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MDedge conference coverage features onsite reporting of the latest study results and expert perspectives from leading researchers.
Understudied Patients With COPD Benefit From BLVR
BLVR has shown promising results in previous studies for carefully selected patients with COPD, said Michael J. Nicholson, DO, of Temple University Hospital, Philadelphia. However, those with AATD have often been excluded from large BLVR trials, so data on its effectiveness in this population are limited, he said.
“The distinct pathophysiology of AATD poses challenges in extrapolating findings from trials involving COPD patients without AATD,” Dr. Nicholson noted. “Variations in affected lung lobes and disease progression are major differences between the AATD and non-AATD populations; we sought to examine if BLVR could provide significant, sustained benefit to AATD patients despite their differences from the typical COPD cohort,” he said.
Patients With COPD and AATD
In a study presented at the American Thoracic Society (ATS) 2024 International Conference, Dr. Nicholson and colleagues reviewed data from 238 adults with COPD including 14 with AATD who underwent BLVR at a single center between August 2018 and December 2022. Pulmonary function test data were collected at baseline and at a median of 7 months post-BLVR. The mean age of patients with AATD was 61.5 years, and 79% were men.
The primary outcome was the percentage of patients with forced expiratory volume per second (FEV1) improvement greater than 15%. Half of the patients with AATD achieved this outcome, with a median improvement in FEV1 of 110 mL and a significant difference in pre- and post-BLVR FEV1 volume based on a Wilcoxon signed rank test (W = 11.5; P < .05).
Patients with AATD also showed significant improvement in several secondary outcomes including BODE index, residual volume (RV), total lung capacity (TLC), RV/TLC ratio, and inspiratory capacity/RV ratio between pre- and post-BLVR.
“The sustained improvements seen at 7 months post-BLVR in patients with lower lobe disease were unexpected and promising,” Dr. Nicholson said in an interview. “In contrast to the National Emphysema Treatment Trial (NETT), which found lung volume reduction surgery ineffective for lower lobe disease, our study revealed significant improvements in lower lobe disease following BLVR,” he said. The sustained improvements up to 7 months post-BLVR are encouraging, given clinical concerns that the ongoing destruction of lung tissue in AATD could cause initial BLVR improvements to regress, he added.
Overall, the results suggest that BLVR is an effective therapy for appropriately selected patients with AATD and COPD, and that significant improvement in lung function can be achieved regardless of the affected lobe, Dr. Nicholson said.
“The primary obstacles to widespread BLVR implementation include the scarcity of equipment, as well as insufficient education and training for pulmonologists outside of major academic institutions,” Dr. Nicholson told this news organization. “Successful outcomes in BLVR require clinicians to have a deep understanding of patient selection criteria, extensive training in BLVR techniques, and access to the necessary technology within their facilities,” he said. However, BLVR has been integrated into pulmonary and interventional pulmonary fellowships nationwide, which paves the way for a new generation of pulmonologists to expand the use of the procedure, he said.
Looking ahead, prospective examination of BLVR vs the current standard of care in patients with AATD would provide invaluable data, Dr. Nicholson said. Since the presentation of the study at the meeting, additional patient data have been added to the analysis and increased the power of the findings, he said. “We intend to extend our assessment of pulmonary function testing beyond 7 months post-BLVR to evaluate the persistence of improvements in the long term,” he added.
Study Confirms Benefits for Wider Patient Population
“Lung volume reduction is an important intervention in patients with severe emphysema,” said David M. Mannino, MD, of the University of Kentucky, Lexington, Kentucky, in an interview. Most emphysema is in the upper lobes, but it tends to occur more in the lower lobes in patients with AATD, said Dr. Mannino, who was not involved in the study.
The findings were not especially surprising, but they were reassuring, Dr. Mannino told this news organization. “We know this intervention works in those with severe emphysema,” and it was helpful to confirm similar success in patients with AATD, he said.
The implications for practice are that BLVR is both a safe and an effective intervention for patients with lower or upper lobe emphysema, although longer-term follow-up studies are needed, he said.
The study received no outside funding. Dr. Nicholson and Dr. Mannino had no financial conflicts to disclose.
A version of this article appeared on Medscape.com.
BLVR has shown promising results in previous studies for carefully selected patients with COPD, said Michael J. Nicholson, DO, of Temple University Hospital, Philadelphia. However, those with AATD have often been excluded from large BLVR trials, so data on its effectiveness in this population are limited, he said.
“The distinct pathophysiology of AATD poses challenges in extrapolating findings from trials involving COPD patients without AATD,” Dr. Nicholson noted. “Variations in affected lung lobes and disease progression are major differences between the AATD and non-AATD populations; we sought to examine if BLVR could provide significant, sustained benefit to AATD patients despite their differences from the typical COPD cohort,” he said.
Patients With COPD and AATD
In a study presented at the American Thoracic Society (ATS) 2024 International Conference, Dr. Nicholson and colleagues reviewed data from 238 adults with COPD including 14 with AATD who underwent BLVR at a single center between August 2018 and December 2022. Pulmonary function test data were collected at baseline and at a median of 7 months post-BLVR. The mean age of patients with AATD was 61.5 years, and 79% were men.
The primary outcome was the percentage of patients with forced expiratory volume per second (FEV1) improvement greater than 15%. Half of the patients with AATD achieved this outcome, with a median improvement in FEV1 of 110 mL and a significant difference in pre- and post-BLVR FEV1 volume based on a Wilcoxon signed rank test (W = 11.5; P < .05).
Patients with AATD also showed significant improvement in several secondary outcomes including BODE index, residual volume (RV), total lung capacity (TLC), RV/TLC ratio, and inspiratory capacity/RV ratio between pre- and post-BLVR.
“The sustained improvements seen at 7 months post-BLVR in patients with lower lobe disease were unexpected and promising,” Dr. Nicholson said in an interview. “In contrast to the National Emphysema Treatment Trial (NETT), which found lung volume reduction surgery ineffective for lower lobe disease, our study revealed significant improvements in lower lobe disease following BLVR,” he said. The sustained improvements up to 7 months post-BLVR are encouraging, given clinical concerns that the ongoing destruction of lung tissue in AATD could cause initial BLVR improvements to regress, he added.
Overall, the results suggest that BLVR is an effective therapy for appropriately selected patients with AATD and COPD, and that significant improvement in lung function can be achieved regardless of the affected lobe, Dr. Nicholson said.
“The primary obstacles to widespread BLVR implementation include the scarcity of equipment, as well as insufficient education and training for pulmonologists outside of major academic institutions,” Dr. Nicholson told this news organization. “Successful outcomes in BLVR require clinicians to have a deep understanding of patient selection criteria, extensive training in BLVR techniques, and access to the necessary technology within their facilities,” he said. However, BLVR has been integrated into pulmonary and interventional pulmonary fellowships nationwide, which paves the way for a new generation of pulmonologists to expand the use of the procedure, he said.
Looking ahead, prospective examination of BLVR vs the current standard of care in patients with AATD would provide invaluable data, Dr. Nicholson said. Since the presentation of the study at the meeting, additional patient data have been added to the analysis and increased the power of the findings, he said. “We intend to extend our assessment of pulmonary function testing beyond 7 months post-BLVR to evaluate the persistence of improvements in the long term,” he added.
Study Confirms Benefits for Wider Patient Population
“Lung volume reduction is an important intervention in patients with severe emphysema,” said David M. Mannino, MD, of the University of Kentucky, Lexington, Kentucky, in an interview. Most emphysema is in the upper lobes, but it tends to occur more in the lower lobes in patients with AATD, said Dr. Mannino, who was not involved in the study.
The findings were not especially surprising, but they were reassuring, Dr. Mannino told this news organization. “We know this intervention works in those with severe emphysema,” and it was helpful to confirm similar success in patients with AATD, he said.
The implications for practice are that BLVR is both a safe and an effective intervention for patients with lower or upper lobe emphysema, although longer-term follow-up studies are needed, he said.
The study received no outside funding. Dr. Nicholson and Dr. Mannino had no financial conflicts to disclose.
A version of this article appeared on Medscape.com.
BLVR has shown promising results in previous studies for carefully selected patients with COPD, said Michael J. Nicholson, DO, of Temple University Hospital, Philadelphia. However, those with AATD have often been excluded from large BLVR trials, so data on its effectiveness in this population are limited, he said.
“The distinct pathophysiology of AATD poses challenges in extrapolating findings from trials involving COPD patients without AATD,” Dr. Nicholson noted. “Variations in affected lung lobes and disease progression are major differences between the AATD and non-AATD populations; we sought to examine if BLVR could provide significant, sustained benefit to AATD patients despite their differences from the typical COPD cohort,” he said.
Patients With COPD and AATD
In a study presented at the American Thoracic Society (ATS) 2024 International Conference, Dr. Nicholson and colleagues reviewed data from 238 adults with COPD including 14 with AATD who underwent BLVR at a single center between August 2018 and December 2022. Pulmonary function test data were collected at baseline and at a median of 7 months post-BLVR. The mean age of patients with AATD was 61.5 years, and 79% were men.
The primary outcome was the percentage of patients with forced expiratory volume per second (FEV1) improvement greater than 15%. Half of the patients with AATD achieved this outcome, with a median improvement in FEV1 of 110 mL and a significant difference in pre- and post-BLVR FEV1 volume based on a Wilcoxon signed rank test (W = 11.5; P < .05).
Patients with AATD also showed significant improvement in several secondary outcomes including BODE index, residual volume (RV), total lung capacity (TLC), RV/TLC ratio, and inspiratory capacity/RV ratio between pre- and post-BLVR.
“The sustained improvements seen at 7 months post-BLVR in patients with lower lobe disease were unexpected and promising,” Dr. Nicholson said in an interview. “In contrast to the National Emphysema Treatment Trial (NETT), which found lung volume reduction surgery ineffective for lower lobe disease, our study revealed significant improvements in lower lobe disease following BLVR,” he said. The sustained improvements up to 7 months post-BLVR are encouraging, given clinical concerns that the ongoing destruction of lung tissue in AATD could cause initial BLVR improvements to regress, he added.
Overall, the results suggest that BLVR is an effective therapy for appropriately selected patients with AATD and COPD, and that significant improvement in lung function can be achieved regardless of the affected lobe, Dr. Nicholson said.
“The primary obstacles to widespread BLVR implementation include the scarcity of equipment, as well as insufficient education and training for pulmonologists outside of major academic institutions,” Dr. Nicholson told this news organization. “Successful outcomes in BLVR require clinicians to have a deep understanding of patient selection criteria, extensive training in BLVR techniques, and access to the necessary technology within their facilities,” he said. However, BLVR has been integrated into pulmonary and interventional pulmonary fellowships nationwide, which paves the way for a new generation of pulmonologists to expand the use of the procedure, he said.
Looking ahead, prospective examination of BLVR vs the current standard of care in patients with AATD would provide invaluable data, Dr. Nicholson said. Since the presentation of the study at the meeting, additional patient data have been added to the analysis and increased the power of the findings, he said. “We intend to extend our assessment of pulmonary function testing beyond 7 months post-BLVR to evaluate the persistence of improvements in the long term,” he added.
Study Confirms Benefits for Wider Patient Population
“Lung volume reduction is an important intervention in patients with severe emphysema,” said David M. Mannino, MD, of the University of Kentucky, Lexington, Kentucky, in an interview. Most emphysema is in the upper lobes, but it tends to occur more in the lower lobes in patients with AATD, said Dr. Mannino, who was not involved in the study.
The findings were not especially surprising, but they were reassuring, Dr. Mannino told this news organization. “We know this intervention works in those with severe emphysema,” and it was helpful to confirm similar success in patients with AATD, he said.
The implications for practice are that BLVR is both a safe and an effective intervention for patients with lower or upper lobe emphysema, although longer-term follow-up studies are needed, he said.
The study received no outside funding. Dr. Nicholson and Dr. Mannino had no financial conflicts to disclose.
A version of this article appeared on Medscape.com.
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
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
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
How Can Patients With Diabetes and Obesity Lose Weight?
BERLIN — What is the best way to help patients with diabetes, heart problems, and obesity lose weight and improve their outcomes? Is it exercise or medication (such as glucagon-like peptide 1 or gastric inhibitory polypeptide receptor agonists)? This was the focus of a “Battle of Experts” at the 2024 Diabetes Congress in Berlin.
Benefits of Exercise
“Exercise is ‘omnipotent,’ ” said Christine Joisten, MD, general, sports, and nutrition physician at the Sports University in Cologne, Germany. She pointed out that exercise not only helps with weight loss but also improves overall fitness, body composition, eating habits, cardiometabolic health, and quality of life, listing the benefits of exercise.
In a conversation with this news organization, Stephan Kress, MD, a diabetologist at Vinzentius Hospital in Landau, Germany, and first chair of the German Diabetes Society’s Diabetes, Sports, and Exercise Working Group, referred to a study by Pedersen et al. that examined the effect of exercise on 26 conditions. It indicated that exercise had moderate to strong positive effects on disease progression. The benefits of exercise extended beyond metabolic, cardiological, pneumological, and musculoskeletal diseases to neurological and psychiatric conditions.
The so-called myokines, which are “good” cytokines released by muscles, could play a role in this process, according to a presentation by study author Bente Klarlund Pedersen, MD, of Rigshospitalet in Copenhagen, Denmark.
For example, exercise could elevate mood in patients with depression and reduce inflammation in individuals with chronic inflammatory diseases, said Dr. Kress. Many patients, including those with diabetes, could benefit from physical activity even if their A1c levels do not decrease as desired.
Exercise As a Snack
Fat loss can be achieved with prolonged activity or with “short and intense” sessions if followed by refraining from eating immediately afterward, Dr. Joisten explained during the expert battle at the Diabetes Congress.
Different recommendations exist regarding how much exercise is necessary. According to the World Health Organization’s (WHO) recommendation, “Every step counts.” “As sports physicians, we consider physical activity to be any form of energy expenditure achieved through muscle activity,” said Dr. Joisten.
This means that even occasional standing up, walking around, climbing stairs, and everyday activities are a start. They help motivate stigmatized, discouraged patients with obesity. Dr. Joisten highlighted a clear advantage of exercise over the “weight loss injection.” “You can promise your patients that when they start or resume physical activity, they will experience the greatest increase in fitness and health right from the start.”
Just 500 more steps per day can decrease cardiovascular mortality by 7%, while a daily increase of 1000 steps reduces overall mortality by 15%, according to a recent meta-analysis. For movement in a confined space, such as a home office, one can engage in “exercise snacks.” To do this, one interrupts sedentary activities throughout the day with short bursts of movement, said Dr. Joisten.
Dr. Kress agreed with this introductory concept. “With lower intensity and longer duration, you can achieve even more than with short, intense exercise sessions,” he told this news organization. For starters, he recommended “walking without panting,” such as walking or jogging at a pace that allows for conversation.
Even the first walk improves the condition of coronary arteries, Dr. Kress explained. Fragmented exercise sessions, such as three times for 10 min/d, benefit circulation and fitness, the expert emphasized. Moderate aerobic training also ensures effective fat burning and prevents lactic acid buildup.
The Next Step
Gradual progression can lead to longer or brisker walks. The goal does not always have to be 10,000 steps per day, as shown in a meta-analysis presented by Dr. Joisten. In individuals aged < 60 years, 8000-10,000 steps significantly reduced mortality. For those aged > 60 years, 6000-8000 steps were sufficient.
More exercise is even better. The WHO recommends 150-300 min/wk of exercise for adults, including seniors, equivalent to 30-60 min/d for 5 days a week. Additionally, strength training is recommended on 2 days a week — or for seniors, 3 days of combined training sessions with strength and balance components.
In a network meta-analysis, the following exercise regimens were compared for overweight or obese individuals:
- Interval training (very high intensity, 2-3 d/wk, averaging 91 min/wk)
- Strength training (2-3 d/wk, averaging 126 min/wk)
- Continuous endurance training (moderate intensity, 3-5 d/wk, averaging 176 min/wk)
- Combined training (3-4 d/wk, averaging 187 min/wk)
- Hybrid training (high intensity, such as dancing, jumping rope, ball sports, etc., 2-3 d/wk, averaging 128 min/wk).
Participants in the combined training group (which included the longest weekly training times) performed the best in all five endpoints: Body composition, blood lipid levels, blood sugar control, blood pressure, and cardiorespiratory fitness. However, hybrid training also produced good results.
First, Visit the Doctor
Patients who wish to exercise and have not done so in a while or who have cardiac-respiratory or orthopedic conditions should first undergo a medical checkup, Dr. Kress told this news organization.
In most cases, a test on a stationary bicycle at the primary care physician’s office would be sufficient. If higher athletic goals are sought, a sports physician or a cardiologist should be consulted.
However, when looking at weight loss alone, exercise may not go very far, said Dr. Joisten. Approximately 1.5-3.5 kg of body weight can be lost, as shown in a meta-analysis. Of this amount, about 1.3-2.6 kg is fat mass. Only 330-560 g of this total is visceral fat, which matters the most.
A Direct Comparison
Matthias Blüher, MD, an endocrinologist and diabetologist at the University Hospital Leipzig in Leipzig, Germany, represented the pro-injection position. He initially focused on body weight and presented a highly publicized study by Lundgren et al., which showed that treatment with 3.0 mg/d liraglutide was significantly more effective in terms of weight loss than moderate to intensive physical activity. After 12 months, patients who received the injection lost 6.8 kg, while those who exercised lost only 4.1 kg. “The injection wins in a direct comparison,” said Dr. Blüher.
The diabetologist also pointed out the risk for injury associated with exercise. Patients may become less active after a sports injury, he noted.
The LOOK-AHEAD study investigated whether a lifestyle program involving exercise and dietary changes brought cardiovascular benefits. In the long run, it did not. Patients regained weight after some time, and the combined cardiovascular endpoint did not differ between the group with an active, healthy lifestyle and the inactive control group. The study was discontinued.
The SELECT study compared the effect of treatment with once-weekly semaglutide 2.4 mg and placebo on cardiovascular events in patients with cardiovascular conditions and overweight or obesity (n = 17,604). Patients in the semaglutide arm had significantly fewer cardiovascular events over nearly 3 years than the comparison patients receiving placebo (6.5% vs 8.0%). Although the study participants did not have diabetes, they had relatively high baseline A1c levels; two thirds of the patients (n = 11,696) had prediabetes, with an A1c level ≥ 5.7%. Semaglutide significantly delayed the onset of diabetes in these patients, said Dr. Blüher.
A review in which Dr. Blüher was involved showed that treatment with 2.4 mg semaglutide or 15 mg tirzepatide over 12 months was more effective than many older medications (including orlistat) but not as effective as bariatric surgery. Participants in the Exercise and Nutrition study performed even worse than with the older medications.
Combination Therapy
Dr. Blüher and Dr. Joisten agreed that the combined prescription and use of exercise and incretin-based medications yields the best results for relevant endpoints such as weight loss and blood sugar control.
For example, data from the Lundgren study mentioned previously showed that participants in the combination group with liraglutide plus exercise lost an average of 9.5 kg of body weight. In addition, the A1c level, insulin sensitivity, and cardiorespiratory fitness of the participants in the combination group improved significantly over the course of the study.
The suggestion of an interval therapy (alternating between exercise and injections) enjoyed widespread approval during the audience discussion. Dr. Kress also supported the idea of interval therapy with incretin-based injections because it minimizes costs and could enhance insurance companies’ acceptance of this therapy.
But exercise should not be interrupted, he said, and perhaps patients would not want to take breaks either, hoping that “once someone has lost weight (for example, even under injection therapy) they gain new motivation to move and achieve more.”
This story was translated from the 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 first appeared on Medscape.com.
BERLIN — What is the best way to help patients with diabetes, heart problems, and obesity lose weight and improve their outcomes? Is it exercise or medication (such as glucagon-like peptide 1 or gastric inhibitory polypeptide receptor agonists)? This was the focus of a “Battle of Experts” at the 2024 Diabetes Congress in Berlin.
Benefits of Exercise
“Exercise is ‘omnipotent,’ ” said Christine Joisten, MD, general, sports, and nutrition physician at the Sports University in Cologne, Germany. She pointed out that exercise not only helps with weight loss but also improves overall fitness, body composition, eating habits, cardiometabolic health, and quality of life, listing the benefits of exercise.
In a conversation with this news organization, Stephan Kress, MD, a diabetologist at Vinzentius Hospital in Landau, Germany, and first chair of the German Diabetes Society’s Diabetes, Sports, and Exercise Working Group, referred to a study by Pedersen et al. that examined the effect of exercise on 26 conditions. It indicated that exercise had moderate to strong positive effects on disease progression. The benefits of exercise extended beyond metabolic, cardiological, pneumological, and musculoskeletal diseases to neurological and psychiatric conditions.
The so-called myokines, which are “good” cytokines released by muscles, could play a role in this process, according to a presentation by study author Bente Klarlund Pedersen, MD, of Rigshospitalet in Copenhagen, Denmark.
For example, exercise could elevate mood in patients with depression and reduce inflammation in individuals with chronic inflammatory diseases, said Dr. Kress. Many patients, including those with diabetes, could benefit from physical activity even if their A1c levels do not decrease as desired.
Exercise As a Snack
Fat loss can be achieved with prolonged activity or with “short and intense” sessions if followed by refraining from eating immediately afterward, Dr. Joisten explained during the expert battle at the Diabetes Congress.
Different recommendations exist regarding how much exercise is necessary. According to the World Health Organization’s (WHO) recommendation, “Every step counts.” “As sports physicians, we consider physical activity to be any form of energy expenditure achieved through muscle activity,” said Dr. Joisten.
This means that even occasional standing up, walking around, climbing stairs, and everyday activities are a start. They help motivate stigmatized, discouraged patients with obesity. Dr. Joisten highlighted a clear advantage of exercise over the “weight loss injection.” “You can promise your patients that when they start or resume physical activity, they will experience the greatest increase in fitness and health right from the start.”
Just 500 more steps per day can decrease cardiovascular mortality by 7%, while a daily increase of 1000 steps reduces overall mortality by 15%, according to a recent meta-analysis. For movement in a confined space, such as a home office, one can engage in “exercise snacks.” To do this, one interrupts sedentary activities throughout the day with short bursts of movement, said Dr. Joisten.
Dr. Kress agreed with this introductory concept. “With lower intensity and longer duration, you can achieve even more than with short, intense exercise sessions,” he told this news organization. For starters, he recommended “walking without panting,” such as walking or jogging at a pace that allows for conversation.
Even the first walk improves the condition of coronary arteries, Dr. Kress explained. Fragmented exercise sessions, such as three times for 10 min/d, benefit circulation and fitness, the expert emphasized. Moderate aerobic training also ensures effective fat burning and prevents lactic acid buildup.
The Next Step
Gradual progression can lead to longer or brisker walks. The goal does not always have to be 10,000 steps per day, as shown in a meta-analysis presented by Dr. Joisten. In individuals aged < 60 years, 8000-10,000 steps significantly reduced mortality. For those aged > 60 years, 6000-8000 steps were sufficient.
More exercise is even better. The WHO recommends 150-300 min/wk of exercise for adults, including seniors, equivalent to 30-60 min/d for 5 days a week. Additionally, strength training is recommended on 2 days a week — or for seniors, 3 days of combined training sessions with strength and balance components.
In a network meta-analysis, the following exercise regimens were compared for overweight or obese individuals:
- Interval training (very high intensity, 2-3 d/wk, averaging 91 min/wk)
- Strength training (2-3 d/wk, averaging 126 min/wk)
- Continuous endurance training (moderate intensity, 3-5 d/wk, averaging 176 min/wk)
- Combined training (3-4 d/wk, averaging 187 min/wk)
- Hybrid training (high intensity, such as dancing, jumping rope, ball sports, etc., 2-3 d/wk, averaging 128 min/wk).
Participants in the combined training group (which included the longest weekly training times) performed the best in all five endpoints: Body composition, blood lipid levels, blood sugar control, blood pressure, and cardiorespiratory fitness. However, hybrid training also produced good results.
First, Visit the Doctor
Patients who wish to exercise and have not done so in a while or who have cardiac-respiratory or orthopedic conditions should first undergo a medical checkup, Dr. Kress told this news organization.
In most cases, a test on a stationary bicycle at the primary care physician’s office would be sufficient. If higher athletic goals are sought, a sports physician or a cardiologist should be consulted.
However, when looking at weight loss alone, exercise may not go very far, said Dr. Joisten. Approximately 1.5-3.5 kg of body weight can be lost, as shown in a meta-analysis. Of this amount, about 1.3-2.6 kg is fat mass. Only 330-560 g of this total is visceral fat, which matters the most.
A Direct Comparison
Matthias Blüher, MD, an endocrinologist and diabetologist at the University Hospital Leipzig in Leipzig, Germany, represented the pro-injection position. He initially focused on body weight and presented a highly publicized study by Lundgren et al., which showed that treatment with 3.0 mg/d liraglutide was significantly more effective in terms of weight loss than moderate to intensive physical activity. After 12 months, patients who received the injection lost 6.8 kg, while those who exercised lost only 4.1 kg. “The injection wins in a direct comparison,” said Dr. Blüher.
The diabetologist also pointed out the risk for injury associated with exercise. Patients may become less active after a sports injury, he noted.
The LOOK-AHEAD study investigated whether a lifestyle program involving exercise and dietary changes brought cardiovascular benefits. In the long run, it did not. Patients regained weight after some time, and the combined cardiovascular endpoint did not differ between the group with an active, healthy lifestyle and the inactive control group. The study was discontinued.
The SELECT study compared the effect of treatment with once-weekly semaglutide 2.4 mg and placebo on cardiovascular events in patients with cardiovascular conditions and overweight or obesity (n = 17,604). Patients in the semaglutide arm had significantly fewer cardiovascular events over nearly 3 years than the comparison patients receiving placebo (6.5% vs 8.0%). Although the study participants did not have diabetes, they had relatively high baseline A1c levels; two thirds of the patients (n = 11,696) had prediabetes, with an A1c level ≥ 5.7%. Semaglutide significantly delayed the onset of diabetes in these patients, said Dr. Blüher.
A review in which Dr. Blüher was involved showed that treatment with 2.4 mg semaglutide or 15 mg tirzepatide over 12 months was more effective than many older medications (including orlistat) but not as effective as bariatric surgery. Participants in the Exercise and Nutrition study performed even worse than with the older medications.
Combination Therapy
Dr. Blüher and Dr. Joisten agreed that the combined prescription and use of exercise and incretin-based medications yields the best results for relevant endpoints such as weight loss and blood sugar control.
For example, data from the Lundgren study mentioned previously showed that participants in the combination group with liraglutide plus exercise lost an average of 9.5 kg of body weight. In addition, the A1c level, insulin sensitivity, and cardiorespiratory fitness of the participants in the combination group improved significantly over the course of the study.
The suggestion of an interval therapy (alternating between exercise and injections) enjoyed widespread approval during the audience discussion. Dr. Kress also supported the idea of interval therapy with incretin-based injections because it minimizes costs and could enhance insurance companies’ acceptance of this therapy.
But exercise should not be interrupted, he said, and perhaps patients would not want to take breaks either, hoping that “once someone has lost weight (for example, even under injection therapy) they gain new motivation to move and achieve more.”
This story was translated from the 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 first appeared on Medscape.com.
BERLIN — What is the best way to help patients with diabetes, heart problems, and obesity lose weight and improve their outcomes? Is it exercise or medication (such as glucagon-like peptide 1 or gastric inhibitory polypeptide receptor agonists)? This was the focus of a “Battle of Experts” at the 2024 Diabetes Congress in Berlin.
Benefits of Exercise
“Exercise is ‘omnipotent,’ ” said Christine Joisten, MD, general, sports, and nutrition physician at the Sports University in Cologne, Germany. She pointed out that exercise not only helps with weight loss but also improves overall fitness, body composition, eating habits, cardiometabolic health, and quality of life, listing the benefits of exercise.
In a conversation with this news organization, Stephan Kress, MD, a diabetologist at Vinzentius Hospital in Landau, Germany, and first chair of the German Diabetes Society’s Diabetes, Sports, and Exercise Working Group, referred to a study by Pedersen et al. that examined the effect of exercise on 26 conditions. It indicated that exercise had moderate to strong positive effects on disease progression. The benefits of exercise extended beyond metabolic, cardiological, pneumological, and musculoskeletal diseases to neurological and psychiatric conditions.
The so-called myokines, which are “good” cytokines released by muscles, could play a role in this process, according to a presentation by study author Bente Klarlund Pedersen, MD, of Rigshospitalet in Copenhagen, Denmark.
For example, exercise could elevate mood in patients with depression and reduce inflammation in individuals with chronic inflammatory diseases, said Dr. Kress. Many patients, including those with diabetes, could benefit from physical activity even if their A1c levels do not decrease as desired.
Exercise As a Snack
Fat loss can be achieved with prolonged activity or with “short and intense” sessions if followed by refraining from eating immediately afterward, Dr. Joisten explained during the expert battle at the Diabetes Congress.
Different recommendations exist regarding how much exercise is necessary. According to the World Health Organization’s (WHO) recommendation, “Every step counts.” “As sports physicians, we consider physical activity to be any form of energy expenditure achieved through muscle activity,” said Dr. Joisten.
This means that even occasional standing up, walking around, climbing stairs, and everyday activities are a start. They help motivate stigmatized, discouraged patients with obesity. Dr. Joisten highlighted a clear advantage of exercise over the “weight loss injection.” “You can promise your patients that when they start or resume physical activity, they will experience the greatest increase in fitness and health right from the start.”
Just 500 more steps per day can decrease cardiovascular mortality by 7%, while a daily increase of 1000 steps reduces overall mortality by 15%, according to a recent meta-analysis. For movement in a confined space, such as a home office, one can engage in “exercise snacks.” To do this, one interrupts sedentary activities throughout the day with short bursts of movement, said Dr. Joisten.
Dr. Kress agreed with this introductory concept. “With lower intensity and longer duration, you can achieve even more than with short, intense exercise sessions,” he told this news organization. For starters, he recommended “walking without panting,” such as walking or jogging at a pace that allows for conversation.
Even the first walk improves the condition of coronary arteries, Dr. Kress explained. Fragmented exercise sessions, such as three times for 10 min/d, benefit circulation and fitness, the expert emphasized. Moderate aerobic training also ensures effective fat burning and prevents lactic acid buildup.
The Next Step
Gradual progression can lead to longer or brisker walks. The goal does not always have to be 10,000 steps per day, as shown in a meta-analysis presented by Dr. Joisten. In individuals aged < 60 years, 8000-10,000 steps significantly reduced mortality. For those aged > 60 years, 6000-8000 steps were sufficient.
More exercise is even better. The WHO recommends 150-300 min/wk of exercise for adults, including seniors, equivalent to 30-60 min/d for 5 days a week. Additionally, strength training is recommended on 2 days a week — or for seniors, 3 days of combined training sessions with strength and balance components.
In a network meta-analysis, the following exercise regimens were compared for overweight or obese individuals:
- Interval training (very high intensity, 2-3 d/wk, averaging 91 min/wk)
- Strength training (2-3 d/wk, averaging 126 min/wk)
- Continuous endurance training (moderate intensity, 3-5 d/wk, averaging 176 min/wk)
- Combined training (3-4 d/wk, averaging 187 min/wk)
- Hybrid training (high intensity, such as dancing, jumping rope, ball sports, etc., 2-3 d/wk, averaging 128 min/wk).
Participants in the combined training group (which included the longest weekly training times) performed the best in all five endpoints: Body composition, blood lipid levels, blood sugar control, blood pressure, and cardiorespiratory fitness. However, hybrid training also produced good results.
First, Visit the Doctor
Patients who wish to exercise and have not done so in a while or who have cardiac-respiratory or orthopedic conditions should first undergo a medical checkup, Dr. Kress told this news organization.
In most cases, a test on a stationary bicycle at the primary care physician’s office would be sufficient. If higher athletic goals are sought, a sports physician or a cardiologist should be consulted.
However, when looking at weight loss alone, exercise may not go very far, said Dr. Joisten. Approximately 1.5-3.5 kg of body weight can be lost, as shown in a meta-analysis. Of this amount, about 1.3-2.6 kg is fat mass. Only 330-560 g of this total is visceral fat, which matters the most.
A Direct Comparison
Matthias Blüher, MD, an endocrinologist and diabetologist at the University Hospital Leipzig in Leipzig, Germany, represented the pro-injection position. He initially focused on body weight and presented a highly publicized study by Lundgren et al., which showed that treatment with 3.0 mg/d liraglutide was significantly more effective in terms of weight loss than moderate to intensive physical activity. After 12 months, patients who received the injection lost 6.8 kg, while those who exercised lost only 4.1 kg. “The injection wins in a direct comparison,” said Dr. Blüher.
The diabetologist also pointed out the risk for injury associated with exercise. Patients may become less active after a sports injury, he noted.
The LOOK-AHEAD study investigated whether a lifestyle program involving exercise and dietary changes brought cardiovascular benefits. In the long run, it did not. Patients regained weight after some time, and the combined cardiovascular endpoint did not differ between the group with an active, healthy lifestyle and the inactive control group. The study was discontinued.
The SELECT study compared the effect of treatment with once-weekly semaglutide 2.4 mg and placebo on cardiovascular events in patients with cardiovascular conditions and overweight or obesity (n = 17,604). Patients in the semaglutide arm had significantly fewer cardiovascular events over nearly 3 years than the comparison patients receiving placebo (6.5% vs 8.0%). Although the study participants did not have diabetes, they had relatively high baseline A1c levels; two thirds of the patients (n = 11,696) had prediabetes, with an A1c level ≥ 5.7%. Semaglutide significantly delayed the onset of diabetes in these patients, said Dr. Blüher.
A review in which Dr. Blüher was involved showed that treatment with 2.4 mg semaglutide or 15 mg tirzepatide over 12 months was more effective than many older medications (including orlistat) but not as effective as bariatric surgery. Participants in the Exercise and Nutrition study performed even worse than with the older medications.
Combination Therapy
Dr. Blüher and Dr. Joisten agreed that the combined prescription and use of exercise and incretin-based medications yields the best results for relevant endpoints such as weight loss and blood sugar control.
For example, data from the Lundgren study mentioned previously showed that participants in the combination group with liraglutide plus exercise lost an average of 9.5 kg of body weight. In addition, the A1c level, insulin sensitivity, and cardiorespiratory fitness of the participants in the combination group improved significantly over the course of the study.
The suggestion of an interval therapy (alternating between exercise and injections) enjoyed widespread approval during the audience discussion. Dr. Kress also supported the idea of interval therapy with incretin-based injections because it minimizes costs and could enhance insurance companies’ acceptance of this therapy.
But exercise should not be interrupted, he said, and perhaps patients would not want to take breaks either, hoping that “once someone has lost weight (for example, even under injection therapy) they gain new motivation to move and achieve more.”
This story was translated from the 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 first appeared on Medscape.com.
Colorectal Cancer Is Spiking Among Some Young Americans
WASHINGTON — Despite encouraging drops in overall colorectal cancer rates in the past two decades, one group stands out as an exception: Americans younger than 45.
, according to new research presented at the annual Digestive Disease Week®.
As high as those percentages appear, the number of people affected at these ages remains small compared with rates in Americans 45 and older, said Loren Laine, MD, AGAF, professor of medicine (digestive diseases) at Yale School of Medicine, who co-moderated a news briefing discussing the research.
“The trends are alarming [but] the actual numbers of colorectal cancer cases among children and teens are not high enough to suggest widespread screening,” agreed lead investigator Islam Mohamed, MD, an internal medicine resident at the University of Missouri-Kansas City.
For example, 1 out of every 333,000 15- to-19-year-olds developed colorectal cancer in 1999. Colorectal cancer became more common by 2020, when 1 out of every 77,000 teens developed it.
At the same time, the number of cases in young adults 20 to 24 increased from less than 1 to 2 per 100,000 in 2020.
Even if the risk is relatively low in terms of absolute numbers, experts are keeping an eye on why the rates are increasing. It’s also about raising awareness. If someone younger than 45 experiences colorectal cancer symptoms like blood in their stool, stomach pain, changes in bowel habits, or others, they should seek medical attention, Dr. Laine said.
“If you have symptoms like rectal bleeding, you shouldn’t take it lightly. It’s still pretty unlikely that they’re going to have colon cancer ... but obviously you should still not totally dismiss it,” Dr. Laine said.
“Colorectal cancer is no longer considered just a disease of the elderly population,” Dr. Mohamed said during the briefing. “It’s important that the public is aware of signs and symptoms of colorectal cancer.”
Dr. Mohamed and colleagues studied colorectal cancer cases using numbers from the CDC Wonder Database, a central database of public health information. They calculated increases by comparing rates in 1999 to 2020.
Colorectal cancer is a major cause of cancer-related death in the United States. It currently ranks third in terms of new cases and cancer-related deaths once some skin cancers are excluded, American Cancer Society data indicates.
Some Risk Factors Can Be Changed
The colorectal cancer rates in younger people “have been consistently rising. It might be related to the environmental factors, lifestyle factors, and genetic factors as well,” Dr. Mohamed said. “It also might mean that we are doing better. Maybe we’re screening patients more, and maybe we’re doing a greater job of picking patients who are at high risk of colorectal cancer in the younger population.”
“Adopting a healthy lifestyle would be a great approach to curb the rising incidence of colorectal cancer as we saw metabolic syndrome is a big [factor],” Dr. Mohamed added. Patients should be encouraged to maintain a balanced diet, engage in regular physical activity, and maybe limit alcohol consumption, he said.
On the other hand, up to one third of early-onset colorectal cancer cases are linked to factors that cannot be changed. A family history of colorectal cancer, presence of inflammatory bowel disease, and certain types of cancers linked to genetic mutations are examples. “When you think about it, most of those young people [with colorectal cancer] probably have genetic syndromes,” Dr. Laine said. “The big issue is, frankly, finding better ways to identify families that have genetic syndromes. That’s probably the biggest message.”
Risk Varied by Age
In addition to the increases in the 15- to 19-year-old and 20- to 24-year-old groups, the rates in 2020 compared with 1999 showed a
- 68% increase for ages 25 to 29.
- 71% increase for ages 30 to 34.
- 58% increase for ages 35 to 39.
- 45% increase for ages 40 to 44.
“These findings all emphasize the urgent needs for public awareness and personalized screening approaches,” Dr. Mohamed said, “particularly among younger populations who had the most substantial increase in colorectal cancer incidence we observed.”
The US Preventive Services Task Force lowered the recommended age for colorectal cancer screening from 50 to 45 in 2021. Dr. Mohamed suggested more targeted screening for people under 45 at higher risk.
“I think also staying informed about the rising incidence and the latest research and recommendations in terms of colorectal cancer prevention and screening will be really, really helpful.”
A version of this article appeared on WebMD Health News.
WASHINGTON — Despite encouraging drops in overall colorectal cancer rates in the past two decades, one group stands out as an exception: Americans younger than 45.
, according to new research presented at the annual Digestive Disease Week®.
As high as those percentages appear, the number of people affected at these ages remains small compared with rates in Americans 45 and older, said Loren Laine, MD, AGAF, professor of medicine (digestive diseases) at Yale School of Medicine, who co-moderated a news briefing discussing the research.
“The trends are alarming [but] the actual numbers of colorectal cancer cases among children and teens are not high enough to suggest widespread screening,” agreed lead investigator Islam Mohamed, MD, an internal medicine resident at the University of Missouri-Kansas City.
For example, 1 out of every 333,000 15- to-19-year-olds developed colorectal cancer in 1999. Colorectal cancer became more common by 2020, when 1 out of every 77,000 teens developed it.
At the same time, the number of cases in young adults 20 to 24 increased from less than 1 to 2 per 100,000 in 2020.
Even if the risk is relatively low in terms of absolute numbers, experts are keeping an eye on why the rates are increasing. It’s also about raising awareness. If someone younger than 45 experiences colorectal cancer symptoms like blood in their stool, stomach pain, changes in bowel habits, or others, they should seek medical attention, Dr. Laine said.
“If you have symptoms like rectal bleeding, you shouldn’t take it lightly. It’s still pretty unlikely that they’re going to have colon cancer ... but obviously you should still not totally dismiss it,” Dr. Laine said.
“Colorectal cancer is no longer considered just a disease of the elderly population,” Dr. Mohamed said during the briefing. “It’s important that the public is aware of signs and symptoms of colorectal cancer.”
Dr. Mohamed and colleagues studied colorectal cancer cases using numbers from the CDC Wonder Database, a central database of public health information. They calculated increases by comparing rates in 1999 to 2020.
Colorectal cancer is a major cause of cancer-related death in the United States. It currently ranks third in terms of new cases and cancer-related deaths once some skin cancers are excluded, American Cancer Society data indicates.
Some Risk Factors Can Be Changed
The colorectal cancer rates in younger people “have been consistently rising. It might be related to the environmental factors, lifestyle factors, and genetic factors as well,” Dr. Mohamed said. “It also might mean that we are doing better. Maybe we’re screening patients more, and maybe we’re doing a greater job of picking patients who are at high risk of colorectal cancer in the younger population.”
“Adopting a healthy lifestyle would be a great approach to curb the rising incidence of colorectal cancer as we saw metabolic syndrome is a big [factor],” Dr. Mohamed added. Patients should be encouraged to maintain a balanced diet, engage in regular physical activity, and maybe limit alcohol consumption, he said.
On the other hand, up to one third of early-onset colorectal cancer cases are linked to factors that cannot be changed. A family history of colorectal cancer, presence of inflammatory bowel disease, and certain types of cancers linked to genetic mutations are examples. “When you think about it, most of those young people [with colorectal cancer] probably have genetic syndromes,” Dr. Laine said. “The big issue is, frankly, finding better ways to identify families that have genetic syndromes. That’s probably the biggest message.”
Risk Varied by Age
In addition to the increases in the 15- to 19-year-old and 20- to 24-year-old groups, the rates in 2020 compared with 1999 showed a
- 68% increase for ages 25 to 29.
- 71% increase for ages 30 to 34.
- 58% increase for ages 35 to 39.
- 45% increase for ages 40 to 44.
“These findings all emphasize the urgent needs for public awareness and personalized screening approaches,” Dr. Mohamed said, “particularly among younger populations who had the most substantial increase in colorectal cancer incidence we observed.”
The US Preventive Services Task Force lowered the recommended age for colorectal cancer screening from 50 to 45 in 2021. Dr. Mohamed suggested more targeted screening for people under 45 at higher risk.
“I think also staying informed about the rising incidence and the latest research and recommendations in terms of colorectal cancer prevention and screening will be really, really helpful.”
A version of this article appeared on WebMD Health News.
WASHINGTON — Despite encouraging drops in overall colorectal cancer rates in the past two decades, one group stands out as an exception: Americans younger than 45.
, according to new research presented at the annual Digestive Disease Week®.
As high as those percentages appear, the number of people affected at these ages remains small compared with rates in Americans 45 and older, said Loren Laine, MD, AGAF, professor of medicine (digestive diseases) at Yale School of Medicine, who co-moderated a news briefing discussing the research.
“The trends are alarming [but] the actual numbers of colorectal cancer cases among children and teens are not high enough to suggest widespread screening,” agreed lead investigator Islam Mohamed, MD, an internal medicine resident at the University of Missouri-Kansas City.
For example, 1 out of every 333,000 15- to-19-year-olds developed colorectal cancer in 1999. Colorectal cancer became more common by 2020, when 1 out of every 77,000 teens developed it.
At the same time, the number of cases in young adults 20 to 24 increased from less than 1 to 2 per 100,000 in 2020.
Even if the risk is relatively low in terms of absolute numbers, experts are keeping an eye on why the rates are increasing. It’s also about raising awareness. If someone younger than 45 experiences colorectal cancer symptoms like blood in their stool, stomach pain, changes in bowel habits, or others, they should seek medical attention, Dr. Laine said.
“If you have symptoms like rectal bleeding, you shouldn’t take it lightly. It’s still pretty unlikely that they’re going to have colon cancer ... but obviously you should still not totally dismiss it,” Dr. Laine said.
“Colorectal cancer is no longer considered just a disease of the elderly population,” Dr. Mohamed said during the briefing. “It’s important that the public is aware of signs and symptoms of colorectal cancer.”
Dr. Mohamed and colleagues studied colorectal cancer cases using numbers from the CDC Wonder Database, a central database of public health information. They calculated increases by comparing rates in 1999 to 2020.
Colorectal cancer is a major cause of cancer-related death in the United States. It currently ranks third in terms of new cases and cancer-related deaths once some skin cancers are excluded, American Cancer Society data indicates.
Some Risk Factors Can Be Changed
The colorectal cancer rates in younger people “have been consistently rising. It might be related to the environmental factors, lifestyle factors, and genetic factors as well,” Dr. Mohamed said. “It also might mean that we are doing better. Maybe we’re screening patients more, and maybe we’re doing a greater job of picking patients who are at high risk of colorectal cancer in the younger population.”
“Adopting a healthy lifestyle would be a great approach to curb the rising incidence of colorectal cancer as we saw metabolic syndrome is a big [factor],” Dr. Mohamed added. Patients should be encouraged to maintain a balanced diet, engage in regular physical activity, and maybe limit alcohol consumption, he said.
On the other hand, up to one third of early-onset colorectal cancer cases are linked to factors that cannot be changed. A family history of colorectal cancer, presence of inflammatory bowel disease, and certain types of cancers linked to genetic mutations are examples. “When you think about it, most of those young people [with colorectal cancer] probably have genetic syndromes,” Dr. Laine said. “The big issue is, frankly, finding better ways to identify families that have genetic syndromes. That’s probably the biggest message.”
Risk Varied by Age
In addition to the increases in the 15- to 19-year-old and 20- to 24-year-old groups, the rates in 2020 compared with 1999 showed a
- 68% increase for ages 25 to 29.
- 71% increase for ages 30 to 34.
- 58% increase for ages 35 to 39.
- 45% increase for ages 40 to 44.
“These findings all emphasize the urgent needs for public awareness and personalized screening approaches,” Dr. Mohamed said, “particularly among younger populations who had the most substantial increase in colorectal cancer incidence we observed.”
The US Preventive Services Task Force lowered the recommended age for colorectal cancer screening from 50 to 45 in 2021. Dr. Mohamed suggested more targeted screening for people under 45 at higher risk.
“I think also staying informed about the rising incidence and the latest research and recommendations in terms of colorectal cancer prevention and screening will be really, really helpful.”
A version of this article appeared on WebMD Health News.
FROM DDW 2024
Semaglutide Kidney Benefits Extend to Those Without Diabetes
STOCKHOLM — Improvements in kidney function outcomes observed with glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes extend to patients who are overweight or obese but don›t yet have type 2 diabetes, new research shows.
“These data are important because they are the first data to suggest a kidney benefit of semaglutide in this patient population in the absence of diabetes,” lead author Helen M. Colhoun, MD, of the Institute of Genetics and Cancer, University of Edinburgh, Scotland, United Kingdom, told this news organization.
“This is a population at high risk of chronic kidney disease with an increased need for kidney protection,” she said.
The late-breaking study was presented this week at the 61st European Renal Association (ERA) Congress 2024 and simultaneously published in Nature Medicine.
SELECT Trial Patients Without Diabetes
The findings are from a secondary analysis of the randomized SELECT (Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity) trial, which evaluated cardiovascular outcomes of semaglutide treatment among 17,604 adults with preexisting cardiovascular disease who were overweight or obese — but did not have diabetes.
For its primary endpoint, the trial showed semaglutide was associated with a 20% reduction in major adverse cardiovascular events compared with placebo.
With obesity also associated with a significantly increased risk of chronic kidney disease — and the headline-making FLOW trial, also presented at the congress, showing key benefits of semaglutide in improving kidney function in people with CKD and type 2 diabetes the secondary analysis of SELECT was conducted to investigate whether those kidney benefits extended to people without type 2 diabetes.
Patients were randomized 1:1 to once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo. Baseline patient characteristics were well-balanced, including kidney function and albuminuria status.
The primary endpoint for the analysis was a nephropathy composite of time from randomization to the first occurrence of death from kidney causes; initiation of chronic kidney replacement therapy; onset of persistent estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m2; persistent ≥ 50% reduction in eGFR compared with baseline; or onset of persistent macroalbuminuria.
With a median follow-up of 182 weeks, the results showed that the semaglutide group was significantly less likely to develop the primary composite endpoint compared with the placebo group (1.8% vs 2.2%; hazard ratio [HR], 0.78; P = .02).
A significantly reduced decline in eGFR in the semaglutide group was observed at a prespecified 104-week time point, with a treatment effect of 0.75 mL/min/1.73 m2 (P < .001), and the effect was more pronounced among participants with baseline eGFR < 60 mL/min/1.73 m2 (P < .001).
Furthermore, those in the semaglutide group had a significantly lower proportionate increase in urinary albumin-to-creatinine ratio (UACR) compared with placebo (–10.7%; P < .001) at the prespecified 104 weeks, with a net treatment benefit of –27.2% and –31.4% among those with randomization to UACR 30 to < 300 mg/g and 2300 mg/g, respectively.
Improvements varied according to baseline UACR status and were more pronounced among those with macroalbuminuria, at –8.1% for those with normoalbuminuria (n = 14,848), –27% for microalbuminuria (n = 1968), and –31% for macroalbuminuria (n = 325).
There were no reports of acute kidney injury associated with semaglutide, regardless of baseline eGFR.
“We were hopeful that there would be similar benefits as those observed in the diabetes studies, but there are differences in kidney disease among those with and without type 2 diabetes, so we weren’t sure,” Dr. Colhoun told this news organization.
Benefits the Result of Weight Loss or Something Else?
Considering the beneficial effects of semaglutide on weight loss, underscored in an analysis also published this month that showed a mean 10.2% reduction in weight sustained for up to 4 years, a key question is whether the kidney benefits are a direct result of weight loss — or the drug mechanism or something else.
But Dr. Colhoun said the role of weight loss in terms of the kidney benefits is still uncertain, particularly considering the various other factors, including cardiometabolic improvements, which could also have an effect.
“It’s a very difficult question to answer,” she said. “We did do a mediation exploratory analysis suggesting a substantial part of the effect might be due to the weight change, but it’s difficult to demonstrate that because you have weight change going on in the placebo arm as well, but for different reasons,” she said.
“So, I would say the data suggest there is some component of this that is attributable to weight, but we certainly can’t attribute all of the [effects] to weight change.”
Small studies involving animals have shown a direct effect of semaglutide on kidney hemodynamics “but they’re small and not definitive,” Dr. Colhoun added.
And although weight loss achieved through other measures such as lifestyle changes show a small benefit on eGFR, “interestingly, those studies showed no effect at all on albuminuria, whereas we see a really substantial effect on albuminuria with semaglutide,” Dr. Colhoun said.
Studies of weight loss through bariatric surgery have shown kidney benefits; however, those were in the context of type 2 diabetes, unlike the current analysis.
In terms of whether the benefits may extend to tirzepatide, the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist, increasingly used in weight loss, results from another secondary analysis also show encouraging kidney benefits in people with type 2 diabetes, and there is ongoing research in patients with type 2 diabetes and those with obesity without diabetes, Dr. Colhoun noted.
Primary Prevention of CKD?
Limitations of the current analysis include that only about a fifth of participants in SELECT had an eGFR < 60 mL/min/1.73 m2 or UACR ≥ 30 mg/g at baseline, suggesting a relatively low proportion of participants with kidney disease.
Importantly, however, the kidney benefits observed in patients who are at such high risk of kidney disease but do not yet have diabetes or CKD, is encouraging, said Alberto Ortiz, MD, PhD, commenting on the study. Dr. Ortiz is chief of nephrology and the Hypertension Renal Unit, Health Research Institute of the Jiménez Díaz Foundation, Madrid, Spain.
“It is especially significant that protection was observed in participants with an eGFR > 60 mL/min/1.73 m2 and across UACR categories, ie, including people without CKD at baseline, in whom it appeared to decrease the incidence of de novo CKD,” Dr. Ortiz told this news organization.
“This suggests a potential role in primary prevention of CKD in this population,” he said.
To further investigate this, he said, “It would have been extremely interesting to assess whether there is a potential role for primary prevention of CKD in people without baseline CKD by assessing subgroup results for the no-CKD, low-risk KDIGO [Kidney Disease: Improving Global Outcomes] category [of patients].”
SELECT was funded by Novo Nordisk. Dr. Colhoun has reported consulting, research, and/or other relationships with Novo Nordisk, Bayer, Sanofi, Roche, and IQVIA. Dr. Ortiz has reported being a member of the European Renal Association council and Madrid Society of Nephrology (SOMANE), which developed a document in 2022 on the treatment of diabetic kidney disease sponsored by Novo Nordisk. He also reported collaborating with companies developing drugs for kidney disease.
A version of this article first appeared on Medscape.com.
STOCKHOLM — Improvements in kidney function outcomes observed with glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes extend to patients who are overweight or obese but don›t yet have type 2 diabetes, new research shows.
“These data are important because they are the first data to suggest a kidney benefit of semaglutide in this patient population in the absence of diabetes,” lead author Helen M. Colhoun, MD, of the Institute of Genetics and Cancer, University of Edinburgh, Scotland, United Kingdom, told this news organization.
“This is a population at high risk of chronic kidney disease with an increased need for kidney protection,” she said.
The late-breaking study was presented this week at the 61st European Renal Association (ERA) Congress 2024 and simultaneously published in Nature Medicine.
SELECT Trial Patients Without Diabetes
The findings are from a secondary analysis of the randomized SELECT (Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity) trial, which evaluated cardiovascular outcomes of semaglutide treatment among 17,604 adults with preexisting cardiovascular disease who were overweight or obese — but did not have diabetes.
For its primary endpoint, the trial showed semaglutide was associated with a 20% reduction in major adverse cardiovascular events compared with placebo.
With obesity also associated with a significantly increased risk of chronic kidney disease — and the headline-making FLOW trial, also presented at the congress, showing key benefits of semaglutide in improving kidney function in people with CKD and type 2 diabetes the secondary analysis of SELECT was conducted to investigate whether those kidney benefits extended to people without type 2 diabetes.
Patients were randomized 1:1 to once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo. Baseline patient characteristics were well-balanced, including kidney function and albuminuria status.
The primary endpoint for the analysis was a nephropathy composite of time from randomization to the first occurrence of death from kidney causes; initiation of chronic kidney replacement therapy; onset of persistent estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m2; persistent ≥ 50% reduction in eGFR compared with baseline; or onset of persistent macroalbuminuria.
With a median follow-up of 182 weeks, the results showed that the semaglutide group was significantly less likely to develop the primary composite endpoint compared with the placebo group (1.8% vs 2.2%; hazard ratio [HR], 0.78; P = .02).
A significantly reduced decline in eGFR in the semaglutide group was observed at a prespecified 104-week time point, with a treatment effect of 0.75 mL/min/1.73 m2 (P < .001), and the effect was more pronounced among participants with baseline eGFR < 60 mL/min/1.73 m2 (P < .001).
Furthermore, those in the semaglutide group had a significantly lower proportionate increase in urinary albumin-to-creatinine ratio (UACR) compared with placebo (–10.7%; P < .001) at the prespecified 104 weeks, with a net treatment benefit of –27.2% and –31.4% among those with randomization to UACR 30 to < 300 mg/g and 2300 mg/g, respectively.
Improvements varied according to baseline UACR status and were more pronounced among those with macroalbuminuria, at –8.1% for those with normoalbuminuria (n = 14,848), –27% for microalbuminuria (n = 1968), and –31% for macroalbuminuria (n = 325).
There were no reports of acute kidney injury associated with semaglutide, regardless of baseline eGFR.
“We were hopeful that there would be similar benefits as those observed in the diabetes studies, but there are differences in kidney disease among those with and without type 2 diabetes, so we weren’t sure,” Dr. Colhoun told this news organization.
Benefits the Result of Weight Loss or Something Else?
Considering the beneficial effects of semaglutide on weight loss, underscored in an analysis also published this month that showed a mean 10.2% reduction in weight sustained for up to 4 years, a key question is whether the kidney benefits are a direct result of weight loss — or the drug mechanism or something else.
But Dr. Colhoun said the role of weight loss in terms of the kidney benefits is still uncertain, particularly considering the various other factors, including cardiometabolic improvements, which could also have an effect.
“It’s a very difficult question to answer,” she said. “We did do a mediation exploratory analysis suggesting a substantial part of the effect might be due to the weight change, but it’s difficult to demonstrate that because you have weight change going on in the placebo arm as well, but for different reasons,” she said.
“So, I would say the data suggest there is some component of this that is attributable to weight, but we certainly can’t attribute all of the [effects] to weight change.”
Small studies involving animals have shown a direct effect of semaglutide on kidney hemodynamics “but they’re small and not definitive,” Dr. Colhoun added.
And although weight loss achieved through other measures such as lifestyle changes show a small benefit on eGFR, “interestingly, those studies showed no effect at all on albuminuria, whereas we see a really substantial effect on albuminuria with semaglutide,” Dr. Colhoun said.
Studies of weight loss through bariatric surgery have shown kidney benefits; however, those were in the context of type 2 diabetes, unlike the current analysis.
In terms of whether the benefits may extend to tirzepatide, the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist, increasingly used in weight loss, results from another secondary analysis also show encouraging kidney benefits in people with type 2 diabetes, and there is ongoing research in patients with type 2 diabetes and those with obesity without diabetes, Dr. Colhoun noted.
Primary Prevention of CKD?
Limitations of the current analysis include that only about a fifth of participants in SELECT had an eGFR < 60 mL/min/1.73 m2 or UACR ≥ 30 mg/g at baseline, suggesting a relatively low proportion of participants with kidney disease.
Importantly, however, the kidney benefits observed in patients who are at such high risk of kidney disease but do not yet have diabetes or CKD, is encouraging, said Alberto Ortiz, MD, PhD, commenting on the study. Dr. Ortiz is chief of nephrology and the Hypertension Renal Unit, Health Research Institute of the Jiménez Díaz Foundation, Madrid, Spain.
“It is especially significant that protection was observed in participants with an eGFR > 60 mL/min/1.73 m2 and across UACR categories, ie, including people without CKD at baseline, in whom it appeared to decrease the incidence of de novo CKD,” Dr. Ortiz told this news organization.
“This suggests a potential role in primary prevention of CKD in this population,” he said.
To further investigate this, he said, “It would have been extremely interesting to assess whether there is a potential role for primary prevention of CKD in people without baseline CKD by assessing subgroup results for the no-CKD, low-risk KDIGO [Kidney Disease: Improving Global Outcomes] category [of patients].”
SELECT was funded by Novo Nordisk. Dr. Colhoun has reported consulting, research, and/or other relationships with Novo Nordisk, Bayer, Sanofi, Roche, and IQVIA. Dr. Ortiz has reported being a member of the European Renal Association council and Madrid Society of Nephrology (SOMANE), which developed a document in 2022 on the treatment of diabetic kidney disease sponsored by Novo Nordisk. He also reported collaborating with companies developing drugs for kidney disease.
A version of this article first appeared on Medscape.com.
STOCKHOLM — Improvements in kidney function outcomes observed with glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes extend to patients who are overweight or obese but don›t yet have type 2 diabetes, new research shows.
“These data are important because they are the first data to suggest a kidney benefit of semaglutide in this patient population in the absence of diabetes,” lead author Helen M. Colhoun, MD, of the Institute of Genetics and Cancer, University of Edinburgh, Scotland, United Kingdom, told this news organization.
“This is a population at high risk of chronic kidney disease with an increased need for kidney protection,” she said.
The late-breaking study was presented this week at the 61st European Renal Association (ERA) Congress 2024 and simultaneously published in Nature Medicine.
SELECT Trial Patients Without Diabetes
The findings are from a secondary analysis of the randomized SELECT (Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity) trial, which evaluated cardiovascular outcomes of semaglutide treatment among 17,604 adults with preexisting cardiovascular disease who were overweight or obese — but did not have diabetes.
For its primary endpoint, the trial showed semaglutide was associated with a 20% reduction in major adverse cardiovascular events compared with placebo.
With obesity also associated with a significantly increased risk of chronic kidney disease — and the headline-making FLOW trial, also presented at the congress, showing key benefits of semaglutide in improving kidney function in people with CKD and type 2 diabetes the secondary analysis of SELECT was conducted to investigate whether those kidney benefits extended to people without type 2 diabetes.
Patients were randomized 1:1 to once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo. Baseline patient characteristics were well-balanced, including kidney function and albuminuria status.
The primary endpoint for the analysis was a nephropathy composite of time from randomization to the first occurrence of death from kidney causes; initiation of chronic kidney replacement therapy; onset of persistent estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m2; persistent ≥ 50% reduction in eGFR compared with baseline; or onset of persistent macroalbuminuria.
With a median follow-up of 182 weeks, the results showed that the semaglutide group was significantly less likely to develop the primary composite endpoint compared with the placebo group (1.8% vs 2.2%; hazard ratio [HR], 0.78; P = .02).
A significantly reduced decline in eGFR in the semaglutide group was observed at a prespecified 104-week time point, with a treatment effect of 0.75 mL/min/1.73 m2 (P < .001), and the effect was more pronounced among participants with baseline eGFR < 60 mL/min/1.73 m2 (P < .001).
Furthermore, those in the semaglutide group had a significantly lower proportionate increase in urinary albumin-to-creatinine ratio (UACR) compared with placebo (–10.7%; P < .001) at the prespecified 104 weeks, with a net treatment benefit of –27.2% and –31.4% among those with randomization to UACR 30 to < 300 mg/g and 2300 mg/g, respectively.
Improvements varied according to baseline UACR status and were more pronounced among those with macroalbuminuria, at –8.1% for those with normoalbuminuria (n = 14,848), –27% for microalbuminuria (n = 1968), and –31% for macroalbuminuria (n = 325).
There were no reports of acute kidney injury associated with semaglutide, regardless of baseline eGFR.
“We were hopeful that there would be similar benefits as those observed in the diabetes studies, but there are differences in kidney disease among those with and without type 2 diabetes, so we weren’t sure,” Dr. Colhoun told this news organization.
Benefits the Result of Weight Loss or Something Else?
Considering the beneficial effects of semaglutide on weight loss, underscored in an analysis also published this month that showed a mean 10.2% reduction in weight sustained for up to 4 years, a key question is whether the kidney benefits are a direct result of weight loss — or the drug mechanism or something else.
But Dr. Colhoun said the role of weight loss in terms of the kidney benefits is still uncertain, particularly considering the various other factors, including cardiometabolic improvements, which could also have an effect.
“It’s a very difficult question to answer,” she said. “We did do a mediation exploratory analysis suggesting a substantial part of the effect might be due to the weight change, but it’s difficult to demonstrate that because you have weight change going on in the placebo arm as well, but for different reasons,” she said.
“So, I would say the data suggest there is some component of this that is attributable to weight, but we certainly can’t attribute all of the [effects] to weight change.”
Small studies involving animals have shown a direct effect of semaglutide on kidney hemodynamics “but they’re small and not definitive,” Dr. Colhoun added.
And although weight loss achieved through other measures such as lifestyle changes show a small benefit on eGFR, “interestingly, those studies showed no effect at all on albuminuria, whereas we see a really substantial effect on albuminuria with semaglutide,” Dr. Colhoun said.
Studies of weight loss through bariatric surgery have shown kidney benefits; however, those were in the context of type 2 diabetes, unlike the current analysis.
In terms of whether the benefits may extend to tirzepatide, the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist, increasingly used in weight loss, results from another secondary analysis also show encouraging kidney benefits in people with type 2 diabetes, and there is ongoing research in patients with type 2 diabetes and those with obesity without diabetes, Dr. Colhoun noted.
Primary Prevention of CKD?
Limitations of the current analysis include that only about a fifth of participants in SELECT had an eGFR < 60 mL/min/1.73 m2 or UACR ≥ 30 mg/g at baseline, suggesting a relatively low proportion of participants with kidney disease.
Importantly, however, the kidney benefits observed in patients who are at such high risk of kidney disease but do not yet have diabetes or CKD, is encouraging, said Alberto Ortiz, MD, PhD, commenting on the study. Dr. Ortiz is chief of nephrology and the Hypertension Renal Unit, Health Research Institute of the Jiménez Díaz Foundation, Madrid, Spain.
“It is especially significant that protection was observed in participants with an eGFR > 60 mL/min/1.73 m2 and across UACR categories, ie, including people without CKD at baseline, in whom it appeared to decrease the incidence of de novo CKD,” Dr. Ortiz told this news organization.
“This suggests a potential role in primary prevention of CKD in this population,” he said.
To further investigate this, he said, “It would have been extremely interesting to assess whether there is a potential role for primary prevention of CKD in people without baseline CKD by assessing subgroup results for the no-CKD, low-risk KDIGO [Kidney Disease: Improving Global Outcomes] category [of patients].”
SELECT was funded by Novo Nordisk. Dr. Colhoun has reported consulting, research, and/or other relationships with Novo Nordisk, Bayer, Sanofi, Roche, and IQVIA. Dr. Ortiz has reported being a member of the European Renal Association council and Madrid Society of Nephrology (SOMANE), which developed a document in 2022 on the treatment of diabetic kidney disease sponsored by Novo Nordisk. He also reported collaborating with companies developing drugs for kidney disease.
A version of this article first appeared on Medscape.com.
FROM ERA 2024