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MDedge conference coverage features onsite reporting of the latest study results and expert perspectives from leading researchers.
Postmenopausal stress linked to mood, cognitive symptoms
PHILADELPHIA – , according to research presented at the annual meeting of the Menopause Society (formerly the North American Menopause Society).
“This work suggests that markers of hypothalamic-pituitary-axis activation that capture total cortisol secretion over multiple months, [such as] hair cortisol, strongly correlate with cognitive performance on attention and working memory tasks, whereas measures of more acute cortisol, [such as] salivary cortisol, may be more strongly associated with depression symptom severity and verbal learning,” Christina Metcalf, PhD, an assistant professor of psychiatry in the Colorado Center for Women’s Behavioral Health and Wellness at the University of Colorado at Denver, Aurora, told attendees. “Given the associations with chronic stress, there’s a lot of potential here to increase our knowledge about how women are doing and managing stress and life stressors during this life transition,” she said.
The study involved collecting hair and saliva samples from 43 healthy women in late perimenopause or early postmenopause with an average age of 51. The participants were predominantly white and college educated. The hair sample was taken within 2 cm of the scalp, and the saliva samples were collected the day after the hair sample collection, at the start and end of a 30-minute rest period that took place between 2:00 and 3:00 p.m. local time.
All the participants had an intact uterus and at least one ovary. None of the participants were current smokers or had recent alcohol or drug dependence, and none had used hormones within the previous 6 months. The study also excluded women who were pregnant or breastfeeding, who had bleached hair or no hair, who were taking steroids, beta blockers or opioid medication, and who had recently taken NSAIDS.
Measuring hair cortisol more feasible
The study was conducted remotely, with participants using video conferencing to communicate with the study personnel and then completing study procedures at home, including 2 days of cognitive testing with the California Verbal Learning Test – Third Edition and the n-back and continuous performance tasks. The participants also completed the Center for Epidemiologic Studies Depression Scale (CES-D).
Participants with higher levels of hair cortisol and salivary cortisol also had more severe depression symptoms (P < .001). Hair cortisol was also significantly associated with attention and working memory: Women with higher levels had fewer correct answers on the 0-back and 1-back trials (P < .01) and made more mistakes on the 2-back trial (P < .001). They also scored with less specificity on the continuous performance tasks (P = .022).
Although no association existed between hair cortisol levels and verbal learning or verbal memory (P > .05), participants with higher hair cortisol did score worse on the immediate recall trials (P = .034). Salivary cortisol levels, on the other hand, showed no association with memory recall trials, attention or working memory (P > .05).
Measuring cortisol from hair samples is more feasible than using saliva samples and may offer valuable insights regarding hypothalamic-pituitary-axis activity “to consider alongside the cognitive and mental health of late peri-/early postmenopausal women,” Dr. Metcalf told attendees. The next step is to find out whether the hypothalamic-pituitary-axis axis is a modifiable biomarker that can be used to improve executive function.
The study was limited by its small population, its cross-sectional design, and the lack of covariates in the current analyses.
Monitor symptoms in midlife
Hadine Joffe, MD, MSc, a professor of psychiatry and executive director of the Mary Horrigan Connors Center for Women’s Health and Gender Biology at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, said the study findings were not surprising given how common the complaints of stress and depressive symptoms are.
“Mood changes are linked with acute, immediate cortisol levels at the same point in time, and cognitive symptoms were linked to more chronically elevated cortisol levels,” Dr. Joffe said in an interview. “Women and their providers should monitor for these challenging brain symptoms in midlife as they affect performance and quality of life and are linked with changes in the HPA axis as stress biomarkers.”
Because the study is small and has a cross-sectional design, it’s not possible to determine the direction of the associations or to make any inferences about causation, Dr. Joffe said.
“We cannot make the conclusion that stress is adversely affecting mood and cognitive performance given the design limitations. It is possible that mood and cognitive issues contributed to these stress markers,” Dr. Joffe said.“However, it is known that the experience of stress is linked with vulnerability to mood and cognitive symptoms, and also that mood and cognitive symptoms induce significant stress.”
The research was funded by the Menopause Society, Colorado University, the Ludeman Family Center for Women’s Health Research, the National Institute of Mental Health, and the National Institute of Aging. Dr. Metcalf had no disclosures. Dr. Joffe has received grant support from Merck, Pfizer and Sage, and has been a consultant or advisor for Bayer, Merck and Hello Therapeutics.
PHILADELPHIA – , according to research presented at the annual meeting of the Menopause Society (formerly the North American Menopause Society).
“This work suggests that markers of hypothalamic-pituitary-axis activation that capture total cortisol secretion over multiple months, [such as] hair cortisol, strongly correlate with cognitive performance on attention and working memory tasks, whereas measures of more acute cortisol, [such as] salivary cortisol, may be more strongly associated with depression symptom severity and verbal learning,” Christina Metcalf, PhD, an assistant professor of psychiatry in the Colorado Center for Women’s Behavioral Health and Wellness at the University of Colorado at Denver, Aurora, told attendees. “Given the associations with chronic stress, there’s a lot of potential here to increase our knowledge about how women are doing and managing stress and life stressors during this life transition,” she said.
The study involved collecting hair and saliva samples from 43 healthy women in late perimenopause or early postmenopause with an average age of 51. The participants were predominantly white and college educated. The hair sample was taken within 2 cm of the scalp, and the saliva samples were collected the day after the hair sample collection, at the start and end of a 30-minute rest period that took place between 2:00 and 3:00 p.m. local time.
All the participants had an intact uterus and at least one ovary. None of the participants were current smokers or had recent alcohol or drug dependence, and none had used hormones within the previous 6 months. The study also excluded women who were pregnant or breastfeeding, who had bleached hair or no hair, who were taking steroids, beta blockers or opioid medication, and who had recently taken NSAIDS.
Measuring hair cortisol more feasible
The study was conducted remotely, with participants using video conferencing to communicate with the study personnel and then completing study procedures at home, including 2 days of cognitive testing with the California Verbal Learning Test – Third Edition and the n-back and continuous performance tasks. The participants also completed the Center for Epidemiologic Studies Depression Scale (CES-D).
Participants with higher levels of hair cortisol and salivary cortisol also had more severe depression symptoms (P < .001). Hair cortisol was also significantly associated with attention and working memory: Women with higher levels had fewer correct answers on the 0-back and 1-back trials (P < .01) and made more mistakes on the 2-back trial (P < .001). They also scored with less specificity on the continuous performance tasks (P = .022).
Although no association existed between hair cortisol levels and verbal learning or verbal memory (P > .05), participants with higher hair cortisol did score worse on the immediate recall trials (P = .034). Salivary cortisol levels, on the other hand, showed no association with memory recall trials, attention or working memory (P > .05).
Measuring cortisol from hair samples is more feasible than using saliva samples and may offer valuable insights regarding hypothalamic-pituitary-axis activity “to consider alongside the cognitive and mental health of late peri-/early postmenopausal women,” Dr. Metcalf told attendees. The next step is to find out whether the hypothalamic-pituitary-axis axis is a modifiable biomarker that can be used to improve executive function.
The study was limited by its small population, its cross-sectional design, and the lack of covariates in the current analyses.
Monitor symptoms in midlife
Hadine Joffe, MD, MSc, a professor of psychiatry and executive director of the Mary Horrigan Connors Center for Women’s Health and Gender Biology at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, said the study findings were not surprising given how common the complaints of stress and depressive symptoms are.
“Mood changes are linked with acute, immediate cortisol levels at the same point in time, and cognitive symptoms were linked to more chronically elevated cortisol levels,” Dr. Joffe said in an interview. “Women and their providers should monitor for these challenging brain symptoms in midlife as they affect performance and quality of life and are linked with changes in the HPA axis as stress biomarkers.”
Because the study is small and has a cross-sectional design, it’s not possible to determine the direction of the associations or to make any inferences about causation, Dr. Joffe said.
“We cannot make the conclusion that stress is adversely affecting mood and cognitive performance given the design limitations. It is possible that mood and cognitive issues contributed to these stress markers,” Dr. Joffe said.“However, it is known that the experience of stress is linked with vulnerability to mood and cognitive symptoms, and also that mood and cognitive symptoms induce significant stress.”
The research was funded by the Menopause Society, Colorado University, the Ludeman Family Center for Women’s Health Research, the National Institute of Mental Health, and the National Institute of Aging. Dr. Metcalf had no disclosures. Dr. Joffe has received grant support from Merck, Pfizer and Sage, and has been a consultant or advisor for Bayer, Merck and Hello Therapeutics.
PHILADELPHIA – , according to research presented at the annual meeting of the Menopause Society (formerly the North American Menopause Society).
“This work suggests that markers of hypothalamic-pituitary-axis activation that capture total cortisol secretion over multiple months, [such as] hair cortisol, strongly correlate with cognitive performance on attention and working memory tasks, whereas measures of more acute cortisol, [such as] salivary cortisol, may be more strongly associated with depression symptom severity and verbal learning,” Christina Metcalf, PhD, an assistant professor of psychiatry in the Colorado Center for Women’s Behavioral Health and Wellness at the University of Colorado at Denver, Aurora, told attendees. “Given the associations with chronic stress, there’s a lot of potential here to increase our knowledge about how women are doing and managing stress and life stressors during this life transition,” she said.
The study involved collecting hair and saliva samples from 43 healthy women in late perimenopause or early postmenopause with an average age of 51. The participants were predominantly white and college educated. The hair sample was taken within 2 cm of the scalp, and the saliva samples were collected the day after the hair sample collection, at the start and end of a 30-minute rest period that took place between 2:00 and 3:00 p.m. local time.
All the participants had an intact uterus and at least one ovary. None of the participants were current smokers or had recent alcohol or drug dependence, and none had used hormones within the previous 6 months. The study also excluded women who were pregnant or breastfeeding, who had bleached hair or no hair, who were taking steroids, beta blockers or opioid medication, and who had recently taken NSAIDS.
Measuring hair cortisol more feasible
The study was conducted remotely, with participants using video conferencing to communicate with the study personnel and then completing study procedures at home, including 2 days of cognitive testing with the California Verbal Learning Test – Third Edition and the n-back and continuous performance tasks. The participants also completed the Center for Epidemiologic Studies Depression Scale (CES-D).
Participants with higher levels of hair cortisol and salivary cortisol also had more severe depression symptoms (P < .001). Hair cortisol was also significantly associated with attention and working memory: Women with higher levels had fewer correct answers on the 0-back and 1-back trials (P < .01) and made more mistakes on the 2-back trial (P < .001). They also scored with less specificity on the continuous performance tasks (P = .022).
Although no association existed between hair cortisol levels and verbal learning or verbal memory (P > .05), participants with higher hair cortisol did score worse on the immediate recall trials (P = .034). Salivary cortisol levels, on the other hand, showed no association with memory recall trials, attention or working memory (P > .05).
Measuring cortisol from hair samples is more feasible than using saliva samples and may offer valuable insights regarding hypothalamic-pituitary-axis activity “to consider alongside the cognitive and mental health of late peri-/early postmenopausal women,” Dr. Metcalf told attendees. The next step is to find out whether the hypothalamic-pituitary-axis axis is a modifiable biomarker that can be used to improve executive function.
The study was limited by its small population, its cross-sectional design, and the lack of covariates in the current analyses.
Monitor symptoms in midlife
Hadine Joffe, MD, MSc, a professor of psychiatry and executive director of the Mary Horrigan Connors Center for Women’s Health and Gender Biology at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, said the study findings were not surprising given how common the complaints of stress and depressive symptoms are.
“Mood changes are linked with acute, immediate cortisol levels at the same point in time, and cognitive symptoms were linked to more chronically elevated cortisol levels,” Dr. Joffe said in an interview. “Women and their providers should monitor for these challenging brain symptoms in midlife as they affect performance and quality of life and are linked with changes in the HPA axis as stress biomarkers.”
Because the study is small and has a cross-sectional design, it’s not possible to determine the direction of the associations or to make any inferences about causation, Dr. Joffe said.
“We cannot make the conclusion that stress is adversely affecting mood and cognitive performance given the design limitations. It is possible that mood and cognitive issues contributed to these stress markers,” Dr. Joffe said.“However, it is known that the experience of stress is linked with vulnerability to mood and cognitive symptoms, and also that mood and cognitive symptoms induce significant stress.”
The research was funded by the Menopause Society, Colorado University, the Ludeman Family Center for Women’s Health Research, the National Institute of Mental Health, and the National Institute of Aging. Dr. Metcalf had no disclosures. Dr. Joffe has received grant support from Merck, Pfizer and Sage, and has been a consultant or advisor for Bayer, Merck and Hello Therapeutics.
AT NAMS 2023
Bariatric surgery, including sleeve gastrectomy, linked to fracture risk
VANCOUVER – Patients who undergo either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy are at an increased risk of fracture, compared with patients with obesity who do not undergo surgery, according to a new analysis of a predominantly male group of U.S. veterans.
Previous studies involving premenopausal women have found a risk of bone mineral density loss and fracture with bariatric surgery, but little was known about the risk among men. Research has also shown an increase in risk after RYGB, but there is less information on risks associated with sleeve gastrectomy, though it is now the most common surgery for weight loss.
Bone density loss after bariatric surgery has been shown to be significant, according to Eileen H. Koh, MD. “It’s quite a lot of bone loss, quickly,” said Dr. Koh, a graduated fellow from the endocrinology program at the University of California, San Francisco, who is moving to the University of Washington, Seattle.
Those observations generally come from studies of younger women. The purpose of the new study “was to see if we see the same risk of fracture in veterans who are older men, so kind of the opposite of the typical bariatric patient,” said Dr. Koh, who presented the research at the annual meeting of the American Society for Bone and Mineral Research.
The researchers analyzed data from 8,299 U.S. veterans who underwent sleeve gastrectomy (41%), RYGB (51%), adjustable gastric banding (4%), or an unspecified bariatric procedure (4%) between 2000 and 2020. They were matched with 24,877 individuals with obesity who did not undergo surgery. The investigators excluded individuals who were at high risk of fracture because of another condition, such as organ transplantation or dialysis. Men made up 70% of both surgical and nonsurgical groups. The mean age was 52 years for both, and 89% and 88% were not Hispanic or Latino, respectively. The proportion of White individuals was 72% and 64%, and the proportion of Black individuals was 18% and 24%.
After adjustment for demographic variables and comorbidities, bariatric surgery was associated with a 68% increased risk of fracture (hazard ratio, 1.68; 95% confidence interval, 1.57-1.80), including hip fractures (HR, 2.42; 95% CI, 1.98-2.97), spine (HR, 1.82; 95% CI, 1.61-2.06), radius/ulna (HR, 2.38; 95% CI, 2.05-2.77), humerus (HR, 1.56; 95% CI, 1.28-1.89), pelvis (HR, 2.41; 95% CI, 1.68-3.46), and tibia/fibula/ankle (HR, 1.50; 95% CI, 1.33-1.69). Increased fracture risk was associated with RYGB (HR, 1.93; 95% CI, 1.75-2.12) and sleeve gastrectomy (HR, 1.50; 95% CI, 1.33-1.69) but not adjustable gastric banding.
Compared with sleeve gastrectomy, adjustable gastric banding was associated with a decreased risk of fracture (HR, 0.64; 95% CI, 0.49-0.84; P = .0012).
The study’s predominantly male population is important because men also get osteoporosis and are frequently overlooked, according to Anne Schafer, MD, who was the lead author of the study. “Even after they fracture, men are sometimes less likely to get care to prevent the next fracture. We’ve shown here that especially men who are on the older side, who go through surgical weight loss, do have a higher risk of fracture compared to those who are similarly obese but have not had the operation,” said Dr. Schafer, a professor of medicine at the University of California, San Francisco, and chief of endocrinology and metabolism at the San Francisco VA Medical Center.
There are limited data on fracture risk after sleeve gastrectomy. “I think this is one of the first times that I’ve been able to demonstrate that there was a higher risk of fracture with sleeve gastrectomy in comparison with nonsurgical cohorts. Of course, it’s necessary to confirm these findings in further studies, but it’s interesting,” said Julien Paccou, MD, who attended the poster session and was asked for comment. His group’s study of a French population showed an increased fracture risk associated with RYGB but not sleeve gastrectomy. Another study found a reduction of fracture risk associated with sleeve gastrectomy and no difference between RYGB and nonsurgical matched control patients in a Medicare population.
In fact, there is a belief that fracture risk may be lower with sleeve gastrectomy, according to Dr. Schafer. “It’s part of why it’s so popular,” she said.
The reasons for increased fracture risk following surgical weight loss remains unknown, according to Dr. Paccou, but they could include mechanical unloading, loss of lean mass, and hormone and nutrition changes. “There are many, many factors,” said Dr. Paccou, a professor of rheumatology at Hospital Roger Salengro in Lille, France.
The study’s findings of increased risk of fracture after sleeve gastrectomy may be an argument against malabsorption because the procedure shouldn’t affect nutrient absorption. It suggests that other factors are at play. “It’s not the only reason,” Dr. Schafer said.
There are recommendations for postbariatric surgery care to optimize bone health, such as protein intake and calcium and vitamin D targets, along with lifestyle factors. “Despite all those [efforts], we still know that bone loss occurs,” Dr. Koh said. In fact, the group is conducting a study funded by Amgen of the use of denosumab (Prolia) for the prevention of high-turnover bone loss after RYGB and sleeve gastrectomy.
Dr. Schafer has received research support from Bone Health Technologies and Amgen. Dr. Koh and Dr. Paccou have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
VANCOUVER – Patients who undergo either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy are at an increased risk of fracture, compared with patients with obesity who do not undergo surgery, according to a new analysis of a predominantly male group of U.S. veterans.
Previous studies involving premenopausal women have found a risk of bone mineral density loss and fracture with bariatric surgery, but little was known about the risk among men. Research has also shown an increase in risk after RYGB, but there is less information on risks associated with sleeve gastrectomy, though it is now the most common surgery for weight loss.
Bone density loss after bariatric surgery has been shown to be significant, according to Eileen H. Koh, MD. “It’s quite a lot of bone loss, quickly,” said Dr. Koh, a graduated fellow from the endocrinology program at the University of California, San Francisco, who is moving to the University of Washington, Seattle.
Those observations generally come from studies of younger women. The purpose of the new study “was to see if we see the same risk of fracture in veterans who are older men, so kind of the opposite of the typical bariatric patient,” said Dr. Koh, who presented the research at the annual meeting of the American Society for Bone and Mineral Research.
The researchers analyzed data from 8,299 U.S. veterans who underwent sleeve gastrectomy (41%), RYGB (51%), adjustable gastric banding (4%), or an unspecified bariatric procedure (4%) between 2000 and 2020. They were matched with 24,877 individuals with obesity who did not undergo surgery. The investigators excluded individuals who were at high risk of fracture because of another condition, such as organ transplantation or dialysis. Men made up 70% of both surgical and nonsurgical groups. The mean age was 52 years for both, and 89% and 88% were not Hispanic or Latino, respectively. The proportion of White individuals was 72% and 64%, and the proportion of Black individuals was 18% and 24%.
After adjustment for demographic variables and comorbidities, bariatric surgery was associated with a 68% increased risk of fracture (hazard ratio, 1.68; 95% confidence interval, 1.57-1.80), including hip fractures (HR, 2.42; 95% CI, 1.98-2.97), spine (HR, 1.82; 95% CI, 1.61-2.06), radius/ulna (HR, 2.38; 95% CI, 2.05-2.77), humerus (HR, 1.56; 95% CI, 1.28-1.89), pelvis (HR, 2.41; 95% CI, 1.68-3.46), and tibia/fibula/ankle (HR, 1.50; 95% CI, 1.33-1.69). Increased fracture risk was associated with RYGB (HR, 1.93; 95% CI, 1.75-2.12) and sleeve gastrectomy (HR, 1.50; 95% CI, 1.33-1.69) but not adjustable gastric banding.
Compared with sleeve gastrectomy, adjustable gastric banding was associated with a decreased risk of fracture (HR, 0.64; 95% CI, 0.49-0.84; P = .0012).
The study’s predominantly male population is important because men also get osteoporosis and are frequently overlooked, according to Anne Schafer, MD, who was the lead author of the study. “Even after they fracture, men are sometimes less likely to get care to prevent the next fracture. We’ve shown here that especially men who are on the older side, who go through surgical weight loss, do have a higher risk of fracture compared to those who are similarly obese but have not had the operation,” said Dr. Schafer, a professor of medicine at the University of California, San Francisco, and chief of endocrinology and metabolism at the San Francisco VA Medical Center.
There are limited data on fracture risk after sleeve gastrectomy. “I think this is one of the first times that I’ve been able to demonstrate that there was a higher risk of fracture with sleeve gastrectomy in comparison with nonsurgical cohorts. Of course, it’s necessary to confirm these findings in further studies, but it’s interesting,” said Julien Paccou, MD, who attended the poster session and was asked for comment. His group’s study of a French population showed an increased fracture risk associated with RYGB but not sleeve gastrectomy. Another study found a reduction of fracture risk associated with sleeve gastrectomy and no difference between RYGB and nonsurgical matched control patients in a Medicare population.
In fact, there is a belief that fracture risk may be lower with sleeve gastrectomy, according to Dr. Schafer. “It’s part of why it’s so popular,” she said.
The reasons for increased fracture risk following surgical weight loss remains unknown, according to Dr. Paccou, but they could include mechanical unloading, loss of lean mass, and hormone and nutrition changes. “There are many, many factors,” said Dr. Paccou, a professor of rheumatology at Hospital Roger Salengro in Lille, France.
The study’s findings of increased risk of fracture after sleeve gastrectomy may be an argument against malabsorption because the procedure shouldn’t affect nutrient absorption. It suggests that other factors are at play. “It’s not the only reason,” Dr. Schafer said.
There are recommendations for postbariatric surgery care to optimize bone health, such as protein intake and calcium and vitamin D targets, along with lifestyle factors. “Despite all those [efforts], we still know that bone loss occurs,” Dr. Koh said. In fact, the group is conducting a study funded by Amgen of the use of denosumab (Prolia) for the prevention of high-turnover bone loss after RYGB and sleeve gastrectomy.
Dr. Schafer has received research support from Bone Health Technologies and Amgen. Dr. Koh and Dr. Paccou have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
VANCOUVER – Patients who undergo either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy are at an increased risk of fracture, compared with patients with obesity who do not undergo surgery, according to a new analysis of a predominantly male group of U.S. veterans.
Previous studies involving premenopausal women have found a risk of bone mineral density loss and fracture with bariatric surgery, but little was known about the risk among men. Research has also shown an increase in risk after RYGB, but there is less information on risks associated with sleeve gastrectomy, though it is now the most common surgery for weight loss.
Bone density loss after bariatric surgery has been shown to be significant, according to Eileen H. Koh, MD. “It’s quite a lot of bone loss, quickly,” said Dr. Koh, a graduated fellow from the endocrinology program at the University of California, San Francisco, who is moving to the University of Washington, Seattle.
Those observations generally come from studies of younger women. The purpose of the new study “was to see if we see the same risk of fracture in veterans who are older men, so kind of the opposite of the typical bariatric patient,” said Dr. Koh, who presented the research at the annual meeting of the American Society for Bone and Mineral Research.
The researchers analyzed data from 8,299 U.S. veterans who underwent sleeve gastrectomy (41%), RYGB (51%), adjustable gastric banding (4%), or an unspecified bariatric procedure (4%) between 2000 and 2020. They were matched with 24,877 individuals with obesity who did not undergo surgery. The investigators excluded individuals who were at high risk of fracture because of another condition, such as organ transplantation or dialysis. Men made up 70% of both surgical and nonsurgical groups. The mean age was 52 years for both, and 89% and 88% were not Hispanic or Latino, respectively. The proportion of White individuals was 72% and 64%, and the proportion of Black individuals was 18% and 24%.
After adjustment for demographic variables and comorbidities, bariatric surgery was associated with a 68% increased risk of fracture (hazard ratio, 1.68; 95% confidence interval, 1.57-1.80), including hip fractures (HR, 2.42; 95% CI, 1.98-2.97), spine (HR, 1.82; 95% CI, 1.61-2.06), radius/ulna (HR, 2.38; 95% CI, 2.05-2.77), humerus (HR, 1.56; 95% CI, 1.28-1.89), pelvis (HR, 2.41; 95% CI, 1.68-3.46), and tibia/fibula/ankle (HR, 1.50; 95% CI, 1.33-1.69). Increased fracture risk was associated with RYGB (HR, 1.93; 95% CI, 1.75-2.12) and sleeve gastrectomy (HR, 1.50; 95% CI, 1.33-1.69) but not adjustable gastric banding.
Compared with sleeve gastrectomy, adjustable gastric banding was associated with a decreased risk of fracture (HR, 0.64; 95% CI, 0.49-0.84; P = .0012).
The study’s predominantly male population is important because men also get osteoporosis and are frequently overlooked, according to Anne Schafer, MD, who was the lead author of the study. “Even after they fracture, men are sometimes less likely to get care to prevent the next fracture. We’ve shown here that especially men who are on the older side, who go through surgical weight loss, do have a higher risk of fracture compared to those who are similarly obese but have not had the operation,” said Dr. Schafer, a professor of medicine at the University of California, San Francisco, and chief of endocrinology and metabolism at the San Francisco VA Medical Center.
There are limited data on fracture risk after sleeve gastrectomy. “I think this is one of the first times that I’ve been able to demonstrate that there was a higher risk of fracture with sleeve gastrectomy in comparison with nonsurgical cohorts. Of course, it’s necessary to confirm these findings in further studies, but it’s interesting,” said Julien Paccou, MD, who attended the poster session and was asked for comment. His group’s study of a French population showed an increased fracture risk associated with RYGB but not sleeve gastrectomy. Another study found a reduction of fracture risk associated with sleeve gastrectomy and no difference between RYGB and nonsurgical matched control patients in a Medicare population.
In fact, there is a belief that fracture risk may be lower with sleeve gastrectomy, according to Dr. Schafer. “It’s part of why it’s so popular,” she said.
The reasons for increased fracture risk following surgical weight loss remains unknown, according to Dr. Paccou, but they could include mechanical unloading, loss of lean mass, and hormone and nutrition changes. “There are many, many factors,” said Dr. Paccou, a professor of rheumatology at Hospital Roger Salengro in Lille, France.
The study’s findings of increased risk of fracture after sleeve gastrectomy may be an argument against malabsorption because the procedure shouldn’t affect nutrient absorption. It suggests that other factors are at play. “It’s not the only reason,” Dr. Schafer said.
There are recommendations for postbariatric surgery care to optimize bone health, such as protein intake and calcium and vitamin D targets, along with lifestyle factors. “Despite all those [efforts], we still know that bone loss occurs,” Dr. Koh said. In fact, the group is conducting a study funded by Amgen of the use of denosumab (Prolia) for the prevention of high-turnover bone loss after RYGB and sleeve gastrectomy.
Dr. Schafer has received research support from Bone Health Technologies and Amgen. Dr. Koh and Dr. Paccou have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ASBMR 2023
Tricyclics may raise fracture risk in type 2 diabetes
VANCOUVER – , independent of any prevalent neuropathy, according to findings from an analysis of a large, randomized clinical trial.
Although the findings are suggestive, they don’t definitively pin blame on TCAs, said Rachel Elam, MD, who presented the study at the annual meeting of the American Society for Bone and Mineral Research. “I think that there’s not enough information to conclude that tricyclic antidepressants directly lead to fractures, but I think it opens the door [to] something we should look into more. Is it being mediated by a better predictor, or is it the medication itself? I think it’s more hypothesis generating,” said Dr. Elam, an assistant professor of medicine in the division of rheumatology at the Medical College of Georgia, Augusta.
Patients with type 2 diabetes are known to be at increased risk of fracture, but prediction tools tend to underestimate this risk, Dr. Elam said. “Type 2 diabetes–specific clinical risk factors may be helpful for finding out fracture risk in this population,” Dr. Elam said during her talk.
Glycemic control is one candidate risk factor because advanced glycation end products are linked to reduced bone strength. Other factors include antidiabetic medication use, neuropathy, and microvascular disease, which has been linked to increased cortical porosity.
The study examined a somewhat younger population than previous surveys, having drawn from the Look AHEAD-C clinical trial, which examined the effects of an intensive lifestyle intervention on type 2 diabetes. Look AHEAD-C included 4,697 participants aged 45-75 from 16 U.S. clinical sites. Participants had a body mass index of 25.0 kg/m2 or higher and hemoglobin A1c levels of 11% or below.
Dr. Elam cited the database’s inclusion of factors like A1c levels, renal parameters, and diabetic neuropathy. “It gave us a really good population to look at those risk factors” in a large group of people with type 2 diabetes, she said.
Over a median follow-up of 16.6 years, there were 649 participants with incident first clinical fracture(s). Statistically significant factors predicting fracture risk included TCA use (hazard ratio, 2.24; 95% confidence interval, 1.14-4.43), female gender (HR, 2.20; 95% CI, 1.83-2.66), insulin use (HR, 1.26; 95% CI, 1.02-1.57), increases in A1c level (per 1% increase: HR, 1.12; 95% CI, 1.04-1.20), age (HR, 1.02; 95% CI, 1.01-1.04), other or mixed race/ethnicity (HR, 0.68; 95% CI, 0.52-0.87), Hispanic White race/ethnicity (HR, 0.60; 95% CI, 0.39-0.91), non-Hispanic Black race/ethnicity (HR, 0.35; 95% CI, 0.26-0.47), and estrogen use (HR, 0.65; 95% CI, 0.44-0.98).
During the Q&A session following the presentation, Elsa Strotmeyer, PhD, commented that TCAs have been linked to central nervous system pathways in falls in other populations. “It’s a very nice study. It’s important to look at the diabetes complications related to the fracture risk, but I thought that they should have emphasized some more of the diabetes complications being related to fracture rather than these tricyclic antidepressants, because that is not a unique factor to that population,” said Dr. Strotmeyer, who is an associate professor of epidemiology at the University of Pittsburgh.
Instead, she noted a different strength of the study. “The study population is important because they’re a relatively young population with type 2 diabetes, compared to many studies [that] have been published in older populations. Showing similar things that we found in older populations was the unique piece and the important piece of this study,” Dr. Strotmeyer said.
Ultimately, the model wasn’t sufficient to be used as a fall risk predictor, but it should inform future work, according to Dr. Elam. “I think it does lay some new groundwork that when we’re looking forward, it may [help in building] other models to better predict fracture risk in type 2 diabetes. Things that would be important to include [in future models] would be medication use, such as tricyclic antidepressants,” and to make sure we include glycemic control, A1c, and insulin medication.
The study was independently funded. Dr. Elam and Dr. Strotmeyer report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
VANCOUVER – , independent of any prevalent neuropathy, according to findings from an analysis of a large, randomized clinical trial.
Although the findings are suggestive, they don’t definitively pin blame on TCAs, said Rachel Elam, MD, who presented the study at the annual meeting of the American Society for Bone and Mineral Research. “I think that there’s not enough information to conclude that tricyclic antidepressants directly lead to fractures, but I think it opens the door [to] something we should look into more. Is it being mediated by a better predictor, or is it the medication itself? I think it’s more hypothesis generating,” said Dr. Elam, an assistant professor of medicine in the division of rheumatology at the Medical College of Georgia, Augusta.
Patients with type 2 diabetes are known to be at increased risk of fracture, but prediction tools tend to underestimate this risk, Dr. Elam said. “Type 2 diabetes–specific clinical risk factors may be helpful for finding out fracture risk in this population,” Dr. Elam said during her talk.
Glycemic control is one candidate risk factor because advanced glycation end products are linked to reduced bone strength. Other factors include antidiabetic medication use, neuropathy, and microvascular disease, which has been linked to increased cortical porosity.
The study examined a somewhat younger population than previous surveys, having drawn from the Look AHEAD-C clinical trial, which examined the effects of an intensive lifestyle intervention on type 2 diabetes. Look AHEAD-C included 4,697 participants aged 45-75 from 16 U.S. clinical sites. Participants had a body mass index of 25.0 kg/m2 or higher and hemoglobin A1c levels of 11% or below.
Dr. Elam cited the database’s inclusion of factors like A1c levels, renal parameters, and diabetic neuropathy. “It gave us a really good population to look at those risk factors” in a large group of people with type 2 diabetes, she said.
Over a median follow-up of 16.6 years, there were 649 participants with incident first clinical fracture(s). Statistically significant factors predicting fracture risk included TCA use (hazard ratio, 2.24; 95% confidence interval, 1.14-4.43), female gender (HR, 2.20; 95% CI, 1.83-2.66), insulin use (HR, 1.26; 95% CI, 1.02-1.57), increases in A1c level (per 1% increase: HR, 1.12; 95% CI, 1.04-1.20), age (HR, 1.02; 95% CI, 1.01-1.04), other or mixed race/ethnicity (HR, 0.68; 95% CI, 0.52-0.87), Hispanic White race/ethnicity (HR, 0.60; 95% CI, 0.39-0.91), non-Hispanic Black race/ethnicity (HR, 0.35; 95% CI, 0.26-0.47), and estrogen use (HR, 0.65; 95% CI, 0.44-0.98).
During the Q&A session following the presentation, Elsa Strotmeyer, PhD, commented that TCAs have been linked to central nervous system pathways in falls in other populations. “It’s a very nice study. It’s important to look at the diabetes complications related to the fracture risk, but I thought that they should have emphasized some more of the diabetes complications being related to fracture rather than these tricyclic antidepressants, because that is not a unique factor to that population,” said Dr. Strotmeyer, who is an associate professor of epidemiology at the University of Pittsburgh.
Instead, she noted a different strength of the study. “The study population is important because they’re a relatively young population with type 2 diabetes, compared to many studies [that] have been published in older populations. Showing similar things that we found in older populations was the unique piece and the important piece of this study,” Dr. Strotmeyer said.
Ultimately, the model wasn’t sufficient to be used as a fall risk predictor, but it should inform future work, according to Dr. Elam. “I think it does lay some new groundwork that when we’re looking forward, it may [help in building] other models to better predict fracture risk in type 2 diabetes. Things that would be important to include [in future models] would be medication use, such as tricyclic antidepressants,” and to make sure we include glycemic control, A1c, and insulin medication.
The study was independently funded. Dr. Elam and Dr. Strotmeyer report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
VANCOUVER – , independent of any prevalent neuropathy, according to findings from an analysis of a large, randomized clinical trial.
Although the findings are suggestive, they don’t definitively pin blame on TCAs, said Rachel Elam, MD, who presented the study at the annual meeting of the American Society for Bone and Mineral Research. “I think that there’s not enough information to conclude that tricyclic antidepressants directly lead to fractures, but I think it opens the door [to] something we should look into more. Is it being mediated by a better predictor, or is it the medication itself? I think it’s more hypothesis generating,” said Dr. Elam, an assistant professor of medicine in the division of rheumatology at the Medical College of Georgia, Augusta.
Patients with type 2 diabetes are known to be at increased risk of fracture, but prediction tools tend to underestimate this risk, Dr. Elam said. “Type 2 diabetes–specific clinical risk factors may be helpful for finding out fracture risk in this population,” Dr. Elam said during her talk.
Glycemic control is one candidate risk factor because advanced glycation end products are linked to reduced bone strength. Other factors include antidiabetic medication use, neuropathy, and microvascular disease, which has been linked to increased cortical porosity.
The study examined a somewhat younger population than previous surveys, having drawn from the Look AHEAD-C clinical trial, which examined the effects of an intensive lifestyle intervention on type 2 diabetes. Look AHEAD-C included 4,697 participants aged 45-75 from 16 U.S. clinical sites. Participants had a body mass index of 25.0 kg/m2 or higher and hemoglobin A1c levels of 11% or below.
Dr. Elam cited the database’s inclusion of factors like A1c levels, renal parameters, and diabetic neuropathy. “It gave us a really good population to look at those risk factors” in a large group of people with type 2 diabetes, she said.
Over a median follow-up of 16.6 years, there were 649 participants with incident first clinical fracture(s). Statistically significant factors predicting fracture risk included TCA use (hazard ratio, 2.24; 95% confidence interval, 1.14-4.43), female gender (HR, 2.20; 95% CI, 1.83-2.66), insulin use (HR, 1.26; 95% CI, 1.02-1.57), increases in A1c level (per 1% increase: HR, 1.12; 95% CI, 1.04-1.20), age (HR, 1.02; 95% CI, 1.01-1.04), other or mixed race/ethnicity (HR, 0.68; 95% CI, 0.52-0.87), Hispanic White race/ethnicity (HR, 0.60; 95% CI, 0.39-0.91), non-Hispanic Black race/ethnicity (HR, 0.35; 95% CI, 0.26-0.47), and estrogen use (HR, 0.65; 95% CI, 0.44-0.98).
During the Q&A session following the presentation, Elsa Strotmeyer, PhD, commented that TCAs have been linked to central nervous system pathways in falls in other populations. “It’s a very nice study. It’s important to look at the diabetes complications related to the fracture risk, but I thought that they should have emphasized some more of the diabetes complications being related to fracture rather than these tricyclic antidepressants, because that is not a unique factor to that population,” said Dr. Strotmeyer, who is an associate professor of epidemiology at the University of Pittsburgh.
Instead, she noted a different strength of the study. “The study population is important because they’re a relatively young population with type 2 diabetes, compared to many studies [that] have been published in older populations. Showing similar things that we found in older populations was the unique piece and the important piece of this study,” Dr. Strotmeyer said.
Ultimately, the model wasn’t sufficient to be used as a fall risk predictor, but it should inform future work, according to Dr. Elam. “I think it does lay some new groundwork that when we’re looking forward, it may [help in building] other models to better predict fracture risk in type 2 diabetes. Things that would be important to include [in future models] would be medication use, such as tricyclic antidepressants,” and to make sure we include glycemic control, A1c, and insulin medication.
The study was independently funded. Dr. Elam and Dr. Strotmeyer report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ASBMR 2023
Recombinant IL-2 shows potential in atopic dermatitis
BERLIN – A novel regulatory T cell–stimulating therapy appears to significantly improve atopic dermatitis in patients with moderate to severe disease and may even benefit quality of life, suggest results from a phase 1b trial.
The research was presented at the annual congress of the European Academy of Dermatology and Venereology.
, after which responders were observed out to 48 weeks. The higher dosage was associated with significant improvements in Eczema Area and Severity Index (EASI) and Body Surface Area (BSA) scores, which were maintained over the course of the study, as well as trends for improved patient-reported outcomes.
“This is the first study to demonstrate the therapeutic potential of rezpegaldesleukin,” said presenter Jonathan Silverberg, MD, PhD, MPH, professor of dermatology and director of clinical research at George Washington University, Washington. He added, “These may be some of the most compelling data to date for the field, proving that, at a high level, if you causally increase regulator T cells, you will take down inflammation and improve a disease state.
“For me, this is proof of concept for so many things, and it gets me very excited.”
Dr. Silverberg noted that with the response maintained out to 48 weeks, despite stopping therapy at week 12, the “hope” with the approach of inducing regulator T cells “is that we could induce tolerance and that we could have some potential for disease modification.”
He continued, “Maybe I daren’t use the word ‘cure,’ but can we at least get to something that is truly remitted, where they can stop the drug and maintain that response?”
Dr. Silverberg said rezpegaldesleukin is now being evaluated in a phase 2b study for moderate to severe atopic dermatitis, and a phase 2b trial for alopecia areata is in development.
Tiago dos Reis Matos, MD, PhD, MSc, Amsterdam University Medical Centers, who was not involved in the study, told this news organization that “recombinant human interleukin-2 is an original therapy.”
Instead of blocking or inhibiting inflammation, it stimulates the patient’s immune system to “restore a healthy balance.”
He explained that it “stimulates regulatory T cells, which can be seen as the Peace Corps of the immune system, responsible for maintaining the equilibrium and avoiding uncontrolled inflammation.”
At the meeting, Dr. Silverberg told the audience that although they are the “beneficiaries of riches of new advances” in atopic dermatitis, “still, many observational studies have shown that the majority of patients do not achieve adequate control by the end of their induction periods and clinical trials, in the real world,” with currently available treatments.
Moreover, “there are challenges that come up with any of the different therapies,” he said, with adverse effects an important issue. For example, biologic therapies are associated with conjunctivitis, facial erythema, and arthralgia, and there are boxed warnings for Janus kinase inhibitors.
Dr. Silverberg continued, “Even patients with a favorable response can experience a loss of disease control when they come off therapy.” Consequently, “new strategies are certainly welcome that could potentially induce both deep and potentially therapy-free remission.”
To those ends, he explained that regulatory T cells play a central role in immune homeostasis but have not been “therapeutically relevant until very recently,” when it was posited that increasing their function can “induce that homeostasis, to normalize the inflammatory cascades” seen in a range of conditions, including atopic dermatitis.
Rezpegaldesleukin has high selectivity for regulatory T cells, without causing activation of effector T cells, and has been shown to increase cell numbers in a dose-dependent manner that is sustained for up to 30 days.
The current study involved patients aged 18-70 years with moderate to severe atopic dermatitis and a history of inadequate responses or intolerance to topical medications, and an EASI score ≥ 16.
Participants were randomly assigned to receive subcutaneous rezpegaldesleukin 12 mcg/kg or 24 mcg/kg or placebo every 2 weeks for 12 weeks. They then discontinued treatment and were followed up until week 19, when responders, defined as having a reduction in EASI score ≥ 50%, continued follow-up out to week 48.
Seventeen patients were randomized to higher-dose rezpegaldesleukin, whereas 16 received the lower dose and 10 were assigned to placebo. Dr. Silverberg said that the three groups were “fairly well balanced,” with “fairly good representation” across age, race, and ethnicity groups.
The mean baseline EASI score was between 21.9 and 23.7, and the Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) suggested that there was an even split between moderate and severe atopic dermatitis, although the higher-dose rezpegaldesleukin group had more patients with moderate disease.
By week 12, rezpegaldesleukin was associated with significantly greater improvements in EASI scores vs. placebo. Patients on the higher dose had a mean 83% improvement over baseline vs. 65% with the lower dose and 47% with placebo (P = .002 for the higher dose vs. placebo).
Crucially, these differences were maintained up to week 48 in patients, particularly in the higher-dose group.
There was also a nonsignificant increase in the proportion of patients who achieved a reduction in EASI scores ≥ 75% over baseline with the active drug: 41% at week 12 with higher-dose rezpegaldesleukin, 25% with the lower dose, and 20% with placebo. Again, the benefit was maintained up to week 48.
The mean improvement in BSA score from baseline with rezpegaldesleukin was significantly greater than that seen with placebo, at 72% with the higher dose, 55% with the lower dose, and 36% with placebo (P = .0158 for the higher dose vs. placebo).
Although improvements in vIGA-AD scores over baseline with rezpegaldesleukin were not substantial at week 12, by week 48 there was a marked difference between higher-dose rezpegaldesleukin and placebo, with 40.0% of patients responding to the drug vs. 0% in the latter group.
A similar pattern was seen for the Itch Numeric Rating Scale, in which 55.6% of patients treated with higher-dose rezpegaldesleukin responding by week 48, compared with 0% of those who received placebo.
Greater improvements in the Dermatology Life Quality Index (DLQI) and Patient Oriented Eczema Measure (POEM) over baseline with higher-dose rezpegaldesleukin vs. plain placebo were also noted, despite a strong response in the latter group.
Dr. Silverberg reported that all treatment-emergent adverse effects in the two rezpegaldesleukin treatment arms were mild to moderate, with no severe or serious events observed.
The most common adverse events were mild to moderate injection-site reactions, seen in 75.0% of the lower-dose rezpegaldesleukin group and 58.8% the of higher-dose group. There were no cases of conjunctivitis.
The study was sponsored by Eli Lilly and Company in collaboration with Nektar Therapeutics.
Dr. Silverberg declares relationships with AbbVie, Alamar, Aldena, Amgen, AOBiome, Arcutis, Arena, Asana, ASLAN, BioMX, Biosion, Bodewell, Boehringer-Ingelheim, Bristol-Myers Squibb, Cara, Castle Biosciences, Celgene, Connect Biopharma, CorEvitas, Dermavant, DermTech, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Kiniksa, LEO Pharma, Nektar, Novartis, Optum, Pfizer, RAPT, Recludix, Regeneron, Sanofi-Genzyme, Shaperon, Target RWE, Union, and UpToDate.
A version of this article appeared on Medscape.com.
BERLIN – A novel regulatory T cell–stimulating therapy appears to significantly improve atopic dermatitis in patients with moderate to severe disease and may even benefit quality of life, suggest results from a phase 1b trial.
The research was presented at the annual congress of the European Academy of Dermatology and Venereology.
, after which responders were observed out to 48 weeks. The higher dosage was associated with significant improvements in Eczema Area and Severity Index (EASI) and Body Surface Area (BSA) scores, which were maintained over the course of the study, as well as trends for improved patient-reported outcomes.
“This is the first study to demonstrate the therapeutic potential of rezpegaldesleukin,” said presenter Jonathan Silverberg, MD, PhD, MPH, professor of dermatology and director of clinical research at George Washington University, Washington. He added, “These may be some of the most compelling data to date for the field, proving that, at a high level, if you causally increase regulator T cells, you will take down inflammation and improve a disease state.
“For me, this is proof of concept for so many things, and it gets me very excited.”
Dr. Silverberg noted that with the response maintained out to 48 weeks, despite stopping therapy at week 12, the “hope” with the approach of inducing regulator T cells “is that we could induce tolerance and that we could have some potential for disease modification.”
He continued, “Maybe I daren’t use the word ‘cure,’ but can we at least get to something that is truly remitted, where they can stop the drug and maintain that response?”
Dr. Silverberg said rezpegaldesleukin is now being evaluated in a phase 2b study for moderate to severe atopic dermatitis, and a phase 2b trial for alopecia areata is in development.
Tiago dos Reis Matos, MD, PhD, MSc, Amsterdam University Medical Centers, who was not involved in the study, told this news organization that “recombinant human interleukin-2 is an original therapy.”
Instead of blocking or inhibiting inflammation, it stimulates the patient’s immune system to “restore a healthy balance.”
He explained that it “stimulates regulatory T cells, which can be seen as the Peace Corps of the immune system, responsible for maintaining the equilibrium and avoiding uncontrolled inflammation.”
At the meeting, Dr. Silverberg told the audience that although they are the “beneficiaries of riches of new advances” in atopic dermatitis, “still, many observational studies have shown that the majority of patients do not achieve adequate control by the end of their induction periods and clinical trials, in the real world,” with currently available treatments.
Moreover, “there are challenges that come up with any of the different therapies,” he said, with adverse effects an important issue. For example, biologic therapies are associated with conjunctivitis, facial erythema, and arthralgia, and there are boxed warnings for Janus kinase inhibitors.
Dr. Silverberg continued, “Even patients with a favorable response can experience a loss of disease control when they come off therapy.” Consequently, “new strategies are certainly welcome that could potentially induce both deep and potentially therapy-free remission.”
To those ends, he explained that regulatory T cells play a central role in immune homeostasis but have not been “therapeutically relevant until very recently,” when it was posited that increasing their function can “induce that homeostasis, to normalize the inflammatory cascades” seen in a range of conditions, including atopic dermatitis.
Rezpegaldesleukin has high selectivity for regulatory T cells, without causing activation of effector T cells, and has been shown to increase cell numbers in a dose-dependent manner that is sustained for up to 30 days.
The current study involved patients aged 18-70 years with moderate to severe atopic dermatitis and a history of inadequate responses or intolerance to topical medications, and an EASI score ≥ 16.
Participants were randomly assigned to receive subcutaneous rezpegaldesleukin 12 mcg/kg or 24 mcg/kg or placebo every 2 weeks for 12 weeks. They then discontinued treatment and were followed up until week 19, when responders, defined as having a reduction in EASI score ≥ 50%, continued follow-up out to week 48.
Seventeen patients were randomized to higher-dose rezpegaldesleukin, whereas 16 received the lower dose and 10 were assigned to placebo. Dr. Silverberg said that the three groups were “fairly well balanced,” with “fairly good representation” across age, race, and ethnicity groups.
The mean baseline EASI score was between 21.9 and 23.7, and the Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) suggested that there was an even split between moderate and severe atopic dermatitis, although the higher-dose rezpegaldesleukin group had more patients with moderate disease.
By week 12, rezpegaldesleukin was associated with significantly greater improvements in EASI scores vs. placebo. Patients on the higher dose had a mean 83% improvement over baseline vs. 65% with the lower dose and 47% with placebo (P = .002 for the higher dose vs. placebo).
Crucially, these differences were maintained up to week 48 in patients, particularly in the higher-dose group.
There was also a nonsignificant increase in the proportion of patients who achieved a reduction in EASI scores ≥ 75% over baseline with the active drug: 41% at week 12 with higher-dose rezpegaldesleukin, 25% with the lower dose, and 20% with placebo. Again, the benefit was maintained up to week 48.
The mean improvement in BSA score from baseline with rezpegaldesleukin was significantly greater than that seen with placebo, at 72% with the higher dose, 55% with the lower dose, and 36% with placebo (P = .0158 for the higher dose vs. placebo).
Although improvements in vIGA-AD scores over baseline with rezpegaldesleukin were not substantial at week 12, by week 48 there was a marked difference between higher-dose rezpegaldesleukin and placebo, with 40.0% of patients responding to the drug vs. 0% in the latter group.
A similar pattern was seen for the Itch Numeric Rating Scale, in which 55.6% of patients treated with higher-dose rezpegaldesleukin responding by week 48, compared with 0% of those who received placebo.
Greater improvements in the Dermatology Life Quality Index (DLQI) and Patient Oriented Eczema Measure (POEM) over baseline with higher-dose rezpegaldesleukin vs. plain placebo were also noted, despite a strong response in the latter group.
Dr. Silverberg reported that all treatment-emergent adverse effects in the two rezpegaldesleukin treatment arms were mild to moderate, with no severe or serious events observed.
The most common adverse events were mild to moderate injection-site reactions, seen in 75.0% of the lower-dose rezpegaldesleukin group and 58.8% the of higher-dose group. There were no cases of conjunctivitis.
The study was sponsored by Eli Lilly and Company in collaboration with Nektar Therapeutics.
Dr. Silverberg declares relationships with AbbVie, Alamar, Aldena, Amgen, AOBiome, Arcutis, Arena, Asana, ASLAN, BioMX, Biosion, Bodewell, Boehringer-Ingelheim, Bristol-Myers Squibb, Cara, Castle Biosciences, Celgene, Connect Biopharma, CorEvitas, Dermavant, DermTech, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Kiniksa, LEO Pharma, Nektar, Novartis, Optum, Pfizer, RAPT, Recludix, Regeneron, Sanofi-Genzyme, Shaperon, Target RWE, Union, and UpToDate.
A version of this article appeared on Medscape.com.
BERLIN – A novel regulatory T cell–stimulating therapy appears to significantly improve atopic dermatitis in patients with moderate to severe disease and may even benefit quality of life, suggest results from a phase 1b trial.
The research was presented at the annual congress of the European Academy of Dermatology and Venereology.
, after which responders were observed out to 48 weeks. The higher dosage was associated with significant improvements in Eczema Area and Severity Index (EASI) and Body Surface Area (BSA) scores, which were maintained over the course of the study, as well as trends for improved patient-reported outcomes.
“This is the first study to demonstrate the therapeutic potential of rezpegaldesleukin,” said presenter Jonathan Silverberg, MD, PhD, MPH, professor of dermatology and director of clinical research at George Washington University, Washington. He added, “These may be some of the most compelling data to date for the field, proving that, at a high level, if you causally increase regulator T cells, you will take down inflammation and improve a disease state.
“For me, this is proof of concept for so many things, and it gets me very excited.”
Dr. Silverberg noted that with the response maintained out to 48 weeks, despite stopping therapy at week 12, the “hope” with the approach of inducing regulator T cells “is that we could induce tolerance and that we could have some potential for disease modification.”
He continued, “Maybe I daren’t use the word ‘cure,’ but can we at least get to something that is truly remitted, where they can stop the drug and maintain that response?”
Dr. Silverberg said rezpegaldesleukin is now being evaluated in a phase 2b study for moderate to severe atopic dermatitis, and a phase 2b trial for alopecia areata is in development.
Tiago dos Reis Matos, MD, PhD, MSc, Amsterdam University Medical Centers, who was not involved in the study, told this news organization that “recombinant human interleukin-2 is an original therapy.”
Instead of blocking or inhibiting inflammation, it stimulates the patient’s immune system to “restore a healthy balance.”
He explained that it “stimulates regulatory T cells, which can be seen as the Peace Corps of the immune system, responsible for maintaining the equilibrium and avoiding uncontrolled inflammation.”
At the meeting, Dr. Silverberg told the audience that although they are the “beneficiaries of riches of new advances” in atopic dermatitis, “still, many observational studies have shown that the majority of patients do not achieve adequate control by the end of their induction periods and clinical trials, in the real world,” with currently available treatments.
Moreover, “there are challenges that come up with any of the different therapies,” he said, with adverse effects an important issue. For example, biologic therapies are associated with conjunctivitis, facial erythema, and arthralgia, and there are boxed warnings for Janus kinase inhibitors.
Dr. Silverberg continued, “Even patients with a favorable response can experience a loss of disease control when they come off therapy.” Consequently, “new strategies are certainly welcome that could potentially induce both deep and potentially therapy-free remission.”
To those ends, he explained that regulatory T cells play a central role in immune homeostasis but have not been “therapeutically relevant until very recently,” when it was posited that increasing their function can “induce that homeostasis, to normalize the inflammatory cascades” seen in a range of conditions, including atopic dermatitis.
Rezpegaldesleukin has high selectivity for regulatory T cells, without causing activation of effector T cells, and has been shown to increase cell numbers in a dose-dependent manner that is sustained for up to 30 days.
The current study involved patients aged 18-70 years with moderate to severe atopic dermatitis and a history of inadequate responses or intolerance to topical medications, and an EASI score ≥ 16.
Participants were randomly assigned to receive subcutaneous rezpegaldesleukin 12 mcg/kg or 24 mcg/kg or placebo every 2 weeks for 12 weeks. They then discontinued treatment and were followed up until week 19, when responders, defined as having a reduction in EASI score ≥ 50%, continued follow-up out to week 48.
Seventeen patients were randomized to higher-dose rezpegaldesleukin, whereas 16 received the lower dose and 10 were assigned to placebo. Dr. Silverberg said that the three groups were “fairly well balanced,” with “fairly good representation” across age, race, and ethnicity groups.
The mean baseline EASI score was between 21.9 and 23.7, and the Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) suggested that there was an even split between moderate and severe atopic dermatitis, although the higher-dose rezpegaldesleukin group had more patients with moderate disease.
By week 12, rezpegaldesleukin was associated with significantly greater improvements in EASI scores vs. placebo. Patients on the higher dose had a mean 83% improvement over baseline vs. 65% with the lower dose and 47% with placebo (P = .002 for the higher dose vs. placebo).
Crucially, these differences were maintained up to week 48 in patients, particularly in the higher-dose group.
There was also a nonsignificant increase in the proportion of patients who achieved a reduction in EASI scores ≥ 75% over baseline with the active drug: 41% at week 12 with higher-dose rezpegaldesleukin, 25% with the lower dose, and 20% with placebo. Again, the benefit was maintained up to week 48.
The mean improvement in BSA score from baseline with rezpegaldesleukin was significantly greater than that seen with placebo, at 72% with the higher dose, 55% with the lower dose, and 36% with placebo (P = .0158 for the higher dose vs. placebo).
Although improvements in vIGA-AD scores over baseline with rezpegaldesleukin were not substantial at week 12, by week 48 there was a marked difference between higher-dose rezpegaldesleukin and placebo, with 40.0% of patients responding to the drug vs. 0% in the latter group.
A similar pattern was seen for the Itch Numeric Rating Scale, in which 55.6% of patients treated with higher-dose rezpegaldesleukin responding by week 48, compared with 0% of those who received placebo.
Greater improvements in the Dermatology Life Quality Index (DLQI) and Patient Oriented Eczema Measure (POEM) over baseline with higher-dose rezpegaldesleukin vs. plain placebo were also noted, despite a strong response in the latter group.
Dr. Silverberg reported that all treatment-emergent adverse effects in the two rezpegaldesleukin treatment arms were mild to moderate, with no severe or serious events observed.
The most common adverse events were mild to moderate injection-site reactions, seen in 75.0% of the lower-dose rezpegaldesleukin group and 58.8% the of higher-dose group. There were no cases of conjunctivitis.
The study was sponsored by Eli Lilly and Company in collaboration with Nektar Therapeutics.
Dr. Silverberg declares relationships with AbbVie, Alamar, Aldena, Amgen, AOBiome, Arcutis, Arena, Asana, ASLAN, BioMX, Biosion, Bodewell, Boehringer-Ingelheim, Bristol-Myers Squibb, Cara, Castle Biosciences, Celgene, Connect Biopharma, CorEvitas, Dermavant, DermTech, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Kiniksa, LEO Pharma, Nektar, Novartis, Optum, Pfizer, RAPT, Recludix, Regeneron, Sanofi-Genzyme, Shaperon, Target RWE, Union, and UpToDate.
A version of this article appeared on Medscape.com.
AT THE EADV CONGRESS
Fathers’ postpartum depression linked to children’s adversity
WASHINGTON – , according to research presented at the annual meeting of the American Academy of Pediatrics.
The findings held even after taking into account postpartum depression in the child’s mother and other factors that might increase risk of adverse childhood experiences, reported Kristine H. Schmitz, MD, an assistant professor of pediatrics at Robert Wood Johnson Medical School, New Brunswick, N.J.
Paternal postpartum depression has not been studied very well, so it’s difficult to pin down its prevalence, but some research has found rates as high as 25%, Dr. Schmitz told attendees.
”We recognize that it’s very under-recognized and often under-reported, but we also know that it has lots of downstream effects on child outcomes, including difficulties with parenting, difficulties with child behavior, as well as school performance and school attainment and employment,” Dr. Schmitz said.
Paternal depression and adverse childhood experiences
The study involved an analysis of six waves of data from the Future of Families & Child Wellbeing Study, which follows a national cohort of children born in large U.S. cities between 1998 and 2000. The cohort includes an intentional over-representation of unmarried mothers, who make up about 75% of the overall population.
The researchers used the World Health Organization’s Composite International Diagnosis Interview Short Form (CIDI-SF) to assess fathers’ depression when their children were 1 year old. Then the researchers looked at the number of adverse childhood experiences (ACEs) children had at 5 years old.
The analysis was adjusted to account for the child’s sex and the father’s age, race/ethnicity, and education as well as whether he was born inside or outside the United States. The findings were also adjusted for the whether the child’s parents were married or cohabiting, whether the child had low birth weight, whether the birth was covered by Medicaid, and whether the mother had postpartum depression.
Among the 1,933 pairs of fathers and children in the analysis, nearly half the fathers were non-Hispanic Black (48%) and more than half (64%) had a high school education or lower level of education. Medicaid paid for half the children’s births.
Nine percent of the fathers experienced depression during their child’s first year, and 70% of the children had at least one ACE at 5 years old. Two in five children (39%) had two ACEs at age 5, and 21% of children had three ACEs.
Children were twice as likely to have three ACEs at 5 years old if their father had depression during the child’s first year (adjusted odds ratio, 2.04; 95% confidence interval, 1.42-2.93). Paternal depression was also significantly associated with children having one ACE (OR, 2.35; 95% CI, 1.45-3.81) and two ACES (OR, 1.89; 95% CI, 1.35-2.63) at age 5.
The ACE with the highest association with paternal depression was the father’s absence from children’s lives (aOR, 2.65; 95% CI, 1.74-4.04). In addition, children of fathers with depression had 60% greater odds of exposure to substance use (aOR, 1.6; 95% CI, 1.08-2.34).
Children also had greater odds of child maltreatment at age 5 if their father had depression in their child’s first year. Odds were greater for psychological maltreatment (aOR, 1.55; 95% CI, 1.02-2.34), neglect (aOR, 1.63; 95% CI, 1.08-2.46), and physical maltreatment (aOR, 1.56; 95% CI, 1.04-2.35). The researchers did not find any association between paternal depression and the ACEs of sexual maltreatment, maternal depression, incarceration of someone in the home, or violence toward the mother.
”We know that dads play a critical role in the family,” Dr. Schmitz said. “We as pediatricians have a really unique position with families, and we should capitalize on that opportunity to engage with fathers just like we do with mothers and postpartum depression. Hopefully by doing that, we’ll reduce hardships for children and families down the road.”
Dr. Schmitz also said it’s important for pediatricians to advocate at a policy level “to really include dads more explicitly in maternal and child health policy and advocate for better father-focused interventions from father-focused research.” She further acknowledged the stigma that exists around men’s mental health in general and the need to find out the best ways to help overcome that stigma.
‘Concerning’ findings may suggest a need for screening
Jason Terk, MD, a pediatrician practicing in north Texas and past president of the Texas Pediatric Society, was not surprised to see a link between depression in fathers and adversity in their children. Dr. Terk was not involved in the research but noted that the 9% rate of paternal depression seen in the study is similar to national rates of depression in U.S. adults.
“I think that the presence of paternal depression being associated with ACEs in their children in their first 5 years of life is certainly concerning and worthy of intervention for both the fathers and their children,” Dr. Terk said. “The key take-home message for clinicians who care for infants and small children is that the presence of paternal depression should increase awareness of adverse effects on those children. We need to consider screening for this at 12 months of age in much the same way we screen for maternal depression for younger infants.”
Dr. Terk noted one limitation of the study was that it didn’t suggest any specific risk factors pediatricians might look for to increase surveillance of potential depression in fathers.
“Also, unlike maternal depression, in which moms may be connected with their obstetricians if they screen positive on an Edinburgh questionnaire, we will be hard-pressed to know where to refer dads who are found to be depressed when their babies are 12 months old,” Dr. Terk said. “Screening must lead to helpful responses if the screening reveals a problem.”
The research was funded by the Robert Wood Johnson Foundation, the National Institutes of Health, and the Health Resources and Services Administration. Dr. Schmitz had no disclosures. Dr. Terk has been a speaker for Sanofi on a topic unrelated to this research.
WASHINGTON – , according to research presented at the annual meeting of the American Academy of Pediatrics.
The findings held even after taking into account postpartum depression in the child’s mother and other factors that might increase risk of adverse childhood experiences, reported Kristine H. Schmitz, MD, an assistant professor of pediatrics at Robert Wood Johnson Medical School, New Brunswick, N.J.
Paternal postpartum depression has not been studied very well, so it’s difficult to pin down its prevalence, but some research has found rates as high as 25%, Dr. Schmitz told attendees.
”We recognize that it’s very under-recognized and often under-reported, but we also know that it has lots of downstream effects on child outcomes, including difficulties with parenting, difficulties with child behavior, as well as school performance and school attainment and employment,” Dr. Schmitz said.
Paternal depression and adverse childhood experiences
The study involved an analysis of six waves of data from the Future of Families & Child Wellbeing Study, which follows a national cohort of children born in large U.S. cities between 1998 and 2000. The cohort includes an intentional over-representation of unmarried mothers, who make up about 75% of the overall population.
The researchers used the World Health Organization’s Composite International Diagnosis Interview Short Form (CIDI-SF) to assess fathers’ depression when their children were 1 year old. Then the researchers looked at the number of adverse childhood experiences (ACEs) children had at 5 years old.
The analysis was adjusted to account for the child’s sex and the father’s age, race/ethnicity, and education as well as whether he was born inside or outside the United States. The findings were also adjusted for the whether the child’s parents were married or cohabiting, whether the child had low birth weight, whether the birth was covered by Medicaid, and whether the mother had postpartum depression.
Among the 1,933 pairs of fathers and children in the analysis, nearly half the fathers were non-Hispanic Black (48%) and more than half (64%) had a high school education or lower level of education. Medicaid paid for half the children’s births.
Nine percent of the fathers experienced depression during their child’s first year, and 70% of the children had at least one ACE at 5 years old. Two in five children (39%) had two ACEs at age 5, and 21% of children had three ACEs.
Children were twice as likely to have three ACEs at 5 years old if their father had depression during the child’s first year (adjusted odds ratio, 2.04; 95% confidence interval, 1.42-2.93). Paternal depression was also significantly associated with children having one ACE (OR, 2.35; 95% CI, 1.45-3.81) and two ACES (OR, 1.89; 95% CI, 1.35-2.63) at age 5.
The ACE with the highest association with paternal depression was the father’s absence from children’s lives (aOR, 2.65; 95% CI, 1.74-4.04). In addition, children of fathers with depression had 60% greater odds of exposure to substance use (aOR, 1.6; 95% CI, 1.08-2.34).
Children also had greater odds of child maltreatment at age 5 if their father had depression in their child’s first year. Odds were greater for psychological maltreatment (aOR, 1.55; 95% CI, 1.02-2.34), neglect (aOR, 1.63; 95% CI, 1.08-2.46), and physical maltreatment (aOR, 1.56; 95% CI, 1.04-2.35). The researchers did not find any association between paternal depression and the ACEs of sexual maltreatment, maternal depression, incarceration of someone in the home, or violence toward the mother.
”We know that dads play a critical role in the family,” Dr. Schmitz said. “We as pediatricians have a really unique position with families, and we should capitalize on that opportunity to engage with fathers just like we do with mothers and postpartum depression. Hopefully by doing that, we’ll reduce hardships for children and families down the road.”
Dr. Schmitz also said it’s important for pediatricians to advocate at a policy level “to really include dads more explicitly in maternal and child health policy and advocate for better father-focused interventions from father-focused research.” She further acknowledged the stigma that exists around men’s mental health in general and the need to find out the best ways to help overcome that stigma.
‘Concerning’ findings may suggest a need for screening
Jason Terk, MD, a pediatrician practicing in north Texas and past president of the Texas Pediatric Society, was not surprised to see a link between depression in fathers and adversity in their children. Dr. Terk was not involved in the research but noted that the 9% rate of paternal depression seen in the study is similar to national rates of depression in U.S. adults.
“I think that the presence of paternal depression being associated with ACEs in their children in their first 5 years of life is certainly concerning and worthy of intervention for both the fathers and their children,” Dr. Terk said. “The key take-home message for clinicians who care for infants and small children is that the presence of paternal depression should increase awareness of adverse effects on those children. We need to consider screening for this at 12 months of age in much the same way we screen for maternal depression for younger infants.”
Dr. Terk noted one limitation of the study was that it didn’t suggest any specific risk factors pediatricians might look for to increase surveillance of potential depression in fathers.
“Also, unlike maternal depression, in which moms may be connected with their obstetricians if they screen positive on an Edinburgh questionnaire, we will be hard-pressed to know where to refer dads who are found to be depressed when their babies are 12 months old,” Dr. Terk said. “Screening must lead to helpful responses if the screening reveals a problem.”
The research was funded by the Robert Wood Johnson Foundation, the National Institutes of Health, and the Health Resources and Services Administration. Dr. Schmitz had no disclosures. Dr. Terk has been a speaker for Sanofi on a topic unrelated to this research.
WASHINGTON – , according to research presented at the annual meeting of the American Academy of Pediatrics.
The findings held even after taking into account postpartum depression in the child’s mother and other factors that might increase risk of adverse childhood experiences, reported Kristine H. Schmitz, MD, an assistant professor of pediatrics at Robert Wood Johnson Medical School, New Brunswick, N.J.
Paternal postpartum depression has not been studied very well, so it’s difficult to pin down its prevalence, but some research has found rates as high as 25%, Dr. Schmitz told attendees.
”We recognize that it’s very under-recognized and often under-reported, but we also know that it has lots of downstream effects on child outcomes, including difficulties with parenting, difficulties with child behavior, as well as school performance and school attainment and employment,” Dr. Schmitz said.
Paternal depression and adverse childhood experiences
The study involved an analysis of six waves of data from the Future of Families & Child Wellbeing Study, which follows a national cohort of children born in large U.S. cities between 1998 and 2000. The cohort includes an intentional over-representation of unmarried mothers, who make up about 75% of the overall population.
The researchers used the World Health Organization’s Composite International Diagnosis Interview Short Form (CIDI-SF) to assess fathers’ depression when their children were 1 year old. Then the researchers looked at the number of adverse childhood experiences (ACEs) children had at 5 years old.
The analysis was adjusted to account for the child’s sex and the father’s age, race/ethnicity, and education as well as whether he was born inside or outside the United States. The findings were also adjusted for the whether the child’s parents were married or cohabiting, whether the child had low birth weight, whether the birth was covered by Medicaid, and whether the mother had postpartum depression.
Among the 1,933 pairs of fathers and children in the analysis, nearly half the fathers were non-Hispanic Black (48%) and more than half (64%) had a high school education or lower level of education. Medicaid paid for half the children’s births.
Nine percent of the fathers experienced depression during their child’s first year, and 70% of the children had at least one ACE at 5 years old. Two in five children (39%) had two ACEs at age 5, and 21% of children had three ACEs.
Children were twice as likely to have three ACEs at 5 years old if their father had depression during the child’s first year (adjusted odds ratio, 2.04; 95% confidence interval, 1.42-2.93). Paternal depression was also significantly associated with children having one ACE (OR, 2.35; 95% CI, 1.45-3.81) and two ACES (OR, 1.89; 95% CI, 1.35-2.63) at age 5.
The ACE with the highest association with paternal depression was the father’s absence from children’s lives (aOR, 2.65; 95% CI, 1.74-4.04). In addition, children of fathers with depression had 60% greater odds of exposure to substance use (aOR, 1.6; 95% CI, 1.08-2.34).
Children also had greater odds of child maltreatment at age 5 if their father had depression in their child’s first year. Odds were greater for psychological maltreatment (aOR, 1.55; 95% CI, 1.02-2.34), neglect (aOR, 1.63; 95% CI, 1.08-2.46), and physical maltreatment (aOR, 1.56; 95% CI, 1.04-2.35). The researchers did not find any association between paternal depression and the ACEs of sexual maltreatment, maternal depression, incarceration of someone in the home, or violence toward the mother.
”We know that dads play a critical role in the family,” Dr. Schmitz said. “We as pediatricians have a really unique position with families, and we should capitalize on that opportunity to engage with fathers just like we do with mothers and postpartum depression. Hopefully by doing that, we’ll reduce hardships for children and families down the road.”
Dr. Schmitz also said it’s important for pediatricians to advocate at a policy level “to really include dads more explicitly in maternal and child health policy and advocate for better father-focused interventions from father-focused research.” She further acknowledged the stigma that exists around men’s mental health in general and the need to find out the best ways to help overcome that stigma.
‘Concerning’ findings may suggest a need for screening
Jason Terk, MD, a pediatrician practicing in north Texas and past president of the Texas Pediatric Society, was not surprised to see a link between depression in fathers and adversity in their children. Dr. Terk was not involved in the research but noted that the 9% rate of paternal depression seen in the study is similar to national rates of depression in U.S. adults.
“I think that the presence of paternal depression being associated with ACEs in their children in their first 5 years of life is certainly concerning and worthy of intervention for both the fathers and their children,” Dr. Terk said. “The key take-home message for clinicians who care for infants and small children is that the presence of paternal depression should increase awareness of adverse effects on those children. We need to consider screening for this at 12 months of age in much the same way we screen for maternal depression for younger infants.”
Dr. Terk noted one limitation of the study was that it didn’t suggest any specific risk factors pediatricians might look for to increase surveillance of potential depression in fathers.
“Also, unlike maternal depression, in which moms may be connected with their obstetricians if they screen positive on an Edinburgh questionnaire, we will be hard-pressed to know where to refer dads who are found to be depressed when their babies are 12 months old,” Dr. Terk said. “Screening must lead to helpful responses if the screening reveals a problem.”
The research was funded by the Robert Wood Johnson Foundation, the National Institutes of Health, and the Health Resources and Services Administration. Dr. Schmitz had no disclosures. Dr. Terk has been a speaker for Sanofi on a topic unrelated to this research.
AT AAP 2023
In ILD, ECMO linked to good outcomes as bridge to transplant
Extracorporeal membrane oxygen support appears to be beneficial in patients with advanced interstitial lung disease (ILD), according to a new meta-analysis. Specifically, , although the confidence in the finding was low.
ECMO has been used increasingly in ILD patients over the past 10-15 years for acute decompensation as well as a bridge to lung transplant, according to Prasanth Balasubramanian, MD, but clinical evidence for its use is limited to case series or short-term retrospective studies. “We don’t have robust evidence on whether it really helps with the outcome, and which mode is better, so that’s why we decided to do a study on this,” said Dr. Balasubramanian, who is a fellow in pulmonary critical care at Mayo Clinic (Jacksonville, Fla.). He presented the new research at the annual meeting of the American College of Chest Physicians (CHEST).
The results were encouraging, according to the study’s lead author Pramod Guru, MD. “I think what we take from this analysis is that ECMO should not be considered as a contraindication for people you are considering for lung transplant. If we have this population of people who are very sick, but we have the opportunity to solve them with VA ECMO and then give the transplantation possibly, that may be the way,” said Dr. Guru, who is a critical care specialist at Mayo Clinic, Jacksonville, Fla. He acknowledged that more work needs to be done to determine whether VA or VV is best in specific patient populations.
The meta-analysis included 18 studies with a total of 1,341 patients, who were a mean age of 55.89 years and 61.08% of whom were male. Most procedures (75.3%) were VV. The overall mortality was 52.6%, including 59.7% for VV ECMO and 34.2% for VA ECMO. The survival difference did not reach statistical significance (odds ratio, 0.48; P = .11). There was also no significant difference in survival between patients who underwent ECMO and those who did not undergo ECMO (OR, 0.48; P = .43).
The researchers also analyzed 13 studies with 1,002 patients that looked at ECMO as a bridge to transplant (mean age, 52.1; 52.2% male; 49.3% VV, 31.1% VA, 32.4% cardiopulmonary bypass). Mortality was lower in the VA group than in the VV group (odds ratio, 0.62; P = .04).
“VA ECMO is generally for sicker patients, so it’s odd that the patients who are on the more aggressive support had lower mortality. But it’s good, it says it works,” said Chris Carroll, MD, an intensivist at the University of Florida, Jacksonville, who was asked to comment on the study.
The finding may also be an artifact of bias in the retrospective data, according to Joshua Diamond, MD, who comoderated the session where the study was presented. He noted age, physical function, and illness severity, among other factors can play a role in decision-making. “I have a feeling that what you’re seeing is a very carefully selected patient population as opposed to a true mortality benefit with VA versus VV ECMO,” said Dr. Diamond, who is associate medical director of the Penn Lung Transplant Program in Philadelphia.
Another weakness of the study is that ECMO techniques and devices have changed over time, making some of the older data less relevant to current practice. Overall Dr. Diamond described the study as interesting, but “I’d like to see a bit more granularity of data to figure out who makes or doesn’t make a good candidate,” said Dr. Diamond.
Patients with ILD undergoing ECMO as a bridge to transplant had a higher 1-year posttransplant mortality than patients with other causes for transplant (OR, 1.78; P<.01). However, this finding relied on two retrospective studies using the UNOS database at different time points (2001-2012 and 2015-2020), leading to potential confounders and risk of bias.
Dr. Balasubramanian recognized the limitations of the analysis. “We do think that further prospective studies comparing various modalities would be essential, although it would be challenging,” he said.
Nevertheless, Dr. Guru said that his own center is changing its patient selection criteria for ECMO and will begin to collect prospective data: “I would say that in 12 months we’ll have our own data to support what we are doing.”
The study can also inform patients and family who are trying to make a potential end-of-life decision about pursuing aggressive ECMO therapy. “This study says that if you choose to pursue that more aggressive therapy, you may still have a good outcome. A patient might say, ‘Why am I going to go through all this? Is it just prolonging my death, or is there a chance of saving my life? I think what this study shows is that it does have potential of saving their life,” said Dr. Carroll.
Dr. Balasubramanian, Dr. Guru, and Dr. Carroll have no relevant financial disclosures.
Extracorporeal membrane oxygen support appears to be beneficial in patients with advanced interstitial lung disease (ILD), according to a new meta-analysis. Specifically, , although the confidence in the finding was low.
ECMO has been used increasingly in ILD patients over the past 10-15 years for acute decompensation as well as a bridge to lung transplant, according to Prasanth Balasubramanian, MD, but clinical evidence for its use is limited to case series or short-term retrospective studies. “We don’t have robust evidence on whether it really helps with the outcome, and which mode is better, so that’s why we decided to do a study on this,” said Dr. Balasubramanian, who is a fellow in pulmonary critical care at Mayo Clinic (Jacksonville, Fla.). He presented the new research at the annual meeting of the American College of Chest Physicians (CHEST).
The results were encouraging, according to the study’s lead author Pramod Guru, MD. “I think what we take from this analysis is that ECMO should not be considered as a contraindication for people you are considering for lung transplant. If we have this population of people who are very sick, but we have the opportunity to solve them with VA ECMO and then give the transplantation possibly, that may be the way,” said Dr. Guru, who is a critical care specialist at Mayo Clinic, Jacksonville, Fla. He acknowledged that more work needs to be done to determine whether VA or VV is best in specific patient populations.
The meta-analysis included 18 studies with a total of 1,341 patients, who were a mean age of 55.89 years and 61.08% of whom were male. Most procedures (75.3%) were VV. The overall mortality was 52.6%, including 59.7% for VV ECMO and 34.2% for VA ECMO. The survival difference did not reach statistical significance (odds ratio, 0.48; P = .11). There was also no significant difference in survival between patients who underwent ECMO and those who did not undergo ECMO (OR, 0.48; P = .43).
The researchers also analyzed 13 studies with 1,002 patients that looked at ECMO as a bridge to transplant (mean age, 52.1; 52.2% male; 49.3% VV, 31.1% VA, 32.4% cardiopulmonary bypass). Mortality was lower in the VA group than in the VV group (odds ratio, 0.62; P = .04).
“VA ECMO is generally for sicker patients, so it’s odd that the patients who are on the more aggressive support had lower mortality. But it’s good, it says it works,” said Chris Carroll, MD, an intensivist at the University of Florida, Jacksonville, who was asked to comment on the study.
The finding may also be an artifact of bias in the retrospective data, according to Joshua Diamond, MD, who comoderated the session where the study was presented. He noted age, physical function, and illness severity, among other factors can play a role in decision-making. “I have a feeling that what you’re seeing is a very carefully selected patient population as opposed to a true mortality benefit with VA versus VV ECMO,” said Dr. Diamond, who is associate medical director of the Penn Lung Transplant Program in Philadelphia.
Another weakness of the study is that ECMO techniques and devices have changed over time, making some of the older data less relevant to current practice. Overall Dr. Diamond described the study as interesting, but “I’d like to see a bit more granularity of data to figure out who makes or doesn’t make a good candidate,” said Dr. Diamond.
Patients with ILD undergoing ECMO as a bridge to transplant had a higher 1-year posttransplant mortality than patients with other causes for transplant (OR, 1.78; P<.01). However, this finding relied on two retrospective studies using the UNOS database at different time points (2001-2012 and 2015-2020), leading to potential confounders and risk of bias.
Dr. Balasubramanian recognized the limitations of the analysis. “We do think that further prospective studies comparing various modalities would be essential, although it would be challenging,” he said.
Nevertheless, Dr. Guru said that his own center is changing its patient selection criteria for ECMO and will begin to collect prospective data: “I would say that in 12 months we’ll have our own data to support what we are doing.”
The study can also inform patients and family who are trying to make a potential end-of-life decision about pursuing aggressive ECMO therapy. “This study says that if you choose to pursue that more aggressive therapy, you may still have a good outcome. A patient might say, ‘Why am I going to go through all this? Is it just prolonging my death, or is there a chance of saving my life? I think what this study shows is that it does have potential of saving their life,” said Dr. Carroll.
Dr. Balasubramanian, Dr. Guru, and Dr. Carroll have no relevant financial disclosures.
Extracorporeal membrane oxygen support appears to be beneficial in patients with advanced interstitial lung disease (ILD), according to a new meta-analysis. Specifically, , although the confidence in the finding was low.
ECMO has been used increasingly in ILD patients over the past 10-15 years for acute decompensation as well as a bridge to lung transplant, according to Prasanth Balasubramanian, MD, but clinical evidence for its use is limited to case series or short-term retrospective studies. “We don’t have robust evidence on whether it really helps with the outcome, and which mode is better, so that’s why we decided to do a study on this,” said Dr. Balasubramanian, who is a fellow in pulmonary critical care at Mayo Clinic (Jacksonville, Fla.). He presented the new research at the annual meeting of the American College of Chest Physicians (CHEST).
The results were encouraging, according to the study’s lead author Pramod Guru, MD. “I think what we take from this analysis is that ECMO should not be considered as a contraindication for people you are considering for lung transplant. If we have this population of people who are very sick, but we have the opportunity to solve them with VA ECMO and then give the transplantation possibly, that may be the way,” said Dr. Guru, who is a critical care specialist at Mayo Clinic, Jacksonville, Fla. He acknowledged that more work needs to be done to determine whether VA or VV is best in specific patient populations.
The meta-analysis included 18 studies with a total of 1,341 patients, who were a mean age of 55.89 years and 61.08% of whom were male. Most procedures (75.3%) were VV. The overall mortality was 52.6%, including 59.7% for VV ECMO and 34.2% for VA ECMO. The survival difference did not reach statistical significance (odds ratio, 0.48; P = .11). There was also no significant difference in survival between patients who underwent ECMO and those who did not undergo ECMO (OR, 0.48; P = .43).
The researchers also analyzed 13 studies with 1,002 patients that looked at ECMO as a bridge to transplant (mean age, 52.1; 52.2% male; 49.3% VV, 31.1% VA, 32.4% cardiopulmonary bypass). Mortality was lower in the VA group than in the VV group (odds ratio, 0.62; P = .04).
“VA ECMO is generally for sicker patients, so it’s odd that the patients who are on the more aggressive support had lower mortality. But it’s good, it says it works,” said Chris Carroll, MD, an intensivist at the University of Florida, Jacksonville, who was asked to comment on the study.
The finding may also be an artifact of bias in the retrospective data, according to Joshua Diamond, MD, who comoderated the session where the study was presented. He noted age, physical function, and illness severity, among other factors can play a role in decision-making. “I have a feeling that what you’re seeing is a very carefully selected patient population as opposed to a true mortality benefit with VA versus VV ECMO,” said Dr. Diamond, who is associate medical director of the Penn Lung Transplant Program in Philadelphia.
Another weakness of the study is that ECMO techniques and devices have changed over time, making some of the older data less relevant to current practice. Overall Dr. Diamond described the study as interesting, but “I’d like to see a bit more granularity of data to figure out who makes or doesn’t make a good candidate,” said Dr. Diamond.
Patients with ILD undergoing ECMO as a bridge to transplant had a higher 1-year posttransplant mortality than patients with other causes for transplant (OR, 1.78; P<.01). However, this finding relied on two retrospective studies using the UNOS database at different time points (2001-2012 and 2015-2020), leading to potential confounders and risk of bias.
Dr. Balasubramanian recognized the limitations of the analysis. “We do think that further prospective studies comparing various modalities would be essential, although it would be challenging,” he said.
Nevertheless, Dr. Guru said that his own center is changing its patient selection criteria for ECMO and will begin to collect prospective data: “I would say that in 12 months we’ll have our own data to support what we are doing.”
The study can also inform patients and family who are trying to make a potential end-of-life decision about pursuing aggressive ECMO therapy. “This study says that if you choose to pursue that more aggressive therapy, you may still have a good outcome. A patient might say, ‘Why am I going to go through all this? Is it just prolonging my death, or is there a chance of saving my life? I think what this study shows is that it does have potential of saving their life,” said Dr. Carroll.
Dr. Balasubramanian, Dr. Guru, and Dr. Carroll have no relevant financial disclosures.
FROM CHEST 2023
Cold snare polypectomy underused despite recommendations
, shows new research presented this week in Vancouver at the annual meeting of the American College of Gastroenterology.
Polypectomy is a key part of colorectal cancer prevention, but endoscopists’ choice of polypectomy is a major factor in quality, and the characteristics of polypectomies in clinical practice are highly variable, said Seth D. Crockett, MD, of Oregon Health & Science University, Portland, in a presentation at the meeting.
Cold snare polypectomy is preferred for the removal of polyps less than 1 cm because of a high complete resection rate and a strong safety profile, compared to forceps and hot snares, which tend to be associated with high incomplete resection rates, inadequate histopathologic specimens, and/or complication rates. The adherence of endoscopists to the recommendations was not known until now, Dr. Crockett said.
This was a cross-sectional study of 1,589,499 colonoscopies that were conducted between 2019 and 2022 in patients (aged 40-80 years) who underwent a screening or surveillance colonoscopy in which at least one small polyp of less than 1 cm was removed. The final analysis included 3,082 endoscopists. Colonoscopies in which larger polyps were detected, or there was a confirmed case of cancer, were not included.
The mean endoscopist cold snare polypectomy rate (CSPR) was 51.2%, which was “lower than expected based on current guideline recommendations,” Dr. Crockett said.
Higher cold snare polypectomy rates were more common among specialists with training in gastroenterology, and more common among those who practiced in the Midwest (69%), as compared with practitioners in the Northeast who, at 40%, had the lowest rate. Colonoscopy volume, adenoma detection rate (ADR), serrated polyp detection rate (SDR), and cecal intubation rate (CIR), were all associated with a higher CSPR.
CSPR was more than 30% higher for endoscopists with an adenoma detection rate (ADR) of greater than 35%, compared with those with an ADR of less than 25% (58% vs. 27%, respectively; P < .0001). Lower usage rates among endoscopists with low ADRs could compound the problem of interval cancer if polyps are missed, Dr. Crockett said. Endoscopist serrated polyp detection rates of 7% of higher, cecal intubation rates of 95% or higher, and mean withdrawal times greater than 9 minutes were significantly associated with higher CSPR (P < .0001 for all).
The findings suggest a correlation between higher cold snare usage and improved quality metrics, such as adenoma detection rate and cecal intubation rate, said Jonathan A. Leighton, MD, of the Mayo Clinic, Scottsdale, Ariz., in an interview.
“I would agree with the authors that much of the focus on colonoscopy quality has been directed toward polyp detection, and little on the quality of polyp resection, which can be difficult to measure,” he said. “Their results suggest that cold snare polypectomy for removal of small polyps is currently underutilized, but as with any polypectomy, it is important that all of the dysplastic tissue is removed using good technique.”
The results were strengthened by the large sample size and high fidelity of measurements of polyp size, polypectomy tools, and quality measures. But more research is needed to determine the impact of polypectomy technique on outcomes of colonoscopy efficacy and safety. In terms of limitations, small polyps carry a relatively low risk of recurrence, and the associations between an endoscopist’s polypectomy practice and polyp recurrence, interval cancer, and adverse events were not examined, Dr. Crockett said.
The study was supported by a grant from the ACG. Dr. Crockett disclosed relationships with Carelon, Exact Sciences, Freenome, and Guardant.
, shows new research presented this week in Vancouver at the annual meeting of the American College of Gastroenterology.
Polypectomy is a key part of colorectal cancer prevention, but endoscopists’ choice of polypectomy is a major factor in quality, and the characteristics of polypectomies in clinical practice are highly variable, said Seth D. Crockett, MD, of Oregon Health & Science University, Portland, in a presentation at the meeting.
Cold snare polypectomy is preferred for the removal of polyps less than 1 cm because of a high complete resection rate and a strong safety profile, compared to forceps and hot snares, which tend to be associated with high incomplete resection rates, inadequate histopathologic specimens, and/or complication rates. The adherence of endoscopists to the recommendations was not known until now, Dr. Crockett said.
This was a cross-sectional study of 1,589,499 colonoscopies that were conducted between 2019 and 2022 in patients (aged 40-80 years) who underwent a screening or surveillance colonoscopy in which at least one small polyp of less than 1 cm was removed. The final analysis included 3,082 endoscopists. Colonoscopies in which larger polyps were detected, or there was a confirmed case of cancer, were not included.
The mean endoscopist cold snare polypectomy rate (CSPR) was 51.2%, which was “lower than expected based on current guideline recommendations,” Dr. Crockett said.
Higher cold snare polypectomy rates were more common among specialists with training in gastroenterology, and more common among those who practiced in the Midwest (69%), as compared with practitioners in the Northeast who, at 40%, had the lowest rate. Colonoscopy volume, adenoma detection rate (ADR), serrated polyp detection rate (SDR), and cecal intubation rate (CIR), were all associated with a higher CSPR.
CSPR was more than 30% higher for endoscopists with an adenoma detection rate (ADR) of greater than 35%, compared with those with an ADR of less than 25% (58% vs. 27%, respectively; P < .0001). Lower usage rates among endoscopists with low ADRs could compound the problem of interval cancer if polyps are missed, Dr. Crockett said. Endoscopist serrated polyp detection rates of 7% of higher, cecal intubation rates of 95% or higher, and mean withdrawal times greater than 9 minutes were significantly associated with higher CSPR (P < .0001 for all).
The findings suggest a correlation between higher cold snare usage and improved quality metrics, such as adenoma detection rate and cecal intubation rate, said Jonathan A. Leighton, MD, of the Mayo Clinic, Scottsdale, Ariz., in an interview.
“I would agree with the authors that much of the focus on colonoscopy quality has been directed toward polyp detection, and little on the quality of polyp resection, which can be difficult to measure,” he said. “Their results suggest that cold snare polypectomy for removal of small polyps is currently underutilized, but as with any polypectomy, it is important that all of the dysplastic tissue is removed using good technique.”
The results were strengthened by the large sample size and high fidelity of measurements of polyp size, polypectomy tools, and quality measures. But more research is needed to determine the impact of polypectomy technique on outcomes of colonoscopy efficacy and safety. In terms of limitations, small polyps carry a relatively low risk of recurrence, and the associations between an endoscopist’s polypectomy practice and polyp recurrence, interval cancer, and adverse events were not examined, Dr. Crockett said.
The study was supported by a grant from the ACG. Dr. Crockett disclosed relationships with Carelon, Exact Sciences, Freenome, and Guardant.
, shows new research presented this week in Vancouver at the annual meeting of the American College of Gastroenterology.
Polypectomy is a key part of colorectal cancer prevention, but endoscopists’ choice of polypectomy is a major factor in quality, and the characteristics of polypectomies in clinical practice are highly variable, said Seth D. Crockett, MD, of Oregon Health & Science University, Portland, in a presentation at the meeting.
Cold snare polypectomy is preferred for the removal of polyps less than 1 cm because of a high complete resection rate and a strong safety profile, compared to forceps and hot snares, which tend to be associated with high incomplete resection rates, inadequate histopathologic specimens, and/or complication rates. The adherence of endoscopists to the recommendations was not known until now, Dr. Crockett said.
This was a cross-sectional study of 1,589,499 colonoscopies that were conducted between 2019 and 2022 in patients (aged 40-80 years) who underwent a screening or surveillance colonoscopy in which at least one small polyp of less than 1 cm was removed. The final analysis included 3,082 endoscopists. Colonoscopies in which larger polyps were detected, or there was a confirmed case of cancer, were not included.
The mean endoscopist cold snare polypectomy rate (CSPR) was 51.2%, which was “lower than expected based on current guideline recommendations,” Dr. Crockett said.
Higher cold snare polypectomy rates were more common among specialists with training in gastroenterology, and more common among those who practiced in the Midwest (69%), as compared with practitioners in the Northeast who, at 40%, had the lowest rate. Colonoscopy volume, adenoma detection rate (ADR), serrated polyp detection rate (SDR), and cecal intubation rate (CIR), were all associated with a higher CSPR.
CSPR was more than 30% higher for endoscopists with an adenoma detection rate (ADR) of greater than 35%, compared with those with an ADR of less than 25% (58% vs. 27%, respectively; P < .0001). Lower usage rates among endoscopists with low ADRs could compound the problem of interval cancer if polyps are missed, Dr. Crockett said. Endoscopist serrated polyp detection rates of 7% of higher, cecal intubation rates of 95% or higher, and mean withdrawal times greater than 9 minutes were significantly associated with higher CSPR (P < .0001 for all).
The findings suggest a correlation between higher cold snare usage and improved quality metrics, such as adenoma detection rate and cecal intubation rate, said Jonathan A. Leighton, MD, of the Mayo Clinic, Scottsdale, Ariz., in an interview.
“I would agree with the authors that much of the focus on colonoscopy quality has been directed toward polyp detection, and little on the quality of polyp resection, which can be difficult to measure,” he said. “Their results suggest that cold snare polypectomy for removal of small polyps is currently underutilized, but as with any polypectomy, it is important that all of the dysplastic tissue is removed using good technique.”
The results were strengthened by the large sample size and high fidelity of measurements of polyp size, polypectomy tools, and quality measures. But more research is needed to determine the impact of polypectomy technique on outcomes of colonoscopy efficacy and safety. In terms of limitations, small polyps carry a relatively low risk of recurrence, and the associations between an endoscopist’s polypectomy practice and polyp recurrence, interval cancer, and adverse events were not examined, Dr. Crockett said.
The study was supported by a grant from the ACG. Dr. Crockett disclosed relationships with Carelon, Exact Sciences, Freenome, and Guardant.
FROM ACG 2023
Enzalutamide improves metastasis-free survival, QoL in prostate cancer
Adding enzalutamide (Xtandi) to androgen deprivation therapy (ADT) can extend metastasis-free survival (MFS) while maintaining quality of life in men with prostate cancer who have a high risk for biochemical recurrence, according to new research presented at the European Society of Medical Oncology meeting in Madrid.
, while 80% of those receiving only enzalutamide and about 71% of those receiving only leuprolide were metastasis-free.
In a related analysis of patient-reported outcomes, investigators found that patients who received enzalutamide did not appear to have worse quality of life, compared with those treated with leuprolide alone.
“This could be a game-changer for one of the most common disease states in prostate cancer,” lead author Stephen Freedland, MD, director of the Center for Integrated Research in Cancer and Lifestyle at Cedars-Sinai Cancer, Los Angeles, said. The study was published online in the New England Journal of Medicine.
The results “confirm that in this population, as in men with more advanced stages, adding an androgen-receptor inhibitor [enzalutamide] increases the efficacy of androgen deprivation therapy,” Ana Aparicio, MD, from University of Texas MD Anderson Cancer Center, Houston, wrote in an accompanying editorial.
Standard care in this patient population relies on ADT to suppress testosterone, which would otherwise stimulate cancer cell growth. However, Dr. Freedland explained that “when you go on androgen deprivation therapy, the testosterone level in the blood is reduced but not completely eliminated. The concern is that the testosterone that remains may still be enough to stimulate tumor growth.”
Enzalutamide, an oral androgen receptor inhibitor, has already shown benefits in patients with metastases, and the current EMBARK trial explored whether the inhibitor can help men with earlier-stage disease who are at risk for metastases.
The findings from the phase 3 EMBARK trial, also published in NEJM Evidence, included 1,068 patients with prostate cancer at high-risk for biochemical recurrence. Patients, who had a median age of 69 years, spanned 244 sites across 17 countries.
Patients had a median prostate-specific antigen (PSA) doubling time of 4.9 months, with a median PSA of 5.2 ng/mL. Those with PSA doubling times of 9 months or less are considered at high-risk for biochemical recurrence and increased risk for death from prostate cancer.
Dr. Freedland and colleagues randomly assigned patients to three groups – enzalutamide 160 mg plus leuprolide every 12 weeks (n = 355), enzalutamide monotherapy (n = 355), and placebo plus leuprolide (n = 358). Patients received treatment for 38.7 months on average.
At 5-years, 87.3% of men in the combination group were metastasis-free, compared with 80% in the monotherapy group and 71.4% in the leuprolide-only group. Compared with leuprolide alone, combining enzalutamide and leuprolide reduced the risk for metastasis or death by 58% (hazard ratio, 0.42; P < .001). And compared with enzalutamide monotherapy, the combination also significantly reduced the risk for metastasis or death, compared with leuprolide alone (HR, 0.63; P = .005).
The estimated proportion of patients free from PSA progression at 5 years was 97.4% in the combination group, 88.9% in the monotherapy group, and 70% in the leuprolide-only group.
At the time of data cutoff, 33 (9%) patients in the combination group, 42 (12%) in the monotherapy group, and 55 (15%) in the leuprolide-only group had died.
Nearly all (97%) patients experienced adverse events, most of which (86.4%) were treatment-related. Overall, 46.5% of patients in the combination group experienced a grade 3 or higher adverse event, compared with 50% in the enzalutamide monotherapy group and 42.7% in the leuprolide-only group. Clustered adverse effects occurred in 80% or more patients in all three groups, with the most common cluster combining fatigue, falls, fractures, hypertension, and musculoskeletal events.
The most common adverse events in the enzalutamide monotherapy group, occurring in at least 30% of patients, included gynecomastia, joint pain, hot flashes, and fatigue. Nipple pain and breast tenderness were also common side effects in the enzalutamide monotherapy arm – occurring in 15.3% and 14.4% of patients, respectively – compared with the combination (3.1% and 1.1%) or leuprolide-only (1.1% and 1.1%) groups.
However, Dr. Freedland explained, “our quality-of-life data show that you don’t need to sacrifice global quality of life to get these cancer benefits.”
Patient-reported outcomes from EMBARK revealed that both enzalutamide combination and monotherapy versus leuprolide alone preserved high health-related quality of life in patients with a high-risk for biochemical recurrence.
More specifically, Dr. Freedland and colleagues found no differences in the time to first clinically meaningful deterioration based on questionnaires that rated pain and functional status. Functional status measures included physical, social, and emotional well-being as well as symptom severity.
However, some differences emerged. For instance, time to confirmed clinically meaningful deterioration in physical well-being score was significantly shorter among patients receiving enzalutamide, compared with leuprolide monotherapy – 24.8 months in the combination group and 27.6 months in the enzalutamide-only group versus 49.8 months in the leuprolide-only group (HR, 1.41 and 1.35, respectively).
However, sexual activity appeared to be better preserved among patients receiving enzalutamide monotherapy, compared with leuprolide alone. The median time to confirmed clinically meaningful deterioration in sexual activity score was 5.6 months with enzalutamide monotherapy versus 3 months for leuprolide alone (HR, 0.76).
Given the slightly different side-effect profiles in the enzalutamide combination and monotherapy groups, Dr. Freedland noted that “it will be up to patients and care providers to decide which is the right choice for them. I think the important message is that both are a major step forward from the current standard of care, which is androgen deprivation therapy alone.”
Pedro Barata, MD, who was not involved in the research, also noted that “this is the first time we have seen this kind of results with a novel hormonal therapy without castration.”
Overall, “the findings of this trial confirm the benefit of adding a novel hormonal therapy such as enzalutamide earlier in the course of this disease,” said Dr. Barata, a medical oncologist and director of the Clinical Genitourinary Medical Oncology Research Program at University Hospitals Seidman Cancer Center, Cleveland.
However, he explained that many patients with “rising PSA and short doubling time are known to have metastatic disease as detected by PSMA PET and are already being offered a novel hormonal therapy combined with castration. Perhaps it will be an opportunity for men who don’t want to be castrated to be offered an anti–androgen-like enzalutamide by itself without castration in this patient population.”
Research was funded by Pfizer and Astellas Pharma, manufacturers of enzalutamide.
A version of this article first appeared on Medscape.com.
Adding enzalutamide (Xtandi) to androgen deprivation therapy (ADT) can extend metastasis-free survival (MFS) while maintaining quality of life in men with prostate cancer who have a high risk for biochemical recurrence, according to new research presented at the European Society of Medical Oncology meeting in Madrid.
, while 80% of those receiving only enzalutamide and about 71% of those receiving only leuprolide were metastasis-free.
In a related analysis of patient-reported outcomes, investigators found that patients who received enzalutamide did not appear to have worse quality of life, compared with those treated with leuprolide alone.
“This could be a game-changer for one of the most common disease states in prostate cancer,” lead author Stephen Freedland, MD, director of the Center for Integrated Research in Cancer and Lifestyle at Cedars-Sinai Cancer, Los Angeles, said. The study was published online in the New England Journal of Medicine.
The results “confirm that in this population, as in men with more advanced stages, adding an androgen-receptor inhibitor [enzalutamide] increases the efficacy of androgen deprivation therapy,” Ana Aparicio, MD, from University of Texas MD Anderson Cancer Center, Houston, wrote in an accompanying editorial.
Standard care in this patient population relies on ADT to suppress testosterone, which would otherwise stimulate cancer cell growth. However, Dr. Freedland explained that “when you go on androgen deprivation therapy, the testosterone level in the blood is reduced but not completely eliminated. The concern is that the testosterone that remains may still be enough to stimulate tumor growth.”
Enzalutamide, an oral androgen receptor inhibitor, has already shown benefits in patients with metastases, and the current EMBARK trial explored whether the inhibitor can help men with earlier-stage disease who are at risk for metastases.
The findings from the phase 3 EMBARK trial, also published in NEJM Evidence, included 1,068 patients with prostate cancer at high-risk for biochemical recurrence. Patients, who had a median age of 69 years, spanned 244 sites across 17 countries.
Patients had a median prostate-specific antigen (PSA) doubling time of 4.9 months, with a median PSA of 5.2 ng/mL. Those with PSA doubling times of 9 months or less are considered at high-risk for biochemical recurrence and increased risk for death from prostate cancer.
Dr. Freedland and colleagues randomly assigned patients to three groups – enzalutamide 160 mg plus leuprolide every 12 weeks (n = 355), enzalutamide monotherapy (n = 355), and placebo plus leuprolide (n = 358). Patients received treatment for 38.7 months on average.
At 5-years, 87.3% of men in the combination group were metastasis-free, compared with 80% in the monotherapy group and 71.4% in the leuprolide-only group. Compared with leuprolide alone, combining enzalutamide and leuprolide reduced the risk for metastasis or death by 58% (hazard ratio, 0.42; P < .001). And compared with enzalutamide monotherapy, the combination also significantly reduced the risk for metastasis or death, compared with leuprolide alone (HR, 0.63; P = .005).
The estimated proportion of patients free from PSA progression at 5 years was 97.4% in the combination group, 88.9% in the monotherapy group, and 70% in the leuprolide-only group.
At the time of data cutoff, 33 (9%) patients in the combination group, 42 (12%) in the monotherapy group, and 55 (15%) in the leuprolide-only group had died.
Nearly all (97%) patients experienced adverse events, most of which (86.4%) were treatment-related. Overall, 46.5% of patients in the combination group experienced a grade 3 or higher adverse event, compared with 50% in the enzalutamide monotherapy group and 42.7% in the leuprolide-only group. Clustered adverse effects occurred in 80% or more patients in all three groups, with the most common cluster combining fatigue, falls, fractures, hypertension, and musculoskeletal events.
The most common adverse events in the enzalutamide monotherapy group, occurring in at least 30% of patients, included gynecomastia, joint pain, hot flashes, and fatigue. Nipple pain and breast tenderness were also common side effects in the enzalutamide monotherapy arm – occurring in 15.3% and 14.4% of patients, respectively – compared with the combination (3.1% and 1.1%) or leuprolide-only (1.1% and 1.1%) groups.
However, Dr. Freedland explained, “our quality-of-life data show that you don’t need to sacrifice global quality of life to get these cancer benefits.”
Patient-reported outcomes from EMBARK revealed that both enzalutamide combination and monotherapy versus leuprolide alone preserved high health-related quality of life in patients with a high-risk for biochemical recurrence.
More specifically, Dr. Freedland and colleagues found no differences in the time to first clinically meaningful deterioration based on questionnaires that rated pain and functional status. Functional status measures included physical, social, and emotional well-being as well as symptom severity.
However, some differences emerged. For instance, time to confirmed clinically meaningful deterioration in physical well-being score was significantly shorter among patients receiving enzalutamide, compared with leuprolide monotherapy – 24.8 months in the combination group and 27.6 months in the enzalutamide-only group versus 49.8 months in the leuprolide-only group (HR, 1.41 and 1.35, respectively).
However, sexual activity appeared to be better preserved among patients receiving enzalutamide monotherapy, compared with leuprolide alone. The median time to confirmed clinically meaningful deterioration in sexual activity score was 5.6 months with enzalutamide monotherapy versus 3 months for leuprolide alone (HR, 0.76).
Given the slightly different side-effect profiles in the enzalutamide combination and monotherapy groups, Dr. Freedland noted that “it will be up to patients and care providers to decide which is the right choice for them. I think the important message is that both are a major step forward from the current standard of care, which is androgen deprivation therapy alone.”
Pedro Barata, MD, who was not involved in the research, also noted that “this is the first time we have seen this kind of results with a novel hormonal therapy without castration.”
Overall, “the findings of this trial confirm the benefit of adding a novel hormonal therapy such as enzalutamide earlier in the course of this disease,” said Dr. Barata, a medical oncologist and director of the Clinical Genitourinary Medical Oncology Research Program at University Hospitals Seidman Cancer Center, Cleveland.
However, he explained that many patients with “rising PSA and short doubling time are known to have metastatic disease as detected by PSMA PET and are already being offered a novel hormonal therapy combined with castration. Perhaps it will be an opportunity for men who don’t want to be castrated to be offered an anti–androgen-like enzalutamide by itself without castration in this patient population.”
Research was funded by Pfizer and Astellas Pharma, manufacturers of enzalutamide.
A version of this article first appeared on Medscape.com.
Adding enzalutamide (Xtandi) to androgen deprivation therapy (ADT) can extend metastasis-free survival (MFS) while maintaining quality of life in men with prostate cancer who have a high risk for biochemical recurrence, according to new research presented at the European Society of Medical Oncology meeting in Madrid.
, while 80% of those receiving only enzalutamide and about 71% of those receiving only leuprolide were metastasis-free.
In a related analysis of patient-reported outcomes, investigators found that patients who received enzalutamide did not appear to have worse quality of life, compared with those treated with leuprolide alone.
“This could be a game-changer for one of the most common disease states in prostate cancer,” lead author Stephen Freedland, MD, director of the Center for Integrated Research in Cancer and Lifestyle at Cedars-Sinai Cancer, Los Angeles, said. The study was published online in the New England Journal of Medicine.
The results “confirm that in this population, as in men with more advanced stages, adding an androgen-receptor inhibitor [enzalutamide] increases the efficacy of androgen deprivation therapy,” Ana Aparicio, MD, from University of Texas MD Anderson Cancer Center, Houston, wrote in an accompanying editorial.
Standard care in this patient population relies on ADT to suppress testosterone, which would otherwise stimulate cancer cell growth. However, Dr. Freedland explained that “when you go on androgen deprivation therapy, the testosterone level in the blood is reduced but not completely eliminated. The concern is that the testosterone that remains may still be enough to stimulate tumor growth.”
Enzalutamide, an oral androgen receptor inhibitor, has already shown benefits in patients with metastases, and the current EMBARK trial explored whether the inhibitor can help men with earlier-stage disease who are at risk for metastases.
The findings from the phase 3 EMBARK trial, also published in NEJM Evidence, included 1,068 patients with prostate cancer at high-risk for biochemical recurrence. Patients, who had a median age of 69 years, spanned 244 sites across 17 countries.
Patients had a median prostate-specific antigen (PSA) doubling time of 4.9 months, with a median PSA of 5.2 ng/mL. Those with PSA doubling times of 9 months or less are considered at high-risk for biochemical recurrence and increased risk for death from prostate cancer.
Dr. Freedland and colleagues randomly assigned patients to three groups – enzalutamide 160 mg plus leuprolide every 12 weeks (n = 355), enzalutamide monotherapy (n = 355), and placebo plus leuprolide (n = 358). Patients received treatment for 38.7 months on average.
At 5-years, 87.3% of men in the combination group were metastasis-free, compared with 80% in the monotherapy group and 71.4% in the leuprolide-only group. Compared with leuprolide alone, combining enzalutamide and leuprolide reduced the risk for metastasis or death by 58% (hazard ratio, 0.42; P < .001). And compared with enzalutamide monotherapy, the combination also significantly reduced the risk for metastasis or death, compared with leuprolide alone (HR, 0.63; P = .005).
The estimated proportion of patients free from PSA progression at 5 years was 97.4% in the combination group, 88.9% in the monotherapy group, and 70% in the leuprolide-only group.
At the time of data cutoff, 33 (9%) patients in the combination group, 42 (12%) in the monotherapy group, and 55 (15%) in the leuprolide-only group had died.
Nearly all (97%) patients experienced adverse events, most of which (86.4%) were treatment-related. Overall, 46.5% of patients in the combination group experienced a grade 3 or higher adverse event, compared with 50% in the enzalutamide monotherapy group and 42.7% in the leuprolide-only group. Clustered adverse effects occurred in 80% or more patients in all three groups, with the most common cluster combining fatigue, falls, fractures, hypertension, and musculoskeletal events.
The most common adverse events in the enzalutamide monotherapy group, occurring in at least 30% of patients, included gynecomastia, joint pain, hot flashes, and fatigue. Nipple pain and breast tenderness were also common side effects in the enzalutamide monotherapy arm – occurring in 15.3% and 14.4% of patients, respectively – compared with the combination (3.1% and 1.1%) or leuprolide-only (1.1% and 1.1%) groups.
However, Dr. Freedland explained, “our quality-of-life data show that you don’t need to sacrifice global quality of life to get these cancer benefits.”
Patient-reported outcomes from EMBARK revealed that both enzalutamide combination and monotherapy versus leuprolide alone preserved high health-related quality of life in patients with a high-risk for biochemical recurrence.
More specifically, Dr. Freedland and colleagues found no differences in the time to first clinically meaningful deterioration based on questionnaires that rated pain and functional status. Functional status measures included physical, social, and emotional well-being as well as symptom severity.
However, some differences emerged. For instance, time to confirmed clinically meaningful deterioration in physical well-being score was significantly shorter among patients receiving enzalutamide, compared with leuprolide monotherapy – 24.8 months in the combination group and 27.6 months in the enzalutamide-only group versus 49.8 months in the leuprolide-only group (HR, 1.41 and 1.35, respectively).
However, sexual activity appeared to be better preserved among patients receiving enzalutamide monotherapy, compared with leuprolide alone. The median time to confirmed clinically meaningful deterioration in sexual activity score was 5.6 months with enzalutamide monotherapy versus 3 months for leuprolide alone (HR, 0.76).
Given the slightly different side-effect profiles in the enzalutamide combination and monotherapy groups, Dr. Freedland noted that “it will be up to patients and care providers to decide which is the right choice for them. I think the important message is that both are a major step forward from the current standard of care, which is androgen deprivation therapy alone.”
Pedro Barata, MD, who was not involved in the research, also noted that “this is the first time we have seen this kind of results with a novel hormonal therapy without castration.”
Overall, “the findings of this trial confirm the benefit of adding a novel hormonal therapy such as enzalutamide earlier in the course of this disease,” said Dr. Barata, a medical oncologist and director of the Clinical Genitourinary Medical Oncology Research Program at University Hospitals Seidman Cancer Center, Cleveland.
However, he explained that many patients with “rising PSA and short doubling time are known to have metastatic disease as detected by PSMA PET and are already being offered a novel hormonal therapy combined with castration. Perhaps it will be an opportunity for men who don’t want to be castrated to be offered an anti–androgen-like enzalutamide by itself without castration in this patient population.”
Research was funded by Pfizer and Astellas Pharma, manufacturers of enzalutamide.
A version of this article first appeared on Medscape.com.
Treatment options for vitiligo reviewed
CARLSBAD, CALIF. – According to Delphine J. Lee, MD, PhD, some patients report that their dermatologists tell them there are no effective treatments for vitiligo.
However, this is not supported by the ongoing level of research on vitiligo, with more than 100 randomized controlled trials published over the last 5 years, Dr. Lee, chief of dermatology at Harbor-UCLA Medical Center, Los Angeles, said at the annual symposium of the California Society of Dermatology & Dermatologic Surgery. And, in 2022, ruxolitinib cream became the first FDA-approved treatment for vitiligo. “There’s a lot of research happening now, and I’m pleased to say that despite the fact that some of these medications are not all brand new and exciting, they’re still new in that we have new evidence for them,” she said. “Of the 100 randomized, controlled trials, UV therapy remains a strong part of our armamentarium.”
Stabilizing disease
Dr. Lee underscored the importance of stabilizing existing vitiligo and arresting progressive disease, which may be indicated by four key signs: koebnerization; trichrome lesions; inflammation, which can appear as erythema, scaling, and pruritus; and confetti-like macules that are typically 1 mm to 5 mm in size. Key principles of vitiligo treatment are to stop immune destruction and to stimulate melanocyte differentiation, migration, and melanin production, which is “probably why phototherapy is so important and helpful,” she said.
Managing patients’ expectations is also important, added Dr. Lee, who shows patients photos from published clinical trials “so they can see what excellent repigmentation really means.”
Dexamethasone vs. mycophenolate
In a randomized, controlled trial published in 2021, researchers compared dexamethasone oral mini-pulse (OMP), 2.5 mg, on two successive days a week, with oral mycophenolate mofetil, 500 mg b.i.d., up to 2 g every day, for 180 days as a stabilizing treatment for patients with progressive, nonsegmental vitiligo, with 90 days of treatment-free follow-up. Assessments included the vitiligo disease activity (VIDA) score, the number of new lesions in the past 30 days, and the Vitiligo Area Scoring Index (VASI). Arrest of disease progression was defined as the absence of any new lesions in the previous 30 days.
Over the treatment and follow-up period, both groups showed a significant trend for reduction in VIDA and in the number of new lesions in the previous 30 days, compared with baseline (P < .001). The difference between VASI at baseline and VASI at 180 and at 270 days was not significant in both groups.
Adverse side effects reported with dexamethasone included acne, weight gain, headache, insomnia, and menstrual irregularity. “The misconception is that because we only give patients a tiny dose of steroids – 2.5 mg two days per week – that they aren’t going to have any side effects,” Dr. Lee commented. “But in fact, they do.” The most common side effects with mycophenolate were nausea and diarrhea. Two patients on mycophenolate discontinued treatment: one for leukopenia and one for transaminitis, but both conditions resolved after treatment was stopped.
The researchers concluded that both dexamethasone OMP and mycophenolate mofetil halt actively spreading vitiligo. “Relapse occurred earlier with mycophenolate, and the relapse rate was higher than with dexamethasone OMP, but this was not statistically significant,” said Dr. Lee, who also leads an immunology research team at The Lundquist Institute at Harbor-UCLA Medical Center.
Other vitiligo treatment options she discussed included the following:
Betamethasone OMP and oral azathioprine. In a comparative study, researchers compared betamethasone OMP with oral azathioprine in arresting disease progression and inducing repigmentation in adults with vitiligo. Significantly more patients in the betamethasone OMP group achieved arrest of progression at 2 months than those in the azathioprine group, but at 6 months the difference was not significant. At 6 months, of the 19 patients who completed 6 months of betamethasone OMP, 2, 2, and 9 patients had more than 20%, 10%-20%, and 5%-10% repigmentation, respectively; and of the 18 patients who completed 6 months of azathioprine, 2 patients had 10%-20% repigmentation, with the remaining patients having no repigmentation or less than 5% repigmentation.
One patient in the azathioprine group developed acute pancreatitis but none developed transaminitis or leukopenia. “Azathioprine is another agent to add to our toolbox,” Dr. Lee said of the study findings. “Both betamethasone OMP and daily azathioprine are effective” in halting disease progression.
Low-dose cyclosporine. In a comparative study, 50 patients with active vitiligo were randomized into two groups: 25 to dexamethasone OMP 2.5 mg on two consecutive days/week for 4 months, and 25 to cyclosporine 3 mg/kg per day for 4 months, stopped treatment, and were then followed up for another 2 months. After 6 months, 84% of patients in the dexamethasone OMP group and 88% of patients in the cyclosporine group achieved arrest of disease progression (P = 1.00), but the mean time to achieve that endpoint was shorter for those in the cyclosporine group, compared with those in the dexamethasone OMP group (a mean of 3.92 weeks vs. 4.12 weeks, respectively; P = .01).
The list of adverse side effects for cyclosporine was “quite lengthy compared to the usual you would expect for dexamethasone,” said Dr. Lee, who was not involved with the study. “This is something we want to take seriously and discuss with our patients. Still, I would say that low-dose cyclosporine is another possibility to add to our toolbox.”
Phototherapy combined with polypodium leucotomos. Dr. Lee highlighted a randomized, controlled trial in which 21 patients with generalized vitiligo received narrow band (NB)-UVB phototherapy plus polypodium leucotomos extract (480 mg b.i.d.) and 21 patients received NB-UVB phototherapy plus placebo. After 6 months of treatment, patients in the NB-UVB plus oral polypodium leucotomos extract group had a better response rate, compared with those in the NB-UVB plus placebo group (47.8% vs. 22%). “We know from studies of polypodium leucotomos that it seems to have an impact on adaptive immunity as well as helps to decrease oxidative stress, so that may help with melanocyte stability in vitiligo,” said Dr. Lee, who was not affiliated with the study. “As with all treatments, the head and neck is very responsive to this combination treatment. The next most responsive area would be the trunk, followed by the extremities, and hands, and feet.”
Topical treatments
What about topical options for vitiligo? In a randomized, double-blind, comparative study, researchers evaluated the efficacy and safety of combination treatment with 308-nm excimer light and topical calcipotriol or topical clobetasol ointment for acral vitiligo. Combination treatment (excimer light and topical medication) was applied in the first 12 weeks, followed by topical medication alone for 12 weeks. Calcipotriol 0.005% ointment was applied on one hand vs. clobetasol propionate 0.05% ointment on the other for 24 weeks.
Of the hands treated with excimer light and calcipotriol, 7.7% achieved excellent repigmentation at the end of the combination treatment period and 23% achieved good to excellent improvement after 12 weeks of calcipotriol monotherapy. More than 85% and 77% of the hands treated with calcipotriol-based and clobetasol-based regimens showed some repigmentation at the end of the study, respectively (P < .05). However, no significant difference was found between the two treatments. “The evaluation from study participants was similar in that they felt that there was clearly a difference from baseline, but there was no difference across the two-hand therapy,” Dr. Lee said.
Adverse side effects included the development of blisters in some of patients who received clobetasol. “The take-home here is that you get excellent repigmentation with calcipotriol, though it’s a small percentage, 7.7%,” Dr. Lee said. “No excellent repigmentation was observed with excimer light and topical clobetasol. These data support two possible topical regimens that could be added to phototherapy or excimer light therapy to improve results.”
In another study of 42 patients, researchers compared twice-daily tacrolimus 0.1% ointment with vehicle for facial vitiligo through 24 weeks of intervention and 24 weeks of follow-up. The researchers defined treatment success as a change of 75% or greater in repigmentation of the target lesion between baseline and week 24, as measured by computer imaging software.
They found that 65% of tacrolimus-treated patients achieved therapeutic success, compared with none of the vehicle-treated patients at week 24 (P < .0001). “Tacrolimus is thought to be an old drug, but it does deserve to have continued proper study based on much anecdotal evidence I hear,” Dr. Lee said. “There was also efficacy over vehicle during the 24 weeks of follow-up. I find that tacrolimus works very well on the face. I’ve had very good results in children.”
Another topical option is the cream formulation of the JAK inhibitor ruxolitinib (Opzelura), approved in 2022 for the treatment of nonsegmental vitiligo in patients ages 12 and older, the first FDA-approved treatment for vitiligo. “As with the tacrolimus study, there are patients who achieve 100% repigmentation [with ruxolitinib], but others who may not,” Dr. Lee said. In addition, she noted that the combination of JAK inhibitors with phototherapy is emerging as another possible treatment choice, referring to a recently published systematic review suggesting that concurrent UVB phototherapy appears to improve efficacy of JAK inhibitors for vitiligo.
Dr. Lee reported having no relevant financial disclosures.
CARLSBAD, CALIF. – According to Delphine J. Lee, MD, PhD, some patients report that their dermatologists tell them there are no effective treatments for vitiligo.
However, this is not supported by the ongoing level of research on vitiligo, with more than 100 randomized controlled trials published over the last 5 years, Dr. Lee, chief of dermatology at Harbor-UCLA Medical Center, Los Angeles, said at the annual symposium of the California Society of Dermatology & Dermatologic Surgery. And, in 2022, ruxolitinib cream became the first FDA-approved treatment for vitiligo. “There’s a lot of research happening now, and I’m pleased to say that despite the fact that some of these medications are not all brand new and exciting, they’re still new in that we have new evidence for them,” she said. “Of the 100 randomized, controlled trials, UV therapy remains a strong part of our armamentarium.”
Stabilizing disease
Dr. Lee underscored the importance of stabilizing existing vitiligo and arresting progressive disease, which may be indicated by four key signs: koebnerization; trichrome lesions; inflammation, which can appear as erythema, scaling, and pruritus; and confetti-like macules that are typically 1 mm to 5 mm in size. Key principles of vitiligo treatment are to stop immune destruction and to stimulate melanocyte differentiation, migration, and melanin production, which is “probably why phototherapy is so important and helpful,” she said.
Managing patients’ expectations is also important, added Dr. Lee, who shows patients photos from published clinical trials “so they can see what excellent repigmentation really means.”
Dexamethasone vs. mycophenolate
In a randomized, controlled trial published in 2021, researchers compared dexamethasone oral mini-pulse (OMP), 2.5 mg, on two successive days a week, with oral mycophenolate mofetil, 500 mg b.i.d., up to 2 g every day, for 180 days as a stabilizing treatment for patients with progressive, nonsegmental vitiligo, with 90 days of treatment-free follow-up. Assessments included the vitiligo disease activity (VIDA) score, the number of new lesions in the past 30 days, and the Vitiligo Area Scoring Index (VASI). Arrest of disease progression was defined as the absence of any new lesions in the previous 30 days.
Over the treatment and follow-up period, both groups showed a significant trend for reduction in VIDA and in the number of new lesions in the previous 30 days, compared with baseline (P < .001). The difference between VASI at baseline and VASI at 180 and at 270 days was not significant in both groups.
Adverse side effects reported with dexamethasone included acne, weight gain, headache, insomnia, and menstrual irregularity. “The misconception is that because we only give patients a tiny dose of steroids – 2.5 mg two days per week – that they aren’t going to have any side effects,” Dr. Lee commented. “But in fact, they do.” The most common side effects with mycophenolate were nausea and diarrhea. Two patients on mycophenolate discontinued treatment: one for leukopenia and one for transaminitis, but both conditions resolved after treatment was stopped.
The researchers concluded that both dexamethasone OMP and mycophenolate mofetil halt actively spreading vitiligo. “Relapse occurred earlier with mycophenolate, and the relapse rate was higher than with dexamethasone OMP, but this was not statistically significant,” said Dr. Lee, who also leads an immunology research team at The Lundquist Institute at Harbor-UCLA Medical Center.
Other vitiligo treatment options she discussed included the following:
Betamethasone OMP and oral azathioprine. In a comparative study, researchers compared betamethasone OMP with oral azathioprine in arresting disease progression and inducing repigmentation in adults with vitiligo. Significantly more patients in the betamethasone OMP group achieved arrest of progression at 2 months than those in the azathioprine group, but at 6 months the difference was not significant. At 6 months, of the 19 patients who completed 6 months of betamethasone OMP, 2, 2, and 9 patients had more than 20%, 10%-20%, and 5%-10% repigmentation, respectively; and of the 18 patients who completed 6 months of azathioprine, 2 patients had 10%-20% repigmentation, with the remaining patients having no repigmentation or less than 5% repigmentation.
One patient in the azathioprine group developed acute pancreatitis but none developed transaminitis or leukopenia. “Azathioprine is another agent to add to our toolbox,” Dr. Lee said of the study findings. “Both betamethasone OMP and daily azathioprine are effective” in halting disease progression.
Low-dose cyclosporine. In a comparative study, 50 patients with active vitiligo were randomized into two groups: 25 to dexamethasone OMP 2.5 mg on two consecutive days/week for 4 months, and 25 to cyclosporine 3 mg/kg per day for 4 months, stopped treatment, and were then followed up for another 2 months. After 6 months, 84% of patients in the dexamethasone OMP group and 88% of patients in the cyclosporine group achieved arrest of disease progression (P = 1.00), but the mean time to achieve that endpoint was shorter for those in the cyclosporine group, compared with those in the dexamethasone OMP group (a mean of 3.92 weeks vs. 4.12 weeks, respectively; P = .01).
The list of adverse side effects for cyclosporine was “quite lengthy compared to the usual you would expect for dexamethasone,” said Dr. Lee, who was not involved with the study. “This is something we want to take seriously and discuss with our patients. Still, I would say that low-dose cyclosporine is another possibility to add to our toolbox.”
Phototherapy combined with polypodium leucotomos. Dr. Lee highlighted a randomized, controlled trial in which 21 patients with generalized vitiligo received narrow band (NB)-UVB phototherapy plus polypodium leucotomos extract (480 mg b.i.d.) and 21 patients received NB-UVB phototherapy plus placebo. After 6 months of treatment, patients in the NB-UVB plus oral polypodium leucotomos extract group had a better response rate, compared with those in the NB-UVB plus placebo group (47.8% vs. 22%). “We know from studies of polypodium leucotomos that it seems to have an impact on adaptive immunity as well as helps to decrease oxidative stress, so that may help with melanocyte stability in vitiligo,” said Dr. Lee, who was not affiliated with the study. “As with all treatments, the head and neck is very responsive to this combination treatment. The next most responsive area would be the trunk, followed by the extremities, and hands, and feet.”
Topical treatments
What about topical options for vitiligo? In a randomized, double-blind, comparative study, researchers evaluated the efficacy and safety of combination treatment with 308-nm excimer light and topical calcipotriol or topical clobetasol ointment for acral vitiligo. Combination treatment (excimer light and topical medication) was applied in the first 12 weeks, followed by topical medication alone for 12 weeks. Calcipotriol 0.005% ointment was applied on one hand vs. clobetasol propionate 0.05% ointment on the other for 24 weeks.
Of the hands treated with excimer light and calcipotriol, 7.7% achieved excellent repigmentation at the end of the combination treatment period and 23% achieved good to excellent improvement after 12 weeks of calcipotriol monotherapy. More than 85% and 77% of the hands treated with calcipotriol-based and clobetasol-based regimens showed some repigmentation at the end of the study, respectively (P < .05). However, no significant difference was found between the two treatments. “The evaluation from study participants was similar in that they felt that there was clearly a difference from baseline, but there was no difference across the two-hand therapy,” Dr. Lee said.
Adverse side effects included the development of blisters in some of patients who received clobetasol. “The take-home here is that you get excellent repigmentation with calcipotriol, though it’s a small percentage, 7.7%,” Dr. Lee said. “No excellent repigmentation was observed with excimer light and topical clobetasol. These data support two possible topical regimens that could be added to phototherapy or excimer light therapy to improve results.”
In another study of 42 patients, researchers compared twice-daily tacrolimus 0.1% ointment with vehicle for facial vitiligo through 24 weeks of intervention and 24 weeks of follow-up. The researchers defined treatment success as a change of 75% or greater in repigmentation of the target lesion between baseline and week 24, as measured by computer imaging software.
They found that 65% of tacrolimus-treated patients achieved therapeutic success, compared with none of the vehicle-treated patients at week 24 (P < .0001). “Tacrolimus is thought to be an old drug, but it does deserve to have continued proper study based on much anecdotal evidence I hear,” Dr. Lee said. “There was also efficacy over vehicle during the 24 weeks of follow-up. I find that tacrolimus works very well on the face. I’ve had very good results in children.”
Another topical option is the cream formulation of the JAK inhibitor ruxolitinib (Opzelura), approved in 2022 for the treatment of nonsegmental vitiligo in patients ages 12 and older, the first FDA-approved treatment for vitiligo. “As with the tacrolimus study, there are patients who achieve 100% repigmentation [with ruxolitinib], but others who may not,” Dr. Lee said. In addition, she noted that the combination of JAK inhibitors with phototherapy is emerging as another possible treatment choice, referring to a recently published systematic review suggesting that concurrent UVB phototherapy appears to improve efficacy of JAK inhibitors for vitiligo.
Dr. Lee reported having no relevant financial disclosures.
CARLSBAD, CALIF. – According to Delphine J. Lee, MD, PhD, some patients report that their dermatologists tell them there are no effective treatments for vitiligo.
However, this is not supported by the ongoing level of research on vitiligo, with more than 100 randomized controlled trials published over the last 5 years, Dr. Lee, chief of dermatology at Harbor-UCLA Medical Center, Los Angeles, said at the annual symposium of the California Society of Dermatology & Dermatologic Surgery. And, in 2022, ruxolitinib cream became the first FDA-approved treatment for vitiligo. “There’s a lot of research happening now, and I’m pleased to say that despite the fact that some of these medications are not all brand new and exciting, they’re still new in that we have new evidence for them,” she said. “Of the 100 randomized, controlled trials, UV therapy remains a strong part of our armamentarium.”
Stabilizing disease
Dr. Lee underscored the importance of stabilizing existing vitiligo and arresting progressive disease, which may be indicated by four key signs: koebnerization; trichrome lesions; inflammation, which can appear as erythema, scaling, and pruritus; and confetti-like macules that are typically 1 mm to 5 mm in size. Key principles of vitiligo treatment are to stop immune destruction and to stimulate melanocyte differentiation, migration, and melanin production, which is “probably why phototherapy is so important and helpful,” she said.
Managing patients’ expectations is also important, added Dr. Lee, who shows patients photos from published clinical trials “so they can see what excellent repigmentation really means.”
Dexamethasone vs. mycophenolate
In a randomized, controlled trial published in 2021, researchers compared dexamethasone oral mini-pulse (OMP), 2.5 mg, on two successive days a week, with oral mycophenolate mofetil, 500 mg b.i.d., up to 2 g every day, for 180 days as a stabilizing treatment for patients with progressive, nonsegmental vitiligo, with 90 days of treatment-free follow-up. Assessments included the vitiligo disease activity (VIDA) score, the number of new lesions in the past 30 days, and the Vitiligo Area Scoring Index (VASI). Arrest of disease progression was defined as the absence of any new lesions in the previous 30 days.
Over the treatment and follow-up period, both groups showed a significant trend for reduction in VIDA and in the number of new lesions in the previous 30 days, compared with baseline (P < .001). The difference between VASI at baseline and VASI at 180 and at 270 days was not significant in both groups.
Adverse side effects reported with dexamethasone included acne, weight gain, headache, insomnia, and menstrual irregularity. “The misconception is that because we only give patients a tiny dose of steroids – 2.5 mg two days per week – that they aren’t going to have any side effects,” Dr. Lee commented. “But in fact, they do.” The most common side effects with mycophenolate were nausea and diarrhea. Two patients on mycophenolate discontinued treatment: one for leukopenia and one for transaminitis, but both conditions resolved after treatment was stopped.
The researchers concluded that both dexamethasone OMP and mycophenolate mofetil halt actively spreading vitiligo. “Relapse occurred earlier with mycophenolate, and the relapse rate was higher than with dexamethasone OMP, but this was not statistically significant,” said Dr. Lee, who also leads an immunology research team at The Lundquist Institute at Harbor-UCLA Medical Center.
Other vitiligo treatment options she discussed included the following:
Betamethasone OMP and oral azathioprine. In a comparative study, researchers compared betamethasone OMP with oral azathioprine in arresting disease progression and inducing repigmentation in adults with vitiligo. Significantly more patients in the betamethasone OMP group achieved arrest of progression at 2 months than those in the azathioprine group, but at 6 months the difference was not significant. At 6 months, of the 19 patients who completed 6 months of betamethasone OMP, 2, 2, and 9 patients had more than 20%, 10%-20%, and 5%-10% repigmentation, respectively; and of the 18 patients who completed 6 months of azathioprine, 2 patients had 10%-20% repigmentation, with the remaining patients having no repigmentation or less than 5% repigmentation.
One patient in the azathioprine group developed acute pancreatitis but none developed transaminitis or leukopenia. “Azathioprine is another agent to add to our toolbox,” Dr. Lee said of the study findings. “Both betamethasone OMP and daily azathioprine are effective” in halting disease progression.
Low-dose cyclosporine. In a comparative study, 50 patients with active vitiligo were randomized into two groups: 25 to dexamethasone OMP 2.5 mg on two consecutive days/week for 4 months, and 25 to cyclosporine 3 mg/kg per day for 4 months, stopped treatment, and were then followed up for another 2 months. After 6 months, 84% of patients in the dexamethasone OMP group and 88% of patients in the cyclosporine group achieved arrest of disease progression (P = 1.00), but the mean time to achieve that endpoint was shorter for those in the cyclosporine group, compared with those in the dexamethasone OMP group (a mean of 3.92 weeks vs. 4.12 weeks, respectively; P = .01).
The list of adverse side effects for cyclosporine was “quite lengthy compared to the usual you would expect for dexamethasone,” said Dr. Lee, who was not involved with the study. “This is something we want to take seriously and discuss with our patients. Still, I would say that low-dose cyclosporine is another possibility to add to our toolbox.”
Phototherapy combined with polypodium leucotomos. Dr. Lee highlighted a randomized, controlled trial in which 21 patients with generalized vitiligo received narrow band (NB)-UVB phototherapy plus polypodium leucotomos extract (480 mg b.i.d.) and 21 patients received NB-UVB phototherapy plus placebo. After 6 months of treatment, patients in the NB-UVB plus oral polypodium leucotomos extract group had a better response rate, compared with those in the NB-UVB plus placebo group (47.8% vs. 22%). “We know from studies of polypodium leucotomos that it seems to have an impact on adaptive immunity as well as helps to decrease oxidative stress, so that may help with melanocyte stability in vitiligo,” said Dr. Lee, who was not affiliated with the study. “As with all treatments, the head and neck is very responsive to this combination treatment. The next most responsive area would be the trunk, followed by the extremities, and hands, and feet.”
Topical treatments
What about topical options for vitiligo? In a randomized, double-blind, comparative study, researchers evaluated the efficacy and safety of combination treatment with 308-nm excimer light and topical calcipotriol or topical clobetasol ointment for acral vitiligo. Combination treatment (excimer light and topical medication) was applied in the first 12 weeks, followed by topical medication alone for 12 weeks. Calcipotriol 0.005% ointment was applied on one hand vs. clobetasol propionate 0.05% ointment on the other for 24 weeks.
Of the hands treated with excimer light and calcipotriol, 7.7% achieved excellent repigmentation at the end of the combination treatment period and 23% achieved good to excellent improvement after 12 weeks of calcipotriol monotherapy. More than 85% and 77% of the hands treated with calcipotriol-based and clobetasol-based regimens showed some repigmentation at the end of the study, respectively (P < .05). However, no significant difference was found between the two treatments. “The evaluation from study participants was similar in that they felt that there was clearly a difference from baseline, but there was no difference across the two-hand therapy,” Dr. Lee said.
Adverse side effects included the development of blisters in some of patients who received clobetasol. “The take-home here is that you get excellent repigmentation with calcipotriol, though it’s a small percentage, 7.7%,” Dr. Lee said. “No excellent repigmentation was observed with excimer light and topical clobetasol. These data support two possible topical regimens that could be added to phototherapy or excimer light therapy to improve results.”
In another study of 42 patients, researchers compared twice-daily tacrolimus 0.1% ointment with vehicle for facial vitiligo through 24 weeks of intervention and 24 weeks of follow-up. The researchers defined treatment success as a change of 75% or greater in repigmentation of the target lesion between baseline and week 24, as measured by computer imaging software.
They found that 65% of tacrolimus-treated patients achieved therapeutic success, compared with none of the vehicle-treated patients at week 24 (P < .0001). “Tacrolimus is thought to be an old drug, but it does deserve to have continued proper study based on much anecdotal evidence I hear,” Dr. Lee said. “There was also efficacy over vehicle during the 24 weeks of follow-up. I find that tacrolimus works very well on the face. I’ve had very good results in children.”
Another topical option is the cream formulation of the JAK inhibitor ruxolitinib (Opzelura), approved in 2022 for the treatment of nonsegmental vitiligo in patients ages 12 and older, the first FDA-approved treatment for vitiligo. “As with the tacrolimus study, there are patients who achieve 100% repigmentation [with ruxolitinib], but others who may not,” Dr. Lee said. In addition, she noted that the combination of JAK inhibitors with phototherapy is emerging as another possible treatment choice, referring to a recently published systematic review suggesting that concurrent UVB phototherapy appears to improve efficacy of JAK inhibitors for vitiligo.
Dr. Lee reported having no relevant financial disclosures.
AT CALDERM 2023
Three-quarters of menopausal women report unexpected symptoms
GLASGOW – Three-quarters of women going through perimenopause and menopause experience unexpected distressing, debilitating, and embarrassing symptoms but often fail to receive appropriate treatment, a large U.K.-based survey found.
“For too long, many people have thought of menopause as just hot flashes and vaginal dryness. But we know hormones work all over our body, so there are many symptoms beyond that,” said Daniel Reisel, MBBS, PhD, a gynecologist at University College London, who presented the survey findings at the 2023 annual meeting of the Royal College of General Practitioners.
Primary care physicians in the United Kingdom have seen an increase in cases of women presenting with symptoms associated with menopause at a time when the country’s Parliament is debating whether all women should have a menopause check-up in their early 40s, he said.
Still, only around 14% of menopausal women in the United Kingdom are prescribed hormone replacement therapy (HRT), despite national and international guidelines clearly stating the benefits of the treatment generally outweigh the risks.
Louise Newson, MBChB, who runs the U.K.’s largest menopause clinic, said many women with symptoms of menopause feel the medical system “gaslights” them – dismissing their concerns as trivial or even fabricated.
In her clinic, she typically sees many women with poor sleep, as well as muscle and joint pains. “Yet [when they visit their GPs], they are incorrectly told that it can’t be hormones because they’re still having periods,” she said.
Prescribed antidepressants often precede HRT
The new study sought to learn what women knew and experienced with respect to menopause symptoms and what they thought was important.
Of the 5,744 women who responded to the survey, 79.4% were aged 40-60 years and 84.6% were White. “The survey respondents were not different from the distribution of ethnicities we see in NHS menopause care,” said Dr. Reisel, adding that “the barriers are greater for women in poorer areas and for those who are non-White.”
A total of 30.4% had two to five hospital consultations before the health care professional considered that symptoms were related to changing hormone levels; 38.5% were offered antidepressants before HRT. Nearly all (94.6%) said they had experienced negative mood changes and emotions since becoming perimenopausal or menopausal; of these, 19.1% were formally diagnosed with depression or a mood disorder.
“This all just highlights the frustrations I feel around menopause care,” Dr. Newson said. “Women are often not given the tools to properly understand what’s going on and then they don’t ask for the right treatment, and many are given antidepressants. It’s still medicalizing the menopause but in a different way.”
Education gap
The researchers also asked women if they had experienced any surprising or unexpected symptoms since becoming perimenopausal or menopausal. To this question, 74.2% said they had. Joint pain was the most common unexpected issue (34%), followed by dry eyes (26%), heart palpitations (25%), and hair issues such as dryness, thinning, and loss (20%).
Dr. Reisel said words used to describe these symptoms in free text responses included “distressing,” “debilitating,” “depressing,” and “embarrassing.”
“When an early-50s woman comes to the GP with dry eyes, joint pain, or recurrent urinary tract infections, for example, before prescribing ibuprofen, or antibiotics, GPs should consider replacing a woman’s hormones and then see what is left in terms of symptoms,” he said.
Cognitive problems and negative mood changes also are common and often overlooked, Dr. Reisel noted. “We often see striking improvements in mood and cognition in women who are prescribed testosterone for low libido, yet symptoms in these areas are not currently an indication to start treatment,” he said. “Data from Newson Health show that 18% have suicidal thoughts in the past 2 weeks, and not many people think about this.”
Much of this lack of understanding around unexpected symptoms relates to a lack of awareness and education. “It goes back to primary and secondary school, and more broadly, these issues are not often talked about in society,” he said.
Dr. Reisel also noted that language and cultural barriers often stand in the way. “Many cultures don’t discuss menopause and hormone health in general at all. For example, in Bengali, spoken by 300 million people, there is no word in for menopause. So many women are gaslighted when they try and describe their symptoms, or they’re simply just unaware.”
Dr. Reisel and Dr. Newson reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
GLASGOW – Three-quarters of women going through perimenopause and menopause experience unexpected distressing, debilitating, and embarrassing symptoms but often fail to receive appropriate treatment, a large U.K.-based survey found.
“For too long, many people have thought of menopause as just hot flashes and vaginal dryness. But we know hormones work all over our body, so there are many symptoms beyond that,” said Daniel Reisel, MBBS, PhD, a gynecologist at University College London, who presented the survey findings at the 2023 annual meeting of the Royal College of General Practitioners.
Primary care physicians in the United Kingdom have seen an increase in cases of women presenting with symptoms associated with menopause at a time when the country’s Parliament is debating whether all women should have a menopause check-up in their early 40s, he said.
Still, only around 14% of menopausal women in the United Kingdom are prescribed hormone replacement therapy (HRT), despite national and international guidelines clearly stating the benefits of the treatment generally outweigh the risks.
Louise Newson, MBChB, who runs the U.K.’s largest menopause clinic, said many women with symptoms of menopause feel the medical system “gaslights” them – dismissing their concerns as trivial or even fabricated.
In her clinic, she typically sees many women with poor sleep, as well as muscle and joint pains. “Yet [when they visit their GPs], they are incorrectly told that it can’t be hormones because they’re still having periods,” she said.
Prescribed antidepressants often precede HRT
The new study sought to learn what women knew and experienced with respect to menopause symptoms and what they thought was important.
Of the 5,744 women who responded to the survey, 79.4% were aged 40-60 years and 84.6% were White. “The survey respondents were not different from the distribution of ethnicities we see in NHS menopause care,” said Dr. Reisel, adding that “the barriers are greater for women in poorer areas and for those who are non-White.”
A total of 30.4% had two to five hospital consultations before the health care professional considered that symptoms were related to changing hormone levels; 38.5% were offered antidepressants before HRT. Nearly all (94.6%) said they had experienced negative mood changes and emotions since becoming perimenopausal or menopausal; of these, 19.1% were formally diagnosed with depression or a mood disorder.
“This all just highlights the frustrations I feel around menopause care,” Dr. Newson said. “Women are often not given the tools to properly understand what’s going on and then they don’t ask for the right treatment, and many are given antidepressants. It’s still medicalizing the menopause but in a different way.”
Education gap
The researchers also asked women if they had experienced any surprising or unexpected symptoms since becoming perimenopausal or menopausal. To this question, 74.2% said they had. Joint pain was the most common unexpected issue (34%), followed by dry eyes (26%), heart palpitations (25%), and hair issues such as dryness, thinning, and loss (20%).
Dr. Reisel said words used to describe these symptoms in free text responses included “distressing,” “debilitating,” “depressing,” and “embarrassing.”
“When an early-50s woman comes to the GP with dry eyes, joint pain, or recurrent urinary tract infections, for example, before prescribing ibuprofen, or antibiotics, GPs should consider replacing a woman’s hormones and then see what is left in terms of symptoms,” he said.
Cognitive problems and negative mood changes also are common and often overlooked, Dr. Reisel noted. “We often see striking improvements in mood and cognition in women who are prescribed testosterone for low libido, yet symptoms in these areas are not currently an indication to start treatment,” he said. “Data from Newson Health show that 18% have suicidal thoughts in the past 2 weeks, and not many people think about this.”
Much of this lack of understanding around unexpected symptoms relates to a lack of awareness and education. “It goes back to primary and secondary school, and more broadly, these issues are not often talked about in society,” he said.
Dr. Reisel also noted that language and cultural barriers often stand in the way. “Many cultures don’t discuss menopause and hormone health in general at all. For example, in Bengali, spoken by 300 million people, there is no word in for menopause. So many women are gaslighted when they try and describe their symptoms, or they’re simply just unaware.”
Dr. Reisel and Dr. Newson reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
GLASGOW – Three-quarters of women going through perimenopause and menopause experience unexpected distressing, debilitating, and embarrassing symptoms but often fail to receive appropriate treatment, a large U.K.-based survey found.
“For too long, many people have thought of menopause as just hot flashes and vaginal dryness. But we know hormones work all over our body, so there are many symptoms beyond that,” said Daniel Reisel, MBBS, PhD, a gynecologist at University College London, who presented the survey findings at the 2023 annual meeting of the Royal College of General Practitioners.
Primary care physicians in the United Kingdom have seen an increase in cases of women presenting with symptoms associated with menopause at a time when the country’s Parliament is debating whether all women should have a menopause check-up in their early 40s, he said.
Still, only around 14% of menopausal women in the United Kingdom are prescribed hormone replacement therapy (HRT), despite national and international guidelines clearly stating the benefits of the treatment generally outweigh the risks.
Louise Newson, MBChB, who runs the U.K.’s largest menopause clinic, said many women with symptoms of menopause feel the medical system “gaslights” them – dismissing their concerns as trivial or even fabricated.
In her clinic, she typically sees many women with poor sleep, as well as muscle and joint pains. “Yet [when they visit their GPs], they are incorrectly told that it can’t be hormones because they’re still having periods,” she said.
Prescribed antidepressants often precede HRT
The new study sought to learn what women knew and experienced with respect to menopause symptoms and what they thought was important.
Of the 5,744 women who responded to the survey, 79.4% were aged 40-60 years and 84.6% were White. “The survey respondents were not different from the distribution of ethnicities we see in NHS menopause care,” said Dr. Reisel, adding that “the barriers are greater for women in poorer areas and for those who are non-White.”
A total of 30.4% had two to five hospital consultations before the health care professional considered that symptoms were related to changing hormone levels; 38.5% were offered antidepressants before HRT. Nearly all (94.6%) said they had experienced negative mood changes and emotions since becoming perimenopausal or menopausal; of these, 19.1% were formally diagnosed with depression or a mood disorder.
“This all just highlights the frustrations I feel around menopause care,” Dr. Newson said. “Women are often not given the tools to properly understand what’s going on and then they don’t ask for the right treatment, and many are given antidepressants. It’s still medicalizing the menopause but in a different way.”
Education gap
The researchers also asked women if they had experienced any surprising or unexpected symptoms since becoming perimenopausal or menopausal. To this question, 74.2% said they had. Joint pain was the most common unexpected issue (34%), followed by dry eyes (26%), heart palpitations (25%), and hair issues such as dryness, thinning, and loss (20%).
Dr. Reisel said words used to describe these symptoms in free text responses included “distressing,” “debilitating,” “depressing,” and “embarrassing.”
“When an early-50s woman comes to the GP with dry eyes, joint pain, or recurrent urinary tract infections, for example, before prescribing ibuprofen, or antibiotics, GPs should consider replacing a woman’s hormones and then see what is left in terms of symptoms,” he said.
Cognitive problems and negative mood changes also are common and often overlooked, Dr. Reisel noted. “We often see striking improvements in mood and cognition in women who are prescribed testosterone for low libido, yet symptoms in these areas are not currently an indication to start treatment,” he said. “Data from Newson Health show that 18% have suicidal thoughts in the past 2 weeks, and not many people think about this.”
Much of this lack of understanding around unexpected symptoms relates to a lack of awareness and education. “It goes back to primary and secondary school, and more broadly, these issues are not often talked about in society,” he said.
Dr. Reisel also noted that language and cultural barriers often stand in the way. “Many cultures don’t discuss menopause and hormone health in general at all. For example, in Bengali, spoken by 300 million people, there is no word in for menopause. So many women are gaslighted when they try and describe their symptoms, or they’re simply just unaware.”
Dr. Reisel and Dr. Newson reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.