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Educational Tool Reduces Unnecessary Inhaler Use in ILD
Use of an electronic tool contributed to the deprescribing of unnecessary inhalers in patients with interstitial lung disease (ILD), based on data from nearly 200 individuals.
Patients with ILD often have symptoms that overlap with those of obstructive airways diseases, Stephanie Nevison, MD, of the University of Toronto, and colleagues wrote in a study presented at the American Thoracic Society’s international conference.
, they noted.
“Our aim was twofold: To quantify the extent of inappropriate inhaler use in patients with ILD and to discontinue them where appropriate,” the researchers wrote.
“We hypothesized that inappropriate inhaler use in ILD is common and that an electronic initiative would improve deprescribing rates,” they said.
The researchers conducted a quality improvement project in an ILD clinic at a single center. They reviewed 5 months of baseline data for 191 patients with ILD to assess baseline frequency of inappropriate inhaler use, defined as one or more of the following criteria: Reported asthma history, smoking history of > 15 pack/years, emphysema on chest CT, patient-reported benefits from therapy, airflow obstruction, or bronchodilator response on spirometry.
A total of 48 patients (25.1%) were on inhalers, and 15 (7.8%) had no indication for them (9% of new referrals and 7% of follow-up patients). The most-prescribed inhalers for patients with no indication were corticosteroids (10 patients), short-acting beta-agonists (8 patients), and long-acting beta-agonists (7 patients).
None of the patients on inhalers received counseling about discontinuing their use. The results of the baseline assessment were shared with clinicians along with education about reducing unnecessary inhaler use in the form of a prompt linked to electronic medical records to discuss deprescription of unnecessary inhalers.
The electronic intervention was applied in 400 of 518 patient encounters, and the researchers reviewed data over another 5-month period. A total of 99 patients were on inhalers, and 3.3% had no indication (5.3% of new referrals and 3.0% of follow-up patients). In the wake of the intervention, “all patients on unnecessary inhalers were counseled on deprescribing, representing a significant increase compared to the preintervention period,” the researchers wrote.
Intervention Shows Potential to Curb Unnecessary Inhaler Use
More research is needed as the findings were limited by the relatively small sample size and use of data from a single center, the researchers noted.
However, the results suggest that electronic reminders are effective for prompting a review of inhaler use, and deprescribing inappropriate inhalers for patients with ILD could reduce the potential for adverse events associated with their use, they concluded.
The current study is important because some patients with ILD may not benefit from inhaler use, David Mannino, MD, of the University of Kentucky, Lexington, said in an interview. In the study, “I was a bit surprised that only 3.3% of patients had no indication for them; this seems rather low,” said Dr. Mannino, who was not involved in the study.
Use of an electronic system that evaluates patients and flags inappropriate therapy is an effective way to decrease overprescribing of medications, Dr. Mannino told this news organization.
As for additional research, application of the tool used in this study to other pulmonary populations could be interesting and potentially useful, he said.
The study received no outside funding. The researchers and Dr. Mannino had no financial conflicts to disclose.
A version of this article appeared on Medscape.com.
Use of an electronic tool contributed to the deprescribing of unnecessary inhalers in patients with interstitial lung disease (ILD), based on data from nearly 200 individuals.
Patients with ILD often have symptoms that overlap with those of obstructive airways diseases, Stephanie Nevison, MD, of the University of Toronto, and colleagues wrote in a study presented at the American Thoracic Society’s international conference.
, they noted.
“Our aim was twofold: To quantify the extent of inappropriate inhaler use in patients with ILD and to discontinue them where appropriate,” the researchers wrote.
“We hypothesized that inappropriate inhaler use in ILD is common and that an electronic initiative would improve deprescribing rates,” they said.
The researchers conducted a quality improvement project in an ILD clinic at a single center. They reviewed 5 months of baseline data for 191 patients with ILD to assess baseline frequency of inappropriate inhaler use, defined as one or more of the following criteria: Reported asthma history, smoking history of > 15 pack/years, emphysema on chest CT, patient-reported benefits from therapy, airflow obstruction, or bronchodilator response on spirometry.
A total of 48 patients (25.1%) were on inhalers, and 15 (7.8%) had no indication for them (9% of new referrals and 7% of follow-up patients). The most-prescribed inhalers for patients with no indication were corticosteroids (10 patients), short-acting beta-agonists (8 patients), and long-acting beta-agonists (7 patients).
None of the patients on inhalers received counseling about discontinuing their use. The results of the baseline assessment were shared with clinicians along with education about reducing unnecessary inhaler use in the form of a prompt linked to electronic medical records to discuss deprescription of unnecessary inhalers.
The electronic intervention was applied in 400 of 518 patient encounters, and the researchers reviewed data over another 5-month period. A total of 99 patients were on inhalers, and 3.3% had no indication (5.3% of new referrals and 3.0% of follow-up patients). In the wake of the intervention, “all patients on unnecessary inhalers were counseled on deprescribing, representing a significant increase compared to the preintervention period,” the researchers wrote.
Intervention Shows Potential to Curb Unnecessary Inhaler Use
More research is needed as the findings were limited by the relatively small sample size and use of data from a single center, the researchers noted.
However, the results suggest that electronic reminders are effective for prompting a review of inhaler use, and deprescribing inappropriate inhalers for patients with ILD could reduce the potential for adverse events associated with their use, they concluded.
The current study is important because some patients with ILD may not benefit from inhaler use, David Mannino, MD, of the University of Kentucky, Lexington, said in an interview. In the study, “I was a bit surprised that only 3.3% of patients had no indication for them; this seems rather low,” said Dr. Mannino, who was not involved in the study.
Use of an electronic system that evaluates patients and flags inappropriate therapy is an effective way to decrease overprescribing of medications, Dr. Mannino told this news organization.
As for additional research, application of the tool used in this study to other pulmonary populations could be interesting and potentially useful, he said.
The study received no outside funding. The researchers and Dr. Mannino had no financial conflicts to disclose.
A version of this article appeared on Medscape.com.
Use of an electronic tool contributed to the deprescribing of unnecessary inhalers in patients with interstitial lung disease (ILD), based on data from nearly 200 individuals.
Patients with ILD often have symptoms that overlap with those of obstructive airways diseases, Stephanie Nevison, MD, of the University of Toronto, and colleagues wrote in a study presented at the American Thoracic Society’s international conference.
, they noted.
“Our aim was twofold: To quantify the extent of inappropriate inhaler use in patients with ILD and to discontinue them where appropriate,” the researchers wrote.
“We hypothesized that inappropriate inhaler use in ILD is common and that an electronic initiative would improve deprescribing rates,” they said.
The researchers conducted a quality improvement project in an ILD clinic at a single center. They reviewed 5 months of baseline data for 191 patients with ILD to assess baseline frequency of inappropriate inhaler use, defined as one or more of the following criteria: Reported asthma history, smoking history of > 15 pack/years, emphysema on chest CT, patient-reported benefits from therapy, airflow obstruction, or bronchodilator response on spirometry.
A total of 48 patients (25.1%) were on inhalers, and 15 (7.8%) had no indication for them (9% of new referrals and 7% of follow-up patients). The most-prescribed inhalers for patients with no indication were corticosteroids (10 patients), short-acting beta-agonists (8 patients), and long-acting beta-agonists (7 patients).
None of the patients on inhalers received counseling about discontinuing their use. The results of the baseline assessment were shared with clinicians along with education about reducing unnecessary inhaler use in the form of a prompt linked to electronic medical records to discuss deprescription of unnecessary inhalers.
The electronic intervention was applied in 400 of 518 patient encounters, and the researchers reviewed data over another 5-month period. A total of 99 patients were on inhalers, and 3.3% had no indication (5.3% of new referrals and 3.0% of follow-up patients). In the wake of the intervention, “all patients on unnecessary inhalers were counseled on deprescribing, representing a significant increase compared to the preintervention period,” the researchers wrote.
Intervention Shows Potential to Curb Unnecessary Inhaler Use
More research is needed as the findings were limited by the relatively small sample size and use of data from a single center, the researchers noted.
However, the results suggest that electronic reminders are effective for prompting a review of inhaler use, and deprescribing inappropriate inhalers for patients with ILD could reduce the potential for adverse events associated with their use, they concluded.
The current study is important because some patients with ILD may not benefit from inhaler use, David Mannino, MD, of the University of Kentucky, Lexington, said in an interview. In the study, “I was a bit surprised that only 3.3% of patients had no indication for them; this seems rather low,” said Dr. Mannino, who was not involved in the study.
Use of an electronic system that evaluates patients and flags inappropriate therapy is an effective way to decrease overprescribing of medications, Dr. Mannino told this news organization.
As for additional research, application of the tool used in this study to other pulmonary populations could be interesting and potentially useful, he said.
The study received no outside funding. The researchers and Dr. Mannino had no financial conflicts to disclose.
A version of this article appeared on Medscape.com.
FROM ATS 2024
Analysis Finds Minority of Chronic Wounds Treated by Dermatologists
. However, fewer than 8% of chronic wounds were managed by dermatologists during this time.
Those are among key findings from an analysis of National Ambulatory Medical Care Survey (NAMCS) data between 2011 and 2019 presented as a late-breaking abstract at the annual meeting of the Society for Investigative Dermatology. “Cutaneous wounds were estimated to account for 28.1 to 96.1 billion dollars in US health care costs in 2014,” one of the study authors, Rithi Chandy, MD, MS, a research fellow at the Center for Dermatology Research at Wake Forest University School of Medicine, Winston-Salem, North Carolina, said in an interview following the meeting. “By examining national trends in patient visits and treatment, we may be able to better inform health care utilization for cutaneous wounds.”
Dr. Chandy and colleagues analyzed de-identified patient data from the 2011 to 2019 NAMCS for acute and chronic wound diagnoses, medications prescribed, and physician specialty categories. During the time studied, 5.76 billion patient visits were made, including 45.1 million visits for cutaneous wounds. Of these, the most common diagnoses were open wounds of the thumb without nail damage (7.96%), the lower leg (5.75%), nonpressure chronic ulcers of other parts of the foot (5.08%), and open wounds of the ear (5%).
Among all visits for cutaneous wounds, about one third were chronic cutaneous wounds, with the following descriptions: “Nonpressure chronic ulcer of other part of foot” (17.8%); “nonpressure chronic ulcer of skin, not elsewhere classified” (9.38%); and “ulcer of lower limbs, excluding decubitus, unspecified” (8.72%). “The frequency of patient visits per year during the study period remained stable for both acute and chronic wounds,” Dr. Chandy said. The number of visits for which antimicrobials were used was stable over time for both acute and chronic cutaneous wounds, with the exception of increased use of antivirals for chronic cutaneous wounds, he added.
Specifically, prescriptions were issued in 156 million visits over the time studied, most commonly cephalexin (4.22%), topical silver sulfadiazine (1.59%), topical mupirocin (1.12%), and miscellaneous antibiotics (1.18%).
“Our data shows that topical mupirocin is the most commonly used topical antimicrobial for cutaneous wounds,” Dr. Chandy said. “However, there are reports of emerging bacterial resistance to mupirocin. Our data can inform ongoing efforts to promote antimicrobial stewardship and drug development to provide alternative options that are less likely to induce antimicrobial resistance.”
In findings limited to specialty-specific NAMCS data available from 2011 and from 2013 to 2016, dermatologists managed 3.85% of overall cutaneous wounds, 2.35% of acute wounds, and 7.39% of chronic wounds. By contrast, Dr. Chandy said, 21.1% of chronic wounds were managed by general/family practice physicians, 20.7% by internists, 6.84% by general surgeons, and 5.65% by orthopedic surgeons.
“As dermatologists are experts in the structure and function of the skin and are trained to manage cutaneous disorders including wound healing, we [believe that] dermatologists are equipped with the skill set” for managing wounds, especially for chronic ulcers, he said. The decline in dermatologists who specialize in wound care, he added, “underscores the need for structured dermatology fellowship programs to prepare next-generation dermatologists to address this shortage and ensure dermatology leadership in cutaneous wound healing.”
Dr. Chandy acknowledged certain limitations of the study, including the potential for misclassification of diagnoses or medications prescribed and the fact that the NAMCS database is unable to provide insight into individual patient experiences such as continual cutaneous wound management for the same patient over time.
In the opinion of Shari R. Lipner, MD, PhD, associate professor of clinical dermatology and director of the Nail Division at Weill Cornell Medicine, New York, who was asked to comment on the study, the most interesting finding was that dermatologists cared for a small minority of patients with cutaneous wounds. “It would be interesting to know whether this is due to dermatologist shortages or knowledge gaps on the part of primary care physicians or patients that dermatologists are trained to care for wounds,” Dr. Lipner told this news organization. Other unanswered questions, she noted, “are patient demographics, geographic locations, and comorbidities.”
One of the study authors, Steven R. Feldman, MD, PhD, professor of dermatology at Wake Forest University, disclosed that he has received research, speaking and/or consulting support from numerous pharmaceutical companies. No other authors reported having relevant disclosures. Dr. Lipner reported having no disclosures.
A version of this article appeared on Medscape.com .
. However, fewer than 8% of chronic wounds were managed by dermatologists during this time.
Those are among key findings from an analysis of National Ambulatory Medical Care Survey (NAMCS) data between 2011 and 2019 presented as a late-breaking abstract at the annual meeting of the Society for Investigative Dermatology. “Cutaneous wounds were estimated to account for 28.1 to 96.1 billion dollars in US health care costs in 2014,” one of the study authors, Rithi Chandy, MD, MS, a research fellow at the Center for Dermatology Research at Wake Forest University School of Medicine, Winston-Salem, North Carolina, said in an interview following the meeting. “By examining national trends in patient visits and treatment, we may be able to better inform health care utilization for cutaneous wounds.”
Dr. Chandy and colleagues analyzed de-identified patient data from the 2011 to 2019 NAMCS for acute and chronic wound diagnoses, medications prescribed, and physician specialty categories. During the time studied, 5.76 billion patient visits were made, including 45.1 million visits for cutaneous wounds. Of these, the most common diagnoses were open wounds of the thumb without nail damage (7.96%), the lower leg (5.75%), nonpressure chronic ulcers of other parts of the foot (5.08%), and open wounds of the ear (5%).
Among all visits for cutaneous wounds, about one third were chronic cutaneous wounds, with the following descriptions: “Nonpressure chronic ulcer of other part of foot” (17.8%); “nonpressure chronic ulcer of skin, not elsewhere classified” (9.38%); and “ulcer of lower limbs, excluding decubitus, unspecified” (8.72%). “The frequency of patient visits per year during the study period remained stable for both acute and chronic wounds,” Dr. Chandy said. The number of visits for which antimicrobials were used was stable over time for both acute and chronic cutaneous wounds, with the exception of increased use of antivirals for chronic cutaneous wounds, he added.
Specifically, prescriptions were issued in 156 million visits over the time studied, most commonly cephalexin (4.22%), topical silver sulfadiazine (1.59%), topical mupirocin (1.12%), and miscellaneous antibiotics (1.18%).
“Our data shows that topical mupirocin is the most commonly used topical antimicrobial for cutaneous wounds,” Dr. Chandy said. “However, there are reports of emerging bacterial resistance to mupirocin. Our data can inform ongoing efforts to promote antimicrobial stewardship and drug development to provide alternative options that are less likely to induce antimicrobial resistance.”
In findings limited to specialty-specific NAMCS data available from 2011 and from 2013 to 2016, dermatologists managed 3.85% of overall cutaneous wounds, 2.35% of acute wounds, and 7.39% of chronic wounds. By contrast, Dr. Chandy said, 21.1% of chronic wounds were managed by general/family practice physicians, 20.7% by internists, 6.84% by general surgeons, and 5.65% by orthopedic surgeons.
“As dermatologists are experts in the structure and function of the skin and are trained to manage cutaneous disorders including wound healing, we [believe that] dermatologists are equipped with the skill set” for managing wounds, especially for chronic ulcers, he said. The decline in dermatologists who specialize in wound care, he added, “underscores the need for structured dermatology fellowship programs to prepare next-generation dermatologists to address this shortage and ensure dermatology leadership in cutaneous wound healing.”
Dr. Chandy acknowledged certain limitations of the study, including the potential for misclassification of diagnoses or medications prescribed and the fact that the NAMCS database is unable to provide insight into individual patient experiences such as continual cutaneous wound management for the same patient over time.
In the opinion of Shari R. Lipner, MD, PhD, associate professor of clinical dermatology and director of the Nail Division at Weill Cornell Medicine, New York, who was asked to comment on the study, the most interesting finding was that dermatologists cared for a small minority of patients with cutaneous wounds. “It would be interesting to know whether this is due to dermatologist shortages or knowledge gaps on the part of primary care physicians or patients that dermatologists are trained to care for wounds,” Dr. Lipner told this news organization. Other unanswered questions, she noted, “are patient demographics, geographic locations, and comorbidities.”
One of the study authors, Steven R. Feldman, MD, PhD, professor of dermatology at Wake Forest University, disclosed that he has received research, speaking and/or consulting support from numerous pharmaceutical companies. No other authors reported having relevant disclosures. Dr. Lipner reported having no disclosures.
A version of this article appeared on Medscape.com .
. However, fewer than 8% of chronic wounds were managed by dermatologists during this time.
Those are among key findings from an analysis of National Ambulatory Medical Care Survey (NAMCS) data between 2011 and 2019 presented as a late-breaking abstract at the annual meeting of the Society for Investigative Dermatology. “Cutaneous wounds were estimated to account for 28.1 to 96.1 billion dollars in US health care costs in 2014,” one of the study authors, Rithi Chandy, MD, MS, a research fellow at the Center for Dermatology Research at Wake Forest University School of Medicine, Winston-Salem, North Carolina, said in an interview following the meeting. “By examining national trends in patient visits and treatment, we may be able to better inform health care utilization for cutaneous wounds.”
Dr. Chandy and colleagues analyzed de-identified patient data from the 2011 to 2019 NAMCS for acute and chronic wound diagnoses, medications prescribed, and physician specialty categories. During the time studied, 5.76 billion patient visits were made, including 45.1 million visits for cutaneous wounds. Of these, the most common diagnoses were open wounds of the thumb without nail damage (7.96%), the lower leg (5.75%), nonpressure chronic ulcers of other parts of the foot (5.08%), and open wounds of the ear (5%).
Among all visits for cutaneous wounds, about one third were chronic cutaneous wounds, with the following descriptions: “Nonpressure chronic ulcer of other part of foot” (17.8%); “nonpressure chronic ulcer of skin, not elsewhere classified” (9.38%); and “ulcer of lower limbs, excluding decubitus, unspecified” (8.72%). “The frequency of patient visits per year during the study period remained stable for both acute and chronic wounds,” Dr. Chandy said. The number of visits for which antimicrobials were used was stable over time for both acute and chronic cutaneous wounds, with the exception of increased use of antivirals for chronic cutaneous wounds, he added.
Specifically, prescriptions were issued in 156 million visits over the time studied, most commonly cephalexin (4.22%), topical silver sulfadiazine (1.59%), topical mupirocin (1.12%), and miscellaneous antibiotics (1.18%).
“Our data shows that topical mupirocin is the most commonly used topical antimicrobial for cutaneous wounds,” Dr. Chandy said. “However, there are reports of emerging bacterial resistance to mupirocin. Our data can inform ongoing efforts to promote antimicrobial stewardship and drug development to provide alternative options that are less likely to induce antimicrobial resistance.”
In findings limited to specialty-specific NAMCS data available from 2011 and from 2013 to 2016, dermatologists managed 3.85% of overall cutaneous wounds, 2.35% of acute wounds, and 7.39% of chronic wounds. By contrast, Dr. Chandy said, 21.1% of chronic wounds were managed by general/family practice physicians, 20.7% by internists, 6.84% by general surgeons, and 5.65% by orthopedic surgeons.
“As dermatologists are experts in the structure and function of the skin and are trained to manage cutaneous disorders including wound healing, we [believe that] dermatologists are equipped with the skill set” for managing wounds, especially for chronic ulcers, he said. The decline in dermatologists who specialize in wound care, he added, “underscores the need for structured dermatology fellowship programs to prepare next-generation dermatologists to address this shortage and ensure dermatology leadership in cutaneous wound healing.”
Dr. Chandy acknowledged certain limitations of the study, including the potential for misclassification of diagnoses or medications prescribed and the fact that the NAMCS database is unable to provide insight into individual patient experiences such as continual cutaneous wound management for the same patient over time.
In the opinion of Shari R. Lipner, MD, PhD, associate professor of clinical dermatology and director of the Nail Division at Weill Cornell Medicine, New York, who was asked to comment on the study, the most interesting finding was that dermatologists cared for a small minority of patients with cutaneous wounds. “It would be interesting to know whether this is due to dermatologist shortages or knowledge gaps on the part of primary care physicians or patients that dermatologists are trained to care for wounds,” Dr. Lipner told this news organization. Other unanswered questions, she noted, “are patient demographics, geographic locations, and comorbidities.”
One of the study authors, Steven R. Feldman, MD, PhD, professor of dermatology at Wake Forest University, disclosed that he has received research, speaking and/or consulting support from numerous pharmaceutical companies. No other authors reported having relevant disclosures. Dr. Lipner reported having no disclosures.
A version of this article appeared on Medscape.com .
FROM SID 2024
Prenatal Antibiotics May Increase Seborrheic Dermatitis Risk in Babies
, but this association was not as strong for childhood-onset SD.
The findings come from a large analysis of data from the United Kingdom that was presented during a late-breaking abstract session at the annual meeting of the Society for Investigative Dermatology.
SD is a common skin disease “that shares similarities with atopic dermatitis or atopic eczema as both are prevalent inflammatory skin diseases that can present with a chronic relapsing, remitting course,” the study’s corresponding author Zelma C. Chiesa Fuxench, MD, MSCE, assistant professor of dermatology at the University of Pennsylvania, Philadelphia, said in an interview. “Like atopic dermatitis, the pathophysiology of seborrheic dermatitis is thought to be complex and involves an interplay between genetics, immune dysregulation, and alterations in lipid composition and the skin microbiome, among others.”
In a previous study, she and colleagues showed that exposure to antibiotics both in utero and during the first 90 days of life increases the risk for atopic dermatitis (AD) in children, with risk being highest with exposure to penicillin even among children whose mothers did not have a history of AD.
For the current study, the researchers drew from a large electronic medical records database in the United Kingdom to perform a prospective cohort analysis of mother-child pairs that used proportional hazards models to examine the association between maternal in utero antibiotic exposure and SD in the child. The population included 1,023,140 children with linked maternal data who were followed for a mean of 10.2 years, which amounts to more than 10-million-person years of data. At baseline, the mean age of mothers was 28 years, 3% had SD, 14% had AD, and 51% of the children were male.
In unadjusted analyses, mothers with SD were more likely to receive an antibiotic during pregnancy than were those who did not have SD (odds ratio [OR], 1.42; 95% CI, 1.39-1.46). In addition, maternal in utero exposure to any antibiotic was associated with an increased risk for infantile SD (OR, 1.70; 95% CI, 1.65-1.76) but less for childhood-onset SD (OR, 1.26; 95% CI, 1.20-1.32). “This effect changed little after adjustment and was still observed if mothers with SD and their babies were excluded,” the authors wrote in their poster abstract.
Any penicillin exposure during pregnancy increased the likelihood of a child having SD (OR, 1.54; 95% CI, 1.50-1.59), with the greater risk for infantile SD (OR, 1.70; 95% CI, 1.65-1.76) than for childhood-onset SD (OR, 1.25; 95% CI, 1.18-1.32). “The trimester of the in utero penicillin exposure did not seem to affect the association with SD,” the authors wrote. The risk was also increased with cephalosporin exposure but was less for sulfonamides and not for childhood-onset SD.
“We observed that antibiotic exposure in utero was primarily associated with an increased risk of infantile SD regardless of the mother’s history of SD, but this association was not as strong for childhood-onset SD,” Dr. Chiesa Fuxench said. “This would suggest that in utero exposure to antibiotics, particularly penicillin, may have its greatest effect on the colonization of skin microbiota in the newborn period leading to the development of infantile SD. Aside from seeking to improve our understanding of the pathophysiology of SD, our findings also suggest that infantile SD and childhood-onset SD may be separate entities with different risk factors, a hypothesis that needs to be further studied.”
She acknowledged certain limitations of the analysis, including the potential for unrecorded diagnoses of SD or misclassified cases in the database. For example, AD and psoriasis “may appear clinically like SD,” she said, although they performed sensitivity analysis excluding patients with these diagnoses and found similar results. In addition, there is the possibility that not all antibiotic exposures were captured in this database, and data on antibiotic exposure may be missing, she added.
Dr. Chiesa Fuxench disclosed that she received research grants from Lilly, LEO Pharma, Regeneron, Sanofi, Tioga, Vanda, and Incyte for work related to AD and from Menlo Therapeutics and Galderma for work related to prurigo nodularis. She has served as a consultant for the Asthma and Allergy Foundation of America, National Eczema Association, AbbVie, Incyte Corporation, and Pfizer and received honoraria for CME work in AD sponsored by education grants from Regeneron/Sanofi and Pfizer and from Beiersdorf for work related to skin cancer and sun protection.
A version of this article appeared on Medscape.com .
, but this association was not as strong for childhood-onset SD.
The findings come from a large analysis of data from the United Kingdom that was presented during a late-breaking abstract session at the annual meeting of the Society for Investigative Dermatology.
SD is a common skin disease “that shares similarities with atopic dermatitis or atopic eczema as both are prevalent inflammatory skin diseases that can present with a chronic relapsing, remitting course,” the study’s corresponding author Zelma C. Chiesa Fuxench, MD, MSCE, assistant professor of dermatology at the University of Pennsylvania, Philadelphia, said in an interview. “Like atopic dermatitis, the pathophysiology of seborrheic dermatitis is thought to be complex and involves an interplay between genetics, immune dysregulation, and alterations in lipid composition and the skin microbiome, among others.”
In a previous study, she and colleagues showed that exposure to antibiotics both in utero and during the first 90 days of life increases the risk for atopic dermatitis (AD) in children, with risk being highest with exposure to penicillin even among children whose mothers did not have a history of AD.
For the current study, the researchers drew from a large electronic medical records database in the United Kingdom to perform a prospective cohort analysis of mother-child pairs that used proportional hazards models to examine the association between maternal in utero antibiotic exposure and SD in the child. The population included 1,023,140 children with linked maternal data who were followed for a mean of 10.2 years, which amounts to more than 10-million-person years of data. At baseline, the mean age of mothers was 28 years, 3% had SD, 14% had AD, and 51% of the children were male.
In unadjusted analyses, mothers with SD were more likely to receive an antibiotic during pregnancy than were those who did not have SD (odds ratio [OR], 1.42; 95% CI, 1.39-1.46). In addition, maternal in utero exposure to any antibiotic was associated with an increased risk for infantile SD (OR, 1.70; 95% CI, 1.65-1.76) but less for childhood-onset SD (OR, 1.26; 95% CI, 1.20-1.32). “This effect changed little after adjustment and was still observed if mothers with SD and their babies were excluded,” the authors wrote in their poster abstract.
Any penicillin exposure during pregnancy increased the likelihood of a child having SD (OR, 1.54; 95% CI, 1.50-1.59), with the greater risk for infantile SD (OR, 1.70; 95% CI, 1.65-1.76) than for childhood-onset SD (OR, 1.25; 95% CI, 1.18-1.32). “The trimester of the in utero penicillin exposure did not seem to affect the association with SD,” the authors wrote. The risk was also increased with cephalosporin exposure but was less for sulfonamides and not for childhood-onset SD.
“We observed that antibiotic exposure in utero was primarily associated with an increased risk of infantile SD regardless of the mother’s history of SD, but this association was not as strong for childhood-onset SD,” Dr. Chiesa Fuxench said. “This would suggest that in utero exposure to antibiotics, particularly penicillin, may have its greatest effect on the colonization of skin microbiota in the newborn period leading to the development of infantile SD. Aside from seeking to improve our understanding of the pathophysiology of SD, our findings also suggest that infantile SD and childhood-onset SD may be separate entities with different risk factors, a hypothesis that needs to be further studied.”
She acknowledged certain limitations of the analysis, including the potential for unrecorded diagnoses of SD or misclassified cases in the database. For example, AD and psoriasis “may appear clinically like SD,” she said, although they performed sensitivity analysis excluding patients with these diagnoses and found similar results. In addition, there is the possibility that not all antibiotic exposures were captured in this database, and data on antibiotic exposure may be missing, she added.
Dr. Chiesa Fuxench disclosed that she received research grants from Lilly, LEO Pharma, Regeneron, Sanofi, Tioga, Vanda, and Incyte for work related to AD and from Menlo Therapeutics and Galderma for work related to prurigo nodularis. She has served as a consultant for the Asthma and Allergy Foundation of America, National Eczema Association, AbbVie, Incyte Corporation, and Pfizer and received honoraria for CME work in AD sponsored by education grants from Regeneron/Sanofi and Pfizer and from Beiersdorf for work related to skin cancer and sun protection.
A version of this article appeared on Medscape.com .
, but this association was not as strong for childhood-onset SD.
The findings come from a large analysis of data from the United Kingdom that was presented during a late-breaking abstract session at the annual meeting of the Society for Investigative Dermatology.
SD is a common skin disease “that shares similarities with atopic dermatitis or atopic eczema as both are prevalent inflammatory skin diseases that can present with a chronic relapsing, remitting course,” the study’s corresponding author Zelma C. Chiesa Fuxench, MD, MSCE, assistant professor of dermatology at the University of Pennsylvania, Philadelphia, said in an interview. “Like atopic dermatitis, the pathophysiology of seborrheic dermatitis is thought to be complex and involves an interplay between genetics, immune dysregulation, and alterations in lipid composition and the skin microbiome, among others.”
In a previous study, she and colleagues showed that exposure to antibiotics both in utero and during the first 90 days of life increases the risk for atopic dermatitis (AD) in children, with risk being highest with exposure to penicillin even among children whose mothers did not have a history of AD.
For the current study, the researchers drew from a large electronic medical records database in the United Kingdom to perform a prospective cohort analysis of mother-child pairs that used proportional hazards models to examine the association between maternal in utero antibiotic exposure and SD in the child. The population included 1,023,140 children with linked maternal data who were followed for a mean of 10.2 years, which amounts to more than 10-million-person years of data. At baseline, the mean age of mothers was 28 years, 3% had SD, 14% had AD, and 51% of the children were male.
In unadjusted analyses, mothers with SD were more likely to receive an antibiotic during pregnancy than were those who did not have SD (odds ratio [OR], 1.42; 95% CI, 1.39-1.46). In addition, maternal in utero exposure to any antibiotic was associated with an increased risk for infantile SD (OR, 1.70; 95% CI, 1.65-1.76) but less for childhood-onset SD (OR, 1.26; 95% CI, 1.20-1.32). “This effect changed little after adjustment and was still observed if mothers with SD and their babies were excluded,” the authors wrote in their poster abstract.
Any penicillin exposure during pregnancy increased the likelihood of a child having SD (OR, 1.54; 95% CI, 1.50-1.59), with the greater risk for infantile SD (OR, 1.70; 95% CI, 1.65-1.76) than for childhood-onset SD (OR, 1.25; 95% CI, 1.18-1.32). “The trimester of the in utero penicillin exposure did not seem to affect the association with SD,” the authors wrote. The risk was also increased with cephalosporin exposure but was less for sulfonamides and not for childhood-onset SD.
“We observed that antibiotic exposure in utero was primarily associated with an increased risk of infantile SD regardless of the mother’s history of SD, but this association was not as strong for childhood-onset SD,” Dr. Chiesa Fuxench said. “This would suggest that in utero exposure to antibiotics, particularly penicillin, may have its greatest effect on the colonization of skin microbiota in the newborn period leading to the development of infantile SD. Aside from seeking to improve our understanding of the pathophysiology of SD, our findings also suggest that infantile SD and childhood-onset SD may be separate entities with different risk factors, a hypothesis that needs to be further studied.”
She acknowledged certain limitations of the analysis, including the potential for unrecorded diagnoses of SD or misclassified cases in the database. For example, AD and psoriasis “may appear clinically like SD,” she said, although they performed sensitivity analysis excluding patients with these diagnoses and found similar results. In addition, there is the possibility that not all antibiotic exposures were captured in this database, and data on antibiotic exposure may be missing, she added.
Dr. Chiesa Fuxench disclosed that she received research grants from Lilly, LEO Pharma, Regeneron, Sanofi, Tioga, Vanda, and Incyte for work related to AD and from Menlo Therapeutics and Galderma for work related to prurigo nodularis. She has served as a consultant for the Asthma and Allergy Foundation of America, National Eczema Association, AbbVie, Incyte Corporation, and Pfizer and received honoraria for CME work in AD sponsored by education grants from Regeneron/Sanofi and Pfizer and from Beiersdorf for work related to skin cancer and sun protection.
A version of this article appeared on Medscape.com .
FROM SID 2024
Counting Steps or Watching the Clock for a Longer Life?
Exercise recommendations typically focus on the duration of physical activity. For example, the World Health Organization advises at least 150 minutes of moderate physical activity per week. A new analysis of data from the Women’s Health Study, published in JAMA Internal Medicine, suggested that step count could also be a useful metric. For some, such a recommendation might be easier to follow.
“It’s not so easy to keep track of how long you’ve been moderately active in a given week,” Cary P. Gross, MD, from the Department of Medicine at Yale University in New Haven, Connecticut, wrote in an editorial. “Counting steps might be easier for some people, especially since most carry a phone that can serve as a pedometer.”
The 10,000-Step Recommendation
However, there are no well-founded recommendations for step counts, partly due to a lack of scientific evidence linking steps with mortality and cardiovascular diseases. The often-cited 10,000 steps per day originated from a marketing campaign in Japan in the 1960s.
The research team led by Rikuta Hamaya, MD, from the Division of Preventive Medicine at Brigham and Women’s Hospital in Boston, analyzed data from participants in the Women’s Health Study. This clinical trial in the United States from 1992 to 2004 investigated the use of aspirin and vitamin E for cancer and cardiovascular disease prevention.
The current analysis included 14,399 women who were aged ≥ 62 years and had not developed cardiovascular disease or cancer. Between 2011 and 2015, they measured their physical activity and step count over 7 days using an accelerometer. They were followed-up for an average of 9 years.
Risk Reduction With Both Parameters
Moderate physical activity among the participants amounted to a median of 62 minutes per week, with a median daily step count of 5183. Hamaya and his colleagues found that both physical activity parameters were associated with lower mortality and reduced risk for cardiovascular diseases.
Participants who engaged in more than the recommended 150 minutes of moderate-intensity activity per week had a 32% lower mortality risk than those who were the least physically active. Women with > 7000 steps per day had a 42% lower mortality risk than those with the lowest daily step count.
Women in the top three quartiles of physical activity outlived those in the lowest quartile by an average of 2.22 months (time) or 2.36 months (steps), according to Hamaya and his team. The survival advantage was independent of body mass index.
For the endpoint of cardiovascular diseases (heart attack, stroke, and cardiovascular mortality), the researchers observed similar results as for mortality.
More Ways to Reach the Goal
Dr. Hamaya emphasized the importance of offering multiple ways to meet exercise recommendations: “For some, especially younger people, physical activity includes sports like tennis, soccer, walking, or jogging. All these can be tracked well with step counting. But for others, activity means cycling or swimming, which is easier to measure by duration.”
For Dr. Gross, the new findings provide a basis for using step counts to set physical activity goals — both in individual patient counseling and in formal guidelines. However, he stressed that further studies are necessary.
“The results need to be replicated in various populations, not just among men and younger people but also among ethnic minorities and lower-income populations, who often have less time and space for structured physical activity.”
This story was translated from Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Exercise recommendations typically focus on the duration of physical activity. For example, the World Health Organization advises at least 150 minutes of moderate physical activity per week. A new analysis of data from the Women’s Health Study, published in JAMA Internal Medicine, suggested that step count could also be a useful metric. For some, such a recommendation might be easier to follow.
“It’s not so easy to keep track of how long you’ve been moderately active in a given week,” Cary P. Gross, MD, from the Department of Medicine at Yale University in New Haven, Connecticut, wrote in an editorial. “Counting steps might be easier for some people, especially since most carry a phone that can serve as a pedometer.”
The 10,000-Step Recommendation
However, there are no well-founded recommendations for step counts, partly due to a lack of scientific evidence linking steps with mortality and cardiovascular diseases. The often-cited 10,000 steps per day originated from a marketing campaign in Japan in the 1960s.
The research team led by Rikuta Hamaya, MD, from the Division of Preventive Medicine at Brigham and Women’s Hospital in Boston, analyzed data from participants in the Women’s Health Study. This clinical trial in the United States from 1992 to 2004 investigated the use of aspirin and vitamin E for cancer and cardiovascular disease prevention.
The current analysis included 14,399 women who were aged ≥ 62 years and had not developed cardiovascular disease or cancer. Between 2011 and 2015, they measured their physical activity and step count over 7 days using an accelerometer. They were followed-up for an average of 9 years.
Risk Reduction With Both Parameters
Moderate physical activity among the participants amounted to a median of 62 minutes per week, with a median daily step count of 5183. Hamaya and his colleagues found that both physical activity parameters were associated with lower mortality and reduced risk for cardiovascular diseases.
Participants who engaged in more than the recommended 150 minutes of moderate-intensity activity per week had a 32% lower mortality risk than those who were the least physically active. Women with > 7000 steps per day had a 42% lower mortality risk than those with the lowest daily step count.
Women in the top three quartiles of physical activity outlived those in the lowest quartile by an average of 2.22 months (time) or 2.36 months (steps), according to Hamaya and his team. The survival advantage was independent of body mass index.
For the endpoint of cardiovascular diseases (heart attack, stroke, and cardiovascular mortality), the researchers observed similar results as for mortality.
More Ways to Reach the Goal
Dr. Hamaya emphasized the importance of offering multiple ways to meet exercise recommendations: “For some, especially younger people, physical activity includes sports like tennis, soccer, walking, or jogging. All these can be tracked well with step counting. But for others, activity means cycling or swimming, which is easier to measure by duration.”
For Dr. Gross, the new findings provide a basis for using step counts to set physical activity goals — both in individual patient counseling and in formal guidelines. However, he stressed that further studies are necessary.
“The results need to be replicated in various populations, not just among men and younger people but also among ethnic minorities and lower-income populations, who often have less time and space for structured physical activity.”
This story was translated from Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Exercise recommendations typically focus on the duration of physical activity. For example, the World Health Organization advises at least 150 minutes of moderate physical activity per week. A new analysis of data from the Women’s Health Study, published in JAMA Internal Medicine, suggested that step count could also be a useful metric. For some, such a recommendation might be easier to follow.
“It’s not so easy to keep track of how long you’ve been moderately active in a given week,” Cary P. Gross, MD, from the Department of Medicine at Yale University in New Haven, Connecticut, wrote in an editorial. “Counting steps might be easier for some people, especially since most carry a phone that can serve as a pedometer.”
The 10,000-Step Recommendation
However, there are no well-founded recommendations for step counts, partly due to a lack of scientific evidence linking steps with mortality and cardiovascular diseases. The often-cited 10,000 steps per day originated from a marketing campaign in Japan in the 1960s.
The research team led by Rikuta Hamaya, MD, from the Division of Preventive Medicine at Brigham and Women’s Hospital in Boston, analyzed data from participants in the Women’s Health Study. This clinical trial in the United States from 1992 to 2004 investigated the use of aspirin and vitamin E for cancer and cardiovascular disease prevention.
The current analysis included 14,399 women who were aged ≥ 62 years and had not developed cardiovascular disease or cancer. Between 2011 and 2015, they measured their physical activity and step count over 7 days using an accelerometer. They were followed-up for an average of 9 years.
Risk Reduction With Both Parameters
Moderate physical activity among the participants amounted to a median of 62 minutes per week, with a median daily step count of 5183. Hamaya and his colleagues found that both physical activity parameters were associated with lower mortality and reduced risk for cardiovascular diseases.
Participants who engaged in more than the recommended 150 minutes of moderate-intensity activity per week had a 32% lower mortality risk than those who were the least physically active. Women with > 7000 steps per day had a 42% lower mortality risk than those with the lowest daily step count.
Women in the top three quartiles of physical activity outlived those in the lowest quartile by an average of 2.22 months (time) or 2.36 months (steps), according to Hamaya and his team. The survival advantage was independent of body mass index.
For the endpoint of cardiovascular diseases (heart attack, stroke, and cardiovascular mortality), the researchers observed similar results as for mortality.
More Ways to Reach the Goal
Dr. Hamaya emphasized the importance of offering multiple ways to meet exercise recommendations: “For some, especially younger people, physical activity includes sports like tennis, soccer, walking, or jogging. All these can be tracked well with step counting. But for others, activity means cycling or swimming, which is easier to measure by duration.”
For Dr. Gross, the new findings provide a basis for using step counts to set physical activity goals — both in individual patient counseling and in formal guidelines. However, he stressed that further studies are necessary.
“The results need to be replicated in various populations, not just among men and younger people but also among ethnic minorities and lower-income populations, who often have less time and space for structured physical activity.”
This story was translated from Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Investigational Male Contraceptive Suppresses Sperm Rapidly
BOSTON — An investigational male contraceptive gel suppresses sperm more rapidly than previous products in development, new data suggested.
The product, 8 mg segesterone acetate (Nestorone) combined with 74 mg testosterone (“NesT”) is a gel that a man applies daily to both shoulders. The progesterone blocks spermatogenesis, and the testosterone restores blood levels to maintain sexual function. It is under development by the National Institute of Child Health and Human Development (NICHD) in collaboration with the Population Council, the Los Angeles Biomedical Research Institute, and the University of Washington School of Medicine.
Currently, the only available male contraceptives are vasectomy, which isn’t easily reversible, and condoms, which have a high failure rate. Previous attempts to develop a “male pill” have been unsuccessful for a variety of reasons, but so far, this product appears effective and safe, Diana Blithe, PhD, chief of the Contraceptive Development Program at NICHD, said at a press briefing held on June 2, 2024, during the annual meeting of the Endocrine Society.
“It’s been a long time coming. … Men need and want more contraceptive options such as an effective reversible method,” she told this news organization.
New phase 2b data show that among 222 couples in which the man initially had normal (> 15 million/mL) sperm counts, the median time to suppression (< 1 million/mL) was less than 8 weeks with NesT compared with 9-15 weeks seen in previous trials of injected male hormonal contraceptives. Nearly all (86%) had achieved suppression by 15 weeks.
After two consecutive counts of < 1 million/mL, the couples entered the trial’s ongoing 2-year efficacy phase. There have been no major safety concerns thus far, but “we need more data,” Dr. Blithe noted.
Asked to comment, session moderator Frances Hayes, MBBCh, associate clinical chief of the Division of Reproductive Endocrinology at Massachusetts General Hospital, Boston, said, “certainly, I think it’s a big advance on what we have so far. … I think it’s showing great promise.”
Dr. Hayes did caution, though, that “with real-world use, daily application of a gel might be a bit more challenging than taking an injection…an injection is more consistent. With a gel, patients might forget or shower it off. But I don’t think 1 day of interruption would be a significant thing.”
Transference of the topical to a partner or a child is another potential concern, Dr. Hayes noted, although this is true of current testosterone gel products as well. During the briefing, Dr. Blithe said that this issue is why the product is recommended to be placed on the upper arms rather than the abdomen or another spot more likely to come into contact with another person. Also, in the trial, men were instructed to wear shirts during intercourse.
Regarding the rapidity of sperm suppression, Dr. Hayes said, “It’s surprising. It looks great as a reversible contraceptive. … Normally, you think of the life cycle of the sperm being about 72 days. So to see 50% suppression by 8 weeks, and then 85%-90% by 15 weeks, that’s very rapid. It may be that the progesterone that they’re using is very potent. Progestins can have some negative effects on lipids and mood. We didn’t really see the safety data in this presentation. So that will be interesting to see.”
During the briefing, Dr. Blithe said that the phase 2b trial is expected to finish by the end of this year, and in the meantime, the researchers are communicating with the US Food and Drug Administration about the design of a phase 3 trial because this is an unprecedented area. “They don’t have guidelines yet. They’ll need to develop them first.”
Dr. Blithe has been the NICHD principal investigator on cooperative research and development agreements with HRA Pharma and Daré Bioscience. Dr. Hayes had no disclosures.
A version of this article appeared on Medscape.com .
BOSTON — An investigational male contraceptive gel suppresses sperm more rapidly than previous products in development, new data suggested.
The product, 8 mg segesterone acetate (Nestorone) combined with 74 mg testosterone (“NesT”) is a gel that a man applies daily to both shoulders. The progesterone blocks spermatogenesis, and the testosterone restores blood levels to maintain sexual function. It is under development by the National Institute of Child Health and Human Development (NICHD) in collaboration with the Population Council, the Los Angeles Biomedical Research Institute, and the University of Washington School of Medicine.
Currently, the only available male contraceptives are vasectomy, which isn’t easily reversible, and condoms, which have a high failure rate. Previous attempts to develop a “male pill” have been unsuccessful for a variety of reasons, but so far, this product appears effective and safe, Diana Blithe, PhD, chief of the Contraceptive Development Program at NICHD, said at a press briefing held on June 2, 2024, during the annual meeting of the Endocrine Society.
“It’s been a long time coming. … Men need and want more contraceptive options such as an effective reversible method,” she told this news organization.
New phase 2b data show that among 222 couples in which the man initially had normal (> 15 million/mL) sperm counts, the median time to suppression (< 1 million/mL) was less than 8 weeks with NesT compared with 9-15 weeks seen in previous trials of injected male hormonal contraceptives. Nearly all (86%) had achieved suppression by 15 weeks.
After two consecutive counts of < 1 million/mL, the couples entered the trial’s ongoing 2-year efficacy phase. There have been no major safety concerns thus far, but “we need more data,” Dr. Blithe noted.
Asked to comment, session moderator Frances Hayes, MBBCh, associate clinical chief of the Division of Reproductive Endocrinology at Massachusetts General Hospital, Boston, said, “certainly, I think it’s a big advance on what we have so far. … I think it’s showing great promise.”
Dr. Hayes did caution, though, that “with real-world use, daily application of a gel might be a bit more challenging than taking an injection…an injection is more consistent. With a gel, patients might forget or shower it off. But I don’t think 1 day of interruption would be a significant thing.”
Transference of the topical to a partner or a child is another potential concern, Dr. Hayes noted, although this is true of current testosterone gel products as well. During the briefing, Dr. Blithe said that this issue is why the product is recommended to be placed on the upper arms rather than the abdomen or another spot more likely to come into contact with another person. Also, in the trial, men were instructed to wear shirts during intercourse.
Regarding the rapidity of sperm suppression, Dr. Hayes said, “It’s surprising. It looks great as a reversible contraceptive. … Normally, you think of the life cycle of the sperm being about 72 days. So to see 50% suppression by 8 weeks, and then 85%-90% by 15 weeks, that’s very rapid. It may be that the progesterone that they’re using is very potent. Progestins can have some negative effects on lipids and mood. We didn’t really see the safety data in this presentation. So that will be interesting to see.”
During the briefing, Dr. Blithe said that the phase 2b trial is expected to finish by the end of this year, and in the meantime, the researchers are communicating with the US Food and Drug Administration about the design of a phase 3 trial because this is an unprecedented area. “They don’t have guidelines yet. They’ll need to develop them first.”
Dr. Blithe has been the NICHD principal investigator on cooperative research and development agreements with HRA Pharma and Daré Bioscience. Dr. Hayes had no disclosures.
A version of this article appeared on Medscape.com .
BOSTON — An investigational male contraceptive gel suppresses sperm more rapidly than previous products in development, new data suggested.
The product, 8 mg segesterone acetate (Nestorone) combined with 74 mg testosterone (“NesT”) is a gel that a man applies daily to both shoulders. The progesterone blocks spermatogenesis, and the testosterone restores blood levels to maintain sexual function. It is under development by the National Institute of Child Health and Human Development (NICHD) in collaboration with the Population Council, the Los Angeles Biomedical Research Institute, and the University of Washington School of Medicine.
Currently, the only available male contraceptives are vasectomy, which isn’t easily reversible, and condoms, which have a high failure rate. Previous attempts to develop a “male pill” have been unsuccessful for a variety of reasons, but so far, this product appears effective and safe, Diana Blithe, PhD, chief of the Contraceptive Development Program at NICHD, said at a press briefing held on June 2, 2024, during the annual meeting of the Endocrine Society.
“It’s been a long time coming. … Men need and want more contraceptive options such as an effective reversible method,” she told this news organization.
New phase 2b data show that among 222 couples in which the man initially had normal (> 15 million/mL) sperm counts, the median time to suppression (< 1 million/mL) was less than 8 weeks with NesT compared with 9-15 weeks seen in previous trials of injected male hormonal contraceptives. Nearly all (86%) had achieved suppression by 15 weeks.
After two consecutive counts of < 1 million/mL, the couples entered the trial’s ongoing 2-year efficacy phase. There have been no major safety concerns thus far, but “we need more data,” Dr. Blithe noted.
Asked to comment, session moderator Frances Hayes, MBBCh, associate clinical chief of the Division of Reproductive Endocrinology at Massachusetts General Hospital, Boston, said, “certainly, I think it’s a big advance on what we have so far. … I think it’s showing great promise.”
Dr. Hayes did caution, though, that “with real-world use, daily application of a gel might be a bit more challenging than taking an injection…an injection is more consistent. With a gel, patients might forget or shower it off. But I don’t think 1 day of interruption would be a significant thing.”
Transference of the topical to a partner or a child is another potential concern, Dr. Hayes noted, although this is true of current testosterone gel products as well. During the briefing, Dr. Blithe said that this issue is why the product is recommended to be placed on the upper arms rather than the abdomen or another spot more likely to come into contact with another person. Also, in the trial, men were instructed to wear shirts during intercourse.
Regarding the rapidity of sperm suppression, Dr. Hayes said, “It’s surprising. It looks great as a reversible contraceptive. … Normally, you think of the life cycle of the sperm being about 72 days. So to see 50% suppression by 8 weeks, and then 85%-90% by 15 weeks, that’s very rapid. It may be that the progesterone that they’re using is very potent. Progestins can have some negative effects on lipids and mood. We didn’t really see the safety data in this presentation. So that will be interesting to see.”
During the briefing, Dr. Blithe said that the phase 2b trial is expected to finish by the end of this year, and in the meantime, the researchers are communicating with the US Food and Drug Administration about the design of a phase 3 trial because this is an unprecedented area. “They don’t have guidelines yet. They’ll need to develop them first.”
Dr. Blithe has been the NICHD principal investigator on cooperative research and development agreements with HRA Pharma and Daré Bioscience. Dr. Hayes had no disclosures.
A version of this article appeared on Medscape.com .
FROM ENDO 2024
Eating More Vegetables Improves Glucose Tolerance
TOPLINE:
A diet rich in green, leafy, cruciferous, and colorful vegetables may improve glucose tolerance and insulin sensitivity, whereas a high intake of potato fries or chips may worsen these outcomes, an Australian study shows.
METHODOLOGY:
- Researchers assessed the association between the intake of vegetables and potatoes with markers of type 2 diabetes (T2D) in 8009 participants (median age, 52 years; 55% women) from the Australian Diabetes, Obesity, and Lifestyle Study.
- A self-administered 74-item food frequency questionnaire was used to assess participants’ eating habits over 12 months prior to baseline.
- Participants were categorized into four quartiles of vegetable intake, from the highest intake (Q4) to the lowest intake (Q1).
- The association between vegetable intake and various metabolic markers such as fasting plasma glucose (FPG), 2-hour post-load plasma glucose, updated homeostasis model assessment of beta cell function (HOMA2-%beta), HOMA2 of insulin sensitivity (HOMA2-%S), and fasting insulin were evaluated over a 12-year follow-up period.
TAKEAWAY:
- The post-load glucose was 3% lower in participants in the highest vs lowest quartile of total vegetable intake (ratio of means [RoM], 0.97; 95% CI, 0.96-0.99).
- Post-load glucose was 4% lower (RoM, 0.96; 95% CI, 0.95-0.98), HOMA2-%beta was 3% lower (RoM, 0.97; 95% CI, 0.96-0.99), and serum insulin was 5% lower (RoM, 0.95; 95% CI, 0.93-0.98) in those in the highest vs lowest quartile of green leafy vegetable intake.
- Those in the highest vs lowest quartile of potato fries or chips intake had 1% higher FPG, 3% higher HOMA2-%beta, and 8% higher serum insulin but 6% lower HOMA2-%S, revealing a negative impact on glucose tolerance and insulin sensitivity.
- The risk for T2D over 12 years was 26% and 25% lower among those in the highest and moderate quartiles of cruciferous vegetable intake, respectively, than among those in the lowest quartile of cruciferous vegetable intake.
IN PRACTICE:
The authors wrote that their study “sheds light on the physiological alterations in insulin regulation and glucose tolerance resulting from higher vegetable and subgroups of vegetable intake and supports the notion that vegetable subgroups may act differently in regulating insulin and blood glucose levels.”
SOURCE:
The study was led by Pratik Pokharel, MPH, Nutrition & Health Innovation Research Institute, School of Medical and Health Sciences, Edith Cowan University, Perth, Australia, and was published online in The Journal of Clinical Endocrinology & Metabolism.
LIMITATIONS:
The study’s observational nature precluded the inference of causality. Potential measurement errors in dietary exposures and recall bias linked to the food frequency questionnaire could have affected the findings. The overrepresentation of participants from higher education and socioeconomic subgroups and loss to follow-up could limit the generalizability of the findings.
DISCLOSURES:
The study was funded by the National Health and Medical Research Council, National Heart Foundation of Australia, and Royal Perth Hospital Medical Research Foundation. Several authors reported receiving grants from various sources during the conduct of this study. The other authors reported no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
A diet rich in green, leafy, cruciferous, and colorful vegetables may improve glucose tolerance and insulin sensitivity, whereas a high intake of potato fries or chips may worsen these outcomes, an Australian study shows.
METHODOLOGY:
- Researchers assessed the association between the intake of vegetables and potatoes with markers of type 2 diabetes (T2D) in 8009 participants (median age, 52 years; 55% women) from the Australian Diabetes, Obesity, and Lifestyle Study.
- A self-administered 74-item food frequency questionnaire was used to assess participants’ eating habits over 12 months prior to baseline.
- Participants were categorized into four quartiles of vegetable intake, from the highest intake (Q4) to the lowest intake (Q1).
- The association between vegetable intake and various metabolic markers such as fasting plasma glucose (FPG), 2-hour post-load plasma glucose, updated homeostasis model assessment of beta cell function (HOMA2-%beta), HOMA2 of insulin sensitivity (HOMA2-%S), and fasting insulin were evaluated over a 12-year follow-up period.
TAKEAWAY:
- The post-load glucose was 3% lower in participants in the highest vs lowest quartile of total vegetable intake (ratio of means [RoM], 0.97; 95% CI, 0.96-0.99).
- Post-load glucose was 4% lower (RoM, 0.96; 95% CI, 0.95-0.98), HOMA2-%beta was 3% lower (RoM, 0.97; 95% CI, 0.96-0.99), and serum insulin was 5% lower (RoM, 0.95; 95% CI, 0.93-0.98) in those in the highest vs lowest quartile of green leafy vegetable intake.
- Those in the highest vs lowest quartile of potato fries or chips intake had 1% higher FPG, 3% higher HOMA2-%beta, and 8% higher serum insulin but 6% lower HOMA2-%S, revealing a negative impact on glucose tolerance and insulin sensitivity.
- The risk for T2D over 12 years was 26% and 25% lower among those in the highest and moderate quartiles of cruciferous vegetable intake, respectively, than among those in the lowest quartile of cruciferous vegetable intake.
IN PRACTICE:
The authors wrote that their study “sheds light on the physiological alterations in insulin regulation and glucose tolerance resulting from higher vegetable and subgroups of vegetable intake and supports the notion that vegetable subgroups may act differently in regulating insulin and blood glucose levels.”
SOURCE:
The study was led by Pratik Pokharel, MPH, Nutrition & Health Innovation Research Institute, School of Medical and Health Sciences, Edith Cowan University, Perth, Australia, and was published online in The Journal of Clinical Endocrinology & Metabolism.
LIMITATIONS:
The study’s observational nature precluded the inference of causality. Potential measurement errors in dietary exposures and recall bias linked to the food frequency questionnaire could have affected the findings. The overrepresentation of participants from higher education and socioeconomic subgroups and loss to follow-up could limit the generalizability of the findings.
DISCLOSURES:
The study was funded by the National Health and Medical Research Council, National Heart Foundation of Australia, and Royal Perth Hospital Medical Research Foundation. Several authors reported receiving grants from various sources during the conduct of this study. The other authors reported no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
A diet rich in green, leafy, cruciferous, and colorful vegetables may improve glucose tolerance and insulin sensitivity, whereas a high intake of potato fries or chips may worsen these outcomes, an Australian study shows.
METHODOLOGY:
- Researchers assessed the association between the intake of vegetables and potatoes with markers of type 2 diabetes (T2D) in 8009 participants (median age, 52 years; 55% women) from the Australian Diabetes, Obesity, and Lifestyle Study.
- A self-administered 74-item food frequency questionnaire was used to assess participants’ eating habits over 12 months prior to baseline.
- Participants were categorized into four quartiles of vegetable intake, from the highest intake (Q4) to the lowest intake (Q1).
- The association between vegetable intake and various metabolic markers such as fasting plasma glucose (FPG), 2-hour post-load plasma glucose, updated homeostasis model assessment of beta cell function (HOMA2-%beta), HOMA2 of insulin sensitivity (HOMA2-%S), and fasting insulin were evaluated over a 12-year follow-up period.
TAKEAWAY:
- The post-load glucose was 3% lower in participants in the highest vs lowest quartile of total vegetable intake (ratio of means [RoM], 0.97; 95% CI, 0.96-0.99).
- Post-load glucose was 4% lower (RoM, 0.96; 95% CI, 0.95-0.98), HOMA2-%beta was 3% lower (RoM, 0.97; 95% CI, 0.96-0.99), and serum insulin was 5% lower (RoM, 0.95; 95% CI, 0.93-0.98) in those in the highest vs lowest quartile of green leafy vegetable intake.
- Those in the highest vs lowest quartile of potato fries or chips intake had 1% higher FPG, 3% higher HOMA2-%beta, and 8% higher serum insulin but 6% lower HOMA2-%S, revealing a negative impact on glucose tolerance and insulin sensitivity.
- The risk for T2D over 12 years was 26% and 25% lower among those in the highest and moderate quartiles of cruciferous vegetable intake, respectively, than among those in the lowest quartile of cruciferous vegetable intake.
IN PRACTICE:
The authors wrote that their study “sheds light on the physiological alterations in insulin regulation and glucose tolerance resulting from higher vegetable and subgroups of vegetable intake and supports the notion that vegetable subgroups may act differently in regulating insulin and blood glucose levels.”
SOURCE:
The study was led by Pratik Pokharel, MPH, Nutrition & Health Innovation Research Institute, School of Medical and Health Sciences, Edith Cowan University, Perth, Australia, and was published online in The Journal of Clinical Endocrinology & Metabolism.
LIMITATIONS:
The study’s observational nature precluded the inference of causality. Potential measurement errors in dietary exposures and recall bias linked to the food frequency questionnaire could have affected the findings. The overrepresentation of participants from higher education and socioeconomic subgroups and loss to follow-up could limit the generalizability of the findings.
DISCLOSURES:
The study was funded by the National Health and Medical Research Council, National Heart Foundation of Australia, and Royal Perth Hospital Medical Research Foundation. Several authors reported receiving grants from various sources during the conduct of this study. The other authors reported no conflicts of interest.
A version of this article appeared on Medscape.com.
Frontal Fibrosing Alopecia: Study Finds Oral Contraceptive Use Modulates Risk In Women with Genetic Variant
TOPLINE:
Investigators found that .
METHODOLOGY:
- OC use has been considered a possible factor behind the increased incidence of FFA because it was first documented in 1994, and a recent genome-wide association study of FFA identified a signal for an association with a variant in CYP1B1.
- The same researchers conducted a gene-environment interaction study with a case-control design involving 489 White female patients (mean age, 65.8 years) with FFA and 34,254 controls, matched for age and genetic ancestry.
- Data were collected from July 2015 to September 2017 and analyzed from October 2022 to December 2023.
- The study aimed to investigate the modulatory effect of OC use on the CYP1B1 variant’s impact on FFA risk, using logistic regression models for analysis.
TAKEAWAY:
- The use of OCs was associated with a 1.9 times greater risk for FFA in individuals with the specific CYP1B1 genetic variant, but there was no association among those with no history of OC use.
- The study suggests a significant gene-environment interaction, indicating that OC use may influence FFA risk in genetically predisposed individuals.
IN PRACTICE:
“This gene-environment interaction analysis suggests that the protective effect of the CYPIB1 missense variant on FFA risk might be mediated by exposure” to OCs, the authors wrote. The study, they added, “underscores the importance of considering genetic predispositions and environmental factors, such as oral contraceptive use, in understanding and managing frontal fibrosing alopecia.”
SOURCE:
Tuntas Rayinda, MD, MSc, PhD, of St. John’s Institute of Dermatology, King’s College London, led the study, which was published online May 29, 2024, in JAMA Dermatology.
LIMITATIONS:
The study’s reliance on self-reported OC use may have introduced recall and differences in ascertainment of OC use between patient and control groups and could have affected the study’s findings. The study also did not collect information on the type of OC used, which could have influenced the observed interaction.
DISCLOSURES:
The study was supported by the British Skin Foundation Young Investigator Award. One investigator reported being a subinvestigator on an alopecia areata study funded by Pfizer. No other disclosures were reported.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article appeared on Medscape.com.
TOPLINE:
Investigators found that .
METHODOLOGY:
- OC use has been considered a possible factor behind the increased incidence of FFA because it was first documented in 1994, and a recent genome-wide association study of FFA identified a signal for an association with a variant in CYP1B1.
- The same researchers conducted a gene-environment interaction study with a case-control design involving 489 White female patients (mean age, 65.8 years) with FFA and 34,254 controls, matched for age and genetic ancestry.
- Data were collected from July 2015 to September 2017 and analyzed from October 2022 to December 2023.
- The study aimed to investigate the modulatory effect of OC use on the CYP1B1 variant’s impact on FFA risk, using logistic regression models for analysis.
TAKEAWAY:
- The use of OCs was associated with a 1.9 times greater risk for FFA in individuals with the specific CYP1B1 genetic variant, but there was no association among those with no history of OC use.
- The study suggests a significant gene-environment interaction, indicating that OC use may influence FFA risk in genetically predisposed individuals.
IN PRACTICE:
“This gene-environment interaction analysis suggests that the protective effect of the CYPIB1 missense variant on FFA risk might be mediated by exposure” to OCs, the authors wrote. The study, they added, “underscores the importance of considering genetic predispositions and environmental factors, such as oral contraceptive use, in understanding and managing frontal fibrosing alopecia.”
SOURCE:
Tuntas Rayinda, MD, MSc, PhD, of St. John’s Institute of Dermatology, King’s College London, led the study, which was published online May 29, 2024, in JAMA Dermatology.
LIMITATIONS:
The study’s reliance on self-reported OC use may have introduced recall and differences in ascertainment of OC use between patient and control groups and could have affected the study’s findings. The study also did not collect information on the type of OC used, which could have influenced the observed interaction.
DISCLOSURES:
The study was supported by the British Skin Foundation Young Investigator Award. One investigator reported being a subinvestigator on an alopecia areata study funded by Pfizer. No other disclosures were reported.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article appeared on Medscape.com.
TOPLINE:
Investigators found that .
METHODOLOGY:
- OC use has been considered a possible factor behind the increased incidence of FFA because it was first documented in 1994, and a recent genome-wide association study of FFA identified a signal for an association with a variant in CYP1B1.
- The same researchers conducted a gene-environment interaction study with a case-control design involving 489 White female patients (mean age, 65.8 years) with FFA and 34,254 controls, matched for age and genetic ancestry.
- Data were collected from July 2015 to September 2017 and analyzed from October 2022 to December 2023.
- The study aimed to investigate the modulatory effect of OC use on the CYP1B1 variant’s impact on FFA risk, using logistic regression models for analysis.
TAKEAWAY:
- The use of OCs was associated with a 1.9 times greater risk for FFA in individuals with the specific CYP1B1 genetic variant, but there was no association among those with no history of OC use.
- The study suggests a significant gene-environment interaction, indicating that OC use may influence FFA risk in genetically predisposed individuals.
IN PRACTICE:
“This gene-environment interaction analysis suggests that the protective effect of the CYPIB1 missense variant on FFA risk might be mediated by exposure” to OCs, the authors wrote. The study, they added, “underscores the importance of considering genetic predispositions and environmental factors, such as oral contraceptive use, in understanding and managing frontal fibrosing alopecia.”
SOURCE:
Tuntas Rayinda, MD, MSc, PhD, of St. John’s Institute of Dermatology, King’s College London, led the study, which was published online May 29, 2024, in JAMA Dermatology.
LIMITATIONS:
The study’s reliance on self-reported OC use may have introduced recall and differences in ascertainment of OC use between patient and control groups and could have affected the study’s findings. The study also did not collect information on the type of OC used, which could have influenced the observed interaction.
DISCLOSURES:
The study was supported by the British Skin Foundation Young Investigator Award. One investigator reported being a subinvestigator on an alopecia areata study funded by Pfizer. No other disclosures were reported.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article appeared on Medscape.com.
USPSTF Recommends Exercise To Prevent Falls in Older Adults
Exercise interventions are recommended to help prevent falls and fall-related morbidity in community-dwelling adults aged 65 years and older who are at increased risk of falls, according to a new recommendation statement from the U.S. Preventive Services Task Force (USPSTF) (JAMA. 2024 Jun 4. doi: 10.1001/jama.2024.8481).
Falls remain the leading cause of injury-related morbidity and mortality among older adults in the United States, with approximately 27% of community-dwelling individuals aged 65 years and older reporting at least one fall in the past year, wrote lead author Wanda K. Nicholson, MD, of George Washington University, Washington, and colleagues.
The task force concluded with moderate certainty that exercise interventions yielded a moderate benefit in fall reduction among older adults at risk (grade B recommendation).
The decision to offer multifactorial fall prevention interventions to older adults at risk for falls should be individualized based on assessment of potential risks and benefits of these interventions, including circumstances of prior falls, presence of comorbid medical conditions, and the patient’s values and preferences (grade C recommendation), the authors wrote.
The exercise intervention could include individual or group activity, although most of the studies in the systematic review involved group exercise, the authors noted.
The recommendation was based on data from a systematic evidence review published in JAMA (2024 Jun 4. doi: 10.1001/jama.2024.4166). The task force reviewed data from 83 randomized trials published between January 1, 2016, and May 8, 2023, deemed fair to good quality that examined six types of fall prevention interventions in a total of 48,839 individuals. Of these, 28 studies involved multifactorial interventions and 27 involved exercise interventions.
Overall, multifactorial interventions and exercise interventions were associated with a significant reduction in falls (incidence rate ratio 0.84 and 0.85, respectively).
Exercise interventions were significantly associated with reduced individual risk of one or more falls and injurious falls, but not with reduced individual risk of injurious falls. However, multifactorial interventions were not significantly associated with reductions in risk of one or more falls, injurious falls, fall-related fractures, individual risk of injurious falls, or individual risk of fall-related fractures.
Although teasing out the specific exercise components that are most effective for fall prevention is challenging, the most commonly studied components associated with reduced risk of falls included gait training, balance training, and functional training, followed by strength and resistance training, the task force noted.
Duration of exercise interventions in the reviewed studies ranged from 2 to 30 months and the most common frequency of sessions was 2 to 3 per week.
Based on these findings, the task force found that exercise had the most consistent benefits for reduced risk across several fall-related outcomes. Although individuals in the studies of multifactorial interventions were at increased risk for falls, the multistep process of interventions to address an individual’s multiple risk factors limited their effectiveness, in part because of logistical challenges and inconsistent adherence, the authors wrote.
The results of the review were limited by several factors, including the focus on studies with a primary or secondary aim of fall prevention, the fact that the recommendation does not apply to many subgroups of older adults, and the lack of data on health outcomes unrelated to falls that were associated with the interventions, the authors noted.
The new recommendation is consistent with and replaces the 2018 USPSTF recommendation on interventions for fall prevention in community-dwelling older adults, but without the recommendation against vitamin D supplementation as a fall prevention intervention. The new recommendation does not address vitamin D use; evidence will be examined in a separate recommendation, the task force wrote.
How to Get Older Adults Moving
“The biggest obstacle to exercise is patient inertia and choice to engage in other sedentary activities,” David B. Reuben, MD, and David A. Ganz, MD, both of the University of California, Los Angeles, wrote in an accompanying editorial (JAMA. 2024 Jun 4. doi: 10.1001/jama.2024.9063).
“Given the demonstrated benefits of exercise for cardiovascular disease, cognitive function, and favorable associations with all-cause, cardiovascular, and cancer mortality, specific fall prevention exercise recommendations need to be considered in the context of universal exercise recommendations, including aerobic and muscle strengthening exercise,” the authors wrote. However, maintaining regular exercise is a challenge for many older adults, and more research is needed on factors that drive exercise initiation and adherence in this population, they said.
Multifactorial fall assessments in particular take time, and more fall prevention programs are needed that include multifactorial assessments and interventions, the editorialists said. “Even if primary care clinicians faithfully implement the USPSTF recommendations, a significant reduction in falls and their resulting injuries is still far off,” in part, because of the need for more programs and policies, and the need to improve access to exercise programs and provide insurance coverage for them, they noted.
“Above all, older persons need to be active participants in exercise and reduction of risk factors for falls,” the editorialists concluded.
The research for the recommendation was funded by the Agency for Healthcare Research and Quality (AHRQ). The authors had no financial conflicts to disclose. Dr. Ganz disclosed serving as an author of the 2022 World Guidelines for Falls Prevention and Management for Older Adults.
Exercise interventions are recommended to help prevent falls and fall-related morbidity in community-dwelling adults aged 65 years and older who are at increased risk of falls, according to a new recommendation statement from the U.S. Preventive Services Task Force (USPSTF) (JAMA. 2024 Jun 4. doi: 10.1001/jama.2024.8481).
Falls remain the leading cause of injury-related morbidity and mortality among older adults in the United States, with approximately 27% of community-dwelling individuals aged 65 years and older reporting at least one fall in the past year, wrote lead author Wanda K. Nicholson, MD, of George Washington University, Washington, and colleagues.
The task force concluded with moderate certainty that exercise interventions yielded a moderate benefit in fall reduction among older adults at risk (grade B recommendation).
The decision to offer multifactorial fall prevention interventions to older adults at risk for falls should be individualized based on assessment of potential risks and benefits of these interventions, including circumstances of prior falls, presence of comorbid medical conditions, and the patient’s values and preferences (grade C recommendation), the authors wrote.
The exercise intervention could include individual or group activity, although most of the studies in the systematic review involved group exercise, the authors noted.
The recommendation was based on data from a systematic evidence review published in JAMA (2024 Jun 4. doi: 10.1001/jama.2024.4166). The task force reviewed data from 83 randomized trials published between January 1, 2016, and May 8, 2023, deemed fair to good quality that examined six types of fall prevention interventions in a total of 48,839 individuals. Of these, 28 studies involved multifactorial interventions and 27 involved exercise interventions.
Overall, multifactorial interventions and exercise interventions were associated with a significant reduction in falls (incidence rate ratio 0.84 and 0.85, respectively).
Exercise interventions were significantly associated with reduced individual risk of one or more falls and injurious falls, but not with reduced individual risk of injurious falls. However, multifactorial interventions were not significantly associated with reductions in risk of one or more falls, injurious falls, fall-related fractures, individual risk of injurious falls, or individual risk of fall-related fractures.
Although teasing out the specific exercise components that are most effective for fall prevention is challenging, the most commonly studied components associated with reduced risk of falls included gait training, balance training, and functional training, followed by strength and resistance training, the task force noted.
Duration of exercise interventions in the reviewed studies ranged from 2 to 30 months and the most common frequency of sessions was 2 to 3 per week.
Based on these findings, the task force found that exercise had the most consistent benefits for reduced risk across several fall-related outcomes. Although individuals in the studies of multifactorial interventions were at increased risk for falls, the multistep process of interventions to address an individual’s multiple risk factors limited their effectiveness, in part because of logistical challenges and inconsistent adherence, the authors wrote.
The results of the review were limited by several factors, including the focus on studies with a primary or secondary aim of fall prevention, the fact that the recommendation does not apply to many subgroups of older adults, and the lack of data on health outcomes unrelated to falls that were associated with the interventions, the authors noted.
The new recommendation is consistent with and replaces the 2018 USPSTF recommendation on interventions for fall prevention in community-dwelling older adults, but without the recommendation against vitamin D supplementation as a fall prevention intervention. The new recommendation does not address vitamin D use; evidence will be examined in a separate recommendation, the task force wrote.
How to Get Older Adults Moving
“The biggest obstacle to exercise is patient inertia and choice to engage in other sedentary activities,” David B. Reuben, MD, and David A. Ganz, MD, both of the University of California, Los Angeles, wrote in an accompanying editorial (JAMA. 2024 Jun 4. doi: 10.1001/jama.2024.9063).
“Given the demonstrated benefits of exercise for cardiovascular disease, cognitive function, and favorable associations with all-cause, cardiovascular, and cancer mortality, specific fall prevention exercise recommendations need to be considered in the context of universal exercise recommendations, including aerobic and muscle strengthening exercise,” the authors wrote. However, maintaining regular exercise is a challenge for many older adults, and more research is needed on factors that drive exercise initiation and adherence in this population, they said.
Multifactorial fall assessments in particular take time, and more fall prevention programs are needed that include multifactorial assessments and interventions, the editorialists said. “Even if primary care clinicians faithfully implement the USPSTF recommendations, a significant reduction in falls and their resulting injuries is still far off,” in part, because of the need for more programs and policies, and the need to improve access to exercise programs and provide insurance coverage for them, they noted.
“Above all, older persons need to be active participants in exercise and reduction of risk factors for falls,” the editorialists concluded.
The research for the recommendation was funded by the Agency for Healthcare Research and Quality (AHRQ). The authors had no financial conflicts to disclose. Dr. Ganz disclosed serving as an author of the 2022 World Guidelines for Falls Prevention and Management for Older Adults.
Exercise interventions are recommended to help prevent falls and fall-related morbidity in community-dwelling adults aged 65 years and older who are at increased risk of falls, according to a new recommendation statement from the U.S. Preventive Services Task Force (USPSTF) (JAMA. 2024 Jun 4. doi: 10.1001/jama.2024.8481).
Falls remain the leading cause of injury-related morbidity and mortality among older adults in the United States, with approximately 27% of community-dwelling individuals aged 65 years and older reporting at least one fall in the past year, wrote lead author Wanda K. Nicholson, MD, of George Washington University, Washington, and colleagues.
The task force concluded with moderate certainty that exercise interventions yielded a moderate benefit in fall reduction among older adults at risk (grade B recommendation).
The decision to offer multifactorial fall prevention interventions to older adults at risk for falls should be individualized based on assessment of potential risks and benefits of these interventions, including circumstances of prior falls, presence of comorbid medical conditions, and the patient’s values and preferences (grade C recommendation), the authors wrote.
The exercise intervention could include individual or group activity, although most of the studies in the systematic review involved group exercise, the authors noted.
The recommendation was based on data from a systematic evidence review published in JAMA (2024 Jun 4. doi: 10.1001/jama.2024.4166). The task force reviewed data from 83 randomized trials published between January 1, 2016, and May 8, 2023, deemed fair to good quality that examined six types of fall prevention interventions in a total of 48,839 individuals. Of these, 28 studies involved multifactorial interventions and 27 involved exercise interventions.
Overall, multifactorial interventions and exercise interventions were associated with a significant reduction in falls (incidence rate ratio 0.84 and 0.85, respectively).
Exercise interventions were significantly associated with reduced individual risk of one or more falls and injurious falls, but not with reduced individual risk of injurious falls. However, multifactorial interventions were not significantly associated with reductions in risk of one or more falls, injurious falls, fall-related fractures, individual risk of injurious falls, or individual risk of fall-related fractures.
Although teasing out the specific exercise components that are most effective for fall prevention is challenging, the most commonly studied components associated with reduced risk of falls included gait training, balance training, and functional training, followed by strength and resistance training, the task force noted.
Duration of exercise interventions in the reviewed studies ranged from 2 to 30 months and the most common frequency of sessions was 2 to 3 per week.
Based on these findings, the task force found that exercise had the most consistent benefits for reduced risk across several fall-related outcomes. Although individuals in the studies of multifactorial interventions were at increased risk for falls, the multistep process of interventions to address an individual’s multiple risk factors limited their effectiveness, in part because of logistical challenges and inconsistent adherence, the authors wrote.
The results of the review were limited by several factors, including the focus on studies with a primary or secondary aim of fall prevention, the fact that the recommendation does not apply to many subgroups of older adults, and the lack of data on health outcomes unrelated to falls that were associated with the interventions, the authors noted.
The new recommendation is consistent with and replaces the 2018 USPSTF recommendation on interventions for fall prevention in community-dwelling older adults, but without the recommendation against vitamin D supplementation as a fall prevention intervention. The new recommendation does not address vitamin D use; evidence will be examined in a separate recommendation, the task force wrote.
How to Get Older Adults Moving
“The biggest obstacle to exercise is patient inertia and choice to engage in other sedentary activities,” David B. Reuben, MD, and David A. Ganz, MD, both of the University of California, Los Angeles, wrote in an accompanying editorial (JAMA. 2024 Jun 4. doi: 10.1001/jama.2024.9063).
“Given the demonstrated benefits of exercise for cardiovascular disease, cognitive function, and favorable associations with all-cause, cardiovascular, and cancer mortality, specific fall prevention exercise recommendations need to be considered in the context of universal exercise recommendations, including aerobic and muscle strengthening exercise,” the authors wrote. However, maintaining regular exercise is a challenge for many older adults, and more research is needed on factors that drive exercise initiation and adherence in this population, they said.
Multifactorial fall assessments in particular take time, and more fall prevention programs are needed that include multifactorial assessments and interventions, the editorialists said. “Even if primary care clinicians faithfully implement the USPSTF recommendations, a significant reduction in falls and their resulting injuries is still far off,” in part, because of the need for more programs and policies, and the need to improve access to exercise programs and provide insurance coverage for them, they noted.
“Above all, older persons need to be active participants in exercise and reduction of risk factors for falls,” the editorialists concluded.
The research for the recommendation was funded by the Agency for Healthcare Research and Quality (AHRQ). The authors had no financial conflicts to disclose. Dr. Ganz disclosed serving as an author of the 2022 World Guidelines for Falls Prevention and Management for Older Adults.
FROM JAMA
New Drug Combo Boosts PFS
At a median follow-up of 4 years, progression-free survival for the new treatment, known as BrECADD, was 94.3% vs. 90.9% for BEACOPP (hazard ratio, 0.66, 95% CI, P = .035), researchers led by Peter Borchmann, MD, assistant medical director of hematology and oncology at the University Hospital of Cologne, Germany, reported at the annual meeting of the American Society of Clinical Oncology (ASCO).
“These results are really striking,” said hematologist-oncologist Oreofe O. Odejide, MD, MPH, of the Dana-Farber Cancer Institute and Harvard Medical School, Boston, who was not involved in the study and commented on it during an ASCO news briefing. “This is really poised to impact the standard-of-care treatment for patients with advanced-stage classical Hodgkin lymphoma.”
As Dr. Borchmann explained at the briefing, Hodgkin lymphoma is the most common cancer among young adults. “The median age at onset is around 30 years, and it can be primarily cured with chemotherapy. Intensified chemotherapy probably is better primary lymphoma control than less intensive treatment, but this comes at the cost of treatment-related adverse events.”
Dr. Borchmann and colleagues developed the existing treatment known as BEACOPP, a combination of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone. “It’s our standard of care due to its high primary cure rate, which is reflected by compelling progression-free survival,” he said.
However, he said, “it’s a high burden of treatment.” The investigational treatment, BrECADD, includes six drugs instead of seven: brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone. Two of the additions — brentuximab vedotin and dacarbazine — are cancer drugs, and dexamethasone is a steroid. There is one fewer cancer drug in the new formulation.
In the international HD21 trial (9 countries, 233 sites), researchers recruited patients aged 18-60 who received four or six cycles of either BEACOPP or BrECADD. The doses were guided by PET2 findings.
In the intention-to-treat cohort of 1,482 subjects (median age 31.1, 44% female), 742 were assigned to BrECADD and 740 to BEACOPP.
There were few early treatment failures in the BrECADD group vs. BEACOPP. The numbers who had primary progression within the first 3 months were 5 vs. 15, respectively, and the numbers reaching early relapse between months 3 and 12 were 11 vs. 23, respectively.
Four-year overall survival rates in the groups were nearly identical at 98.5% for BrECADD and 98.2% for BEACOPP. In regard to fertility, follicle-stimulating hormone recovery rates after 1 year were higher in the BrECADD group in both men (67% vs. 24%, respectively) and women (89% vs. 68%, respectively). Birth rates were also higher in the BrECADD group (n = 60 vs. n = 43 in the BEACOPP group).
Nearly two-thirds of those in BrECADD group (64%) required 12 weeks of therapy — four cycles. As for treatment-related morbidity toxicities, they were less common in the BrECADD group vs. the BEACOPP group (42% vs. 59%, respectively, P < .0001), and 1% of BrECADD-treated had them at 1 year.
Oncologist Julie R. Gralow, MD, chief medical officer and executive vice president of ASCO, welcomed the findings at the ACO news briefing. “By replacing some pretty toxic chemo with an antibody-drug conjugate [brentuximab vedotin], and changing the regimen a bit, and using PET scan to determine the number of cycles received, the long-term outcomes were maintained, if not even improved upon,” said Dr. Dr. Gralow, who was not involved in the study.
In addition, she said, the findings about fertility are good news because “these are young people who probably haven’t started a family yet, and we’re increasing the odds that they will be able to do so after survival.”
Moving forward, she said, “we will need to have some discussion on how this relates to ABVD, which is a more commonly used regimen in the United States right now.” ABVD refers to a combination of doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, and dacarbazine.
Takeda funded the study. Dr. Borchmann reported ties with BMS, GmbH & Co, Incyte, MSD/Merck, Roche, Takeda/Millennium, Miltenyi, Amgen, and Novartis. Some of the other study authors reported various disclosures. Dr. Odejide and Dr. Gralow have no disclosures.
At a median follow-up of 4 years, progression-free survival for the new treatment, known as BrECADD, was 94.3% vs. 90.9% for BEACOPP (hazard ratio, 0.66, 95% CI, P = .035), researchers led by Peter Borchmann, MD, assistant medical director of hematology and oncology at the University Hospital of Cologne, Germany, reported at the annual meeting of the American Society of Clinical Oncology (ASCO).
“These results are really striking,” said hematologist-oncologist Oreofe O. Odejide, MD, MPH, of the Dana-Farber Cancer Institute and Harvard Medical School, Boston, who was not involved in the study and commented on it during an ASCO news briefing. “This is really poised to impact the standard-of-care treatment for patients with advanced-stage classical Hodgkin lymphoma.”
As Dr. Borchmann explained at the briefing, Hodgkin lymphoma is the most common cancer among young adults. “The median age at onset is around 30 years, and it can be primarily cured with chemotherapy. Intensified chemotherapy probably is better primary lymphoma control than less intensive treatment, but this comes at the cost of treatment-related adverse events.”
Dr. Borchmann and colleagues developed the existing treatment known as BEACOPP, a combination of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone. “It’s our standard of care due to its high primary cure rate, which is reflected by compelling progression-free survival,” he said.
However, he said, “it’s a high burden of treatment.” The investigational treatment, BrECADD, includes six drugs instead of seven: brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone. Two of the additions — brentuximab vedotin and dacarbazine — are cancer drugs, and dexamethasone is a steroid. There is one fewer cancer drug in the new formulation.
In the international HD21 trial (9 countries, 233 sites), researchers recruited patients aged 18-60 who received four or six cycles of either BEACOPP or BrECADD. The doses were guided by PET2 findings.
In the intention-to-treat cohort of 1,482 subjects (median age 31.1, 44% female), 742 were assigned to BrECADD and 740 to BEACOPP.
There were few early treatment failures in the BrECADD group vs. BEACOPP. The numbers who had primary progression within the first 3 months were 5 vs. 15, respectively, and the numbers reaching early relapse between months 3 and 12 were 11 vs. 23, respectively.
Four-year overall survival rates in the groups were nearly identical at 98.5% for BrECADD and 98.2% for BEACOPP. In regard to fertility, follicle-stimulating hormone recovery rates after 1 year were higher in the BrECADD group in both men (67% vs. 24%, respectively) and women (89% vs. 68%, respectively). Birth rates were also higher in the BrECADD group (n = 60 vs. n = 43 in the BEACOPP group).
Nearly two-thirds of those in BrECADD group (64%) required 12 weeks of therapy — four cycles. As for treatment-related morbidity toxicities, they were less common in the BrECADD group vs. the BEACOPP group (42% vs. 59%, respectively, P < .0001), and 1% of BrECADD-treated had them at 1 year.
Oncologist Julie R. Gralow, MD, chief medical officer and executive vice president of ASCO, welcomed the findings at the ACO news briefing. “By replacing some pretty toxic chemo with an antibody-drug conjugate [brentuximab vedotin], and changing the regimen a bit, and using PET scan to determine the number of cycles received, the long-term outcomes were maintained, if not even improved upon,” said Dr. Dr. Gralow, who was not involved in the study.
In addition, she said, the findings about fertility are good news because “these are young people who probably haven’t started a family yet, and we’re increasing the odds that they will be able to do so after survival.”
Moving forward, she said, “we will need to have some discussion on how this relates to ABVD, which is a more commonly used regimen in the United States right now.” ABVD refers to a combination of doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, and dacarbazine.
Takeda funded the study. Dr. Borchmann reported ties with BMS, GmbH & Co, Incyte, MSD/Merck, Roche, Takeda/Millennium, Miltenyi, Amgen, and Novartis. Some of the other study authors reported various disclosures. Dr. Odejide and Dr. Gralow have no disclosures.
At a median follow-up of 4 years, progression-free survival for the new treatment, known as BrECADD, was 94.3% vs. 90.9% for BEACOPP (hazard ratio, 0.66, 95% CI, P = .035), researchers led by Peter Borchmann, MD, assistant medical director of hematology and oncology at the University Hospital of Cologne, Germany, reported at the annual meeting of the American Society of Clinical Oncology (ASCO).
“These results are really striking,” said hematologist-oncologist Oreofe O. Odejide, MD, MPH, of the Dana-Farber Cancer Institute and Harvard Medical School, Boston, who was not involved in the study and commented on it during an ASCO news briefing. “This is really poised to impact the standard-of-care treatment for patients with advanced-stage classical Hodgkin lymphoma.”
As Dr. Borchmann explained at the briefing, Hodgkin lymphoma is the most common cancer among young adults. “The median age at onset is around 30 years, and it can be primarily cured with chemotherapy. Intensified chemotherapy probably is better primary lymphoma control than less intensive treatment, but this comes at the cost of treatment-related adverse events.”
Dr. Borchmann and colleagues developed the existing treatment known as BEACOPP, a combination of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone. “It’s our standard of care due to its high primary cure rate, which is reflected by compelling progression-free survival,” he said.
However, he said, “it’s a high burden of treatment.” The investigational treatment, BrECADD, includes six drugs instead of seven: brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone. Two of the additions — brentuximab vedotin and dacarbazine — are cancer drugs, and dexamethasone is a steroid. There is one fewer cancer drug in the new formulation.
In the international HD21 trial (9 countries, 233 sites), researchers recruited patients aged 18-60 who received four or six cycles of either BEACOPP or BrECADD. The doses were guided by PET2 findings.
In the intention-to-treat cohort of 1,482 subjects (median age 31.1, 44% female), 742 were assigned to BrECADD and 740 to BEACOPP.
There were few early treatment failures in the BrECADD group vs. BEACOPP. The numbers who had primary progression within the first 3 months were 5 vs. 15, respectively, and the numbers reaching early relapse between months 3 and 12 were 11 vs. 23, respectively.
Four-year overall survival rates in the groups were nearly identical at 98.5% for BrECADD and 98.2% for BEACOPP. In regard to fertility, follicle-stimulating hormone recovery rates after 1 year were higher in the BrECADD group in both men (67% vs. 24%, respectively) and women (89% vs. 68%, respectively). Birth rates were also higher in the BrECADD group (n = 60 vs. n = 43 in the BEACOPP group).
Nearly two-thirds of those in BrECADD group (64%) required 12 weeks of therapy — four cycles. As for treatment-related morbidity toxicities, they were less common in the BrECADD group vs. the BEACOPP group (42% vs. 59%, respectively, P < .0001), and 1% of BrECADD-treated had them at 1 year.
Oncologist Julie R. Gralow, MD, chief medical officer and executive vice president of ASCO, welcomed the findings at the ACO news briefing. “By replacing some pretty toxic chemo with an antibody-drug conjugate [brentuximab vedotin], and changing the regimen a bit, and using PET scan to determine the number of cycles received, the long-term outcomes were maintained, if not even improved upon,” said Dr. Dr. Gralow, who was not involved in the study.
In addition, she said, the findings about fertility are good news because “these are young people who probably haven’t started a family yet, and we’re increasing the odds that they will be able to do so after survival.”
Moving forward, she said, “we will need to have some discussion on how this relates to ABVD, which is a more commonly used regimen in the United States right now.” ABVD refers to a combination of doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, and dacarbazine.
Takeda funded the study. Dr. Borchmann reported ties with BMS, GmbH & Co, Incyte, MSD/Merck, Roche, Takeda/Millennium, Miltenyi, Amgen, and Novartis. Some of the other study authors reported various disclosures. Dr. Odejide and Dr. Gralow have no disclosures.
FROM ASCO 2024
CML: Asciminib Bests Standard TKIs as Frontline Therapy
“In the ASC4FIRST trial, asciminib is the first and only agent to demonstrate statistically significant efficacy versus standard-of-care frontline TKIs in newly diagnosed CML patients,” said senior author Jorge E. Cortes, MD, director of the Georgia Cancer Center at Augusta University in Georgia, in presenting the findings at a press briefing for the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.
”Asciminib’s strong benefit-risk profile may transform the CML treatment paradigm,” Dr. Cortes said.
The study was published concurrently in The New England Journal of Medicine.
While TKIs have transformed the treatment of CML, improving the 5-year survival rates from 22% in the 1970s to 70% in recent years, nearly half of patients do not achieve a major molecular response within a year, due to either resistance or intolerance, causing the common switching of drugs.
Long-term use is further associated with common side effects, including gastrointestinal and cardiovascular events, due to off-target effects.
Asciminib is a potent and highly specific agent is an allosteric inhibitor targeting ABL myristoyl pocket, which is important in avoiding off-target effects that cause the common side effects.
The drug already has approval from the US Food and Drug Administration (FDA) for the treatment of patients with chronic phase CML who are resistant or intolerant to at least 2 prior TKIs or those with T315I mutation.
For the current pivotal phase 3 ASC4FIRST trial to evaluate the drug as a frontline therapy in recently diagnosed patients with chronic phase CML, 405 patients from cancer centers in 29 countries were enrolled.
The participants were randomized to treatment either with asciminib 80 mg once daily (n = 201) or to an investigator-selected TKI (n = 204), determined based on factors including patient age, preference, and overall health.
In the latter group, 102 patients were receiving imatinib and an equal number receive a stronger, second-generation TKI.
Overall, the patients had a median age of 52 and 65% were male. About 54% were White and 44% were Asian. Those receiving second-generation TKIs were more likely to be younger and without additional health concerns, allowing them to tolerate the more potent drugs.
The median follow-up was 16.3 months in the asciminib group and 15.7 months in the other TKIs group.
For the primary outcome, a major molecular response occurred at week 48 among 67.7% of patients in the asciminib group, compared with 49% in the combined TKI arm of imatinib and second-generation TKI groups (P < .001).
In a subanalysis of patients who were randomized to receive imatinib, a major molecular response occurred at week 48 in 69.3% in the asciminib group versus 40.2% of patients in the imatinib arm (P < .001).
The corresponding rates in the comparison of patients on second-generation TKIs were 66.0% and 57.8%, which was not a statistically significant difference.
Furthermore, a deep molecular response, which may lead to remission and discontinuation of treatment, occurred at week 48 in among 38.8% in the asciminib arm compared with the 20.6% in the combined investigator-selected TKI arm.
In the imatinib comparison analysis, the deep molecular response occurred in 42.6% of patients in the asciminib arm versus 17.8% in the imatinib arm, and in the second-generation TKI arm, the deep molecular response occurred in 35% versus 26.5%, respectively.
Importantly, in the TKI-treated group, significantly more patients in the asciminib group — 86%, remained on therapy at the data cut-off, compared with 62% of those receiving imatinib and 75% of those receiving a second generation TKI.
Adverse events of grade 3 or higher that led to discontinuation were lower with asciminib versus imatinib and second-generation TKIs (38% vs 44.4% and 54.9%, respectively), as were events leading to discontinuation (4.5% versus 11.1% and 9.8%, respectively).
The most common adverse events occurring with asciminib were low platelet count (13%) and low neutrophil count (10%). In terms of severe side effects, blood clots, a known severe side effect of TKIs, occurred in only 1% of patients.
In addition, dose adjustments and treatment interruptions were also more significantly less common in the asciminib group.
Overall, the results indicate that “asciminib has the potential to become a therapy of choice for patients with newly diagnosed chronic phase CML,” said first author Timothy P. Hughes, MD, of South Australian Health and Medical Research Institute and University of Adelaide, Australia, in presenting the findings.
Commenting on the study in an interview, Dr. Cortes underscored the importance of molecular responses as indicators of longer-term responses.
“Early responses correlate with better long-term outcomes,” he said. “Most importantly, they are associated with better probabilities of having a deep molecular response, a requirement for considerations of treatment discontinuation,” which is a highly desirable goal for many patients, he noted.
“If we can get more patients to be eligible for treatment discontinuation and to discontinue successfully, this could be a major advance,” Dr. Cortes emphasized.
“Also, for the patients who do have to stay on therapy for the rest of their lives, a treatment option that has fewer adverse events would be very desirable,” he said.
“We need to see that longer follow-up confirms the current trends, but we are very encouraged by what we see so far.”
Impressive Results; Financial Toxicity Concerns
In discussing the significance of the findings at the meeting, Pankit Vachhani, MD, assistant professor of medicine at the University of Alabama at Birmingham, said the efficacy and toxicity profiles with asciminib were impressive.
“The nearly 70% major molecular response is one of the highest rates that we have seen in clinical trials at week 48,” he said. “That’s great and maybe we will see deeper responses with time.”
He added that the toxicity profile “was better than imagined — frankly I did not expect that, so that’s a welcome surprise, but we do need longer-term data especially on arterial occlusive events not to mention some other adverse events as well.”
“The question to ask ourselves, though, is whether the use of lower dose first- or second-generation TKIs leads to comparable amounts of toxicities.”
Dr. Vachhani raised the concern of cost: “There is the issue of financial toxicity,” he noted. “At current prices, treatment using asciminib would come to approximately $260,000 per year in terms of the cost to the healthcare system,” he said.
“Meanwhile, imatinib right now, in the US, can be obtained for $500 per year, and additional TKIs are going generic [soon],” he said, noting that survival differences remain unclear.
Further commenting, Eunice Wang, MD, associate professor of medicine at the Roswell Park Cancer Institute in Buffalo, New York, agreed that the results are impressive, saying the trial supports asciminib as “the new standard of care of first line therapy of newly diagnosed CML based on both efficacy.”
Dr. Wang, who moderated the ASCO session, noted the caveat that “given the chronicity of this disease, it is important to continue to follow the patients enrolled on this study for longevity and durability of these efficacy endpoints.”
Nevertheless, “given the lower discontinuation rates versus other TKIs and the fact that, in my opinion, most patients who stop drug will do so in the first 6-12 months if not tolerated, these results are highly promising,” she said.
Dr. Wang also agreed, however, that the rising costs of the TKIs are an important concern.
“All of the BCR-ABL TKIs except imatinib already cost several thousand dollars per month, but there is a trend that newer agents are priced higher than prior,” she said. “This needs to be addressed as $10-$20K per month is not reasonable, and the pharmaceutical companies need to be aware.
“Yes, the data with asciminib is better, but if many patients who respond to imatinib just take longer and there is no difference in overall or disease-free survival long-term, the financial costs are a serious topic of discussion,” Dr. Wang noted.
The study was funded by Novartis. Dr. Cortes disclosed ties with Ascentage Pharma, Bio-Path Holdings, BMS, Novartis, Pfizer, Rigel Pharmeuticals, Sun Pharmaceutical Industries, and Takeda Oncology. Dr. Vachhani and Dr. Wang reported various disclosures.
“In the ASC4FIRST trial, asciminib is the first and only agent to demonstrate statistically significant efficacy versus standard-of-care frontline TKIs in newly diagnosed CML patients,” said senior author Jorge E. Cortes, MD, director of the Georgia Cancer Center at Augusta University in Georgia, in presenting the findings at a press briefing for the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.
”Asciminib’s strong benefit-risk profile may transform the CML treatment paradigm,” Dr. Cortes said.
The study was published concurrently in The New England Journal of Medicine.
While TKIs have transformed the treatment of CML, improving the 5-year survival rates from 22% in the 1970s to 70% in recent years, nearly half of patients do not achieve a major molecular response within a year, due to either resistance or intolerance, causing the common switching of drugs.
Long-term use is further associated with common side effects, including gastrointestinal and cardiovascular events, due to off-target effects.
Asciminib is a potent and highly specific agent is an allosteric inhibitor targeting ABL myristoyl pocket, which is important in avoiding off-target effects that cause the common side effects.
The drug already has approval from the US Food and Drug Administration (FDA) for the treatment of patients with chronic phase CML who are resistant or intolerant to at least 2 prior TKIs or those with T315I mutation.
For the current pivotal phase 3 ASC4FIRST trial to evaluate the drug as a frontline therapy in recently diagnosed patients with chronic phase CML, 405 patients from cancer centers in 29 countries were enrolled.
The participants were randomized to treatment either with asciminib 80 mg once daily (n = 201) or to an investigator-selected TKI (n = 204), determined based on factors including patient age, preference, and overall health.
In the latter group, 102 patients were receiving imatinib and an equal number receive a stronger, second-generation TKI.
Overall, the patients had a median age of 52 and 65% were male. About 54% were White and 44% were Asian. Those receiving second-generation TKIs were more likely to be younger and without additional health concerns, allowing them to tolerate the more potent drugs.
The median follow-up was 16.3 months in the asciminib group and 15.7 months in the other TKIs group.
For the primary outcome, a major molecular response occurred at week 48 among 67.7% of patients in the asciminib group, compared with 49% in the combined TKI arm of imatinib and second-generation TKI groups (P < .001).
In a subanalysis of patients who were randomized to receive imatinib, a major molecular response occurred at week 48 in 69.3% in the asciminib group versus 40.2% of patients in the imatinib arm (P < .001).
The corresponding rates in the comparison of patients on second-generation TKIs were 66.0% and 57.8%, which was not a statistically significant difference.
Furthermore, a deep molecular response, which may lead to remission and discontinuation of treatment, occurred at week 48 in among 38.8% in the asciminib arm compared with the 20.6% in the combined investigator-selected TKI arm.
In the imatinib comparison analysis, the deep molecular response occurred in 42.6% of patients in the asciminib arm versus 17.8% in the imatinib arm, and in the second-generation TKI arm, the deep molecular response occurred in 35% versus 26.5%, respectively.
Importantly, in the TKI-treated group, significantly more patients in the asciminib group — 86%, remained on therapy at the data cut-off, compared with 62% of those receiving imatinib and 75% of those receiving a second generation TKI.
Adverse events of grade 3 or higher that led to discontinuation were lower with asciminib versus imatinib and second-generation TKIs (38% vs 44.4% and 54.9%, respectively), as were events leading to discontinuation (4.5% versus 11.1% and 9.8%, respectively).
The most common adverse events occurring with asciminib were low platelet count (13%) and low neutrophil count (10%). In terms of severe side effects, blood clots, a known severe side effect of TKIs, occurred in only 1% of patients.
In addition, dose adjustments and treatment interruptions were also more significantly less common in the asciminib group.
Overall, the results indicate that “asciminib has the potential to become a therapy of choice for patients with newly diagnosed chronic phase CML,” said first author Timothy P. Hughes, MD, of South Australian Health and Medical Research Institute and University of Adelaide, Australia, in presenting the findings.
Commenting on the study in an interview, Dr. Cortes underscored the importance of molecular responses as indicators of longer-term responses.
“Early responses correlate with better long-term outcomes,” he said. “Most importantly, they are associated with better probabilities of having a deep molecular response, a requirement for considerations of treatment discontinuation,” which is a highly desirable goal for many patients, he noted.
“If we can get more patients to be eligible for treatment discontinuation and to discontinue successfully, this could be a major advance,” Dr. Cortes emphasized.
“Also, for the patients who do have to stay on therapy for the rest of their lives, a treatment option that has fewer adverse events would be very desirable,” he said.
“We need to see that longer follow-up confirms the current trends, but we are very encouraged by what we see so far.”
Impressive Results; Financial Toxicity Concerns
In discussing the significance of the findings at the meeting, Pankit Vachhani, MD, assistant professor of medicine at the University of Alabama at Birmingham, said the efficacy and toxicity profiles with asciminib were impressive.
“The nearly 70% major molecular response is one of the highest rates that we have seen in clinical trials at week 48,” he said. “That’s great and maybe we will see deeper responses with time.”
He added that the toxicity profile “was better than imagined — frankly I did not expect that, so that’s a welcome surprise, but we do need longer-term data especially on arterial occlusive events not to mention some other adverse events as well.”
“The question to ask ourselves, though, is whether the use of lower dose first- or second-generation TKIs leads to comparable amounts of toxicities.”
Dr. Vachhani raised the concern of cost: “There is the issue of financial toxicity,” he noted. “At current prices, treatment using asciminib would come to approximately $260,000 per year in terms of the cost to the healthcare system,” he said.
“Meanwhile, imatinib right now, in the US, can be obtained for $500 per year, and additional TKIs are going generic [soon],” he said, noting that survival differences remain unclear.
Further commenting, Eunice Wang, MD, associate professor of medicine at the Roswell Park Cancer Institute in Buffalo, New York, agreed that the results are impressive, saying the trial supports asciminib as “the new standard of care of first line therapy of newly diagnosed CML based on both efficacy.”
Dr. Wang, who moderated the ASCO session, noted the caveat that “given the chronicity of this disease, it is important to continue to follow the patients enrolled on this study for longevity and durability of these efficacy endpoints.”
Nevertheless, “given the lower discontinuation rates versus other TKIs and the fact that, in my opinion, most patients who stop drug will do so in the first 6-12 months if not tolerated, these results are highly promising,” she said.
Dr. Wang also agreed, however, that the rising costs of the TKIs are an important concern.
“All of the BCR-ABL TKIs except imatinib already cost several thousand dollars per month, but there is a trend that newer agents are priced higher than prior,” she said. “This needs to be addressed as $10-$20K per month is not reasonable, and the pharmaceutical companies need to be aware.
“Yes, the data with asciminib is better, but if many patients who respond to imatinib just take longer and there is no difference in overall or disease-free survival long-term, the financial costs are a serious topic of discussion,” Dr. Wang noted.
The study was funded by Novartis. Dr. Cortes disclosed ties with Ascentage Pharma, Bio-Path Holdings, BMS, Novartis, Pfizer, Rigel Pharmeuticals, Sun Pharmaceutical Industries, and Takeda Oncology. Dr. Vachhani and Dr. Wang reported various disclosures.
“In the ASC4FIRST trial, asciminib is the first and only agent to demonstrate statistically significant efficacy versus standard-of-care frontline TKIs in newly diagnosed CML patients,” said senior author Jorge E. Cortes, MD, director of the Georgia Cancer Center at Augusta University in Georgia, in presenting the findings at a press briefing for the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.
”Asciminib’s strong benefit-risk profile may transform the CML treatment paradigm,” Dr. Cortes said.
The study was published concurrently in The New England Journal of Medicine.
While TKIs have transformed the treatment of CML, improving the 5-year survival rates from 22% in the 1970s to 70% in recent years, nearly half of patients do not achieve a major molecular response within a year, due to either resistance or intolerance, causing the common switching of drugs.
Long-term use is further associated with common side effects, including gastrointestinal and cardiovascular events, due to off-target effects.
Asciminib is a potent and highly specific agent is an allosteric inhibitor targeting ABL myristoyl pocket, which is important in avoiding off-target effects that cause the common side effects.
The drug already has approval from the US Food and Drug Administration (FDA) for the treatment of patients with chronic phase CML who are resistant or intolerant to at least 2 prior TKIs or those with T315I mutation.
For the current pivotal phase 3 ASC4FIRST trial to evaluate the drug as a frontline therapy in recently diagnosed patients with chronic phase CML, 405 patients from cancer centers in 29 countries were enrolled.
The participants were randomized to treatment either with asciminib 80 mg once daily (n = 201) or to an investigator-selected TKI (n = 204), determined based on factors including patient age, preference, and overall health.
In the latter group, 102 patients were receiving imatinib and an equal number receive a stronger, second-generation TKI.
Overall, the patients had a median age of 52 and 65% were male. About 54% were White and 44% were Asian. Those receiving second-generation TKIs were more likely to be younger and without additional health concerns, allowing them to tolerate the more potent drugs.
The median follow-up was 16.3 months in the asciminib group and 15.7 months in the other TKIs group.
For the primary outcome, a major molecular response occurred at week 48 among 67.7% of patients in the asciminib group, compared with 49% in the combined TKI arm of imatinib and second-generation TKI groups (P < .001).
In a subanalysis of patients who were randomized to receive imatinib, a major molecular response occurred at week 48 in 69.3% in the asciminib group versus 40.2% of patients in the imatinib arm (P < .001).
The corresponding rates in the comparison of patients on second-generation TKIs were 66.0% and 57.8%, which was not a statistically significant difference.
Furthermore, a deep molecular response, which may lead to remission and discontinuation of treatment, occurred at week 48 in among 38.8% in the asciminib arm compared with the 20.6% in the combined investigator-selected TKI arm.
In the imatinib comparison analysis, the deep molecular response occurred in 42.6% of patients in the asciminib arm versus 17.8% in the imatinib arm, and in the second-generation TKI arm, the deep molecular response occurred in 35% versus 26.5%, respectively.
Importantly, in the TKI-treated group, significantly more patients in the asciminib group — 86%, remained on therapy at the data cut-off, compared with 62% of those receiving imatinib and 75% of those receiving a second generation TKI.
Adverse events of grade 3 or higher that led to discontinuation were lower with asciminib versus imatinib and second-generation TKIs (38% vs 44.4% and 54.9%, respectively), as were events leading to discontinuation (4.5% versus 11.1% and 9.8%, respectively).
The most common adverse events occurring with asciminib were low platelet count (13%) and low neutrophil count (10%). In terms of severe side effects, blood clots, a known severe side effect of TKIs, occurred in only 1% of patients.
In addition, dose adjustments and treatment interruptions were also more significantly less common in the asciminib group.
Overall, the results indicate that “asciminib has the potential to become a therapy of choice for patients with newly diagnosed chronic phase CML,” said first author Timothy P. Hughes, MD, of South Australian Health and Medical Research Institute and University of Adelaide, Australia, in presenting the findings.
Commenting on the study in an interview, Dr. Cortes underscored the importance of molecular responses as indicators of longer-term responses.
“Early responses correlate with better long-term outcomes,” he said. “Most importantly, they are associated with better probabilities of having a deep molecular response, a requirement for considerations of treatment discontinuation,” which is a highly desirable goal for many patients, he noted.
“If we can get more patients to be eligible for treatment discontinuation and to discontinue successfully, this could be a major advance,” Dr. Cortes emphasized.
“Also, for the patients who do have to stay on therapy for the rest of their lives, a treatment option that has fewer adverse events would be very desirable,” he said.
“We need to see that longer follow-up confirms the current trends, but we are very encouraged by what we see so far.”
Impressive Results; Financial Toxicity Concerns
In discussing the significance of the findings at the meeting, Pankit Vachhani, MD, assistant professor of medicine at the University of Alabama at Birmingham, said the efficacy and toxicity profiles with asciminib were impressive.
“The nearly 70% major molecular response is one of the highest rates that we have seen in clinical trials at week 48,” he said. “That’s great and maybe we will see deeper responses with time.”
He added that the toxicity profile “was better than imagined — frankly I did not expect that, so that’s a welcome surprise, but we do need longer-term data especially on arterial occlusive events not to mention some other adverse events as well.”
“The question to ask ourselves, though, is whether the use of lower dose first- or second-generation TKIs leads to comparable amounts of toxicities.”
Dr. Vachhani raised the concern of cost: “There is the issue of financial toxicity,” he noted. “At current prices, treatment using asciminib would come to approximately $260,000 per year in terms of the cost to the healthcare system,” he said.
“Meanwhile, imatinib right now, in the US, can be obtained for $500 per year, and additional TKIs are going generic [soon],” he said, noting that survival differences remain unclear.
Further commenting, Eunice Wang, MD, associate professor of medicine at the Roswell Park Cancer Institute in Buffalo, New York, agreed that the results are impressive, saying the trial supports asciminib as “the new standard of care of first line therapy of newly diagnosed CML based on both efficacy.”
Dr. Wang, who moderated the ASCO session, noted the caveat that “given the chronicity of this disease, it is important to continue to follow the patients enrolled on this study for longevity and durability of these efficacy endpoints.”
Nevertheless, “given the lower discontinuation rates versus other TKIs and the fact that, in my opinion, most patients who stop drug will do so in the first 6-12 months if not tolerated, these results are highly promising,” she said.
Dr. Wang also agreed, however, that the rising costs of the TKIs are an important concern.
“All of the BCR-ABL TKIs except imatinib already cost several thousand dollars per month, but there is a trend that newer agents are priced higher than prior,” she said. “This needs to be addressed as $10-$20K per month is not reasonable, and the pharmaceutical companies need to be aware.
“Yes, the data with asciminib is better, but if many patients who respond to imatinib just take longer and there is no difference in overall or disease-free survival long-term, the financial costs are a serious topic of discussion,” Dr. Wang noted.
The study was funded by Novartis. Dr. Cortes disclosed ties with Ascentage Pharma, Bio-Path Holdings, BMS, Novartis, Pfizer, Rigel Pharmeuticals, Sun Pharmaceutical Industries, and Takeda Oncology. Dr. Vachhani and Dr. Wang reported various disclosures.
FROM ASCO 2024