure, Atara, Biogen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Gossamer, Janssen/Actelion, Medimmune, Merck/EMD Serono, Novartis, Roche/Genentech, and Sanofi-Genzyme. Dr. Hua reported financial relationships with Alexion, EMD Serono, Genentech, Horizon, Novartis, and TG Therapeutics.

COPENHAGEN — Relative to starting on an immunomodulator and then switching to a more potent anti-CD20 monoclonal antibody, the likelihood of long-term accumulation of disability in patients with multiple sclerosis (MS) is significantly lower if the more potent drug is started first, according to extension data out to 6 years.

By the most recent analysis of a phase 3 extension study, there were “fewer disability worsening events and greater likelihood of being progression free among those started on ofatumumab than those started on teriflunomide and switched,” reported Amit Bar-Or, MD, director of the Center of Neuroinflammation and Neurotherapeutics, University of Pennsylvania, Philadelphia.

Stated differently, if ofatumumab is delayed, it never fully compensates for the advantage of better early MS control in treatment-naïve patients, according to Dr. Bar-Or, who presented these data at the 2024 ECTRIMS annual meeting.
 

Anti-CD20 Disability Protection Already Seen in Pivotal Trial

In two phase 3 trials called ASCLEPIOS I and II that were published together several years ago in The New England Journal of Medicine, the anti-CD20 monoclonal antibody ofatumumab reduced the annualized relapse rate (ARR) by half (0.11 vs. 0.22). While ARR was the primary endpoint, ofatumumab was also associated with a 34% reduction (P = .002) in risk of confirmed disability worsening at 3 months (3mCDW) at a medium follow-up of 1.6 years.

After the completion of ASCLEPIOS I and II, the majority of both arms of the study were enrolled in the ALITHIOS extension study. Patients in ofatumumab arm have remained on their initially assigned drug. Patients in the teriflunomide group were switched. Characterized as the delayed ofatumumab group, they have been receiving the same 20-mg, once-monthly subcutaneous (SQ) dose of ofatumumab as those initially assigned to this drug. ALITHIOS will continue to follow both groups until 2028.

Patients have now been followed for up to 6 years. In the latest results presented at ECTRIMS, data were available for 690 patients on continuous treatment and 677 switch patients. Baseline characteristics of the two groups were similar. About half of each group were treatment naive when enrolled in the ASCLEPIOS trials.

Whether compared for 6-month confirmed disability worsening (6mCDW), 6-month progression independent of relapse activity (6mPIRA) or 6-month relapse-associated worsening (6mRAW), disease progression was consistently worse for those with delayed ofatumumab. The differences were most pronounced in those who were treatment naive when started on therapy.
 

Anti-CD20 MAB sustains Disability Protection for up to Years

For those who were treatment naive, the rates of 6mCDW at the most recent follow-up were 16.61% vs 23.74% (P = .033) for continuous and delayed ofatumumab, respectively. For the entire study, these rates were 21.09% versus 24.77%, respectively, which represented a strong trend (P = .063).

The relative rates for 6mPIRA (11.12% vs 16.75%) and 6mRAW (4.26% vs 4.82%) in treatment-naive patients also favored continuous over delayed ofatumumab, and the numerical advantage was also seen with up to 6 years of follow-up in the overall study population for 6mPIRA (15.45% vs 16.56%) and 6mRAW (5.24% vs 5.81%).

Translating these into freedom from disability, Dr. Bar-Or reported that more than 80% (83.4%) of patients on continuous ofatumumab were progression free for up to 6 years, a figure that exceeded the 76.3% free of progression in the delayed ofatumumab group.

On the basis of 6mPIRA, that absence of disability progression neared 90% (88.9%) on continuous ofatumumab relative to 83.3% for delayed ofatumumab.

An advantage for a reduction in disability accumulation for ofatumumab relative to teriflunomide was established at the end of the ASCLEPIOS I and II trial, but the latest follow-up shows that it is “sustained out to 6 years.” The advantage is achieved with no greater cost in adverse events during the early treatment period, according to Dr. Bar-Or, who noted that ofatumumab and teriflunomide were similarly well tolerated in ASCLEPIOS I and II.
 

No New Gd T1 Lesions Observed Over 12 Months

Although other anti-CD20 monoclonal antibodies have also been shown to be highly effective and often more effective than immunomodulators in the first- and second-line treatment of relapsing remitting MS (RRMS), another set of data presented at ECTRIMS 2024 looked specifically at transitioning from intravenous (IV) anti-CD20 drugs to SQ ofatumumab.

In this study, called OLIKOS, 102 RRMS patients who had received either IV ocrelizumab or IV rituximab were followed after transitioning to ofatumumab administered SQ with an autoinjector pen. The primary endpoint was the proportion of patients with no change or a reduction gadolinium-enhancing (Gd) T1 lesions over 12 months of follow-up.

“At month 12, 84 of 84 evaluable patients with evaluable MRI assessments met the primary endpoint,” reported the principal investigator Le Hua, MD, director of the Multiple Sclerosis Program, Cleveland Clinic in Ohio.

At 12 months, there were also no new or enlarging T2 lesions in 98% of patients receiving SQ ofatumumab following the transition from one of the other anti-CD20 IV drugs, but Dr. Hua characterized this as an exploratory endpoint.

The safety and tolerability data during the OLIKOS study was also reassuring with no new or unexpected safety signals for SQ ofatumumab, which has been well tolerated in the phase 3 development program. IgM and IgG levels remained stable over the course of follow-up.

High-efficacy anti-CD20 drugs were once reserved for RRMS patients with highly active disease, but long-term data, such as those generated by the ALITHIOS extension study, suggest greater efficacy with acceptable safety of these agents relative to conventional first-line RRMS therapies. Based on ALITHIOS data, Dr. Bar-Or suggested that early use of the most effective therapy appears to lead to better long-term protection from increased cumulative disability.

Dr. Bar-Or reported financial relationships with Accure, Atara, Biogen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Gossamer, Janssen/Actelion, Medimmune, Merck/EMD Serono, Novartis, Roche/Genentech, and Sanofi-Genzyme. Dr. Hua reported financial relationships with Alexion, EMD Serono, Genentech, Horizon, Novartis, and TG Therapeutics.

There’s an unexpected treatment for hot flashes and other menopause symptoms that’s getting more popular: clinical hypnosis. 

Hypnosis is a state of highly focused attention that works through disassociating, or putting aside your conscious awareness of things that would ordinarily be in your consciousness, said David Spiegel, MD, a psychiatrist with Stanford Medical School in Califonrnia. 

“It increases your cognitive flexibility – a way to approach an old problem from a new point of view and just let go of your older ways of thinking about it,” he said. 

Usually around age 50, women have menopause, which is the end of their menstrual cycles. Estrogen levels drop, and hot flashes can happen 12-15 times per day, said Gary Elkins, PhD, a psychology and neuroscience professor at Baylor University in Waco, Texas.

Both clinical hypnosis and cognitive-behavioral therapy, a common form of talk therapy, have been shown to work as non-hormonal treatments for hot flashes, particularly for women who are unable to take hormones for health reasons, such as having a history with an estrogen-sensitive cancer (like breast cancer), according to research published by the Menopause Society in 2023. 

A new review presented at the 2024 annual meeting of the Menopause Society in Chicago analyzed 23 studies from 1996 to 2022 and compared how well clinical hypnosis and cognitive behavioral therapy worked as treatments for hot flashes and other menopause symptoms. Researchers found that clinical hypnosis is better at helping make hot flashes less frequent and less intense, even reducing symptoms by 60%. Findings on cognitive-behavioral therapy, on the other hand, showed only slight hot flash reduction, though it helped reduce daily stress linked with hot flashes. 

Hypnosis can address the “perfect storm” of mental and physical issues that come with menopause symptoms, explained Dr. Spiegel, who created a popular self-hypnosis app called Reveri. “You’re having a reduction in your levels of estrogen and progesterone, but it’s also a reminder that you’re going into a different stage of life where you’re no longer fertile, you’re getting older,” he said. “[With hypnosis], you can disassociate pain and your awareness of things that ordinarily would impede your consciousness and make you miserable.”

A hypnosis session can help you separate psychological discomfort from physical discomfort, Dr. Spiegel said. “Typically, people in hypnosis dealing with menopause will imagine they’re floating in a lake, feeling cool, tingling, numbness. They can literally change how hot they feel. They can change the hot flash and imagine themselves cool, comfortable. If they’re worried about something, picture it on an imaginary screen. Just picture it, but not feel it.”
 

Hypnosis for Sleep

Hot flashes that happen at night are called night sweats and can hinder your sleep. Hypnotherapy can help reduce both hot flashes and night sweats, to the point where sleep is not interrupted, Dr. Elkins said. “While sleep improves with the hypnotherapy intervention, it also involves general relaxation,” said Dr. Elkins, who is the director of the Mind-Body Medicine Research Laboratory at Baylor University. “As women practice self-hypnosis at night, they’re entering a more calm and relaxed state, which also may facilitate good sleep or improve sleep duration and sleep quality.”

Our subconscious mind influences our sleep patterns largely through experiences vs. words or thoughts, according to Emilie Leyes, a certified hypnotherapist based in Philadelphia. This explains why simply reciting the words “I’m relaxed,” when you’re stressed, is often less effective than a few deep breaths or a warm hug from a family member or friend, said Ms. Leyes, who hosts a brain-training podcast for mindset transformation called How to Like Your Life.

“In a similar way, hypnosis, which directly accesses the subconscious, allows us to offer our minds new, powerful experiences to reduce our stress, improve our mood, and increase our access to positive emotions,” she said. “Repeatedly exposing ourselves to these positive experiences in our minds can increase our capacity to feel good, and impact how we feel in our everyday lives.”
 

Your First Hypnosis Session

A hypnosis session always begins with deep relaxation, which can help your mind and body grow accustomed to what it’s like to feel calm, said Ms. Leyes. “By giving the brain and body experiences of safety, relaxation, and inner peace, we can more easily let go of our stressful thoughts of the day and drift off to sleep with ease at night.”

You will often start by sitting or lying in a comfortable position, and then the hypnotic induction begins with a focus of attention, according to Dr. Elkins. The person concentrates, with their eyelids closed, and then are given suggestions for deepening their relaxed state. “Usually that’s a safe, pleasant place, such as walking through the mountains or being near a beach,” he said. “And within that, suggestions are given that target the mechanism that underlies the symptoms [such as hot flashes].”

Dr. Spiegel usually starts off with a neutral test that can help measure how hypnotizable a person is on a 0-to-10 scale. For example, instructing the client to imagine that their hand is floating in the air. If they pull their hand down and it floats back up, the client finds they can “actually dissociate the psychological from the physiological aspects of their experience – their left hand feels different from their right hand,” Dr. Spiegel said. “I use that as an example for them to say, ‘look how you can change how your body feels. Now, let’s use it to help you with your anxiety with your menopausal symptoms.’ ”

A version of this article appeared on WebMD.com.

There’s an unexpected treatment for hot flashes and other menopause symptoms that’s getting more popular: clinical hypnosis. 

Hypnosis is a state of highly focused attention that works through disassociating, or putting aside your conscious awareness of things that would ordinarily be in your consciousness, said David Spiegel, MD, a psychiatrist with Stanford Medical School in Califonrnia. 

“It increases your cognitive flexibility – a way to approach an old problem from a new point of view and just let go of your older ways of thinking about it,” he said. 

Usually around age 50, women have menopause, which is the end of their menstrual cycles. Estrogen levels drop, and hot flashes can happen 12-15 times per day, said Gary Elkins, PhD, a psychology and neuroscience professor at Baylor University in Waco, Texas.

Both clinical hypnosis and cognitive-behavioral therapy, a common form of talk therapy, have been shown to work as non-hormonal treatments for hot flashes, particularly for women who are unable to take hormones for health reasons, such as having a history with an estrogen-sensitive cancer (like breast cancer), according to research published by the Menopause Society in 2023. 

A new review presented at the 2024 annual meeting of the Menopause Society in Chicago analyzed 23 studies from 1996 to 2022 and compared how well clinical hypnosis and cognitive behavioral therapy worked as treatments for hot flashes and other menopause symptoms. Researchers found that clinical hypnosis is better at helping make hot flashes less frequent and less intense, even reducing symptoms by 60%. Findings on cognitive-behavioral therapy, on the other hand, showed only slight hot flash reduction, though it helped reduce daily stress linked with hot flashes. 

Hypnosis can address the “perfect storm” of mental and physical issues that come with menopause symptoms, explained Dr. Spiegel, who created a popular self-hypnosis app called Reveri. “You’re having a reduction in your levels of estrogen and progesterone, but it’s also a reminder that you’re going into a different stage of life where you’re no longer fertile, you’re getting older,” he said. “[With hypnosis], you can disassociate pain and your awareness of things that ordinarily would impede your consciousness and make you miserable.”

A hypnosis session can help you separate psychological discomfort from physical discomfort, Dr. Spiegel said. “Typically, people in hypnosis dealing with menopause will imagine they’re floating in a lake, feeling cool, tingling, numbness. They can literally change how hot they feel. They can change the hot flash and imagine themselves cool, comfortable. If they’re worried about something, picture it on an imaginary screen. Just picture it, but not feel it.”
 

Hypnosis for Sleep

Hot flashes that happen at night are called night sweats and can hinder your sleep. Hypnotherapy can help reduce both hot flashes and night sweats, to the point where sleep is not interrupted, Dr. Elkins said. “While sleep improves with the hypnotherapy intervention, it also involves general relaxation,” said Dr. Elkins, who is the director of the Mind-Body Medicine Research Laboratory at Baylor University. “As women practice self-hypnosis at night, they’re entering a more calm and relaxed state, which also may facilitate good sleep or improve sleep duration and sleep quality.”

Our subconscious mind influences our sleep patterns largely through experiences vs. words or thoughts, according to Emilie Leyes, a certified hypnotherapist based in Philadelphia. This explains why simply reciting the words “I’m relaxed,” when you’re stressed, is often less effective than a few deep breaths or a warm hug from a family member or friend, said Ms. Leyes, who hosts a brain-training podcast for mindset transformation called How to Like Your Life.

“In a similar way, hypnosis, which directly accesses the subconscious, allows us to offer our minds new, powerful experiences to reduce our stress, improve our mood, and increase our access to positive emotions,” she said. “Repeatedly exposing ourselves to these positive experiences in our minds can increase our capacity to feel good, and impact how we feel in our everyday lives.”
 

Your First Hypnosis Session

A hypnosis session always begins with deep relaxation, which can help your mind and body grow accustomed to what it’s like to feel calm, said Ms. Leyes. “By giving the brain and body experiences of safety, relaxation, and inner peace, we can more easily let go of our stressful thoughts of the day and drift off to sleep with ease at night.”

You will often start by sitting or lying in a comfortable position, and then the hypnotic induction begins with a focus of attention, according to Dr. Elkins. The person concentrates, with their eyelids closed, and then are given suggestions for deepening their relaxed state. “Usually that’s a safe, pleasant place, such as walking through the mountains or being near a beach,” he said. “And within that, suggestions are given that target the mechanism that underlies the symptoms [such as hot flashes].”

Dr. Spiegel usually starts off with a neutral test that can help measure how hypnotizable a person is on a 0-to-10 scale. For example, instructing the client to imagine that their hand is floating in the air. If they pull their hand down and it floats back up, the client finds they can “actually dissociate the psychological from the physiological aspects of their experience – their left hand feels different from their right hand,” Dr. Spiegel said. “I use that as an example for them to say, ‘look how you can change how your body feels. Now, let’s use it to help you with your anxiety with your menopausal symptoms.’ ”

A version of this article appeared on WebMD.com.

There’s an unexpected treatment for hot flashes and other menopause symptoms that’s getting more popular: clinical hypnosis. 

Hypnosis is a state of highly focused attention that works through disassociating, or putting aside your conscious awareness of things that would ordinarily be in your consciousness, said David Spiegel, MD, a psychiatrist with Stanford Medical School in Califonrnia. 

“It increases your cognitive flexibility – a way to approach an old problem from a new point of view and just let go of your older ways of thinking about it,” he said. 

Usually around age 50, women have menopause, which is the end of their menstrual cycles. Estrogen levels drop, and hot flashes can happen 12-15 times per day, said Gary Elkins, PhD, a psychology and neuroscience professor at Baylor University in Waco, Texas.

Both clinical hypnosis and cognitive-behavioral therapy, a common form of talk therapy, have been shown to work as non-hormonal treatments for hot flashes, particularly for women who are unable to take hormones for health reasons, such as having a history with an estrogen-sensitive cancer (like breast cancer), according to research published by the Menopause Society in 2023. 

A new review presented at the 2024 annual meeting of the Menopause Society in Chicago analyzed 23 studies from 1996 to 2022 and compared how well clinical hypnosis and cognitive behavioral therapy worked as treatments for hot flashes and other menopause symptoms. Researchers found that clinical hypnosis is better at helping make hot flashes less frequent and less intense, even reducing symptoms by 60%. Findings on cognitive-behavioral therapy, on the other hand, showed only slight hot flash reduction, though it helped reduce daily stress linked with hot flashes. 

Hypnosis can address the “perfect storm” of mental and physical issues that come with menopause symptoms, explained Dr. Spiegel, who created a popular self-hypnosis app called Reveri. “You’re having a reduction in your levels of estrogen and progesterone, but it’s also a reminder that you’re going into a different stage of life where you’re no longer fertile, you’re getting older,” he said. “[With hypnosis], you can disassociate pain and your awareness of things that ordinarily would impede your consciousness and make you miserable.”

A hypnosis session can help you separate psychological discomfort from physical discomfort, Dr. Spiegel said. “Typically, people in hypnosis dealing with menopause will imagine they’re floating in a lake, feeling cool, tingling, numbness. They can literally change how hot they feel. They can change the hot flash and imagine themselves cool, comfortable. If they’re worried about something, picture it on an imaginary screen. Just picture it, but not feel it.”
 

Hypnosis for Sleep

Hot flashes that happen at night are called night sweats and can hinder your sleep. Hypnotherapy can help reduce both hot flashes and night sweats, to the point where sleep is not interrupted, Dr. Elkins said. “While sleep improves with the hypnotherapy intervention, it also involves general relaxation,” said Dr. Elkins, who is the director of the Mind-Body Medicine Research Laboratory at Baylor University. “As women practice self-hypnosis at night, they’re entering a more calm and relaxed state, which also may facilitate good sleep or improve sleep duration and sleep quality.”

Our subconscious mind influences our sleep patterns largely through experiences vs. words or thoughts, according to Emilie Leyes, a certified hypnotherapist based in Philadelphia. This explains why simply reciting the words “I’m relaxed,” when you’re stressed, is often less effective than a few deep breaths or a warm hug from a family member or friend, said Ms. Leyes, who hosts a brain-training podcast for mindset transformation called How to Like Your Life.

“In a similar way, hypnosis, which directly accesses the subconscious, allows us to offer our minds new, powerful experiences to reduce our stress, improve our mood, and increase our access to positive emotions,” she said. “Repeatedly exposing ourselves to these positive experiences in our minds can increase our capacity to feel good, and impact how we feel in our everyday lives.”
 

Your First Hypnosis Session

A hypnosis session always begins with deep relaxation, which can help your mind and body grow accustomed to what it’s like to feel calm, said Ms. Leyes. “By giving the brain and body experiences of safety, relaxation, and inner peace, we can more easily let go of our stressful thoughts of the day and drift off to sleep with ease at night.”

You will often start by sitting or lying in a comfortable position, and then the hypnotic induction begins with a focus of attention, according to Dr. Elkins. The person concentrates, with their eyelids closed, and then are given suggestions for deepening their relaxed state. “Usually that’s a safe, pleasant place, such as walking through the mountains or being near a beach,” he said. “And within that, suggestions are given that target the mechanism that underlies the symptoms [such as hot flashes].”

Dr. Spiegel usually starts off with a neutral test that can help measure how hypnotizable a person is on a 0-to-10 scale. For example, instructing the client to imagine that their hand is floating in the air. If they pull their hand down and it floats back up, the client finds they can “actually dissociate the psychological from the physiological aspects of their experience – their left hand feels different from their right hand,” Dr. Spiegel said. “I use that as an example for them to say, ‘look how you can change how your body feels. Now, let’s use it to help you with your anxiety with your menopausal symptoms.’ ”

A version of this article appeared on WebMD.com.

MILAN — Psilocybin leads to a better overall outcome in the treatment of moderate to severe major depressive disorder (MDD) than the selective serotonin reuptake inhibitor (SSRI) escitalopram, results of the first long-term comparison of the two treatments suggest.

“This is the first work to compare the long-term effects of these two drugs in the context of overall well-being, not just freedom from depression,” study investigator Tommaso Barba, PhD candidate at Imperial College London in England, said in a press release. “Psilocybin outperformed escitalopram in several measures of well-being, meaning in life, work, and social functioning.”

Findings from the 6-month follow-up study of a phase 2 double-blind, randomized, controlled trial were presented at the 37th European College of Neuropsychopharmacology (ECNP) Congress and published simultaneously in The Lancet eClinicalMedicine

Addressing a Treatment ‘Mismatch’

The findings are important because they address “a mismatch” between what psychiatrists and what patients think is important, Mr. Barba said in an interview.

“Psychiatrists really focus on negative symptoms of depression. So, if you are not sad anymore, if your sleep or appetite is not impaired, they think you’re better. But if you look at what patients define as important, they say it’s the degree in which their life is meaningful, in which they can connect with people around them, in which they can function in everyday life,” Mr. Barba said.

“The study suggests that psilocybin therapy might be a more holistic treatment option for depression,” added co–first author David Erritzoe, MD, PhD, clinical director and deputy head of the Centre for Psychedelic Research, Imperial College London. “This could make a substantial difference in the overall happiness and daily activities of those suffering from depression, providing a more joined-up approach to mental health treatment.”

The initial single-center study included 59 adults with MDD (mean age, 41 years) who were randomized to receive either psilocybin or escitalopram over a 6-week period. The psilocybin arm (n = 30) received two 25-mg oral doses of psilocybin therapy (PT), and the escitalopram arm (n = 29) received 10-20 mg of daily escitalopram plus two (placebo-like) 1-mg doses of psilocybin (ET). Both groups received psychological support.

Based on change in depression scores on the 16-item Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR-16) at week 6, the initial study results suggested noninferiority between the two treatments in terms of depressive symptoms (primary outcome), but superiority of PT for secondary outcomes including “well-being, anhedonia, social functioning, sexual functioning, and related variables, with fewer side effects compared to ET,” the researchers noted.

The new 6-month follow-up findings, with monthly questionnaires and no additional study treatment or psychiatric treatment restrictions, measured the QIDS-SR-16, plus Work and Social Adjustment Scale (WSAS), Meaning in Life Questionnaire, Flourishing Scale (FS), and Watts Connectedness Scale (WCS).

Again, both groups maintained similar results on the QIDS-SR-16, with slightly greater reductions in depressive symptoms for PT in the first month (positive false discovery rate [pFDR] = 0.021), but not thereafter.

At both 3 and 6 months, there were greater improvements in WSAS scores for the PT group (pFDR < 0.001 and pFDR = 0.01, respectively), and also greater improvements in meaning in life across all follow-up timepoints (pFDR < 0.001).

There was also greater improvement in the PT group regarding WCS at both 3 and 6 months (pFDR = 0.02, and pFDR = 0.04) and comparable FS improvements for both groups across all timepoints.

Confounding follow-up interventions may have muddied the results, with 30.7% of PT participants and 43.5% of ET participants receiving an additional intervention during this period.

The researchers conclude that while a short course of SSRIs combined with intensive therapeutic support (around 20 hours) “might be enough to induce sustained antidepressant effects,” patients treated with psilocybin showed greater improvements in general functioning, connectedness, and meaning in life.

Although not reassessed in the follow-up, the initial study showed that adverse events, particularly sexual functioning, favored psilocybin, said Mr. Barba. “The two treatments seemed to go in opposite directions with psilocybin seeming to improve it and the antidepressant to suppress it. Other side effects associated with psilocybin were less diverse — mainly headaches at the end of the day — but with escitalopram they were way more diverse and more impairing.”

Although many therapists may be unfamiliar with psilocybin-assisted psychotherapy, “it’s not a difficult skill to master. It might require some specialization, but I think if you’re a good psychotherapist, you can learn how to implement psilocybin into your practice,” he said.

“Normally the journey is quite inward, so patients do not require active support during the psychedelic experience [around 6 hours]. Sometimes they do require some hand-holding, or helping them to ‘let go’, or breathing exercises. The important part is the integration work that comes afterwards,” Mr. Barba added.

He said he envisions a therapy program that involves “psychiatrists working together with psychotherapists. The psychotherapists would be more in charge of the active guiding, and the psychiatrist would do the prescribing, with the follow-up psychological support on Zoom.”

He added a word of caution for therapists that “psilocybin requires active confrontation of painful, negative emotions and people who take this drug need to be open and prepared for the idea that they are going into a state where they may probably end up crying and confronting whatever they are maybe running away from in their lives. Not everyone may want to do this.”
 

A New Treatment Paradigm?

In a comment, Johan Lundberg, MD, PhD, adjunct professor of psychiatry at the Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden, said the study addresses a key outstanding question about the long-term effects of one or two doses of psilocybin.

“It’s a 6-month follow-up of a short treatment intervention, so in that sense, it’s of high interest. It has been talked about that psilocybin might have a long-term effect, but this is the first study that has followed this for a longer term.”

But Dr. Lundberg also pointed out that one shortcoming of the study is the diversity of treatments following the intervention.

“They didn’t have control over whether patients received other treatments or when they started. So, that is a key concern. But they transparently reported that, and we do know there was a difference in reported ability to perform activities of daily life, and that is important.”

He added that if psilocybin is eventually approved, it would likely come with an education package for providers — “which is already the case with other treatments like ECT [electroconvulsive therapy] or TMS [transcranial magnetic stimulation] — you have to learn how to do it.”

James Rucker, MD, PhD, psychiatrist and senior clinical lecturer at King’s College London, who was not involved in the research, also noted that they have tended to attribute differences observed in this study to comparative differences between the drugs themselves.

However, he noted, it is also possible that the results reflect biased reporting between groups. This is more likely here because studies involving psilocybin tend to attract those with positive preconceptions about psilocybin and negative preconceptions about conventional antidepressants, and study participants were unblinded during the long-term follow-up phase, so knew which condition they were allocated to.

“This said, the nature of depression varies hugely between individuals, and this calls for the development of a similarly varied suite of treatment paradigms. Psilocybin therapy is certainly a different paradigm of treatment to escitalopram. The observation of similar levels of effectiveness to antidepressants here is encouraging to see alongside the much larger trials of psilocybin currently underway here in the UK, Europe, and the US,” Dr. Rucker added.

This work was supported by The Alexander Mosley Charitable Trust and by the founding partners of Imperial College London’s Centre for Psychedelic Research.

Mr. Barba reported having received consulting fees from Adamo Bioscience. Both Dr. Lundberg and Dr. Rucker are involved in psilocybin research, but neither reported financial links.

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

MILAN — Psilocybin leads to a better overall outcome in the treatment of moderate to severe major depressive disorder (MDD) than the selective serotonin reuptake inhibitor (SSRI) escitalopram, results of the first long-term comparison of the two treatments suggest.

“This is the first work to compare the long-term effects of these two drugs in the context of overall well-being, not just freedom from depression,” study investigator Tommaso Barba, PhD candidate at Imperial College London in England, said in a press release. “Psilocybin outperformed escitalopram in several measures of well-being, meaning in life, work, and social functioning.”

Findings from the 6-month follow-up study of a phase 2 double-blind, randomized, controlled trial were presented at the 37th European College of Neuropsychopharmacology (ECNP) Congress and published simultaneously in The Lancet eClinicalMedicine

Addressing a Treatment ‘Mismatch’

The findings are important because they address “a mismatch” between what psychiatrists and what patients think is important, Mr. Barba said in an interview.

“Psychiatrists really focus on negative symptoms of depression. So, if you are not sad anymore, if your sleep or appetite is not impaired, they think you’re better. But if you look at what patients define as important, they say it’s the degree in which their life is meaningful, in which they can connect with people around them, in which they can function in everyday life,” Mr. Barba said.

“The study suggests that psilocybin therapy might be a more holistic treatment option for depression,” added co–first author David Erritzoe, MD, PhD, clinical director and deputy head of the Centre for Psychedelic Research, Imperial College London. “This could make a substantial difference in the overall happiness and daily activities of those suffering from depression, providing a more joined-up approach to mental health treatment.”

The initial single-center study included 59 adults with MDD (mean age, 41 years) who were randomized to receive either psilocybin or escitalopram over a 6-week period. The psilocybin arm (n = 30) received two 25-mg oral doses of psilocybin therapy (PT), and the escitalopram arm (n = 29) received 10-20 mg of daily escitalopram plus two (placebo-like) 1-mg doses of psilocybin (ET). Both groups received psychological support.

Based on change in depression scores on the 16-item Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR-16) at week 6, the initial study results suggested noninferiority between the two treatments in terms of depressive symptoms (primary outcome), but superiority of PT for secondary outcomes including “well-being, anhedonia, social functioning, sexual functioning, and related variables, with fewer side effects compared to ET,” the researchers noted.

The new 6-month follow-up findings, with monthly questionnaires and no additional study treatment or psychiatric treatment restrictions, measured the QIDS-SR-16, plus Work and Social Adjustment Scale (WSAS), Meaning in Life Questionnaire, Flourishing Scale (FS), and Watts Connectedness Scale (WCS).

Again, both groups maintained similar results on the QIDS-SR-16, with slightly greater reductions in depressive symptoms for PT in the first month (positive false discovery rate [pFDR] = 0.021), but not thereafter.

At both 3 and 6 months, there were greater improvements in WSAS scores for the PT group (pFDR < 0.001 and pFDR = 0.01, respectively), and also greater improvements in meaning in life across all follow-up timepoints (pFDR < 0.001).

There was also greater improvement in the PT group regarding WCS at both 3 and 6 months (pFDR = 0.02, and pFDR = 0.04) and comparable FS improvements for both groups across all timepoints.

Confounding follow-up interventions may have muddied the results, with 30.7% of PT participants and 43.5% of ET participants receiving an additional intervention during this period.

The researchers conclude that while a short course of SSRIs combined with intensive therapeutic support (around 20 hours) “might be enough to induce sustained antidepressant effects,” patients treated with psilocybin showed greater improvements in general functioning, connectedness, and meaning in life.

Although not reassessed in the follow-up, the initial study showed that adverse events, particularly sexual functioning, favored psilocybin, said Mr. Barba. “The two treatments seemed to go in opposite directions with psilocybin seeming to improve it and the antidepressant to suppress it. Other side effects associated with psilocybin were less diverse — mainly headaches at the end of the day — but with escitalopram they were way more diverse and more impairing.”

Although many therapists may be unfamiliar with psilocybin-assisted psychotherapy, “it’s not a difficult skill to master. It might require some specialization, but I think if you’re a good psychotherapist, you can learn how to implement psilocybin into your practice,” he said.

“Normally the journey is quite inward, so patients do not require active support during the psychedelic experience [around 6 hours]. Sometimes they do require some hand-holding, or helping them to ‘let go’, or breathing exercises. The important part is the integration work that comes afterwards,” Mr. Barba added.

He said he envisions a therapy program that involves “psychiatrists working together with psychotherapists. The psychotherapists would be more in charge of the active guiding, and the psychiatrist would do the prescribing, with the follow-up psychological support on Zoom.”

He added a word of caution for therapists that “psilocybin requires active confrontation of painful, negative emotions and people who take this drug need to be open and prepared for the idea that they are going into a state where they may probably end up crying and confronting whatever they are maybe running away from in their lives. Not everyone may want to do this.”
 

A New Treatment Paradigm?

In a comment, Johan Lundberg, MD, PhD, adjunct professor of psychiatry at the Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden, said the study addresses a key outstanding question about the long-term effects of one or two doses of psilocybin.

“It’s a 6-month follow-up of a short treatment intervention, so in that sense, it’s of high interest. It has been talked about that psilocybin might have a long-term effect, but this is the first study that has followed this for a longer term.”

But Dr. Lundberg also pointed out that one shortcoming of the study is the diversity of treatments following the intervention.

“They didn’t have control over whether patients received other treatments or when they started. So, that is a key concern. But they transparently reported that, and we do know there was a difference in reported ability to perform activities of daily life, and that is important.”

He added that if psilocybin is eventually approved, it would likely come with an education package for providers — “which is already the case with other treatments like ECT [electroconvulsive therapy] or TMS [transcranial magnetic stimulation] — you have to learn how to do it.”

James Rucker, MD, PhD, psychiatrist and senior clinical lecturer at King’s College London, who was not involved in the research, also noted that they have tended to attribute differences observed in this study to comparative differences between the drugs themselves.

However, he noted, it is also possible that the results reflect biased reporting between groups. This is more likely here because studies involving psilocybin tend to attract those with positive preconceptions about psilocybin and negative preconceptions about conventional antidepressants, and study participants were unblinded during the long-term follow-up phase, so knew which condition they were allocated to.

“This said, the nature of depression varies hugely between individuals, and this calls for the development of a similarly varied suite of treatment paradigms. Psilocybin therapy is certainly a different paradigm of treatment to escitalopram. The observation of similar levels of effectiveness to antidepressants here is encouraging to see alongside the much larger trials of psilocybin currently underway here in the UK, Europe, and the US,” Dr. Rucker added.

This work was supported by The Alexander Mosley Charitable Trust and by the founding partners of Imperial College London’s Centre for Psychedelic Research.

Mr. Barba reported having received consulting fees from Adamo Bioscience. Both Dr. Lundberg and Dr. Rucker are involved in psilocybin research, but neither reported financial links.

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

MILAN — Psilocybin leads to a better overall outcome in the treatment of moderate to severe major depressive disorder (MDD) than the selective serotonin reuptake inhibitor (SSRI) escitalopram, results of the first long-term comparison of the two treatments suggest.

“This is the first work to compare the long-term effects of these two drugs in the context of overall well-being, not just freedom from depression,” study investigator Tommaso Barba, PhD candidate at Imperial College London in England, said in a press release. “Psilocybin outperformed escitalopram in several measures of well-being, meaning in life, work, and social functioning.”

Findings from the 6-month follow-up study of a phase 2 double-blind, randomized, controlled trial were presented at the 37th European College of Neuropsychopharmacology (ECNP) Congress and published simultaneously in The Lancet eClinicalMedicine

Addressing a Treatment ‘Mismatch’

The findings are important because they address “a mismatch” between what psychiatrists and what patients think is important, Mr. Barba said in an interview.

“Psychiatrists really focus on negative symptoms of depression. So, if you are not sad anymore, if your sleep or appetite is not impaired, they think you’re better. But if you look at what patients define as important, they say it’s the degree in which their life is meaningful, in which they can connect with people around them, in which they can function in everyday life,” Mr. Barba said.

“The study suggests that psilocybin therapy might be a more holistic treatment option for depression,” added co–first author David Erritzoe, MD, PhD, clinical director and deputy head of the Centre for Psychedelic Research, Imperial College London. “This could make a substantial difference in the overall happiness and daily activities of those suffering from depression, providing a more joined-up approach to mental health treatment.”

The initial single-center study included 59 adults with MDD (mean age, 41 years) who were randomized to receive either psilocybin or escitalopram over a 6-week period. The psilocybin arm (n = 30) received two 25-mg oral doses of psilocybin therapy (PT), and the escitalopram arm (n = 29) received 10-20 mg of daily escitalopram plus two (placebo-like) 1-mg doses of psilocybin (ET). Both groups received psychological support.

Based on change in depression scores on the 16-item Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR-16) at week 6, the initial study results suggested noninferiority between the two treatments in terms of depressive symptoms (primary outcome), but superiority of PT for secondary outcomes including “well-being, anhedonia, social functioning, sexual functioning, and related variables, with fewer side effects compared to ET,” the researchers noted.

The new 6-month follow-up findings, with monthly questionnaires and no additional study treatment or psychiatric treatment restrictions, measured the QIDS-SR-16, plus Work and Social Adjustment Scale (WSAS), Meaning in Life Questionnaire, Flourishing Scale (FS), and Watts Connectedness Scale (WCS).

Again, both groups maintained similar results on the QIDS-SR-16, with slightly greater reductions in depressive symptoms for PT in the first month (positive false discovery rate [pFDR] = 0.021), but not thereafter.

At both 3 and 6 months, there were greater improvements in WSAS scores for the PT group (pFDR < 0.001 and pFDR = 0.01, respectively), and also greater improvements in meaning in life across all follow-up timepoints (pFDR < 0.001).

There was also greater improvement in the PT group regarding WCS at both 3 and 6 months (pFDR = 0.02, and pFDR = 0.04) and comparable FS improvements for both groups across all timepoints.

Confounding follow-up interventions may have muddied the results, with 30.7% of PT participants and 43.5% of ET participants receiving an additional intervention during this period.

The researchers conclude that while a short course of SSRIs combined with intensive therapeutic support (around 20 hours) “might be enough to induce sustained antidepressant effects,” patients treated with psilocybin showed greater improvements in general functioning, connectedness, and meaning in life.

Although not reassessed in the follow-up, the initial study showed that adverse events, particularly sexual functioning, favored psilocybin, said Mr. Barba. “The two treatments seemed to go in opposite directions with psilocybin seeming to improve it and the antidepressant to suppress it. Other side effects associated with psilocybin were less diverse — mainly headaches at the end of the day — but with escitalopram they were way more diverse and more impairing.”

Although many therapists may be unfamiliar with psilocybin-assisted psychotherapy, “it’s not a difficult skill to master. It might require some specialization, but I think if you’re a good psychotherapist, you can learn how to implement psilocybin into your practice,” he said.

“Normally the journey is quite inward, so patients do not require active support during the psychedelic experience [around 6 hours]. Sometimes they do require some hand-holding, or helping them to ‘let go’, or breathing exercises. The important part is the integration work that comes afterwards,” Mr. Barba added.

He said he envisions a therapy program that involves “psychiatrists working together with psychotherapists. The psychotherapists would be more in charge of the active guiding, and the psychiatrist would do the prescribing, with the follow-up psychological support on Zoom.”

He added a word of caution for therapists that “psilocybin requires active confrontation of painful, negative emotions and people who take this drug need to be open and prepared for the idea that they are going into a state where they may probably end up crying and confronting whatever they are maybe running away from in their lives. Not everyone may want to do this.”
 

A New Treatment Paradigm?

In a comment, Johan Lundberg, MD, PhD, adjunct professor of psychiatry at the Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden, said the study addresses a key outstanding question about the long-term effects of one or two doses of psilocybin.

“It’s a 6-month follow-up of a short treatment intervention, so in that sense, it’s of high interest. It has been talked about that psilocybin might have a long-term effect, but this is the first study that has followed this for a longer term.”

But Dr. Lundberg also pointed out that one shortcoming of the study is the diversity of treatments following the intervention.

“They didn’t have control over whether patients received other treatments or when they started. So, that is a key concern. But they transparently reported that, and we do know there was a difference in reported ability to perform activities of daily life, and that is important.”

He added that if psilocybin is eventually approved, it would likely come with an education package for providers — “which is already the case with other treatments like ECT [electroconvulsive therapy] or TMS [transcranial magnetic stimulation] — you have to learn how to do it.”

James Rucker, MD, PhD, psychiatrist and senior clinical lecturer at King’s College London, who was not involved in the research, also noted that they have tended to attribute differences observed in this study to comparative differences between the drugs themselves.

However, he noted, it is also possible that the results reflect biased reporting between groups. This is more likely here because studies involving psilocybin tend to attract those with positive preconceptions about psilocybin and negative preconceptions about conventional antidepressants, and study participants were unblinded during the long-term follow-up phase, so knew which condition they were allocated to.

“This said, the nature of depression varies hugely between individuals, and this calls for the development of a similarly varied suite of treatment paradigms. Psilocybin therapy is certainly a different paradigm of treatment to escitalopram. The observation of similar levels of effectiveness to antidepressants here is encouraging to see alongside the much larger trials of psilocybin currently underway here in the UK, Europe, and the US,” Dr. Rucker added.

This work was supported by The Alexander Mosley Charitable Trust and by the founding partners of Imperial College London’s Centre for Psychedelic Research.

Mr. Barba reported having received consulting fees from Adamo Bioscience. Both Dr. Lundberg and Dr. Rucker are involved in psilocybin research, but neither reported financial links.

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

COPENHAGEN — A new investigational drug has become the first agent to slow disability in patients with nonrelapsing secondary progressive multiple sclerosis (nrSPMS).

The phase 3 HERCULES trial showed tolebrutinib, an oral Bruton’s tyrosine kinase (BTK) inhibitor, delayed the time to onset of 6-month confirmed disability progression by 31%, compared with placebo.

In addition, tolebrutinib almost doubled the number of patients who experienced confirmed disability improvement from 5% to 10%.

However, these benefits come with the potential safety issue of liver toxicity, with raised liver enzymes reported in 4% of patients and very severe liver enzyme rises occurring in 0.5% of patients, one of whom died after undergoing a liver transplant.  

The results were presented by Robert Fox, MD, vice chair of research at the Cleveland Clinic’s Neurological Institute in Ohio, at the 2024 ECTRIMS annual meeting. 

“We have finally found a therapy that can alter the compartmentalized inflammation that is driving progressive MS,” he said. 

Dr. Fox pointed out that the population enrolled in the HERCULES trial had stopped having clinical relapses. “These are the patients for whom current immunomodulator therapies really don’t work at all — they don’t slow disability. This trial suggests that tolebrutinib can fill that void and now we have something to offer this patient group,” he said. 

He estimated that up to 30% of patients with MS at his clinic may fall into this category. 

A typical patient with nrSPMS who was included in this trial may have experienced a gradual decline in the distance they can walk or the ease with which they could climb stairs, he explained. 

“I would project that this therapy will slow down that gradual decline, and, in some patients, it may actually stop the decline,” he added.

Dr. Fox said that BTK inhibitors are believed to have two main mechanisms of action relevant to MS — down-regulating B cells, probably mostly in the periphery, and, as these agents can cross the blood-brain barrier, they also appear to reduce the inflammatory activity of microglia and macrophages in the brain.

He noted that the disability progression in nrSPMS patients is thought to be caused by compartmentalized inflammation in the brain, which is what tolebrutinib may be targeting. 

He noted that siponimod has also shown benefit in secondary progressive MS in the EXPAND trial, but the benefit was almost entirely restricted to patients who had experienced recent relapses. 

Ocrelizumab has been shown to be beneficial in a trial in primary progressive MS, but again, a large proportion of patients in that study had active focal inflammation at baselineEngl J Med. 2017;376:209-220).
 

Trial Results 

The HERCULES trial included 1131 patients with nrSPMS, defined as having an Expanded Disability Status Scale score (EDSS) between 3.0 and 6.5, no clinical relapses in the previous 24 months, and documented evidence of disability accumulation in the previous 12 months. 

They were randomly assigned (2:1) to receive 60 mg tolebrutinib as an oral daily dose or placebo for up to approximately 48 months. This was an event-driven trial, with 288 6-month confirmed disability progression events required. 

About 23% of patients in each group discontinued treatment and 12%-17% who had confirmed disability progression elected to crossover to open-label tolebrutinib.

The study population had an average age of 49 years, had a median EDSS score of 6, and a mean time since last clinical relapse of over 7 years. 

“So, this was a really very quiescent patient population in terms of focal inflammation,” Dr. Fox noted.

Results showed that the primary endpoint showed a 31% reduction in the risk of 6-month confirmed disability progression (26.9% tolebrutinib vs. 37.2% placebo; hazard ratio [HR], 0.69; 95% CI, 0.55-0.88). 

Rates of 3-month confirmed disability progression were 32.6% in the tolebrutinib group versus 41.5% with placebo — a 24% risk reduction.

In addition, 6-month confirmed disability improvement was achieved by 10% of tolebrutinib patients versus 5% in the placebo group (HR, 1.88; 95% CI, 1.10-3.21).
 

A ‘Head-scratcher’ Finding

Surprisingly, he noted, tolebrutinib did not appear to slow brain atrophy. 

“Despite seeing a benefit on disability progression, we saw no significant slowing of brain atrophy or brain volume loss over the course of the study,” Dr. Fox reported. 

He described this discordance between disability rates and brain volume loss rates as “a bit of a head-scratcher.” 

In terms of safety, the main concern is liver enzyme elevations, which occurred at greater than three times the upper limit of normal (ULN) in 4.1% of the tolebrutinib group vs 1.6% in the placebo group.

A small (0.5%) proportion of patients treated with tolebrutinib experienced very severe elevations (> 20 x ULN) in liver enzymes, and one of these patients had to have a liver transplant and died because of postoperative complications, “a reminder that this can be a very serious complication of this drug,” said Dr. Fox. 

However, he noted that all the very severe liver enzyme rises occurred in the first 3 months and it is now recommended that patients undergo weekly liver enzyme monitoring for the first 12 weeks of treatment. 

Other adverse effects that were increased slightly in tolebrutinib group were upper respiratory infections and possibly hypertension.  
 

Weekly Liver Enzyme Testing 

Dr. Fox cautioned that patients starting tolebrutinib would need to undergo weekly liver enzyme testing in the first few months of treatment. “They would need to be very attentive to this monitoring, but if they are willing to do that, then I think many of these patients will be very eager to take this drug that may slow down their disability progression.”

The drug’s manufacturer, Sanofi, said the trial results will form the basis for applications to global regulatory authorities with submissions starting later in 2024. 

Commenting on the trial, Ludwig Kappos, MD, professor of neurology at University Hospital and University of Basel, Switzerland, said the trial was important as it had shown “a robust effect on confirmed disability progression in a population of secondary progressive MS with no or very low signs of focal inflammation.”

“The effect is similar and probably more pronounced than that seen in the siponimod trial also in advanced secondary progressive MS,” he added. 

Dr. Kappos believes more work will be needed to make sure the liver toxicity can be prevented, “but if that can be resolved then patients could have a significant delay in accumulating disability.”
 

GEMINI Trials Also Show Slowed Disability 

Two other phase 3 trials of tolebrutinib were presented during the same ECTRIMS session — GEMINI 1 and 2 — which compared the new drug with teriflunomide, a standard of care treatment, in participants with relapsing MS. Neither study met the primary endpoint of an improvement in annualized relapse rates, compared with teriflunomide. 

However, with respect to the key secondary endpoint, in a pooled analysis of data from GEMINI 1 and 2, tolebrutinib delayed the time to onset of 6-month confirmed disability worsening by 29%, a finding in line with the main results of the HERCULES trial. 

“The significant impact of tolebrutinib on disability accumulation versus teriflunomide, in the absence of a statistically superior impact on relapses, also suggests that tolebrutinib may address smoldering neuroinflammation, which manifests as progression independent of relapses” Dr. Fox said. 

The HERCULES trial was sponsored by Sanofi. Dr. Fox is a paid adviser to Sanofi. Dr. Kappos led the EXPAND trial of siponimod in SPMS.

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

COPENHAGEN — A new investigational drug has become the first agent to slow disability in patients with nonrelapsing secondary progressive multiple sclerosis (nrSPMS).

The phase 3 HERCULES trial showed tolebrutinib, an oral Bruton’s tyrosine kinase (BTK) inhibitor, delayed the time to onset of 6-month confirmed disability progression by 31%, compared with placebo.

In addition, tolebrutinib almost doubled the number of patients who experienced confirmed disability improvement from 5% to 10%.

However, these benefits come with the potential safety issue of liver toxicity, with raised liver enzymes reported in 4% of patients and very severe liver enzyme rises occurring in 0.5% of patients, one of whom died after undergoing a liver transplant.  

The results were presented by Robert Fox, MD, vice chair of research at the Cleveland Clinic’s Neurological Institute in Ohio, at the 2024 ECTRIMS annual meeting. 

“We have finally found a therapy that can alter the compartmentalized inflammation that is driving progressive MS,” he said. 

Dr. Fox pointed out that the population enrolled in the HERCULES trial had stopped having clinical relapses. “These are the patients for whom current immunomodulator therapies really don’t work at all — they don’t slow disability. This trial suggests that tolebrutinib can fill that void and now we have something to offer this patient group,” he said. 

He estimated that up to 30% of patients with MS at his clinic may fall into this category. 

A typical patient with nrSPMS who was included in this trial may have experienced a gradual decline in the distance they can walk or the ease with which they could climb stairs, he explained. 

“I would project that this therapy will slow down that gradual decline, and, in some patients, it may actually stop the decline,” he added.

Dr. Fox said that BTK inhibitors are believed to have two main mechanisms of action relevant to MS — down-regulating B cells, probably mostly in the periphery, and, as these agents can cross the blood-brain barrier, they also appear to reduce the inflammatory activity of microglia and macrophages in the brain.

He noted that the disability progression in nrSPMS patients is thought to be caused by compartmentalized inflammation in the brain, which is what tolebrutinib may be targeting. 

He noted that siponimod has also shown benefit in secondary progressive MS in the EXPAND trial, but the benefit was almost entirely restricted to patients who had experienced recent relapses. 

Ocrelizumab has been shown to be beneficial in a trial in primary progressive MS, but again, a large proportion of patients in that study had active focal inflammation at baselineEngl J Med. 2017;376:209-220).
 

Trial Results 

The HERCULES trial included 1131 patients with nrSPMS, defined as having an Expanded Disability Status Scale score (EDSS) between 3.0 and 6.5, no clinical relapses in the previous 24 months, and documented evidence of disability accumulation in the previous 12 months. 

They were randomly assigned (2:1) to receive 60 mg tolebrutinib as an oral daily dose or placebo for up to approximately 48 months. This was an event-driven trial, with 288 6-month confirmed disability progression events required. 

About 23% of patients in each group discontinued treatment and 12%-17% who had confirmed disability progression elected to crossover to open-label tolebrutinib.

The study population had an average age of 49 years, had a median EDSS score of 6, and a mean time since last clinical relapse of over 7 years. 

“So, this was a really very quiescent patient population in terms of focal inflammation,” Dr. Fox noted.

Results showed that the primary endpoint showed a 31% reduction in the risk of 6-month confirmed disability progression (26.9% tolebrutinib vs. 37.2% placebo; hazard ratio [HR], 0.69; 95% CI, 0.55-0.88). 

Rates of 3-month confirmed disability progression were 32.6% in the tolebrutinib group versus 41.5% with placebo — a 24% risk reduction.

In addition, 6-month confirmed disability improvement was achieved by 10% of tolebrutinib patients versus 5% in the placebo group (HR, 1.88; 95% CI, 1.10-3.21).
 

A ‘Head-scratcher’ Finding

Surprisingly, he noted, tolebrutinib did not appear to slow brain atrophy. 

“Despite seeing a benefit on disability progression, we saw no significant slowing of brain atrophy or brain volume loss over the course of the study,” Dr. Fox reported. 

He described this discordance between disability rates and brain volume loss rates as “a bit of a head-scratcher.” 

In terms of safety, the main concern is liver enzyme elevations, which occurred at greater than three times the upper limit of normal (ULN) in 4.1% of the tolebrutinib group vs 1.6% in the placebo group.

A small (0.5%) proportion of patients treated with tolebrutinib experienced very severe elevations (> 20 x ULN) in liver enzymes, and one of these patients had to have a liver transplant and died because of postoperative complications, “a reminder that this can be a very serious complication of this drug,” said Dr. Fox. 

However, he noted that all the very severe liver enzyme rises occurred in the first 3 months and it is now recommended that patients undergo weekly liver enzyme monitoring for the first 12 weeks of treatment. 

Other adverse effects that were increased slightly in tolebrutinib group were upper respiratory infections and possibly hypertension.  
 

Weekly Liver Enzyme Testing 

Dr. Fox cautioned that patients starting tolebrutinib would need to undergo weekly liver enzyme testing in the first few months of treatment. “They would need to be very attentive to this monitoring, but if they are willing to do that, then I think many of these patients will be very eager to take this drug that may slow down their disability progression.”

The drug’s manufacturer, Sanofi, said the trial results will form the basis for applications to global regulatory authorities with submissions starting later in 2024. 

Commenting on the trial, Ludwig Kappos, MD, professor of neurology at University Hospital and University of Basel, Switzerland, said the trial was important as it had shown “a robust effect on confirmed disability progression in a population of secondary progressive MS with no or very low signs of focal inflammation.”

“The effect is similar and probably more pronounced than that seen in the siponimod trial also in advanced secondary progressive MS,” he added. 

Dr. Kappos believes more work will be needed to make sure the liver toxicity can be prevented, “but if that can be resolved then patients could have a significant delay in accumulating disability.”
 

GEMINI Trials Also Show Slowed Disability 

Two other phase 3 trials of tolebrutinib were presented during the same ECTRIMS session — GEMINI 1 and 2 — which compared the new drug with teriflunomide, a standard of care treatment, in participants with relapsing MS. Neither study met the primary endpoint of an improvement in annualized relapse rates, compared with teriflunomide. 

However, with respect to the key secondary endpoint, in a pooled analysis of data from GEMINI 1 and 2, tolebrutinib delayed the time to onset of 6-month confirmed disability worsening by 29%, a finding in line with the main results of the HERCULES trial. 

“The significant impact of tolebrutinib on disability accumulation versus teriflunomide, in the absence of a statistically superior impact on relapses, also suggests that tolebrutinib may address smoldering neuroinflammation, which manifests as progression independent of relapses” Dr. Fox said. 

The HERCULES trial was sponsored by Sanofi. Dr. Fox is a paid adviser to Sanofi. Dr. Kappos led the EXPAND trial of siponimod in SPMS.

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

COPENHAGEN — A new investigational drug has become the first agent to slow disability in patients with nonrelapsing secondary progressive multiple sclerosis (nrSPMS).

The phase 3 HERCULES trial showed tolebrutinib, an oral Bruton’s tyrosine kinase (BTK) inhibitor, delayed the time to onset of 6-month confirmed disability progression by 31%, compared with placebo.

In addition, tolebrutinib almost doubled the number of patients who experienced confirmed disability improvement from 5% to 10%.

However, these benefits come with the potential safety issue of liver toxicity, with raised liver enzymes reported in 4% of patients and very severe liver enzyme rises occurring in 0.5% of patients, one of whom died after undergoing a liver transplant.  

The results were presented by Robert Fox, MD, vice chair of research at the Cleveland Clinic’s Neurological Institute in Ohio, at the 2024 ECTRIMS annual meeting. 

“We have finally found a therapy that can alter the compartmentalized inflammation that is driving progressive MS,” he said. 

Dr. Fox pointed out that the population enrolled in the HERCULES trial had stopped having clinical relapses. “These are the patients for whom current immunomodulator therapies really don’t work at all — they don’t slow disability. This trial suggests that tolebrutinib can fill that void and now we have something to offer this patient group,” he said. 

He estimated that up to 30% of patients with MS at his clinic may fall into this category. 

A typical patient with nrSPMS who was included in this trial may have experienced a gradual decline in the distance they can walk or the ease with which they could climb stairs, he explained. 

“I would project that this therapy will slow down that gradual decline, and, in some patients, it may actually stop the decline,” he added.

Dr. Fox said that BTK inhibitors are believed to have two main mechanisms of action relevant to MS — down-regulating B cells, probably mostly in the periphery, and, as these agents can cross the blood-brain barrier, they also appear to reduce the inflammatory activity of microglia and macrophages in the brain.

He noted that the disability progression in nrSPMS patients is thought to be caused by compartmentalized inflammation in the brain, which is what tolebrutinib may be targeting. 

He noted that siponimod has also shown benefit in secondary progressive MS in the EXPAND trial, but the benefit was almost entirely restricted to patients who had experienced recent relapses. 

Ocrelizumab has been shown to be beneficial in a trial in primary progressive MS, but again, a large proportion of patients in that study had active focal inflammation at baselineEngl J Med. 2017;376:209-220).
 

Trial Results 

The HERCULES trial included 1131 patients with nrSPMS, defined as having an Expanded Disability Status Scale score (EDSS) between 3.0 and 6.5, no clinical relapses in the previous 24 months, and documented evidence of disability accumulation in the previous 12 months. 

They were randomly assigned (2:1) to receive 60 mg tolebrutinib as an oral daily dose or placebo for up to approximately 48 months. This was an event-driven trial, with 288 6-month confirmed disability progression events required. 

About 23% of patients in each group discontinued treatment and 12%-17% who had confirmed disability progression elected to crossover to open-label tolebrutinib.

The study population had an average age of 49 years, had a median EDSS score of 6, and a mean time since last clinical relapse of over 7 years. 

“So, this was a really very quiescent patient population in terms of focal inflammation,” Dr. Fox noted.

Results showed that the primary endpoint showed a 31% reduction in the risk of 6-month confirmed disability progression (26.9% tolebrutinib vs. 37.2% placebo; hazard ratio [HR], 0.69; 95% CI, 0.55-0.88). 

Rates of 3-month confirmed disability progression were 32.6% in the tolebrutinib group versus 41.5% with placebo — a 24% risk reduction.

In addition, 6-month confirmed disability improvement was achieved by 10% of tolebrutinib patients versus 5% in the placebo group (HR, 1.88; 95% CI, 1.10-3.21).
 

A ‘Head-scratcher’ Finding

Surprisingly, he noted, tolebrutinib did not appear to slow brain atrophy. 

“Despite seeing a benefit on disability progression, we saw no significant slowing of brain atrophy or brain volume loss over the course of the study,” Dr. Fox reported. 

He described this discordance between disability rates and brain volume loss rates as “a bit of a head-scratcher.” 

In terms of safety, the main concern is liver enzyme elevations, which occurred at greater than three times the upper limit of normal (ULN) in 4.1% of the tolebrutinib group vs 1.6% in the placebo group.

A small (0.5%) proportion of patients treated with tolebrutinib experienced very severe elevations (> 20 x ULN) in liver enzymes, and one of these patients had to have a liver transplant and died because of postoperative complications, “a reminder that this can be a very serious complication of this drug,” said Dr. Fox. 

However, he noted that all the very severe liver enzyme rises occurred in the first 3 months and it is now recommended that patients undergo weekly liver enzyme monitoring for the first 12 weeks of treatment. 

Other adverse effects that were increased slightly in tolebrutinib group were upper respiratory infections and possibly hypertension.  
 

Weekly Liver Enzyme Testing 

Dr. Fox cautioned that patients starting tolebrutinib would need to undergo weekly liver enzyme testing in the first few months of treatment. “They would need to be very attentive to this monitoring, but if they are willing to do that, then I think many of these patients will be very eager to take this drug that may slow down their disability progression.”

The drug’s manufacturer, Sanofi, said the trial results will form the basis for applications to global regulatory authorities with submissions starting later in 2024. 

Commenting on the trial, Ludwig Kappos, MD, professor of neurology at University Hospital and University of Basel, Switzerland, said the trial was important as it had shown “a robust effect on confirmed disability progression in a population of secondary progressive MS with no or very low signs of focal inflammation.”

“The effect is similar and probably more pronounced than that seen in the siponimod trial also in advanced secondary progressive MS,” he added. 

Dr. Kappos believes more work will be needed to make sure the liver toxicity can be prevented, “but if that can be resolved then patients could have a significant delay in accumulating disability.”
 

GEMINI Trials Also Show Slowed Disability 

Two other phase 3 trials of tolebrutinib were presented during the same ECTRIMS session — GEMINI 1 and 2 — which compared the new drug with teriflunomide, a standard of care treatment, in participants with relapsing MS. Neither study met the primary endpoint of an improvement in annualized relapse rates, compared with teriflunomide. 

However, with respect to the key secondary endpoint, in a pooled analysis of data from GEMINI 1 and 2, tolebrutinib delayed the time to onset of 6-month confirmed disability worsening by 29%, a finding in line with the main results of the HERCULES trial. 

“The significant impact of tolebrutinib on disability accumulation versus teriflunomide, in the absence of a statistically superior impact on relapses, also suggests that tolebrutinib may address smoldering neuroinflammation, which manifests as progression independent of relapses” Dr. Fox said. 

The HERCULES trial was sponsored by Sanofi. Dr. Fox is a paid adviser to Sanofi. Dr. Kappos led the EXPAND trial of siponimod in SPMS.

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