TOPLINE:

Individuals on an intermittent-fasting and protein-pacing (IF-P) diet had fewer gastrointestinal symptoms and increased diversity in gut microbiota than those on a calorie-restricted (CR) Mediterranean-style diet in a small, randomized trial.

METHODOLOGY:

• Researchers compared the effects on gastrointestinal symptoms, the gut microbiome, and circulating cytokines and metabolites of two low-calorie, 8-week dietary interventions: A Mediterranean-style continuous CR diet based on US dietary recommendations and an IF-P diet. The interventions were matched for energy intake.
• Participants included men and women with overweight/obesity who were randomly assigned to one of the two groups: CR diet (n = 20) and IF-P diet (n = 21).
• Researchers used samples and data from an ongoing randomized controlled trial (https://clinicaltrials.gov/study/NCT04327141) comparing the effects of the CR diet vs the IF-P diet on anthropometric and cardiometabolic outcomes.
• In a subanalysis for the current study, researchers compared outcomes in “high” and “low” responders to the IF-P regimen, based on relative weight loss.

TAKEAWAY:

• The IF-P diet resulted in more substantial reductions in patient-reported symptoms of gastrointestinal problems and more pronounced increases in gut microbiota diversity and in the abundance of microbial families and genera associated with favorable metabolic profiles, such as Christensenellaceae, Rikenellaceae, and Marvinbryantia, than the CR diet.
• The IF-P diet significantly increased cytokines linked to lipolysis, weight loss, inflammation, and the immune response.
• With the CR diet, metabolites associated with a longevity-related metabolic pathway increased.
• The subgroup analysis of high and low responders to the IF-P diet showed an increased abundance of certain bacteria associated with metabolic benefits and anti-inflammatory effects among high responders, whereas low responders showed an increased abundance of butyrate-producing and nutritionally adaptive species such as Eubacterium ventriosum and Roseburia inulinivorans.
• A fecal metabolome analysis revealed that high responders showed enrichment of fecal metabolites involved in lipid metabolism, whereas more prominent pathways in low responders were related to the metabolism of amino acids and peptides, as well as tyrosine metabolism and arginine biosynthesis.

IN PRACTICE:

“These findings shed light on the differential effects of IF regimens, including IF-P, as a promising dietary intervention for obesity management and microbiotic and metabolic health.”

SOURCE:

The study, with corresponding author Paul J. Arciero, PhD, of the Human Nutrition and Metabolism Laboratory at Skidmore College, Saratoga Springs, New York, was published online in Nature Communications.

LIMITATIONS:

The reliance on fecal samples to represent the gut microbiome may have overlooked potential microbial populations in the upper gastrointestinal tract. Other limitations include the short, 8-week duration of the trial and small number of patients.

DISCLOSURES:

The study was primarily funded by an unrestricted grant from Isagenix International LLC to Arciero, with secondary funding provided to a coauthor. Dr. Arciero is a consultant for Isagenix International LLC, is an advisory board member of the International Protein Board, and received financial compensation for books and keynote presentations on protein pacing. One coauthor is employed by the funder.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Individuals on an intermittent-fasting and protein-pacing (IF-P) diet had fewer gastrointestinal symptoms and increased diversity in gut microbiota than those on a calorie-restricted (CR) Mediterranean-style diet in a small, randomized trial.

METHODOLOGY:

• Researchers compared the effects on gastrointestinal symptoms, the gut microbiome, and circulating cytokines and metabolites of two low-calorie, 8-week dietary interventions: A Mediterranean-style continuous CR diet based on US dietary recommendations and an IF-P diet. The interventions were matched for energy intake.
• Participants included men and women with overweight/obesity who were randomly assigned to one of the two groups: CR diet (n = 20) and IF-P diet (n = 21).
• Researchers used samples and data from an ongoing randomized controlled trial (https://clinicaltrials.gov/study/NCT04327141) comparing the effects of the CR diet vs the IF-P diet on anthropometric and cardiometabolic outcomes.
• In a subanalysis for the current study, researchers compared outcomes in “high” and “low” responders to the IF-P regimen, based on relative weight loss.

TAKEAWAY:

• The IF-P diet resulted in more substantial reductions in patient-reported symptoms of gastrointestinal problems and more pronounced increases in gut microbiota diversity and in the abundance of microbial families and genera associated with favorable metabolic profiles, such as Christensenellaceae, Rikenellaceae, and Marvinbryantia, than the CR diet.
• The IF-P diet significantly increased cytokines linked to lipolysis, weight loss, inflammation, and the immune response.
• With the CR diet, metabolites associated with a longevity-related metabolic pathway increased.
• The subgroup analysis of high and low responders to the IF-P diet showed an increased abundance of certain bacteria associated with metabolic benefits and anti-inflammatory effects among high responders, whereas low responders showed an increased abundance of butyrate-producing and nutritionally adaptive species such as Eubacterium ventriosum and Roseburia inulinivorans.
• A fecal metabolome analysis revealed that high responders showed enrichment of fecal metabolites involved in lipid metabolism, whereas more prominent pathways in low responders were related to the metabolism of amino acids and peptides, as well as tyrosine metabolism and arginine biosynthesis.

IN PRACTICE:

“These findings shed light on the differential effects of IF regimens, including IF-P, as a promising dietary intervention for obesity management and microbiotic and metabolic health.”

SOURCE:

The study, with corresponding author Paul J. Arciero, PhD, of the Human Nutrition and Metabolism Laboratory at Skidmore College, Saratoga Springs, New York, was published online in Nature Communications.

LIMITATIONS:

The reliance on fecal samples to represent the gut microbiome may have overlooked potential microbial populations in the upper gastrointestinal tract. Other limitations include the short, 8-week duration of the trial and small number of patients.

DISCLOSURES:

The study was primarily funded by an unrestricted grant from Isagenix International LLC to Arciero, with secondary funding provided to a coauthor. Dr. Arciero is a consultant for Isagenix International LLC, is an advisory board member of the International Protein Board, and received financial compensation for books and keynote presentations on protein pacing. One coauthor is employed by the funder.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Individuals on an intermittent-fasting and protein-pacing (IF-P) diet had fewer gastrointestinal symptoms and increased diversity in gut microbiota than those on a calorie-restricted (CR) Mediterranean-style diet in a small, randomized trial.

METHODOLOGY:

• Researchers compared the effects on gastrointestinal symptoms, the gut microbiome, and circulating cytokines and metabolites of two low-calorie, 8-week dietary interventions: A Mediterranean-style continuous CR diet based on US dietary recommendations and an IF-P diet. The interventions were matched for energy intake.
• Participants included men and women with overweight/obesity who were randomly assigned to one of the two groups: CR diet (n = 20) and IF-P diet (n = 21).
• Researchers used samples and data from an ongoing randomized controlled trial (https://clinicaltrials.gov/study/NCT04327141) comparing the effects of the CR diet vs the IF-P diet on anthropometric and cardiometabolic outcomes.
• In a subanalysis for the current study, researchers compared outcomes in “high” and “low” responders to the IF-P regimen, based on relative weight loss.

TAKEAWAY:

• The IF-P diet resulted in more substantial reductions in patient-reported symptoms of gastrointestinal problems and more pronounced increases in gut microbiota diversity and in the abundance of microbial families and genera associated with favorable metabolic profiles, such as Christensenellaceae, Rikenellaceae, and Marvinbryantia, than the CR diet.
• The IF-P diet significantly increased cytokines linked to lipolysis, weight loss, inflammation, and the immune response.
• With the CR diet, metabolites associated with a longevity-related metabolic pathway increased.
• The subgroup analysis of high and low responders to the IF-P diet showed an increased abundance of certain bacteria associated with metabolic benefits and anti-inflammatory effects among high responders, whereas low responders showed an increased abundance of butyrate-producing and nutritionally adaptive species such as Eubacterium ventriosum and Roseburia inulinivorans.
• A fecal metabolome analysis revealed that high responders showed enrichment of fecal metabolites involved in lipid metabolism, whereas more prominent pathways in low responders were related to the metabolism of amino acids and peptides, as well as tyrosine metabolism and arginine biosynthesis.

IN PRACTICE:

“These findings shed light on the differential effects of IF regimens, including IF-P, as a promising dietary intervention for obesity management and microbiotic and metabolic health.”

SOURCE:

The study, with corresponding author Paul J. Arciero, PhD, of the Human Nutrition and Metabolism Laboratory at Skidmore College, Saratoga Springs, New York, was published online in Nature Communications.

LIMITATIONS:

The reliance on fecal samples to represent the gut microbiome may have overlooked potential microbial populations in the upper gastrointestinal tract. Other limitations include the short, 8-week duration of the trial and small number of patients.

DISCLOSURES:

The study was primarily funded by an unrestricted grant from Isagenix International LLC to Arciero, with secondary funding provided to a coauthor. Dr. Arciero is a consultant for Isagenix International LLC, is an advisory board member of the International Protein Board, and received financial compensation for books and keynote presentations on protein pacing. One coauthor is employed by the funder.
 

A version of this article appeared on Medscape.com.

SAN DIEGO — A new analysis of patients with new daily persistent headache (NDPH) lends insight into the condition and provides some hints as to some of the more effective treatments, including some calcitonin gene-related peptide (CGRP) inhibitors.

“There’s just not a lot [of information] about these patients,” Mark Burish, MD, PhD, associate professor of neurology at UT Houston, said in an interview. He presented the results of the survey at the annual meeting of the American Headache Society.

There have been some retrospective analyses of patient data, but that has a lot of potential for bias. “It’s only the patients who can afford to be there, and who needed those treatments, and so we want to do more of a general survey,” said Dr. Burish.

The results weren’t particularly surprising, and tended to reaffirm what was known anecdotally, including symptoms similar to those of migraine, but it gave some insight into treatments. “Some of the CGRP inhibitors and the onabotulinum toxin seem to be some of the more effective treatments, according to our survey, so those are probably worth looking into for these patients if you can get them approved by insurance, and if you can get patients to accept the idea they might have to give themselves an injection of some sort,” said Dr. Burish.

Despite having some promise, there was variation among CGRP inhibitors. Eptinezumab, rimegepant, and atogepant were commonly reported as effective, but others, such as erenumab and galcanezumab, were less often reported. “None of them were incredibly effective. These were just the best things we have at this time,” said Dr. Burish.
 

Additional Information on a Rare, Hard-to-Treat Condition

Jason Sico, MD, who moderated the session, was asked for comment. “I’m so appreciative that the team has looked at a new daily persistent headache. It’s a rare type of headache disorder. It’s also one that is notoriously difficult to treat and something that we that we really need to know more about. It is difficult to really get good, robust in-depth information on these patients, and the team did a really nice job with that,” said Dr. Sico, associate professor of neurology and internal medicine at Yale School of Medicine and national director of the Headache Centers of Excellence Program within the Veterans Health Administration.

He noted that the researchers found that opioids were the most commonly used acute treatment. That’s not surprising, but “it would be interesting to see what was tried before someone had gotten to opioids,” he said.

The findings also gave some unexpected insight into the condition. “I really found it striking that an overwhelming majority of patients reported brain fog. Given the context that it is daily persistent headache, one could surmise that they have brain fog a lot of the time,” said Dr. Sico.
 

‘A Good Data Set’

The researchers analyzed data from 337 international patients who responded to a survey. They also randomly selected 34 patients for an interview, and 32 of those were deemed likely to have NDPH. “So we really spent some effort making sure this was a good data set,” said Dr. Burish. The participant population was 72% female, 83.7% White, and 70.7% were based in the United States, though other countries included Canada, the United Kingdom, Australia, Ireland, Germany, Sweden, and Switzerland. The mean age was 41.2 years. The peak ages of onset were between 11 and 40 years, though there were a few cases in the 0-5 age range and over 70. Possible triggers that occurred in the 3 months before onset included psychological stressors (34%), infection or inflammation (32%, COVID infection (5%), injury or surgery (8%), or a change in medications (4%). No clear trigger was identified by 22% of respondents.

The survey included information on associated features, and frequently reported issues included brain fog (approximate 75%), sound sensitivity (about 62%), light sensitivity (57%), nausea (39%), smell sensitivity (32%), visual disturbances (28%), vomiting (13%), and chills (9%).
 

Insights Into Treatment Efficacy

Dr. Burish showed a slide of responses to questions about acute treatments that respondents had tried at least once and viewed as ‘completely effective,’ ‘mostly effective,’ or ‘somewhat effective.’

“No medicine was completely effective, which I think a lot of people know from NDPH. It is notoriously difficult to treat. The things on the top of the list are mostly opioids. There’s one (non-opioid), the DHE (dihydroergotamine) injection. All the way on the other side, you have diphenhydramine. The NSAIDs and triptans are mostly in the middle. We did ask about some of the wearable devices, and we had extra questions about, are you using it appropriately? Those are kind of in the middle or towards the bottom [in frequency],” said Dr. Burish.

There was a similar question regarding effective preventive medications that had been tried for at least 2 months or 3 months in the cause of onabotulinum toxin or CGRP medications. “This one had a little bit more of a pattern to it: A lot of the CGRP medications are up toward the top. It’s not perfect. Erenumab and galcanezumab are closer to the bottom, but it was interesting that a lot of the CGRP medicines were toward the top. Onabotulinum toxin was also somewhat toward the top. We looked at a few different anti-inflammatories. Methylprednisolone is kind of toward the upper half at least, whereas prednisone and montelukast are at the absolute bottom. And the prednisone is a pretty good dose, 50 milligrams or higher. There are some people thinking that this is an inflammation or infectious etiology, (but) it wasn’t that all of the anti-inflammatories were necessarily toward the top of the list,” said Dr. Burish.

Dr. Burish has received funding from Lundbeck. Dr. Sico has no relevant financial disclosures.

SAN DIEGO — A new analysis of patients with new daily persistent headache (NDPH) lends insight into the condition and provides some hints as to some of the more effective treatments, including some calcitonin gene-related peptide (CGRP) inhibitors.

“There’s just not a lot [of information] about these patients,” Mark Burish, MD, PhD, associate professor of neurology at UT Houston, said in an interview. He presented the results of the survey at the annual meeting of the American Headache Society.

There have been some retrospective analyses of patient data, but that has a lot of potential for bias. “It’s only the patients who can afford to be there, and who needed those treatments, and so we want to do more of a general survey,” said Dr. Burish.

The results weren’t particularly surprising, and tended to reaffirm what was known anecdotally, including symptoms similar to those of migraine, but it gave some insight into treatments. “Some of the CGRP inhibitors and the onabotulinum toxin seem to be some of the more effective treatments, according to our survey, so those are probably worth looking into for these patients if you can get them approved by insurance, and if you can get patients to accept the idea they might have to give themselves an injection of some sort,” said Dr. Burish.

Despite having some promise, there was variation among CGRP inhibitors. Eptinezumab, rimegepant, and atogepant were commonly reported as effective, but others, such as erenumab and galcanezumab, were less often reported. “None of them were incredibly effective. These were just the best things we have at this time,” said Dr. Burish.
 

Additional Information on a Rare, Hard-to-Treat Condition

Jason Sico, MD, who moderated the session, was asked for comment. “I’m so appreciative that the team has looked at a new daily persistent headache. It’s a rare type of headache disorder. It’s also one that is notoriously difficult to treat and something that we that we really need to know more about. It is difficult to really get good, robust in-depth information on these patients, and the team did a really nice job with that,” said Dr. Sico, associate professor of neurology and internal medicine at Yale School of Medicine and national director of the Headache Centers of Excellence Program within the Veterans Health Administration.

He noted that the researchers found that opioids were the most commonly used acute treatment. That’s not surprising, but “it would be interesting to see what was tried before someone had gotten to opioids,” he said.

The findings also gave some unexpected insight into the condition. “I really found it striking that an overwhelming majority of patients reported brain fog. Given the context that it is daily persistent headache, one could surmise that they have brain fog a lot of the time,” said Dr. Sico.
 

‘A Good Data Set’

The researchers analyzed data from 337 international patients who responded to a survey. They also randomly selected 34 patients for an interview, and 32 of those were deemed likely to have NDPH. “So we really spent some effort making sure this was a good data set,” said Dr. Burish. The participant population was 72% female, 83.7% White, and 70.7% were based in the United States, though other countries included Canada, the United Kingdom, Australia, Ireland, Germany, Sweden, and Switzerland. The mean age was 41.2 years. The peak ages of onset were between 11 and 40 years, though there were a few cases in the 0-5 age range and over 70. Possible triggers that occurred in the 3 months before onset included psychological stressors (34%), infection or inflammation (32%, COVID infection (5%), injury or surgery (8%), or a change in medications (4%). No clear trigger was identified by 22% of respondents.

The survey included information on associated features, and frequently reported issues included brain fog (approximate 75%), sound sensitivity (about 62%), light sensitivity (57%), nausea (39%), smell sensitivity (32%), visual disturbances (28%), vomiting (13%), and chills (9%).
 

Insights Into Treatment Efficacy

Dr. Burish showed a slide of responses to questions about acute treatments that respondents had tried at least once and viewed as ‘completely effective,’ ‘mostly effective,’ or ‘somewhat effective.’

“No medicine was completely effective, which I think a lot of people know from NDPH. It is notoriously difficult to treat. The things on the top of the list are mostly opioids. There’s one (non-opioid), the DHE (dihydroergotamine) injection. All the way on the other side, you have diphenhydramine. The NSAIDs and triptans are mostly in the middle. We did ask about some of the wearable devices, and we had extra questions about, are you using it appropriately? Those are kind of in the middle or towards the bottom [in frequency],” said Dr. Burish.

There was a similar question regarding effective preventive medications that had been tried for at least 2 months or 3 months in the cause of onabotulinum toxin or CGRP medications. “This one had a little bit more of a pattern to it: A lot of the CGRP medications are up toward the top. It’s not perfect. Erenumab and galcanezumab are closer to the bottom, but it was interesting that a lot of the CGRP medicines were toward the top. Onabotulinum toxin was also somewhat toward the top. We looked at a few different anti-inflammatories. Methylprednisolone is kind of toward the upper half at least, whereas prednisone and montelukast are at the absolute bottom. And the prednisone is a pretty good dose, 50 milligrams or higher. There are some people thinking that this is an inflammation or infectious etiology, (but) it wasn’t that all of the anti-inflammatories were necessarily toward the top of the list,” said Dr. Burish.

Dr. Burish has received funding from Lundbeck. Dr. Sico has no relevant financial disclosures.

SAN DIEGO — A new analysis of patients with new daily persistent headache (NDPH) lends insight into the condition and provides some hints as to some of the more effective treatments, including some calcitonin gene-related peptide (CGRP) inhibitors.

“There’s just not a lot [of information] about these patients,” Mark Burish, MD, PhD, associate professor of neurology at UT Houston, said in an interview. He presented the results of the survey at the annual meeting of the American Headache Society.

There have been some retrospective analyses of patient data, but that has a lot of potential for bias. “It’s only the patients who can afford to be there, and who needed those treatments, and so we want to do more of a general survey,” said Dr. Burish.

The results weren’t particularly surprising, and tended to reaffirm what was known anecdotally, including symptoms similar to those of migraine, but it gave some insight into treatments. “Some of the CGRP inhibitors and the onabotulinum toxin seem to be some of the more effective treatments, according to our survey, so those are probably worth looking into for these patients if you can get them approved by insurance, and if you can get patients to accept the idea they might have to give themselves an injection of some sort,” said Dr. Burish.

Despite having some promise, there was variation among CGRP inhibitors. Eptinezumab, rimegepant, and atogepant were commonly reported as effective, but others, such as erenumab and galcanezumab, were less often reported. “None of them were incredibly effective. These were just the best things we have at this time,” said Dr. Burish.
 

Additional Information on a Rare, Hard-to-Treat Condition

Jason Sico, MD, who moderated the session, was asked for comment. “I’m so appreciative that the team has looked at a new daily persistent headache. It’s a rare type of headache disorder. It’s also one that is notoriously difficult to treat and something that we that we really need to know more about. It is difficult to really get good, robust in-depth information on these patients, and the team did a really nice job with that,” said Dr. Sico, associate professor of neurology and internal medicine at Yale School of Medicine and national director of the Headache Centers of Excellence Program within the Veterans Health Administration.

He noted that the researchers found that opioids were the most commonly used acute treatment. That’s not surprising, but “it would be interesting to see what was tried before someone had gotten to opioids,” he said.

The findings also gave some unexpected insight into the condition. “I really found it striking that an overwhelming majority of patients reported brain fog. Given the context that it is daily persistent headache, one could surmise that they have brain fog a lot of the time,” said Dr. Sico.
 

‘A Good Data Set’

The researchers analyzed data from 337 international patients who responded to a survey. They also randomly selected 34 patients for an interview, and 32 of those were deemed likely to have NDPH. “So we really spent some effort making sure this was a good data set,” said Dr. Burish. The participant population was 72% female, 83.7% White, and 70.7% were based in the United States, though other countries included Canada, the United Kingdom, Australia, Ireland, Germany, Sweden, and Switzerland. The mean age was 41.2 years. The peak ages of onset were between 11 and 40 years, though there were a few cases in the 0-5 age range and over 70. Possible triggers that occurred in the 3 months before onset included psychological stressors (34%), infection or inflammation (32%, COVID infection (5%), injury or surgery (8%), or a change in medications (4%). No clear trigger was identified by 22% of respondents.

The survey included information on associated features, and frequently reported issues included brain fog (approximate 75%), sound sensitivity (about 62%), light sensitivity (57%), nausea (39%), smell sensitivity (32%), visual disturbances (28%), vomiting (13%), and chills (9%).
 

Insights Into Treatment Efficacy

Dr. Burish showed a slide of responses to questions about acute treatments that respondents had tried at least once and viewed as ‘completely effective,’ ‘mostly effective,’ or ‘somewhat effective.’

“No medicine was completely effective, which I think a lot of people know from NDPH. It is notoriously difficult to treat. The things on the top of the list are mostly opioids. There’s one (non-opioid), the DHE (dihydroergotamine) injection. All the way on the other side, you have diphenhydramine. The NSAIDs and triptans are mostly in the middle. We did ask about some of the wearable devices, and we had extra questions about, are you using it appropriately? Those are kind of in the middle or towards the bottom [in frequency],” said Dr. Burish.

There was a similar question regarding effective preventive medications that had been tried for at least 2 months or 3 months in the cause of onabotulinum toxin or CGRP medications. “This one had a little bit more of a pattern to it: A lot of the CGRP medications are up toward the top. It’s not perfect. Erenumab and galcanezumab are closer to the bottom, but it was interesting that a lot of the CGRP medicines were toward the top. Onabotulinum toxin was also somewhat toward the top. We looked at a few different anti-inflammatories. Methylprednisolone is kind of toward the upper half at least, whereas prednisone and montelukast are at the absolute bottom. And the prednisone is a pretty good dose, 50 milligrams or higher. There are some people thinking that this is an inflammation or infectious etiology, (but) it wasn’t that all of the anti-inflammatories were necessarily toward the top of the list,” said Dr. Burish.

Dr. Burish has received funding from Lundbeck. Dr. Sico has no relevant financial disclosures.

For decades it’s been thought that preconception use of the oral antidiabetic metformin by mothers and fathers might result in adverse fetal outcomes, including congenital malformations and stillbirths.

Women with type 2 diabetes (T2D) are often advised to switch to insulin before or during early pregnancy out of concern for fetal safety. But two studies from the Harvard T.H. Chan School of Public Health in Boston, Massachusetts — one in mothers, the other in fathers — report that metformin, a common and cost-effective antidiabetic agent, is not associated with a significant increased risk of teratogenicity and negative perinatal outcomes. The studies appear in Annals of Internal Medicine.

The studies may make it easier for physicians to reassure diabetic parents-to-be about the safety of metformin use before conception and in early pregnancy,

In the context of sparse existing safety data, the maternal analysis looked at Medicaid data on 12,489 mothers (mean age, about 30) receiving metformin for pregestational T2D during the period 2000-2018. “Many women become pregnant while still taking noninsulin oral antidiabetics, mostly metformin, and one safety concern is whether metformin could cause birth defects,” lead author Yu-Han Chiu, MD, ScD, an epidemiologist, said in an interview, commenting on the impetus for the study.

Metformin in Fathers

Turning to fathers, a much larger cohort study by Harvard T.H. Chan investigators looked at the effect of paternal metformin use and also found it to be safe.

The Harvard investigators analyzed diabetic men in 383,851 live births from 1999 to 2020 in an Israeli health fund cohort, excluding those with diabetic spouses. Across different T2D medication groups, paternal age ranged from about 35 to about 43 years. The data revealed that paternal use of metformin monotherapy in the preconception sperm production period was, after adjustment of crude numbers, not associated with major congenital malformations (MCMs) in newborns.

“While metformin has an overall good safety profile, it can lower androgen levels, and there had been some concerns that its use in fathers could alter the sperm, causing adverse effects to the fetus,” lead author and neuroepidemiologist Ran S. Rotem, MD, ScD, of the Harvard School of Public Health, Boston, Massachusetts, said in interview. “Given the increasing prevalence of diabetes in young individuals, more fathers are conceiving a child while using the medication, which could lead to a substantial population effect even if the individual risk is low. But our study suggests that the medication is safe to use by fathers before conception.”

For decades it’s been thought that preconception use of the oral antidiabetic metformin by mothers and fathers might result in adverse fetal outcomes, including congenital malformations and stillbirths.

Women with type 2 diabetes (T2D) are often advised to switch to insulin before or during early pregnancy out of concern for fetal safety. But two studies from the Harvard T.H. Chan School of Public Health in Boston, Massachusetts — one in mothers, the other in fathers — report that metformin, a common and cost-effective antidiabetic agent, is not associated with a significant increased risk of teratogenicity and negative perinatal outcomes. The studies appear in Annals of Internal Medicine.

The studies may make it easier for physicians to reassure diabetic parents-to-be about the safety of metformin use before conception and in early pregnancy,

In the context of sparse existing safety data, the maternal analysis looked at Medicaid data on 12,489 mothers (mean age, about 30) receiving metformin for pregestational T2D during the period 2000-2018. “Many women become pregnant while still taking noninsulin oral antidiabetics, mostly metformin, and one safety concern is whether metformin could cause birth defects,” lead author Yu-Han Chiu, MD, ScD, an epidemiologist, said in an interview, commenting on the impetus for the study.

Metformin in Fathers

Turning to fathers, a much larger cohort study by Harvard T.H. Chan investigators looked at the effect of paternal metformin use and also found it to be safe.

The Harvard investigators analyzed diabetic men in 383,851 live births from 1999 to 2020 in an Israeli health fund cohort, excluding those with diabetic spouses. Across different T2D medication groups, paternal age ranged from about 35 to about 43 years. The data revealed that paternal use of metformin monotherapy in the preconception sperm production period was, after adjustment of crude numbers, not associated with major congenital malformations (MCMs) in newborns.

“While metformin has an overall good safety profile, it can lower androgen levels, and there had been some concerns that its use in fathers could alter the sperm, causing adverse effects to the fetus,” lead author and neuroepidemiologist Ran S. Rotem, MD, ScD, of the Harvard School of Public Health, Boston, Massachusetts, said in interview. “Given the increasing prevalence of diabetes in young individuals, more fathers are conceiving a child while using the medication, which could lead to a substantial population effect even if the individual risk is low. But our study suggests that the medication is safe to use by fathers before conception.”

For decades it’s been thought that preconception use of the oral antidiabetic metformin by mothers and fathers might result in adverse fetal outcomes, including congenital malformations and stillbirths.

Women with type 2 diabetes (T2D) are often advised to switch to insulin before or during early pregnancy out of concern for fetal safety. But two studies from the Harvard T.H. Chan School of Public Health in Boston, Massachusetts — one in mothers, the other in fathers — report that metformin, a common and cost-effective antidiabetic agent, is not associated with a significant increased risk of teratogenicity and negative perinatal outcomes. The studies appear in Annals of Internal Medicine.

The studies may make it easier for physicians to reassure diabetic parents-to-be about the safety of metformin use before conception and in early pregnancy,

In the context of sparse existing safety data, the maternal analysis looked at Medicaid data on 12,489 mothers (mean age, about 30) receiving metformin for pregestational T2D during the period 2000-2018. “Many women become pregnant while still taking noninsulin oral antidiabetics, mostly metformin, and one safety concern is whether metformin could cause birth defects,” lead author Yu-Han Chiu, MD, ScD, an epidemiologist, said in an interview, commenting on the impetus for the study.

Metformin in Fathers

Turning to fathers, a much larger cohort study by Harvard T.H. Chan investigators looked at the effect of paternal metformin use and also found it to be safe.

The Harvard investigators analyzed diabetic men in 383,851 live births from 1999 to 2020 in an Israeli health fund cohort, excluding those with diabetic spouses. Across different T2D medication groups, paternal age ranged from about 35 to about 43 years. The data revealed that paternal use of metformin monotherapy in the preconception sperm production period was, after adjustment of crude numbers, not associated with major congenital malformations (MCMs) in newborns.

“While metformin has an overall good safety profile, it can lower androgen levels, and there had been some concerns that its use in fathers could alter the sperm, causing adverse effects to the fetus,” lead author and neuroepidemiologist Ran S. Rotem, MD, ScD, of the Harvard School of Public Health, Boston, Massachusetts, said in interview. “Given the increasing prevalence of diabetes in young individuals, more fathers are conceiving a child while using the medication, which could lead to a substantial population effect even if the individual risk is low. But our study suggests that the medication is safe to use by fathers before conception.”

TOPLINE:

Whether they have normal weight, overweight, or obesity, individuals with metabolically healthy (MH) phenotypes show a lower frequency of impaired glucose metabolism than their unhealthy counterparts across all weight categories.

METHODOLOGY:

• The concepts of MH overweight and MH obesity refer to a subset of people who exhibit an absence of cardiometabolic risk factors despite excess body fat, but the prevalence of prediabetes has not been investigated by metabolic phenotype and body mass index (BMI).
• This study first validated the use of estimated glucose disposal rate (eGDR), an index of insulin sensitivity calculated from clinical variables, in 350 individuals without diabetes (mean age, 37 years; 219 women; mean BMI, 30.3) from the EUGENE2 project who had varying glucose tolerance values originally assessed by insulin-stimulated glucose disposal.
• Researchers then stratified 2201 participants without diabetes (mean age, 46 years; White; 1290 women; mean BMI, 31.2) from the CATAMERI study according to BMI into three groups — individuals with normal weight (BMI, 18-24.9), overweight (BMI, 25-29.9), and obesity (BMI, ≥ 30).
• The men and women in each BMI group were separated into quartiles of insulin sensitivity based on eGDR index:
• In the normal weight group, men and women were defined as MH in the top three eGDR quartiles and metabolically unhealthy (MU) in the lowest quartile.
• In the overweight and obesity groups, people were defined as MH in the top eGDR quartile and MU in the lower three quartiles.
• Impaired glucose tolerance (IGT), impaired fasting glucose (IFG), and combined IFG+IGT conditions (from an oral glucose tolerance test) were compared in individuals without diabetes based on MH or unhealthy phenotypes across normal weight, overweight, and obese categories.

TAKEAWAY:

• eGDR demonstrated good accuracy in detecting individuals with higher insulin sensitivity in the EUGENE2 cohort.
• The MH overweight and MH obesity groups showed comparable glycemic parameters as the MH normal weight group, whereas the MU overweight and MU obesity groups exhibited higher A1c levels and fasting and 2-hour post-load glucose than the MH normal weight group.
• The frequencies of IFG, IGT, and IFG+IGT conditions were similar among the MH normal weight, MH overweight, and MH obesity groups but were higher in the MU overweight and MU obesity groups than in the MU normal weight group.
• Furthermore, compared with those in the MH normal weight group, the odds of prediabetes were at least two times higher in the MU obesity (odds ratio [OR], 2.54; P < .001) and MU overweight (OR, 2.06; P < .001) groups but not significantly different in the MU normal weight, MH obesity, and MH overweight groups.

IN PRACTICE:

The authors wrote, “Overall, the results of this cross-sectional study support the notion that metabolically healthy individuals with overweight or obesity have a more favorable metabolic risk profile in comparison to metabolically unhealthy subjects with overweight or obesity.”

SOURCE:

The study was conducted by Chiara M.A. Cefalo, MD, department of clinical and molecular medicine, Sapienza University of Rome, Rome, Italy, and was published online in Diabetes, Obesity and Metabolism.

LIMITATIONS:

There was no consensus on the parameters and cutoff values for defining metabolic health status, allowing for potential variations in results. The study design suggested an association with prevalent IFG and IGT conditions but not with incident IFG and IGT conditions. All participants in this study were White, limiting the generalizability of its findings.

DISCLOSURES:

The study was supported by Sapienza University of Rome and the Italian Ministry of University. The authors declared no conflicts of interest.

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

TOPLINE:

Whether they have normal weight, overweight, or obesity, individuals with metabolically healthy (MH) phenotypes show a lower frequency of impaired glucose metabolism than their unhealthy counterparts across all weight categories.

METHODOLOGY:

• The concepts of MH overweight and MH obesity refer to a subset of people who exhibit an absence of cardiometabolic risk factors despite excess body fat, but the prevalence of prediabetes has not been investigated by metabolic phenotype and body mass index (BMI).
• This study first validated the use of estimated glucose disposal rate (eGDR), an index of insulin sensitivity calculated from clinical variables, in 350 individuals without diabetes (mean age, 37 years; 219 women; mean BMI, 30.3) from the EUGENE2 project who had varying glucose tolerance values originally assessed by insulin-stimulated glucose disposal.
• Researchers then stratified 2201 participants without diabetes (mean age, 46 years; White; 1290 women; mean BMI, 31.2) from the CATAMERI study according to BMI into three groups — individuals with normal weight (BMI, 18-24.9), overweight (BMI, 25-29.9), and obesity (BMI, ≥ 30).
• The men and women in each BMI group were separated into quartiles of insulin sensitivity based on eGDR index:
• In the normal weight group, men and women were defined as MH in the top three eGDR quartiles and metabolically unhealthy (MU) in the lowest quartile.
• In the overweight and obesity groups, people were defined as MH in the top eGDR quartile and MU in the lower three quartiles.
• Impaired glucose tolerance (IGT), impaired fasting glucose (IFG), and combined IFG+IGT conditions (from an oral glucose tolerance test) were compared in individuals without diabetes based on MH or unhealthy phenotypes across normal weight, overweight, and obese categories.

TAKEAWAY:

• eGDR demonstrated good accuracy in detecting individuals with higher insulin sensitivity in the EUGENE2 cohort.
• The MH overweight and MH obesity groups showed comparable glycemic parameters as the MH normal weight group, whereas the MU overweight and MU obesity groups exhibited higher A1c levels and fasting and 2-hour post-load glucose than the MH normal weight group.
• The frequencies of IFG, IGT, and IFG+IGT conditions were similar among the MH normal weight, MH overweight, and MH obesity groups but were higher in the MU overweight and MU obesity groups than in the MU normal weight group.
• Furthermore, compared with those in the MH normal weight group, the odds of prediabetes were at least two times higher in the MU obesity (odds ratio [OR], 2.54; P < .001) and MU overweight (OR, 2.06; P < .001) groups but not significantly different in the MU normal weight, MH obesity, and MH overweight groups.

IN PRACTICE:

The authors wrote, “Overall, the results of this cross-sectional study support the notion that metabolically healthy individuals with overweight or obesity have a more favorable metabolic risk profile in comparison to metabolically unhealthy subjects with overweight or obesity.”

SOURCE:

The study was conducted by Chiara M.A. Cefalo, MD, department of clinical and molecular medicine, Sapienza University of Rome, Rome, Italy, and was published online in Diabetes, Obesity and Metabolism.

LIMITATIONS:

There was no consensus on the parameters and cutoff values for defining metabolic health status, allowing for potential variations in results. The study design suggested an association with prevalent IFG and IGT conditions but not with incident IFG and IGT conditions. All participants in this study were White, limiting the generalizability of its findings.

DISCLOSURES:

The study was supported by Sapienza University of Rome and the Italian Ministry of University. The authors declared no conflicts of interest.

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

TOPLINE:

Whether they have normal weight, overweight, or obesity, individuals with metabolically healthy (MH) phenotypes show a lower frequency of impaired glucose metabolism than their unhealthy counterparts across all weight categories.

METHODOLOGY:

• The concepts of MH overweight and MH obesity refer to a subset of people who exhibit an absence of cardiometabolic risk factors despite excess body fat, but the prevalence of prediabetes has not been investigated by metabolic phenotype and body mass index (BMI).
• This study first validated the use of estimated glucose disposal rate (eGDR), an index of insulin sensitivity calculated from clinical variables, in 350 individuals without diabetes (mean age, 37 years; 219 women; mean BMI, 30.3) from the EUGENE2 project who had varying glucose tolerance values originally assessed by insulin-stimulated glucose disposal.
• Researchers then stratified 2201 participants without diabetes (mean age, 46 years; White; 1290 women; mean BMI, 31.2) from the CATAMERI study according to BMI into three groups — individuals with normal weight (BMI, 18-24.9), overweight (BMI, 25-29.9), and obesity (BMI, ≥ 30).
• The men and women in each BMI group were separated into quartiles of insulin sensitivity based on eGDR index:
• In the normal weight group, men and women were defined as MH in the top three eGDR quartiles and metabolically unhealthy (MU) in the lowest quartile.
• In the overweight and obesity groups, people were defined as MH in the top eGDR quartile and MU in the lower three quartiles.
• Impaired glucose tolerance (IGT), impaired fasting glucose (IFG), and combined IFG+IGT conditions (from an oral glucose tolerance test) were compared in individuals without diabetes based on MH or unhealthy phenotypes across normal weight, overweight, and obese categories.

TAKEAWAY:

• eGDR demonstrated good accuracy in detecting individuals with higher insulin sensitivity in the EUGENE2 cohort.
• The MH overweight and MH obesity groups showed comparable glycemic parameters as the MH normal weight group, whereas the MU overweight and MU obesity groups exhibited higher A1c levels and fasting and 2-hour post-load glucose than the MH normal weight group.
• The frequencies of IFG, IGT, and IFG+IGT conditions were similar among the MH normal weight, MH overweight, and MH obesity groups but were higher in the MU overweight and MU obesity groups than in the MU normal weight group.
• Furthermore, compared with those in the MH normal weight group, the odds of prediabetes were at least two times higher in the MU obesity (odds ratio [OR], 2.54; P < .001) and MU overweight (OR, 2.06; P < .001) groups but not significantly different in the MU normal weight, MH obesity, and MH overweight groups.

IN PRACTICE:

The authors wrote, “Overall, the results of this cross-sectional study support the notion that metabolically healthy individuals with overweight or obesity have a more favorable metabolic risk profile in comparison to metabolically unhealthy subjects with overweight or obesity.”

SOURCE:

The study was conducted by Chiara M.A. Cefalo, MD, department of clinical and molecular medicine, Sapienza University of Rome, Rome, Italy, and was published online in Diabetes, Obesity and Metabolism.

LIMITATIONS:

There was no consensus on the parameters and cutoff values for defining metabolic health status, allowing for potential variations in results. The study design suggested an association with prevalent IFG and IGT conditions but not with incident IFG and IGT conditions. All participants in this study were White, limiting the generalizability of its findings.

DISCLOSURES:

The study was supported by Sapienza University of Rome and the Italian Ministry of University. The authors declared no conflicts of interest.

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

TOPLINE:

Mortality and disability-adjusted life years (DALYs) among people with type 1 diabetes (T1D) aged ≥ 65 years dropped significantly from 1990 to 2019. Both were lower among women and those living in higher sociodemographic areas.

METHODOLOGY:

• A population-based study of adults aged ≥ 65 years from 21 regions and 204 countries and territories, 1990-2019, was conducted.

TAKEAWAY:

• Globally, the prevalence of T1D among people aged ≥ 65 years increased by 180% between 1990 and 2019, from 1.3 million to 3.7 million.
• The proportion of older people with T1D has consistently trended upward, from 12% of all people with T1D in 1990 to 17% in 2019.
• Age-standardized mortality from T1D among this age group significantly decreased by 25%, from 4.7/100,000 population in 1990 to 3.5/100,000 in 2019.
• Age-standardized increases in T1D prevalence have occurred in both men and women worldwide, while the increase was more rapid among men (average annual percent change, 1.00% vs 0.74%).
• Globally, T1D prevalence at least tripled in every age subgroup of those aged ≥ 65 years, and even fivefold to sixfold for those ≥ 90-95 years (0.02-0.11 million for ages 90-94 years; 0.005-0.03 million for ages ≥ 95 years).
• No decreases occurred in T1D prevalence among those aged ≥ 65 years in any of the 21 global regions.
• Three primary risk factors associated with DALYs for T1D among people aged ≥ 65 years were high fasting plasma glucose levels, low temperature, and high temperature, accounting for 103 DALYs per 100,000 people, 3/100,000 people, and 1/100,000 people, respectively, in 2019.

IN PRACTICE:

“The results suggest that T1DM is no longer a contributory factor in decreased life expectancy owing to improvements in medical care over the three decades,” the authors wrote. “Management of high fasting plasma glucose levels remains a major challenge for older people with T1D, and targeted clinical guidelines are needed.”

SOURCE:

The study was conducted by Kaijie Yang, the Department of Endocrinology and Metabolism, the Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, First Hospital of China Medical University, Shenyang, China, and colleagues. The study was published online in the BMJ.

LIMITATIONS:

Data were extrapolated from countries that have epidemiologic data. Health information systems and reporting mechanisms vary across countries and regions. Disease burden data include a time lag. Diagnosing T1D in older people can be challenging.

DISCLOSURES:

The study was supported by the National Natural Science Foundation of China and the China Postdoctoral Science Foundation. The authors reported no additional financial relationships.

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

TOPLINE:

Mortality and disability-adjusted life years (DALYs) among people with type 1 diabetes (T1D) aged ≥ 65 years dropped significantly from 1990 to 2019. Both were lower among women and those living in higher sociodemographic areas.

METHODOLOGY:

• A population-based study of adults aged ≥ 65 years from 21 regions and 204 countries and territories, 1990-2019, was conducted.

TAKEAWAY:

• Globally, the prevalence of T1D among people aged ≥ 65 years increased by 180% between 1990 and 2019, from 1.3 million to 3.7 million.
• The proportion of older people with T1D has consistently trended upward, from 12% of all people with T1D in 1990 to 17% in 2019.
• Age-standardized mortality from T1D among this age group significantly decreased by 25%, from 4.7/100,000 population in 1990 to 3.5/100,000 in 2019.
• Age-standardized increases in T1D prevalence have occurred in both men and women worldwide, while the increase was more rapid among men (average annual percent change, 1.00% vs 0.74%).
• Globally, T1D prevalence at least tripled in every age subgroup of those aged ≥ 65 years, and even fivefold to sixfold for those ≥ 90-95 years (0.02-0.11 million for ages 90-94 years; 0.005-0.03 million for ages ≥ 95 years).
• No decreases occurred in T1D prevalence among those aged ≥ 65 years in any of the 21 global regions.
• Three primary risk factors associated with DALYs for T1D among people aged ≥ 65 years were high fasting plasma glucose levels, low temperature, and high temperature, accounting for 103 DALYs per 100,000 people, 3/100,000 people, and 1/100,000 people, respectively, in 2019.

IN PRACTICE:

“The results suggest that T1DM is no longer a contributory factor in decreased life expectancy owing to improvements in medical care over the three decades,” the authors wrote. “Management of high fasting plasma glucose levels remains a major challenge for older people with T1D, and targeted clinical guidelines are needed.”

SOURCE:

The study was conducted by Kaijie Yang, the Department of Endocrinology and Metabolism, the Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, First Hospital of China Medical University, Shenyang, China, and colleagues. The study was published online in the BMJ.

LIMITATIONS:

Data were extrapolated from countries that have epidemiologic data. Health information systems and reporting mechanisms vary across countries and regions. Disease burden data include a time lag. Diagnosing T1D in older people can be challenging.

DISCLOSURES:

The study was supported by the National Natural Science Foundation of China and the China Postdoctoral Science Foundation. The authors reported no additional financial relationships.

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

TOPLINE:

Mortality and disability-adjusted life years (DALYs) among people with type 1 diabetes (T1D) aged ≥ 65 years dropped significantly from 1990 to 2019. Both were lower among women and those living in higher sociodemographic areas.

METHODOLOGY:

• A population-based study of adults aged ≥ 65 years from 21 regions and 204 countries and territories, 1990-2019, was conducted.

TAKEAWAY:

• Globally, the prevalence of T1D among people aged ≥ 65 years increased by 180% between 1990 and 2019, from 1.3 million to 3.7 million.
• The proportion of older people with T1D has consistently trended upward, from 12% of all people with T1D in 1990 to 17% in 2019.
• Age-standardized mortality from T1D among this age group significantly decreased by 25%, from 4.7/100,000 population in 1990 to 3.5/100,000 in 2019.
• Age-standardized increases in T1D prevalence have occurred in both men and women worldwide, while the increase was more rapid among men (average annual percent change, 1.00% vs 0.74%).
• Globally, T1D prevalence at least tripled in every age subgroup of those aged ≥ 65 years, and even fivefold to sixfold for those ≥ 90-95 years (0.02-0.11 million for ages 90-94 years; 0.005-0.03 million for ages ≥ 95 years).
• No decreases occurred in T1D prevalence among those aged ≥ 65 years in any of the 21 global regions.
• Three primary risk factors associated with DALYs for T1D among people aged ≥ 65 years were high fasting plasma glucose levels, low temperature, and high temperature, accounting for 103 DALYs per 100,000 people, 3/100,000 people, and 1/100,000 people, respectively, in 2019.

IN PRACTICE:

“The results suggest that T1DM is no longer a contributory factor in decreased life expectancy owing to improvements in medical care over the three decades,” the authors wrote. “Management of high fasting plasma glucose levels remains a major challenge for older people with T1D, and targeted clinical guidelines are needed.”

SOURCE:

The study was conducted by Kaijie Yang, the Department of Endocrinology and Metabolism, the Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, First Hospital of China Medical University, Shenyang, China, and colleagues. The study was published online in the BMJ.

LIMITATIONS:

Data were extrapolated from countries that have epidemiologic data. Health information systems and reporting mechanisms vary across countries and regions. Disease burden data include a time lag. Diagnosing T1D in older people can be challenging.

DISCLOSURES:

The study was supported by the National Natural Science Foundation of China and the China Postdoctoral Science Foundation. The authors reported no additional financial relationships.

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

TOPLINE:

Bariatric metabolic surgery (BMS) offers a survival advantage over glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in adults with obesity and diabetes for 10 years or less, which may be explained by greater weight loss with surgery, new research shows.

METHODOLOGY:

• There is limited evidence regarding the relative effectiveness of BMS and GLP-1 RAs in reducing mortality and major adverse cardiovascular events (MACE).
• This observational, retrospective cohort study analyzed the electronic medical records of Clalit Health Services, Israel’s largest healthcare organization.
• Researchers included patients aged 24 years or older who had diabetes and obesity but no prior cardiovascular disease and who either underwent BMS or received a GLP-1 RA.
• The primary outcome was all-cause mortality, assessed by multivariate Cox proportional hazards regression models. The secondary outcome was nonfatal MACE, assessed by multivariate competing risk models.

TAKEAWAY:

• Researchers included 3035 matched pairs of patients (total, 6070; mean age, 51 years; 65% women), who were followed for a median of 6.8 years.
• Among patients with diabetes for 10 years or less, those who underwent BMS had a 62% lower risk for mortality than those treated with a GLP-1 RA (hazard ratio [HR], 0.38).
• The survival advantage associated with BMS vs GLP-1 RA may be explained by the greater relative decrease in body mass index in the surgery group (–31.4% vs –12.8%, respectively).
• Among patients with diabetes for more than 10 years, no survival advantage was observed for BMS over GLP-1 RA (HR, 0.65), which may be explained by the adverse effects of prolonged diabetes duration masking the benefit associated with weight loss.
• The risk for nonfatal MACE did not differ significantly between the treatment groups in both diabetes duration categories.

IN PRACTICE:

“This study suggests that BMS was associated with greater reduced mortality compared with GLP-1 RAs among individuals with a diabetes duration of 10 years or less, mediated via greater weight loss,” the authors wrote.

SOURCE:

The study, with first author Dror Dicker, MD, Hasharon Hospital, Rabin Medical Center, Petah Tikva, Israel, was published online in JAMA Network Open.

LIMITATIONS:

The observational design may have introduced residual confounding despite matching and multivariable adjustment. The analyses did not account for the types of BMS or GLP-1 RAs or the level of adherence to GLP-1 RA treatment. Information regarding cause of death was unavailable.

DISCLOSURES:

The study was funded by the Israel Science Foundation. Dicker reported financial relationships with Novo Nordisk, Eli Lilly, and Boehringer Ingelheim.

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

TOPLINE:

Bariatric metabolic surgery (BMS) offers a survival advantage over glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in adults with obesity and diabetes for 10 years or less, which may be explained by greater weight loss with surgery, new research shows.

METHODOLOGY:

• There is limited evidence regarding the relative effectiveness of BMS and GLP-1 RAs in reducing mortality and major adverse cardiovascular events (MACE).
• This observational, retrospective cohort study analyzed the electronic medical records of Clalit Health Services, Israel’s largest healthcare organization.
• Researchers included patients aged 24 years or older who had diabetes and obesity but no prior cardiovascular disease and who either underwent BMS or received a GLP-1 RA.
• The primary outcome was all-cause mortality, assessed by multivariate Cox proportional hazards regression models. The secondary outcome was nonfatal MACE, assessed by multivariate competing risk models.

TAKEAWAY:

• Researchers included 3035 matched pairs of patients (total, 6070; mean age, 51 years; 65% women), who were followed for a median of 6.8 years.
• Among patients with diabetes for 10 years or less, those who underwent BMS had a 62% lower risk for mortality than those treated with a GLP-1 RA (hazard ratio [HR], 0.38).
• The survival advantage associated with BMS vs GLP-1 RA may be explained by the greater relative decrease in body mass index in the surgery group (–31.4% vs –12.8%, respectively).
• Among patients with diabetes for more than 10 years, no survival advantage was observed for BMS over GLP-1 RA (HR, 0.65), which may be explained by the adverse effects of prolonged diabetes duration masking the benefit associated with weight loss.
• The risk for nonfatal MACE did not differ significantly between the treatment groups in both diabetes duration categories.

IN PRACTICE:

“This study suggests that BMS was associated with greater reduced mortality compared with GLP-1 RAs among individuals with a diabetes duration of 10 years or less, mediated via greater weight loss,” the authors wrote.

SOURCE:

The study, with first author Dror Dicker, MD, Hasharon Hospital, Rabin Medical Center, Petah Tikva, Israel, was published online in JAMA Network Open.

LIMITATIONS:

The observational design may have introduced residual confounding despite matching and multivariable adjustment. The analyses did not account for the types of BMS or GLP-1 RAs or the level of adherence to GLP-1 RA treatment. Information regarding cause of death was unavailable.

DISCLOSURES:

The study was funded by the Israel Science Foundation. Dicker reported financial relationships with Novo Nordisk, Eli Lilly, and Boehringer Ingelheim.

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

TOPLINE:

Bariatric metabolic surgery (BMS) offers a survival advantage over glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in adults with obesity and diabetes for 10 years or less, which may be explained by greater weight loss with surgery, new research shows.

METHODOLOGY:

• There is limited evidence regarding the relative effectiveness of BMS and GLP-1 RAs in reducing mortality and major adverse cardiovascular events (MACE).
• This observational, retrospective cohort study analyzed the electronic medical records of Clalit Health Services, Israel’s largest healthcare organization.
• Researchers included patients aged 24 years or older who had diabetes and obesity but no prior cardiovascular disease and who either underwent BMS or received a GLP-1 RA.
• The primary outcome was all-cause mortality, assessed by multivariate Cox proportional hazards regression models. The secondary outcome was nonfatal MACE, assessed by multivariate competing risk models.

TAKEAWAY:

• Researchers included 3035 matched pairs of patients (total, 6070; mean age, 51 years; 65% women), who were followed for a median of 6.8 years.
• Among patients with diabetes for 10 years or less, those who underwent BMS had a 62% lower risk for mortality than those treated with a GLP-1 RA (hazard ratio [HR], 0.38).
• The survival advantage associated with BMS vs GLP-1 RA may be explained by the greater relative decrease in body mass index in the surgery group (–31.4% vs –12.8%, respectively).
• Among patients with diabetes for more than 10 years, no survival advantage was observed for BMS over GLP-1 RA (HR, 0.65), which may be explained by the adverse effects of prolonged diabetes duration masking the benefit associated with weight loss.
• The risk for nonfatal MACE did not differ significantly between the treatment groups in both diabetes duration categories.

IN PRACTICE:

“This study suggests that BMS was associated with greater reduced mortality compared with GLP-1 RAs among individuals with a diabetes duration of 10 years or less, mediated via greater weight loss,” the authors wrote.

SOURCE:

The study, with first author Dror Dicker, MD, Hasharon Hospital, Rabin Medical Center, Petah Tikva, Israel, was published online in JAMA Network Open.

LIMITATIONS:

The observational design may have introduced residual confounding despite matching and multivariable adjustment. The analyses did not account for the types of BMS or GLP-1 RAs or the level of adherence to GLP-1 RA treatment. Information regarding cause of death was unavailable.

DISCLOSURES:

The study was funded by the Israel Science Foundation. Dicker reported financial relationships with Novo Nordisk, Eli Lilly, and Boehringer Ingelheim.

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

TOPLINE:

Anorexia nervosa (AN) is associated with a 4.5-fold increased risk for mortality — a rate that nearly doubles when AN patients have psychiatric comorbidities.

METHODOLOGY:

• Researchers analyzed data from 14,774 patients diagnosed with AN at age ≥ 6 years from 1977 to 2018.
• Patients were followed-up for a median time of 9.1 years, with some followed-up for ≤ 40 years and matched 1:10 with age- and sex-matched controls.
• Investigators calculated adjusted hazard ratios for mortality, considering psychiatric comorbidity, sex, and age at diagnosis.

TAKEAWAY:

• AN is associated with a 4.5-fold increased mortality risk vs the general population.
• About half of the sample with AN (47%) had a psychiatric comorbidity, which is associated with a 7.7% mortality risk at 10 years.
• Psychiatric comorbidity in anorexia nervosa patients nearly doubles the 10-year mortality risk.
• Suicide was the primary cause of unnatural death (9% died by suicide), and the rate was higher among patients with a psychiatric comorbidity.

IN PRACTICE:

“These findings highlight the crucial need for clinicians to recognize additional mental health disorders in adolescents and adults with anorexia,” author Mette Søeby, MD, Aarhus University/Aarhus University Hospital, in Aarhus, Denmark, said in a press release.

SOURCE:

The study was led by Dr. Søeby and was published online on June 12, 2024, in the International Journal of Eating Disorders.

LIMITATIONS:

The transition from International Classification of Diseases, 8th edition (ICD-8) to ICD-10 and inclusion of outpatient visits may have influenced the study’s results by including more patients with less severe illness. The ICD-10 diagnosis code for anorexia nervosa in Danish registers has not been validated, potentially affecting the accuracy of the study’s findings.

DISCLOSURES:

The study was supported by grants from the Novo Nordic Foundation and The Danish Foundation for Research in Mental Disorders. The authors declared no conflicts of interest.


This article was created 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.

TOPLINE:

Anorexia nervosa (AN) is associated with a 4.5-fold increased risk for mortality — a rate that nearly doubles when AN patients have psychiatric comorbidities.

METHODOLOGY:

• Researchers analyzed data from 14,774 patients diagnosed with AN at age ≥ 6 years from 1977 to 2018.
• Patients were followed-up for a median time of 9.1 years, with some followed-up for ≤ 40 years and matched 1:10 with age- and sex-matched controls.
• Investigators calculated adjusted hazard ratios for mortality, considering psychiatric comorbidity, sex, and age at diagnosis.

TAKEAWAY:

• AN is associated with a 4.5-fold increased mortality risk vs the general population.
• About half of the sample with AN (47%) had a psychiatric comorbidity, which is associated with a 7.7% mortality risk at 10 years.
• Psychiatric comorbidity in anorexia nervosa patients nearly doubles the 10-year mortality risk.
• Suicide was the primary cause of unnatural death (9% died by suicide), and the rate was higher among patients with a psychiatric comorbidity.

IN PRACTICE:

“These findings highlight the crucial need for clinicians to recognize additional mental health disorders in adolescents and adults with anorexia,” author Mette Søeby, MD, Aarhus University/Aarhus University Hospital, in Aarhus, Denmark, said in a press release.

SOURCE:

The study was led by Dr. Søeby and was published online on June 12, 2024, in the International Journal of Eating Disorders.

LIMITATIONS:

The transition from International Classification of Diseases, 8th edition (ICD-8) to ICD-10 and inclusion of outpatient visits may have influenced the study’s results by including more patients with less severe illness. The ICD-10 diagnosis code for anorexia nervosa in Danish registers has not been validated, potentially affecting the accuracy of the study’s findings.

DISCLOSURES:

The study was supported by grants from the Novo Nordic Foundation and The Danish Foundation for Research in Mental Disorders. The authors declared no conflicts of interest.


This article was created 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.

TOPLINE:

Anorexia nervosa (AN) is associated with a 4.5-fold increased risk for mortality — a rate that nearly doubles when AN patients have psychiatric comorbidities.

METHODOLOGY:

• Researchers analyzed data from 14,774 patients diagnosed with AN at age ≥ 6 years from 1977 to 2018.
• Patients were followed-up for a median time of 9.1 years, with some followed-up for ≤ 40 years and matched 1:10 with age- and sex-matched controls.
• Investigators calculated adjusted hazard ratios for mortality, considering psychiatric comorbidity, sex, and age at diagnosis.

TAKEAWAY:

• AN is associated with a 4.5-fold increased mortality risk vs the general population.
• About half of the sample with AN (47%) had a psychiatric comorbidity, which is associated with a 7.7% mortality risk at 10 years.
• Psychiatric comorbidity in anorexia nervosa patients nearly doubles the 10-year mortality risk.
• Suicide was the primary cause of unnatural death (9% died by suicide), and the rate was higher among patients with a psychiatric comorbidity.

IN PRACTICE:

“These findings highlight the crucial need for clinicians to recognize additional mental health disorders in adolescents and adults with anorexia,” author Mette Søeby, MD, Aarhus University/Aarhus University Hospital, in Aarhus, Denmark, said in a press release.

SOURCE:

The study was led by Dr. Søeby and was published online on June 12, 2024, in the International Journal of Eating Disorders.

LIMITATIONS:

The transition from International Classification of Diseases, 8th edition (ICD-8) to ICD-10 and inclusion of outpatient visits may have influenced the study’s results by including more patients with less severe illness. The ICD-10 diagnosis code for anorexia nervosa in Danish registers has not been validated, potentially affecting the accuracy of the study’s findings.

DISCLOSURES:

The study was supported by grants from the Novo Nordic Foundation and The Danish Foundation for Research in Mental Disorders. The authors declared no conflicts of interest.


This article was created 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.

An intervention combining an individualized walking program and education and significantly reduced low back pain recurrence in adults, compared with controls, based on data from approximately 700 individuals.

Exercise, including walking, is recommended to prevent recurrence of low back pain, but data on the effectiveness and cost-effectiveness of walking as an intervention are lacking, wrote Natasha C. Pocovi, PhD, of Macquarie University, Sydney, Australia, and colleagues.

In a study known as WalkBack, published in the Lancet, the researchers randomized 351 adults aged 18 years and older with a history of more than two prior episodes of low back pain to an intervention and 350 to no intervention.

The intervention consisted of six sessions of education and progressive walking with a physiotherapist over 6 months; both intervention and control groups were followed for a minimum of 12 months and a maximum of 36 months. The mean age of the participants was 54 years, and 81% were female. The primary outcome was the number of days to recurrence of low back pain severe enough to limit activity, based on monthly self-reports.

The intervention was significantly more effective at preventing activity-limiting low back pain recurrence, compared with no intervention (hazard ratio, 0.72; P = .0002), with a median of 208 days and 112 days to recurrence in the intervention and control groups, respectively.

The risk of any low back pain recurrence also was significantly reduced in the intervention group, compared with the controls (HR, 0.80; P = .0066); as was the risk of care-seeking recurrence of low back pain (HR, 0.57; P < .0001).

Overall, the experience of at least one adverse event over 12 months was similar between the intervention and control groups (52% and 54%, respectively), but significantly more adverse events related to lower extremities occurred in the intervention group, compared with the control group (100 vs 54). The intervention also was more likely to be cost effective, compared with a no-treatment control, the researchers wrote.

The findings were limited by several factors including the relatively homogeneous population and that neither the therapists nor participants were masked to group allocation. In addition, the study was conducted during the COVID-19 pandemic, so a telehealth model of video consultations was used instead of in-person meetings, but this protocol change allowed for inclusion of participants from diverse locations including rural and remote areas, the researchers said.

More research is needed to assess the implementation of a walking and exercise intervention as part of a discharge plan after an episode of low back pain and to examine the effectiveness of an intervention involving fewer sessions and a range of healthcare providers, they added. However, the results support the value of the intervention, which has a strong potential for successful implementation because of accessibility and low cost.
 

Preventive Interventions Need More Real-World Research

“Preventive interventions for back pain are an important yet neglected consideration,” Diarmuid Denneny, a doctoral candidate at Brunel University London, and Jackie Walumbe, PhD, of the University of Oxford (England), wrote in an accompanying editorial.

Although recurrence of low back pain is common, guidance on prevention and management is lacking, they said. Strengths of the current study include attention to patient and public preferences in the study design; however, the majority of the participants were of relatively high socioeconomic status and 89% reported post-secondary education.

“Given that pain is known to have a higher impact on marginalized and minoritized groups and those experiencing socioeconomic deprivation, we recommend caution in extrapolating these findings to different contexts,” the editorialists wrote.

They also cautioned that the complex nature of the intervention, which included not only walking but education and physiotherapist appointments, might make it difficult to isolate walking as the key factor in the patients’ improvement. The editorialists also emphasized the need for studies of similar interventions conducted by alternative providers including exercise professionals and digital platforms.

However, the WalkBack trial represents progress toward greater support for individuals with recurrent back pain and may be a foundation for other research involving how other forms of physical activity compare in improving back pain, with attention to the role of publish health in delivering physical activity interventions, they said.

The study was supported by the National Health and Medical Research Council, Australia. Dr. Pocovi disclosed scholarships funded by the National Health and Medical Research Council Low Back Pain Centre of Research Excellence (ANZBACK) and Macquarie University. Mr. Denneny disclosed support from an Economic and Social Research Council fellowship, and disclosed consulting fees from Live Well with Pain and Leva clinic; a grant from the Chartered Society of Physiotherapy. Dr. Walumbe disclosed travel support from the Chartered Society of Physiotherapy Charitable Trust.

An intervention combining an individualized walking program and education and significantly reduced low back pain recurrence in adults, compared with controls, based on data from approximately 700 individuals.

Exercise, including walking, is recommended to prevent recurrence of low back pain, but data on the effectiveness and cost-effectiveness of walking as an intervention are lacking, wrote Natasha C. Pocovi, PhD, of Macquarie University, Sydney, Australia, and colleagues.

In a study known as WalkBack, published in the Lancet, the researchers randomized 351 adults aged 18 years and older with a history of more than two prior episodes of low back pain to an intervention and 350 to no intervention.

The intervention consisted of six sessions of education and progressive walking with a physiotherapist over 6 months; both intervention and control groups were followed for a minimum of 12 months and a maximum of 36 months. The mean age of the participants was 54 years, and 81% were female. The primary outcome was the number of days to recurrence of low back pain severe enough to limit activity, based on monthly self-reports.

The intervention was significantly more effective at preventing activity-limiting low back pain recurrence, compared with no intervention (hazard ratio, 0.72; P = .0002), with a median of 208 days and 112 days to recurrence in the intervention and control groups, respectively.

The risk of any low back pain recurrence also was significantly reduced in the intervention group, compared with the controls (HR, 0.80; P = .0066); as was the risk of care-seeking recurrence of low back pain (HR, 0.57; P < .0001).

Overall, the experience of at least one adverse event over 12 months was similar between the intervention and control groups (52% and 54%, respectively), but significantly more adverse events related to lower extremities occurred in the intervention group, compared with the control group (100 vs 54). The intervention also was more likely to be cost effective, compared with a no-treatment control, the researchers wrote.

The findings were limited by several factors including the relatively homogeneous population and that neither the therapists nor participants were masked to group allocation. In addition, the study was conducted during the COVID-19 pandemic, so a telehealth model of video consultations was used instead of in-person meetings, but this protocol change allowed for inclusion of participants from diverse locations including rural and remote areas, the researchers said.

More research is needed to assess the implementation of a walking and exercise intervention as part of a discharge plan after an episode of low back pain and to examine the effectiveness of an intervention involving fewer sessions and a range of healthcare providers, they added. However, the results support the value of the intervention, which has a strong potential for successful implementation because of accessibility and low cost.
 

Preventive Interventions Need More Real-World Research

“Preventive interventions for back pain are an important yet neglected consideration,” Diarmuid Denneny, a doctoral candidate at Brunel University London, and Jackie Walumbe, PhD, of the University of Oxford (England), wrote in an accompanying editorial.

Although recurrence of low back pain is common, guidance on prevention and management is lacking, they said. Strengths of the current study include attention to patient and public preferences in the study design; however, the majority of the participants were of relatively high socioeconomic status and 89% reported post-secondary education.

“Given that pain is known to have a higher impact on marginalized and minoritized groups and those experiencing socioeconomic deprivation, we recommend caution in extrapolating these findings to different contexts,” the editorialists wrote.

They also cautioned that the complex nature of the intervention, which included not only walking but education and physiotherapist appointments, might make it difficult to isolate walking as the key factor in the patients’ improvement. The editorialists also emphasized the need for studies of similar interventions conducted by alternative providers including exercise professionals and digital platforms.

However, the WalkBack trial represents progress toward greater support for individuals with recurrent back pain and may be a foundation for other research involving how other forms of physical activity compare in improving back pain, with attention to the role of publish health in delivering physical activity interventions, they said.

The study was supported by the National Health and Medical Research Council, Australia. Dr. Pocovi disclosed scholarships funded by the National Health and Medical Research Council Low Back Pain Centre of Research Excellence (ANZBACK) and Macquarie University. Mr. Denneny disclosed support from an Economic and Social Research Council fellowship, and disclosed consulting fees from Live Well with Pain and Leva clinic; a grant from the Chartered Society of Physiotherapy. Dr. Walumbe disclosed travel support from the Chartered Society of Physiotherapy Charitable Trust.

An intervention combining an individualized walking program and education and significantly reduced low back pain recurrence in adults, compared with controls, based on data from approximately 700 individuals.

Exercise, including walking, is recommended to prevent recurrence of low back pain, but data on the effectiveness and cost-effectiveness of walking as an intervention are lacking, wrote Natasha C. Pocovi, PhD, of Macquarie University, Sydney, Australia, and colleagues.

In a study known as WalkBack, published in the Lancet, the researchers randomized 351 adults aged 18 years and older with a history of more than two prior episodes of low back pain to an intervention and 350 to no intervention.

The intervention consisted of six sessions of education and progressive walking with a physiotherapist over 6 months; both intervention and control groups were followed for a minimum of 12 months and a maximum of 36 months. The mean age of the participants was 54 years, and 81% were female. The primary outcome was the number of days to recurrence of low back pain severe enough to limit activity, based on monthly self-reports.

The intervention was significantly more effective at preventing activity-limiting low back pain recurrence, compared with no intervention (hazard ratio, 0.72; P = .0002), with a median of 208 days and 112 days to recurrence in the intervention and control groups, respectively.

The risk of any low back pain recurrence also was significantly reduced in the intervention group, compared with the controls (HR, 0.80; P = .0066); as was the risk of care-seeking recurrence of low back pain (HR, 0.57; P < .0001).

Overall, the experience of at least one adverse event over 12 months was similar between the intervention and control groups (52% and 54%, respectively), but significantly more adverse events related to lower extremities occurred in the intervention group, compared with the control group (100 vs 54). The intervention also was more likely to be cost effective, compared with a no-treatment control, the researchers wrote.

The findings were limited by several factors including the relatively homogeneous population and that neither the therapists nor participants were masked to group allocation. In addition, the study was conducted during the COVID-19 pandemic, so a telehealth model of video consultations was used instead of in-person meetings, but this protocol change allowed for inclusion of participants from diverse locations including rural and remote areas, the researchers said.

More research is needed to assess the implementation of a walking and exercise intervention as part of a discharge plan after an episode of low back pain and to examine the effectiveness of an intervention involving fewer sessions and a range of healthcare providers, they added. However, the results support the value of the intervention, which has a strong potential for successful implementation because of accessibility and low cost.
 

Preventive Interventions Need More Real-World Research

“Preventive interventions for back pain are an important yet neglected consideration,” Diarmuid Denneny, a doctoral candidate at Brunel University London, and Jackie Walumbe, PhD, of the University of Oxford (England), wrote in an accompanying editorial.

Although recurrence of low back pain is common, guidance on prevention and management is lacking, they said. Strengths of the current study include attention to patient and public preferences in the study design; however, the majority of the participants were of relatively high socioeconomic status and 89% reported post-secondary education.

“Given that pain is known to have a higher impact on marginalized and minoritized groups and those experiencing socioeconomic deprivation, we recommend caution in extrapolating these findings to different contexts,” the editorialists wrote.

They also cautioned that the complex nature of the intervention, which included not only walking but education and physiotherapist appointments, might make it difficult to isolate walking as the key factor in the patients’ improvement. The editorialists also emphasized the need for studies of similar interventions conducted by alternative providers including exercise professionals and digital platforms.

However, the WalkBack trial represents progress toward greater support for individuals with recurrent back pain and may be a foundation for other research involving how other forms of physical activity compare in improving back pain, with attention to the role of publish health in delivering physical activity interventions, they said.

The study was supported by the National Health and Medical Research Council, Australia. Dr. Pocovi disclosed scholarships funded by the National Health and Medical Research Council Low Back Pain Centre of Research Excellence (ANZBACK) and Macquarie University. Mr. Denneny disclosed support from an Economic and Social Research Council fellowship, and disclosed consulting fees from Live Well with Pain and Leva clinic; a grant from the Chartered Society of Physiotherapy. Dr. Walumbe disclosed travel support from the Chartered Society of Physiotherapy Charitable Trust.

The US Food and Drug Administration (FDA) has approved Skyrizi (risankizumab-rzaa; AbbVie) for the treatment of moderately to severely active ulcerative colitis in adults. This approval makes it the first specific anti-interleukin 23 monoclonal antibody indicated for both ulcerative colitis and moderate to severe Crohn’s disease. 

The drug is also approved in the United States for the treatment of adults with active psoriatic arthritis and moderate to severe plaque psoriasis.

The safety and efficacy of Skyrizi for ulcerative colitis is supported by data from two phase 3 clinical trials: a 12-week induction study (INSPIRE) and a 52-week maintenance study (COMMAND). 

The data showed that clinical remission, the primary endpoint in both the induction and maintenance studies, was achieved along with endoscopic improvement, which was a key secondary endpoint.

“When treating patients with ulcerative colitis, it’s important to prioritize both early and sustained clinical remission as well as endoscopic improvement,” Edward V. Loftus Jr., MD, AGAF, gastroenterologist at Mayo Clinic in Rochester, Minnesota, said in a news release. “This approval for Skyrizi is an important step toward addressing these treatment goals.”

For the treatment of ulcerative colitis, dosing includes a 12-week induction period with three 1200-mg doses delivered every 4 weeks followed by maintenance therapy of either 180 mg or 360 mg delivered every 8 weeks.

After the induction period, Skyrizi treatment can be maintained at home using an on-body injector (OBI). “The OBI is a hands-free device designed with patients in mind that adheres to the body and takes about 5 minutes to deliver the medication following preparation steps,” according to the news release. 

Full prescribing information is available online. 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved Skyrizi (risankizumab-rzaa; AbbVie) for the treatment of moderately to severely active ulcerative colitis in adults. This approval makes it the first specific anti-interleukin 23 monoclonal antibody indicated for both ulcerative colitis and moderate to severe Crohn’s disease. 

The drug is also approved in the United States for the treatment of adults with active psoriatic arthritis and moderate to severe plaque psoriasis.

The safety and efficacy of Skyrizi for ulcerative colitis is supported by data from two phase 3 clinical trials: a 12-week induction study (INSPIRE) and a 52-week maintenance study (COMMAND). 

The data showed that clinical remission, the primary endpoint in both the induction and maintenance studies, was achieved along with endoscopic improvement, which was a key secondary endpoint.

“When treating patients with ulcerative colitis, it’s important to prioritize both early and sustained clinical remission as well as endoscopic improvement,” Edward V. Loftus Jr., MD, AGAF, gastroenterologist at Mayo Clinic in Rochester, Minnesota, said in a news release. “This approval for Skyrizi is an important step toward addressing these treatment goals.”

For the treatment of ulcerative colitis, dosing includes a 12-week induction period with three 1200-mg doses delivered every 4 weeks followed by maintenance therapy of either 180 mg or 360 mg delivered every 8 weeks.

After the induction period, Skyrizi treatment can be maintained at home using an on-body injector (OBI). “The OBI is a hands-free device designed with patients in mind that adheres to the body and takes about 5 minutes to deliver the medication following preparation steps,” according to the news release. 

Full prescribing information is available online. 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved Skyrizi (risankizumab-rzaa; AbbVie) for the treatment of moderately to severely active ulcerative colitis in adults. This approval makes it the first specific anti-interleukin 23 monoclonal antibody indicated for both ulcerative colitis and moderate to severe Crohn’s disease. 

The drug is also approved in the United States for the treatment of adults with active psoriatic arthritis and moderate to severe plaque psoriasis.

The safety and efficacy of Skyrizi for ulcerative colitis is supported by data from two phase 3 clinical trials: a 12-week induction study (INSPIRE) and a 52-week maintenance study (COMMAND). 

The data showed that clinical remission, the primary endpoint in both the induction and maintenance studies, was achieved along with endoscopic improvement, which was a key secondary endpoint.

“When treating patients with ulcerative colitis, it’s important to prioritize both early and sustained clinical remission as well as endoscopic improvement,” Edward V. Loftus Jr., MD, AGAF, gastroenterologist at Mayo Clinic in Rochester, Minnesota, said in a news release. “This approval for Skyrizi is an important step toward addressing these treatment goals.”

For the treatment of ulcerative colitis, dosing includes a 12-week induction period with three 1200-mg doses delivered every 4 weeks followed by maintenance therapy of either 180 mg or 360 mg delivered every 8 weeks.

After the induction period, Skyrizi treatment can be maintained at home using an on-body injector (OBI). “The OBI is a hands-free device designed with patients in mind that adheres to the body and takes about 5 minutes to deliver the medication following preparation steps,” according to the news release. 

Full prescribing information is available online. 

A version of this article appeared on Medscape.com.

Glofitamab, a fixed-duration CD20xCD3 bispecific antibody, combined with a chemotherapy regimen of gemcitabine and oxaliplatin (GemOx), shows significant survival benefits in the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), compared with the standard-of-care regimen.

“Glofitamab is the first CD20xCD3 bispecific antibody to demonstrate an overall survival benefit in DLBCL in a randomized phase 3 trial,” said first author Jeremy Abramson, MD, of the Massachusetts General Hospital Cancer Center, Boston, Massachusetts, in a press briefing at the annual meeting of the European Hematology Association (EHA) in Madrid.

“These results support the use of glofitamab GemOx as new, off-the-shelf treatment for relapsed/refractory DLBCL in patients who are transplant ineligible in the second-line or later setting,” he said.

The findings are from the phase 3 STARGLO study involving 274 patients with R/R DLBCL who had previously been treated either with at least two prior lines of therapy, or—if only one prior line of therapy—were determined to be ineligible for autologous stem cell transplant (ASCT).

At a median follow-up of 21 months, those treated with glofitamab combined with GemOx had a significantly higher median overall survival of 25.5 months, compared with those treated with the standard of care of rituximab and GemOx (12.9 months; hazard ratio [HR], 0.62; P = .006).

“The results show a 38% lower risk of death with the glofitamab plus GemOx, compared with [the rituximab regimen],” Dr. Abramson said.

Secondary endpoints showed consistent benefits with the glofitamab regimen, with significant improvements in progression-free survival and complete remission.
 

Unmet Need for Accessible Therapies

Relapsed/refractory DLBCL, the most common form of non-Hodgkin lymphoma (NHL) in the United States, is an aggressive blood cancer. The standard second-line therapy is high-dose chemotherapy followed by ASCT. However, factors including older age or coexisting medical conditions can compromise response, and those who relapse or are refractory to subsequent therapies have poor outcomes.

“Relapsed DLBCL in the second-line setting or later continues to represent an area of medical need,” Dr. Abramson said.

While several CD20xCD3 bispecific antibody drugs are under development to address the need, glofitamab was the first off-the-shelf, fixed-duration bispecific antibody to receive accelerated approval from the US Food and Drug Administration (FDA) for the treatment of R/R DLBCL, specifically as monotherapy after two or more lines of systemic therapy.

That approval was based on results from a pivotal phase 1/2 study, which showed high rates of deep and durable complete remission with the monotherapy.

To further evaluate glofitamab in combination with GemOx, the authors conducted the multicenter, open-label STARGLO trial, which extended enrollment to patients with just one prior therapy if they were determined to be stem cell transplant ineligible. Patients were also required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

Patients were randomized 2:1 either to treatment with glofitamab combined with GemOx, involving 8 cycles, in addition to 4 cycles of glofitamab monotherapy (n = 183), or to the rituximab plus GemOx regimen in 8 cycles (n = 91).

Overall, 153 (55.8%) of patients had primary refractory disease and 166 (60.6%) were refractory to their last therapy. The median age was 68, and 37% had two or more lines of therapy, including some who had received chimeric antigen receptor T-cell (CAR T) therapy (8.8% in the glofitamab group and 7.1% in the rituximab group).

In addition to the significant overall survival benefit, the glofitamab regimen also showed significantly improved progression-free survival at a median follow-up of 16.1 months, as observed by IRC-assessed PFS, with a median progression-free survival rate of 13.8 months vs 3.6 months (HR, 0.40; P < .0001).

The complete remission rate was doubled with glofitamab-GemOx, with a rate of 58.5% vs 25.3%, respectively; P < .0001.

Similar results were observed in subgroups, including relapsed vs refractory patients and those treated as a second or third line of care.

The median number of cycles received was higher among those receiving glofitamab (11 vs four cycles).

Adverse event (AE) rates were higher with glofitamab vs rituximab, including grade 3-4 AEs (69.4 vs 36.4%), grade 5 AEs (8.3 vs 4.5%; primarily driven by an imbalance of COVID-19 AEs), and serious AEs (54.4 vs 17.0%; primarily cytokine release syndrome [CRS]).

CRS was the most frequently reported AE in the glofitamab group (grade 1: 31.4%; grade 2: 10.5%; and grade 3: 2.3%), and events consistent with immune effector cell–associated neurotoxicity syndrome were reported in four patients (2.3%), all of which were concurrent with CRS.

Other AEs were consistent with the known risks associated with the therapy regimens.

“We found that with glofitamab GemOx, the toxicities were manageable, and the most common toxicity of CRS was predominantly low-grade and occurred with step-up dosing in cycle one and was completely reversible,” Dr. Abramson said.

He noted that the higher rate of grade 5 AEs with glofitamab GemOx “was far outweighed by the survival benefit for disease control.”

Overall, “these findings represent the best outcomes observed in a phase 3 trial for relapsed/refractory diffuse large B-cell lymphoma patients who are considered transplant ineligible,” Dr. Abramson said in an interview.
 

Improved Accessibility Vs CAR-T Therapy

Among key developments in the treatment of R/R DLBCL has been the advent and approval of potentially highly effective CAR T-cell therapy, with the anti-CD19 CAR T cell isiocabtagene maraleucel also FDA approved in the non–transplant eligible DLBCL second-line setting.

Asked in the press briefing about the role of glofitamab GemOx in relation to CAR T cell’s significant benefits, Dr. Abramson underscored the important limitations in CAR T-cell accessibility.

“What I would say is a rising tide lifts all boats,” he responded. “It’s great to have multiple effective immunotherapy strategies.”

However, “CAR T cells of course are not available to most people in the US or worldwide,” he explained.

“They are more difficult to access, they require lymphodepleting chemotherapy, and so ultimately, the majority of patients who could potentially benefit from a CAR T cell probably don’t have access to them in the first place.”

He noted that “the appeal of a regimen like [glofitamab] is that it is an off-the-shelf, targeted immunotherapy combined with a well-tolerated chemotherapy backbone and should be more broadly accessible outside of just tertiary care centers in major cities.”
 

Long-Term Durability?

Looking ahead, Dr. Abramson noted that a key issue of focus is how long the encouraging results actually last.

“The major ongoing question with this trial is the long-term durability of remissions,” he said.

“Thus far, with a median of 21 months of follow-up for overall survival, the results are encouraging but longer follow-up is needed,” he added.

“Further trials are needed in a broader large B-cell lymphoma population as this trial was limited to DLBCL not otherwise specified, so did not include patients with transformed lymphoma, primary mediastinal B-cell lymphoma, high grade B-cell lymphoma, etc.” 
 

Is Chemo Necessary?

Commenting on the findings, Jonathan W. Friedberg, MD, director of the Wilmot Cancer Institute, University of Rochester School of Medicine, in Rochester, New York, underscored that, “given the overall survival benefit, these findings are clearly clinically significant.”

Noting that “these results add to evidence of high activity of bispecific antibodies in this disease,” Dr. Friedberg speculated on the role of chemotherapy with the therapy.

“Indeed, an important question in this study is whether the addition of chemotherapy to glofitamab is necessary, as high response rates with durable responses in patients who achieve complete remission have been demonstrated with single agent bispecific antibody therapy,” he said. 

With the durability of CAR T therapy shown in long-term follow-up of trials to exceed 5 years, Dr. Friedberg added that “it is not known how bispecific antibody therapy, with or without chemotherapy, compares to CAR T-cell therapy and how to sequence CAR T and bispecific antibody therapy.”

Dr. Friedberg agreed that longer-term results are needed get a clearer, fuller picture of the therapy’s effects.

“I have no doubt that the overall survival benefit will endure, but in DLBCL our goal should be cure, and whether glofitamab cures as many patients as CAR T-cell therapy is not currently known and will require further follow-up of this and other trials.”

The study was sponsored by F. Hoffman-La Roche Ltd. Dr. Abramson reported ties with AbbVie, ADC Therapeutics, AstraZeneca, BeiGene, BMS, Cellectar, Caribou Biosciences, Celgene, Genentech, Gilead, Incyte, Interius, Janssen, Lilly, Novartis, F. Hoffmann-La Roche Ltd, Seagen, and Takeda. Dr. Friedberg had no disclosures.

Glofitamab, a fixed-duration CD20xCD3 bispecific antibody, combined with a chemotherapy regimen of gemcitabine and oxaliplatin (GemOx), shows significant survival benefits in the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), compared with the standard-of-care regimen.

“Glofitamab is the first CD20xCD3 bispecific antibody to demonstrate an overall survival benefit in DLBCL in a randomized phase 3 trial,” said first author Jeremy Abramson, MD, of the Massachusetts General Hospital Cancer Center, Boston, Massachusetts, in a press briefing at the annual meeting of the European Hematology Association (EHA) in Madrid.

“These results support the use of glofitamab GemOx as new, off-the-shelf treatment for relapsed/refractory DLBCL in patients who are transplant ineligible in the second-line or later setting,” he said.

The findings are from the phase 3 STARGLO study involving 274 patients with R/R DLBCL who had previously been treated either with at least two prior lines of therapy, or—if only one prior line of therapy—were determined to be ineligible for autologous stem cell transplant (ASCT).

At a median follow-up of 21 months, those treated with glofitamab combined with GemOx had a significantly higher median overall survival of 25.5 months, compared with those treated with the standard of care of rituximab and GemOx (12.9 months; hazard ratio [HR], 0.62; P = .006).

“The results show a 38% lower risk of death with the glofitamab plus GemOx, compared with [the rituximab regimen],” Dr. Abramson said.

Secondary endpoints showed consistent benefits with the glofitamab regimen, with significant improvements in progression-free survival and complete remission.
 

Unmet Need for Accessible Therapies

Relapsed/refractory DLBCL, the most common form of non-Hodgkin lymphoma (NHL) in the United States, is an aggressive blood cancer. The standard second-line therapy is high-dose chemotherapy followed by ASCT. However, factors including older age or coexisting medical conditions can compromise response, and those who relapse or are refractory to subsequent therapies have poor outcomes.

“Relapsed DLBCL in the second-line setting or later continues to represent an area of medical need,” Dr. Abramson said.

While several CD20xCD3 bispecific antibody drugs are under development to address the need, glofitamab was the first off-the-shelf, fixed-duration bispecific antibody to receive accelerated approval from the US Food and Drug Administration (FDA) for the treatment of R/R DLBCL, specifically as monotherapy after two or more lines of systemic therapy.

That approval was based on results from a pivotal phase 1/2 study, which showed high rates of deep and durable complete remission with the monotherapy.

To further evaluate glofitamab in combination with GemOx, the authors conducted the multicenter, open-label STARGLO trial, which extended enrollment to patients with just one prior therapy if they were determined to be stem cell transplant ineligible. Patients were also required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

Patients were randomized 2:1 either to treatment with glofitamab combined with GemOx, involving 8 cycles, in addition to 4 cycles of glofitamab monotherapy (n = 183), or to the rituximab plus GemOx regimen in 8 cycles (n = 91).

Overall, 153 (55.8%) of patients had primary refractory disease and 166 (60.6%) were refractory to their last therapy. The median age was 68, and 37% had two or more lines of therapy, including some who had received chimeric antigen receptor T-cell (CAR T) therapy (8.8% in the glofitamab group and 7.1% in the rituximab group).

In addition to the significant overall survival benefit, the glofitamab regimen also showed significantly improved progression-free survival at a median follow-up of 16.1 months, as observed by IRC-assessed PFS, with a median progression-free survival rate of 13.8 months vs 3.6 months (HR, 0.40; P < .0001).

The complete remission rate was doubled with glofitamab-GemOx, with a rate of 58.5% vs 25.3%, respectively; P < .0001.

Similar results were observed in subgroups, including relapsed vs refractory patients and those treated as a second or third line of care.

The median number of cycles received was higher among those receiving glofitamab (11 vs four cycles).

Adverse event (AE) rates were higher with glofitamab vs rituximab, including grade 3-4 AEs (69.4 vs 36.4%), grade 5 AEs (8.3 vs 4.5%; primarily driven by an imbalance of COVID-19 AEs), and serious AEs (54.4 vs 17.0%; primarily cytokine release syndrome [CRS]).

CRS was the most frequently reported AE in the glofitamab group (grade 1: 31.4%; grade 2: 10.5%; and grade 3: 2.3%), and events consistent with immune effector cell–associated neurotoxicity syndrome were reported in four patients (2.3%), all of which were concurrent with CRS.

Other AEs were consistent with the known risks associated with the therapy regimens.

“We found that with glofitamab GemOx, the toxicities were manageable, and the most common toxicity of CRS was predominantly low-grade and occurred with step-up dosing in cycle one and was completely reversible,” Dr. Abramson said.

He noted that the higher rate of grade 5 AEs with glofitamab GemOx “was far outweighed by the survival benefit for disease control.”

Overall, “these findings represent the best outcomes observed in a phase 3 trial for relapsed/refractory diffuse large B-cell lymphoma patients who are considered transplant ineligible,” Dr. Abramson said in an interview.
 

Improved Accessibility Vs CAR-T Therapy

Among key developments in the treatment of R/R DLBCL has been the advent and approval of potentially highly effective CAR T-cell therapy, with the anti-CD19 CAR T cell isiocabtagene maraleucel also FDA approved in the non–transplant eligible DLBCL second-line setting.

Asked in the press briefing about the role of glofitamab GemOx in relation to CAR T cell’s significant benefits, Dr. Abramson underscored the important limitations in CAR T-cell accessibility.

“What I would say is a rising tide lifts all boats,” he responded. “It’s great to have multiple effective immunotherapy strategies.”

However, “CAR T cells of course are not available to most people in the US or worldwide,” he explained.

“They are more difficult to access, they require lymphodepleting chemotherapy, and so ultimately, the majority of patients who could potentially benefit from a CAR T cell probably don’t have access to them in the first place.”

He noted that “the appeal of a regimen like [glofitamab] is that it is an off-the-shelf, targeted immunotherapy combined with a well-tolerated chemotherapy backbone and should be more broadly accessible outside of just tertiary care centers in major cities.”
 

Long-Term Durability?

Looking ahead, Dr. Abramson noted that a key issue of focus is how long the encouraging results actually last.

“The major ongoing question with this trial is the long-term durability of remissions,” he said.

“Thus far, with a median of 21 months of follow-up for overall survival, the results are encouraging but longer follow-up is needed,” he added.

“Further trials are needed in a broader large B-cell lymphoma population as this trial was limited to DLBCL not otherwise specified, so did not include patients with transformed lymphoma, primary mediastinal B-cell lymphoma, high grade B-cell lymphoma, etc.” 
 

Is Chemo Necessary?

Commenting on the findings, Jonathan W. Friedberg, MD, director of the Wilmot Cancer Institute, University of Rochester School of Medicine, in Rochester, New York, underscored that, “given the overall survival benefit, these findings are clearly clinically significant.”

Noting that “these results add to evidence of high activity of bispecific antibodies in this disease,” Dr. Friedberg speculated on the role of chemotherapy with the therapy.

“Indeed, an important question in this study is whether the addition of chemotherapy to glofitamab is necessary, as high response rates with durable responses in patients who achieve complete remission have been demonstrated with single agent bispecific antibody therapy,” he said. 

With the durability of CAR T therapy shown in long-term follow-up of trials to exceed 5 years, Dr. Friedberg added that “it is not known how bispecific antibody therapy, with or without chemotherapy, compares to CAR T-cell therapy and how to sequence CAR T and bispecific antibody therapy.”

Dr. Friedberg agreed that longer-term results are needed get a clearer, fuller picture of the therapy’s effects.

“I have no doubt that the overall survival benefit will endure, but in DLBCL our goal should be cure, and whether glofitamab cures as many patients as CAR T-cell therapy is not currently known and will require further follow-up of this and other trials.”

The study was sponsored by F. Hoffman-La Roche Ltd. Dr. Abramson reported ties with AbbVie, ADC Therapeutics, AstraZeneca, BeiGene, BMS, Cellectar, Caribou Biosciences, Celgene, Genentech, Gilead, Incyte, Interius, Janssen, Lilly, Novartis, F. Hoffmann-La Roche Ltd, Seagen, and Takeda. Dr. Friedberg had no disclosures.

Glofitamab, a fixed-duration CD20xCD3 bispecific antibody, combined with a chemotherapy regimen of gemcitabine and oxaliplatin (GemOx), shows significant survival benefits in the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), compared with the standard-of-care regimen.

“Glofitamab is the first CD20xCD3 bispecific antibody to demonstrate an overall survival benefit in DLBCL in a randomized phase 3 trial,” said first author Jeremy Abramson, MD, of the Massachusetts General Hospital Cancer Center, Boston, Massachusetts, in a press briefing at the annual meeting of the European Hematology Association (EHA) in Madrid.

“These results support the use of glofitamab GemOx as new, off-the-shelf treatment for relapsed/refractory DLBCL in patients who are transplant ineligible in the second-line or later setting,” he said.

The findings are from the phase 3 STARGLO study involving 274 patients with R/R DLBCL who had previously been treated either with at least two prior lines of therapy, or—if only one prior line of therapy—were determined to be ineligible for autologous stem cell transplant (ASCT).

At a median follow-up of 21 months, those treated with glofitamab combined with GemOx had a significantly higher median overall survival of 25.5 months, compared with those treated with the standard of care of rituximab and GemOx (12.9 months; hazard ratio [HR], 0.62; P = .006).

“The results show a 38% lower risk of death with the glofitamab plus GemOx, compared with [the rituximab regimen],” Dr. Abramson said.

Secondary endpoints showed consistent benefits with the glofitamab regimen, with significant improvements in progression-free survival and complete remission.
 

Unmet Need for Accessible Therapies

Relapsed/refractory DLBCL, the most common form of non-Hodgkin lymphoma (NHL) in the United States, is an aggressive blood cancer. The standard second-line therapy is high-dose chemotherapy followed by ASCT. However, factors including older age or coexisting medical conditions can compromise response, and those who relapse or are refractory to subsequent therapies have poor outcomes.

“Relapsed DLBCL in the second-line setting or later continues to represent an area of medical need,” Dr. Abramson said.

While several CD20xCD3 bispecific antibody drugs are under development to address the need, glofitamab was the first off-the-shelf, fixed-duration bispecific antibody to receive accelerated approval from the US Food and Drug Administration (FDA) for the treatment of R/R DLBCL, specifically as monotherapy after two or more lines of systemic therapy.

That approval was based on results from a pivotal phase 1/2 study, which showed high rates of deep and durable complete remission with the monotherapy.

To further evaluate glofitamab in combination with GemOx, the authors conducted the multicenter, open-label STARGLO trial, which extended enrollment to patients with just one prior therapy if they were determined to be stem cell transplant ineligible. Patients were also required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

Patients were randomized 2:1 either to treatment with glofitamab combined with GemOx, involving 8 cycles, in addition to 4 cycles of glofitamab monotherapy (n = 183), or to the rituximab plus GemOx regimen in 8 cycles (n = 91).

Overall, 153 (55.8%) of patients had primary refractory disease and 166 (60.6%) were refractory to their last therapy. The median age was 68, and 37% had two or more lines of therapy, including some who had received chimeric antigen receptor T-cell (CAR T) therapy (8.8% in the glofitamab group and 7.1% in the rituximab group).

In addition to the significant overall survival benefit, the glofitamab regimen also showed significantly improved progression-free survival at a median follow-up of 16.1 months, as observed by IRC-assessed PFS, with a median progression-free survival rate of 13.8 months vs 3.6 months (HR, 0.40; P < .0001).

The complete remission rate was doubled with glofitamab-GemOx, with a rate of 58.5% vs 25.3%, respectively; P < .0001.

Similar results were observed in subgroups, including relapsed vs refractory patients and those treated as a second or third line of care.

The median number of cycles received was higher among those receiving glofitamab (11 vs four cycles).

Adverse event (AE) rates were higher with glofitamab vs rituximab, including grade 3-4 AEs (69.4 vs 36.4%), grade 5 AEs (8.3 vs 4.5%; primarily driven by an imbalance of COVID-19 AEs), and serious AEs (54.4 vs 17.0%; primarily cytokine release syndrome [CRS]).

CRS was the most frequently reported AE in the glofitamab group (grade 1: 31.4%; grade 2: 10.5%; and grade 3: 2.3%), and events consistent with immune effector cell–associated neurotoxicity syndrome were reported in four patients (2.3%), all of which were concurrent with CRS.

Other AEs were consistent with the known risks associated with the therapy regimens.

“We found that with glofitamab GemOx, the toxicities were manageable, and the most common toxicity of CRS was predominantly low-grade and occurred with step-up dosing in cycle one and was completely reversible,” Dr. Abramson said.

He noted that the higher rate of grade 5 AEs with glofitamab GemOx “was far outweighed by the survival benefit for disease control.”

Overall, “these findings represent the best outcomes observed in a phase 3 trial for relapsed/refractory diffuse large B-cell lymphoma patients who are considered transplant ineligible,” Dr. Abramson said in an interview.
 

Improved Accessibility Vs CAR-T Therapy

Among key developments in the treatment of R/R DLBCL has been the advent and approval of potentially highly effective CAR T-cell therapy, with the anti-CD19 CAR T cell isiocabtagene maraleucel also FDA approved in the non–transplant eligible DLBCL second-line setting.

Asked in the press briefing about the role of glofitamab GemOx in relation to CAR T cell’s significant benefits, Dr. Abramson underscored the important limitations in CAR T-cell accessibility.

“What I would say is a rising tide lifts all boats,” he responded. “It’s great to have multiple effective immunotherapy strategies.”

However, “CAR T cells of course are not available to most people in the US or worldwide,” he explained.

“They are more difficult to access, they require lymphodepleting chemotherapy, and so ultimately, the majority of patients who could potentially benefit from a CAR T cell probably don’t have access to them in the first place.”

He noted that “the appeal of a regimen like [glofitamab] is that it is an off-the-shelf, targeted immunotherapy combined with a well-tolerated chemotherapy backbone and should be more broadly accessible outside of just tertiary care centers in major cities.”
 

Long-Term Durability?

Looking ahead, Dr. Abramson noted that a key issue of focus is how long the encouraging results actually last.

“The major ongoing question with this trial is the long-term durability of remissions,” he said.

“Thus far, with a median of 21 months of follow-up for overall survival, the results are encouraging but longer follow-up is needed,” he added.

“Further trials are needed in a broader large B-cell lymphoma population as this trial was limited to DLBCL not otherwise specified, so did not include patients with transformed lymphoma, primary mediastinal B-cell lymphoma, high grade B-cell lymphoma, etc.” 
 

Is Chemo Necessary?

Commenting on the findings, Jonathan W. Friedberg, MD, director of the Wilmot Cancer Institute, University of Rochester School of Medicine, in Rochester, New York, underscored that, “given the overall survival benefit, these findings are clearly clinically significant.”

Noting that “these results add to evidence of high activity of bispecific antibodies in this disease,” Dr. Friedberg speculated on the role of chemotherapy with the therapy.

“Indeed, an important question in this study is whether the addition of chemotherapy to glofitamab is necessary, as high response rates with durable responses in patients who achieve complete remission have been demonstrated with single agent bispecific antibody therapy,” he said. 

With the durability of CAR T therapy shown in long-term follow-up of trials to exceed 5 years, Dr. Friedberg added that “it is not known how bispecific antibody therapy, with or without chemotherapy, compares to CAR T-cell therapy and how to sequence CAR T and bispecific antibody therapy.”

Dr. Friedberg agreed that longer-term results are needed get a clearer, fuller picture of the therapy’s effects.

“I have no doubt that the overall survival benefit will endure, but in DLBCL our goal should be cure, and whether glofitamab cures as many patients as CAR T-cell therapy is not currently known and will require further follow-up of this and other trials.”

The study was sponsored by F. Hoffman-La Roche Ltd. Dr. Abramson reported ties with AbbVie, ADC Therapeutics, AstraZeneca, BeiGene, BMS, Cellectar, Caribou Biosciences, Celgene, Genentech, Gilead, Incyte, Interius, Janssen, Lilly, Novartis, F. Hoffmann-La Roche Ltd, Seagen, and Takeda. Dr. Friedberg had no disclosures.