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Biosimilars Have Driven Down Cost of Infliximab
LAS VEGAS — , according to two new retrospective analyses that separately looked at private insurance and Medicare patients.
“It is interesting to see that biosimilar use is increasing in patients with Medicare insurance in the U.S. since introduction into the market. This shows that clinicians are getting more comfortable with their use in clinical practice,” said Sara Horst, MD, associate professor of gastroenterology, hepatology, and nutrition at Vanderbilt University Medical Center in Nashville, Tennessee. That “is a continued important question in use, especially in the older population,” Dr. Horst said at the poster session where the two studies were presented, at the annual Crohn’s & Colitis Congress®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
One study examined Medicare part D participants. The researchers included infliximab prescriptions between 2013 and 2021, with a break in 2017 when biosimilars were first introduced. Between 2013 and 2017, there was a 93.7% annual increase in infliximab cost, and a 29.0% increase in annual claims. Between 2017 and 2021, those numbers declined to 23.9% and 12.1%, respectively. The researchers also examined trends by individual states and found a wide range of results. “Nationwide, it seems to be doing exactly what you’d expect, and I’d say it’s encouraging. This is exactly what you want with the introduction of biosimilars, and this is what you want for the patient population. But there are some states that have not really kept up with the rest of the country, and may need to look further into what types of trends are there,” said Modan Goldman, who presented the study. He is a medical student at Carle Illinois College of Medicine in Urbana, Illinois.
The other study looked at use of infliximab versus a biosimilar between 2015 and 2021 in 42,009 patients 64 or younger, drawing data from Merative Marketscan Commercial Claims and Encounters Database. They excluded government-funded insurance. Between January 2015 and December 2017, the cost of a vial of infliximab increased by $6.31 per month, reaching a maxim cost of $1,491 per vial. In January 2018, the cost decreased by $62 per vial, with a downward trend after that of $12.93 per vial per month.
“[Getting] access to these drugs, especially for pediatric IBD, has been an uphill battle with insurance companies and getting the medication and the doses we want,” said Samantha Paglinco, DO, who presented the Marketscan study.
The findings demonstrated clear cost reductions. “At the beginning of our period, infliximab originator Remicade was a little over $1,200 per vial, and at the end of our period of 2021, we expected it to be around $1,800 per vial. However, with the introduction of multiple infliximab biosimilars, we did see it come down to $800 per vial, which generated a savings of $1,000, which is pretty significant. We’re hoping that by generating overall cost savings to insurance companies, this will allow for greater access, because we know infliximab is such a good medication for pediatric IBD and for many other autoimmune conditions,” said Dr. Paglinco, a pediatric GI fellow at Nationwide Children’s Hospital in Columbus, Ohio.
The decrease in the cost of medication per vial in both the originator and biosimilar is an important finding in light of cost containment strategies, although Dr. Horst pointed out that the study didn’t determine if there were any savings to patients. “That is what clinicians and patients care about the most. I worry that while these savings were seen at insurance and health care organizational levels, patients may not have experienced any cost savings, and this is something we need to consider in the future,” she said.
The FDA created the biosimilar regulatory pathway in 2010 in an effort to reduce costs. “And they have. The cost savings however, has not directly translated to the individual patient in their copays or necessarily in changes to access when prescribing. Nor has it allowed dose escalation more easily, which is frequently needed,” said David T. Rubin, MD, AGAF, who was asked for comment.
Although the changes in prescribing patterns may reflect cost savings to patients, there are some limits to this interpretation, according to Dr. Rubin, of the University of Chicago. Payers are often the ones who determine a switch to biosimilar. The study also does not account for disease activity or phenotype, which can be an important confounder. Newer biologics that have come on to the market in recent years may also have affected the prescribing patterns for infliximab.
Nevertheless, an association between introduction of biosimilars and declining cost in the originator product (Remicade) is welcome, according to Dr. Rubin. “This is nice to see and we have seen it in our practices,” he said.
Unfortunately, “it has also not been seen to translate into reduced costs for patients nor has it been associated with increased access or changes in payer policies to allow these drugs to be used, or dose escalations to occur,” Dr. Rubin added.
Dr. Paglinco and Mr. Goldman have no relevant financial disclosures. Dr. Horst has consulted for Janssen, Takeda, Bristol-Myers Squibb, and Abbvie. Dr. Rubin has received grant support from Takeda and has consulted for Abbvie, Bristol-Myers Squibb, Janssen Pharmaceuticals, Lilly, Pfizer, and Takeda.
LAS VEGAS — , according to two new retrospective analyses that separately looked at private insurance and Medicare patients.
“It is interesting to see that biosimilar use is increasing in patients with Medicare insurance in the U.S. since introduction into the market. This shows that clinicians are getting more comfortable with their use in clinical practice,” said Sara Horst, MD, associate professor of gastroenterology, hepatology, and nutrition at Vanderbilt University Medical Center in Nashville, Tennessee. That “is a continued important question in use, especially in the older population,” Dr. Horst said at the poster session where the two studies were presented, at the annual Crohn’s & Colitis Congress®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
One study examined Medicare part D participants. The researchers included infliximab prescriptions between 2013 and 2021, with a break in 2017 when biosimilars were first introduced. Between 2013 and 2017, there was a 93.7% annual increase in infliximab cost, and a 29.0% increase in annual claims. Between 2017 and 2021, those numbers declined to 23.9% and 12.1%, respectively. The researchers also examined trends by individual states and found a wide range of results. “Nationwide, it seems to be doing exactly what you’d expect, and I’d say it’s encouraging. This is exactly what you want with the introduction of biosimilars, and this is what you want for the patient population. But there are some states that have not really kept up with the rest of the country, and may need to look further into what types of trends are there,” said Modan Goldman, who presented the study. He is a medical student at Carle Illinois College of Medicine in Urbana, Illinois.
The other study looked at use of infliximab versus a biosimilar between 2015 and 2021 in 42,009 patients 64 or younger, drawing data from Merative Marketscan Commercial Claims and Encounters Database. They excluded government-funded insurance. Between January 2015 and December 2017, the cost of a vial of infliximab increased by $6.31 per month, reaching a maxim cost of $1,491 per vial. In January 2018, the cost decreased by $62 per vial, with a downward trend after that of $12.93 per vial per month.
“[Getting] access to these drugs, especially for pediatric IBD, has been an uphill battle with insurance companies and getting the medication and the doses we want,” said Samantha Paglinco, DO, who presented the Marketscan study.
The findings demonstrated clear cost reductions. “At the beginning of our period, infliximab originator Remicade was a little over $1,200 per vial, and at the end of our period of 2021, we expected it to be around $1,800 per vial. However, with the introduction of multiple infliximab biosimilars, we did see it come down to $800 per vial, which generated a savings of $1,000, which is pretty significant. We’re hoping that by generating overall cost savings to insurance companies, this will allow for greater access, because we know infliximab is such a good medication for pediatric IBD and for many other autoimmune conditions,” said Dr. Paglinco, a pediatric GI fellow at Nationwide Children’s Hospital in Columbus, Ohio.
The decrease in the cost of medication per vial in both the originator and biosimilar is an important finding in light of cost containment strategies, although Dr. Horst pointed out that the study didn’t determine if there were any savings to patients. “That is what clinicians and patients care about the most. I worry that while these savings were seen at insurance and health care organizational levels, patients may not have experienced any cost savings, and this is something we need to consider in the future,” she said.
The FDA created the biosimilar regulatory pathway in 2010 in an effort to reduce costs. “And they have. The cost savings however, has not directly translated to the individual patient in their copays or necessarily in changes to access when prescribing. Nor has it allowed dose escalation more easily, which is frequently needed,” said David T. Rubin, MD, AGAF, who was asked for comment.
Although the changes in prescribing patterns may reflect cost savings to patients, there are some limits to this interpretation, according to Dr. Rubin, of the University of Chicago. Payers are often the ones who determine a switch to biosimilar. The study also does not account for disease activity or phenotype, which can be an important confounder. Newer biologics that have come on to the market in recent years may also have affected the prescribing patterns for infliximab.
Nevertheless, an association between introduction of biosimilars and declining cost in the originator product (Remicade) is welcome, according to Dr. Rubin. “This is nice to see and we have seen it in our practices,” he said.
Unfortunately, “it has also not been seen to translate into reduced costs for patients nor has it been associated with increased access or changes in payer policies to allow these drugs to be used, or dose escalations to occur,” Dr. Rubin added.
Dr. Paglinco and Mr. Goldman have no relevant financial disclosures. Dr. Horst has consulted for Janssen, Takeda, Bristol-Myers Squibb, and Abbvie. Dr. Rubin has received grant support from Takeda and has consulted for Abbvie, Bristol-Myers Squibb, Janssen Pharmaceuticals, Lilly, Pfizer, and Takeda.
LAS VEGAS — , according to two new retrospective analyses that separately looked at private insurance and Medicare patients.
“It is interesting to see that biosimilar use is increasing in patients with Medicare insurance in the U.S. since introduction into the market. This shows that clinicians are getting more comfortable with their use in clinical practice,” said Sara Horst, MD, associate professor of gastroenterology, hepatology, and nutrition at Vanderbilt University Medical Center in Nashville, Tennessee. That “is a continued important question in use, especially in the older population,” Dr. Horst said at the poster session where the two studies were presented, at the annual Crohn’s & Colitis Congress®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
One study examined Medicare part D participants. The researchers included infliximab prescriptions between 2013 and 2021, with a break in 2017 when biosimilars were first introduced. Between 2013 and 2017, there was a 93.7% annual increase in infliximab cost, and a 29.0% increase in annual claims. Between 2017 and 2021, those numbers declined to 23.9% and 12.1%, respectively. The researchers also examined trends by individual states and found a wide range of results. “Nationwide, it seems to be doing exactly what you’d expect, and I’d say it’s encouraging. This is exactly what you want with the introduction of biosimilars, and this is what you want for the patient population. But there are some states that have not really kept up with the rest of the country, and may need to look further into what types of trends are there,” said Modan Goldman, who presented the study. He is a medical student at Carle Illinois College of Medicine in Urbana, Illinois.
The other study looked at use of infliximab versus a biosimilar between 2015 and 2021 in 42,009 patients 64 or younger, drawing data from Merative Marketscan Commercial Claims and Encounters Database. They excluded government-funded insurance. Between January 2015 and December 2017, the cost of a vial of infliximab increased by $6.31 per month, reaching a maxim cost of $1,491 per vial. In January 2018, the cost decreased by $62 per vial, with a downward trend after that of $12.93 per vial per month.
“[Getting] access to these drugs, especially for pediatric IBD, has been an uphill battle with insurance companies and getting the medication and the doses we want,” said Samantha Paglinco, DO, who presented the Marketscan study.
The findings demonstrated clear cost reductions. “At the beginning of our period, infliximab originator Remicade was a little over $1,200 per vial, and at the end of our period of 2021, we expected it to be around $1,800 per vial. However, with the introduction of multiple infliximab biosimilars, we did see it come down to $800 per vial, which generated a savings of $1,000, which is pretty significant. We’re hoping that by generating overall cost savings to insurance companies, this will allow for greater access, because we know infliximab is such a good medication for pediatric IBD and for many other autoimmune conditions,” said Dr. Paglinco, a pediatric GI fellow at Nationwide Children’s Hospital in Columbus, Ohio.
The decrease in the cost of medication per vial in both the originator and biosimilar is an important finding in light of cost containment strategies, although Dr. Horst pointed out that the study didn’t determine if there were any savings to patients. “That is what clinicians and patients care about the most. I worry that while these savings were seen at insurance and health care organizational levels, patients may not have experienced any cost savings, and this is something we need to consider in the future,” she said.
The FDA created the biosimilar regulatory pathway in 2010 in an effort to reduce costs. “And they have. The cost savings however, has not directly translated to the individual patient in their copays or necessarily in changes to access when prescribing. Nor has it allowed dose escalation more easily, which is frequently needed,” said David T. Rubin, MD, AGAF, who was asked for comment.
Although the changes in prescribing patterns may reflect cost savings to patients, there are some limits to this interpretation, according to Dr. Rubin, of the University of Chicago. Payers are often the ones who determine a switch to biosimilar. The study also does not account for disease activity or phenotype, which can be an important confounder. Newer biologics that have come on to the market in recent years may also have affected the prescribing patterns for infliximab.
Nevertheless, an association between introduction of biosimilars and declining cost in the originator product (Remicade) is welcome, according to Dr. Rubin. “This is nice to see and we have seen it in our practices,” he said.
Unfortunately, “it has also not been seen to translate into reduced costs for patients nor has it been associated with increased access or changes in payer policies to allow these drugs to be used, or dose escalations to occur,” Dr. Rubin added.
Dr. Paglinco and Mr. Goldman have no relevant financial disclosures. Dr. Horst has consulted for Janssen, Takeda, Bristol-Myers Squibb, and Abbvie. Dr. Rubin has received grant support from Takeda and has consulted for Abbvie, Bristol-Myers Squibb, Janssen Pharmaceuticals, Lilly, Pfizer, and Takeda.
FROM CROHN’S AND COLITIS CONGRESS
How to Prescribe Physical Activity in Patients With Obesity
Exercise should no longer be a mere “complement” or a standard recommendation within healthy lifestyle guidelines, say experts. Recent evidence confirms its physiological importance and endorses its beneficial and therapeutic effects on overall health, particularly in the case of obesity and its comorbidities. These findings emphasized the reasons to include exercise prescription in addressing this condition. This conclusion emerged from discussions among experts in Physical Activity and Sports Sciences during the XIX Congress of the Spanish Society for Obesity, where the role of physical exercise as a therapeutic strategy was analyzed from various perspectives.
Javier Butragueño, PhD, coordinator of the Exercise Working Group at the Spanish Society of Obesity, emphasized the need to “reposition” the role of exercise and the message conveyed to the population. “We must move beyond the typical recommendation to ‘just walk’ and rethink this message. When working with patients with obesity, you realize that, for example, the guideline of 10,000 steps per day makes little sense for those who weigh 140 kg, have been sedentary for a long time, and have not reached 2000 daily steps. Clinically, it becomes evident that current recommendations may not align with the needs of these patients,” he said.
Precision Focus
Dr. Butragueño highlighted the necessity of shifting the central focus from weight-related variables alone. While weight is crucial, evidence suggests that it should be evaluated along with other strategies, such as nutrition and pharmacology.
“The approach must change to view exercise as a metabolism regulator,” said Dr. Butragueño. “For specialists, this means educating the population about the need to stay active for overall health. This is a disruptive message because the prevailing idea, almost obsessive, associates exercise primarily with weight loss, a completely incorrect approach that can even be detrimental in some cases.”
Dr. Butragueño emphasized the supportive role of physical exercise in interventions for these patients. “Data show that it is both an enhancer and a co-adjuvant in strategies that also include psychology and endocrinology. It should be part of the approach to obesity but individualized and phenotyped to give physical activity the necessary dimension in each specific case.”
As an example of this adaptability in therapeutic strategy, Dr. Butragueño referred to addressing binge eating disorder. “In this case, specialists must acknowledge that sports are a third-line option, always behind the psychologist, who plays a primary role. Exercise is used to enhance the emotions triggered through its practice, considering that many of these patients maintain a very negative relationship with their bodies.”
Spanish ‘Prescription Guide’
During his presentation, Dr. Butragueño introduced the positioning document from the Exercise Group of the Spanish Society of Obesity, which is aimed at designing physical activity programs for patients with obesity. He emphasized its importance as a much-needed effort at proposing intervention strategies to guide health professionals and establish a reference framework for collaboration across different approaches to obesity.
Among the noteworthy aspects of the guidelines outlined in this document, Dr. Butragueño highlighted the assessment and classification of physical activity into four levels based on each patient’s physical condition. “This aspect should be studied by the scientific community because ‘humanizing’ exercise prescription by understanding individuals’ needs beyond their BMI is crucial.”
He also discussed the strategy outlined in the document that he said is crucial for implementing an exercise program. “Essentially, it involves two guidelines: First, engage in physical activity for at least 30-60 minutes in what we call zone 2. This includes activities like walking, cycling, or rowing, where one can speak easily with another person or sing without getting out of breath. This is a fundamental part of addressing obesity, as it improves mitochondrial biogenesis, the correct utilization of fatty acids, which is a significant concern in the pathophysiology of obesity and other diseases like cancer.”
The second strategy involves strength training alone or combined with aerobic-cardiovascular exercise. “Studies show that just 20 minutes of strength training 1 day a week for 10 consecutive weeks significantly improves strength levels in sedentary individuals.”
Dr. Butragueño emphasized that to date, there is no doubt that the most effective approach is to combine strength exercises with cardiorespiratory exercises. “This is not only to address obesity but also because, beyond weight impact, this training has proven additional benefits, such as increased oxygenation and improved cognitive capacity.”
Finally, regarding the challenges this shift in focus poses for exercise specialists, Dr. Butragueño pointed out, “Synergies in obesity treatment require sports experts to receive training in other disciplines, elevating our knowledge level and communication with the medical community to emphasize that we are indeed talking about exercise physiology applied to a condition like obesity.”
“In addition, as scientists, we must challenge ourselves to disseminate information at the societal level, surpassing the typical and outdated message of ‘eat less and move more,’ which we know is incorrect. This simplistic formula doesn’t help many patients resolve their issues like fatty liver, diabetes, and other metabolic disorders,” he concluded.
Active Breaks
Other topics debated during the congress included the importance of making exercise prescription a de facto reality in clinical practice and the challenge of achieving therapeutic compliance.
According to experts, one of the well-positioned trends in this regard is the concept of “active breaks” or “exercise snacks.” These breaks involve engaging in short-duration, moderate- to high-intensity activities throughout the day or working hours.
César Bustos, a board member of the Spanish Society of Obesity, mentioned that several studies have demonstrated that simple activities like climbing three flights of stairs or engaging in 1-minute training sessions can increase the metabolic equivalent of cardiovascular capacity and cardiorespiratory fitness. This approach could help reduce cardiovascular disease risk and all-cause mortality by 13%-15%.
“Cardiorespiratory fitness is the ability to engage in physical activity. It has been proven to be a more powerful predictor of mortality risk than traditional risk factors such as hypertension, smoking, obesity, hyperlipidemia, and type 2 diabetes,” said Mr. Bustos.
The expert added that these findings on the benefits of exercise snacks are particularly relevant in the current context, where lack of time is the primary obstacle cited by individuals with obesity for not engaging in regular physical activity. In addition, exercise prescription is considered the primary preventive measure for obesity and its associated diseases.
“Exercise is an essential complement to various treatments and strategies aimed at managing obesity and maintaining long-term weight reductions. However, patient compliance with recommended measures to stay active remains low. This deficiency can be overcome with the adoption of exercise snacks or small doses of exercise, which have become the most effective tool for achieving this goal,” he emphasized.
Also, in line with other experts, Mr. Bustos emphasized the importance of combined strength and cardiovascular training within the same session. “Undoubtedly, this is the most effective modality, as recent meta-analyses reflect. There is also a second effective modality for improving cardiometabolic parameters in patients with obesity: Hybrid training, including games, skipping ropes, and various devices.”
Exerkines and Poly Pills
Antonio García-Hermoso, PhD, a specialist in physical activity and sports at Navarrabiomed, University Hospital of Navarra in Pamplona, Spain, provided an update on the latest evidence regarding exerkines, which are molecules released during exercise. Research into these molecules attempts to analyze and understand the complex network of interactions between various exercise response systems.
Dr. García-Hermoso said that in the case of obesity and type 2 diabetes, research focuses on how exercise can affect patients’ exerkine levels and how these molecules can affect cardiometabolic control.
“The results demonstrate that these molecules are associated with multiple benefits, including improved insulin sensitivity and glucose homeostasis,” said Dr. García-Hermoso. “Concerning obesity, regular exercise has been shown to reduce interleukin-6 levels, positively affecting inflammation in these patients, also being associated with increased lipolysis and fatty acid utilization.”
Dr. García-Hermoso considered that studying exerkines supports the importance of individualized exercise prescription, like prescription of diet or medications.
He emphasized the importance of intensity, “which is even more crucial than the type of physical activity. Intense exercise activates physiological mechanisms, such as increased blood lactate levels, favoring the inhibition of ghrelin signaling associated with appetite. Therefore, higher exercise intensity leads to more lactate and greater inhibition of post-training hunger.”
“It is essential to understand that exercise is a poly pill with many advantages, and one of them is that even in small amounts, if intensity is increased, health benefits increase considerably,” Dr. García-Hermoso concluded.
Dr. Butragueño, Mr. Bustos, and Dr. García-Hermoso declared no relevant economic conflicts of interest.
This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.
Exercise should no longer be a mere “complement” or a standard recommendation within healthy lifestyle guidelines, say experts. Recent evidence confirms its physiological importance and endorses its beneficial and therapeutic effects on overall health, particularly in the case of obesity and its comorbidities. These findings emphasized the reasons to include exercise prescription in addressing this condition. This conclusion emerged from discussions among experts in Physical Activity and Sports Sciences during the XIX Congress of the Spanish Society for Obesity, where the role of physical exercise as a therapeutic strategy was analyzed from various perspectives.
Javier Butragueño, PhD, coordinator of the Exercise Working Group at the Spanish Society of Obesity, emphasized the need to “reposition” the role of exercise and the message conveyed to the population. “We must move beyond the typical recommendation to ‘just walk’ and rethink this message. When working with patients with obesity, you realize that, for example, the guideline of 10,000 steps per day makes little sense for those who weigh 140 kg, have been sedentary for a long time, and have not reached 2000 daily steps. Clinically, it becomes evident that current recommendations may not align with the needs of these patients,” he said.
Precision Focus
Dr. Butragueño highlighted the necessity of shifting the central focus from weight-related variables alone. While weight is crucial, evidence suggests that it should be evaluated along with other strategies, such as nutrition and pharmacology.
“The approach must change to view exercise as a metabolism regulator,” said Dr. Butragueño. “For specialists, this means educating the population about the need to stay active for overall health. This is a disruptive message because the prevailing idea, almost obsessive, associates exercise primarily with weight loss, a completely incorrect approach that can even be detrimental in some cases.”
Dr. Butragueño emphasized the supportive role of physical exercise in interventions for these patients. “Data show that it is both an enhancer and a co-adjuvant in strategies that also include psychology and endocrinology. It should be part of the approach to obesity but individualized and phenotyped to give physical activity the necessary dimension in each specific case.”
As an example of this adaptability in therapeutic strategy, Dr. Butragueño referred to addressing binge eating disorder. “In this case, specialists must acknowledge that sports are a third-line option, always behind the psychologist, who plays a primary role. Exercise is used to enhance the emotions triggered through its practice, considering that many of these patients maintain a very negative relationship with their bodies.”
Spanish ‘Prescription Guide’
During his presentation, Dr. Butragueño introduced the positioning document from the Exercise Group of the Spanish Society of Obesity, which is aimed at designing physical activity programs for patients with obesity. He emphasized its importance as a much-needed effort at proposing intervention strategies to guide health professionals and establish a reference framework for collaboration across different approaches to obesity.
Among the noteworthy aspects of the guidelines outlined in this document, Dr. Butragueño highlighted the assessment and classification of physical activity into four levels based on each patient’s physical condition. “This aspect should be studied by the scientific community because ‘humanizing’ exercise prescription by understanding individuals’ needs beyond their BMI is crucial.”
He also discussed the strategy outlined in the document that he said is crucial for implementing an exercise program. “Essentially, it involves two guidelines: First, engage in physical activity for at least 30-60 minutes in what we call zone 2. This includes activities like walking, cycling, or rowing, where one can speak easily with another person or sing without getting out of breath. This is a fundamental part of addressing obesity, as it improves mitochondrial biogenesis, the correct utilization of fatty acids, which is a significant concern in the pathophysiology of obesity and other diseases like cancer.”
The second strategy involves strength training alone or combined with aerobic-cardiovascular exercise. “Studies show that just 20 minutes of strength training 1 day a week for 10 consecutive weeks significantly improves strength levels in sedentary individuals.”
Dr. Butragueño emphasized that to date, there is no doubt that the most effective approach is to combine strength exercises with cardiorespiratory exercises. “This is not only to address obesity but also because, beyond weight impact, this training has proven additional benefits, such as increased oxygenation and improved cognitive capacity.”
Finally, regarding the challenges this shift in focus poses for exercise specialists, Dr. Butragueño pointed out, “Synergies in obesity treatment require sports experts to receive training in other disciplines, elevating our knowledge level and communication with the medical community to emphasize that we are indeed talking about exercise physiology applied to a condition like obesity.”
“In addition, as scientists, we must challenge ourselves to disseminate information at the societal level, surpassing the typical and outdated message of ‘eat less and move more,’ which we know is incorrect. This simplistic formula doesn’t help many patients resolve their issues like fatty liver, diabetes, and other metabolic disorders,” he concluded.
Active Breaks
Other topics debated during the congress included the importance of making exercise prescription a de facto reality in clinical practice and the challenge of achieving therapeutic compliance.
According to experts, one of the well-positioned trends in this regard is the concept of “active breaks” or “exercise snacks.” These breaks involve engaging in short-duration, moderate- to high-intensity activities throughout the day or working hours.
César Bustos, a board member of the Spanish Society of Obesity, mentioned that several studies have demonstrated that simple activities like climbing three flights of stairs or engaging in 1-minute training sessions can increase the metabolic equivalent of cardiovascular capacity and cardiorespiratory fitness. This approach could help reduce cardiovascular disease risk and all-cause mortality by 13%-15%.
“Cardiorespiratory fitness is the ability to engage in physical activity. It has been proven to be a more powerful predictor of mortality risk than traditional risk factors such as hypertension, smoking, obesity, hyperlipidemia, and type 2 diabetes,” said Mr. Bustos.
The expert added that these findings on the benefits of exercise snacks are particularly relevant in the current context, where lack of time is the primary obstacle cited by individuals with obesity for not engaging in regular physical activity. In addition, exercise prescription is considered the primary preventive measure for obesity and its associated diseases.
“Exercise is an essential complement to various treatments and strategies aimed at managing obesity and maintaining long-term weight reductions. However, patient compliance with recommended measures to stay active remains low. This deficiency can be overcome with the adoption of exercise snacks or small doses of exercise, which have become the most effective tool for achieving this goal,” he emphasized.
Also, in line with other experts, Mr. Bustos emphasized the importance of combined strength and cardiovascular training within the same session. “Undoubtedly, this is the most effective modality, as recent meta-analyses reflect. There is also a second effective modality for improving cardiometabolic parameters in patients with obesity: Hybrid training, including games, skipping ropes, and various devices.”
Exerkines and Poly Pills
Antonio García-Hermoso, PhD, a specialist in physical activity and sports at Navarrabiomed, University Hospital of Navarra in Pamplona, Spain, provided an update on the latest evidence regarding exerkines, which are molecules released during exercise. Research into these molecules attempts to analyze and understand the complex network of interactions between various exercise response systems.
Dr. García-Hermoso said that in the case of obesity and type 2 diabetes, research focuses on how exercise can affect patients’ exerkine levels and how these molecules can affect cardiometabolic control.
“The results demonstrate that these molecules are associated with multiple benefits, including improved insulin sensitivity and glucose homeostasis,” said Dr. García-Hermoso. “Concerning obesity, regular exercise has been shown to reduce interleukin-6 levels, positively affecting inflammation in these patients, also being associated with increased lipolysis and fatty acid utilization.”
Dr. García-Hermoso considered that studying exerkines supports the importance of individualized exercise prescription, like prescription of diet or medications.
He emphasized the importance of intensity, “which is even more crucial than the type of physical activity. Intense exercise activates physiological mechanisms, such as increased blood lactate levels, favoring the inhibition of ghrelin signaling associated with appetite. Therefore, higher exercise intensity leads to more lactate and greater inhibition of post-training hunger.”
“It is essential to understand that exercise is a poly pill with many advantages, and one of them is that even in small amounts, if intensity is increased, health benefits increase considerably,” Dr. García-Hermoso concluded.
Dr. Butragueño, Mr. Bustos, and Dr. García-Hermoso declared no relevant economic conflicts of interest.
This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.
Exercise should no longer be a mere “complement” or a standard recommendation within healthy lifestyle guidelines, say experts. Recent evidence confirms its physiological importance and endorses its beneficial and therapeutic effects on overall health, particularly in the case of obesity and its comorbidities. These findings emphasized the reasons to include exercise prescription in addressing this condition. This conclusion emerged from discussions among experts in Physical Activity and Sports Sciences during the XIX Congress of the Spanish Society for Obesity, where the role of physical exercise as a therapeutic strategy was analyzed from various perspectives.
Javier Butragueño, PhD, coordinator of the Exercise Working Group at the Spanish Society of Obesity, emphasized the need to “reposition” the role of exercise and the message conveyed to the population. “We must move beyond the typical recommendation to ‘just walk’ and rethink this message. When working with patients with obesity, you realize that, for example, the guideline of 10,000 steps per day makes little sense for those who weigh 140 kg, have been sedentary for a long time, and have not reached 2000 daily steps. Clinically, it becomes evident that current recommendations may not align with the needs of these patients,” he said.
Precision Focus
Dr. Butragueño highlighted the necessity of shifting the central focus from weight-related variables alone. While weight is crucial, evidence suggests that it should be evaluated along with other strategies, such as nutrition and pharmacology.
“The approach must change to view exercise as a metabolism regulator,” said Dr. Butragueño. “For specialists, this means educating the population about the need to stay active for overall health. This is a disruptive message because the prevailing idea, almost obsessive, associates exercise primarily with weight loss, a completely incorrect approach that can even be detrimental in some cases.”
Dr. Butragueño emphasized the supportive role of physical exercise in interventions for these patients. “Data show that it is both an enhancer and a co-adjuvant in strategies that also include psychology and endocrinology. It should be part of the approach to obesity but individualized and phenotyped to give physical activity the necessary dimension in each specific case.”
As an example of this adaptability in therapeutic strategy, Dr. Butragueño referred to addressing binge eating disorder. “In this case, specialists must acknowledge that sports are a third-line option, always behind the psychologist, who plays a primary role. Exercise is used to enhance the emotions triggered through its practice, considering that many of these patients maintain a very negative relationship with their bodies.”
Spanish ‘Prescription Guide’
During his presentation, Dr. Butragueño introduced the positioning document from the Exercise Group of the Spanish Society of Obesity, which is aimed at designing physical activity programs for patients with obesity. He emphasized its importance as a much-needed effort at proposing intervention strategies to guide health professionals and establish a reference framework for collaboration across different approaches to obesity.
Among the noteworthy aspects of the guidelines outlined in this document, Dr. Butragueño highlighted the assessment and classification of physical activity into four levels based on each patient’s physical condition. “This aspect should be studied by the scientific community because ‘humanizing’ exercise prescription by understanding individuals’ needs beyond their BMI is crucial.”
He also discussed the strategy outlined in the document that he said is crucial for implementing an exercise program. “Essentially, it involves two guidelines: First, engage in physical activity for at least 30-60 minutes in what we call zone 2. This includes activities like walking, cycling, or rowing, where one can speak easily with another person or sing without getting out of breath. This is a fundamental part of addressing obesity, as it improves mitochondrial biogenesis, the correct utilization of fatty acids, which is a significant concern in the pathophysiology of obesity and other diseases like cancer.”
The second strategy involves strength training alone or combined with aerobic-cardiovascular exercise. “Studies show that just 20 minutes of strength training 1 day a week for 10 consecutive weeks significantly improves strength levels in sedentary individuals.”
Dr. Butragueño emphasized that to date, there is no doubt that the most effective approach is to combine strength exercises with cardiorespiratory exercises. “This is not only to address obesity but also because, beyond weight impact, this training has proven additional benefits, such as increased oxygenation and improved cognitive capacity.”
Finally, regarding the challenges this shift in focus poses for exercise specialists, Dr. Butragueño pointed out, “Synergies in obesity treatment require sports experts to receive training in other disciplines, elevating our knowledge level and communication with the medical community to emphasize that we are indeed talking about exercise physiology applied to a condition like obesity.”
“In addition, as scientists, we must challenge ourselves to disseminate information at the societal level, surpassing the typical and outdated message of ‘eat less and move more,’ which we know is incorrect. This simplistic formula doesn’t help many patients resolve their issues like fatty liver, diabetes, and other metabolic disorders,” he concluded.
Active Breaks
Other topics debated during the congress included the importance of making exercise prescription a de facto reality in clinical practice and the challenge of achieving therapeutic compliance.
According to experts, one of the well-positioned trends in this regard is the concept of “active breaks” or “exercise snacks.” These breaks involve engaging in short-duration, moderate- to high-intensity activities throughout the day or working hours.
César Bustos, a board member of the Spanish Society of Obesity, mentioned that several studies have demonstrated that simple activities like climbing three flights of stairs or engaging in 1-minute training sessions can increase the metabolic equivalent of cardiovascular capacity and cardiorespiratory fitness. This approach could help reduce cardiovascular disease risk and all-cause mortality by 13%-15%.
“Cardiorespiratory fitness is the ability to engage in physical activity. It has been proven to be a more powerful predictor of mortality risk than traditional risk factors such as hypertension, smoking, obesity, hyperlipidemia, and type 2 diabetes,” said Mr. Bustos.
The expert added that these findings on the benefits of exercise snacks are particularly relevant in the current context, where lack of time is the primary obstacle cited by individuals with obesity for not engaging in regular physical activity. In addition, exercise prescription is considered the primary preventive measure for obesity and its associated diseases.
“Exercise is an essential complement to various treatments and strategies aimed at managing obesity and maintaining long-term weight reductions. However, patient compliance with recommended measures to stay active remains low. This deficiency can be overcome with the adoption of exercise snacks or small doses of exercise, which have become the most effective tool for achieving this goal,” he emphasized.
Also, in line with other experts, Mr. Bustos emphasized the importance of combined strength and cardiovascular training within the same session. “Undoubtedly, this is the most effective modality, as recent meta-analyses reflect. There is also a second effective modality for improving cardiometabolic parameters in patients with obesity: Hybrid training, including games, skipping ropes, and various devices.”
Exerkines and Poly Pills
Antonio García-Hermoso, PhD, a specialist in physical activity and sports at Navarrabiomed, University Hospital of Navarra in Pamplona, Spain, provided an update on the latest evidence regarding exerkines, which are molecules released during exercise. Research into these molecules attempts to analyze and understand the complex network of interactions between various exercise response systems.
Dr. García-Hermoso said that in the case of obesity and type 2 diabetes, research focuses on how exercise can affect patients’ exerkine levels and how these molecules can affect cardiometabolic control.
“The results demonstrate that these molecules are associated with multiple benefits, including improved insulin sensitivity and glucose homeostasis,” said Dr. García-Hermoso. “Concerning obesity, regular exercise has been shown to reduce interleukin-6 levels, positively affecting inflammation in these patients, also being associated with increased lipolysis and fatty acid utilization.”
Dr. García-Hermoso considered that studying exerkines supports the importance of individualized exercise prescription, like prescription of diet or medications.
He emphasized the importance of intensity, “which is even more crucial than the type of physical activity. Intense exercise activates physiological mechanisms, such as increased blood lactate levels, favoring the inhibition of ghrelin signaling associated with appetite. Therefore, higher exercise intensity leads to more lactate and greater inhibition of post-training hunger.”
“It is essential to understand that exercise is a poly pill with many advantages, and one of them is that even in small amounts, if intensity is increased, health benefits increase considerably,” Dr. García-Hermoso concluded.
Dr. Butragueño, Mr. Bustos, and Dr. García-Hermoso declared no relevant economic conflicts of interest.
This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.
Oral IL-23 Inhibitor Calms Moderate to Severe Psoriasis
A novel oral drug for plaque psoriasis that targets the same inflammatory pathway as currently available parenteral therapies showed promise for treating moderate to severe disease in a phase 2 dose-finding trial.
Among 255 at week 16 of at least 75% (PASI 75) compared with 9% of patients assigned to placebo, reported Robert Bissonnette, MD, from Innovaderm Research in Montreal, Quebec, Canada, and colleagues.
“The level of reduction of psoriasis that was observed with higher doses of JNJ-77242113 at week 16 was similar in magnitude to the responses seen with several of the injectable biologics that are currently approved for psoriasis,” investigators in the FRONTIER 1 trial wrote in The New England Journal of Medicine.
The investigators noted that among patients assigned to the 100-mg dose of the active drug, 60% had a PASI 90 response, which compares favorably with that seen in phase 3 trials of two other orally available therapies for psoriasis, deucravacitinib (Sotyktu) and apremilast (Otezla). They cautioned, however, against drawing any further inferences from these data, because these agents have not been tested head-to-head against JNJ-77242113 in comparison trials.
Targets IL-23 and IL-17
The investigational agent is an oral IL-23 receptor antagonist peptide that selectively blocks IL-23 proximal signaling as well as the production of downstream inflammatory cytokines such as IL-17, according to the authors.
“Modulation of the interleukin-23 pathway with the use of monoclonal antibodies has shown efficacy in the treatment of psoriasis and is considered to be associated with a more favorable safety profile than older oral therapies (eg, cyclosporine, acitretin, methotrexate, and dimethyl fumarate),” the investigators wrote.
Currently available biologic agents targeting IL-23 include guselkumab (Tremfya), risankizumab (Skyrizi) and tildrakizumab (Ilumya). These agents require intravenous or subcutaneous administration, whereas JNJ-77242113 is taken orally, giving it a theoretical advantage in terms of patient preference.
The novel drug must be taken twice daily on an empty stomach at least 2 hours before food or drink, and those who take it must wait an additional 30 minutes to eat or drink after taking the drug. (This news organization has learned that in planned phase 3 studies, patients will be instructed to take a double daily dose on awakening and then wait 30 minutes for eating or drinking.)
‘Profoundly Effective’
The results of this study have convinced at least one former skeptic of the efficacy of the novel agent.
“They asked me to do the trial, and I turned it down, because I didn’t believe it would work,” said Mark G. Lebwohl, MD, dean for Clinical Therapeutics at the Icahn School of Medicine at Mount Sinai and professor and chairman emeritus of the Department of Dermatology at Mount Sinai Medicine in New York, NY.
In an interview with this news organization, Dr. Lebwohl said that he was initially dubious that a peptide, a short chain of amino acids directed against a receptor, could be effective because it would likely be digested in the intestinal tract.
“Indeed, more than 99% of it is digested, but the data show that the tiny amount that gets through is profoundly effective,” he said.
“I would never have believed that this was going to work – and it did,” Dr. Lebwohl added.
He has signed on as an investigator in the currently recruiting phase 3 ICONIC-LEAD trial, in which JNJ-77242113 will be tested against placebo in adolescents and adults with moderate to severe plaque psoriasis.
In an editorial accompanying the study in the NEJM, Joel M. Gelfand, MD, MSCE, vice chair of clinical research and medical director of the Dermatology Clinical Studies Unit at the University of Pennsylvania in Philadelphia, noted that if confirmed in larger studies, the PASI 90 rate at the highest dose “would be similar to the most effective injectable biologics,” with no evidence of increased adverse events at higher doses.
“However, two occurrences of infection (COVID-19 and an infected cyst) and a suicide attempt were reported as serious adverse events; larger trials will be needed to determine whether such events are attributable to chance, psoriasis itself, or inhibition of interleukin-23 signaling,” cautioned Dr. Gelfand, director of the psoriasis and phototherapy treatment center at the University of Pennsylvania.
In an interview, Dr. Lebwohl said that currently available IL-23 signaling inhibitors have an excellent safety profile and that the investigational oral agent also appears to be very safe. “It’s seeing a target whose effects are known, and the effects are all good and not bad,” he said.
FRONTIER-1 Details
The investigators enrolled eligible adults aged 18 years or older who had moderate to severe plaque psoriasis as defined by an Investigator’s Global Assessment score ≥ 3, a total body-surface area of psoriasis involvement of at least 10%, and a PASI score ≥ 12 who had received their diagnosis of plaque psoriasis at least 6 months before starting the trial. The participants had to be candidates for phototherapy or systemic psoriasis therapy.
Patients were randomly assigned to the active agent at doses of 25 mg once or twice daily, 50 mg once daily, or 100 mg once or twice daily for 16 weeks.
There was a clear dose response, with 37% of patients assigned to 25-mg once-daily dose meeting the primary endpoint of a PASI 75 response at week 16 compared with 51% of those assigned to the 25-mg twice-daily dose, 58% assigned to 50-mg once-daily dose, 65% assigned to 100-mg once-daily dose, and 79% assigned to 100-mg twice-daily dose (P for dose response < .001).
As noted previously, 9% of patients in the placebo group had a PASI 75 response at week 16.
After a mean duration of 15.9 weeks, adverse events after the first dose of JNJ-77242113 (all dose groups were pooled for the safety analysis) were reported in 47% of patients on the 25-mg once-daily dose, 49% on 25-mg twice-daily dose, 60% on 50-mg once-daily dose, 44% on 100-mg once-daily dose, and 62% on 100-mg twice-daily dose. Adverse events after the first dose occurred in 51% of patients assigned to placebo.
The incidence of adverse events did not increase significantly with successively higher dose levels.
As noted by Dr. Gelfand in his editorial, there were three serious adverse events, all occurring in patients on the active drug: a case of COVID-19 in one patient and a suicide attempt in one patient, both in the 100-mg once-daily dose group, and an infected cyst in the 50-mg once-daily group. All three events were determined by the principal investigator and the sponsor to be unrelated to JNJ-77242113.
There were no reports of deaths, major adverse cardiovascular events, or incident cancers during the trial.
The study was supported by Janssen Research and Development. Dr. Bissonnette disclosed institutional research funding and advisory board participation and honoraria with Janssen. Dr. Gelfand disclosed consulting for Janssen Biotech. Dr. Lebwohl disclosed institutional research funding from Janssen but no personal fees.
A version of this article first appeared on Medscape.com.
A novel oral drug for plaque psoriasis that targets the same inflammatory pathway as currently available parenteral therapies showed promise for treating moderate to severe disease in a phase 2 dose-finding trial.
Among 255 at week 16 of at least 75% (PASI 75) compared with 9% of patients assigned to placebo, reported Robert Bissonnette, MD, from Innovaderm Research in Montreal, Quebec, Canada, and colleagues.
“The level of reduction of psoriasis that was observed with higher doses of JNJ-77242113 at week 16 was similar in magnitude to the responses seen with several of the injectable biologics that are currently approved for psoriasis,” investigators in the FRONTIER 1 trial wrote in The New England Journal of Medicine.
The investigators noted that among patients assigned to the 100-mg dose of the active drug, 60% had a PASI 90 response, which compares favorably with that seen in phase 3 trials of two other orally available therapies for psoriasis, deucravacitinib (Sotyktu) and apremilast (Otezla). They cautioned, however, against drawing any further inferences from these data, because these agents have not been tested head-to-head against JNJ-77242113 in comparison trials.
Targets IL-23 and IL-17
The investigational agent is an oral IL-23 receptor antagonist peptide that selectively blocks IL-23 proximal signaling as well as the production of downstream inflammatory cytokines such as IL-17, according to the authors.
“Modulation of the interleukin-23 pathway with the use of monoclonal antibodies has shown efficacy in the treatment of psoriasis and is considered to be associated with a more favorable safety profile than older oral therapies (eg, cyclosporine, acitretin, methotrexate, and dimethyl fumarate),” the investigators wrote.
Currently available biologic agents targeting IL-23 include guselkumab (Tremfya), risankizumab (Skyrizi) and tildrakizumab (Ilumya). These agents require intravenous or subcutaneous administration, whereas JNJ-77242113 is taken orally, giving it a theoretical advantage in terms of patient preference.
The novel drug must be taken twice daily on an empty stomach at least 2 hours before food or drink, and those who take it must wait an additional 30 minutes to eat or drink after taking the drug. (This news organization has learned that in planned phase 3 studies, patients will be instructed to take a double daily dose on awakening and then wait 30 minutes for eating or drinking.)
‘Profoundly Effective’
The results of this study have convinced at least one former skeptic of the efficacy of the novel agent.
“They asked me to do the trial, and I turned it down, because I didn’t believe it would work,” said Mark G. Lebwohl, MD, dean for Clinical Therapeutics at the Icahn School of Medicine at Mount Sinai and professor and chairman emeritus of the Department of Dermatology at Mount Sinai Medicine in New York, NY.
In an interview with this news organization, Dr. Lebwohl said that he was initially dubious that a peptide, a short chain of amino acids directed against a receptor, could be effective because it would likely be digested in the intestinal tract.
“Indeed, more than 99% of it is digested, but the data show that the tiny amount that gets through is profoundly effective,” he said.
“I would never have believed that this was going to work – and it did,” Dr. Lebwohl added.
He has signed on as an investigator in the currently recruiting phase 3 ICONIC-LEAD trial, in which JNJ-77242113 will be tested against placebo in adolescents and adults with moderate to severe plaque psoriasis.
In an editorial accompanying the study in the NEJM, Joel M. Gelfand, MD, MSCE, vice chair of clinical research and medical director of the Dermatology Clinical Studies Unit at the University of Pennsylvania in Philadelphia, noted that if confirmed in larger studies, the PASI 90 rate at the highest dose “would be similar to the most effective injectable biologics,” with no evidence of increased adverse events at higher doses.
“However, two occurrences of infection (COVID-19 and an infected cyst) and a suicide attempt were reported as serious adverse events; larger trials will be needed to determine whether such events are attributable to chance, psoriasis itself, or inhibition of interleukin-23 signaling,” cautioned Dr. Gelfand, director of the psoriasis and phototherapy treatment center at the University of Pennsylvania.
In an interview, Dr. Lebwohl said that currently available IL-23 signaling inhibitors have an excellent safety profile and that the investigational oral agent also appears to be very safe. “It’s seeing a target whose effects are known, and the effects are all good and not bad,” he said.
FRONTIER-1 Details
The investigators enrolled eligible adults aged 18 years or older who had moderate to severe plaque psoriasis as defined by an Investigator’s Global Assessment score ≥ 3, a total body-surface area of psoriasis involvement of at least 10%, and a PASI score ≥ 12 who had received their diagnosis of plaque psoriasis at least 6 months before starting the trial. The participants had to be candidates for phototherapy or systemic psoriasis therapy.
Patients were randomly assigned to the active agent at doses of 25 mg once or twice daily, 50 mg once daily, or 100 mg once or twice daily for 16 weeks.
There was a clear dose response, with 37% of patients assigned to 25-mg once-daily dose meeting the primary endpoint of a PASI 75 response at week 16 compared with 51% of those assigned to the 25-mg twice-daily dose, 58% assigned to 50-mg once-daily dose, 65% assigned to 100-mg once-daily dose, and 79% assigned to 100-mg twice-daily dose (P for dose response < .001).
As noted previously, 9% of patients in the placebo group had a PASI 75 response at week 16.
After a mean duration of 15.9 weeks, adverse events after the first dose of JNJ-77242113 (all dose groups were pooled for the safety analysis) were reported in 47% of patients on the 25-mg once-daily dose, 49% on 25-mg twice-daily dose, 60% on 50-mg once-daily dose, 44% on 100-mg once-daily dose, and 62% on 100-mg twice-daily dose. Adverse events after the first dose occurred in 51% of patients assigned to placebo.
The incidence of adverse events did not increase significantly with successively higher dose levels.
As noted by Dr. Gelfand in his editorial, there were three serious adverse events, all occurring in patients on the active drug: a case of COVID-19 in one patient and a suicide attempt in one patient, both in the 100-mg once-daily dose group, and an infected cyst in the 50-mg once-daily group. All three events were determined by the principal investigator and the sponsor to be unrelated to JNJ-77242113.
There were no reports of deaths, major adverse cardiovascular events, or incident cancers during the trial.
The study was supported by Janssen Research and Development. Dr. Bissonnette disclosed institutional research funding and advisory board participation and honoraria with Janssen. Dr. Gelfand disclosed consulting for Janssen Biotech. Dr. Lebwohl disclosed institutional research funding from Janssen but no personal fees.
A version of this article first appeared on Medscape.com.
A novel oral drug for plaque psoriasis that targets the same inflammatory pathway as currently available parenteral therapies showed promise for treating moderate to severe disease in a phase 2 dose-finding trial.
Among 255 at week 16 of at least 75% (PASI 75) compared with 9% of patients assigned to placebo, reported Robert Bissonnette, MD, from Innovaderm Research in Montreal, Quebec, Canada, and colleagues.
“The level of reduction of psoriasis that was observed with higher doses of JNJ-77242113 at week 16 was similar in magnitude to the responses seen with several of the injectable biologics that are currently approved for psoriasis,” investigators in the FRONTIER 1 trial wrote in The New England Journal of Medicine.
The investigators noted that among patients assigned to the 100-mg dose of the active drug, 60% had a PASI 90 response, which compares favorably with that seen in phase 3 trials of two other orally available therapies for psoriasis, deucravacitinib (Sotyktu) and apremilast (Otezla). They cautioned, however, against drawing any further inferences from these data, because these agents have not been tested head-to-head against JNJ-77242113 in comparison trials.
Targets IL-23 and IL-17
The investigational agent is an oral IL-23 receptor antagonist peptide that selectively blocks IL-23 proximal signaling as well as the production of downstream inflammatory cytokines such as IL-17, according to the authors.
“Modulation of the interleukin-23 pathway with the use of monoclonal antibodies has shown efficacy in the treatment of psoriasis and is considered to be associated with a more favorable safety profile than older oral therapies (eg, cyclosporine, acitretin, methotrexate, and dimethyl fumarate),” the investigators wrote.
Currently available biologic agents targeting IL-23 include guselkumab (Tremfya), risankizumab (Skyrizi) and tildrakizumab (Ilumya). These agents require intravenous or subcutaneous administration, whereas JNJ-77242113 is taken orally, giving it a theoretical advantage in terms of patient preference.
The novel drug must be taken twice daily on an empty stomach at least 2 hours before food or drink, and those who take it must wait an additional 30 minutes to eat or drink after taking the drug. (This news organization has learned that in planned phase 3 studies, patients will be instructed to take a double daily dose on awakening and then wait 30 minutes for eating or drinking.)
‘Profoundly Effective’
The results of this study have convinced at least one former skeptic of the efficacy of the novel agent.
“They asked me to do the trial, and I turned it down, because I didn’t believe it would work,” said Mark G. Lebwohl, MD, dean for Clinical Therapeutics at the Icahn School of Medicine at Mount Sinai and professor and chairman emeritus of the Department of Dermatology at Mount Sinai Medicine in New York, NY.
In an interview with this news organization, Dr. Lebwohl said that he was initially dubious that a peptide, a short chain of amino acids directed against a receptor, could be effective because it would likely be digested in the intestinal tract.
“Indeed, more than 99% of it is digested, but the data show that the tiny amount that gets through is profoundly effective,” he said.
“I would never have believed that this was going to work – and it did,” Dr. Lebwohl added.
He has signed on as an investigator in the currently recruiting phase 3 ICONIC-LEAD trial, in which JNJ-77242113 will be tested against placebo in adolescents and adults with moderate to severe plaque psoriasis.
In an editorial accompanying the study in the NEJM, Joel M. Gelfand, MD, MSCE, vice chair of clinical research and medical director of the Dermatology Clinical Studies Unit at the University of Pennsylvania in Philadelphia, noted that if confirmed in larger studies, the PASI 90 rate at the highest dose “would be similar to the most effective injectable biologics,” with no evidence of increased adverse events at higher doses.
“However, two occurrences of infection (COVID-19 and an infected cyst) and a suicide attempt were reported as serious adverse events; larger trials will be needed to determine whether such events are attributable to chance, psoriasis itself, or inhibition of interleukin-23 signaling,” cautioned Dr. Gelfand, director of the psoriasis and phototherapy treatment center at the University of Pennsylvania.
In an interview, Dr. Lebwohl said that currently available IL-23 signaling inhibitors have an excellent safety profile and that the investigational oral agent also appears to be very safe. “It’s seeing a target whose effects are known, and the effects are all good and not bad,” he said.
FRONTIER-1 Details
The investigators enrolled eligible adults aged 18 years or older who had moderate to severe plaque psoriasis as defined by an Investigator’s Global Assessment score ≥ 3, a total body-surface area of psoriasis involvement of at least 10%, and a PASI score ≥ 12 who had received their diagnosis of plaque psoriasis at least 6 months before starting the trial. The participants had to be candidates for phototherapy or systemic psoriasis therapy.
Patients were randomly assigned to the active agent at doses of 25 mg once or twice daily, 50 mg once daily, or 100 mg once or twice daily for 16 weeks.
There was a clear dose response, with 37% of patients assigned to 25-mg once-daily dose meeting the primary endpoint of a PASI 75 response at week 16 compared with 51% of those assigned to the 25-mg twice-daily dose, 58% assigned to 50-mg once-daily dose, 65% assigned to 100-mg once-daily dose, and 79% assigned to 100-mg twice-daily dose (P for dose response < .001).
As noted previously, 9% of patients in the placebo group had a PASI 75 response at week 16.
After a mean duration of 15.9 weeks, adverse events after the first dose of JNJ-77242113 (all dose groups were pooled for the safety analysis) were reported in 47% of patients on the 25-mg once-daily dose, 49% on 25-mg twice-daily dose, 60% on 50-mg once-daily dose, 44% on 100-mg once-daily dose, and 62% on 100-mg twice-daily dose. Adverse events after the first dose occurred in 51% of patients assigned to placebo.
The incidence of adverse events did not increase significantly with successively higher dose levels.
As noted by Dr. Gelfand in his editorial, there were three serious adverse events, all occurring in patients on the active drug: a case of COVID-19 in one patient and a suicide attempt in one patient, both in the 100-mg once-daily dose group, and an infected cyst in the 50-mg once-daily group. All three events were determined by the principal investigator and the sponsor to be unrelated to JNJ-77242113.
There were no reports of deaths, major adverse cardiovascular events, or incident cancers during the trial.
The study was supported by Janssen Research and Development. Dr. Bissonnette disclosed institutional research funding and advisory board participation and honoraria with Janssen. Dr. Gelfand disclosed consulting for Janssen Biotech. Dr. Lebwohl disclosed institutional research funding from Janssen but no personal fees.
A version of this article first appeared on Medscape.com.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Surgery Shows Longer-Term Benefits for Dupuytren Contracture
Dupuytren contracture can be treated with three invasive methods, but new data from a randomized controlled trial show better 2-year success rates for surgery than for needle fasciotomy and collagenase injection, despite retreatments.
The common hereditary disorder affects the palmar fascia in middle-aged and older people, more often men. The disease typically affects the ring and little fingers and they may curl toward the palm. The disease can’t be cured, but can be eased.
Findings of the study, led by Mikko Petteri Räisänen, MD, with the Department of Orthopedics, Traumatology and Hand Surgery, Kuopio University Hospital, Kuopio, and Tampere University, Tampere, both in Finland, were published online in Annals of Internal Medicine.
Initially, Outcomes Similar
Initially, in the multisite, randomized controlled, outcome assessor–blinded, superiority trial, the outcomes were similar among the treatments, the authors write, but at 2 years only the surgery group maintained the success rate.
The primary outcome was more than 50% contracture release and patients reaching the patient-acceptable symptom state. Secondary outcomes included hand function, pain, patient satisfaction, quality of life, finger flexion, residual contracture angle, risk for retreatment, and serious adverse events.
A total of 292 (97%) and 284 (94%) patients completed the 3-month and 2-year follow ups, respectively.
Success rates at 3 months were similar: 71% (95% CI, 62%-80%) for surgery; 73% (95% CI, 64%-82%) for needle fasciotomy; and 73% (95% CI, 64%-82%) for collagenase injection.
At 2 Years, Surgery Superior
At 2 years, however, surgery had superior success rates. Surgery success rates vs needle fasciotomy were 78% vs 50% (adjusted risk difference, 0.30; 95% CI, 0.17-0.43).
Surgery success rates vs collagenase injection were 78% vs 65% (aRD, 0.13; 95% CI, 0.01-0.26).
“Secondary analyses paralleled with the primary analysis,” the authors write.
Patients may choose surgery despite initial morbidity which includes potential time off work and higher costs than the other options if the long-term outcome is better, the authors write.
“Collagenase is likely a viable alternative to needle fasciotomy only if its costs are substantially reduced,” the authors write.
A strength of the study is its generalizability, as researchers recruited patients in a setting with universal healthcare where few people seek care outside public hospitals.
Another strength of the trial is that the blinded outcome assessors measured the contracture angles with the participant’s hand covered by a rubber glove and patients were instructed not to reveal their treatment group to the assessor.
Some Physicians Offer Noninvasive Treatments First
Family physician Shannon Scott, DO, medical director of the Midwestern University Multispecialty Clinic in Scottsdale, Arizona, treats many patients with the contracture.
In her practice, patients come to her seeking noninvasive options first. But if they are not satisfied with their hand function after noninvasive treatments such as osteopathic manipulative treatment, physical therapy, and a home exercise program, the next steps are the choices compared in the study. The findings of this randomized controlled trial, she says, will help her in counseling patients choosing among those options.
“What’s important for me as a family physician to understand is more about the path that led to this decision” to seek more invasive treatment and whether the patients in the study had first completed a course of noninvasive care, Dr. Scott says.
The condition, especially in the population most affected — older adults — can greatly affect activities of daily living, she noted. Patients may also often have other conditions contributing to the symptoms of Dupuytren contracture in the neck, arm, or shoulder, for instance, that limit range of motion or cause pain. Addressing those symptoms noninvasively may help relieve the contracture, she says.
Asking patients about their goals is essential, Dr. Scott says. “What patients are looking for is function and the definition for one patient may be different than the level of function for another. Many patients get to a desired level of function with nonsurgical options first.”
A First for the Comparison
Dawn LaPorte, MD, a hand surgeon at Johns Hopkins Medicine in Baltimore, Maryland, who also was not part of the study, says although surgery was thought to have better long-term success rates, this is the first time the data have been able to show that at 2 years.
She added that the results are particularly striking because the endpoint was a 50% release when surgeons hope for a complete release. Even with the 50% release outcome at 2 years, surgery had better success.
She noted that the authors plan to look at outcomes at 5 and 10 years, but, she says, “the fact that surgery is already significantly better at 2 years really says a lot.”
Treatments Have Tradeoffs
She says the conclusions may change the discussions physicians have with patients.
Collagenase injections are an office procedure, and there’s no anesthesia. “There’s usually no lost time from work, and they can use their hand pretty normally the following day,” Dr. LaPorte says. One downside, compared with surgery, is that there may be a more frequent recurrence rate. Patients may have a skin tear that usually heals over a couple of weeks, she added.
Additionally, “the collagenase drug is very expensive,” she notes, so preapproval is important so that the patient doesn’t have to pay out of pocket.
Needle fasciotomy can also be done in the office without anesthesia. There’s less time off work than with surgery.
“With both that and the injection, they should see release of the contracture right away,” Dr. LaPorte says, but the concern is a quicker recurrence rate.
While surgery isn’t a cure, she says, and there is a lower recurrence rate, it typically means time off work, anesthesia, and an incision to heal, and may mean postoperative therapy.
The study was funded by the Research Council of Finland. Disclosures are available with the full text.
Dr. LaPorte and Dr. Scott report no relevant financial relationships.
Dupuytren contracture can be treated with three invasive methods, but new data from a randomized controlled trial show better 2-year success rates for surgery than for needle fasciotomy and collagenase injection, despite retreatments.
The common hereditary disorder affects the palmar fascia in middle-aged and older people, more often men. The disease typically affects the ring and little fingers and they may curl toward the palm. The disease can’t be cured, but can be eased.
Findings of the study, led by Mikko Petteri Räisänen, MD, with the Department of Orthopedics, Traumatology and Hand Surgery, Kuopio University Hospital, Kuopio, and Tampere University, Tampere, both in Finland, were published online in Annals of Internal Medicine.
Initially, Outcomes Similar
Initially, in the multisite, randomized controlled, outcome assessor–blinded, superiority trial, the outcomes were similar among the treatments, the authors write, but at 2 years only the surgery group maintained the success rate.
The primary outcome was more than 50% contracture release and patients reaching the patient-acceptable symptom state. Secondary outcomes included hand function, pain, patient satisfaction, quality of life, finger flexion, residual contracture angle, risk for retreatment, and serious adverse events.
A total of 292 (97%) and 284 (94%) patients completed the 3-month and 2-year follow ups, respectively.
Success rates at 3 months were similar: 71% (95% CI, 62%-80%) for surgery; 73% (95% CI, 64%-82%) for needle fasciotomy; and 73% (95% CI, 64%-82%) for collagenase injection.
At 2 Years, Surgery Superior
At 2 years, however, surgery had superior success rates. Surgery success rates vs needle fasciotomy were 78% vs 50% (adjusted risk difference, 0.30; 95% CI, 0.17-0.43).
Surgery success rates vs collagenase injection were 78% vs 65% (aRD, 0.13; 95% CI, 0.01-0.26).
“Secondary analyses paralleled with the primary analysis,” the authors write.
Patients may choose surgery despite initial morbidity which includes potential time off work and higher costs than the other options if the long-term outcome is better, the authors write.
“Collagenase is likely a viable alternative to needle fasciotomy only if its costs are substantially reduced,” the authors write.
A strength of the study is its generalizability, as researchers recruited patients in a setting with universal healthcare where few people seek care outside public hospitals.
Another strength of the trial is that the blinded outcome assessors measured the contracture angles with the participant’s hand covered by a rubber glove and patients were instructed not to reveal their treatment group to the assessor.
Some Physicians Offer Noninvasive Treatments First
Family physician Shannon Scott, DO, medical director of the Midwestern University Multispecialty Clinic in Scottsdale, Arizona, treats many patients with the contracture.
In her practice, patients come to her seeking noninvasive options first. But if they are not satisfied with their hand function after noninvasive treatments such as osteopathic manipulative treatment, physical therapy, and a home exercise program, the next steps are the choices compared in the study. The findings of this randomized controlled trial, she says, will help her in counseling patients choosing among those options.
“What’s important for me as a family physician to understand is more about the path that led to this decision” to seek more invasive treatment and whether the patients in the study had first completed a course of noninvasive care, Dr. Scott says.
The condition, especially in the population most affected — older adults — can greatly affect activities of daily living, she noted. Patients may also often have other conditions contributing to the symptoms of Dupuytren contracture in the neck, arm, or shoulder, for instance, that limit range of motion or cause pain. Addressing those symptoms noninvasively may help relieve the contracture, she says.
Asking patients about their goals is essential, Dr. Scott says. “What patients are looking for is function and the definition for one patient may be different than the level of function for another. Many patients get to a desired level of function with nonsurgical options first.”
A First for the Comparison
Dawn LaPorte, MD, a hand surgeon at Johns Hopkins Medicine in Baltimore, Maryland, who also was not part of the study, says although surgery was thought to have better long-term success rates, this is the first time the data have been able to show that at 2 years.
She added that the results are particularly striking because the endpoint was a 50% release when surgeons hope for a complete release. Even with the 50% release outcome at 2 years, surgery had better success.
She noted that the authors plan to look at outcomes at 5 and 10 years, but, she says, “the fact that surgery is already significantly better at 2 years really says a lot.”
Treatments Have Tradeoffs
She says the conclusions may change the discussions physicians have with patients.
Collagenase injections are an office procedure, and there’s no anesthesia. “There’s usually no lost time from work, and they can use their hand pretty normally the following day,” Dr. LaPorte says. One downside, compared with surgery, is that there may be a more frequent recurrence rate. Patients may have a skin tear that usually heals over a couple of weeks, she added.
Additionally, “the collagenase drug is very expensive,” she notes, so preapproval is important so that the patient doesn’t have to pay out of pocket.
Needle fasciotomy can also be done in the office without anesthesia. There’s less time off work than with surgery.
“With both that and the injection, they should see release of the contracture right away,” Dr. LaPorte says, but the concern is a quicker recurrence rate.
While surgery isn’t a cure, she says, and there is a lower recurrence rate, it typically means time off work, anesthesia, and an incision to heal, and may mean postoperative therapy.
The study was funded by the Research Council of Finland. Disclosures are available with the full text.
Dr. LaPorte and Dr. Scott report no relevant financial relationships.
Dupuytren contracture can be treated with three invasive methods, but new data from a randomized controlled trial show better 2-year success rates for surgery than for needle fasciotomy and collagenase injection, despite retreatments.
The common hereditary disorder affects the palmar fascia in middle-aged and older people, more often men. The disease typically affects the ring and little fingers and they may curl toward the palm. The disease can’t be cured, but can be eased.
Findings of the study, led by Mikko Petteri Räisänen, MD, with the Department of Orthopedics, Traumatology and Hand Surgery, Kuopio University Hospital, Kuopio, and Tampere University, Tampere, both in Finland, were published online in Annals of Internal Medicine.
Initially, Outcomes Similar
Initially, in the multisite, randomized controlled, outcome assessor–blinded, superiority trial, the outcomes were similar among the treatments, the authors write, but at 2 years only the surgery group maintained the success rate.
The primary outcome was more than 50% contracture release and patients reaching the patient-acceptable symptom state. Secondary outcomes included hand function, pain, patient satisfaction, quality of life, finger flexion, residual contracture angle, risk for retreatment, and serious adverse events.
A total of 292 (97%) and 284 (94%) patients completed the 3-month and 2-year follow ups, respectively.
Success rates at 3 months were similar: 71% (95% CI, 62%-80%) for surgery; 73% (95% CI, 64%-82%) for needle fasciotomy; and 73% (95% CI, 64%-82%) for collagenase injection.
At 2 Years, Surgery Superior
At 2 years, however, surgery had superior success rates. Surgery success rates vs needle fasciotomy were 78% vs 50% (adjusted risk difference, 0.30; 95% CI, 0.17-0.43).
Surgery success rates vs collagenase injection were 78% vs 65% (aRD, 0.13; 95% CI, 0.01-0.26).
“Secondary analyses paralleled with the primary analysis,” the authors write.
Patients may choose surgery despite initial morbidity which includes potential time off work and higher costs than the other options if the long-term outcome is better, the authors write.
“Collagenase is likely a viable alternative to needle fasciotomy only if its costs are substantially reduced,” the authors write.
A strength of the study is its generalizability, as researchers recruited patients in a setting with universal healthcare where few people seek care outside public hospitals.
Another strength of the trial is that the blinded outcome assessors measured the contracture angles with the participant’s hand covered by a rubber glove and patients were instructed not to reveal their treatment group to the assessor.
Some Physicians Offer Noninvasive Treatments First
Family physician Shannon Scott, DO, medical director of the Midwestern University Multispecialty Clinic in Scottsdale, Arizona, treats many patients with the contracture.
In her practice, patients come to her seeking noninvasive options first. But if they are not satisfied with their hand function after noninvasive treatments such as osteopathic manipulative treatment, physical therapy, and a home exercise program, the next steps are the choices compared in the study. The findings of this randomized controlled trial, she says, will help her in counseling patients choosing among those options.
“What’s important for me as a family physician to understand is more about the path that led to this decision” to seek more invasive treatment and whether the patients in the study had first completed a course of noninvasive care, Dr. Scott says.
The condition, especially in the population most affected — older adults — can greatly affect activities of daily living, she noted. Patients may also often have other conditions contributing to the symptoms of Dupuytren contracture in the neck, arm, or shoulder, for instance, that limit range of motion or cause pain. Addressing those symptoms noninvasively may help relieve the contracture, she says.
Asking patients about their goals is essential, Dr. Scott says. “What patients are looking for is function and the definition for one patient may be different than the level of function for another. Many patients get to a desired level of function with nonsurgical options first.”
A First for the Comparison
Dawn LaPorte, MD, a hand surgeon at Johns Hopkins Medicine in Baltimore, Maryland, who also was not part of the study, says although surgery was thought to have better long-term success rates, this is the first time the data have been able to show that at 2 years.
She added that the results are particularly striking because the endpoint was a 50% release when surgeons hope for a complete release. Even with the 50% release outcome at 2 years, surgery had better success.
She noted that the authors plan to look at outcomes at 5 and 10 years, but, she says, “the fact that surgery is already significantly better at 2 years really says a lot.”
Treatments Have Tradeoffs
She says the conclusions may change the discussions physicians have with patients.
Collagenase injections are an office procedure, and there’s no anesthesia. “There’s usually no lost time from work, and they can use their hand pretty normally the following day,” Dr. LaPorte says. One downside, compared with surgery, is that there may be a more frequent recurrence rate. Patients may have a skin tear that usually heals over a couple of weeks, she added.
Additionally, “the collagenase drug is very expensive,” she notes, so preapproval is important so that the patient doesn’t have to pay out of pocket.
Needle fasciotomy can also be done in the office without anesthesia. There’s less time off work than with surgery.
“With both that and the injection, they should see release of the contracture right away,” Dr. LaPorte says, but the concern is a quicker recurrence rate.
While surgery isn’t a cure, she says, and there is a lower recurrence rate, it typically means time off work, anesthesia, and an incision to heal, and may mean postoperative therapy.
The study was funded by the Research Council of Finland. Disclosures are available with the full text.
Dr. LaPorte and Dr. Scott report no relevant financial relationships.
FROM ANNALS OF INTERNAL MEDICINE
Study: Lifetime Cost of Vyjuvek Gene Therapy for DEB Could Be $15-$22 Million
according to the authors of a new study.
The US Food and Drug Administration (FDA) approved Vyjuvek (Krystal Biotech) in May 2023 for the treatment of wounds in patients ages 6 months and older with dystrophic epidermolysis bullosa (DEB), which includes two types, the most severe form (autosomal recessive, or RDEB) and the autosomal dominant form of DEB (DDEB), which tends to be milder.
Treatment with Vyjuvek “represents an important advance in the treatment of RDEB,” wrote Adam J.N. Raymakers, PhD, and colleagues at the Program on Regulation, Therapeutics, and Law; the Department of Dermatology; and the Division of Pulmonary and Critical Care Medicine at Brigham & Women’s Hospital in Boston, Massachusetts, in their paper, published in JAMA Dermatology. But the price “will be high, potentially limiting patients’ access to it,” they added. Evidence to support it in DDEB “is less conclusive,” they wrote, noting that the pivotal phase 3 study that led to approval included one patient with DDEB.
“The wider indication granted by the FDA may lead to friction between payers on the one hand and patients and physicians on the other,” they wrote, noting a potential minimum price of $300,000 per patient a year, which was based on Krystal’s regulatory filings.
There is no cure for DEB. Vyjuvek, applied as a gel on an ongoing basis, uses a nonreplicating herpes simplex virus type 1 vector to deliver the COL7A1 gene directly to skin cells, restoring the COL7 protein fibrils that stabilize skin structure.
The authors estimated that in the United States, 894 individuals – largely children – with both forms of the disease would be eligible for Vyjuvek treatment in the first year. Based on the $300,000 price, spending on gene therapy could range from $179 million to $357 million for those 894 patients, they reported in the study.
Over the first 3 years, spending could range as high as $1 billion, the authors estimated. Even if patients with only the most severe disease (RDEB) — an estimated 442 patients — received treatment, spending could be $132 million and up to $400 million or more over the first 3 years, they wrote.
Some media outlets have reported that Vyjuvek could cost as much as $600,000, said Dr. Raymakers, a research fellow. That price “would double all of our estimates,” he told this news organization.
The study assumed that patients with RDEB would only live to age 50, which led to a lifetime cost estimate of $15 million. But that is likely a conservative estimate, he and his coauthors wrote, noting that many patients with RDEB die from squamous cell carcinoma, but that Vyjuvek could, by attenuating skin damage, also potentially prevent skin cancer.
Dr. Raymakers said he and his colleagues began their study when Vyjuvek was approved, and thus they did not have any real-world data on the price or payer responses. Their estimates also did not include differing dosing regimens, which also could change their spending figures.
Krystal Biotech recently reported that in its third quarter of 2023 – representing just 1 month of Vyjuvek availability – it received requests to begin treatment for 284 patients from 136 unique clinicians. Twenty percent of the start requests were for patients with the milder form (DDEB), and a third of all the requests were for patients 10 years of age or younger. The company also said that it had “received positive coverage determinations from all major commercial national health plans” and that it was on track to receive approval from most state Medicaid plans.
In 1 month, Krystal reported net Vyjuvek revenues of $8.6 million.
The authors suggested that one way to evaluate Vyjuvek’s value — especially for those with DDEB — would be through a cost-effectiveness study. While important, a cost-effectiveness study would not get at the impact on a payer, said Dr. Raymakers. “Something can be cost-effective but unaffordable to the system,” he said.
“When there’s one of these very expensive therapies, that’s one thing,” he said. “But when there’s more and more coming to market, you wonder how much can be tolerated,” said Dr. Raymakers.
CMS Launching Gene Therapy Program
The Biden administration recently announced that it was launching a program aimed at increasing access, curbing costs, and ensuring value of gene therapies, starting with sickle cell disease. The program will begin in early 2025. Among other aspects, the federal government will negotiate the price of the product with the manufacturer.
“The goal of the Cell and Gene Therapy Access Model is to increase access to innovative cell and gene therapies for people with Medicaid by making it easier for states to pay for these therapies,” said Liz Fowler, CMS Deputy Administrator and Director of the CMS Innovation Center, in a statement announcing the program.
Whether the new program takes a look at Vyjuvek – and when – is not clear.
But the authors of the study noted that the lifetime costs of treating a patient with Vyjuvek “exceed the costs of all other one-time gene therapies for other diseases.” And they wrote, even at the most conservative estimates, Vyjuvek “will be the most expensive gene therapy currently marketed in the US.”
The study was funded by a grant from Arnold Ventures, grants from the Kaiser Permanente Institute for Health Policy, the Commonwealth Fund, and the National Heart, Lung, and Blood Institute. Dr. Raymakers and co-authors reported no financial relationships relevant to the work.
according to the authors of a new study.
The US Food and Drug Administration (FDA) approved Vyjuvek (Krystal Biotech) in May 2023 for the treatment of wounds in patients ages 6 months and older with dystrophic epidermolysis bullosa (DEB), which includes two types, the most severe form (autosomal recessive, or RDEB) and the autosomal dominant form of DEB (DDEB), which tends to be milder.
Treatment with Vyjuvek “represents an important advance in the treatment of RDEB,” wrote Adam J.N. Raymakers, PhD, and colleagues at the Program on Regulation, Therapeutics, and Law; the Department of Dermatology; and the Division of Pulmonary and Critical Care Medicine at Brigham & Women’s Hospital in Boston, Massachusetts, in their paper, published in JAMA Dermatology. But the price “will be high, potentially limiting patients’ access to it,” they added. Evidence to support it in DDEB “is less conclusive,” they wrote, noting that the pivotal phase 3 study that led to approval included one patient with DDEB.
“The wider indication granted by the FDA may lead to friction between payers on the one hand and patients and physicians on the other,” they wrote, noting a potential minimum price of $300,000 per patient a year, which was based on Krystal’s regulatory filings.
There is no cure for DEB. Vyjuvek, applied as a gel on an ongoing basis, uses a nonreplicating herpes simplex virus type 1 vector to deliver the COL7A1 gene directly to skin cells, restoring the COL7 protein fibrils that stabilize skin structure.
The authors estimated that in the United States, 894 individuals – largely children – with both forms of the disease would be eligible for Vyjuvek treatment in the first year. Based on the $300,000 price, spending on gene therapy could range from $179 million to $357 million for those 894 patients, they reported in the study.
Over the first 3 years, spending could range as high as $1 billion, the authors estimated. Even if patients with only the most severe disease (RDEB) — an estimated 442 patients — received treatment, spending could be $132 million and up to $400 million or more over the first 3 years, they wrote.
Some media outlets have reported that Vyjuvek could cost as much as $600,000, said Dr. Raymakers, a research fellow. That price “would double all of our estimates,” he told this news organization.
The study assumed that patients with RDEB would only live to age 50, which led to a lifetime cost estimate of $15 million. But that is likely a conservative estimate, he and his coauthors wrote, noting that many patients with RDEB die from squamous cell carcinoma, but that Vyjuvek could, by attenuating skin damage, also potentially prevent skin cancer.
Dr. Raymakers said he and his colleagues began their study when Vyjuvek was approved, and thus they did not have any real-world data on the price or payer responses. Their estimates also did not include differing dosing regimens, which also could change their spending figures.
Krystal Biotech recently reported that in its third quarter of 2023 – representing just 1 month of Vyjuvek availability – it received requests to begin treatment for 284 patients from 136 unique clinicians. Twenty percent of the start requests were for patients with the milder form (DDEB), and a third of all the requests were for patients 10 years of age or younger. The company also said that it had “received positive coverage determinations from all major commercial national health plans” and that it was on track to receive approval from most state Medicaid plans.
In 1 month, Krystal reported net Vyjuvek revenues of $8.6 million.
The authors suggested that one way to evaluate Vyjuvek’s value — especially for those with DDEB — would be through a cost-effectiveness study. While important, a cost-effectiveness study would not get at the impact on a payer, said Dr. Raymakers. “Something can be cost-effective but unaffordable to the system,” he said.
“When there’s one of these very expensive therapies, that’s one thing,” he said. “But when there’s more and more coming to market, you wonder how much can be tolerated,” said Dr. Raymakers.
CMS Launching Gene Therapy Program
The Biden administration recently announced that it was launching a program aimed at increasing access, curbing costs, and ensuring value of gene therapies, starting with sickle cell disease. The program will begin in early 2025. Among other aspects, the federal government will negotiate the price of the product with the manufacturer.
“The goal of the Cell and Gene Therapy Access Model is to increase access to innovative cell and gene therapies for people with Medicaid by making it easier for states to pay for these therapies,” said Liz Fowler, CMS Deputy Administrator and Director of the CMS Innovation Center, in a statement announcing the program.
Whether the new program takes a look at Vyjuvek – and when – is not clear.
But the authors of the study noted that the lifetime costs of treating a patient with Vyjuvek “exceed the costs of all other one-time gene therapies for other diseases.” And they wrote, even at the most conservative estimates, Vyjuvek “will be the most expensive gene therapy currently marketed in the US.”
The study was funded by a grant from Arnold Ventures, grants from the Kaiser Permanente Institute for Health Policy, the Commonwealth Fund, and the National Heart, Lung, and Blood Institute. Dr. Raymakers and co-authors reported no financial relationships relevant to the work.
according to the authors of a new study.
The US Food and Drug Administration (FDA) approved Vyjuvek (Krystal Biotech) in May 2023 for the treatment of wounds in patients ages 6 months and older with dystrophic epidermolysis bullosa (DEB), which includes two types, the most severe form (autosomal recessive, or RDEB) and the autosomal dominant form of DEB (DDEB), which tends to be milder.
Treatment with Vyjuvek “represents an important advance in the treatment of RDEB,” wrote Adam J.N. Raymakers, PhD, and colleagues at the Program on Regulation, Therapeutics, and Law; the Department of Dermatology; and the Division of Pulmonary and Critical Care Medicine at Brigham & Women’s Hospital in Boston, Massachusetts, in their paper, published in JAMA Dermatology. But the price “will be high, potentially limiting patients’ access to it,” they added. Evidence to support it in DDEB “is less conclusive,” they wrote, noting that the pivotal phase 3 study that led to approval included one patient with DDEB.
“The wider indication granted by the FDA may lead to friction between payers on the one hand and patients and physicians on the other,” they wrote, noting a potential minimum price of $300,000 per patient a year, which was based on Krystal’s regulatory filings.
There is no cure for DEB. Vyjuvek, applied as a gel on an ongoing basis, uses a nonreplicating herpes simplex virus type 1 vector to deliver the COL7A1 gene directly to skin cells, restoring the COL7 protein fibrils that stabilize skin structure.
The authors estimated that in the United States, 894 individuals – largely children – with both forms of the disease would be eligible for Vyjuvek treatment in the first year. Based on the $300,000 price, spending on gene therapy could range from $179 million to $357 million for those 894 patients, they reported in the study.
Over the first 3 years, spending could range as high as $1 billion, the authors estimated. Even if patients with only the most severe disease (RDEB) — an estimated 442 patients — received treatment, spending could be $132 million and up to $400 million or more over the first 3 years, they wrote.
Some media outlets have reported that Vyjuvek could cost as much as $600,000, said Dr. Raymakers, a research fellow. That price “would double all of our estimates,” he told this news organization.
The study assumed that patients with RDEB would only live to age 50, which led to a lifetime cost estimate of $15 million. But that is likely a conservative estimate, he and his coauthors wrote, noting that many patients with RDEB die from squamous cell carcinoma, but that Vyjuvek could, by attenuating skin damage, also potentially prevent skin cancer.
Dr. Raymakers said he and his colleagues began their study when Vyjuvek was approved, and thus they did not have any real-world data on the price or payer responses. Their estimates also did not include differing dosing regimens, which also could change their spending figures.
Krystal Biotech recently reported that in its third quarter of 2023 – representing just 1 month of Vyjuvek availability – it received requests to begin treatment for 284 patients from 136 unique clinicians. Twenty percent of the start requests were for patients with the milder form (DDEB), and a third of all the requests were for patients 10 years of age or younger. The company also said that it had “received positive coverage determinations from all major commercial national health plans” and that it was on track to receive approval from most state Medicaid plans.
In 1 month, Krystal reported net Vyjuvek revenues of $8.6 million.
The authors suggested that one way to evaluate Vyjuvek’s value — especially for those with DDEB — would be through a cost-effectiveness study. While important, a cost-effectiveness study would not get at the impact on a payer, said Dr. Raymakers. “Something can be cost-effective but unaffordable to the system,” he said.
“When there’s one of these very expensive therapies, that’s one thing,” he said. “But when there’s more and more coming to market, you wonder how much can be tolerated,” said Dr. Raymakers.
CMS Launching Gene Therapy Program
The Biden administration recently announced that it was launching a program aimed at increasing access, curbing costs, and ensuring value of gene therapies, starting with sickle cell disease. The program will begin in early 2025. Among other aspects, the federal government will negotiate the price of the product with the manufacturer.
“The goal of the Cell and Gene Therapy Access Model is to increase access to innovative cell and gene therapies for people with Medicaid by making it easier for states to pay for these therapies,” said Liz Fowler, CMS Deputy Administrator and Director of the CMS Innovation Center, in a statement announcing the program.
Whether the new program takes a look at Vyjuvek – and when – is not clear.
But the authors of the study noted that the lifetime costs of treating a patient with Vyjuvek “exceed the costs of all other one-time gene therapies for other diseases.” And they wrote, even at the most conservative estimates, Vyjuvek “will be the most expensive gene therapy currently marketed in the US.”
The study was funded by a grant from Arnold Ventures, grants from the Kaiser Permanente Institute for Health Policy, the Commonwealth Fund, and the National Heart, Lung, and Blood Institute. Dr. Raymakers and co-authors reported no financial relationships relevant to the work.
FROM JAMA DERMATOLOGY
Youth Mental Health in ‘Dire Straits’
, suggests a new report that shines a light on the global mental health crisis among young people.
The burden is high in this population, with around one-fifth of all disease-related disability attributable to mental disorders. The data, drawn from the 2019 Global Burden of Disease (GBD) study, examines mental health in the 293 million people worldwide in this age group.
“This concentration of disability burden at an early age raises concern about the potential lifetime impact of these conditions,” wrote the authors, led by Christian Kieling, MD, PhD, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
The study was published online in JAMA Psychiatry.
State of Emergency
Soaring rates of mental health disorders among young people, intensified by the COVID-19 pandemic, have led the American Academy of Child and Adolescent Psychiatry and the American Academy of Pediatrics to declare a state of emergency.
Using the GBD study, Dr. Kieling and colleagues estimated the global prevalence and years lived with disability associated with mental disorders and substance use disorders in people aged 5-24 years.
In 2019, individuals in this age range had at least one mental disorder and 31 million had a substance use disorder — an average prevalence of 11.6% and 1.2%, respectively.
The prevalence of mental disorders doubled from the age range of 5-9 years (6.8%) to 20-24 years (13.6%).
Among mental disorders analyzed, anxiety disorders were most common in the overall population (84 million; 3.35%) and schizophrenia the least common (2 million; 0.08%).
Notably, the researchers said, there was a steep increase in mood disorders, particularly anxiety and substance use disorders, across early to late adolescence and from late adolescence to young adulthood.
Mental disorders and substance use disorders were the leading cause of nonfatal disability in children and youths in 2019, accounting for 31 million and 4.3 million years lived with disability (YLDs), respectively. That represents roughly 20% and 3% of YLDs, respectively, from all causes.
Youth Mental Health Is Not a Monolith
“That youth mental health is in such dire straits is particularly striking given that many measures of global physical health in young people are improving,” wrote the authors of an accompanying editorial.
In their editorial, Jeremy Veenstra-VanderWeele, MD, Department of Psychiatry, Columbia University, New York, and co-authors noted that these and other age- and gender-related findings “represent a meaningful contribution to the literature.”
The granular data underscore that youth mental health is “not a monolith” but rather involves considerable variation in prevalence and morbidity across both age and gender, they wrote.
Therefore, mental health screening, promotion, and prevention efforts may benefit from an age-based approach that targets specific disorders during “high prevalence developmental intervals, with keen attention also paid to gender,” they suggested.
On the basis of the findings in this analysis, healthcare and education resource allocation may need to be adjusted for specific disorders, they added.
“One might propose a community- or school-based mental health initiative that screens for and educates parents and teachers on ADHD and anxiety disorders from kindergarten through third grade (ages 5-9 years, when prevalence and resulting disability grow markedly),” Dr. Veenstra-VanderWeele and colleagues wrote. “Later initiatives could then focus on mood and substance use disorders during high school and college (ages 15-19 years and 20-24 years).”
The study was partially funded by a research grant from the Cundill Centre for Child and Youth Depression. Dr. Kieling is the founder of Wida. Dr. Veenstra-VanderWeele reported receiving grants from the National Institutes of Health and Simon’s Foundation and research support/advisory board/editorial fees from Autism Speaks, Agency for Healthcare Research and Quality, Health Resources and Services Administration Maternal and Child Health Bureau, American Academy of Child and Adolescent Psychiatry, Forest, Janssen, Yamo, MapLight, Acadia, Roche, Novartis, Seaside Therapeutics, Springer, SynapDx, and Wiley.
A version of this article appeared on Medscape.com.
, suggests a new report that shines a light on the global mental health crisis among young people.
The burden is high in this population, with around one-fifth of all disease-related disability attributable to mental disorders. The data, drawn from the 2019 Global Burden of Disease (GBD) study, examines mental health in the 293 million people worldwide in this age group.
“This concentration of disability burden at an early age raises concern about the potential lifetime impact of these conditions,” wrote the authors, led by Christian Kieling, MD, PhD, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
The study was published online in JAMA Psychiatry.
State of Emergency
Soaring rates of mental health disorders among young people, intensified by the COVID-19 pandemic, have led the American Academy of Child and Adolescent Psychiatry and the American Academy of Pediatrics to declare a state of emergency.
Using the GBD study, Dr. Kieling and colleagues estimated the global prevalence and years lived with disability associated with mental disorders and substance use disorders in people aged 5-24 years.
In 2019, individuals in this age range had at least one mental disorder and 31 million had a substance use disorder — an average prevalence of 11.6% and 1.2%, respectively.
The prevalence of mental disorders doubled from the age range of 5-9 years (6.8%) to 20-24 years (13.6%).
Among mental disorders analyzed, anxiety disorders were most common in the overall population (84 million; 3.35%) and schizophrenia the least common (2 million; 0.08%).
Notably, the researchers said, there was a steep increase in mood disorders, particularly anxiety and substance use disorders, across early to late adolescence and from late adolescence to young adulthood.
Mental disorders and substance use disorders were the leading cause of nonfatal disability in children and youths in 2019, accounting for 31 million and 4.3 million years lived with disability (YLDs), respectively. That represents roughly 20% and 3% of YLDs, respectively, from all causes.
Youth Mental Health Is Not a Monolith
“That youth mental health is in such dire straits is particularly striking given that many measures of global physical health in young people are improving,” wrote the authors of an accompanying editorial.
In their editorial, Jeremy Veenstra-VanderWeele, MD, Department of Psychiatry, Columbia University, New York, and co-authors noted that these and other age- and gender-related findings “represent a meaningful contribution to the literature.”
The granular data underscore that youth mental health is “not a monolith” but rather involves considerable variation in prevalence and morbidity across both age and gender, they wrote.
Therefore, mental health screening, promotion, and prevention efforts may benefit from an age-based approach that targets specific disorders during “high prevalence developmental intervals, with keen attention also paid to gender,” they suggested.
On the basis of the findings in this analysis, healthcare and education resource allocation may need to be adjusted for specific disorders, they added.
“One might propose a community- or school-based mental health initiative that screens for and educates parents and teachers on ADHD and anxiety disorders from kindergarten through third grade (ages 5-9 years, when prevalence and resulting disability grow markedly),” Dr. Veenstra-VanderWeele and colleagues wrote. “Later initiatives could then focus on mood and substance use disorders during high school and college (ages 15-19 years and 20-24 years).”
The study was partially funded by a research grant from the Cundill Centre for Child and Youth Depression. Dr. Kieling is the founder of Wida. Dr. Veenstra-VanderWeele reported receiving grants from the National Institutes of Health and Simon’s Foundation and research support/advisory board/editorial fees from Autism Speaks, Agency for Healthcare Research and Quality, Health Resources and Services Administration Maternal and Child Health Bureau, American Academy of Child and Adolescent Psychiatry, Forest, Janssen, Yamo, MapLight, Acadia, Roche, Novartis, Seaside Therapeutics, Springer, SynapDx, and Wiley.
A version of this article appeared on Medscape.com.
, suggests a new report that shines a light on the global mental health crisis among young people.
The burden is high in this population, with around one-fifth of all disease-related disability attributable to mental disorders. The data, drawn from the 2019 Global Burden of Disease (GBD) study, examines mental health in the 293 million people worldwide in this age group.
“This concentration of disability burden at an early age raises concern about the potential lifetime impact of these conditions,” wrote the authors, led by Christian Kieling, MD, PhD, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
The study was published online in JAMA Psychiatry.
State of Emergency
Soaring rates of mental health disorders among young people, intensified by the COVID-19 pandemic, have led the American Academy of Child and Adolescent Psychiatry and the American Academy of Pediatrics to declare a state of emergency.
Using the GBD study, Dr. Kieling and colleagues estimated the global prevalence and years lived with disability associated with mental disorders and substance use disorders in people aged 5-24 years.
In 2019, individuals in this age range had at least one mental disorder and 31 million had a substance use disorder — an average prevalence of 11.6% and 1.2%, respectively.
The prevalence of mental disorders doubled from the age range of 5-9 years (6.8%) to 20-24 years (13.6%).
Among mental disorders analyzed, anxiety disorders were most common in the overall population (84 million; 3.35%) and schizophrenia the least common (2 million; 0.08%).
Notably, the researchers said, there was a steep increase in mood disorders, particularly anxiety and substance use disorders, across early to late adolescence and from late adolescence to young adulthood.
Mental disorders and substance use disorders were the leading cause of nonfatal disability in children and youths in 2019, accounting for 31 million and 4.3 million years lived with disability (YLDs), respectively. That represents roughly 20% and 3% of YLDs, respectively, from all causes.
Youth Mental Health Is Not a Monolith
“That youth mental health is in such dire straits is particularly striking given that many measures of global physical health in young people are improving,” wrote the authors of an accompanying editorial.
In their editorial, Jeremy Veenstra-VanderWeele, MD, Department of Psychiatry, Columbia University, New York, and co-authors noted that these and other age- and gender-related findings “represent a meaningful contribution to the literature.”
The granular data underscore that youth mental health is “not a monolith” but rather involves considerable variation in prevalence and morbidity across both age and gender, they wrote.
Therefore, mental health screening, promotion, and prevention efforts may benefit from an age-based approach that targets specific disorders during “high prevalence developmental intervals, with keen attention also paid to gender,” they suggested.
On the basis of the findings in this analysis, healthcare and education resource allocation may need to be adjusted for specific disorders, they added.
“One might propose a community- or school-based mental health initiative that screens for and educates parents and teachers on ADHD and anxiety disorders from kindergarten through third grade (ages 5-9 years, when prevalence and resulting disability grow markedly),” Dr. Veenstra-VanderWeele and colleagues wrote. “Later initiatives could then focus on mood and substance use disorders during high school and college (ages 15-19 years and 20-24 years).”
The study was partially funded by a research grant from the Cundill Centre for Child and Youth Depression. Dr. Kieling is the founder of Wida. Dr. Veenstra-VanderWeele reported receiving grants from the National Institutes of Health and Simon’s Foundation and research support/advisory board/editorial fees from Autism Speaks, Agency for Healthcare Research and Quality, Health Resources and Services Administration Maternal and Child Health Bureau, American Academy of Child and Adolescent Psychiatry, Forest, Janssen, Yamo, MapLight, Acadia, Roche, Novartis, Seaside Therapeutics, Springer, SynapDx, and Wiley.
A version of this article appeared on Medscape.com.
Dupilumab Improves AD Affecting the Hands, Feet
TOPLINE:
compared with placebo.
METHODOLOGY:
- The multinational phase 3 LIBERTY-AD-HAFT trial of adults and adolescents with moderate to severe chronic atopic dermatitis (AD) of the hands, feet, or both included 67 participants at 48 sites randomized to dupilumab monotherapy and 66 to placebo.
- The primary endpoint was the proportion of patients scoring 0 or 1 on Hand and Foot Investigator’s Global Assessment (HF-IGA) at week 16.
- Secondary endpoints were severity and extent of signs, symptom intensity (itch and pain), sleep, and quality of life.
TAKEAWAY:
- At week 16, 27 patients receiving dupilumab vs 11 receiving placebo achieved an HF-IGA score of 0 or 1 (40.3% vs 16.7%; P = .003).
- At week 16, 35 participants receiving dupilumab vs nine receiving placebo improved at least four points in the weekly average of daily HF-Peak Pruritus Numeric Rating Scale (52.2% vs 13.6%; P < .0001).
- At week 16, Quality of Life Hand Eczema Questionnaire results improved in the dupilumab group compared with controls (P < .0001), and weekly average of daily Sleep Numeric Rating Scale results improved in the dupilumab group compared with controls (P < .05).
- The safety profile was similar to the known profile in adults and adolescents with moderate to severe AD.
IN PRACTICE:
The results of the study “support dupilumab” as an “efficacious systemic therapy for moderate to severe H/F AD,” the authors wrote.
SOURCE:
The study, led by Eric L. Simpson, MD, MCR, professor of dermatology at the Oregon Health & Science University in Portland, was published on January 29, 2024, in the Journal of the American Academy of Dermatology.
LIMITATIONS:
The short duration of the study and the large proportion of patients with positive patch tests (31 of 133) suggested that some participants may have had concurrent AD and allergic contact dermatitis, so the effect of dupilumab on those patients needs further evaluation.
DISCLOSURES:
The study was sponsored by Sanofi and Regeneron. All but one author had financial relationships with Sanofi, Regeneron, or both. Several authors were employees of, and may hold stocks or stock options in, Sanofi or Regeneron.
TOPLINE:
compared with placebo.
METHODOLOGY:
- The multinational phase 3 LIBERTY-AD-HAFT trial of adults and adolescents with moderate to severe chronic atopic dermatitis (AD) of the hands, feet, or both included 67 participants at 48 sites randomized to dupilumab monotherapy and 66 to placebo.
- The primary endpoint was the proportion of patients scoring 0 or 1 on Hand and Foot Investigator’s Global Assessment (HF-IGA) at week 16.
- Secondary endpoints were severity and extent of signs, symptom intensity (itch and pain), sleep, and quality of life.
TAKEAWAY:
- At week 16, 27 patients receiving dupilumab vs 11 receiving placebo achieved an HF-IGA score of 0 or 1 (40.3% vs 16.7%; P = .003).
- At week 16, 35 participants receiving dupilumab vs nine receiving placebo improved at least four points in the weekly average of daily HF-Peak Pruritus Numeric Rating Scale (52.2% vs 13.6%; P < .0001).
- At week 16, Quality of Life Hand Eczema Questionnaire results improved in the dupilumab group compared with controls (P < .0001), and weekly average of daily Sleep Numeric Rating Scale results improved in the dupilumab group compared with controls (P < .05).
- The safety profile was similar to the known profile in adults and adolescents with moderate to severe AD.
IN PRACTICE:
The results of the study “support dupilumab” as an “efficacious systemic therapy for moderate to severe H/F AD,” the authors wrote.
SOURCE:
The study, led by Eric L. Simpson, MD, MCR, professor of dermatology at the Oregon Health & Science University in Portland, was published on January 29, 2024, in the Journal of the American Academy of Dermatology.
LIMITATIONS:
The short duration of the study and the large proportion of patients with positive patch tests (31 of 133) suggested that some participants may have had concurrent AD and allergic contact dermatitis, so the effect of dupilumab on those patients needs further evaluation.
DISCLOSURES:
The study was sponsored by Sanofi and Regeneron. All but one author had financial relationships with Sanofi, Regeneron, or both. Several authors were employees of, and may hold stocks or stock options in, Sanofi or Regeneron.
TOPLINE:
compared with placebo.
METHODOLOGY:
- The multinational phase 3 LIBERTY-AD-HAFT trial of adults and adolescents with moderate to severe chronic atopic dermatitis (AD) of the hands, feet, or both included 67 participants at 48 sites randomized to dupilumab monotherapy and 66 to placebo.
- The primary endpoint was the proportion of patients scoring 0 or 1 on Hand and Foot Investigator’s Global Assessment (HF-IGA) at week 16.
- Secondary endpoints were severity and extent of signs, symptom intensity (itch and pain), sleep, and quality of life.
TAKEAWAY:
- At week 16, 27 patients receiving dupilumab vs 11 receiving placebo achieved an HF-IGA score of 0 or 1 (40.3% vs 16.7%; P = .003).
- At week 16, 35 participants receiving dupilumab vs nine receiving placebo improved at least four points in the weekly average of daily HF-Peak Pruritus Numeric Rating Scale (52.2% vs 13.6%; P < .0001).
- At week 16, Quality of Life Hand Eczema Questionnaire results improved in the dupilumab group compared with controls (P < .0001), and weekly average of daily Sleep Numeric Rating Scale results improved in the dupilumab group compared with controls (P < .05).
- The safety profile was similar to the known profile in adults and adolescents with moderate to severe AD.
IN PRACTICE:
The results of the study “support dupilumab” as an “efficacious systemic therapy for moderate to severe H/F AD,” the authors wrote.
SOURCE:
The study, led by Eric L. Simpson, MD, MCR, professor of dermatology at the Oregon Health & Science University in Portland, was published on January 29, 2024, in the Journal of the American Academy of Dermatology.
LIMITATIONS:
The short duration of the study and the large proportion of patients with positive patch tests (31 of 133) suggested that some participants may have had concurrent AD and allergic contact dermatitis, so the effect of dupilumab on those patients needs further evaluation.
DISCLOSURES:
The study was sponsored by Sanofi and Regeneron. All but one author had financial relationships with Sanofi, Regeneron, or both. Several authors were employees of, and may hold stocks or stock options in, Sanofi or Regeneron.
Number of State Psychiatric Hospital Beds Hits Historic Low
to help establish competency for trial.
“The shortage of psychiatric beds has real consequences for people with SMI — some will wait months in jail despite not yet being found guilty of a crime, others will be denied admission despite being critically ill, and others still will be discharged prematurely onto the streets to free up beds, where they may grow sicker and be at an elevated risk of mortality,” wrote report coauthors Shanti Silver of the Treatment Advocacy Center (TAC) in Arlington and Elizabeth Sinclair Hanq of the National Association of State Mental Health Program Directors in Alexandria, Virginia.
Published online on January 24, Prevention Over Punishment: Finding the Right Balance of Civil and Forensic State Psychiatric Hospital Beds recommends that state and local governments work together to open additional state psychiatric hospital beds for civil and forensic patients with SMI.
To obtain data about the availability of state psychiatric hospital beds, TAC surveyed state officials from April to August 2023. Official responses were provided by 41 states and the District of Columbia.
Information for the remaining states was gathered from state websites, media articles, preexisting reports, hospital admission staff, or personal contacts living in those states.
The median occupancy rate for state-run hospitals in the new report was 90%, well above the 85% level investigators say usually signals a bed shortage. Overall, 73% of states reported occupancy rates above that level, with 11 states operating at 95% capacity.
The proportion of state psychiatric beds occupied by forensic patients has increased by 12% since 2016, largely driven by the growing number of individuals awaiting a competency determination to stand trial. Before they occupy these beds, however, people with SMI can languish in jail for months or even years, waiting for a bed to open.
About 15% of all state hospital beds and 31% of forensic beds across 34 states were occupied by individuals who had been found not guilty of a crime by reasons of insanity.
“The prioritization of admission of forensic patients has effectively created a system where someone must be arrested to access a state hospital bed,” report coauthor Lisa Dailey, TAC executive director, told this news organization. “But there are not enough beds for forensic patients either; thousands of inmates are waiting in jail on any given day for a bed to open up.”
There are several factors contributing to the scarcity of beds, including an existing hospital staffing shortage made worse by the COVID-19 pandemic and a lack of appropriate discharge facilities.
Report authors offered a number of recommendations to federal, state, and local officials to increase the availability of state-run psychiatric hospital beds, including infrastructure changes involving recruiting and retaining staff for state hospitals and funding new discharge or step-down facilities so that patients have a place to recover when they leave the hospital.
Policy changes could also help, the report noted. Policymakers should consider “dismiss and transfer” procedures to address the backlog of nearly 6000 people with SMI waiting for a state hospital bed to achieve competency to stand trial. With “dismiss and transfer,” criminal charges are dismissed or suspended while an application for civil commitment is filed in the probate court. Once a civil commitment order has been issued, the individual is released to an outpatient commitment program for treatment.
“States must strive for prevention over punishment,” the report concluded.
There was no study funding reported, nor were disclosures available.
A version of this article appeared on Medscape.com.
to help establish competency for trial.
“The shortage of psychiatric beds has real consequences for people with SMI — some will wait months in jail despite not yet being found guilty of a crime, others will be denied admission despite being critically ill, and others still will be discharged prematurely onto the streets to free up beds, where they may grow sicker and be at an elevated risk of mortality,” wrote report coauthors Shanti Silver of the Treatment Advocacy Center (TAC) in Arlington and Elizabeth Sinclair Hanq of the National Association of State Mental Health Program Directors in Alexandria, Virginia.
Published online on January 24, Prevention Over Punishment: Finding the Right Balance of Civil and Forensic State Psychiatric Hospital Beds recommends that state and local governments work together to open additional state psychiatric hospital beds for civil and forensic patients with SMI.
To obtain data about the availability of state psychiatric hospital beds, TAC surveyed state officials from April to August 2023. Official responses were provided by 41 states and the District of Columbia.
Information for the remaining states was gathered from state websites, media articles, preexisting reports, hospital admission staff, or personal contacts living in those states.
The median occupancy rate for state-run hospitals in the new report was 90%, well above the 85% level investigators say usually signals a bed shortage. Overall, 73% of states reported occupancy rates above that level, with 11 states operating at 95% capacity.
The proportion of state psychiatric beds occupied by forensic patients has increased by 12% since 2016, largely driven by the growing number of individuals awaiting a competency determination to stand trial. Before they occupy these beds, however, people with SMI can languish in jail for months or even years, waiting for a bed to open.
About 15% of all state hospital beds and 31% of forensic beds across 34 states were occupied by individuals who had been found not guilty of a crime by reasons of insanity.
“The prioritization of admission of forensic patients has effectively created a system where someone must be arrested to access a state hospital bed,” report coauthor Lisa Dailey, TAC executive director, told this news organization. “But there are not enough beds for forensic patients either; thousands of inmates are waiting in jail on any given day for a bed to open up.”
There are several factors contributing to the scarcity of beds, including an existing hospital staffing shortage made worse by the COVID-19 pandemic and a lack of appropriate discharge facilities.
Report authors offered a number of recommendations to federal, state, and local officials to increase the availability of state-run psychiatric hospital beds, including infrastructure changes involving recruiting and retaining staff for state hospitals and funding new discharge or step-down facilities so that patients have a place to recover when they leave the hospital.
Policy changes could also help, the report noted. Policymakers should consider “dismiss and transfer” procedures to address the backlog of nearly 6000 people with SMI waiting for a state hospital bed to achieve competency to stand trial. With “dismiss and transfer,” criminal charges are dismissed or suspended while an application for civil commitment is filed in the probate court. Once a civil commitment order has been issued, the individual is released to an outpatient commitment program for treatment.
“States must strive for prevention over punishment,” the report concluded.
There was no study funding reported, nor were disclosures available.
A version of this article appeared on Medscape.com.
to help establish competency for trial.
“The shortage of psychiatric beds has real consequences for people with SMI — some will wait months in jail despite not yet being found guilty of a crime, others will be denied admission despite being critically ill, and others still will be discharged prematurely onto the streets to free up beds, where they may grow sicker and be at an elevated risk of mortality,” wrote report coauthors Shanti Silver of the Treatment Advocacy Center (TAC) in Arlington and Elizabeth Sinclair Hanq of the National Association of State Mental Health Program Directors in Alexandria, Virginia.
Published online on January 24, Prevention Over Punishment: Finding the Right Balance of Civil and Forensic State Psychiatric Hospital Beds recommends that state and local governments work together to open additional state psychiatric hospital beds for civil and forensic patients with SMI.
To obtain data about the availability of state psychiatric hospital beds, TAC surveyed state officials from April to August 2023. Official responses were provided by 41 states and the District of Columbia.
Information for the remaining states was gathered from state websites, media articles, preexisting reports, hospital admission staff, or personal contacts living in those states.
The median occupancy rate for state-run hospitals in the new report was 90%, well above the 85% level investigators say usually signals a bed shortage. Overall, 73% of states reported occupancy rates above that level, with 11 states operating at 95% capacity.
The proportion of state psychiatric beds occupied by forensic patients has increased by 12% since 2016, largely driven by the growing number of individuals awaiting a competency determination to stand trial. Before they occupy these beds, however, people with SMI can languish in jail for months or even years, waiting for a bed to open.
About 15% of all state hospital beds and 31% of forensic beds across 34 states were occupied by individuals who had been found not guilty of a crime by reasons of insanity.
“The prioritization of admission of forensic patients has effectively created a system where someone must be arrested to access a state hospital bed,” report coauthor Lisa Dailey, TAC executive director, told this news organization. “But there are not enough beds for forensic patients either; thousands of inmates are waiting in jail on any given day for a bed to open up.”
There are several factors contributing to the scarcity of beds, including an existing hospital staffing shortage made worse by the COVID-19 pandemic and a lack of appropriate discharge facilities.
Report authors offered a number of recommendations to federal, state, and local officials to increase the availability of state-run psychiatric hospital beds, including infrastructure changes involving recruiting and retaining staff for state hospitals and funding new discharge or step-down facilities so that patients have a place to recover when they leave the hospital.
Policy changes could also help, the report noted. Policymakers should consider “dismiss and transfer” procedures to address the backlog of nearly 6000 people with SMI waiting for a state hospital bed to achieve competency to stand trial. With “dismiss and transfer,” criminal charges are dismissed or suspended while an application for civil commitment is filed in the probate court. Once a civil commitment order has been issued, the individual is released to an outpatient commitment program for treatment.
“States must strive for prevention over punishment,” the report concluded.
There was no study funding reported, nor were disclosures available.
A version of this article appeared on Medscape.com.
HPV Positive Test: How to Address Patients’ Anxieties
Faced with a positive human papillomavirus (HPV) test, patients are quickly overwhelmed by anxiety-inducing questions. It is crucial to provide them with adequate responses to reassure them, emphasized Jean-Louis Mergui, MD, president of the International Federation for Colposcopy, during the press conference of the Congress of the French Society of Colposcopy and Cervico-Vaginal Pathology.
“Do I have cancer? When did I catch this papillomavirus? Is it dangerous for my partner? How do I get rid of it?” “Not everyone is equipped to answer these four questions. However, it is extremely important that healthcare professionals provide correct answers to patients so that they stop worrying,” Dr. Mergui explained.
Papillomavirus and Cancer
One of the first instincts of patients who receive a positive HPV test is to turn to the Internet. There, they read about “high-risk HPV, which is potentially oncogenic,” and become completely panicked, said Dr. Mergui.
However, among women, the probability of having a high-grade CIN3 lesion or higher on the cervix when the HPV test is positive is about 7%, according to the ATHENA study. “About 93% of patients do not have a severe lesion on the cervix. That’s why colposcopy is not performed on all patients. They need to be reassured,” said Dr. Mergui. When the papillomavirus persists, there is a risk for a cervical lesion. After 11 years, between 20% and 30% of patients develop a high-grade lesion on the cervix. However, on average, a high-risk HPV is spontaneously eliminated within 1-2 years. “After 14 months, 50% of women will test negative for their papillomavirus,” Dr. Mergui noted.
“High-risk HPV does not mean there is a lesion; it means there is a risk of developing a lesion on the cervix one day. That’s why these patients need to be monitored and explored,” he added.
In practice, when a patient aged between 30 and 65 years has a positive HPV test, cytology is performed to look for lesions. Only in the case of an abnormal smear, ASC-US, is colposcopy recommended. In the absence of a lesion, a control HPV test is conducted 1 year later to monitor virus persistence.
It should be noted that patients who have been treated for a cervical lesion have a five times higher risk of developing invasive cervical, vaginal, or vulvar cancer. Therefore, treated patients must be monitored once every 3 years for life.
Time of Infection
Many patients ask, “When did I catch this papillomavirus?” In response, Dr. Mergui first emphasized that HPV infection is common. “Between ages 15 and 30 years, most of us are infected with a high-risk HPV. When we look at the incidence between ages 15 and 25 years, every year, 20% of all young girls are infected with HPV, including 17% with high-risk HPV. The virus is usually caught within the first 5 years of sexual activity, and typically disappears after about a year,” he explained.
However, the most disturbing scenario for patients is when their last examination was negative, and there is no apparent reason for having caught the virus since then. Suspicion often falls on the partner. Once again, the gynecologist seeks to reassure.
It is possible that the last time screening was conducted, the virus was not sought (HPV test), but rather cervical lesions were sought by smear. However, a normal smear does not mean that the papillomavirus is not present. A negative cytology does not mean a negative HPV test. As we have seen, the virus is not always associated with the presence of a lesion, explained Dr. Mergui.
Also, having had a negative HPV test a few years earlier does not mean that one was not already infected. The HPV test determines the quantity of virus. Therefore, it is possible that the virus was present in small quantities that were without clinical significance (hence, a negative test). However, a few years later, the virus may have multiplied, and the HPV test became positive.
“Sometimes, the virus re-emerges 40, 50 years after infection due to age-related immune decline,” said Dr. Mergui. “So, just because the smear was negative or the HPV test was negative at the last examination does not mean that one was infected between the two.” Moreover, only 15% of couples have the same virus present on the penis or vagina, he pointed out.
Protecting One’s Partner
Once the diagnosis is made, it is often too late to protect the partner because they have already been infected. “It is certain that the partner will be infected or has already been infected because when the patient comes to you with a positive HPV test, she has already had sexual intercourse. It is worth noting that the virus can be transmitted through digital touching, and condoms are not very effective in preventing virus transmission,” said Dr. Mergui.
The speaker further clarified that the risk for men is much lower than that for women. “In women, about 40,000 lesions linked to high-risk HPV types, precancerous or cancerous, are observed every year. In men, this number is 1900. So, this represents 20 times fewer neoplastic lesions in men. The problem in men is oropharyngeal lesions, which are three times more common than in women. However, there is no screening for oropharyngeal cancer.”
So, when should the partner consult? Dr. Mergui advised consulting when there are clinically visible lesions (small warts, bumps, or ear, nose, and throat symptoms). “I do not recommend systematic examination of male or female partners,” he added.
Clearing the Virus
There are treatments for cervical lesions but not for papillomavirus infection.
“The only thing that can be suggested is quitting smoking, which increases viral clearance, thus reducing viral load. Also, the use of condoms helps improve viral clearance, but when women have a stable relationship, it seems unrealistic to think they will constantly use condoms. Finally, the prophylactic vaccine has been proposed, but it does not treat the infection. In fact, the real solution is to tell patients that they need to continue regular monitoring,” said Dr. Mergui.
“It should be noted that an ongoing study at the European level seems to show that when women who have undergone surgical treatment for a high-grade cervical lesion are vaccinated at the time of treatment or just after treatment, it reduces the risk of recurrence by 50%. So, the risk of recurrence is around 7%-8%. This strategy could be interesting, but for now, there is no official recommendation,” Dr. Mergui concluded.
This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.
Faced with a positive human papillomavirus (HPV) test, patients are quickly overwhelmed by anxiety-inducing questions. It is crucial to provide them with adequate responses to reassure them, emphasized Jean-Louis Mergui, MD, president of the International Federation for Colposcopy, during the press conference of the Congress of the French Society of Colposcopy and Cervico-Vaginal Pathology.
“Do I have cancer? When did I catch this papillomavirus? Is it dangerous for my partner? How do I get rid of it?” “Not everyone is equipped to answer these four questions. However, it is extremely important that healthcare professionals provide correct answers to patients so that they stop worrying,” Dr. Mergui explained.
Papillomavirus and Cancer
One of the first instincts of patients who receive a positive HPV test is to turn to the Internet. There, they read about “high-risk HPV, which is potentially oncogenic,” and become completely panicked, said Dr. Mergui.
However, among women, the probability of having a high-grade CIN3 lesion or higher on the cervix when the HPV test is positive is about 7%, according to the ATHENA study. “About 93% of patients do not have a severe lesion on the cervix. That’s why colposcopy is not performed on all patients. They need to be reassured,” said Dr. Mergui. When the papillomavirus persists, there is a risk for a cervical lesion. After 11 years, between 20% and 30% of patients develop a high-grade lesion on the cervix. However, on average, a high-risk HPV is spontaneously eliminated within 1-2 years. “After 14 months, 50% of women will test negative for their papillomavirus,” Dr. Mergui noted.
“High-risk HPV does not mean there is a lesion; it means there is a risk of developing a lesion on the cervix one day. That’s why these patients need to be monitored and explored,” he added.
In practice, when a patient aged between 30 and 65 years has a positive HPV test, cytology is performed to look for lesions. Only in the case of an abnormal smear, ASC-US, is colposcopy recommended. In the absence of a lesion, a control HPV test is conducted 1 year later to monitor virus persistence.
It should be noted that patients who have been treated for a cervical lesion have a five times higher risk of developing invasive cervical, vaginal, or vulvar cancer. Therefore, treated patients must be monitored once every 3 years for life.
Time of Infection
Many patients ask, “When did I catch this papillomavirus?” In response, Dr. Mergui first emphasized that HPV infection is common. “Between ages 15 and 30 years, most of us are infected with a high-risk HPV. When we look at the incidence between ages 15 and 25 years, every year, 20% of all young girls are infected with HPV, including 17% with high-risk HPV. The virus is usually caught within the first 5 years of sexual activity, and typically disappears after about a year,” he explained.
However, the most disturbing scenario for patients is when their last examination was negative, and there is no apparent reason for having caught the virus since then. Suspicion often falls on the partner. Once again, the gynecologist seeks to reassure.
It is possible that the last time screening was conducted, the virus was not sought (HPV test), but rather cervical lesions were sought by smear. However, a normal smear does not mean that the papillomavirus is not present. A negative cytology does not mean a negative HPV test. As we have seen, the virus is not always associated with the presence of a lesion, explained Dr. Mergui.
Also, having had a negative HPV test a few years earlier does not mean that one was not already infected. The HPV test determines the quantity of virus. Therefore, it is possible that the virus was present in small quantities that were without clinical significance (hence, a negative test). However, a few years later, the virus may have multiplied, and the HPV test became positive.
“Sometimes, the virus re-emerges 40, 50 years after infection due to age-related immune decline,” said Dr. Mergui. “So, just because the smear was negative or the HPV test was negative at the last examination does not mean that one was infected between the two.” Moreover, only 15% of couples have the same virus present on the penis or vagina, he pointed out.
Protecting One’s Partner
Once the diagnosis is made, it is often too late to protect the partner because they have already been infected. “It is certain that the partner will be infected or has already been infected because when the patient comes to you with a positive HPV test, she has already had sexual intercourse. It is worth noting that the virus can be transmitted through digital touching, and condoms are not very effective in preventing virus transmission,” said Dr. Mergui.
The speaker further clarified that the risk for men is much lower than that for women. “In women, about 40,000 lesions linked to high-risk HPV types, precancerous or cancerous, are observed every year. In men, this number is 1900. So, this represents 20 times fewer neoplastic lesions in men. The problem in men is oropharyngeal lesions, which are three times more common than in women. However, there is no screening for oropharyngeal cancer.”
So, when should the partner consult? Dr. Mergui advised consulting when there are clinically visible lesions (small warts, bumps, or ear, nose, and throat symptoms). “I do not recommend systematic examination of male or female partners,” he added.
Clearing the Virus
There are treatments for cervical lesions but not for papillomavirus infection.
“The only thing that can be suggested is quitting smoking, which increases viral clearance, thus reducing viral load. Also, the use of condoms helps improve viral clearance, but when women have a stable relationship, it seems unrealistic to think they will constantly use condoms. Finally, the prophylactic vaccine has been proposed, but it does not treat the infection. In fact, the real solution is to tell patients that they need to continue regular monitoring,” said Dr. Mergui.
“It should be noted that an ongoing study at the European level seems to show that when women who have undergone surgical treatment for a high-grade cervical lesion are vaccinated at the time of treatment or just after treatment, it reduces the risk of recurrence by 50%. So, the risk of recurrence is around 7%-8%. This strategy could be interesting, but for now, there is no official recommendation,” Dr. Mergui concluded.
This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.
Faced with a positive human papillomavirus (HPV) test, patients are quickly overwhelmed by anxiety-inducing questions. It is crucial to provide them with adequate responses to reassure them, emphasized Jean-Louis Mergui, MD, president of the International Federation for Colposcopy, during the press conference of the Congress of the French Society of Colposcopy and Cervico-Vaginal Pathology.
“Do I have cancer? When did I catch this papillomavirus? Is it dangerous for my partner? How do I get rid of it?” “Not everyone is equipped to answer these four questions. However, it is extremely important that healthcare professionals provide correct answers to patients so that they stop worrying,” Dr. Mergui explained.
Papillomavirus and Cancer
One of the first instincts of patients who receive a positive HPV test is to turn to the Internet. There, they read about “high-risk HPV, which is potentially oncogenic,” and become completely panicked, said Dr. Mergui.
However, among women, the probability of having a high-grade CIN3 lesion or higher on the cervix when the HPV test is positive is about 7%, according to the ATHENA study. “About 93% of patients do not have a severe lesion on the cervix. That’s why colposcopy is not performed on all patients. They need to be reassured,” said Dr. Mergui. When the papillomavirus persists, there is a risk for a cervical lesion. After 11 years, between 20% and 30% of patients develop a high-grade lesion on the cervix. However, on average, a high-risk HPV is spontaneously eliminated within 1-2 years. “After 14 months, 50% of women will test negative for their papillomavirus,” Dr. Mergui noted.
“High-risk HPV does not mean there is a lesion; it means there is a risk of developing a lesion on the cervix one day. That’s why these patients need to be monitored and explored,” he added.
In practice, when a patient aged between 30 and 65 years has a positive HPV test, cytology is performed to look for lesions. Only in the case of an abnormal smear, ASC-US, is colposcopy recommended. In the absence of a lesion, a control HPV test is conducted 1 year later to monitor virus persistence.
It should be noted that patients who have been treated for a cervical lesion have a five times higher risk of developing invasive cervical, vaginal, or vulvar cancer. Therefore, treated patients must be monitored once every 3 years for life.
Time of Infection
Many patients ask, “When did I catch this papillomavirus?” In response, Dr. Mergui first emphasized that HPV infection is common. “Between ages 15 and 30 years, most of us are infected with a high-risk HPV. When we look at the incidence between ages 15 and 25 years, every year, 20% of all young girls are infected with HPV, including 17% with high-risk HPV. The virus is usually caught within the first 5 years of sexual activity, and typically disappears after about a year,” he explained.
However, the most disturbing scenario for patients is when their last examination was negative, and there is no apparent reason for having caught the virus since then. Suspicion often falls on the partner. Once again, the gynecologist seeks to reassure.
It is possible that the last time screening was conducted, the virus was not sought (HPV test), but rather cervical lesions were sought by smear. However, a normal smear does not mean that the papillomavirus is not present. A negative cytology does not mean a negative HPV test. As we have seen, the virus is not always associated with the presence of a lesion, explained Dr. Mergui.
Also, having had a negative HPV test a few years earlier does not mean that one was not already infected. The HPV test determines the quantity of virus. Therefore, it is possible that the virus was present in small quantities that were without clinical significance (hence, a negative test). However, a few years later, the virus may have multiplied, and the HPV test became positive.
“Sometimes, the virus re-emerges 40, 50 years after infection due to age-related immune decline,” said Dr. Mergui. “So, just because the smear was negative or the HPV test was negative at the last examination does not mean that one was infected between the two.” Moreover, only 15% of couples have the same virus present on the penis or vagina, he pointed out.
Protecting One’s Partner
Once the diagnosis is made, it is often too late to protect the partner because they have already been infected. “It is certain that the partner will be infected or has already been infected because when the patient comes to you with a positive HPV test, she has already had sexual intercourse. It is worth noting that the virus can be transmitted through digital touching, and condoms are not very effective in preventing virus transmission,” said Dr. Mergui.
The speaker further clarified that the risk for men is much lower than that for women. “In women, about 40,000 lesions linked to high-risk HPV types, precancerous or cancerous, are observed every year. In men, this number is 1900. So, this represents 20 times fewer neoplastic lesions in men. The problem in men is oropharyngeal lesions, which are three times more common than in women. However, there is no screening for oropharyngeal cancer.”
So, when should the partner consult? Dr. Mergui advised consulting when there are clinically visible lesions (small warts, bumps, or ear, nose, and throat symptoms). “I do not recommend systematic examination of male or female partners,” he added.
Clearing the Virus
There are treatments for cervical lesions but not for papillomavirus infection.
“The only thing that can be suggested is quitting smoking, which increases viral clearance, thus reducing viral load. Also, the use of condoms helps improve viral clearance, but when women have a stable relationship, it seems unrealistic to think they will constantly use condoms. Finally, the prophylactic vaccine has been proposed, but it does not treat the infection. In fact, the real solution is to tell patients that they need to continue regular monitoring,” said Dr. Mergui.
“It should be noted that an ongoing study at the European level seems to show that when women who have undergone surgical treatment for a high-grade cervical lesion are vaccinated at the time of treatment or just after treatment, it reduces the risk of recurrence by 50%. So, the risk of recurrence is around 7%-8%. This strategy could be interesting, but for now, there is no official recommendation,” Dr. Mergui concluded.
This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.
Glycemic control in pregnancy: The role of CGM for T1D and T2D, and intrapartum management
WASHINGTON — Continuous glucose monitoring (CGM) is widely used during pregnancy for individuals with type 1 diabetes — with pregnancy-specific target metrics now chosen and benefits on perinatal outcomes demonstrated — but more research is needed to elucidate its role in the growing population of pregnant people with type 2 diabetes and gestational diabetes (GDM). And overall, there are still “many more questions unanswered about CGM use in pregnancy than what we have answered,” Celeste Durnwald, MD, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.
There’s much to learn about how to best interpret “the detailed and complex data that CGM provides,” and what targets in addition to time in range (TIR) are most important, said Dr. Durnwald, director of the perinatal diabetes program and associate professor of ob.gyn. at the Hospital of the University of Pennsylvania, Philadelphia, in a presentation on CGM.
Among other questions are whether fasting glucose is “as important in the era of CGM,” and whether there should be different glycemic targets for nocturnal versus daytime TIR, she said. Moreover, questions justifiably remain about whether the TIR targets for type 1 diabetes in pregnancy are indeed optimal, she said in a discussion period.
Ongoing research is looking at whether CGM can motivate and guide patients with GDM through diet and lifestyle changes such that “we can see changes in amounts of medication we use,” Dr. Durnwald noted in her presentation. “There’s a whole breadth of research looking at whether CGM can help predict diagnosis of GDM, large for gestational age, or preeclampsia, and what are the targets.”
Maternal hypoglycemia during pregnancy — a time when strict glycemic control is recommended to reduce the risk of congenital malformations and other fetal and neonatal morbidity — remains a concern in type 1 diabetes, even with widespread use of CGM in this population, said Barak Rosenn, MD, during a presentation on glycemic control in type 1 diabetes.
A pilot study of a newly designed pregnancy-specific closed-loop insulin delivery system, published last year (Diabetes Care. 2023;46:1425-31), has offered the first “really encouraging information about the ability to use our most up-to-date technology to help our type 1 patients maintain strict control and at the same time decrease their risk of severe hypoglycemia,” said Dr. Rosenn, a maternal-fetal medicine specialist at the Jersey City Medical Center, Jersey City, New Jersey.
Guidance for tight intrapartum glucose control, meanwhile, has been backed by little evidence, said Michal Fishel Bartal, MD, MS, and some recent studies and reviews have shown little to no effect of such tight control on neonatal hypoglycemia, which is the aim of the guidance.
“We need to reexamine current recommendations,” said Dr. Bartal, assistant professor in the division of maternal-fetal medicine at the University of Texas Health Science Center, Houston, during a presentation on intrapartum care. “There’s very limited evidence-based data for the way we manage people with diabetes [during labor and delivery].”
The Knowns And Unknowns of CGM in Pregnancy
The multicenter, international CONCEPTT trial (Continuous Glucose Monitoring in Pregnant Women With Type 1 Diabetes), published in 2017, was the first trial to demonstrate improvements in perinatal outcomes, and it “brought CGM to the forefront in terms of widespread use,” Dr. Durnwald said.
The trial randomized more than 300 patients with type 1 diabetes who were pregnant or planning pregnancy (both users of insulin pumps and users of multiple insulin injections) to continuous, real-time CGM in addition to finger-stick glucose monitoring, or standard finger-stick glucose tests alone. In addition to small improvements in A1c and 7% more TIR (without an increase in hypoglycemia), pregnant CGM users had reductions in large-for-gestational age (LGA) births (53% vs 69%, P = .0489), neonatal intensive care admissions lasting more than 24 hours, and severe neonatal hypoglycemia.
Numbers needed to treat to prevent adverse outcomes in the CONCEPTT trial were six for LGA, six for NICU admission, and eight for neonatal hypoglycemia.
Data from the CONCEPTT trial featured prominently in the development of consensus recommendations for CGM targets in pregnancy by an international expert panel endorsed by the American Diabetes Association. In its 2019 report, the group recommended a target range of 63-140 mg/dL for type 1 and type 2 diabetes during pregnancy (compared with 70-180 mg/dL outside of pregnancy), and a TIR > 70% for pregnant people with type 1 diabetes. (Targets for time below range and time above range are also defined for type 1.)
More data are needed, the group said, in order to recommend TIR targets for type 2 diabetes in pregnancy or GDM (Diabetes Care. 2019;42:1593-603). “Many argue,” Dr. Durnwald said, “that there could be more stringent targets for those at less risk for [maternal] hypoglycemia, especially our GDM population.”
There’s a question of whether even higher TIR would further improve perinatal outcomes, she said, “or will we reach a threshold where higher TIR doesn’t get us a [further] reduction in LGA or preeclampsia.”
And while TIR is “certainly our buzzword,” lower mean glucose levels have also been associated with a lower risk of LGA and other adverse neonatal outcomes. A 2019 retrospective study from Sweden, for instance, analyzed patterns of CGM data from 186 pregnant women with type 1 diabetes and found significant associations between elevated mean glucose levels (in the second and third trimesters) and both LGA and an adverse neonatal composite outcome (Diabetologia. 2019;62:1143-53).
Elevated TIR was also associated with LGA, but “mean glucose had the strongest association with the rate of LGA,” Dr. Durnwald said.
Similarly, a 2020 subanalysis of the CONCEPTT trial data found that a higher mean glucose at both 24 and 34 weeks of gestation was significantly associated with a greater risk of LGA (Diabetes Care. 2020;43:1178-84), and a smaller 2015 analysis of data from two randomized controlled trials of CGM in pregnant women with type 1 and type 2 diabetes found this association in trimesters 2 and 3 (Diabetes Care. 2015;38;1319-25).
The ADA’s Standards of Care in Diabetes (Diabetes Care. 2024;47:S282-S294) endorse CGM as an adjunctive tool in pregnancy — not as a replacement for all traditional blood glucose monitoring — and advise that the use of CGM-reported mean glucose is superior to the use of estimated A1c, glucose management indicator, and other calculations to estimate A1c. Changes occur in pregnancy, Dr. Durnwald pointed out. “Most experts will identify a [target] mean glucose < 120 mg/dL in those with type 1, but there’s potential to have a mean glucose closer to 100 in certainly our patients with GDM and some of our patients with type 2,” she said. To a lesser extent, researchers have also looked at the effect of CMG-reported glycemic variability on outcomes such as LGA, with at least two studies finding some association, and there has been some research on nocturnal glucose and LGA, Dr. Durnwald said. CGM “gives us the opportunity,” she said, “to think about nocturnal glucose as a possible target” for further optimizing diabetes management during pregnancy.
CGM in Type 2, GDM
CGM in type 2 diabetes in pregnancy was addressed in a recently published systematic review and meta-analysis, which found only three qualifying randomized controlled trials and concluded that CGM use was not associated with improvements in perinatal outcomes, as assessed by LGA and preeclampsia (Am J Obstet Gynecol MFM. 2023;5:100969). “It’s very limited by the small sample size and the fact that most [patients] were using intermittent CGM,” Dr. Durnwald said. “It highlights how important it is to perform larger studies with continuous CGM.”
While the 2024 ADA standards say there are insufficient data to support the use of CGM in all patients with type 2 diabetes or GDM — and that the decision should be individualized “based on treatment regimen, circumstance, preferences, and needs” — real-world access to CGM for type 2, and even a bit for GDM, is improving, she said.
Some insurers require patients to be on insulin, but the trends are such that “we certainly talk about CGM to all our patients with type 2 diabetes and even our patients with GDM,” Dr. Durnwald said in a later interview. “CGMs are being advertised so we definitely have people who ask about them upon diagnosis, and we try to make it work for them.”
Is Preventing Maternal Hypoglycemia Possible?
Advancements in technology and pharmacology aimed at optimizing glycemic control — increased adoption of CGM, the use of insulin pump therapy, and the use of more rapid insulin analogs — appear to have had little to no impact on rates of severe maternal hypoglycemia in type 1 diabetes in pregnancy, said Dr. Rosenn, referring to several published studies.
The CONCEPTT study in type 1 diabetes, for instance, “gave us the best data we have on the use of CGM,” but differences in the percentage of patients with severe hypoglycemia and the total number of severe hypoglycemia episodes were basically the same whether patients used CGM or not, he said.
Closed-loop insulin delivery systems have been found in nonpregnant patients with type 1 diabetes to “be helpful in keeping people in range and also possibly [decreasing nocturnal hypoglycemia],” but the systems are not approved for use in pregnancy. “There’s not enough data on use in pregnancy, but probably more important, the algorithms used in the closed-loop systems are not directed to the targets we consider ideal for pregnancy,” Dr. Rosenn said.
In a pilot study of a closed-loop delivery system customized for pregnancies complicated by type 1 diabetes, 10 pregnant women were recruited at 14-32 weeks and, after a 1- to 2-week run-in period using a regular CGM-augmented pump, they used the closed-loop system targeting a daytime glucose of 80-110 mg/dL and nocturnal glucose of 80-100 mg/dL.
Mean TIR (a target range of 63-140 mg/dL) increased from 65% during the run-in period to 79% on the closed-loop system, and there were significant decreases in both time above range and time in the hypoglycemic ranges of < 63 mg/dL and < 54 mg/dL. Hypoglycemic events per week (defined as < 54 mg/dL for over 15 minutes) decreased from 4 to 0.7 (Diabetes Care. 2023;46:1425-31).
The investigators are continuing their research, and there are currently two randomized controlled trials underway examining use of closed-loop systems designed for pregnancy, said Dr. Rosenn, who was involved in feasibility research leading up to the pilot study. “So I’m hopeful we’ll see some encouraging information in the future.”
Maternal hypoglycemia during pregnancy is more common in type 1 diabetes, but it also affects pregnancies complicated by type 2 diabetes and GDM. In addition to the strict glycemic control imposed to improve maternal and fetal outcomes, pregnancy itself plays a role.
Research several decades ago from the Diabetes in Pregnancy Program Project, a prospective cohort in Cincinnati which Dr. Rosenn co-led, documented impaired counterregulatory physiology in pregnancy. Even in nondiabetic patients, there are declines in secretion of glucagon and growth hormone in response to hypoglycemia, for instance. In patients with type 1 diabetes, the diminishment in counterregulatory response is more severe.
Rethinking Intrapartum Care
Guidance for tight blood glucose control during labor and delivery for insulin-treated individuals — as reflected in the American College of Obstetricians and Gynecologists Practice Bulletin No. 201 on Pregestational Diabetes and in recommendations from the United Kingdom’s National Institute for Health and Care Excellence (NICE) — is based on small case series and overall “poor-quality” evidence that more recent research has failed to back up, Dr. Bartal said.
A systematic review published in 2018, for example, concluded there is a paucity of high-quality data supporting the association of glucose during labor and delivery with neonatal hypoglycemia in pregnancies complicated by diabetes (Diabet Med. 2018;35:173-83). And in a subsequent retrospective cohort study of pregnant women with type 1/type 2/GDM and their neonates, the same investigators reported no difference in the target glucose in labor between those with and without neonatal hypotension, after adjustment for important neonatal factors such as LGA and preterm delivery (Diabet Med. 2020;37:138-46).
Also exemplifying the body of research, Dr. Bartal said, is another single-center retrospective study published in 2020 that evaluated outcomes in the years before and after the institution of a formal intrapartum insulin regimen (a standardized protocol for titration of insulin and glucose infusions) for women with pregestational or gestational diabetes. The protocol was associated with improved maternal glucose control, but an increased frequency of neonatal hypoglycemia (Obstet Gynecol. 2020;136:411-6).
Her own group at the University of Texas in Houston looked retrospectively at 233 insulin-treated pregnancies complicated by type 2 diabetes and found no significant difference in the rate of neonatal hypoglycemia between those placed on a drip and those who were not, Dr. Bartal said. Over 40% of the newborns had hypoglycemia; it occurred irrespective of the route of delivery as well (J Matern Fetal Neonatal Med. 2022;35:7445-51).
Only two published randomized controlled trials have evaluated blood sugar control in labor, she said. The first, published in 2006, compared a continuous insulin drip with a rotation of glucose and non–glucose-containing fluids in insulin-requiring diabetes and found no differences in maternal blood glucose (the primary outcome) and a similar risk of neonatal hypoglycemia (Am J Obstet Gynecol. 2006;195;1095-9).
The second RCT, published in 2019, evaluated tight versus liberalized control (60-100 mg/dL, checking every hour, versus 60-120 mg/dL, checking every 4 hours) in laboring women with GDM. The first neonatal blood glucose level was similar in both groups, while the mean neonatal blood glucose level in the first 24 hours of life was lower with tight control (54 vs 58 mg/dL, P = .49) (Obstet Gynecol. 2019;133:1171-7). Findings from a new RCT conducted at the University of Texas in Houston of usual care versus more permissive glucose control will be presented at the SMFM Pregnancy Meeting in February 2024, she said.
Neonatal hypoglycemia is associated with increased risk of NICU admission, “but it’s also associated with possible long-term developmental deficit,” Dr. Bartal said, with the risk highest in children exposed to severe, recurrent, or clinically undetected hypoglycemia. Research has documented significantly increased risks of low executive function and visual motor function, for instance, in children who experienced neonatal hypoglycemia.
The risk of neonatal hypoglycemia has been linked to a variety of factors outside of the intrapartum period such as diabetes control and weight gain during pregnancy, neonatal birth weight/LGA, neonatal adiposity, gestational age at delivery, maternal body mass index, smoking, and diabetes control prior to pregnancy, Dr. Bartal noted. Also challenging is the reality that neonatal hypoglycemia as a research outcome is not standardized; definitions have varied across studies.
Tight intrapartum control comes with “costs,” from close monitoring of labor to increased resource utilization, and it may affect the labor experience/satisfaction, Dr. Bartal said. “But furthermore,” she said, “there are studies coming out, especially in the anesthesiology journals, that show there may be possible harm,” such as the risk of maternal and neonatal hyponatremia, and maternal hypoglycemia. A 2016 editorial in Anaesthesia (2016;71:750) describes these concerns, she noted.
“I do think we need to rethink our current recommendations,” she said.
Dr. Durnwald reported serving on the Dexcom GDM advisory board and receiving funding from United Health Group and the Helmsley Charitable Trust. Dr. Bartal and Dr. Rosenn reported no conflicts of interest.
WASHINGTON — Continuous glucose monitoring (CGM) is widely used during pregnancy for individuals with type 1 diabetes — with pregnancy-specific target metrics now chosen and benefits on perinatal outcomes demonstrated — but more research is needed to elucidate its role in the growing population of pregnant people with type 2 diabetes and gestational diabetes (GDM). And overall, there are still “many more questions unanswered about CGM use in pregnancy than what we have answered,” Celeste Durnwald, MD, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.
There’s much to learn about how to best interpret “the detailed and complex data that CGM provides,” and what targets in addition to time in range (TIR) are most important, said Dr. Durnwald, director of the perinatal diabetes program and associate professor of ob.gyn. at the Hospital of the University of Pennsylvania, Philadelphia, in a presentation on CGM.
Among other questions are whether fasting glucose is “as important in the era of CGM,” and whether there should be different glycemic targets for nocturnal versus daytime TIR, she said. Moreover, questions justifiably remain about whether the TIR targets for type 1 diabetes in pregnancy are indeed optimal, she said in a discussion period.
Ongoing research is looking at whether CGM can motivate and guide patients with GDM through diet and lifestyle changes such that “we can see changes in amounts of medication we use,” Dr. Durnwald noted in her presentation. “There’s a whole breadth of research looking at whether CGM can help predict diagnosis of GDM, large for gestational age, or preeclampsia, and what are the targets.”
Maternal hypoglycemia during pregnancy — a time when strict glycemic control is recommended to reduce the risk of congenital malformations and other fetal and neonatal morbidity — remains a concern in type 1 diabetes, even with widespread use of CGM in this population, said Barak Rosenn, MD, during a presentation on glycemic control in type 1 diabetes.
A pilot study of a newly designed pregnancy-specific closed-loop insulin delivery system, published last year (Diabetes Care. 2023;46:1425-31), has offered the first “really encouraging information about the ability to use our most up-to-date technology to help our type 1 patients maintain strict control and at the same time decrease their risk of severe hypoglycemia,” said Dr. Rosenn, a maternal-fetal medicine specialist at the Jersey City Medical Center, Jersey City, New Jersey.
Guidance for tight intrapartum glucose control, meanwhile, has been backed by little evidence, said Michal Fishel Bartal, MD, MS, and some recent studies and reviews have shown little to no effect of such tight control on neonatal hypoglycemia, which is the aim of the guidance.
“We need to reexamine current recommendations,” said Dr. Bartal, assistant professor in the division of maternal-fetal medicine at the University of Texas Health Science Center, Houston, during a presentation on intrapartum care. “There’s very limited evidence-based data for the way we manage people with diabetes [during labor and delivery].”
The Knowns And Unknowns of CGM in Pregnancy
The multicenter, international CONCEPTT trial (Continuous Glucose Monitoring in Pregnant Women With Type 1 Diabetes), published in 2017, was the first trial to demonstrate improvements in perinatal outcomes, and it “brought CGM to the forefront in terms of widespread use,” Dr. Durnwald said.
The trial randomized more than 300 patients with type 1 diabetes who were pregnant or planning pregnancy (both users of insulin pumps and users of multiple insulin injections) to continuous, real-time CGM in addition to finger-stick glucose monitoring, or standard finger-stick glucose tests alone. In addition to small improvements in A1c and 7% more TIR (without an increase in hypoglycemia), pregnant CGM users had reductions in large-for-gestational age (LGA) births (53% vs 69%, P = .0489), neonatal intensive care admissions lasting more than 24 hours, and severe neonatal hypoglycemia.
Numbers needed to treat to prevent adverse outcomes in the CONCEPTT trial were six for LGA, six for NICU admission, and eight for neonatal hypoglycemia.
Data from the CONCEPTT trial featured prominently in the development of consensus recommendations for CGM targets in pregnancy by an international expert panel endorsed by the American Diabetes Association. In its 2019 report, the group recommended a target range of 63-140 mg/dL for type 1 and type 2 diabetes during pregnancy (compared with 70-180 mg/dL outside of pregnancy), and a TIR > 70% for pregnant people with type 1 diabetes. (Targets for time below range and time above range are also defined for type 1.)
More data are needed, the group said, in order to recommend TIR targets for type 2 diabetes in pregnancy or GDM (Diabetes Care. 2019;42:1593-603). “Many argue,” Dr. Durnwald said, “that there could be more stringent targets for those at less risk for [maternal] hypoglycemia, especially our GDM population.”
There’s a question of whether even higher TIR would further improve perinatal outcomes, she said, “or will we reach a threshold where higher TIR doesn’t get us a [further] reduction in LGA or preeclampsia.”
And while TIR is “certainly our buzzword,” lower mean glucose levels have also been associated with a lower risk of LGA and other adverse neonatal outcomes. A 2019 retrospective study from Sweden, for instance, analyzed patterns of CGM data from 186 pregnant women with type 1 diabetes and found significant associations between elevated mean glucose levels (in the second and third trimesters) and both LGA and an adverse neonatal composite outcome (Diabetologia. 2019;62:1143-53).
Elevated TIR was also associated with LGA, but “mean glucose had the strongest association with the rate of LGA,” Dr. Durnwald said.
Similarly, a 2020 subanalysis of the CONCEPTT trial data found that a higher mean glucose at both 24 and 34 weeks of gestation was significantly associated with a greater risk of LGA (Diabetes Care. 2020;43:1178-84), and a smaller 2015 analysis of data from two randomized controlled trials of CGM in pregnant women with type 1 and type 2 diabetes found this association in trimesters 2 and 3 (Diabetes Care. 2015;38;1319-25).
The ADA’s Standards of Care in Diabetes (Diabetes Care. 2024;47:S282-S294) endorse CGM as an adjunctive tool in pregnancy — not as a replacement for all traditional blood glucose monitoring — and advise that the use of CGM-reported mean glucose is superior to the use of estimated A1c, glucose management indicator, and other calculations to estimate A1c. Changes occur in pregnancy, Dr. Durnwald pointed out. “Most experts will identify a [target] mean glucose < 120 mg/dL in those with type 1, but there’s potential to have a mean glucose closer to 100 in certainly our patients with GDM and some of our patients with type 2,” she said. To a lesser extent, researchers have also looked at the effect of CMG-reported glycemic variability on outcomes such as LGA, with at least two studies finding some association, and there has been some research on nocturnal glucose and LGA, Dr. Durnwald said. CGM “gives us the opportunity,” she said, “to think about nocturnal glucose as a possible target” for further optimizing diabetes management during pregnancy.
CGM in Type 2, GDM
CGM in type 2 diabetes in pregnancy was addressed in a recently published systematic review and meta-analysis, which found only three qualifying randomized controlled trials and concluded that CGM use was not associated with improvements in perinatal outcomes, as assessed by LGA and preeclampsia (Am J Obstet Gynecol MFM. 2023;5:100969). “It’s very limited by the small sample size and the fact that most [patients] were using intermittent CGM,” Dr. Durnwald said. “It highlights how important it is to perform larger studies with continuous CGM.”
While the 2024 ADA standards say there are insufficient data to support the use of CGM in all patients with type 2 diabetes or GDM — and that the decision should be individualized “based on treatment regimen, circumstance, preferences, and needs” — real-world access to CGM for type 2, and even a bit for GDM, is improving, she said.
Some insurers require patients to be on insulin, but the trends are such that “we certainly talk about CGM to all our patients with type 2 diabetes and even our patients with GDM,” Dr. Durnwald said in a later interview. “CGMs are being advertised so we definitely have people who ask about them upon diagnosis, and we try to make it work for them.”
Is Preventing Maternal Hypoglycemia Possible?
Advancements in technology and pharmacology aimed at optimizing glycemic control — increased adoption of CGM, the use of insulin pump therapy, and the use of more rapid insulin analogs — appear to have had little to no impact on rates of severe maternal hypoglycemia in type 1 diabetes in pregnancy, said Dr. Rosenn, referring to several published studies.
The CONCEPTT study in type 1 diabetes, for instance, “gave us the best data we have on the use of CGM,” but differences in the percentage of patients with severe hypoglycemia and the total number of severe hypoglycemia episodes were basically the same whether patients used CGM or not, he said.
Closed-loop insulin delivery systems have been found in nonpregnant patients with type 1 diabetes to “be helpful in keeping people in range and also possibly [decreasing nocturnal hypoglycemia],” but the systems are not approved for use in pregnancy. “There’s not enough data on use in pregnancy, but probably more important, the algorithms used in the closed-loop systems are not directed to the targets we consider ideal for pregnancy,” Dr. Rosenn said.
In a pilot study of a closed-loop delivery system customized for pregnancies complicated by type 1 diabetes, 10 pregnant women were recruited at 14-32 weeks and, after a 1- to 2-week run-in period using a regular CGM-augmented pump, they used the closed-loop system targeting a daytime glucose of 80-110 mg/dL and nocturnal glucose of 80-100 mg/dL.
Mean TIR (a target range of 63-140 mg/dL) increased from 65% during the run-in period to 79% on the closed-loop system, and there were significant decreases in both time above range and time in the hypoglycemic ranges of < 63 mg/dL and < 54 mg/dL. Hypoglycemic events per week (defined as < 54 mg/dL for over 15 minutes) decreased from 4 to 0.7 (Diabetes Care. 2023;46:1425-31).
The investigators are continuing their research, and there are currently two randomized controlled trials underway examining use of closed-loop systems designed for pregnancy, said Dr. Rosenn, who was involved in feasibility research leading up to the pilot study. “So I’m hopeful we’ll see some encouraging information in the future.”
Maternal hypoglycemia during pregnancy is more common in type 1 diabetes, but it also affects pregnancies complicated by type 2 diabetes and GDM. In addition to the strict glycemic control imposed to improve maternal and fetal outcomes, pregnancy itself plays a role.
Research several decades ago from the Diabetes in Pregnancy Program Project, a prospective cohort in Cincinnati which Dr. Rosenn co-led, documented impaired counterregulatory physiology in pregnancy. Even in nondiabetic patients, there are declines in secretion of glucagon and growth hormone in response to hypoglycemia, for instance. In patients with type 1 diabetes, the diminishment in counterregulatory response is more severe.
Rethinking Intrapartum Care
Guidance for tight blood glucose control during labor and delivery for insulin-treated individuals — as reflected in the American College of Obstetricians and Gynecologists Practice Bulletin No. 201 on Pregestational Diabetes and in recommendations from the United Kingdom’s National Institute for Health and Care Excellence (NICE) — is based on small case series and overall “poor-quality” evidence that more recent research has failed to back up, Dr. Bartal said.
A systematic review published in 2018, for example, concluded there is a paucity of high-quality data supporting the association of glucose during labor and delivery with neonatal hypoglycemia in pregnancies complicated by diabetes (Diabet Med. 2018;35:173-83). And in a subsequent retrospective cohort study of pregnant women with type 1/type 2/GDM and their neonates, the same investigators reported no difference in the target glucose in labor between those with and without neonatal hypotension, after adjustment for important neonatal factors such as LGA and preterm delivery (Diabet Med. 2020;37:138-46).
Also exemplifying the body of research, Dr. Bartal said, is another single-center retrospective study published in 2020 that evaluated outcomes in the years before and after the institution of a formal intrapartum insulin regimen (a standardized protocol for titration of insulin and glucose infusions) for women with pregestational or gestational diabetes. The protocol was associated with improved maternal glucose control, but an increased frequency of neonatal hypoglycemia (Obstet Gynecol. 2020;136:411-6).
Her own group at the University of Texas in Houston looked retrospectively at 233 insulin-treated pregnancies complicated by type 2 diabetes and found no significant difference in the rate of neonatal hypoglycemia between those placed on a drip and those who were not, Dr. Bartal said. Over 40% of the newborns had hypoglycemia; it occurred irrespective of the route of delivery as well (J Matern Fetal Neonatal Med. 2022;35:7445-51).
Only two published randomized controlled trials have evaluated blood sugar control in labor, she said. The first, published in 2006, compared a continuous insulin drip with a rotation of glucose and non–glucose-containing fluids in insulin-requiring diabetes and found no differences in maternal blood glucose (the primary outcome) and a similar risk of neonatal hypoglycemia (Am J Obstet Gynecol. 2006;195;1095-9).
The second RCT, published in 2019, evaluated tight versus liberalized control (60-100 mg/dL, checking every hour, versus 60-120 mg/dL, checking every 4 hours) in laboring women with GDM. The first neonatal blood glucose level was similar in both groups, while the mean neonatal blood glucose level in the first 24 hours of life was lower with tight control (54 vs 58 mg/dL, P = .49) (Obstet Gynecol. 2019;133:1171-7). Findings from a new RCT conducted at the University of Texas in Houston of usual care versus more permissive glucose control will be presented at the SMFM Pregnancy Meeting in February 2024, she said.
Neonatal hypoglycemia is associated with increased risk of NICU admission, “but it’s also associated with possible long-term developmental deficit,” Dr. Bartal said, with the risk highest in children exposed to severe, recurrent, or clinically undetected hypoglycemia. Research has documented significantly increased risks of low executive function and visual motor function, for instance, in children who experienced neonatal hypoglycemia.
The risk of neonatal hypoglycemia has been linked to a variety of factors outside of the intrapartum period such as diabetes control and weight gain during pregnancy, neonatal birth weight/LGA, neonatal adiposity, gestational age at delivery, maternal body mass index, smoking, and diabetes control prior to pregnancy, Dr. Bartal noted. Also challenging is the reality that neonatal hypoglycemia as a research outcome is not standardized; definitions have varied across studies.
Tight intrapartum control comes with “costs,” from close monitoring of labor to increased resource utilization, and it may affect the labor experience/satisfaction, Dr. Bartal said. “But furthermore,” she said, “there are studies coming out, especially in the anesthesiology journals, that show there may be possible harm,” such as the risk of maternal and neonatal hyponatremia, and maternal hypoglycemia. A 2016 editorial in Anaesthesia (2016;71:750) describes these concerns, she noted.
“I do think we need to rethink our current recommendations,” she said.
Dr. Durnwald reported serving on the Dexcom GDM advisory board and receiving funding from United Health Group and the Helmsley Charitable Trust. Dr. Bartal and Dr. Rosenn reported no conflicts of interest.
WASHINGTON — Continuous glucose monitoring (CGM) is widely used during pregnancy for individuals with type 1 diabetes — with pregnancy-specific target metrics now chosen and benefits on perinatal outcomes demonstrated — but more research is needed to elucidate its role in the growing population of pregnant people with type 2 diabetes and gestational diabetes (GDM). And overall, there are still “many more questions unanswered about CGM use in pregnancy than what we have answered,” Celeste Durnwald, MD, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.
There’s much to learn about how to best interpret “the detailed and complex data that CGM provides,” and what targets in addition to time in range (TIR) are most important, said Dr. Durnwald, director of the perinatal diabetes program and associate professor of ob.gyn. at the Hospital of the University of Pennsylvania, Philadelphia, in a presentation on CGM.
Among other questions are whether fasting glucose is “as important in the era of CGM,” and whether there should be different glycemic targets for nocturnal versus daytime TIR, she said. Moreover, questions justifiably remain about whether the TIR targets for type 1 diabetes in pregnancy are indeed optimal, she said in a discussion period.
Ongoing research is looking at whether CGM can motivate and guide patients with GDM through diet and lifestyle changes such that “we can see changes in amounts of medication we use,” Dr. Durnwald noted in her presentation. “There’s a whole breadth of research looking at whether CGM can help predict diagnosis of GDM, large for gestational age, or preeclampsia, and what are the targets.”
Maternal hypoglycemia during pregnancy — a time when strict glycemic control is recommended to reduce the risk of congenital malformations and other fetal and neonatal morbidity — remains a concern in type 1 diabetes, even with widespread use of CGM in this population, said Barak Rosenn, MD, during a presentation on glycemic control in type 1 diabetes.
A pilot study of a newly designed pregnancy-specific closed-loop insulin delivery system, published last year (Diabetes Care. 2023;46:1425-31), has offered the first “really encouraging information about the ability to use our most up-to-date technology to help our type 1 patients maintain strict control and at the same time decrease their risk of severe hypoglycemia,” said Dr. Rosenn, a maternal-fetal medicine specialist at the Jersey City Medical Center, Jersey City, New Jersey.
Guidance for tight intrapartum glucose control, meanwhile, has been backed by little evidence, said Michal Fishel Bartal, MD, MS, and some recent studies and reviews have shown little to no effect of such tight control on neonatal hypoglycemia, which is the aim of the guidance.
“We need to reexamine current recommendations,” said Dr. Bartal, assistant professor in the division of maternal-fetal medicine at the University of Texas Health Science Center, Houston, during a presentation on intrapartum care. “There’s very limited evidence-based data for the way we manage people with diabetes [during labor and delivery].”
The Knowns And Unknowns of CGM in Pregnancy
The multicenter, international CONCEPTT trial (Continuous Glucose Monitoring in Pregnant Women With Type 1 Diabetes), published in 2017, was the first trial to demonstrate improvements in perinatal outcomes, and it “brought CGM to the forefront in terms of widespread use,” Dr. Durnwald said.
The trial randomized more than 300 patients with type 1 diabetes who were pregnant or planning pregnancy (both users of insulin pumps and users of multiple insulin injections) to continuous, real-time CGM in addition to finger-stick glucose monitoring, or standard finger-stick glucose tests alone. In addition to small improvements in A1c and 7% more TIR (without an increase in hypoglycemia), pregnant CGM users had reductions in large-for-gestational age (LGA) births (53% vs 69%, P = .0489), neonatal intensive care admissions lasting more than 24 hours, and severe neonatal hypoglycemia.
Numbers needed to treat to prevent adverse outcomes in the CONCEPTT trial were six for LGA, six for NICU admission, and eight for neonatal hypoglycemia.
Data from the CONCEPTT trial featured prominently in the development of consensus recommendations for CGM targets in pregnancy by an international expert panel endorsed by the American Diabetes Association. In its 2019 report, the group recommended a target range of 63-140 mg/dL for type 1 and type 2 diabetes during pregnancy (compared with 70-180 mg/dL outside of pregnancy), and a TIR > 70% for pregnant people with type 1 diabetes. (Targets for time below range and time above range are also defined for type 1.)
More data are needed, the group said, in order to recommend TIR targets for type 2 diabetes in pregnancy or GDM (Diabetes Care. 2019;42:1593-603). “Many argue,” Dr. Durnwald said, “that there could be more stringent targets for those at less risk for [maternal] hypoglycemia, especially our GDM population.”
There’s a question of whether even higher TIR would further improve perinatal outcomes, she said, “or will we reach a threshold where higher TIR doesn’t get us a [further] reduction in LGA or preeclampsia.”
And while TIR is “certainly our buzzword,” lower mean glucose levels have also been associated with a lower risk of LGA and other adverse neonatal outcomes. A 2019 retrospective study from Sweden, for instance, analyzed patterns of CGM data from 186 pregnant women with type 1 diabetes and found significant associations between elevated mean glucose levels (in the second and third trimesters) and both LGA and an adverse neonatal composite outcome (Diabetologia. 2019;62:1143-53).
Elevated TIR was also associated with LGA, but “mean glucose had the strongest association with the rate of LGA,” Dr. Durnwald said.
Similarly, a 2020 subanalysis of the CONCEPTT trial data found that a higher mean glucose at both 24 and 34 weeks of gestation was significantly associated with a greater risk of LGA (Diabetes Care. 2020;43:1178-84), and a smaller 2015 analysis of data from two randomized controlled trials of CGM in pregnant women with type 1 and type 2 diabetes found this association in trimesters 2 and 3 (Diabetes Care. 2015;38;1319-25).
The ADA’s Standards of Care in Diabetes (Diabetes Care. 2024;47:S282-S294) endorse CGM as an adjunctive tool in pregnancy — not as a replacement for all traditional blood glucose monitoring — and advise that the use of CGM-reported mean glucose is superior to the use of estimated A1c, glucose management indicator, and other calculations to estimate A1c. Changes occur in pregnancy, Dr. Durnwald pointed out. “Most experts will identify a [target] mean glucose < 120 mg/dL in those with type 1, but there’s potential to have a mean glucose closer to 100 in certainly our patients with GDM and some of our patients with type 2,” she said. To a lesser extent, researchers have also looked at the effect of CMG-reported glycemic variability on outcomes such as LGA, with at least two studies finding some association, and there has been some research on nocturnal glucose and LGA, Dr. Durnwald said. CGM “gives us the opportunity,” she said, “to think about nocturnal glucose as a possible target” for further optimizing diabetes management during pregnancy.
CGM in Type 2, GDM
CGM in type 2 diabetes in pregnancy was addressed in a recently published systematic review and meta-analysis, which found only three qualifying randomized controlled trials and concluded that CGM use was not associated with improvements in perinatal outcomes, as assessed by LGA and preeclampsia (Am J Obstet Gynecol MFM. 2023;5:100969). “It’s very limited by the small sample size and the fact that most [patients] were using intermittent CGM,” Dr. Durnwald said. “It highlights how important it is to perform larger studies with continuous CGM.”
While the 2024 ADA standards say there are insufficient data to support the use of CGM in all patients with type 2 diabetes or GDM — and that the decision should be individualized “based on treatment regimen, circumstance, preferences, and needs” — real-world access to CGM for type 2, and even a bit for GDM, is improving, she said.
Some insurers require patients to be on insulin, but the trends are such that “we certainly talk about CGM to all our patients with type 2 diabetes and even our patients with GDM,” Dr. Durnwald said in a later interview. “CGMs are being advertised so we definitely have people who ask about them upon diagnosis, and we try to make it work for them.”
Is Preventing Maternal Hypoglycemia Possible?
Advancements in technology and pharmacology aimed at optimizing glycemic control — increased adoption of CGM, the use of insulin pump therapy, and the use of more rapid insulin analogs — appear to have had little to no impact on rates of severe maternal hypoglycemia in type 1 diabetes in pregnancy, said Dr. Rosenn, referring to several published studies.
The CONCEPTT study in type 1 diabetes, for instance, “gave us the best data we have on the use of CGM,” but differences in the percentage of patients with severe hypoglycemia and the total number of severe hypoglycemia episodes were basically the same whether patients used CGM or not, he said.
Closed-loop insulin delivery systems have been found in nonpregnant patients with type 1 diabetes to “be helpful in keeping people in range and also possibly [decreasing nocturnal hypoglycemia],” but the systems are not approved for use in pregnancy. “There’s not enough data on use in pregnancy, but probably more important, the algorithms used in the closed-loop systems are not directed to the targets we consider ideal for pregnancy,” Dr. Rosenn said.
In a pilot study of a closed-loop delivery system customized for pregnancies complicated by type 1 diabetes, 10 pregnant women were recruited at 14-32 weeks and, after a 1- to 2-week run-in period using a regular CGM-augmented pump, they used the closed-loop system targeting a daytime glucose of 80-110 mg/dL and nocturnal glucose of 80-100 mg/dL.
Mean TIR (a target range of 63-140 mg/dL) increased from 65% during the run-in period to 79% on the closed-loop system, and there were significant decreases in both time above range and time in the hypoglycemic ranges of < 63 mg/dL and < 54 mg/dL. Hypoglycemic events per week (defined as < 54 mg/dL for over 15 minutes) decreased from 4 to 0.7 (Diabetes Care. 2023;46:1425-31).
The investigators are continuing their research, and there are currently two randomized controlled trials underway examining use of closed-loop systems designed for pregnancy, said Dr. Rosenn, who was involved in feasibility research leading up to the pilot study. “So I’m hopeful we’ll see some encouraging information in the future.”
Maternal hypoglycemia during pregnancy is more common in type 1 diabetes, but it also affects pregnancies complicated by type 2 diabetes and GDM. In addition to the strict glycemic control imposed to improve maternal and fetal outcomes, pregnancy itself plays a role.
Research several decades ago from the Diabetes in Pregnancy Program Project, a prospective cohort in Cincinnati which Dr. Rosenn co-led, documented impaired counterregulatory physiology in pregnancy. Even in nondiabetic patients, there are declines in secretion of glucagon and growth hormone in response to hypoglycemia, for instance. In patients with type 1 diabetes, the diminishment in counterregulatory response is more severe.
Rethinking Intrapartum Care
Guidance for tight blood glucose control during labor and delivery for insulin-treated individuals — as reflected in the American College of Obstetricians and Gynecologists Practice Bulletin No. 201 on Pregestational Diabetes and in recommendations from the United Kingdom’s National Institute for Health and Care Excellence (NICE) — is based on small case series and overall “poor-quality” evidence that more recent research has failed to back up, Dr. Bartal said.
A systematic review published in 2018, for example, concluded there is a paucity of high-quality data supporting the association of glucose during labor and delivery with neonatal hypoglycemia in pregnancies complicated by diabetes (Diabet Med. 2018;35:173-83). And in a subsequent retrospective cohort study of pregnant women with type 1/type 2/GDM and their neonates, the same investigators reported no difference in the target glucose in labor between those with and without neonatal hypotension, after adjustment for important neonatal factors such as LGA and preterm delivery (Diabet Med. 2020;37:138-46).
Also exemplifying the body of research, Dr. Bartal said, is another single-center retrospective study published in 2020 that evaluated outcomes in the years before and after the institution of a formal intrapartum insulin regimen (a standardized protocol for titration of insulin and glucose infusions) for women with pregestational or gestational diabetes. The protocol was associated with improved maternal glucose control, but an increased frequency of neonatal hypoglycemia (Obstet Gynecol. 2020;136:411-6).
Her own group at the University of Texas in Houston looked retrospectively at 233 insulin-treated pregnancies complicated by type 2 diabetes and found no significant difference in the rate of neonatal hypoglycemia between those placed on a drip and those who were not, Dr. Bartal said. Over 40% of the newborns had hypoglycemia; it occurred irrespective of the route of delivery as well (J Matern Fetal Neonatal Med. 2022;35:7445-51).
Only two published randomized controlled trials have evaluated blood sugar control in labor, she said. The first, published in 2006, compared a continuous insulin drip with a rotation of glucose and non–glucose-containing fluids in insulin-requiring diabetes and found no differences in maternal blood glucose (the primary outcome) and a similar risk of neonatal hypoglycemia (Am J Obstet Gynecol. 2006;195;1095-9).
The second RCT, published in 2019, evaluated tight versus liberalized control (60-100 mg/dL, checking every hour, versus 60-120 mg/dL, checking every 4 hours) in laboring women with GDM. The first neonatal blood glucose level was similar in both groups, while the mean neonatal blood glucose level in the first 24 hours of life was lower with tight control (54 vs 58 mg/dL, P = .49) (Obstet Gynecol. 2019;133:1171-7). Findings from a new RCT conducted at the University of Texas in Houston of usual care versus more permissive glucose control will be presented at the SMFM Pregnancy Meeting in February 2024, she said.
Neonatal hypoglycemia is associated with increased risk of NICU admission, “but it’s also associated with possible long-term developmental deficit,” Dr. Bartal said, with the risk highest in children exposed to severe, recurrent, or clinically undetected hypoglycemia. Research has documented significantly increased risks of low executive function and visual motor function, for instance, in children who experienced neonatal hypoglycemia.
The risk of neonatal hypoglycemia has been linked to a variety of factors outside of the intrapartum period such as diabetes control and weight gain during pregnancy, neonatal birth weight/LGA, neonatal adiposity, gestational age at delivery, maternal body mass index, smoking, and diabetes control prior to pregnancy, Dr. Bartal noted. Also challenging is the reality that neonatal hypoglycemia as a research outcome is not standardized; definitions have varied across studies.
Tight intrapartum control comes with “costs,” from close monitoring of labor to increased resource utilization, and it may affect the labor experience/satisfaction, Dr. Bartal said. “But furthermore,” she said, “there are studies coming out, especially in the anesthesiology journals, that show there may be possible harm,” such as the risk of maternal and neonatal hyponatremia, and maternal hypoglycemia. A 2016 editorial in Anaesthesia (2016;71:750) describes these concerns, she noted.
“I do think we need to rethink our current recommendations,” she said.
Dr. Durnwald reported serving on the Dexcom GDM advisory board and receiving funding from United Health Group and the Helmsley Charitable Trust. Dr. Bartal and Dr. Rosenn reported no conflicts of interest.
FROM DPSG-NA 2024