CHEST Physician

Humans have used salt for centuries, to preserve or cure food before refrigeration was readily available, and even as currency in some cultures. Though modern food preservation efforts have decreased our reliance on salt, we still heavily incorporate it as a flavor enhancer. 

It’s only relatively recently that we’ve begun limiting salt in our diets, as research has linked high sodium intake with chronic, preventable conditions like hypertension, heart disease, and kidney disease.
 

How to Recommend Restriction in a Helpful Way 

The US Department of Agriculture’s Dietary Guidelines for Americans recommends intake of no more than 2300 mg of sodium daily for adults and children aged 14 years or older. This echoes similar recommendations for people at risk for heart disease, kidney disease, and hypertension. However, the sodium intake of the average American still sits at a whopping 3400 mg daily. 

High sodium intake is primarily the result of modern commercial food processing. Food prepared outside the home accounts for up to 70% of sodium intake in the United States, whereas only about 10% comes from salt that is added to food either during or after cooking. For this reason, I hesitate to recommend withholding salt as a primary focus when counseling on a low-sodium diet. 

To many people, certain foods just taste better with salt. Many of my patients in the southern United States simply will not eat foods like eggs and tomatoes if they cannot salt them. We can spend every moment of patient interaction time explaining why excess sodium is unhealthy, but the fact remains that humans prefer food that tastes good. This is why I try to avoid counseling a “no-added-salt” diet; instead, I recommend a low-sodium diet with a focus on fresh, whole foods and limiting salt to only a few food items. 

Patients should be counseled to slowly restrict their salt intake and be made aware that doing so may increase the time it takes for their sensitivity to the taste of less salty foods to return. But it is also important for them to know that it will return. The surest way to kill progress is for an unprepared patient to believe that their food will taste bland forever. A prepared patient understands that their food may taste different for a couple of weeks, but that the change will not last forever.
 

Types of Salt 

I have often worked with patients who insist that their sodium intake is acceptable because they are using sea salt instead of table salt. This is the result of exceptional marketing and misinformation. 

Specialty salts like sea salt and Himalayan pink salt contain about 560 mg and 590 mg of sodium, respectively, per quarter teaspoon. These products do have a slightly different mineral content, with sea salt typically having a negligible amount of calcium, magnesium, or potassium. The very small amount of these minerals offers no obvious health benefits compared with more affordable table salt. 

The sodium content of iodized table salt is comparable to these products, with about 590 mg of sodium per quarter teaspoon. Though its high sodium content will put some practitioners off, it is also an excellent source of iodine, at about 75 mg per serving. It has been estimated that upward of 35% of the US population has iodine deficiency, most commonly due to pregnancy, avoidance of dairy products, increasing rates of vegetarianism, intake of highly processed foods, and avoidance of added salt. For this reason, and its relative affordability, I find table salt to be far more appropriate for the average American than specialty salts.
 

Salt Substitutes 

Monosodium glutamate (MSG). MSG was previously at the center of public health concern owing to reports of “Chinese restaurant syndrome” that have since been debunked. I often recommend MSG to people trying to decrease sodium intake because the US Food and Drug Administration has designated it as GRAS (“generally recognized as safe”), and it has about one quarter of the sodium content of table salt at 125 mg per quarter teaspoon. Its crystalline structure makes it a lower-sodium salt substitute in savory applications like soups, stews, and gravies. 

Hot sauce. These sauces are generally composed of peppers, vinegar, salt, and sugar. There may be some variation and occasionally added ingredients depending upon the brand. However, I find most hot sauces to be a low-sodium seasoning option that works especially well on proteins like eggs, chicken, and pork. 

Potassium-based substitutes. Salt alternatives such as Nu-Salt and Morton Salt Substitute are sodium-free options with a significant amount of potassium, at 525 mg per quarter-teaspoon serving. These alternatives may not be ideal for patients with kidney problems, but they can be very helpful for those with potassium deficiency. 

Herb-based seasonings. Garlic and onion powder are both sodium-free seasonings that many of my patients have found help to increase palatability while decreasing salt use. Black pepper; lemon and lime juice; salt-free herb mixes like Mrs. Dash; and spices like cumin, paprika, dill, chili powder, and ginger are also sodium-free or low-sodium alternatives that can help to alleviate blandness for someone new to a low-sodium diet. I recommend them often and use them in my own cooking at home.

Plant-based diet. If the goal of care is to improve cardiovascular or kidney health, then I find that working with patients to increase intake of plant foods to be a helpful option. This way of eating encourages replacing highly processed foods that may be high in sodium and sugar with plants that tend to be higher in potassium and calcium. The Dietary Approaches to Stop Hypertension (DASH), Mediterranean, and other plant-based diets have been shown to increase cardiovascular and metabolic health by significantly decreasing serum lipids, blood pressure, and hemoglobin A1c and promoting weight loss. They have also been shown to increase the gut microbiome and promote increased cognitive function. 

I rarely encourage the use of added salt. However, research shows that putting down the salt shaker is probably not the most effective option to restrict sodium intake. For those who can cut back, these options can help keep food flavorful and patients compliant. 

Ms. Winfree is a renal dietitian in private practice in Mary Esther, Florida. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Humans have used salt for centuries, to preserve or cure food before refrigeration was readily available, and even as currency in some cultures. Though modern food preservation efforts have decreased our reliance on salt, we still heavily incorporate it as a flavor enhancer. 

It’s only relatively recently that we’ve begun limiting salt in our diets, as research has linked high sodium intake with chronic, preventable conditions like hypertension, heart disease, and kidney disease.
 

How to Recommend Restriction in a Helpful Way 

The US Department of Agriculture’s Dietary Guidelines for Americans recommends intake of no more than 2300 mg of sodium daily for adults and children aged 14 years or older. This echoes similar recommendations for people at risk for heart disease, kidney disease, and hypertension. However, the sodium intake of the average American still sits at a whopping 3400 mg daily. 

High sodium intake is primarily the result of modern commercial food processing. Food prepared outside the home accounts for up to 70% of sodium intake in the United States, whereas only about 10% comes from salt that is added to food either during or after cooking. For this reason, I hesitate to recommend withholding salt as a primary focus when counseling on a low-sodium diet. 

To many people, certain foods just taste better with salt. Many of my patients in the southern United States simply will not eat foods like eggs and tomatoes if they cannot salt them. We can spend every moment of patient interaction time explaining why excess sodium is unhealthy, but the fact remains that humans prefer food that tastes good. This is why I try to avoid counseling a “no-added-salt” diet; instead, I recommend a low-sodium diet with a focus on fresh, whole foods and limiting salt to only a few food items. 

Patients should be counseled to slowly restrict their salt intake and be made aware that doing so may increase the time it takes for their sensitivity to the taste of less salty foods to return. But it is also important for them to know that it will return. The surest way to kill progress is for an unprepared patient to believe that their food will taste bland forever. A prepared patient understands that their food may taste different for a couple of weeks, but that the change will not last forever.
 

Types of Salt 

I have often worked with patients who insist that their sodium intake is acceptable because they are using sea salt instead of table salt. This is the result of exceptional marketing and misinformation. 

Specialty salts like sea salt and Himalayan pink salt contain about 560 mg and 590 mg of sodium, respectively, per quarter teaspoon. These products do have a slightly different mineral content, with sea salt typically having a negligible amount of calcium, magnesium, or potassium. The very small amount of these minerals offers no obvious health benefits compared with more affordable table salt. 

The sodium content of iodized table salt is comparable to these products, with about 590 mg of sodium per quarter teaspoon. Though its high sodium content will put some practitioners off, it is also an excellent source of iodine, at about 75 mg per serving. It has been estimated that upward of 35% of the US population has iodine deficiency, most commonly due to pregnancy, avoidance of dairy products, increasing rates of vegetarianism, intake of highly processed foods, and avoidance of added salt. For this reason, and its relative affordability, I find table salt to be far more appropriate for the average American than specialty salts.
 

Salt Substitutes 

Monosodium glutamate (MSG). MSG was previously at the center of public health concern owing to reports of “Chinese restaurant syndrome” that have since been debunked. I often recommend MSG to people trying to decrease sodium intake because the US Food and Drug Administration has designated it as GRAS (“generally recognized as safe”), and it has about one quarter of the sodium content of table salt at 125 mg per quarter teaspoon. Its crystalline structure makes it a lower-sodium salt substitute in savory applications like soups, stews, and gravies. 

Hot sauce. These sauces are generally composed of peppers, vinegar, salt, and sugar. There may be some variation and occasionally added ingredients depending upon the brand. However, I find most hot sauces to be a low-sodium seasoning option that works especially well on proteins like eggs, chicken, and pork. 

Potassium-based substitutes. Salt alternatives such as Nu-Salt and Morton Salt Substitute are sodium-free options with a significant amount of potassium, at 525 mg per quarter-teaspoon serving. These alternatives may not be ideal for patients with kidney problems, but they can be very helpful for those with potassium deficiency. 

Herb-based seasonings. Garlic and onion powder are both sodium-free seasonings that many of my patients have found help to increase palatability while decreasing salt use. Black pepper; lemon and lime juice; salt-free herb mixes like Mrs. Dash; and spices like cumin, paprika, dill, chili powder, and ginger are also sodium-free or low-sodium alternatives that can help to alleviate blandness for someone new to a low-sodium diet. I recommend them often and use them in my own cooking at home.

Plant-based diet. If the goal of care is to improve cardiovascular or kidney health, then I find that working with patients to increase intake of plant foods to be a helpful option. This way of eating encourages replacing highly processed foods that may be high in sodium and sugar with plants that tend to be higher in potassium and calcium. The Dietary Approaches to Stop Hypertension (DASH), Mediterranean, and other plant-based diets have been shown to increase cardiovascular and metabolic health by significantly decreasing serum lipids, blood pressure, and hemoglobin A1c and promoting weight loss. They have also been shown to increase the gut microbiome and promote increased cognitive function. 

I rarely encourage the use of added salt. However, research shows that putting down the salt shaker is probably not the most effective option to restrict sodium intake. For those who can cut back, these options can help keep food flavorful and patients compliant. 

Ms. Winfree is a renal dietitian in private practice in Mary Esther, Florida. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Humans have used salt for centuries, to preserve or cure food before refrigeration was readily available, and even as currency in some cultures. Though modern food preservation efforts have decreased our reliance on salt, we still heavily incorporate it as a flavor enhancer. 

It’s only relatively recently that we’ve begun limiting salt in our diets, as research has linked high sodium intake with chronic, preventable conditions like hypertension, heart disease, and kidney disease.
 

How to Recommend Restriction in a Helpful Way 

The US Department of Agriculture’s Dietary Guidelines for Americans recommends intake of no more than 2300 mg of sodium daily for adults and children aged 14 years or older. This echoes similar recommendations for people at risk for heart disease, kidney disease, and hypertension. However, the sodium intake of the average American still sits at a whopping 3400 mg daily. 

High sodium intake is primarily the result of modern commercial food processing. Food prepared outside the home accounts for up to 70% of sodium intake in the United States, whereas only about 10% comes from salt that is added to food either during or after cooking. For this reason, I hesitate to recommend withholding salt as a primary focus when counseling on a low-sodium diet. 

To many people, certain foods just taste better with salt. Many of my patients in the southern United States simply will not eat foods like eggs and tomatoes if they cannot salt them. We can spend every moment of patient interaction time explaining why excess sodium is unhealthy, but the fact remains that humans prefer food that tastes good. This is why I try to avoid counseling a “no-added-salt” diet; instead, I recommend a low-sodium diet with a focus on fresh, whole foods and limiting salt to only a few food items. 

Patients should be counseled to slowly restrict their salt intake and be made aware that doing so may increase the time it takes for their sensitivity to the taste of less salty foods to return. But it is also important for them to know that it will return. The surest way to kill progress is for an unprepared patient to believe that their food will taste bland forever. A prepared patient understands that their food may taste different for a couple of weeks, but that the change will not last forever.
 

Types of Salt 

I have often worked with patients who insist that their sodium intake is acceptable because they are using sea salt instead of table salt. This is the result of exceptional marketing and misinformation. 

Specialty salts like sea salt and Himalayan pink salt contain about 560 mg and 590 mg of sodium, respectively, per quarter teaspoon. These products do have a slightly different mineral content, with sea salt typically having a negligible amount of calcium, magnesium, or potassium. The very small amount of these minerals offers no obvious health benefits compared with more affordable table salt. 

The sodium content of iodized table salt is comparable to these products, with about 590 mg of sodium per quarter teaspoon. Though its high sodium content will put some practitioners off, it is also an excellent source of iodine, at about 75 mg per serving. It has been estimated that upward of 35% of the US population has iodine deficiency, most commonly due to pregnancy, avoidance of dairy products, increasing rates of vegetarianism, intake of highly processed foods, and avoidance of added salt. For this reason, and its relative affordability, I find table salt to be far more appropriate for the average American than specialty salts.
 

Salt Substitutes 

Monosodium glutamate (MSG). MSG was previously at the center of public health concern owing to reports of “Chinese restaurant syndrome” that have since been debunked. I often recommend MSG to people trying to decrease sodium intake because the US Food and Drug Administration has designated it as GRAS (“generally recognized as safe”), and it has about one quarter of the sodium content of table salt at 125 mg per quarter teaspoon. Its crystalline structure makes it a lower-sodium salt substitute in savory applications like soups, stews, and gravies. 

Hot sauce. These sauces are generally composed of peppers, vinegar, salt, and sugar. There may be some variation and occasionally added ingredients depending upon the brand. However, I find most hot sauces to be a low-sodium seasoning option that works especially well on proteins like eggs, chicken, and pork. 

Potassium-based substitutes. Salt alternatives such as Nu-Salt and Morton Salt Substitute are sodium-free options with a significant amount of potassium, at 525 mg per quarter-teaspoon serving. These alternatives may not be ideal for patients with kidney problems, but they can be very helpful for those with potassium deficiency. 

Herb-based seasonings. Garlic and onion powder are both sodium-free seasonings that many of my patients have found help to increase palatability while decreasing salt use. Black pepper; lemon and lime juice; salt-free herb mixes like Mrs. Dash; and spices like cumin, paprika, dill, chili powder, and ginger are also sodium-free or low-sodium alternatives that can help to alleviate blandness for someone new to a low-sodium diet. I recommend them often and use them in my own cooking at home.

Plant-based diet. If the goal of care is to improve cardiovascular or kidney health, then I find that working with patients to increase intake of plant foods to be a helpful option. This way of eating encourages replacing highly processed foods that may be high in sodium and sugar with plants that tend to be higher in potassium and calcium. The Dietary Approaches to Stop Hypertension (DASH), Mediterranean, and other plant-based diets have been shown to increase cardiovascular and metabolic health by significantly decreasing serum lipids, blood pressure, and hemoglobin A1c and promoting weight loss. They have also been shown to increase the gut microbiome and promote increased cognitive function. 

I rarely encourage the use of added salt. However, research shows that putting down the salt shaker is probably not the most effective option to restrict sodium intake. For those who can cut back, these options can help keep food flavorful and patients compliant. 

Ms. Winfree is a renal dietitian in private practice in Mary Esther, Florida. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Do drugs work better if taken by the clock?

A new analysis published in The Lancet journal’s eClinicalMedicine suggests: Yes, they do — if you consider the patient’s individual body clock. The study is the first to find that timing blood pressure drugs to a person’s personal “chronotype” — that is, whether they are a night owl or an early bird — may reduce the risk for a heart attack.

The findings represent a significant advance in the field of circadian medicine or “chronotherapy” — timing drug administration to circadian rhythms. A growing stack of research suggests this approach could reduce side effects and improve the effectiveness of a wide range of therapies, including vaccines, cancer treatments, and drugs for depression, glaucoma, pain, seizures, and other conditions. Still, despite decades of research, time of day is rarely considered in writing prescriptions.

“We are really just at the beginning of an exciting new way of looking at patient care,” said Kenneth A. Dyar, PhD, whose lab at Helmholtz Zentrum München’s Institute for Diabetes and Cancer focuses on metabolic physiology. Dr. Dyar is co-lead author of the new blood pressure analysis.

“Chronotherapy is a rapidly growing field,” he said, “and I suspect we are soon going to see more and more studies focused on ‘personalized chronotherapy,’ not only in hypertension but also potentially in other clinical areas.”
 

The ‘Missing Piece’ in Chronotherapy Research

Blood pressure drugs have long been chronotherapy’s battleground. After all, blood pressure follows a circadian rhythm, peaking in the morning and dropping at night.

That healthy overnight dip can disappear in people with diabetes, kidney disease, and obstructive sleep apnea. Some physicians have suggested a bed-time dose to restore that dip. But studies have had mixed results, so “take at bedtime” has become a less common recommendation in recent years.

But the debate continued. After a large 2019 Spanish study found that bedtime doses had benefits so big that the results drew questions, an even larger, 2022 randomized, controlled trial from the University of Dundee in Dundee, Scotland — called the TIME study — aimed to settle the question.

Researchers assigned over 21,000 people to take morning or night hypertension drugs for several years and found no difference in cardiovascular outcomes.

“We did this study thinking nocturnal blood pressure tablets might be better,” said Thomas MacDonald, MD, professor emeritus of clinical pharmacology and pharmacoepidemiology at the University of Dundee and principal investigator for the TIME study and the recent chronotype analysis. “But there was no difference for heart attacks, strokes, or vascular death.”

So, the researchers then looked at participants’ chronotypes, sorting outcomes based on whether the participants were late-to-bed, late-to-rise “night owls” or early-to-bed, early-to-rise “morning larks.”

Their analysis of these 5358 TIME participants found the following results: Risk for hospitalization for a heart attack was at least 34% lower for “owls” who took their drugs at bedtime. By contrast, owls’ heart attack risk was at least 62% higher with morning doses. For “larks,” the opposite was true. Morning doses were associated with an 11% lower heart attack risk and night doses with an 11% higher risk, according to supplemental data.

The personalized approach could explain why some previous chronotherapy studies have failed to show a benefit. Those studies did not individualize drug timing as this one did. But personalization could be key to circadian medicine’s success.

“Our ‘internal personal time’ appears to be an important variable to consider when dosing antihypertensives,” said co-lead author Filippo Pigazzani, MD, PhD, clinical senior lecturer and honorary consultant cardiologist at the University of Dundee School of Medicine. “Chronotherapy research has been going on for decades. We knew there was something important with time of day. But researchers haven’t considered the internal time of individual people. I think that is the missing piece.”

The analysis has several important limitations, the researchers said. A total of 95% of participants were White. And it was an observational study, not a true randomized comparison. “We started it late in the original TIME study,” Dr. MacDonald said. “You could argue we were reporting on those who survived long enough to get into the analysis.” More research is needed, they concluded.
 

Looking Beyond Blood Pressure

What about the rest of the body? “Almost all the cells of our body contain ‘circadian clocks’ that are synchronized by daily environmental cues, including light-dark, activity-rest, and feeding-fasting cycles,” said Dr. Dyar.

An estimated 50% of prescription drugs hit targets in the body that have circadian patterns. So, experts suspect that syncing a drug with a person’s body clock might increase effectiveness of many drugs.

A handful of US Food and Drug Administration–approved drugs already have time-of-day recommendations on the label for effectiveness or to limit side effects, including bedtime or evening for the insomnia drug Ambien, the HIV antiviral Atripla, and cholesterol-lowering Zocor. Others are intended to be taken with or after your last meal of the day, such as the long-acting insulin Levemir and the cardiovascular drug Xarelto. A morning recommendation comes with the proton pump inhibitor Nexium and the attention-deficit/hyperactivity disorder drug Ritalin.

Interest is expanding. About one third of the papers published about chronotherapy in the past 25 years have come out in the past 5 years. The May 2024 meeting of the Society for Research on Biological Rhythms featured a day-long session aimed at bringing clinicians up to speed. An organization called the International Association of Circadian Health Clinics is trying to bring circadian medicine findings to clinicians and their patients and to support research.

Moreover, while recent research suggests minding the clock could have benefits for a wide range of treatments, ignoring it could cause problems.

In a Massachusetts Institute of Technology study published in April in Science Advances, researchers looked at engineered livers made from human donor cells and found more than 300 genes that operate on a circadian schedule, many with roles in drug metabolism. They also found that circadian patterns affected the toxicity of acetaminophen and atorvastatin. Identifying the time of day to take these drugs could maximize effectiveness and minimize adverse effects, the researchers said.
 

Timing and the Immune System

Circadian rhythms are also seen in immune processes. In a 2023 study in The Journal of Clinical Investigation of vaccine data from 1.5 million people in Israel, researchers found that children and older adults who got their second dose of the Pfizer mRNA COVID vaccine earlier in the day were about 36% less likely to be hospitalized with SARS-CoV-2 infection than those who got an evening shot.

“The sweet spot in our data was somewhere around late morning to late afternoon,” said lead researcher Jeffrey Haspel, MD, PhD, associate professor of medicine in the division of pulmonary and critical care medicine at Washington University School of Medicine in St. Louis.

In a multicenter, 2024 analysis of 13 studies of immunotherapy for advanced cancers in 1663 people, researchers found treatment earlier in the day was associated with longer survival time and longer survival without cancer progression.

“Patients with selected metastatic cancers seemed to largely benefit from early [time of day] infusions, which is consistent with circadian mechanisms in immune-cell functions and trafficking,” the researchers noted. But “retrospective randomized trials are needed to establish recommendations for optimal circadian timing.”

Other research suggests or is investigating possible chronotherapy benefits for depression, glaucoma, respiratory diseases, stroke treatment, epilepsy, and sedatives used in surgery. So why aren’t healthcare providers adding time of day to more prescriptions? “What’s missing is more reliable data,” Dr. Dyar said.
 

Should You Use Chronotherapy Now?

Experts emphasize that more research is needed before doctors use chronotherapy and before medical organizations include it in treatment recommendations. But for some patients, circadian dosing may be worth a try:

Night owls whose blood pressure isn’t well controlled. Dr. Dyar and Dr. Pigazzani said night-time blood pressure drugs may be helpful for people with a “late chronotype.” Of course, patients shouldn’t change their medication schedule on their own, they said. And doctors may want to consider other concerns, like more overnight bathroom visits with evening diuretics.

In their study, the researchers determined participants’ chronotype with a few questions from the Munich Chronotype Questionnaire about what time they fell asleep and woke up on workdays and days off and whether they considered themselves “morning types” or “evening types.” (The questions can be found in supplementary data for the study.)

If a physician thinks matching the timing of a dose with chronotype would help, they can consider it, Dr. Pigazzani said. “However, I must add that this was an observational study, so I would advise healthcare practitioners to wait for our data to be confirmed in new RCTs of personalized chronotherapy of hypertension.”

Children and older adults getting vaccines. Timing COVID shots and possibly other vaccines from late morning to mid-afternoon could have a small benefit for individuals and a bigger public-health benefit, Dr. Haspel said. But the most important thing is getting vaccinated. “If you can only get one in the evening, it’s still worthwhile. Timing may add oomph at a public-health level for more vulnerable groups.”
 

A version of this article appeared on Medscape.com.

Do drugs work better if taken by the clock?

A new analysis published in The Lancet journal’s eClinicalMedicine suggests: Yes, they do — if you consider the patient’s individual body clock. The study is the first to find that timing blood pressure drugs to a person’s personal “chronotype” — that is, whether they are a night owl or an early bird — may reduce the risk for a heart attack.

The findings represent a significant advance in the field of circadian medicine or “chronotherapy” — timing drug administration to circadian rhythms. A growing stack of research suggests this approach could reduce side effects and improve the effectiveness of a wide range of therapies, including vaccines, cancer treatments, and drugs for depression, glaucoma, pain, seizures, and other conditions. Still, despite decades of research, time of day is rarely considered in writing prescriptions.

“We are really just at the beginning of an exciting new way of looking at patient care,” said Kenneth A. Dyar, PhD, whose lab at Helmholtz Zentrum München’s Institute for Diabetes and Cancer focuses on metabolic physiology. Dr. Dyar is co-lead author of the new blood pressure analysis.

“Chronotherapy is a rapidly growing field,” he said, “and I suspect we are soon going to see more and more studies focused on ‘personalized chronotherapy,’ not only in hypertension but also potentially in other clinical areas.”
 

The ‘Missing Piece’ in Chronotherapy Research

Blood pressure drugs have long been chronotherapy’s battleground. After all, blood pressure follows a circadian rhythm, peaking in the morning and dropping at night.

That healthy overnight dip can disappear in people with diabetes, kidney disease, and obstructive sleep apnea. Some physicians have suggested a bed-time dose to restore that dip. But studies have had mixed results, so “take at bedtime” has become a less common recommendation in recent years.

But the debate continued. After a large 2019 Spanish study found that bedtime doses had benefits so big that the results drew questions, an even larger, 2022 randomized, controlled trial from the University of Dundee in Dundee, Scotland — called the TIME study — aimed to settle the question.

Researchers assigned over 21,000 people to take morning or night hypertension drugs for several years and found no difference in cardiovascular outcomes.

“We did this study thinking nocturnal blood pressure tablets might be better,” said Thomas MacDonald, MD, professor emeritus of clinical pharmacology and pharmacoepidemiology at the University of Dundee and principal investigator for the TIME study and the recent chronotype analysis. “But there was no difference for heart attacks, strokes, or vascular death.”

So, the researchers then looked at participants’ chronotypes, sorting outcomes based on whether the participants were late-to-bed, late-to-rise “night owls” or early-to-bed, early-to-rise “morning larks.”

Their analysis of these 5358 TIME participants found the following results: Risk for hospitalization for a heart attack was at least 34% lower for “owls” who took their drugs at bedtime. By contrast, owls’ heart attack risk was at least 62% higher with morning doses. For “larks,” the opposite was true. Morning doses were associated with an 11% lower heart attack risk and night doses with an 11% higher risk, according to supplemental data.

The personalized approach could explain why some previous chronotherapy studies have failed to show a benefit. Those studies did not individualize drug timing as this one did. But personalization could be key to circadian medicine’s success.

“Our ‘internal personal time’ appears to be an important variable to consider when dosing antihypertensives,” said co-lead author Filippo Pigazzani, MD, PhD, clinical senior lecturer and honorary consultant cardiologist at the University of Dundee School of Medicine. “Chronotherapy research has been going on for decades. We knew there was something important with time of day. But researchers haven’t considered the internal time of individual people. I think that is the missing piece.”

The analysis has several important limitations, the researchers said. A total of 95% of participants were White. And it was an observational study, not a true randomized comparison. “We started it late in the original TIME study,” Dr. MacDonald said. “You could argue we were reporting on those who survived long enough to get into the analysis.” More research is needed, they concluded.
 

Looking Beyond Blood Pressure

What about the rest of the body? “Almost all the cells of our body contain ‘circadian clocks’ that are synchronized by daily environmental cues, including light-dark, activity-rest, and feeding-fasting cycles,” said Dr. Dyar.

An estimated 50% of prescription drugs hit targets in the body that have circadian patterns. So, experts suspect that syncing a drug with a person’s body clock might increase effectiveness of many drugs.

A handful of US Food and Drug Administration–approved drugs already have time-of-day recommendations on the label for effectiveness or to limit side effects, including bedtime or evening for the insomnia drug Ambien, the HIV antiviral Atripla, and cholesterol-lowering Zocor. Others are intended to be taken with or after your last meal of the day, such as the long-acting insulin Levemir and the cardiovascular drug Xarelto. A morning recommendation comes with the proton pump inhibitor Nexium and the attention-deficit/hyperactivity disorder drug Ritalin.

Interest is expanding. About one third of the papers published about chronotherapy in the past 25 years have come out in the past 5 years. The May 2024 meeting of the Society for Research on Biological Rhythms featured a day-long session aimed at bringing clinicians up to speed. An organization called the International Association of Circadian Health Clinics is trying to bring circadian medicine findings to clinicians and their patients and to support research.

Moreover, while recent research suggests minding the clock could have benefits for a wide range of treatments, ignoring it could cause problems.

In a Massachusetts Institute of Technology study published in April in Science Advances, researchers looked at engineered livers made from human donor cells and found more than 300 genes that operate on a circadian schedule, many with roles in drug metabolism. They also found that circadian patterns affected the toxicity of acetaminophen and atorvastatin. Identifying the time of day to take these drugs could maximize effectiveness and minimize adverse effects, the researchers said.
 

Timing and the Immune System

Circadian rhythms are also seen in immune processes. In a 2023 study in The Journal of Clinical Investigation of vaccine data from 1.5 million people in Israel, researchers found that children and older adults who got their second dose of the Pfizer mRNA COVID vaccine earlier in the day were about 36% less likely to be hospitalized with SARS-CoV-2 infection than those who got an evening shot.

“The sweet spot in our data was somewhere around late morning to late afternoon,” said lead researcher Jeffrey Haspel, MD, PhD, associate professor of medicine in the division of pulmonary and critical care medicine at Washington University School of Medicine in St. Louis.

In a multicenter, 2024 analysis of 13 studies of immunotherapy for advanced cancers in 1663 people, researchers found treatment earlier in the day was associated with longer survival time and longer survival without cancer progression.

“Patients with selected metastatic cancers seemed to largely benefit from early [time of day] infusions, which is consistent with circadian mechanisms in immune-cell functions and trafficking,” the researchers noted. But “retrospective randomized trials are needed to establish recommendations for optimal circadian timing.”

Other research suggests or is investigating possible chronotherapy benefits for depression, glaucoma, respiratory diseases, stroke treatment, epilepsy, and sedatives used in surgery. So why aren’t healthcare providers adding time of day to more prescriptions? “What’s missing is more reliable data,” Dr. Dyar said.
 

Should You Use Chronotherapy Now?

Experts emphasize that more research is needed before doctors use chronotherapy and before medical organizations include it in treatment recommendations. But for some patients, circadian dosing may be worth a try:

Night owls whose blood pressure isn’t well controlled. Dr. Dyar and Dr. Pigazzani said night-time blood pressure drugs may be helpful for people with a “late chronotype.” Of course, patients shouldn’t change their medication schedule on their own, they said. And doctors may want to consider other concerns, like more overnight bathroom visits with evening diuretics.

In their study, the researchers determined participants’ chronotype with a few questions from the Munich Chronotype Questionnaire about what time they fell asleep and woke up on workdays and days off and whether they considered themselves “morning types” or “evening types.” (The questions can be found in supplementary data for the study.)

If a physician thinks matching the timing of a dose with chronotype would help, they can consider it, Dr. Pigazzani said. “However, I must add that this was an observational study, so I would advise healthcare practitioners to wait for our data to be confirmed in new RCTs of personalized chronotherapy of hypertension.”

Children and older adults getting vaccines. Timing COVID shots and possibly other vaccines from late morning to mid-afternoon could have a small benefit for individuals and a bigger public-health benefit, Dr. Haspel said. But the most important thing is getting vaccinated. “If you can only get one in the evening, it’s still worthwhile. Timing may add oomph at a public-health level for more vulnerable groups.”
 

A version of this article appeared on Medscape.com.

Do drugs work better if taken by the clock?

A new analysis published in The Lancet journal’s eClinicalMedicine suggests: Yes, they do — if you consider the patient’s individual body clock. The study is the first to find that timing blood pressure drugs to a person’s personal “chronotype” — that is, whether they are a night owl or an early bird — may reduce the risk for a heart attack.

The findings represent a significant advance in the field of circadian medicine or “chronotherapy” — timing drug administration to circadian rhythms. A growing stack of research suggests this approach could reduce side effects and improve the effectiveness of a wide range of therapies, including vaccines, cancer treatments, and drugs for depression, glaucoma, pain, seizures, and other conditions. Still, despite decades of research, time of day is rarely considered in writing prescriptions.

“We are really just at the beginning of an exciting new way of looking at patient care,” said Kenneth A. Dyar, PhD, whose lab at Helmholtz Zentrum München’s Institute for Diabetes and Cancer focuses on metabolic physiology. Dr. Dyar is co-lead author of the new blood pressure analysis.

“Chronotherapy is a rapidly growing field,” he said, “and I suspect we are soon going to see more and more studies focused on ‘personalized chronotherapy,’ not only in hypertension but also potentially in other clinical areas.”
 

The ‘Missing Piece’ in Chronotherapy Research

Blood pressure drugs have long been chronotherapy’s battleground. After all, blood pressure follows a circadian rhythm, peaking in the morning and dropping at night.

That healthy overnight dip can disappear in people with diabetes, kidney disease, and obstructive sleep apnea. Some physicians have suggested a bed-time dose to restore that dip. But studies have had mixed results, so “take at bedtime” has become a less common recommendation in recent years.

But the debate continued. After a large 2019 Spanish study found that bedtime doses had benefits so big that the results drew questions, an even larger, 2022 randomized, controlled trial from the University of Dundee in Dundee, Scotland — called the TIME study — aimed to settle the question.

Researchers assigned over 21,000 people to take morning or night hypertension drugs for several years and found no difference in cardiovascular outcomes.

“We did this study thinking nocturnal blood pressure tablets might be better,” said Thomas MacDonald, MD, professor emeritus of clinical pharmacology and pharmacoepidemiology at the University of Dundee and principal investigator for the TIME study and the recent chronotype analysis. “But there was no difference for heart attacks, strokes, or vascular death.”

So, the researchers then looked at participants’ chronotypes, sorting outcomes based on whether the participants were late-to-bed, late-to-rise “night owls” or early-to-bed, early-to-rise “morning larks.”

Their analysis of these 5358 TIME participants found the following results: Risk for hospitalization for a heart attack was at least 34% lower for “owls” who took their drugs at bedtime. By contrast, owls’ heart attack risk was at least 62% higher with morning doses. For “larks,” the opposite was true. Morning doses were associated with an 11% lower heart attack risk and night doses with an 11% higher risk, according to supplemental data.

The personalized approach could explain why some previous chronotherapy studies have failed to show a benefit. Those studies did not individualize drug timing as this one did. But personalization could be key to circadian medicine’s success.

“Our ‘internal personal time’ appears to be an important variable to consider when dosing antihypertensives,” said co-lead author Filippo Pigazzani, MD, PhD, clinical senior lecturer and honorary consultant cardiologist at the University of Dundee School of Medicine. “Chronotherapy research has been going on for decades. We knew there was something important with time of day. But researchers haven’t considered the internal time of individual people. I think that is the missing piece.”

The analysis has several important limitations, the researchers said. A total of 95% of participants were White. And it was an observational study, not a true randomized comparison. “We started it late in the original TIME study,” Dr. MacDonald said. “You could argue we were reporting on those who survived long enough to get into the analysis.” More research is needed, they concluded.
 

Looking Beyond Blood Pressure

What about the rest of the body? “Almost all the cells of our body contain ‘circadian clocks’ that are synchronized by daily environmental cues, including light-dark, activity-rest, and feeding-fasting cycles,” said Dr. Dyar.

An estimated 50% of prescription drugs hit targets in the body that have circadian patterns. So, experts suspect that syncing a drug with a person’s body clock might increase effectiveness of many drugs.

A handful of US Food and Drug Administration–approved drugs already have time-of-day recommendations on the label for effectiveness or to limit side effects, including bedtime or evening for the insomnia drug Ambien, the HIV antiviral Atripla, and cholesterol-lowering Zocor. Others are intended to be taken with or after your last meal of the day, such as the long-acting insulin Levemir and the cardiovascular drug Xarelto. A morning recommendation comes with the proton pump inhibitor Nexium and the attention-deficit/hyperactivity disorder drug Ritalin.

Interest is expanding. About one third of the papers published about chronotherapy in the past 25 years have come out in the past 5 years. The May 2024 meeting of the Society for Research on Biological Rhythms featured a day-long session aimed at bringing clinicians up to speed. An organization called the International Association of Circadian Health Clinics is trying to bring circadian medicine findings to clinicians and their patients and to support research.

Moreover, while recent research suggests minding the clock could have benefits for a wide range of treatments, ignoring it could cause problems.

In a Massachusetts Institute of Technology study published in April in Science Advances, researchers looked at engineered livers made from human donor cells and found more than 300 genes that operate on a circadian schedule, many with roles in drug metabolism. They also found that circadian patterns affected the toxicity of acetaminophen and atorvastatin. Identifying the time of day to take these drugs could maximize effectiveness and minimize adverse effects, the researchers said.
 

Timing and the Immune System

Circadian rhythms are also seen in immune processes. In a 2023 study in The Journal of Clinical Investigation of vaccine data from 1.5 million people in Israel, researchers found that children and older adults who got their second dose of the Pfizer mRNA COVID vaccine earlier in the day were about 36% less likely to be hospitalized with SARS-CoV-2 infection than those who got an evening shot.

“The sweet spot in our data was somewhere around late morning to late afternoon,” said lead researcher Jeffrey Haspel, MD, PhD, associate professor of medicine in the division of pulmonary and critical care medicine at Washington University School of Medicine in St. Louis.

In a multicenter, 2024 analysis of 13 studies of immunotherapy for advanced cancers in 1663 people, researchers found treatment earlier in the day was associated with longer survival time and longer survival without cancer progression.

“Patients with selected metastatic cancers seemed to largely benefit from early [time of day] infusions, which is consistent with circadian mechanisms in immune-cell functions and trafficking,” the researchers noted. But “retrospective randomized trials are needed to establish recommendations for optimal circadian timing.”

Other research suggests or is investigating possible chronotherapy benefits for depression, glaucoma, respiratory diseases, stroke treatment, epilepsy, and sedatives used in surgery. So why aren’t healthcare providers adding time of day to more prescriptions? “What’s missing is more reliable data,” Dr. Dyar said.
 

Should You Use Chronotherapy Now?

Experts emphasize that more research is needed before doctors use chronotherapy and before medical organizations include it in treatment recommendations. But for some patients, circadian dosing may be worth a try:

Night owls whose blood pressure isn’t well controlled. Dr. Dyar and Dr. Pigazzani said night-time blood pressure drugs may be helpful for people with a “late chronotype.” Of course, patients shouldn’t change their medication schedule on their own, they said. And doctors may want to consider other concerns, like more overnight bathroom visits with evening diuretics.

In their study, the researchers determined participants’ chronotype with a few questions from the Munich Chronotype Questionnaire about what time they fell asleep and woke up on workdays and days off and whether they considered themselves “morning types” or “evening types.” (The questions can be found in supplementary data for the study.)

If a physician thinks matching the timing of a dose with chronotype would help, they can consider it, Dr. Pigazzani said. “However, I must add that this was an observational study, so I would advise healthcare practitioners to wait for our data to be confirmed in new RCTs of personalized chronotherapy of hypertension.”

Children and older adults getting vaccines. Timing COVID shots and possibly other vaccines from late morning to mid-afternoon could have a small benefit for individuals and a bigger public-health benefit, Dr. Haspel said. But the most important thing is getting vaccinated. “If you can only get one in the evening, it’s still worthwhile. Timing may add oomph at a public-health level for more vulnerable groups.”
 

A version of this article appeared on Medscape.com.

BARCELONA, SPAIN — Streptococcus pneumoniae, the bacteria that causes pneumococcal disease, is sixfold more likely to colonize adults older than 60 years who have regular contact with children than those who do not, data from a community-based study showed.

However, there is “no clear evidence of adult-to-adult transmission,” and the researchers, led by Anne L. Wyllie, PhD, from the Yale School of Public Health, New Haven, Connecticut, noted that the study results suggest “the main benefit of adult pneumococcal conjugate vaccine (PCV) immunization is to directly protect adults who are exposed to children, who still carry and transmit some vaccine-type pneumococci despite successful pediatric national immunization programs.”

The data show that relatively high pneumococcus carriage rates are seen in people who have regular contact with children, who have had contact in the previous 2 weeks, and who have had contact for extended periods, Dr. Wyllie explained.

Preschoolers in particular were found to be most likely to transmit pneumococcus to older adults. “It is the 24- to 59-month-olds who are most associated with pneumococcal carriage, more than 1- to 2-year-olds,” she reported. However, transmission rates from children younger than 1 year are higher than those from children aged 1-2 years, she added.

The findings were presented at the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) 2024 global conference, formerly known as the ECCMID conference.
 

Originally Designed to Investigate Adult-to-Adult Transmission

The researchers wanted to understand the sources and dynamics of transmission, as well as the risk factors for pneumococcal disease in older adults, to help predict the effect of PCVs in people older than 60 years.

Although “we designed the study to specifically look at transmission between adults, in the end, we were presented with a very unique scenario” — restricted social mixing as a result of the COVID pandemic — during which “no community activities were happening,” Dr. Wyllie said. Because of this, the team was able to determine “the source of acquisition or transmission to the older adults was, very likely, coming from contact with children.”

Pneumococci are commonly found in respiratory tracts of healthy people. The US Centers for Disease Control and Prevention estimated that 20%-60% of school-aged children may be colonized compared with only 5%-10% of adults without children.

The longitudinal study was conducted among household pairs, such as married couples who were both aged at least 60 years and who did not have people younger than 60 years living in the household, in New Haven over two winter seasons: 2020-2021 and 2021-2022.

Self-collected saliva samples were assessed, and surveys on social behaviors and health were completed every 2 weeks for a 10-week period (with six study visits). The saliva sampling method was used because the researchers considered it to be more effective than samples from nasopharyngeal swabs. Quantitative polymerase chain reaction assays were used to test the saliva samples for the presence of pneumococcal DNA (pneumococcus genes piaB and lytA) and the diversity of pneumococcal strains (36 serotypes were targeted).
 

Strongly Suggestive of Transmission From Children to Older Adults

Of the 121 adults living in 61 households who were enrolled in the study, 62 adults participated in both seasons. Mean age was 70.9 years (range, 60-86 years), 51% of participants were women, and 85% were White.

Overall, 52 of 1088 (4.8%) samples tested positive for pneumococcus, and 27 of 121 (22.3%) adults were colonized on at least one sampling visit. Some were colonized at multiple timepoints, and two were colonized throughout the 10-week sampling period. Of the two participants who were colonized at five of six timepoints, one reported daily contact with children younger than 5 years and children aged 5-9 years in the two study seasons. This person was also positive at three of six sampling points during the first study season.

There were five instances in which both members of the household were carriers in the same season, although not necessarily at the same timepoint. Numbers were too small to determine whether transmission had occurred between the household pairs.

Contact with a 24- to 59-month-old child (older than 2 years but younger than 5 years) had the strongest association with elevated odds of carrying pneumococcus, the authors reported in their preprint, although the frequency and intensity of contact also mattered.

At any sampled time (point prevalence), pneumococcal carriage was substantially — just over sixfold — higher among older adults who had contact with children daily or every few days (10%) than among those who had no contact with children (1.6%).

In particular, contact between adults and children younger than 5 years and children aged 5-9 years was found to lead to elevated point prevalences of 13.8% and 14.1%, respectively. Pneumococcal carriage in children older than 10 years was lower, with a point prevalence of 8.3%.

The younger the child, the greater the point prevalence; point prevalences were 13.8% for samples from children aged 1 year and younger, 10.5% for samples from children aged 1-2 years, and 17.8% for children aged 2-5 years.

Carriage prevalence was higher in older adults who reported daily contact with children (15.7%) or contact every few days (14.0%) than in those who reported contact with children only once or twice a month (4.5%) or never (1.8%), they wrote.

“Older people who have a lot of contact with kids and are more susceptible to respiratory viruses can get a secondary infection from pneumococcus, especially during the cold and flu seasons. Vaccination can help to protect them or lessen severity of the illness,” Wyllie pointed out.

However, adult PCV immunization may not have a major impact on onward transmission to other adults, the authors wrote in their preprint.

This study supports prior work demonstrating that pneumococcal colonization is greater in households with children than in those without, said Stephen Pelton, MD, a pediatric infectious disease specialist from Boston University schools of medicine and public health. “The unique aspect is that Dr. Wyllie’s group has looked at individuals over age 60 and used the most sensitive methods currently available to detect pneumococcal carriage.”

“At the most recent ISPPD [International Society of Pneumonia and Pneumococcal Diseases conference], the role of adult-to-adult transmission in the community was discussed. This study confirms the critical role children play in community transmission of the pneumococcus,” Dr. Pelton noted.

Dr. Wyllie received consulting and/or advisory board fees from Pfizer, Merck, Diasorin, PPS Health, Primary Health, Co-Diagnostics, and Global Diagnostic Systems for work unrelated to this project and is the principal investigator on research grants from Pfizer, Merck, NIH RADx-UP, and SalivaDirect, Inc. to Yale University and from NIH RADx, Balvi.io, and Shield T3 to SalivaDirect, Inc. Dr. Pelton received honoraria from Merck, Pfizer, Sanofi, and GSK for participation in Pneumococcal Advisory Boards and DSMB (Sanofi). Boston Medical Center received grant funding for investigator-initiated research from Merck and Pfizer.
 

A version of this article appeared on Medscape.com.

BARCELONA, SPAIN — Streptococcus pneumoniae, the bacteria that causes pneumococcal disease, is sixfold more likely to colonize adults older than 60 years who have regular contact with children than those who do not, data from a community-based study showed.

However, there is “no clear evidence of adult-to-adult transmission,” and the researchers, led by Anne L. Wyllie, PhD, from the Yale School of Public Health, New Haven, Connecticut, noted that the study results suggest “the main benefit of adult pneumococcal conjugate vaccine (PCV) immunization is to directly protect adults who are exposed to children, who still carry and transmit some vaccine-type pneumococci despite successful pediatric national immunization programs.”

The data show that relatively high pneumococcus carriage rates are seen in people who have regular contact with children, who have had contact in the previous 2 weeks, and who have had contact for extended periods, Dr. Wyllie explained.

Preschoolers in particular were found to be most likely to transmit pneumococcus to older adults. “It is the 24- to 59-month-olds who are most associated with pneumococcal carriage, more than 1- to 2-year-olds,” she reported. However, transmission rates from children younger than 1 year are higher than those from children aged 1-2 years, she added.

The findings were presented at the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) 2024 global conference, formerly known as the ECCMID conference.
 

Originally Designed to Investigate Adult-to-Adult Transmission

The researchers wanted to understand the sources and dynamics of transmission, as well as the risk factors for pneumococcal disease in older adults, to help predict the effect of PCVs in people older than 60 years.

Although “we designed the study to specifically look at transmission between adults, in the end, we were presented with a very unique scenario” — restricted social mixing as a result of the COVID pandemic — during which “no community activities were happening,” Dr. Wyllie said. Because of this, the team was able to determine “the source of acquisition or transmission to the older adults was, very likely, coming from contact with children.”

Pneumococci are commonly found in respiratory tracts of healthy people. The US Centers for Disease Control and Prevention estimated that 20%-60% of school-aged children may be colonized compared with only 5%-10% of adults without children.

The longitudinal study was conducted among household pairs, such as married couples who were both aged at least 60 years and who did not have people younger than 60 years living in the household, in New Haven over two winter seasons: 2020-2021 and 2021-2022.

Self-collected saliva samples were assessed, and surveys on social behaviors and health were completed every 2 weeks for a 10-week period (with six study visits). The saliva sampling method was used because the researchers considered it to be more effective than samples from nasopharyngeal swabs. Quantitative polymerase chain reaction assays were used to test the saliva samples for the presence of pneumococcal DNA (pneumococcus genes piaB and lytA) and the diversity of pneumococcal strains (36 serotypes were targeted).
 

Strongly Suggestive of Transmission From Children to Older Adults

Of the 121 adults living in 61 households who were enrolled in the study, 62 adults participated in both seasons. Mean age was 70.9 years (range, 60-86 years), 51% of participants were women, and 85% were White.

Overall, 52 of 1088 (4.8%) samples tested positive for pneumococcus, and 27 of 121 (22.3%) adults were colonized on at least one sampling visit. Some were colonized at multiple timepoints, and two were colonized throughout the 10-week sampling period. Of the two participants who were colonized at five of six timepoints, one reported daily contact with children younger than 5 years and children aged 5-9 years in the two study seasons. This person was also positive at three of six sampling points during the first study season.

There were five instances in which both members of the household were carriers in the same season, although not necessarily at the same timepoint. Numbers were too small to determine whether transmission had occurred between the household pairs.

Contact with a 24- to 59-month-old child (older than 2 years but younger than 5 years) had the strongest association with elevated odds of carrying pneumococcus, the authors reported in their preprint, although the frequency and intensity of contact also mattered.

At any sampled time (point prevalence), pneumococcal carriage was substantially — just over sixfold — higher among older adults who had contact with children daily or every few days (10%) than among those who had no contact with children (1.6%).

In particular, contact between adults and children younger than 5 years and children aged 5-9 years was found to lead to elevated point prevalences of 13.8% and 14.1%, respectively. Pneumococcal carriage in children older than 10 years was lower, with a point prevalence of 8.3%.

The younger the child, the greater the point prevalence; point prevalences were 13.8% for samples from children aged 1 year and younger, 10.5% for samples from children aged 1-2 years, and 17.8% for children aged 2-5 years.

Carriage prevalence was higher in older adults who reported daily contact with children (15.7%) or contact every few days (14.0%) than in those who reported contact with children only once or twice a month (4.5%) or never (1.8%), they wrote.

“Older people who have a lot of contact with kids and are more susceptible to respiratory viruses can get a secondary infection from pneumococcus, especially during the cold and flu seasons. Vaccination can help to protect them or lessen severity of the illness,” Wyllie pointed out.

However, adult PCV immunization may not have a major impact on onward transmission to other adults, the authors wrote in their preprint.

This study supports prior work demonstrating that pneumococcal colonization is greater in households with children than in those without, said Stephen Pelton, MD, a pediatric infectious disease specialist from Boston University schools of medicine and public health. “The unique aspect is that Dr. Wyllie’s group has looked at individuals over age 60 and used the most sensitive methods currently available to detect pneumococcal carriage.”

“At the most recent ISPPD [International Society of Pneumonia and Pneumococcal Diseases conference], the role of adult-to-adult transmission in the community was discussed. This study confirms the critical role children play in community transmission of the pneumococcus,” Dr. Pelton noted.

Dr. Wyllie received consulting and/or advisory board fees from Pfizer, Merck, Diasorin, PPS Health, Primary Health, Co-Diagnostics, and Global Diagnostic Systems for work unrelated to this project and is the principal investigator on research grants from Pfizer, Merck, NIH RADx-UP, and SalivaDirect, Inc. to Yale University and from NIH RADx, Balvi.io, and Shield T3 to SalivaDirect, Inc. Dr. Pelton received honoraria from Merck, Pfizer, Sanofi, and GSK for participation in Pneumococcal Advisory Boards and DSMB (Sanofi). Boston Medical Center received grant funding for investigator-initiated research from Merck and Pfizer.
 

A version of this article appeared on Medscape.com.

BARCELONA, SPAIN — Streptococcus pneumoniae, the bacteria that causes pneumococcal disease, is sixfold more likely to colonize adults older than 60 years who have regular contact with children than those who do not, data from a community-based study showed.

However, there is “no clear evidence of adult-to-adult transmission,” and the researchers, led by Anne L. Wyllie, PhD, from the Yale School of Public Health, New Haven, Connecticut, noted that the study results suggest “the main benefit of adult pneumococcal conjugate vaccine (PCV) immunization is to directly protect adults who are exposed to children, who still carry and transmit some vaccine-type pneumococci despite successful pediatric national immunization programs.”

The data show that relatively high pneumococcus carriage rates are seen in people who have regular contact with children, who have had contact in the previous 2 weeks, and who have had contact for extended periods, Dr. Wyllie explained.

Preschoolers in particular were found to be most likely to transmit pneumococcus to older adults. “It is the 24- to 59-month-olds who are most associated with pneumococcal carriage, more than 1- to 2-year-olds,” she reported. However, transmission rates from children younger than 1 year are higher than those from children aged 1-2 years, she added.

The findings were presented at the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) 2024 global conference, formerly known as the ECCMID conference.
 

Originally Designed to Investigate Adult-to-Adult Transmission

The researchers wanted to understand the sources and dynamics of transmission, as well as the risk factors for pneumococcal disease in older adults, to help predict the effect of PCVs in people older than 60 years.

Although “we designed the study to specifically look at transmission between adults, in the end, we were presented with a very unique scenario” — restricted social mixing as a result of the COVID pandemic — during which “no community activities were happening,” Dr. Wyllie said. Because of this, the team was able to determine “the source of acquisition or transmission to the older adults was, very likely, coming from contact with children.”

Pneumococci are commonly found in respiratory tracts of healthy people. The US Centers for Disease Control and Prevention estimated that 20%-60% of school-aged children may be colonized compared with only 5%-10% of adults without children.

The longitudinal study was conducted among household pairs, such as married couples who were both aged at least 60 years and who did not have people younger than 60 years living in the household, in New Haven over two winter seasons: 2020-2021 and 2021-2022.

Self-collected saliva samples were assessed, and surveys on social behaviors and health were completed every 2 weeks for a 10-week period (with six study visits). The saliva sampling method was used because the researchers considered it to be more effective than samples from nasopharyngeal swabs. Quantitative polymerase chain reaction assays were used to test the saliva samples for the presence of pneumococcal DNA (pneumococcus genes piaB and lytA) and the diversity of pneumococcal strains (36 serotypes were targeted).
 

Strongly Suggestive of Transmission From Children to Older Adults

Of the 121 adults living in 61 households who were enrolled in the study, 62 adults participated in both seasons. Mean age was 70.9 years (range, 60-86 years), 51% of participants were women, and 85% were White.

Overall, 52 of 1088 (4.8%) samples tested positive for pneumococcus, and 27 of 121 (22.3%) adults were colonized on at least one sampling visit. Some were colonized at multiple timepoints, and two were colonized throughout the 10-week sampling period. Of the two participants who were colonized at five of six timepoints, one reported daily contact with children younger than 5 years and children aged 5-9 years in the two study seasons. This person was also positive at three of six sampling points during the first study season.

There were five instances in which both members of the household were carriers in the same season, although not necessarily at the same timepoint. Numbers were too small to determine whether transmission had occurred between the household pairs.

Contact with a 24- to 59-month-old child (older than 2 years but younger than 5 years) had the strongest association with elevated odds of carrying pneumococcus, the authors reported in their preprint, although the frequency and intensity of contact also mattered.

At any sampled time (point prevalence), pneumococcal carriage was substantially — just over sixfold — higher among older adults who had contact with children daily or every few days (10%) than among those who had no contact with children (1.6%).

In particular, contact between adults and children younger than 5 years and children aged 5-9 years was found to lead to elevated point prevalences of 13.8% and 14.1%, respectively. Pneumococcal carriage in children older than 10 years was lower, with a point prevalence of 8.3%.

The younger the child, the greater the point prevalence; point prevalences were 13.8% for samples from children aged 1 year and younger, 10.5% for samples from children aged 1-2 years, and 17.8% for children aged 2-5 years.

Carriage prevalence was higher in older adults who reported daily contact with children (15.7%) or contact every few days (14.0%) than in those who reported contact with children only once or twice a month (4.5%) or never (1.8%), they wrote.

“Older people who have a lot of contact with kids and are more susceptible to respiratory viruses can get a secondary infection from pneumococcus, especially during the cold and flu seasons. Vaccination can help to protect them or lessen severity of the illness,” Wyllie pointed out.

However, adult PCV immunization may not have a major impact on onward transmission to other adults, the authors wrote in their preprint.

This study supports prior work demonstrating that pneumococcal colonization is greater in households with children than in those without, said Stephen Pelton, MD, a pediatric infectious disease specialist from Boston University schools of medicine and public health. “The unique aspect is that Dr. Wyllie’s group has looked at individuals over age 60 and used the most sensitive methods currently available to detect pneumococcal carriage.”

“At the most recent ISPPD [International Society of Pneumonia and Pneumococcal Diseases conference], the role of adult-to-adult transmission in the community was discussed. This study confirms the critical role children play in community transmission of the pneumococcus,” Dr. Pelton noted.

Dr. Wyllie received consulting and/or advisory board fees from Pfizer, Merck, Diasorin, PPS Health, Primary Health, Co-Diagnostics, and Global Diagnostic Systems for work unrelated to this project and is the principal investigator on research grants from Pfizer, Merck, NIH RADx-UP, and SalivaDirect, Inc. to Yale University and from NIH RADx, Balvi.io, and Shield T3 to SalivaDirect, Inc. Dr. Pelton received honoraria from Merck, Pfizer, Sanofi, and GSK for participation in Pneumococcal Advisory Boards and DSMB (Sanofi). Boston Medical Center received grant funding for investigator-initiated research from Merck and Pfizer.
 

A version of this article appeared on Medscape.com.

High levels of xylitol, a low-calorie sweetener used in many reduced-sugar foods as well as gum and toothpaste, are linked to an increased risk of heart attacks, strokes, and death, says a new study published in the European Heart Journal.

The research team studied more than 3000 people in the US and Europe over 3 years and found that people with the highest amount of xylitol in their plasma were more likely to have a problem with their heart or blood vessels.

To show the early effects of xylitol, researchers studied platelet activity in volunteers who consumed a xylitol-sweetened drink and a glucose-sweetened drink. The xylitol levels went up by 1000 times in people after the xylitol drink but not after the glucose-sweetened drink.

Xylitol is naturally found in small amounts in fruit and vegetables, and it’s been used more as a sugar substitute over the past decade in processed foods, toothpaste, chewing gum, and other products.

“This study again shows the immediate need for investigating sugar alcohols and artificial sweeteners, especially as they continue to be recommended in combating conditions like obesity or diabetes,” Stanley Hazen, MD, chair of the Department of Cardiovascular and Metabolic Sciences at Cleveland Clinic’s Lerner Research Institute, Cleveland, Ohio, said in a news release.

“It does not mean throw out your toothpaste if it has xylitol in it, but we should be aware that consumption of a product containing high levels could increase the risk of blood clot-related events.”

A similar link between erythritol, another sugar substance, and problems with the heart and blood vessels was found last year by the same research team, the release said.

In a response to the study, the Calorie Control Council, a trade association representing the low- and reduced-calorie food and beverage industry, said xylitol has been approved for decades by government agencies. The study results may not apply to the general population because some people in the study already had a higher risk of having problems with their heart and blood vessels, it said.

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

High levels of xylitol, a low-calorie sweetener used in many reduced-sugar foods as well as gum and toothpaste, are linked to an increased risk of heart attacks, strokes, and death, says a new study published in the European Heart Journal.

The research team studied more than 3000 people in the US and Europe over 3 years and found that people with the highest amount of xylitol in their plasma were more likely to have a problem with their heart or blood vessels.

To show the early effects of xylitol, researchers studied platelet activity in volunteers who consumed a xylitol-sweetened drink and a glucose-sweetened drink. The xylitol levels went up by 1000 times in people after the xylitol drink but not after the glucose-sweetened drink.

Xylitol is naturally found in small amounts in fruit and vegetables, and it’s been used more as a sugar substitute over the past decade in processed foods, toothpaste, chewing gum, and other products.

“This study again shows the immediate need for investigating sugar alcohols and artificial sweeteners, especially as they continue to be recommended in combating conditions like obesity or diabetes,” Stanley Hazen, MD, chair of the Department of Cardiovascular and Metabolic Sciences at Cleveland Clinic’s Lerner Research Institute, Cleveland, Ohio, said in a news release.

“It does not mean throw out your toothpaste if it has xylitol in it, but we should be aware that consumption of a product containing high levels could increase the risk of blood clot-related events.”

A similar link between erythritol, another sugar substance, and problems with the heart and blood vessels was found last year by the same research team, the release said.

In a response to the study, the Calorie Control Council, a trade association representing the low- and reduced-calorie food and beverage industry, said xylitol has been approved for decades by government agencies. The study results may not apply to the general population because some people in the study already had a higher risk of having problems with their heart and blood vessels, it said.

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

High levels of xylitol, a low-calorie sweetener used in many reduced-sugar foods as well as gum and toothpaste, are linked to an increased risk of heart attacks, strokes, and death, says a new study published in the European Heart Journal.

The research team studied more than 3000 people in the US and Europe over 3 years and found that people with the highest amount of xylitol in their plasma were more likely to have a problem with their heart or blood vessels.

To show the early effects of xylitol, researchers studied platelet activity in volunteers who consumed a xylitol-sweetened drink and a glucose-sweetened drink. The xylitol levels went up by 1000 times in people after the xylitol drink but not after the glucose-sweetened drink.

Xylitol is naturally found in small amounts in fruit and vegetables, and it’s been used more as a sugar substitute over the past decade in processed foods, toothpaste, chewing gum, and other products.

“This study again shows the immediate need for investigating sugar alcohols and artificial sweeteners, especially as they continue to be recommended in combating conditions like obesity or diabetes,” Stanley Hazen, MD, chair of the Department of Cardiovascular and Metabolic Sciences at Cleveland Clinic’s Lerner Research Institute, Cleveland, Ohio, said in a news release.

“It does not mean throw out your toothpaste if it has xylitol in it, but we should be aware that consumption of a product containing high levels could increase the risk of blood clot-related events.”

A similar link between erythritol, another sugar substance, and problems with the heart and blood vessels was found last year by the same research team, the release said.

In a response to the study, the Calorie Control Council, a trade association representing the low- and reduced-calorie food and beverage industry, said xylitol has been approved for decades by government agencies. The study results may not apply to the general population because some people in the study already had a higher risk of having problems with their heart and blood vessels, it said.

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

The results of a large French study comparing the cancer risk in children conceived through assisted reproductive technology (ART) with that of naturally conceived children were published recently in JAMA Network Open. This study is one of the largest to date on this subject: It included 8,526,306 children born in France between 2010 and 2021, of whom 260,236 (3%) were conceived through ART, and followed them up to a median age of 6.7 years.

Motivations for the Study

ART (including artificial insemination, in vitro fertilization [IVF], or intracytoplasmic sperm injection [ICSI] with fresh or frozen embryo transfer) accounts for about 1 in 30 births in France. However, limited and heterogeneous data have suggested an increased risk for certain health disorders, including cancer, among children conceived through ART. Therefore, a large-scale evaluation of cancer risk in these children is important.

No Overall Increase

In all, 9256 children developed cancer, including 292 who were conceived through ART. Thus, this study did not show an increased risk for cancer (of all types combined) in children conceived through ART. Nevertheless, a slight increase in the risk for leukemia was observed in children conceived through IVF or ICSI. The investigators observed approximately one additional case for every 5000 newborns conceived through IVF or ICSI who reached age 10 years.

Epidemiological monitoring should be continued to better evaluate long-term risks and see whether the risk for leukemia is confirmed. If it is, then it will be useful to investigate the mechanisms related to ART techniques or the fertility disorders of parents that could lead to an increased risk for leukemia.

This story was translated from Univadis France, which is part of the Medscape Professional Network, 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.

The results of a large French study comparing the cancer risk in children conceived through assisted reproductive technology (ART) with that of naturally conceived children were published recently in JAMA Network Open. This study is one of the largest to date on this subject: It included 8,526,306 children born in France between 2010 and 2021, of whom 260,236 (3%) were conceived through ART, and followed them up to a median age of 6.7 years.

Motivations for the Study

ART (including artificial insemination, in vitro fertilization [IVF], or intracytoplasmic sperm injection [ICSI] with fresh or frozen embryo transfer) accounts for about 1 in 30 births in France. However, limited and heterogeneous data have suggested an increased risk for certain health disorders, including cancer, among children conceived through ART. Therefore, a large-scale evaluation of cancer risk in these children is important.

No Overall Increase

In all, 9256 children developed cancer, including 292 who were conceived through ART. Thus, this study did not show an increased risk for cancer (of all types combined) in children conceived through ART. Nevertheless, a slight increase in the risk for leukemia was observed in children conceived through IVF or ICSI. The investigators observed approximately one additional case for every 5000 newborns conceived through IVF or ICSI who reached age 10 years.

Epidemiological monitoring should be continued to better evaluate long-term risks and see whether the risk for leukemia is confirmed. If it is, then it will be useful to investigate the mechanisms related to ART techniques or the fertility disorders of parents that could lead to an increased risk for leukemia.

This story was translated from Univadis France, which is part of the Medscape Professional Network, 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.

The results of a large French study comparing the cancer risk in children conceived through assisted reproductive technology (ART) with that of naturally conceived children were published recently in JAMA Network Open. This study is one of the largest to date on this subject: It included 8,526,306 children born in France between 2010 and 2021, of whom 260,236 (3%) were conceived through ART, and followed them up to a median age of 6.7 years.

Motivations for the Study

ART (including artificial insemination, in vitro fertilization [IVF], or intracytoplasmic sperm injection [ICSI] with fresh or frozen embryo transfer) accounts for about 1 in 30 births in France. However, limited and heterogeneous data have suggested an increased risk for certain health disorders, including cancer, among children conceived through ART. Therefore, a large-scale evaluation of cancer risk in these children is important.

No Overall Increase

In all, 9256 children developed cancer, including 292 who were conceived through ART. Thus, this study did not show an increased risk for cancer (of all types combined) in children conceived through ART. Nevertheless, a slight increase in the risk for leukemia was observed in children conceived through IVF or ICSI. The investigators observed approximately one additional case for every 5000 newborns conceived through IVF or ICSI who reached age 10 years.

Epidemiological monitoring should be continued to better evaluate long-term risks and see whether the risk for leukemia is confirmed. If it is, then it will be useful to investigate the mechanisms related to ART techniques or the fertility disorders of parents that could lead to an increased risk for leukemia.

This story was translated from Univadis France, which is part of the Medscape Professional Network, 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.

The antibody-drug conjugate trastuzumab deruxtecan, or T-DXd, is an effective first-line treatment in patients with HER2-low metastatic breast cancer, conferring an additional 5 months’ progression-free survival over chemotherapy.

HER2-low cancers express levels of human epidermal growth factor receptor 2 that are below standard thresholds for HER2-positive immunohistochemistry. In 2022, results from the DESTINY-Breast04 trial showed T-DXd (Enhertu, AstraZeneca) to be an effective second-line chemotherapy in patients with HER2-low metastatic breast cancer.

The highly awaited new findings, from the manufacturer-sponsored, open-label Phase 3 DESTINY-Breast06 trial, were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Illinois.

The findings not only definitively establish a role for T-DXd earlier in the treatment sequence for HER2-low cancers, they also suggest benefit in a group of patients designated for the purposes of this trial to be HER2-ultralow. These patients have cancers with only faintly detectable HER2 expression on currently used assays (J Clin Oncol 42, 2024 [suppl 17; abstr LBA 1000]).

In a separate set of findings also presented at ASCO, from the randomized phase 1B open-label study, DESTINY-Breast07, T-Dxd showed efficacy in previously untreated HER2-positive metastatic breast cancer patients both alone and in combination with the monoclonal antibody pertuzumab (Perjeta, Genentech).
 

DESTINY-Breast06 Methods and Results

The DESTINY-Breast06 findings were presented by lead investigator Guiseppe Curigliano, MD, PhD, of the University of Milan and European Institute of Oncology. Dr. Curigliano and his colleagues randomized 866 patients with metastatic breast cancer: 436 to intravenous T-Dxd and 430 to the investigator’s choice of capecitabine, nab-paclitaxel, or paclitaxel chemotherapy. The investigators chose capecitabine 60% of the time.

Most patients had cancers classed as HER2 low (immunohistochemistry 1+ or 2+), while 153 had cancers classed by investigators as HER2-ultralow (IHC 0 with membrane staining or IHC under 1+). Patients enrolled in the study were those whose disease had progressed after endocrine therapy with or without targeted therapy. Patients’ median age was between 57 and 58, and all were chemotherapy-naive in the metastatic breast cancer setting.

The main outcome of the study was median progression-free survival in the HER2-low group. T-Dxd was seen improving progression-free survival, with median 13.2 months vs. 8.1 months (hazard ratio, 0.62; 95% confidence interval, 0.51-0.74; P < .0001). In the intention-to-treat population, which included the HER2 ultralow patients, the benefit was the same (HR, 0.63; 95% CI, 0.53-0.75; P < .0001). This suggested that T-DXd is also effective in these patients, and it will be extremely important going forward to identify the lowest level of HER2 expression in metastatic breast cancers that can still benefit from therapy with T-DxD, Dr. Curigliano said.

Overall survival could not be assessed in the study cohort because complete data were not yet available, Dr. Curigliano said. However, trends pointed to an advantage for T-DXd, and tumor response rates were markedly higher with T-DXd: 57% compared with 31% for standard chemotherapy in the full cohort.

Serious treatment-emergent adverse events were more common in the T-Dxd–treated patients, with 11% of that arm developing drug-related interstitial lung disease, and three patients dying of it. Five patients in the T-DXd arm died of adverse events deemed treatment-related, and none died from treatment-related adverse events in the standard chemotherapy arm. Altogether 11 patients died in the T-DXd arm and 6 in the chemotherapy arm.
 

Clinical Implications of DESTINY-Breast06

The DESTINY-Breast06 data show that “we have to again change how we think about HER2 expression. Even very low levels of HER2 expression matter, and they can be leveraged to improve the treatment for our patients,” said Ian Krop, MD, PhD, of the Yale Cancer Center in New Haven, Connecticut, during the session where the results were presented.

But T-DXd may not be an appropriate first choice for all patients, especially given the safety concerns associated with T-DXd, he continued. With overall survival and quality-of-life data still lacking, clinicians will have to determine on a case-by-case basis who should get T-DXd in the first line.

“For patients who have symptomatic metastatic disease, who need a response to address those symptoms, those in whom you think chemotherapy may not work as well because they had, for example, a short recurrence interval after their adjuvant chemotherapy — using T-DXd in that first-line setting makes perfect sense to take advantage of the substantially higher response rate compared to chemo,” Dr. Krop said. “But for patients who have asymptomatic low burdens of disease, it seems very reasonable to consider using a well-tolerated chemotherapy like capecitabine in the first line, and then using T-DXd in the second line.”

In an interview, Erica Mayer, MD, of the Dana Farber Cancer Institute in Boston, Massachusetts, said patient choice will also matter in determining whether T-DXd is a first-line option. The known toxicity of T-DXd was underscored by the latest findings, she noted, while capecitabine, one of the chemotherapy choices in the control arm of the study, “really reflects what the majority of breast cancer doctors tend to offer, both because of the efficacy of the drug, but also because it’s oral, it’s well tolerated, and you don’t lose your hair.”
 

DESTINY-Breast07 Results

The DESTINY-Breast07 findings, from a Phase 1B open-label trial measuring safety and tolerability, were presented by Fabrice Andre, MD, PhD, of Université Paris Saclay in Paris, France. Dr. Andre and his colleagues presented the first data comparing T-DXd monotherapy and T-DXd with pertuzumab — a monoclonal antibody targeting HER2 — as a first-line treatment in patients with HER2-overexpressing (immunohistochemistry 3 and above) metastatic breast cancer. (J Clin Oncol 42, 2024 [suppl 16; abstr 1009]).

Current first-line standard of care for these patients is pertuzumab, trastuzumab, and docetaxel, based on results from the 2015 CLEOPATRA trial. T-DXd is currently approved as a second-line treatment.

Dr. Andre and his colleagues randomized 75 patients to monotherapy with T-DXd and 50 to combined therapy, with a median follow-up of 2 years.

After 1 year of treatment, combination of T-DXd and pertuzumab was seen to be associated with a progression-free survival of 89% at 1 year (80% CI, 81.9-93.9), compared with 80% in patients treated with T-DXd alone (80% CI, 73.7-86.1). Objective tumor response rate was 84% for the combined therapy at 12 weeks, with 20% of patients seeing a complete response, compared with 76% and 8%, respectively, for monotherapy.

As in the DESTINY-Breast06 trial, adverse events were high, with interstitial lung disease seen in 9% of patients in the monotherapy group and in 14% of the combined-therapy patients, although no treatment-related deaths occurred.

A randomized phase 3 trial, DESTINY Breast09, will now compare the monotherapy and the combined therapy with standard care.

T-DXd has seen a rapidly expanding role in treating breast and other solid tumors. The DESTINY Breast06 findings will move up its place in the treatment algorithm for metastatic breast cancer, “allowing us to now offer T-DXd as the first chemotherapy choice for patients who are making that transition to chemotherapy over many of the traditional provider choices that we previously have offered,” Dr. Mayer said.

The results “support the use of not only this specific agent, but also the concept of antibody drug conjugates as a very effective way to treat malignancy,” she added.

Dr. Curigliano reported receiving speaker’s fees, research funding, and other support from AstraZeneca and Daiichi Sankyo, among other companies, as did most of his co-authors, of whom three were AstraZeneca employees. Dr. Fabrice disclosed receiving research funding, travel compensation, and/or advisory fees from AstraZeneca and other entities, as did several of his co-authors. Two of his co-authors were employed by AstraZeneca and Roche, manufacturers of the study drugs. Dr. Krop and Dr. Mayer disclosed relationships with AstraZeneca and others.

The antibody-drug conjugate trastuzumab deruxtecan, or T-DXd, is an effective first-line treatment in patients with HER2-low metastatic breast cancer, conferring an additional 5 months’ progression-free survival over chemotherapy.

HER2-low cancers express levels of human epidermal growth factor receptor 2 that are below standard thresholds for HER2-positive immunohistochemistry. In 2022, results from the DESTINY-Breast04 trial showed T-DXd (Enhertu, AstraZeneca) to be an effective second-line chemotherapy in patients with HER2-low metastatic breast cancer.

The highly awaited new findings, from the manufacturer-sponsored, open-label Phase 3 DESTINY-Breast06 trial, were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Illinois.

The findings not only definitively establish a role for T-DXd earlier in the treatment sequence for HER2-low cancers, they also suggest benefit in a group of patients designated for the purposes of this trial to be HER2-ultralow. These patients have cancers with only faintly detectable HER2 expression on currently used assays (J Clin Oncol 42, 2024 [suppl 17; abstr LBA 1000]).

In a separate set of findings also presented at ASCO, from the randomized phase 1B open-label study, DESTINY-Breast07, T-Dxd showed efficacy in previously untreated HER2-positive metastatic breast cancer patients both alone and in combination with the monoclonal antibody pertuzumab (Perjeta, Genentech).
 

DESTINY-Breast06 Methods and Results

The DESTINY-Breast06 findings were presented by lead investigator Guiseppe Curigliano, MD, PhD, of the University of Milan and European Institute of Oncology. Dr. Curigliano and his colleagues randomized 866 patients with metastatic breast cancer: 436 to intravenous T-Dxd and 430 to the investigator’s choice of capecitabine, nab-paclitaxel, or paclitaxel chemotherapy. The investigators chose capecitabine 60% of the time.

Most patients had cancers classed as HER2 low (immunohistochemistry 1+ or 2+), while 153 had cancers classed by investigators as HER2-ultralow (IHC 0 with membrane staining or IHC under 1+). Patients enrolled in the study were those whose disease had progressed after endocrine therapy with or without targeted therapy. Patients’ median age was between 57 and 58, and all were chemotherapy-naive in the metastatic breast cancer setting.

The main outcome of the study was median progression-free survival in the HER2-low group. T-Dxd was seen improving progression-free survival, with median 13.2 months vs. 8.1 months (hazard ratio, 0.62; 95% confidence interval, 0.51-0.74; P < .0001). In the intention-to-treat population, which included the HER2 ultralow patients, the benefit was the same (HR, 0.63; 95% CI, 0.53-0.75; P < .0001). This suggested that T-DXd is also effective in these patients, and it will be extremely important going forward to identify the lowest level of HER2 expression in metastatic breast cancers that can still benefit from therapy with T-DxD, Dr. Curigliano said.

Overall survival could not be assessed in the study cohort because complete data were not yet available, Dr. Curigliano said. However, trends pointed to an advantage for T-DXd, and tumor response rates were markedly higher with T-DXd: 57% compared with 31% for standard chemotherapy in the full cohort.

Serious treatment-emergent adverse events were more common in the T-Dxd–treated patients, with 11% of that arm developing drug-related interstitial lung disease, and three patients dying of it. Five patients in the T-DXd arm died of adverse events deemed treatment-related, and none died from treatment-related adverse events in the standard chemotherapy arm. Altogether 11 patients died in the T-DXd arm and 6 in the chemotherapy arm.
 

Clinical Implications of DESTINY-Breast06

The DESTINY-Breast06 data show that “we have to again change how we think about HER2 expression. Even very low levels of HER2 expression matter, and they can be leveraged to improve the treatment for our patients,” said Ian Krop, MD, PhD, of the Yale Cancer Center in New Haven, Connecticut, during the session where the results were presented.

But T-DXd may not be an appropriate first choice for all patients, especially given the safety concerns associated with T-DXd, he continued. With overall survival and quality-of-life data still lacking, clinicians will have to determine on a case-by-case basis who should get T-DXd in the first line.

“For patients who have symptomatic metastatic disease, who need a response to address those symptoms, those in whom you think chemotherapy may not work as well because they had, for example, a short recurrence interval after their adjuvant chemotherapy — using T-DXd in that first-line setting makes perfect sense to take advantage of the substantially higher response rate compared to chemo,” Dr. Krop said. “But for patients who have asymptomatic low burdens of disease, it seems very reasonable to consider using a well-tolerated chemotherapy like capecitabine in the first line, and then using T-DXd in the second line.”

In an interview, Erica Mayer, MD, of the Dana Farber Cancer Institute in Boston, Massachusetts, said patient choice will also matter in determining whether T-DXd is a first-line option. The known toxicity of T-DXd was underscored by the latest findings, she noted, while capecitabine, one of the chemotherapy choices in the control arm of the study, “really reflects what the majority of breast cancer doctors tend to offer, both because of the efficacy of the drug, but also because it’s oral, it’s well tolerated, and you don’t lose your hair.”
 

DESTINY-Breast07 Results

The DESTINY-Breast07 findings, from a Phase 1B open-label trial measuring safety and tolerability, were presented by Fabrice Andre, MD, PhD, of Université Paris Saclay in Paris, France. Dr. Andre and his colleagues presented the first data comparing T-DXd monotherapy and T-DXd with pertuzumab — a monoclonal antibody targeting HER2 — as a first-line treatment in patients with HER2-overexpressing (immunohistochemistry 3 and above) metastatic breast cancer. (J Clin Oncol 42, 2024 [suppl 16; abstr 1009]).

Current first-line standard of care for these patients is pertuzumab, trastuzumab, and docetaxel, based on results from the 2015 CLEOPATRA trial. T-DXd is currently approved as a second-line treatment.

Dr. Andre and his colleagues randomized 75 patients to monotherapy with T-DXd and 50 to combined therapy, with a median follow-up of 2 years.

After 1 year of treatment, combination of T-DXd and pertuzumab was seen to be associated with a progression-free survival of 89% at 1 year (80% CI, 81.9-93.9), compared with 80% in patients treated with T-DXd alone (80% CI, 73.7-86.1). Objective tumor response rate was 84% for the combined therapy at 12 weeks, with 20% of patients seeing a complete response, compared with 76% and 8%, respectively, for monotherapy.

As in the DESTINY-Breast06 trial, adverse events were high, with interstitial lung disease seen in 9% of patients in the monotherapy group and in 14% of the combined-therapy patients, although no treatment-related deaths occurred.

A randomized phase 3 trial, DESTINY Breast09, will now compare the monotherapy and the combined therapy with standard care.

T-DXd has seen a rapidly expanding role in treating breast and other solid tumors. The DESTINY Breast06 findings will move up its place in the treatment algorithm for metastatic breast cancer, “allowing us to now offer T-DXd as the first chemotherapy choice for patients who are making that transition to chemotherapy over many of the traditional provider choices that we previously have offered,” Dr. Mayer said.

The results “support the use of not only this specific agent, but also the concept of antibody drug conjugates as a very effective way to treat malignancy,” she added.

Dr. Curigliano reported receiving speaker’s fees, research funding, and other support from AstraZeneca and Daiichi Sankyo, among other companies, as did most of his co-authors, of whom three were AstraZeneca employees. Dr. Fabrice disclosed receiving research funding, travel compensation, and/or advisory fees from AstraZeneca and other entities, as did several of his co-authors. Two of his co-authors were employed by AstraZeneca and Roche, manufacturers of the study drugs. Dr. Krop and Dr. Mayer disclosed relationships with AstraZeneca and others.

The antibody-drug conjugate trastuzumab deruxtecan, or T-DXd, is an effective first-line treatment in patients with HER2-low metastatic breast cancer, conferring an additional 5 months’ progression-free survival over chemotherapy.

HER2-low cancers express levels of human epidermal growth factor receptor 2 that are below standard thresholds for HER2-positive immunohistochemistry. In 2022, results from the DESTINY-Breast04 trial showed T-DXd (Enhertu, AstraZeneca) to be an effective second-line chemotherapy in patients with HER2-low metastatic breast cancer.

The highly awaited new findings, from the manufacturer-sponsored, open-label Phase 3 DESTINY-Breast06 trial, were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Illinois.

The findings not only definitively establish a role for T-DXd earlier in the treatment sequence for HER2-low cancers, they also suggest benefit in a group of patients designated for the purposes of this trial to be HER2-ultralow. These patients have cancers with only faintly detectable HER2 expression on currently used assays (J Clin Oncol 42, 2024 [suppl 17; abstr LBA 1000]).

In a separate set of findings also presented at ASCO, from the randomized phase 1B open-label study, DESTINY-Breast07, T-Dxd showed efficacy in previously untreated HER2-positive metastatic breast cancer patients both alone and in combination with the monoclonal antibody pertuzumab (Perjeta, Genentech).
 

DESTINY-Breast06 Methods and Results

The DESTINY-Breast06 findings were presented by lead investigator Guiseppe Curigliano, MD, PhD, of the University of Milan and European Institute of Oncology. Dr. Curigliano and his colleagues randomized 866 patients with metastatic breast cancer: 436 to intravenous T-Dxd and 430 to the investigator’s choice of capecitabine, nab-paclitaxel, or paclitaxel chemotherapy. The investigators chose capecitabine 60% of the time.

Most patients had cancers classed as HER2 low (immunohistochemistry 1+ or 2+), while 153 had cancers classed by investigators as HER2-ultralow (IHC 0 with membrane staining or IHC under 1+). Patients enrolled in the study were those whose disease had progressed after endocrine therapy with or without targeted therapy. Patients’ median age was between 57 and 58, and all were chemotherapy-naive in the metastatic breast cancer setting.

The main outcome of the study was median progression-free survival in the HER2-low group. T-Dxd was seen improving progression-free survival, with median 13.2 months vs. 8.1 months (hazard ratio, 0.62; 95% confidence interval, 0.51-0.74; P < .0001). In the intention-to-treat population, which included the HER2 ultralow patients, the benefit was the same (HR, 0.63; 95% CI, 0.53-0.75; P < .0001). This suggested that T-DXd is also effective in these patients, and it will be extremely important going forward to identify the lowest level of HER2 expression in metastatic breast cancers that can still benefit from therapy with T-DxD, Dr. Curigliano said.

Overall survival could not be assessed in the study cohort because complete data were not yet available, Dr. Curigliano said. However, trends pointed to an advantage for T-DXd, and tumor response rates were markedly higher with T-DXd: 57% compared with 31% for standard chemotherapy in the full cohort.

Serious treatment-emergent adverse events were more common in the T-Dxd–treated patients, with 11% of that arm developing drug-related interstitial lung disease, and three patients dying of it. Five patients in the T-DXd arm died of adverse events deemed treatment-related, and none died from treatment-related adverse events in the standard chemotherapy arm. Altogether 11 patients died in the T-DXd arm and 6 in the chemotherapy arm.
 

Clinical Implications of DESTINY-Breast06

The DESTINY-Breast06 data show that “we have to again change how we think about HER2 expression. Even very low levels of HER2 expression matter, and they can be leveraged to improve the treatment for our patients,” said Ian Krop, MD, PhD, of the Yale Cancer Center in New Haven, Connecticut, during the session where the results were presented.

But T-DXd may not be an appropriate first choice for all patients, especially given the safety concerns associated with T-DXd, he continued. With overall survival and quality-of-life data still lacking, clinicians will have to determine on a case-by-case basis who should get T-DXd in the first line.

“For patients who have symptomatic metastatic disease, who need a response to address those symptoms, those in whom you think chemotherapy may not work as well because they had, for example, a short recurrence interval after their adjuvant chemotherapy — using T-DXd in that first-line setting makes perfect sense to take advantage of the substantially higher response rate compared to chemo,” Dr. Krop said. “But for patients who have asymptomatic low burdens of disease, it seems very reasonable to consider using a well-tolerated chemotherapy like capecitabine in the first line, and then using T-DXd in the second line.”

In an interview, Erica Mayer, MD, of the Dana Farber Cancer Institute in Boston, Massachusetts, said patient choice will also matter in determining whether T-DXd is a first-line option. The known toxicity of T-DXd was underscored by the latest findings, she noted, while capecitabine, one of the chemotherapy choices in the control arm of the study, “really reflects what the majority of breast cancer doctors tend to offer, both because of the efficacy of the drug, but also because it’s oral, it’s well tolerated, and you don’t lose your hair.”
 

DESTINY-Breast07 Results

The DESTINY-Breast07 findings, from a Phase 1B open-label trial measuring safety and tolerability, were presented by Fabrice Andre, MD, PhD, of Université Paris Saclay in Paris, France. Dr. Andre and his colleagues presented the first data comparing T-DXd monotherapy and T-DXd with pertuzumab — a monoclonal antibody targeting HER2 — as a first-line treatment in patients with HER2-overexpressing (immunohistochemistry 3 and above) metastatic breast cancer. (J Clin Oncol 42, 2024 [suppl 16; abstr 1009]).

Current first-line standard of care for these patients is pertuzumab, trastuzumab, and docetaxel, based on results from the 2015 CLEOPATRA trial. T-DXd is currently approved as a second-line treatment.

Dr. Andre and his colleagues randomized 75 patients to monotherapy with T-DXd and 50 to combined therapy, with a median follow-up of 2 years.

After 1 year of treatment, combination of T-DXd and pertuzumab was seen to be associated with a progression-free survival of 89% at 1 year (80% CI, 81.9-93.9), compared with 80% in patients treated with T-DXd alone (80% CI, 73.7-86.1). Objective tumor response rate was 84% for the combined therapy at 12 weeks, with 20% of patients seeing a complete response, compared with 76% and 8%, respectively, for monotherapy.

As in the DESTINY-Breast06 trial, adverse events were high, with interstitial lung disease seen in 9% of patients in the monotherapy group and in 14% of the combined-therapy patients, although no treatment-related deaths occurred.

A randomized phase 3 trial, DESTINY Breast09, will now compare the monotherapy and the combined therapy with standard care.

T-DXd has seen a rapidly expanding role in treating breast and other solid tumors. The DESTINY Breast06 findings will move up its place in the treatment algorithm for metastatic breast cancer, “allowing us to now offer T-DXd as the first chemotherapy choice for patients who are making that transition to chemotherapy over many of the traditional provider choices that we previously have offered,” Dr. Mayer said.

The results “support the use of not only this specific agent, but also the concept of antibody drug conjugates as a very effective way to treat malignancy,” she added.

Dr. Curigliano reported receiving speaker’s fees, research funding, and other support from AstraZeneca and Daiichi Sankyo, among other companies, as did most of his co-authors, of whom three were AstraZeneca employees. Dr. Fabrice disclosed receiving research funding, travel compensation, and/or advisory fees from AstraZeneca and other entities, as did several of his co-authors. Two of his co-authors were employed by AstraZeneca and Roche, manufacturers of the study drugs. Dr. Krop and Dr. Mayer disclosed relationships with AstraZeneca and others.

TOPLINE:

Long-term exposure to fine particulate matter is associated with higher fasting blood glucose (FBG) levels and an increased type 2 diabetes risk, significantly contributing to the diabetes-related health burden among women of reproductive age.

METHODOLOGY:

• Exposure to fine particulate matter < 2.5 µm (PM2.5) is a known risk factor for type 2 diabetes, but its effect on women of reproductive age, who undergo hormonal fluctuations during reproductive events, is not well studied.
• Researchers evaluated the association of long-term exposure to PM2.5 with FBG levels and diabetes risk in 20,076,032 eligible women of reproductive age (average age, 27.04 years) across 350 cities in China between 2010 and 2015.
• They assessed PM2.5 exposure at the participants’ residential addresses and calculated average long-term exposure at 1 (lag 1 year), 2 (lag 2 years), and 3 years (lag 3 years) before the survey date, as defined by the World Health Organization (WHO).
• The primary outcomes were FBG levels and diabetes prevalence (FBG, ≥ 7 mmol/L, classified as diabetes; FBG, 6.1-7 mmol/L, classified as prediabetes).
• The study also evaluated the diabetes burden attributed to long-term PM2.5 exposure as per the Chinese National Ambient Air Quality Standards (annual mean PM2.5 exposure limit, > 35 µg/m³) and the WHO air quality guideline (annual mean PM2.5 exposure limit, > 5 µg/m³).

TAKEAWAY:

• The median PM2.5 exposure levels over lag periods of 1, 2, and 3 years were 67, 67, and 66 µg/m³, respectively, exceeding the WHO limit by more than 13-fold.
• Each interquartile range increase in the 3-year average PM2.5 exposure by 27 μg/m³ raised FBG levels by 0.078 mmol/L (P < .05), risk for diabetes by 18% (odds ratio [OR], 1.18; 95% CI, 1.16-1.19), and risk for prediabetes by 5% (OR, 1.05; 95% CI, 1.04-1.05).
• Long-term exposure to PM2.5 > 5 µg/m³ and 35 µg/m³ in the previous 3 years corresponded to an additional 41.7 (95% CI, 39.3-44.0) and 78.6 (95% CI, 74.5-82.6) thousand cases of diabetes nationwide, respectively.
• A higher PM2.5 exposure increased FBG levels and risk for diabetes in women with overweight or obesity vs those without and in those aged ≥ 35 years vs < 35 years (P < .001).

IN PRACTICE:

“These findings carry significant public health implications for formulating effective intervention strategies and environmental policies to better protect women’s health, particularly in countries with relatively high levels of air pollution and a large population with diabetes, such as China,” the authors wrote.

SOURCE:

The study, led by Yang Shen, Key Laboratory of Public Health Safety of the Ministry of Education and National Health Commission Key Laboratory of Health Technology Assessment, School of Public Health, Fudan University, Shanghai, China, was published online in Diabetes Care.

LIMITATIONS:

An error in the measurement of particulate matter exposure may have been possible as residential address estimates were used as a proxy for actual personal exposure. Questionnaires were used to retrospectively collect information on parameters such as smoking and alcohol consumption, which may have introduced recall bias. Data on potential confounders, such as diet and physical activity, were not included. Distinction between type 1 and type 2 diabetes was not reported owing to data collection–related limitations.

DISCLOSURES:

The study was supported by the National Key Research and Development Program of China, Henan Key Research and Development Program, State Key Laboratory of Resources and Environmental Information System, and Three-Year Public Health Action Plan of Shanghai. The authors declared no conflicts of interest.

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

TOPLINE:

Long-term exposure to fine particulate matter is associated with higher fasting blood glucose (FBG) levels and an increased type 2 diabetes risk, significantly contributing to the diabetes-related health burden among women of reproductive age.

METHODOLOGY:

• Exposure to fine particulate matter < 2.5 µm (PM2.5) is a known risk factor for type 2 diabetes, but its effect on women of reproductive age, who undergo hormonal fluctuations during reproductive events, is not well studied.
• Researchers evaluated the association of long-term exposure to PM2.5 with FBG levels and diabetes risk in 20,076,032 eligible women of reproductive age (average age, 27.04 years) across 350 cities in China between 2010 and 2015.
• They assessed PM2.5 exposure at the participants’ residential addresses and calculated average long-term exposure at 1 (lag 1 year), 2 (lag 2 years), and 3 years (lag 3 years) before the survey date, as defined by the World Health Organization (WHO).
• The primary outcomes were FBG levels and diabetes prevalence (FBG, ≥ 7 mmol/L, classified as diabetes; FBG, 6.1-7 mmol/L, classified as prediabetes).
• The study also evaluated the diabetes burden attributed to long-term PM2.5 exposure as per the Chinese National Ambient Air Quality Standards (annual mean PM2.5 exposure limit, > 35 µg/m³) and the WHO air quality guideline (annual mean PM2.5 exposure limit, > 5 µg/m³).

TAKEAWAY:

• The median PM2.5 exposure levels over lag periods of 1, 2, and 3 years were 67, 67, and 66 µg/m³, respectively, exceeding the WHO limit by more than 13-fold.
• Each interquartile range increase in the 3-year average PM2.5 exposure by 27 μg/m³ raised FBG levels by 0.078 mmol/L (P < .05), risk for diabetes by 18% (odds ratio [OR], 1.18; 95% CI, 1.16-1.19), and risk for prediabetes by 5% (OR, 1.05; 95% CI, 1.04-1.05).
• Long-term exposure to PM2.5 > 5 µg/m³ and 35 µg/m³ in the previous 3 years corresponded to an additional 41.7 (95% CI, 39.3-44.0) and 78.6 (95% CI, 74.5-82.6) thousand cases of diabetes nationwide, respectively.
• A higher PM2.5 exposure increased FBG levels and risk for diabetes in women with overweight or obesity vs those without and in those aged ≥ 35 years vs < 35 years (P < .001).

IN PRACTICE:

“These findings carry significant public health implications for formulating effective intervention strategies and environmental policies to better protect women’s health, particularly in countries with relatively high levels of air pollution and a large population with diabetes, such as China,” the authors wrote.

SOURCE:

The study, led by Yang Shen, Key Laboratory of Public Health Safety of the Ministry of Education and National Health Commission Key Laboratory of Health Technology Assessment, School of Public Health, Fudan University, Shanghai, China, was published online in Diabetes Care.

LIMITATIONS:

An error in the measurement of particulate matter exposure may have been possible as residential address estimates were used as a proxy for actual personal exposure. Questionnaires were used to retrospectively collect information on parameters such as smoking and alcohol consumption, which may have introduced recall bias. Data on potential confounders, such as diet and physical activity, were not included. Distinction between type 1 and type 2 diabetes was not reported owing to data collection–related limitations.

DISCLOSURES:

The study was supported by the National Key Research and Development Program of China, Henan Key Research and Development Program, State Key Laboratory of Resources and Environmental Information System, and Three-Year Public Health Action Plan of Shanghai. The authors declared no conflicts of interest.

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

TOPLINE:

Long-term exposure to fine particulate matter is associated with higher fasting blood glucose (FBG) levels and an increased type 2 diabetes risk, significantly contributing to the diabetes-related health burden among women of reproductive age.

METHODOLOGY:

• Exposure to fine particulate matter < 2.5 µm (PM2.5) is a known risk factor for type 2 diabetes, but its effect on women of reproductive age, who undergo hormonal fluctuations during reproductive events, is not well studied.
• Researchers evaluated the association of long-term exposure to PM2.5 with FBG levels and diabetes risk in 20,076,032 eligible women of reproductive age (average age, 27.04 years) across 350 cities in China between 2010 and 2015.
• They assessed PM2.5 exposure at the participants’ residential addresses and calculated average long-term exposure at 1 (lag 1 year), 2 (lag 2 years), and 3 years (lag 3 years) before the survey date, as defined by the World Health Organization (WHO).
• The primary outcomes were FBG levels and diabetes prevalence (FBG, ≥ 7 mmol/L, classified as diabetes; FBG, 6.1-7 mmol/L, classified as prediabetes).
• The study also evaluated the diabetes burden attributed to long-term PM2.5 exposure as per the Chinese National Ambient Air Quality Standards (annual mean PM2.5 exposure limit, > 35 µg/m³) and the WHO air quality guideline (annual mean PM2.5 exposure limit, > 5 µg/m³).

TAKEAWAY:

• The median PM2.5 exposure levels over lag periods of 1, 2, and 3 years were 67, 67, and 66 µg/m³, respectively, exceeding the WHO limit by more than 13-fold.
• Each interquartile range increase in the 3-year average PM2.5 exposure by 27 μg/m³ raised FBG levels by 0.078 mmol/L (P < .05), risk for diabetes by 18% (odds ratio [OR], 1.18; 95% CI, 1.16-1.19), and risk for prediabetes by 5% (OR, 1.05; 95% CI, 1.04-1.05).
• Long-term exposure to PM2.5 > 5 µg/m³ and 35 µg/m³ in the previous 3 years corresponded to an additional 41.7 (95% CI, 39.3-44.0) and 78.6 (95% CI, 74.5-82.6) thousand cases of diabetes nationwide, respectively.
• A higher PM2.5 exposure increased FBG levels and risk for diabetes in women with overweight or obesity vs those without and in those aged ≥ 35 years vs < 35 years (P < .001).

IN PRACTICE:

“These findings carry significant public health implications for formulating effective intervention strategies and environmental policies to better protect women’s health, particularly in countries with relatively high levels of air pollution and a large population with diabetes, such as China,” the authors wrote.

SOURCE:

The study, led by Yang Shen, Key Laboratory of Public Health Safety of the Ministry of Education and National Health Commission Key Laboratory of Health Technology Assessment, School of Public Health, Fudan University, Shanghai, China, was published online in Diabetes Care.

LIMITATIONS:

An error in the measurement of particulate matter exposure may have been possible as residential address estimates were used as a proxy for actual personal exposure. Questionnaires were used to retrospectively collect information on parameters such as smoking and alcohol consumption, which may have introduced recall bias. Data on potential confounders, such as diet and physical activity, were not included. Distinction between type 1 and type 2 diabetes was not reported owing to data collection–related limitations.

DISCLOSURES:

The study was supported by the National Key Research and Development Program of China, Henan Key Research and Development Program, State Key Laboratory of Resources and Environmental Information System, and Three-Year Public Health Action Plan of Shanghai. The authors declared no conflicts of interest.

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

TOPLINE:

Inebilizumab-cdon, a monoclonal antibody that depletes B cells, reduces the risk for flares without showing any new safety signals in patients with immunoglobulin G4-related disease (IgG4-RD) who have multiorgan disease and are on glucocorticoid therapy.

METHODOLOGY:

• IgG4-RD is an immune-mediated, fibroinflammatory condition that affects multiple organs, causing irreversible organ damage. MITIGATE is the first multinational, placebo-controlled trial involving patients with IgG4-RD.
• Researchers evaluated the efficacy and safety of inebilizumab in 135 adult patients at risk for flares due to a history of multiorgan disease and active disease requiring treatment with glucocorticoids.
• The patients were randomly assigned to receive 300-mg intravenous inebilizumab or placebo on day 1, day 15, and week 26.
• The primary endpoint was the time to the first treated and adjudicated IgG4-RD flare within 52 weeks.
• The secondary endpoints included the annualized flare rate, flare-free and treatment-free complete remission, and flare-free and corticosteroid-free complete remission.

TAKEAWAY:

• Compared with the placebo, inebilizumab reduced the risk for IgG4-RD flares by 87% during the 52-week trial period (hazard ratio, 0.13; P < .0001).
• All the secondary endpoints showed improvement following treatment with inebilizumab.
• The most common adverse reactions with inebilizumab, as observed in a previous trial for neuromyelitis optica spectrum disorder, were urinary tract infection and arthralgia.
• There were no new safety signals in the MITIGATE trial.

IN PRACTICE:

“These data mark a major milestone for the IgG4-RD community and provide substantial insight into not only how inebilizumab can help manage IgG4-RD but also key insights into the nature of this condition,” John Stone, MD, MPH, principal investigator, said in a news release.

SOURCE:

Dr. Stone, a professor of medicine at the Harvard Medical School and the Edward A. Fox Chair in Medicine at the Massachusetts General Hospital, Boston, led this study.

LIMITATIONS:

This press release did not discuss any limitations of the current study.

DISCLOSURES:

This study was funded by Mitsubishi Tanabe Pharma and Hansoh Pharma and sponsored by Amgen. The author disclosures were not available.

A version of this article appeared on Medscape.com.

TOPLINE:

Inebilizumab-cdon, a monoclonal antibody that depletes B cells, reduces the risk for flares without showing any new safety signals in patients with immunoglobulin G4-related disease (IgG4-RD) who have multiorgan disease and are on glucocorticoid therapy.

METHODOLOGY:

• IgG4-RD is an immune-mediated, fibroinflammatory condition that affects multiple organs, causing irreversible organ damage. MITIGATE is the first multinational, placebo-controlled trial involving patients with IgG4-RD.
• Researchers evaluated the efficacy and safety of inebilizumab in 135 adult patients at risk for flares due to a history of multiorgan disease and active disease requiring treatment with glucocorticoids.
• The patients were randomly assigned to receive 300-mg intravenous inebilizumab or placebo on day 1, day 15, and week 26.
• The primary endpoint was the time to the first treated and adjudicated IgG4-RD flare within 52 weeks.
• The secondary endpoints included the annualized flare rate, flare-free and treatment-free complete remission, and flare-free and corticosteroid-free complete remission.

TAKEAWAY:

• Compared with the placebo, inebilizumab reduced the risk for IgG4-RD flares by 87% during the 52-week trial period (hazard ratio, 0.13; P < .0001).
• All the secondary endpoints showed improvement following treatment with inebilizumab.
• The most common adverse reactions with inebilizumab, as observed in a previous trial for neuromyelitis optica spectrum disorder, were urinary tract infection and arthralgia.
• There were no new safety signals in the MITIGATE trial.

IN PRACTICE:

“These data mark a major milestone for the IgG4-RD community and provide substantial insight into not only how inebilizumab can help manage IgG4-RD but also key insights into the nature of this condition,” John Stone, MD, MPH, principal investigator, said in a news release.

SOURCE:

Dr. Stone, a professor of medicine at the Harvard Medical School and the Edward A. Fox Chair in Medicine at the Massachusetts General Hospital, Boston, led this study.

LIMITATIONS:

This press release did not discuss any limitations of the current study.

DISCLOSURES:

This study was funded by Mitsubishi Tanabe Pharma and Hansoh Pharma and sponsored by Amgen. The author disclosures were not available.

A version of this article appeared on Medscape.com.

TOPLINE:

Inebilizumab-cdon, a monoclonal antibody that depletes B cells, reduces the risk for flares without showing any new safety signals in patients with immunoglobulin G4-related disease (IgG4-RD) who have multiorgan disease and are on glucocorticoid therapy.

METHODOLOGY:

• IgG4-RD is an immune-mediated, fibroinflammatory condition that affects multiple organs, causing irreversible organ damage. MITIGATE is the first multinational, placebo-controlled trial involving patients with IgG4-RD.
• Researchers evaluated the efficacy and safety of inebilizumab in 135 adult patients at risk for flares due to a history of multiorgan disease and active disease requiring treatment with glucocorticoids.
• The patients were randomly assigned to receive 300-mg intravenous inebilizumab or placebo on day 1, day 15, and week 26.
• The primary endpoint was the time to the first treated and adjudicated IgG4-RD flare within 52 weeks.
• The secondary endpoints included the annualized flare rate, flare-free and treatment-free complete remission, and flare-free and corticosteroid-free complete remission.

TAKEAWAY:

• Compared with the placebo, inebilizumab reduced the risk for IgG4-RD flares by 87% during the 52-week trial period (hazard ratio, 0.13; P < .0001).
• All the secondary endpoints showed improvement following treatment with inebilizumab.
• The most common adverse reactions with inebilizumab, as observed in a previous trial for neuromyelitis optica spectrum disorder, were urinary tract infection and arthralgia.
• There were no new safety signals in the MITIGATE trial.

IN PRACTICE:

“These data mark a major milestone for the IgG4-RD community and provide substantial insight into not only how inebilizumab can help manage IgG4-RD but also key insights into the nature of this condition,” John Stone, MD, MPH, principal investigator, said in a news release.

SOURCE:

Dr. Stone, a professor of medicine at the Harvard Medical School and the Edward A. Fox Chair in Medicine at the Massachusetts General Hospital, Boston, led this study.

LIMITATIONS:

This press release did not discuss any limitations of the current study.

DISCLOSURES:

This study was funded by Mitsubishi Tanabe Pharma and Hansoh Pharma and sponsored by Amgen. The author disclosures were not available.

A version of this article appeared on Medscape.com.

When Ezra Spier was diagnosed with long COVID in late 2022, his main symptom, postexertional malaise, caused fatigue so severe that it forced him to quit his job as a technology entrepreneur. Since then, it’s been a tough road for Spier, 37, who said he wouldn’t wish his hellish condition on anyone. 

Last spring, he enrolled in a clinical trial of a new long COVID therapy at Stanford University, and he’s about to start another at the University of California, San Francisco. 

For Spier, who lives in Oakland, California, being part of the clinical trials connected him with people dealing with similar health issues while also moving the needle toward better treatments for everyone. Yet many potential participants are unaware that these clinical trials exist. Clinical trial researchers also express frustration over the challenge of enrolling participants.

That’s why Spier created a new website to help match long COVID patients with clinical trials that can help.

“I wanted a way to make long COVID clinical trials more accessible to the general public,” he said. Spier’s website, aptly named Long Covid Studies, launched in March. The site already includes details from about 550 trials globally and, in the future, will include many more.
 

It’s Not the Number of Studies, It’s Navigating Them

In all, nearly 9300 long COVID trials are listed on ClinicalTrials.gov. But many patients find the site difficult to navigate, said David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City. He said Spier’s website helps make trials easier for patients to manage in ways that remove the enrollment challenges.

“Ezra’s platform pulls data from ClinicalTrials.gov and puts it into a space that’s much easier for patients to manage,” said Dr. Putrino. The site only includes the most relevant information, such as the study location, eligibility, and purpose and how to sign up. 

Another of Spier’s goals is to make the process easier for patients who are already marginalized and often excluded from the healthcare system. Long COVID disproportionately impacts people in minority ethnic groups and women, as well as those who are impoverished or live in rural areas. 

According to the National Institutes of Health (NIH), 1 in 4 patients with severe long COVID-19 are Black or Hispanic whereas only 1 in 7 are White. Yet participation by White persons in clinical trials is much higher overall: 77% of participants are White, compared with only 14% for Black persons and 15% for Hispanic persons. Without more balanced representation, research becomes skewed and less accurate, said Grace McComsey, MD, who leads one of the 15 nationwide long COVID centers funded by the federal RECOVER (Researching COVID to Enhance Recovery) Initiative in Cleveland. 

Websites that are easier for the layperson to access would allow for wider participation, said McComsey.
 

Too Many Barriers to Entry

A study published in the Journal of Applied Gerontology found that transportation plays an outsized role in influencing study participation, which may also lead to less diverse participation.

Decentralized trials — in which participants receive therapy at home — also make enrolling in clinical trials easier for marginalized patients and those too sick to make it to a research center, said Dr. Putrino. Research published recently in The American Journal of Medicine demonstrated that for many patients, remote studies are the future of COVID research. The study, focusing on the efficacy of Paxlovid, recruited patients living in the 48 contiguous US states. Participation was entirely remote. 

“We need to have more consideration for bedbound and housebound patients in our research,” said Dr. Putrino. “Some people don’t have the ability to show up to a prestigious university to take part in an academic trial.”

Dr. Putrino and colleagues at Yale School of Medicine’s Yale COVID Recovery Study plan to release a paper in the near future on the methodology for running decentralized or remote studies that could provide guidance for researchers elsewhere. 

Decentralized studies serve a larger audience, but they’re also more expensive and cost has plagued long COVID research from the start, said Michael Peluso, MD, an assistant research professor of infectious medicine at UCSF School of Medicine, University of California, San Francisco. 

“You need to have a staff in place that’s trained to do home visits in order to conduct remote trials,” Dr. Peluso said, adding that his biggest challenge has been connecting patients to appropriate clinical trials. 

Individual eligibility has been an ongoing issue. For example, Dr. Peluso’s current trials are testing monoclonal antibodies — antibodies produced by cloning unique white blood cells to target viral persistence, which is thought to be a cause of long COVID. Only patients who were infected with certain variants of acute COVID are eligible because of the antibodies needed to target SARS-CoV-2 spike proteins. 

“This can lead to a lot of frustration among patients who might think they can participate, but aren’t eligible,” said Dr. Peluso.
 

Long Fight for Better Long COVID Research

For Spier, one of the hardest parts of his health issues and lack of energy is that they have sharply curtailed his social interactions with friends and colleagues. 

He has channeled his energies into researching new treatments that could potentially improve his symptoms. That research is partly what drove him to create the Long Covid Studies website.

His goal is still to help others with long COVID find trials that can improve their symptoms as well. The more people who participate, the closer scientists will come to providing effective treatments for everyone, he said.

“For all my frustrations, we’re still at the forefront of science globally,” he said. “And if we have the level of funding the NIH is equipped to provide, we can show the world what’s possible with long COVID research.”

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

When Ezra Spier was diagnosed with long COVID in late 2022, his main symptom, postexertional malaise, caused fatigue so severe that it forced him to quit his job as a technology entrepreneur. Since then, it’s been a tough road for Spier, 37, who said he wouldn’t wish his hellish condition on anyone. 

Last spring, he enrolled in a clinical trial of a new long COVID therapy at Stanford University, and he’s about to start another at the University of California, San Francisco. 

For Spier, who lives in Oakland, California, being part of the clinical trials connected him with people dealing with similar health issues while also moving the needle toward better treatments for everyone. Yet many potential participants are unaware that these clinical trials exist. Clinical trial researchers also express frustration over the challenge of enrolling participants.

That’s why Spier created a new website to help match long COVID patients with clinical trials that can help.

“I wanted a way to make long COVID clinical trials more accessible to the general public,” he said. Spier’s website, aptly named Long Covid Studies, launched in March. The site already includes details from about 550 trials globally and, in the future, will include many more.
 

It’s Not the Number of Studies, It’s Navigating Them

In all, nearly 9300 long COVID trials are listed on ClinicalTrials.gov. But many patients find the site difficult to navigate, said David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City. He said Spier’s website helps make trials easier for patients to manage in ways that remove the enrollment challenges.

“Ezra’s platform pulls data from ClinicalTrials.gov and puts it into a space that’s much easier for patients to manage,” said Dr. Putrino. The site only includes the most relevant information, such as the study location, eligibility, and purpose and how to sign up. 

Another of Spier’s goals is to make the process easier for patients who are already marginalized and often excluded from the healthcare system. Long COVID disproportionately impacts people in minority ethnic groups and women, as well as those who are impoverished or live in rural areas. 

According to the National Institutes of Health (NIH), 1 in 4 patients with severe long COVID-19 are Black or Hispanic whereas only 1 in 7 are White. Yet participation by White persons in clinical trials is much higher overall: 77% of participants are White, compared with only 14% for Black persons and 15% for Hispanic persons. Without more balanced representation, research becomes skewed and less accurate, said Grace McComsey, MD, who leads one of the 15 nationwide long COVID centers funded by the federal RECOVER (Researching COVID to Enhance Recovery) Initiative in Cleveland. 

Websites that are easier for the layperson to access would allow for wider participation, said McComsey.
 

Too Many Barriers to Entry

A study published in the Journal of Applied Gerontology found that transportation plays an outsized role in influencing study participation, which may also lead to less diverse participation.

Decentralized trials — in which participants receive therapy at home — also make enrolling in clinical trials easier for marginalized patients and those too sick to make it to a research center, said Dr. Putrino. Research published recently in The American Journal of Medicine demonstrated that for many patients, remote studies are the future of COVID research. The study, focusing on the efficacy of Paxlovid, recruited patients living in the 48 contiguous US states. Participation was entirely remote. 

“We need to have more consideration for bedbound and housebound patients in our research,” said Dr. Putrino. “Some people don’t have the ability to show up to a prestigious university to take part in an academic trial.”

Dr. Putrino and colleagues at Yale School of Medicine’s Yale COVID Recovery Study plan to release a paper in the near future on the methodology for running decentralized or remote studies that could provide guidance for researchers elsewhere. 

Decentralized studies serve a larger audience, but they’re also more expensive and cost has plagued long COVID research from the start, said Michael Peluso, MD, an assistant research professor of infectious medicine at UCSF School of Medicine, University of California, San Francisco. 

“You need to have a staff in place that’s trained to do home visits in order to conduct remote trials,” Dr. Peluso said, adding that his biggest challenge has been connecting patients to appropriate clinical trials. 

Individual eligibility has been an ongoing issue. For example, Dr. Peluso’s current trials are testing monoclonal antibodies — antibodies produced by cloning unique white blood cells to target viral persistence, which is thought to be a cause of long COVID. Only patients who were infected with certain variants of acute COVID are eligible because of the antibodies needed to target SARS-CoV-2 spike proteins. 

“This can lead to a lot of frustration among patients who might think they can participate, but aren’t eligible,” said Dr. Peluso.
 

Long Fight for Better Long COVID Research

For Spier, one of the hardest parts of his health issues and lack of energy is that they have sharply curtailed his social interactions with friends and colleagues. 

He has channeled his energies into researching new treatments that could potentially improve his symptoms. That research is partly what drove him to create the Long Covid Studies website.

His goal is still to help others with long COVID find trials that can improve their symptoms as well. The more people who participate, the closer scientists will come to providing effective treatments for everyone, he said.

“For all my frustrations, we’re still at the forefront of science globally,” he said. “And if we have the level of funding the NIH is equipped to provide, we can show the world what’s possible with long COVID research.”

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

When Ezra Spier was diagnosed with long COVID in late 2022, his main symptom, postexertional malaise, caused fatigue so severe that it forced him to quit his job as a technology entrepreneur. Since then, it’s been a tough road for Spier, 37, who said he wouldn’t wish his hellish condition on anyone. 

Last spring, he enrolled in a clinical trial of a new long COVID therapy at Stanford University, and he’s about to start another at the University of California, San Francisco. 

For Spier, who lives in Oakland, California, being part of the clinical trials connected him with people dealing with similar health issues while also moving the needle toward better treatments for everyone. Yet many potential participants are unaware that these clinical trials exist. Clinical trial researchers also express frustration over the challenge of enrolling participants.

That’s why Spier created a new website to help match long COVID patients with clinical trials that can help.

“I wanted a way to make long COVID clinical trials more accessible to the general public,” he said. Spier’s website, aptly named Long Covid Studies, launched in March. The site already includes details from about 550 trials globally and, in the future, will include many more.
 

It’s Not the Number of Studies, It’s Navigating Them

In all, nearly 9300 long COVID trials are listed on ClinicalTrials.gov. But many patients find the site difficult to navigate, said David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City. He said Spier’s website helps make trials easier for patients to manage in ways that remove the enrollment challenges.

“Ezra’s platform pulls data from ClinicalTrials.gov and puts it into a space that’s much easier for patients to manage,” said Dr. Putrino. The site only includes the most relevant information, such as the study location, eligibility, and purpose and how to sign up. 

Another of Spier’s goals is to make the process easier for patients who are already marginalized and often excluded from the healthcare system. Long COVID disproportionately impacts people in minority ethnic groups and women, as well as those who are impoverished or live in rural areas. 

According to the National Institutes of Health (NIH), 1 in 4 patients with severe long COVID-19 are Black or Hispanic whereas only 1 in 7 are White. Yet participation by White persons in clinical trials is much higher overall: 77% of participants are White, compared with only 14% for Black persons and 15% for Hispanic persons. Without more balanced representation, research becomes skewed and less accurate, said Grace McComsey, MD, who leads one of the 15 nationwide long COVID centers funded by the federal RECOVER (Researching COVID to Enhance Recovery) Initiative in Cleveland. 

Websites that are easier for the layperson to access would allow for wider participation, said McComsey.
 

Too Many Barriers to Entry

A study published in the Journal of Applied Gerontology found that transportation plays an outsized role in influencing study participation, which may also lead to less diverse participation.

Decentralized trials — in which participants receive therapy at home — also make enrolling in clinical trials easier for marginalized patients and those too sick to make it to a research center, said Dr. Putrino. Research published recently in The American Journal of Medicine demonstrated that for many patients, remote studies are the future of COVID research. The study, focusing on the efficacy of Paxlovid, recruited patients living in the 48 contiguous US states. Participation was entirely remote. 

“We need to have more consideration for bedbound and housebound patients in our research,” said Dr. Putrino. “Some people don’t have the ability to show up to a prestigious university to take part in an academic trial.”

Dr. Putrino and colleagues at Yale School of Medicine’s Yale COVID Recovery Study plan to release a paper in the near future on the methodology for running decentralized or remote studies that could provide guidance for researchers elsewhere. 

Decentralized studies serve a larger audience, but they’re also more expensive and cost has plagued long COVID research from the start, said Michael Peluso, MD, an assistant research professor of infectious medicine at UCSF School of Medicine, University of California, San Francisco. 

“You need to have a staff in place that’s trained to do home visits in order to conduct remote trials,” Dr. Peluso said, adding that his biggest challenge has been connecting patients to appropriate clinical trials. 

Individual eligibility has been an ongoing issue. For example, Dr. Peluso’s current trials are testing monoclonal antibodies — antibodies produced by cloning unique white blood cells to target viral persistence, which is thought to be a cause of long COVID. Only patients who were infected with certain variants of acute COVID are eligible because of the antibodies needed to target SARS-CoV-2 spike proteins. 

“This can lead to a lot of frustration among patients who might think they can participate, but aren’t eligible,” said Dr. Peluso.
 

Long Fight for Better Long COVID Research

For Spier, one of the hardest parts of his health issues and lack of energy is that they have sharply curtailed his social interactions with friends and colleagues. 

He has channeled his energies into researching new treatments that could potentially improve his symptoms. That research is partly what drove him to create the Long Covid Studies website.

His goal is still to help others with long COVID find trials that can improve their symptoms as well. The more people who participate, the closer scientists will come to providing effective treatments for everyone, he said.

“For all my frustrations, we’re still at the forefront of science globally,” he said. “And if we have the level of funding the NIH is equipped to provide, we can show the world what’s possible with long COVID research.”

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

Non-respiratory symptoms including poor sleep, fatigue, pain, anxiety, and depressive symptoms were prevalent among adults with cystic fibrosis (AwCF) and persisted after 1 year of follow-up, based on data from more than 200 individuals in a study presented at the American Thoracic Society (ATS) 2024 International Conference.

“People with cystic fibrosis have qualitatively reported burden from extrapulmonary symptoms that were not being addressed by their health care providers; this is the first study to examine these symptoms concurrently in a large sample over time,” said lead author Kristin A. Riekert, PhD, of Johns Hopkins University, Baltimore, in an interview.

Previous cross-sectional studies have shown a high prevalence of poor sleep quality, fatigue, pain, depression, and anxiety among AwCF, but longitudinal data showing the persistence of symptoms are lacking, Dr. Riekert and colleagues noted in their abstract.
 

Sleep Quality, Anxiety, and Other Assessments

The researchers recruited a total of 236 AwCF aged 18 years and older from two cystic fibrosis (CF) centers between April 2021 and August 2022. They examined the prevalence of poor sleep quality, fatigue pain, depression, and anxiety in AwCF on the basis of five assessments: At baseline and at 3, 6, 9, and 12 months.

Participants were assessed via an online survey using the Fatigue Severity Scale (cutoff, > 4), Pittsburgh Sleep Quality Index (cutoff, > 5), Patient Health Questionnaire (cutoff, > 9), Generalized Anxiety Disorder (cutoff, > 9), and PROMIS Pain Intensity (cutoff, > 50 T score). Chronic symptoms were defined as positive scores on four or more assessments for individuals who completed four or five time-point assessments. The mean age of the participants was 37 years, 52% were women, 95% were non-Hispanic White, and 86% had been prescribed CF modulator therapy.

At 12 months, 62% of participants reported poor sleep, and 34% reported fatigue. In addition, 17% reported depressive symptoms, 14% reported anxiety symptoms, and 7% reported pain at 12 months.

Overall, 49% of participants met the criteria for chronic poor sleep quality, and 29% met the criteria for chronic fatigue, with positive assessments at four or more time points over the course of a year. In addition, 40%, 30%, and 18% of participants reported taking medication in the past 7 days for pain, mental health, and sleep, respectively.

The findings suggest that patients with CF might benefit from routine assessments of non-pulmonary symptoms in clinical care and from access to health care providers, including mental health professionals, to address non-pulmonary concerns, the researchers wrote in their abstract.

“We delayed starting the study until elexacaftor/tezacaftor/ivacaftor (ETI) was FDA-approved because there was an assumption that people with CF would have less fatigue because of respiratory improvements from ETI,” Dr. Riekert told this news organization. “Instead, the prevalence of fatigue and poor sleep quality was higher and more chronic than we had anticipated,” she noted.

However, “we were pleasantly surprised that depression and anxiety, while still prevalent, were less prevalent and chronic than previously reported,” Dr. Riekert said in an interview. “We attribute this to the CF Foundation’s mental health initiative that has increased the frequency of annual screening for depression and anxiety and provided resources to help people with cystic fibrosis obtain mental health services,” she said.

The study findings suggest that clinicians should assess people with CF for chronic fatigue and poor sleep along with depression and anxiety and provide treatment or referral, Dr. Riekert said. “For example, cognitive behavioral therapy can effectively treat all the symptoms that were measured in our study,” she noted.

Limitations of the study include the lack of data on how the non-respiratory symptoms interact with respiratory symptoms or pulmonary exacerbations, said Dr. Riekert. “While we assessed these symptoms five times, it was for a year; longer-term follow-up seems merited given our findings,” she said. In addition, “we need to study approaches to make cognitive behavioral therapy and other therapy more accessible for people with cystic fibrosis,” Dr. Riekert said.
 

Targeting Non-Pulmonary Dimensions of CF Care

The current study highlights an aspect of quality of life that is often forgotten when managing adults with CF and may affect their well-being despite effective therapy to improve function and prolong life, said Wissam Chatila, MD, professor of thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University, Philadelphia, in an interview.

The high incidence of poor sleep, fatigue, depression, and anxiety seen in the current study was “somewhat surprising,” Dr. Chatila said. Also somewhat surprising was the chronicity of the symptoms considering the cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies (designed to correct the malfunctioning protein made by the CFTR gene) that have changed the face of CF, he noted.

However, recent growth in the number of adult patients with CF (more than 50% in certain countries) has led to a change in pathologies that physicians have to manage, and the current study addresses some of the emerging pathologies, said Dr. Chatila.

“Beyond demonstrating survival data from registries and other epidemiologic studies, this study sheds light on the need to address patient-reported outcomes that may or may not be directly related to the pulmonary and GI effects of the CFTR modulators,” he said. “Recognizing the extent of the dysfunction that many CF patients continue to suffer from will eventually lead to identifying factors that contribute to poor outcomes and the mechanisms involved,” he added.

Overall, the current study illustrates the potential benefits of offering personalized medicine to adults with CF that improves not only their physical function but also their mental health, Dr. Chatila said.

The study was funded by the Cystic Fibrosis Foundation. Dr. Riekert had no financial conflicts to disclose. Dr. Chatila had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Non-respiratory symptoms including poor sleep, fatigue, pain, anxiety, and depressive symptoms were prevalent among adults with cystic fibrosis (AwCF) and persisted after 1 year of follow-up, based on data from more than 200 individuals in a study presented at the American Thoracic Society (ATS) 2024 International Conference.

“People with cystic fibrosis have qualitatively reported burden from extrapulmonary symptoms that were not being addressed by their health care providers; this is the first study to examine these symptoms concurrently in a large sample over time,” said lead author Kristin A. Riekert, PhD, of Johns Hopkins University, Baltimore, in an interview.

Previous cross-sectional studies have shown a high prevalence of poor sleep quality, fatigue, pain, depression, and anxiety among AwCF, but longitudinal data showing the persistence of symptoms are lacking, Dr. Riekert and colleagues noted in their abstract.
 

Sleep Quality, Anxiety, and Other Assessments

The researchers recruited a total of 236 AwCF aged 18 years and older from two cystic fibrosis (CF) centers between April 2021 and August 2022. They examined the prevalence of poor sleep quality, fatigue pain, depression, and anxiety in AwCF on the basis of five assessments: At baseline and at 3, 6, 9, and 12 months.

Participants were assessed via an online survey using the Fatigue Severity Scale (cutoff, > 4), Pittsburgh Sleep Quality Index (cutoff, > 5), Patient Health Questionnaire (cutoff, > 9), Generalized Anxiety Disorder (cutoff, > 9), and PROMIS Pain Intensity (cutoff, > 50 T score). Chronic symptoms were defined as positive scores on four or more assessments for individuals who completed four or five time-point assessments. The mean age of the participants was 37 years, 52% were women, 95% were non-Hispanic White, and 86% had been prescribed CF modulator therapy.

At 12 months, 62% of participants reported poor sleep, and 34% reported fatigue. In addition, 17% reported depressive symptoms, 14% reported anxiety symptoms, and 7% reported pain at 12 months.

Overall, 49% of participants met the criteria for chronic poor sleep quality, and 29% met the criteria for chronic fatigue, with positive assessments at four or more time points over the course of a year. In addition, 40%, 30%, and 18% of participants reported taking medication in the past 7 days for pain, mental health, and sleep, respectively.

The findings suggest that patients with CF might benefit from routine assessments of non-pulmonary symptoms in clinical care and from access to health care providers, including mental health professionals, to address non-pulmonary concerns, the researchers wrote in their abstract.

“We delayed starting the study until elexacaftor/tezacaftor/ivacaftor (ETI) was FDA-approved because there was an assumption that people with CF would have less fatigue because of respiratory improvements from ETI,” Dr. Riekert told this news organization. “Instead, the prevalence of fatigue and poor sleep quality was higher and more chronic than we had anticipated,” she noted.

However, “we were pleasantly surprised that depression and anxiety, while still prevalent, were less prevalent and chronic than previously reported,” Dr. Riekert said in an interview. “We attribute this to the CF Foundation’s mental health initiative that has increased the frequency of annual screening for depression and anxiety and provided resources to help people with cystic fibrosis obtain mental health services,” she said.

The study findings suggest that clinicians should assess people with CF for chronic fatigue and poor sleep along with depression and anxiety and provide treatment or referral, Dr. Riekert said. “For example, cognitive behavioral therapy can effectively treat all the symptoms that were measured in our study,” she noted.

Limitations of the study include the lack of data on how the non-respiratory symptoms interact with respiratory symptoms or pulmonary exacerbations, said Dr. Riekert. “While we assessed these symptoms five times, it was for a year; longer-term follow-up seems merited given our findings,” she said. In addition, “we need to study approaches to make cognitive behavioral therapy and other therapy more accessible for people with cystic fibrosis,” Dr. Riekert said.
 

Targeting Non-Pulmonary Dimensions of CF Care

The current study highlights an aspect of quality of life that is often forgotten when managing adults with CF and may affect their well-being despite effective therapy to improve function and prolong life, said Wissam Chatila, MD, professor of thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University, Philadelphia, in an interview.

The high incidence of poor sleep, fatigue, depression, and anxiety seen in the current study was “somewhat surprising,” Dr. Chatila said. Also somewhat surprising was the chronicity of the symptoms considering the cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies (designed to correct the malfunctioning protein made by the CFTR gene) that have changed the face of CF, he noted.

However, recent growth in the number of adult patients with CF (more than 50% in certain countries) has led to a change in pathologies that physicians have to manage, and the current study addresses some of the emerging pathologies, said Dr. Chatila.

“Beyond demonstrating survival data from registries and other epidemiologic studies, this study sheds light on the need to address patient-reported outcomes that may or may not be directly related to the pulmonary and GI effects of the CFTR modulators,” he said. “Recognizing the extent of the dysfunction that many CF patients continue to suffer from will eventually lead to identifying factors that contribute to poor outcomes and the mechanisms involved,” he added.

Overall, the current study illustrates the potential benefits of offering personalized medicine to adults with CF that improves not only their physical function but also their mental health, Dr. Chatila said.

The study was funded by the Cystic Fibrosis Foundation. Dr. Riekert had no financial conflicts to disclose. Dr. Chatila had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Non-respiratory symptoms including poor sleep, fatigue, pain, anxiety, and depressive symptoms were prevalent among adults with cystic fibrosis (AwCF) and persisted after 1 year of follow-up, based on data from more than 200 individuals in a study presented at the American Thoracic Society (ATS) 2024 International Conference.

“People with cystic fibrosis have qualitatively reported burden from extrapulmonary symptoms that were not being addressed by their health care providers; this is the first study to examine these symptoms concurrently in a large sample over time,” said lead author Kristin A. Riekert, PhD, of Johns Hopkins University, Baltimore, in an interview.

Previous cross-sectional studies have shown a high prevalence of poor sleep quality, fatigue, pain, depression, and anxiety among AwCF, but longitudinal data showing the persistence of symptoms are lacking, Dr. Riekert and colleagues noted in their abstract.
 

Sleep Quality, Anxiety, and Other Assessments

The researchers recruited a total of 236 AwCF aged 18 years and older from two cystic fibrosis (CF) centers between April 2021 and August 2022. They examined the prevalence of poor sleep quality, fatigue pain, depression, and anxiety in AwCF on the basis of five assessments: At baseline and at 3, 6, 9, and 12 months.

Participants were assessed via an online survey using the Fatigue Severity Scale (cutoff, > 4), Pittsburgh Sleep Quality Index (cutoff, > 5), Patient Health Questionnaire (cutoff, > 9), Generalized Anxiety Disorder (cutoff, > 9), and PROMIS Pain Intensity (cutoff, > 50 T score). Chronic symptoms were defined as positive scores on four or more assessments for individuals who completed four or five time-point assessments. The mean age of the participants was 37 years, 52% were women, 95% were non-Hispanic White, and 86% had been prescribed CF modulator therapy.

At 12 months, 62% of participants reported poor sleep, and 34% reported fatigue. In addition, 17% reported depressive symptoms, 14% reported anxiety symptoms, and 7% reported pain at 12 months.

Overall, 49% of participants met the criteria for chronic poor sleep quality, and 29% met the criteria for chronic fatigue, with positive assessments at four or more time points over the course of a year. In addition, 40%, 30%, and 18% of participants reported taking medication in the past 7 days for pain, mental health, and sleep, respectively.

The findings suggest that patients with CF might benefit from routine assessments of non-pulmonary symptoms in clinical care and from access to health care providers, including mental health professionals, to address non-pulmonary concerns, the researchers wrote in their abstract.

“We delayed starting the study until elexacaftor/tezacaftor/ivacaftor (ETI) was FDA-approved because there was an assumption that people with CF would have less fatigue because of respiratory improvements from ETI,” Dr. Riekert told this news organization. “Instead, the prevalence of fatigue and poor sleep quality was higher and more chronic than we had anticipated,” she noted.

However, “we were pleasantly surprised that depression and anxiety, while still prevalent, were less prevalent and chronic than previously reported,” Dr. Riekert said in an interview. “We attribute this to the CF Foundation’s mental health initiative that has increased the frequency of annual screening for depression and anxiety and provided resources to help people with cystic fibrosis obtain mental health services,” she said.

The study findings suggest that clinicians should assess people with CF for chronic fatigue and poor sleep along with depression and anxiety and provide treatment or referral, Dr. Riekert said. “For example, cognitive behavioral therapy can effectively treat all the symptoms that were measured in our study,” she noted.

Limitations of the study include the lack of data on how the non-respiratory symptoms interact with respiratory symptoms or pulmonary exacerbations, said Dr. Riekert. “While we assessed these symptoms five times, it was for a year; longer-term follow-up seems merited given our findings,” she said. In addition, “we need to study approaches to make cognitive behavioral therapy and other therapy more accessible for people with cystic fibrosis,” Dr. Riekert said.
 

Targeting Non-Pulmonary Dimensions of CF Care

The current study highlights an aspect of quality of life that is often forgotten when managing adults with CF and may affect their well-being despite effective therapy to improve function and prolong life, said Wissam Chatila, MD, professor of thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University, Philadelphia, in an interview.

The high incidence of poor sleep, fatigue, depression, and anxiety seen in the current study was “somewhat surprising,” Dr. Chatila said. Also somewhat surprising was the chronicity of the symptoms considering the cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies (designed to correct the malfunctioning protein made by the CFTR gene) that have changed the face of CF, he noted.

However, recent growth in the number of adult patients with CF (more than 50% in certain countries) has led to a change in pathologies that physicians have to manage, and the current study addresses some of the emerging pathologies, said Dr. Chatila.

“Beyond demonstrating survival data from registries and other epidemiologic studies, this study sheds light on the need to address patient-reported outcomes that may or may not be directly related to the pulmonary and GI effects of the CFTR modulators,” he said. “Recognizing the extent of the dysfunction that many CF patients continue to suffer from will eventually lead to identifying factors that contribute to poor outcomes and the mechanisms involved,” he added.

Overall, the current study illustrates the potential benefits of offering personalized medicine to adults with CF that improves not only their physical function but also their mental health, Dr. Chatila said.

The study was funded by the Cystic Fibrosis Foundation. Dr. Riekert had no financial conflicts to disclose. Dr. Chatila had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.