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Study: Lifetime Cost of Vyjuvek Gene Therapy for DEB Could Be $15-$22 Million
according to the authors of a new study.
The US Food and Drug Administration (FDA) approved Vyjuvek (Krystal Biotech) in May 2023 for the treatment of wounds in patients ages 6 months and older with dystrophic epidermolysis bullosa (DEB), which includes two types, the most severe form (autosomal recessive, or RDEB) and the autosomal dominant form of DEB (DDEB), which tends to be milder.
Treatment with Vyjuvek “represents an important advance in the treatment of RDEB,” wrote Adam J.N. Raymakers, PhD, and colleagues at the Program on Regulation, Therapeutics, and Law; the Department of Dermatology; and the Division of Pulmonary and Critical Care Medicine at Brigham & Women’s Hospital in Boston, Massachusetts, in their paper, published in JAMA Dermatology. But the price “will be high, potentially limiting patients’ access to it,” they added. Evidence to support it in DDEB “is less conclusive,” they wrote, noting that the pivotal phase 3 study that led to approval included one patient with DDEB.
“The wider indication granted by the FDA may lead to friction between payers on the one hand and patients and physicians on the other,” they wrote, noting a potential minimum price of $300,000 per patient a year, which was based on Krystal’s regulatory filings.
There is no cure for DEB. Vyjuvek, applied as a gel on an ongoing basis, uses a nonreplicating herpes simplex virus type 1 vector to deliver the COL7A1 gene directly to skin cells, restoring the COL7 protein fibrils that stabilize skin structure.
The authors estimated that in the United States, 894 individuals – largely children – with both forms of the disease would be eligible for Vyjuvek treatment in the first year. Based on the $300,000 price, spending on gene therapy could range from $179 million to $357 million for those 894 patients, they reported in the study.
Over the first 3 years, spending could range as high as $1 billion, the authors estimated. Even if patients with only the most severe disease (RDEB) — an estimated 442 patients — received treatment, spending could be $132 million and up to $400 million or more over the first 3 years, they wrote.
Some media outlets have reported that Vyjuvek could cost as much as $600,000, said Dr. Raymakers, a research fellow. That price “would double all of our estimates,” he told this news organization.
The study assumed that patients with RDEB would only live to age 50, which led to a lifetime cost estimate of $15 million. But that is likely a conservative estimate, he and his coauthors wrote, noting that many patients with RDEB die from squamous cell carcinoma, but that Vyjuvek could, by attenuating skin damage, also potentially prevent skin cancer.
Dr. Raymakers said he and his colleagues began their study when Vyjuvek was approved, and thus they did not have any real-world data on the price or payer responses. Their estimates also did not include differing dosing regimens, which also could change their spending figures.
Krystal Biotech recently reported that in its third quarter of 2023 – representing just 1 month of Vyjuvek availability – it received requests to begin treatment for 284 patients from 136 unique clinicians. Twenty percent of the start requests were for patients with the milder form (DDEB), and a third of all the requests were for patients 10 years of age or younger. The company also said that it had “received positive coverage determinations from all major commercial national health plans” and that it was on track to receive approval from most state Medicaid plans.
In 1 month, Krystal reported net Vyjuvek revenues of $8.6 million.
The authors suggested that one way to evaluate Vyjuvek’s value — especially for those with DDEB — would be through a cost-effectiveness study. While important, a cost-effectiveness study would not get at the impact on a payer, said Dr. Raymakers. “Something can be cost-effective but unaffordable to the system,” he said.
“When there’s one of these very expensive therapies, that’s one thing,” he said. “But when there’s more and more coming to market, you wonder how much can be tolerated,” said Dr. Raymakers.
CMS Launching Gene Therapy Program
The Biden administration recently announced that it was launching a program aimed at increasing access, curbing costs, and ensuring value of gene therapies, starting with sickle cell disease. The program will begin in early 2025. Among other aspects, the federal government will negotiate the price of the product with the manufacturer.
“The goal of the Cell and Gene Therapy Access Model is to increase access to innovative cell and gene therapies for people with Medicaid by making it easier for states to pay for these therapies,” said Liz Fowler, CMS Deputy Administrator and Director of the CMS Innovation Center, in a statement announcing the program.
Whether the new program takes a look at Vyjuvek – and when – is not clear.
But the authors of the study noted that the lifetime costs of treating a patient with Vyjuvek “exceed the costs of all other one-time gene therapies for other diseases.” And they wrote, even at the most conservative estimates, Vyjuvek “will be the most expensive gene therapy currently marketed in the US.”
The study was funded by a grant from Arnold Ventures, grants from the Kaiser Permanente Institute for Health Policy, the Commonwealth Fund, and the National Heart, Lung, and Blood Institute. Dr. Raymakers and co-authors reported no financial relationships relevant to the work.
according to the authors of a new study.
The US Food and Drug Administration (FDA) approved Vyjuvek (Krystal Biotech) in May 2023 for the treatment of wounds in patients ages 6 months and older with dystrophic epidermolysis bullosa (DEB), which includes two types, the most severe form (autosomal recessive, or RDEB) and the autosomal dominant form of DEB (DDEB), which tends to be milder.
Treatment with Vyjuvek “represents an important advance in the treatment of RDEB,” wrote Adam J.N. Raymakers, PhD, and colleagues at the Program on Regulation, Therapeutics, and Law; the Department of Dermatology; and the Division of Pulmonary and Critical Care Medicine at Brigham & Women’s Hospital in Boston, Massachusetts, in their paper, published in JAMA Dermatology. But the price “will be high, potentially limiting patients’ access to it,” they added. Evidence to support it in DDEB “is less conclusive,” they wrote, noting that the pivotal phase 3 study that led to approval included one patient with DDEB.
“The wider indication granted by the FDA may lead to friction between payers on the one hand and patients and physicians on the other,” they wrote, noting a potential minimum price of $300,000 per patient a year, which was based on Krystal’s regulatory filings.
There is no cure for DEB. Vyjuvek, applied as a gel on an ongoing basis, uses a nonreplicating herpes simplex virus type 1 vector to deliver the COL7A1 gene directly to skin cells, restoring the COL7 protein fibrils that stabilize skin structure.
The authors estimated that in the United States, 894 individuals – largely children – with both forms of the disease would be eligible for Vyjuvek treatment in the first year. Based on the $300,000 price, spending on gene therapy could range from $179 million to $357 million for those 894 patients, they reported in the study.
Over the first 3 years, spending could range as high as $1 billion, the authors estimated. Even if patients with only the most severe disease (RDEB) — an estimated 442 patients — received treatment, spending could be $132 million and up to $400 million or more over the first 3 years, they wrote.
Some media outlets have reported that Vyjuvek could cost as much as $600,000, said Dr. Raymakers, a research fellow. That price “would double all of our estimates,” he told this news organization.
The study assumed that patients with RDEB would only live to age 50, which led to a lifetime cost estimate of $15 million. But that is likely a conservative estimate, he and his coauthors wrote, noting that many patients with RDEB die from squamous cell carcinoma, but that Vyjuvek could, by attenuating skin damage, also potentially prevent skin cancer.
Dr. Raymakers said he and his colleagues began their study when Vyjuvek was approved, and thus they did not have any real-world data on the price or payer responses. Their estimates also did not include differing dosing regimens, which also could change their spending figures.
Krystal Biotech recently reported that in its third quarter of 2023 – representing just 1 month of Vyjuvek availability – it received requests to begin treatment for 284 patients from 136 unique clinicians. Twenty percent of the start requests were for patients with the milder form (DDEB), and a third of all the requests were for patients 10 years of age or younger. The company also said that it had “received positive coverage determinations from all major commercial national health plans” and that it was on track to receive approval from most state Medicaid plans.
In 1 month, Krystal reported net Vyjuvek revenues of $8.6 million.
The authors suggested that one way to evaluate Vyjuvek’s value — especially for those with DDEB — would be through a cost-effectiveness study. While important, a cost-effectiveness study would not get at the impact on a payer, said Dr. Raymakers. “Something can be cost-effective but unaffordable to the system,” he said.
“When there’s one of these very expensive therapies, that’s one thing,” he said. “But when there’s more and more coming to market, you wonder how much can be tolerated,” said Dr. Raymakers.
CMS Launching Gene Therapy Program
The Biden administration recently announced that it was launching a program aimed at increasing access, curbing costs, and ensuring value of gene therapies, starting with sickle cell disease. The program will begin in early 2025. Among other aspects, the federal government will negotiate the price of the product with the manufacturer.
“The goal of the Cell and Gene Therapy Access Model is to increase access to innovative cell and gene therapies for people with Medicaid by making it easier for states to pay for these therapies,” said Liz Fowler, CMS Deputy Administrator and Director of the CMS Innovation Center, in a statement announcing the program.
Whether the new program takes a look at Vyjuvek – and when – is not clear.
But the authors of the study noted that the lifetime costs of treating a patient with Vyjuvek “exceed the costs of all other one-time gene therapies for other diseases.” And they wrote, even at the most conservative estimates, Vyjuvek “will be the most expensive gene therapy currently marketed in the US.”
The study was funded by a grant from Arnold Ventures, grants from the Kaiser Permanente Institute for Health Policy, the Commonwealth Fund, and the National Heart, Lung, and Blood Institute. Dr. Raymakers and co-authors reported no financial relationships relevant to the work.
according to the authors of a new study.
The US Food and Drug Administration (FDA) approved Vyjuvek (Krystal Biotech) in May 2023 for the treatment of wounds in patients ages 6 months and older with dystrophic epidermolysis bullosa (DEB), which includes two types, the most severe form (autosomal recessive, or RDEB) and the autosomal dominant form of DEB (DDEB), which tends to be milder.
Treatment with Vyjuvek “represents an important advance in the treatment of RDEB,” wrote Adam J.N. Raymakers, PhD, and colleagues at the Program on Regulation, Therapeutics, and Law; the Department of Dermatology; and the Division of Pulmonary and Critical Care Medicine at Brigham & Women’s Hospital in Boston, Massachusetts, in their paper, published in JAMA Dermatology. But the price “will be high, potentially limiting patients’ access to it,” they added. Evidence to support it in DDEB “is less conclusive,” they wrote, noting that the pivotal phase 3 study that led to approval included one patient with DDEB.
“The wider indication granted by the FDA may lead to friction between payers on the one hand and patients and physicians on the other,” they wrote, noting a potential minimum price of $300,000 per patient a year, which was based on Krystal’s regulatory filings.
There is no cure for DEB. Vyjuvek, applied as a gel on an ongoing basis, uses a nonreplicating herpes simplex virus type 1 vector to deliver the COL7A1 gene directly to skin cells, restoring the COL7 protein fibrils that stabilize skin structure.
The authors estimated that in the United States, 894 individuals – largely children – with both forms of the disease would be eligible for Vyjuvek treatment in the first year. Based on the $300,000 price, spending on gene therapy could range from $179 million to $357 million for those 894 patients, they reported in the study.
Over the first 3 years, spending could range as high as $1 billion, the authors estimated. Even if patients with only the most severe disease (RDEB) — an estimated 442 patients — received treatment, spending could be $132 million and up to $400 million or more over the first 3 years, they wrote.
Some media outlets have reported that Vyjuvek could cost as much as $600,000, said Dr. Raymakers, a research fellow. That price “would double all of our estimates,” he told this news organization.
The study assumed that patients with RDEB would only live to age 50, which led to a lifetime cost estimate of $15 million. But that is likely a conservative estimate, he and his coauthors wrote, noting that many patients with RDEB die from squamous cell carcinoma, but that Vyjuvek could, by attenuating skin damage, also potentially prevent skin cancer.
Dr. Raymakers said he and his colleagues began their study when Vyjuvek was approved, and thus they did not have any real-world data on the price or payer responses. Their estimates also did not include differing dosing regimens, which also could change their spending figures.
Krystal Biotech recently reported that in its third quarter of 2023 – representing just 1 month of Vyjuvek availability – it received requests to begin treatment for 284 patients from 136 unique clinicians. Twenty percent of the start requests were for patients with the milder form (DDEB), and a third of all the requests were for patients 10 years of age or younger. The company also said that it had “received positive coverage determinations from all major commercial national health plans” and that it was on track to receive approval from most state Medicaid plans.
In 1 month, Krystal reported net Vyjuvek revenues of $8.6 million.
The authors suggested that one way to evaluate Vyjuvek’s value — especially for those with DDEB — would be through a cost-effectiveness study. While important, a cost-effectiveness study would not get at the impact on a payer, said Dr. Raymakers. “Something can be cost-effective but unaffordable to the system,” he said.
“When there’s one of these very expensive therapies, that’s one thing,” he said. “But when there’s more and more coming to market, you wonder how much can be tolerated,” said Dr. Raymakers.
CMS Launching Gene Therapy Program
The Biden administration recently announced that it was launching a program aimed at increasing access, curbing costs, and ensuring value of gene therapies, starting with sickle cell disease. The program will begin in early 2025. Among other aspects, the federal government will negotiate the price of the product with the manufacturer.
“The goal of the Cell and Gene Therapy Access Model is to increase access to innovative cell and gene therapies for people with Medicaid by making it easier for states to pay for these therapies,” said Liz Fowler, CMS Deputy Administrator and Director of the CMS Innovation Center, in a statement announcing the program.
Whether the new program takes a look at Vyjuvek – and when – is not clear.
But the authors of the study noted that the lifetime costs of treating a patient with Vyjuvek “exceed the costs of all other one-time gene therapies for other diseases.” And they wrote, even at the most conservative estimates, Vyjuvek “will be the most expensive gene therapy currently marketed in the US.”
The study was funded by a grant from Arnold Ventures, grants from the Kaiser Permanente Institute for Health Policy, the Commonwealth Fund, and the National Heart, Lung, and Blood Institute. Dr. Raymakers and co-authors reported no financial relationships relevant to the work.
FROM JAMA DERMATOLOGY
Youth Mental Health in ‘Dire Straits’
, suggests a new report that shines a light on the global mental health crisis among young people.
The burden is high in this population, with around one-fifth of all disease-related disability attributable to mental disorders. The data, drawn from the 2019 Global Burden of Disease (GBD) study, examines mental health in the 293 million people worldwide in this age group.
“This concentration of disability burden at an early age raises concern about the potential lifetime impact of these conditions,” wrote the authors, led by Christian Kieling, MD, PhD, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
The study was published online in JAMA Psychiatry.
State of Emergency
Soaring rates of mental health disorders among young people, intensified by the COVID-19 pandemic, have led the American Academy of Child and Adolescent Psychiatry and the American Academy of Pediatrics to declare a state of emergency.
Using the GBD study, Dr. Kieling and colleagues estimated the global prevalence and years lived with disability associated with mental disorders and substance use disorders in people aged 5-24 years.
In 2019, individuals in this age range had at least one mental disorder and 31 million had a substance use disorder — an average prevalence of 11.6% and 1.2%, respectively.
The prevalence of mental disorders doubled from the age range of 5-9 years (6.8%) to 20-24 years (13.6%).
Among mental disorders analyzed, anxiety disorders were most common in the overall population (84 million; 3.35%) and schizophrenia the least common (2 million; 0.08%).
Notably, the researchers said, there was a steep increase in mood disorders, particularly anxiety and substance use disorders, across early to late adolescence and from late adolescence to young adulthood.
Mental disorders and substance use disorders were the leading cause of nonfatal disability in children and youths in 2019, accounting for 31 million and 4.3 million years lived with disability (YLDs), respectively. That represents roughly 20% and 3% of YLDs, respectively, from all causes.
Youth Mental Health Is Not a Monolith
“That youth mental health is in such dire straits is particularly striking given that many measures of global physical health in young people are improving,” wrote the authors of an accompanying editorial.
In their editorial, Jeremy Veenstra-VanderWeele, MD, Department of Psychiatry, Columbia University, New York, and co-authors noted that these and other age- and gender-related findings “represent a meaningful contribution to the literature.”
The granular data underscore that youth mental health is “not a monolith” but rather involves considerable variation in prevalence and morbidity across both age and gender, they wrote.
Therefore, mental health screening, promotion, and prevention efforts may benefit from an age-based approach that targets specific disorders during “high prevalence developmental intervals, with keen attention also paid to gender,” they suggested.
On the basis of the findings in this analysis, healthcare and education resource allocation may need to be adjusted for specific disorders, they added.
“One might propose a community- or school-based mental health initiative that screens for and educates parents and teachers on ADHD and anxiety disorders from kindergarten through third grade (ages 5-9 years, when prevalence and resulting disability grow markedly),” Dr. Veenstra-VanderWeele and colleagues wrote. “Later initiatives could then focus on mood and substance use disorders during high school and college (ages 15-19 years and 20-24 years).”
The study was partially funded by a research grant from the Cundill Centre for Child and Youth Depression. Dr. Kieling is the founder of Wida. Dr. Veenstra-VanderWeele reported receiving grants from the National Institutes of Health and Simon’s Foundation and research support/advisory board/editorial fees from Autism Speaks, Agency for Healthcare Research and Quality, Health Resources and Services Administration Maternal and Child Health Bureau, American Academy of Child and Adolescent Psychiatry, Forest, Janssen, Yamo, MapLight, Acadia, Roche, Novartis, Seaside Therapeutics, Springer, SynapDx, and Wiley.
A version of this article appeared on Medscape.com.
, suggests a new report that shines a light on the global mental health crisis among young people.
The burden is high in this population, with around one-fifth of all disease-related disability attributable to mental disorders. The data, drawn from the 2019 Global Burden of Disease (GBD) study, examines mental health in the 293 million people worldwide in this age group.
“This concentration of disability burden at an early age raises concern about the potential lifetime impact of these conditions,” wrote the authors, led by Christian Kieling, MD, PhD, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
The study was published online in JAMA Psychiatry.
State of Emergency
Soaring rates of mental health disorders among young people, intensified by the COVID-19 pandemic, have led the American Academy of Child and Adolescent Psychiatry and the American Academy of Pediatrics to declare a state of emergency.
Using the GBD study, Dr. Kieling and colleagues estimated the global prevalence and years lived with disability associated with mental disorders and substance use disorders in people aged 5-24 years.
In 2019, individuals in this age range had at least one mental disorder and 31 million had a substance use disorder — an average prevalence of 11.6% and 1.2%, respectively.
The prevalence of mental disorders doubled from the age range of 5-9 years (6.8%) to 20-24 years (13.6%).
Among mental disorders analyzed, anxiety disorders were most common in the overall population (84 million; 3.35%) and schizophrenia the least common (2 million; 0.08%).
Notably, the researchers said, there was a steep increase in mood disorders, particularly anxiety and substance use disorders, across early to late adolescence and from late adolescence to young adulthood.
Mental disorders and substance use disorders were the leading cause of nonfatal disability in children and youths in 2019, accounting for 31 million and 4.3 million years lived with disability (YLDs), respectively. That represents roughly 20% and 3% of YLDs, respectively, from all causes.
Youth Mental Health Is Not a Monolith
“That youth mental health is in such dire straits is particularly striking given that many measures of global physical health in young people are improving,” wrote the authors of an accompanying editorial.
In their editorial, Jeremy Veenstra-VanderWeele, MD, Department of Psychiatry, Columbia University, New York, and co-authors noted that these and other age- and gender-related findings “represent a meaningful contribution to the literature.”
The granular data underscore that youth mental health is “not a monolith” but rather involves considerable variation in prevalence and morbidity across both age and gender, they wrote.
Therefore, mental health screening, promotion, and prevention efforts may benefit from an age-based approach that targets specific disorders during “high prevalence developmental intervals, with keen attention also paid to gender,” they suggested.
On the basis of the findings in this analysis, healthcare and education resource allocation may need to be adjusted for specific disorders, they added.
“One might propose a community- or school-based mental health initiative that screens for and educates parents and teachers on ADHD and anxiety disorders from kindergarten through third grade (ages 5-9 years, when prevalence and resulting disability grow markedly),” Dr. Veenstra-VanderWeele and colleagues wrote. “Later initiatives could then focus on mood and substance use disorders during high school and college (ages 15-19 years and 20-24 years).”
The study was partially funded by a research grant from the Cundill Centre for Child and Youth Depression. Dr. Kieling is the founder of Wida. Dr. Veenstra-VanderWeele reported receiving grants from the National Institutes of Health and Simon’s Foundation and research support/advisory board/editorial fees from Autism Speaks, Agency for Healthcare Research and Quality, Health Resources and Services Administration Maternal and Child Health Bureau, American Academy of Child and Adolescent Psychiatry, Forest, Janssen, Yamo, MapLight, Acadia, Roche, Novartis, Seaside Therapeutics, Springer, SynapDx, and Wiley.
A version of this article appeared on Medscape.com.
, suggests a new report that shines a light on the global mental health crisis among young people.
The burden is high in this population, with around one-fifth of all disease-related disability attributable to mental disorders. The data, drawn from the 2019 Global Burden of Disease (GBD) study, examines mental health in the 293 million people worldwide in this age group.
“This concentration of disability burden at an early age raises concern about the potential lifetime impact of these conditions,” wrote the authors, led by Christian Kieling, MD, PhD, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
The study was published online in JAMA Psychiatry.
State of Emergency
Soaring rates of mental health disorders among young people, intensified by the COVID-19 pandemic, have led the American Academy of Child and Adolescent Psychiatry and the American Academy of Pediatrics to declare a state of emergency.
Using the GBD study, Dr. Kieling and colleagues estimated the global prevalence and years lived with disability associated with mental disorders and substance use disorders in people aged 5-24 years.
In 2019, individuals in this age range had at least one mental disorder and 31 million had a substance use disorder — an average prevalence of 11.6% and 1.2%, respectively.
The prevalence of mental disorders doubled from the age range of 5-9 years (6.8%) to 20-24 years (13.6%).
Among mental disorders analyzed, anxiety disorders were most common in the overall population (84 million; 3.35%) and schizophrenia the least common (2 million; 0.08%).
Notably, the researchers said, there was a steep increase in mood disorders, particularly anxiety and substance use disorders, across early to late adolescence and from late adolescence to young adulthood.
Mental disorders and substance use disorders were the leading cause of nonfatal disability in children and youths in 2019, accounting for 31 million and 4.3 million years lived with disability (YLDs), respectively. That represents roughly 20% and 3% of YLDs, respectively, from all causes.
Youth Mental Health Is Not a Monolith
“That youth mental health is in such dire straits is particularly striking given that many measures of global physical health in young people are improving,” wrote the authors of an accompanying editorial.
In their editorial, Jeremy Veenstra-VanderWeele, MD, Department of Psychiatry, Columbia University, New York, and co-authors noted that these and other age- and gender-related findings “represent a meaningful contribution to the literature.”
The granular data underscore that youth mental health is “not a monolith” but rather involves considerable variation in prevalence and morbidity across both age and gender, they wrote.
Therefore, mental health screening, promotion, and prevention efforts may benefit from an age-based approach that targets specific disorders during “high prevalence developmental intervals, with keen attention also paid to gender,” they suggested.
On the basis of the findings in this analysis, healthcare and education resource allocation may need to be adjusted for specific disorders, they added.
“One might propose a community- or school-based mental health initiative that screens for and educates parents and teachers on ADHD and anxiety disorders from kindergarten through third grade (ages 5-9 years, when prevalence and resulting disability grow markedly),” Dr. Veenstra-VanderWeele and colleagues wrote. “Later initiatives could then focus on mood and substance use disorders during high school and college (ages 15-19 years and 20-24 years).”
The study was partially funded by a research grant from the Cundill Centre for Child and Youth Depression. Dr. Kieling is the founder of Wida. Dr. Veenstra-VanderWeele reported receiving grants from the National Institutes of Health and Simon’s Foundation and research support/advisory board/editorial fees from Autism Speaks, Agency for Healthcare Research and Quality, Health Resources and Services Administration Maternal and Child Health Bureau, American Academy of Child and Adolescent Psychiatry, Forest, Janssen, Yamo, MapLight, Acadia, Roche, Novartis, Seaside Therapeutics, Springer, SynapDx, and Wiley.
A version of this article appeared on Medscape.com.
Dupilumab Improves AD Affecting the Hands, Feet
TOPLINE:
compared with placebo.
METHODOLOGY:
- The multinational phase 3 LIBERTY-AD-HAFT trial of adults and adolescents with moderate to severe chronic atopic dermatitis (AD) of the hands, feet, or both included 67 participants at 48 sites randomized to dupilumab monotherapy and 66 to placebo.
- The primary endpoint was the proportion of patients scoring 0 or 1 on Hand and Foot Investigator’s Global Assessment (HF-IGA) at week 16.
- Secondary endpoints were severity and extent of signs, symptom intensity (itch and pain), sleep, and quality of life.
TAKEAWAY:
- At week 16, 27 patients receiving dupilumab vs 11 receiving placebo achieved an HF-IGA score of 0 or 1 (40.3% vs 16.7%; P = .003).
- At week 16, 35 participants receiving dupilumab vs nine receiving placebo improved at least four points in the weekly average of daily HF-Peak Pruritus Numeric Rating Scale (52.2% vs 13.6%; P < .0001).
- At week 16, Quality of Life Hand Eczema Questionnaire results improved in the dupilumab group compared with controls (P < .0001), and weekly average of daily Sleep Numeric Rating Scale results improved in the dupilumab group compared with controls (P < .05).
- The safety profile was similar to the known profile in adults and adolescents with moderate to severe AD.
IN PRACTICE:
The results of the study “support dupilumab” as an “efficacious systemic therapy for moderate to severe H/F AD,” the authors wrote.
SOURCE:
The study, led by Eric L. Simpson, MD, MCR, professor of dermatology at the Oregon Health & Science University in Portland, was published on January 29, 2024, in the Journal of the American Academy of Dermatology.
LIMITATIONS:
The short duration of the study and the large proportion of patients with positive patch tests (31 of 133) suggested that some participants may have had concurrent AD and allergic contact dermatitis, so the effect of dupilumab on those patients needs further evaluation.
DISCLOSURES:
The study was sponsored by Sanofi and Regeneron. All but one author had financial relationships with Sanofi, Regeneron, or both. Several authors were employees of, and may hold stocks or stock options in, Sanofi or Regeneron.
TOPLINE:
compared with placebo.
METHODOLOGY:
- The multinational phase 3 LIBERTY-AD-HAFT trial of adults and adolescents with moderate to severe chronic atopic dermatitis (AD) of the hands, feet, or both included 67 participants at 48 sites randomized to dupilumab monotherapy and 66 to placebo.
- The primary endpoint was the proportion of patients scoring 0 or 1 on Hand and Foot Investigator’s Global Assessment (HF-IGA) at week 16.
- Secondary endpoints were severity and extent of signs, symptom intensity (itch and pain), sleep, and quality of life.
TAKEAWAY:
- At week 16, 27 patients receiving dupilumab vs 11 receiving placebo achieved an HF-IGA score of 0 or 1 (40.3% vs 16.7%; P = .003).
- At week 16, 35 participants receiving dupilumab vs nine receiving placebo improved at least four points in the weekly average of daily HF-Peak Pruritus Numeric Rating Scale (52.2% vs 13.6%; P < .0001).
- At week 16, Quality of Life Hand Eczema Questionnaire results improved in the dupilumab group compared with controls (P < .0001), and weekly average of daily Sleep Numeric Rating Scale results improved in the dupilumab group compared with controls (P < .05).
- The safety profile was similar to the known profile in adults and adolescents with moderate to severe AD.
IN PRACTICE:
The results of the study “support dupilumab” as an “efficacious systemic therapy for moderate to severe H/F AD,” the authors wrote.
SOURCE:
The study, led by Eric L. Simpson, MD, MCR, professor of dermatology at the Oregon Health & Science University in Portland, was published on January 29, 2024, in the Journal of the American Academy of Dermatology.
LIMITATIONS:
The short duration of the study and the large proportion of patients with positive patch tests (31 of 133) suggested that some participants may have had concurrent AD and allergic contact dermatitis, so the effect of dupilumab on those patients needs further evaluation.
DISCLOSURES:
The study was sponsored by Sanofi and Regeneron. All but one author had financial relationships with Sanofi, Regeneron, or both. Several authors were employees of, and may hold stocks or stock options in, Sanofi or Regeneron.
TOPLINE:
compared with placebo.
METHODOLOGY:
- The multinational phase 3 LIBERTY-AD-HAFT trial of adults and adolescents with moderate to severe chronic atopic dermatitis (AD) of the hands, feet, or both included 67 participants at 48 sites randomized to dupilumab monotherapy and 66 to placebo.
- The primary endpoint was the proportion of patients scoring 0 or 1 on Hand and Foot Investigator’s Global Assessment (HF-IGA) at week 16.
- Secondary endpoints were severity and extent of signs, symptom intensity (itch and pain), sleep, and quality of life.
TAKEAWAY:
- At week 16, 27 patients receiving dupilumab vs 11 receiving placebo achieved an HF-IGA score of 0 or 1 (40.3% vs 16.7%; P = .003).
- At week 16, 35 participants receiving dupilumab vs nine receiving placebo improved at least four points in the weekly average of daily HF-Peak Pruritus Numeric Rating Scale (52.2% vs 13.6%; P < .0001).
- At week 16, Quality of Life Hand Eczema Questionnaire results improved in the dupilumab group compared with controls (P < .0001), and weekly average of daily Sleep Numeric Rating Scale results improved in the dupilumab group compared with controls (P < .05).
- The safety profile was similar to the known profile in adults and adolescents with moderate to severe AD.
IN PRACTICE:
The results of the study “support dupilumab” as an “efficacious systemic therapy for moderate to severe H/F AD,” the authors wrote.
SOURCE:
The study, led by Eric L. Simpson, MD, MCR, professor of dermatology at the Oregon Health & Science University in Portland, was published on January 29, 2024, in the Journal of the American Academy of Dermatology.
LIMITATIONS:
The short duration of the study and the large proportion of patients with positive patch tests (31 of 133) suggested that some participants may have had concurrent AD and allergic contact dermatitis, so the effect of dupilumab on those patients needs further evaluation.
DISCLOSURES:
The study was sponsored by Sanofi and Regeneron. All but one author had financial relationships with Sanofi, Regeneron, or both. Several authors were employees of, and may hold stocks or stock options in, Sanofi or Regeneron.
Number of State Psychiatric Hospital Beds Hits Historic Low
to help establish competency for trial.
“The shortage of psychiatric beds has real consequences for people with SMI — some will wait months in jail despite not yet being found guilty of a crime, others will be denied admission despite being critically ill, and others still will be discharged prematurely onto the streets to free up beds, where they may grow sicker and be at an elevated risk of mortality,” wrote report coauthors Shanti Silver of the Treatment Advocacy Center (TAC) in Arlington and Elizabeth Sinclair Hanq of the National Association of State Mental Health Program Directors in Alexandria, Virginia.
Published online on January 24, Prevention Over Punishment: Finding the Right Balance of Civil and Forensic State Psychiatric Hospital Beds recommends that state and local governments work together to open additional state psychiatric hospital beds for civil and forensic patients with SMI.
To obtain data about the availability of state psychiatric hospital beds, TAC surveyed state officials from April to August 2023. Official responses were provided by 41 states and the District of Columbia.
Information for the remaining states was gathered from state websites, media articles, preexisting reports, hospital admission staff, or personal contacts living in those states.
The median occupancy rate for state-run hospitals in the new report was 90%, well above the 85% level investigators say usually signals a bed shortage. Overall, 73% of states reported occupancy rates above that level, with 11 states operating at 95% capacity.
The proportion of state psychiatric beds occupied by forensic patients has increased by 12% since 2016, largely driven by the growing number of individuals awaiting a competency determination to stand trial. Before they occupy these beds, however, people with SMI can languish in jail for months or even years, waiting for a bed to open.
About 15% of all state hospital beds and 31% of forensic beds across 34 states were occupied by individuals who had been found not guilty of a crime by reasons of insanity.
“The prioritization of admission of forensic patients has effectively created a system where someone must be arrested to access a state hospital bed,” report coauthor Lisa Dailey, TAC executive director, told this news organization. “But there are not enough beds for forensic patients either; thousands of inmates are waiting in jail on any given day for a bed to open up.”
There are several factors contributing to the scarcity of beds, including an existing hospital staffing shortage made worse by the COVID-19 pandemic and a lack of appropriate discharge facilities.
Report authors offered a number of recommendations to federal, state, and local officials to increase the availability of state-run psychiatric hospital beds, including infrastructure changes involving recruiting and retaining staff for state hospitals and funding new discharge or step-down facilities so that patients have a place to recover when they leave the hospital.
Policy changes could also help, the report noted. Policymakers should consider “dismiss and transfer” procedures to address the backlog of nearly 6000 people with SMI waiting for a state hospital bed to achieve competency to stand trial. With “dismiss and transfer,” criminal charges are dismissed or suspended while an application for civil commitment is filed in the probate court. Once a civil commitment order has been issued, the individual is released to an outpatient commitment program for treatment.
“States must strive for prevention over punishment,” the report concluded.
There was no study funding reported, nor were disclosures available.
A version of this article appeared on Medscape.com.
to help establish competency for trial.
“The shortage of psychiatric beds has real consequences for people with SMI — some will wait months in jail despite not yet being found guilty of a crime, others will be denied admission despite being critically ill, and others still will be discharged prematurely onto the streets to free up beds, where they may grow sicker and be at an elevated risk of mortality,” wrote report coauthors Shanti Silver of the Treatment Advocacy Center (TAC) in Arlington and Elizabeth Sinclair Hanq of the National Association of State Mental Health Program Directors in Alexandria, Virginia.
Published online on January 24, Prevention Over Punishment: Finding the Right Balance of Civil and Forensic State Psychiatric Hospital Beds recommends that state and local governments work together to open additional state psychiatric hospital beds for civil and forensic patients with SMI.
To obtain data about the availability of state psychiatric hospital beds, TAC surveyed state officials from April to August 2023. Official responses were provided by 41 states and the District of Columbia.
Information for the remaining states was gathered from state websites, media articles, preexisting reports, hospital admission staff, or personal contacts living in those states.
The median occupancy rate for state-run hospitals in the new report was 90%, well above the 85% level investigators say usually signals a bed shortage. Overall, 73% of states reported occupancy rates above that level, with 11 states operating at 95% capacity.
The proportion of state psychiatric beds occupied by forensic patients has increased by 12% since 2016, largely driven by the growing number of individuals awaiting a competency determination to stand trial. Before they occupy these beds, however, people with SMI can languish in jail for months or even years, waiting for a bed to open.
About 15% of all state hospital beds and 31% of forensic beds across 34 states were occupied by individuals who had been found not guilty of a crime by reasons of insanity.
“The prioritization of admission of forensic patients has effectively created a system where someone must be arrested to access a state hospital bed,” report coauthor Lisa Dailey, TAC executive director, told this news organization. “But there are not enough beds for forensic patients either; thousands of inmates are waiting in jail on any given day for a bed to open up.”
There are several factors contributing to the scarcity of beds, including an existing hospital staffing shortage made worse by the COVID-19 pandemic and a lack of appropriate discharge facilities.
Report authors offered a number of recommendations to federal, state, and local officials to increase the availability of state-run psychiatric hospital beds, including infrastructure changes involving recruiting and retaining staff for state hospitals and funding new discharge or step-down facilities so that patients have a place to recover when they leave the hospital.
Policy changes could also help, the report noted. Policymakers should consider “dismiss and transfer” procedures to address the backlog of nearly 6000 people with SMI waiting for a state hospital bed to achieve competency to stand trial. With “dismiss and transfer,” criminal charges are dismissed or suspended while an application for civil commitment is filed in the probate court. Once a civil commitment order has been issued, the individual is released to an outpatient commitment program for treatment.
“States must strive for prevention over punishment,” the report concluded.
There was no study funding reported, nor were disclosures available.
A version of this article appeared on Medscape.com.
to help establish competency for trial.
“The shortage of psychiatric beds has real consequences for people with SMI — some will wait months in jail despite not yet being found guilty of a crime, others will be denied admission despite being critically ill, and others still will be discharged prematurely onto the streets to free up beds, where they may grow sicker and be at an elevated risk of mortality,” wrote report coauthors Shanti Silver of the Treatment Advocacy Center (TAC) in Arlington and Elizabeth Sinclair Hanq of the National Association of State Mental Health Program Directors in Alexandria, Virginia.
Published online on January 24, Prevention Over Punishment: Finding the Right Balance of Civil and Forensic State Psychiatric Hospital Beds recommends that state and local governments work together to open additional state psychiatric hospital beds for civil and forensic patients with SMI.
To obtain data about the availability of state psychiatric hospital beds, TAC surveyed state officials from April to August 2023. Official responses were provided by 41 states and the District of Columbia.
Information for the remaining states was gathered from state websites, media articles, preexisting reports, hospital admission staff, or personal contacts living in those states.
The median occupancy rate for state-run hospitals in the new report was 90%, well above the 85% level investigators say usually signals a bed shortage. Overall, 73% of states reported occupancy rates above that level, with 11 states operating at 95% capacity.
The proportion of state psychiatric beds occupied by forensic patients has increased by 12% since 2016, largely driven by the growing number of individuals awaiting a competency determination to stand trial. Before they occupy these beds, however, people with SMI can languish in jail for months or even years, waiting for a bed to open.
About 15% of all state hospital beds and 31% of forensic beds across 34 states were occupied by individuals who had been found not guilty of a crime by reasons of insanity.
“The prioritization of admission of forensic patients has effectively created a system where someone must be arrested to access a state hospital bed,” report coauthor Lisa Dailey, TAC executive director, told this news organization. “But there are not enough beds for forensic patients either; thousands of inmates are waiting in jail on any given day for a bed to open up.”
There are several factors contributing to the scarcity of beds, including an existing hospital staffing shortage made worse by the COVID-19 pandemic and a lack of appropriate discharge facilities.
Report authors offered a number of recommendations to federal, state, and local officials to increase the availability of state-run psychiatric hospital beds, including infrastructure changes involving recruiting and retaining staff for state hospitals and funding new discharge or step-down facilities so that patients have a place to recover when they leave the hospital.
Policy changes could also help, the report noted. Policymakers should consider “dismiss and transfer” procedures to address the backlog of nearly 6000 people with SMI waiting for a state hospital bed to achieve competency to stand trial. With “dismiss and transfer,” criminal charges are dismissed or suspended while an application for civil commitment is filed in the probate court. Once a civil commitment order has been issued, the individual is released to an outpatient commitment program for treatment.
“States must strive for prevention over punishment,” the report concluded.
There was no study funding reported, nor were disclosures available.
A version of this article appeared on Medscape.com.
HPV Positive Test: How to Address Patients’ Anxieties
Faced with a positive human papillomavirus (HPV) test, patients are quickly overwhelmed by anxiety-inducing questions. It is crucial to provide them with adequate responses to reassure them, emphasized Jean-Louis Mergui, MD, president of the International Federation for Colposcopy, during the press conference of the Congress of the French Society of Colposcopy and Cervico-Vaginal Pathology.
“Do I have cancer? When did I catch this papillomavirus? Is it dangerous for my partner? How do I get rid of it?” “Not everyone is equipped to answer these four questions. However, it is extremely important that healthcare professionals provide correct answers to patients so that they stop worrying,” Dr. Mergui explained.
Papillomavirus and Cancer
One of the first instincts of patients who receive a positive HPV test is to turn to the Internet. There, they read about “high-risk HPV, which is potentially oncogenic,” and become completely panicked, said Dr. Mergui.
However, among women, the probability of having a high-grade CIN3 lesion or higher on the cervix when the HPV test is positive is about 7%, according to the ATHENA study. “About 93% of patients do not have a severe lesion on the cervix. That’s why colposcopy is not performed on all patients. They need to be reassured,” said Dr. Mergui. When the papillomavirus persists, there is a risk for a cervical lesion. After 11 years, between 20% and 30% of patients develop a high-grade lesion on the cervix. However, on average, a high-risk HPV is spontaneously eliminated within 1-2 years. “After 14 months, 50% of women will test negative for their papillomavirus,” Dr. Mergui noted.
“High-risk HPV does not mean there is a lesion; it means there is a risk of developing a lesion on the cervix one day. That’s why these patients need to be monitored and explored,” he added.
In practice, when a patient aged between 30 and 65 years has a positive HPV test, cytology is performed to look for lesions. Only in the case of an abnormal smear, ASC-US, is colposcopy recommended. In the absence of a lesion, a control HPV test is conducted 1 year later to monitor virus persistence.
It should be noted that patients who have been treated for a cervical lesion have a five times higher risk of developing invasive cervical, vaginal, or vulvar cancer. Therefore, treated patients must be monitored once every 3 years for life.
Time of Infection
Many patients ask, “When did I catch this papillomavirus?” In response, Dr. Mergui first emphasized that HPV infection is common. “Between ages 15 and 30 years, most of us are infected with a high-risk HPV. When we look at the incidence between ages 15 and 25 years, every year, 20% of all young girls are infected with HPV, including 17% with high-risk HPV. The virus is usually caught within the first 5 years of sexual activity, and typically disappears after about a year,” he explained.
However, the most disturbing scenario for patients is when their last examination was negative, and there is no apparent reason for having caught the virus since then. Suspicion often falls on the partner. Once again, the gynecologist seeks to reassure.
It is possible that the last time screening was conducted, the virus was not sought (HPV test), but rather cervical lesions were sought by smear. However, a normal smear does not mean that the papillomavirus is not present. A negative cytology does not mean a negative HPV test. As we have seen, the virus is not always associated with the presence of a lesion, explained Dr. Mergui.
Also, having had a negative HPV test a few years earlier does not mean that one was not already infected. The HPV test determines the quantity of virus. Therefore, it is possible that the virus was present in small quantities that were without clinical significance (hence, a negative test). However, a few years later, the virus may have multiplied, and the HPV test became positive.
“Sometimes, the virus re-emerges 40, 50 years after infection due to age-related immune decline,” said Dr. Mergui. “So, just because the smear was negative or the HPV test was negative at the last examination does not mean that one was infected between the two.” Moreover, only 15% of couples have the same virus present on the penis or vagina, he pointed out.
Protecting One’s Partner
Once the diagnosis is made, it is often too late to protect the partner because they have already been infected. “It is certain that the partner will be infected or has already been infected because when the patient comes to you with a positive HPV test, she has already had sexual intercourse. It is worth noting that the virus can be transmitted through digital touching, and condoms are not very effective in preventing virus transmission,” said Dr. Mergui.
The speaker further clarified that the risk for men is much lower than that for women. “In women, about 40,000 lesions linked to high-risk HPV types, precancerous or cancerous, are observed every year. In men, this number is 1900. So, this represents 20 times fewer neoplastic lesions in men. The problem in men is oropharyngeal lesions, which are three times more common than in women. However, there is no screening for oropharyngeal cancer.”
So, when should the partner consult? Dr. Mergui advised consulting when there are clinically visible lesions (small warts, bumps, or ear, nose, and throat symptoms). “I do not recommend systematic examination of male or female partners,” he added.
Clearing the Virus
There are treatments for cervical lesions but not for papillomavirus infection.
“The only thing that can be suggested is quitting smoking, which increases viral clearance, thus reducing viral load. Also, the use of condoms helps improve viral clearance, but when women have a stable relationship, it seems unrealistic to think they will constantly use condoms. Finally, the prophylactic vaccine has been proposed, but it does not treat the infection. In fact, the real solution is to tell patients that they need to continue regular monitoring,” said Dr. Mergui.
“It should be noted that an ongoing study at the European level seems to show that when women who have undergone surgical treatment for a high-grade cervical lesion are vaccinated at the time of treatment or just after treatment, it reduces the risk of recurrence by 50%. So, the risk of recurrence is around 7%-8%. This strategy could be interesting, but for now, there is no official recommendation,” Dr. Mergui concluded.
This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.
Faced with a positive human papillomavirus (HPV) test, patients are quickly overwhelmed by anxiety-inducing questions. It is crucial to provide them with adequate responses to reassure them, emphasized Jean-Louis Mergui, MD, president of the International Federation for Colposcopy, during the press conference of the Congress of the French Society of Colposcopy and Cervico-Vaginal Pathology.
“Do I have cancer? When did I catch this papillomavirus? Is it dangerous for my partner? How do I get rid of it?” “Not everyone is equipped to answer these four questions. However, it is extremely important that healthcare professionals provide correct answers to patients so that they stop worrying,” Dr. Mergui explained.
Papillomavirus and Cancer
One of the first instincts of patients who receive a positive HPV test is to turn to the Internet. There, they read about “high-risk HPV, which is potentially oncogenic,” and become completely panicked, said Dr. Mergui.
However, among women, the probability of having a high-grade CIN3 lesion or higher on the cervix when the HPV test is positive is about 7%, according to the ATHENA study. “About 93% of patients do not have a severe lesion on the cervix. That’s why colposcopy is not performed on all patients. They need to be reassured,” said Dr. Mergui. When the papillomavirus persists, there is a risk for a cervical lesion. After 11 years, between 20% and 30% of patients develop a high-grade lesion on the cervix. However, on average, a high-risk HPV is spontaneously eliminated within 1-2 years. “After 14 months, 50% of women will test negative for their papillomavirus,” Dr. Mergui noted.
“High-risk HPV does not mean there is a lesion; it means there is a risk of developing a lesion on the cervix one day. That’s why these patients need to be monitored and explored,” he added.
In practice, when a patient aged between 30 and 65 years has a positive HPV test, cytology is performed to look for lesions. Only in the case of an abnormal smear, ASC-US, is colposcopy recommended. In the absence of a lesion, a control HPV test is conducted 1 year later to monitor virus persistence.
It should be noted that patients who have been treated for a cervical lesion have a five times higher risk of developing invasive cervical, vaginal, or vulvar cancer. Therefore, treated patients must be monitored once every 3 years for life.
Time of Infection
Many patients ask, “When did I catch this papillomavirus?” In response, Dr. Mergui first emphasized that HPV infection is common. “Between ages 15 and 30 years, most of us are infected with a high-risk HPV. When we look at the incidence between ages 15 and 25 years, every year, 20% of all young girls are infected with HPV, including 17% with high-risk HPV. The virus is usually caught within the first 5 years of sexual activity, and typically disappears after about a year,” he explained.
However, the most disturbing scenario for patients is when their last examination was negative, and there is no apparent reason for having caught the virus since then. Suspicion often falls on the partner. Once again, the gynecologist seeks to reassure.
It is possible that the last time screening was conducted, the virus was not sought (HPV test), but rather cervical lesions were sought by smear. However, a normal smear does not mean that the papillomavirus is not present. A negative cytology does not mean a negative HPV test. As we have seen, the virus is not always associated with the presence of a lesion, explained Dr. Mergui.
Also, having had a negative HPV test a few years earlier does not mean that one was not already infected. The HPV test determines the quantity of virus. Therefore, it is possible that the virus was present in small quantities that were without clinical significance (hence, a negative test). However, a few years later, the virus may have multiplied, and the HPV test became positive.
“Sometimes, the virus re-emerges 40, 50 years after infection due to age-related immune decline,” said Dr. Mergui. “So, just because the smear was negative or the HPV test was negative at the last examination does not mean that one was infected between the two.” Moreover, only 15% of couples have the same virus present on the penis or vagina, he pointed out.
Protecting One’s Partner
Once the diagnosis is made, it is often too late to protect the partner because they have already been infected. “It is certain that the partner will be infected or has already been infected because when the patient comes to you with a positive HPV test, she has already had sexual intercourse. It is worth noting that the virus can be transmitted through digital touching, and condoms are not very effective in preventing virus transmission,” said Dr. Mergui.
The speaker further clarified that the risk for men is much lower than that for women. “In women, about 40,000 lesions linked to high-risk HPV types, precancerous or cancerous, are observed every year. In men, this number is 1900. So, this represents 20 times fewer neoplastic lesions in men. The problem in men is oropharyngeal lesions, which are three times more common than in women. However, there is no screening for oropharyngeal cancer.”
So, when should the partner consult? Dr. Mergui advised consulting when there are clinically visible lesions (small warts, bumps, or ear, nose, and throat symptoms). “I do not recommend systematic examination of male or female partners,” he added.
Clearing the Virus
There are treatments for cervical lesions but not for papillomavirus infection.
“The only thing that can be suggested is quitting smoking, which increases viral clearance, thus reducing viral load. Also, the use of condoms helps improve viral clearance, but when women have a stable relationship, it seems unrealistic to think they will constantly use condoms. Finally, the prophylactic vaccine has been proposed, but it does not treat the infection. In fact, the real solution is to tell patients that they need to continue regular monitoring,” said Dr. Mergui.
“It should be noted that an ongoing study at the European level seems to show that when women who have undergone surgical treatment for a high-grade cervical lesion are vaccinated at the time of treatment or just after treatment, it reduces the risk of recurrence by 50%. So, the risk of recurrence is around 7%-8%. This strategy could be interesting, but for now, there is no official recommendation,” Dr. Mergui concluded.
This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.
Faced with a positive human papillomavirus (HPV) test, patients are quickly overwhelmed by anxiety-inducing questions. It is crucial to provide them with adequate responses to reassure them, emphasized Jean-Louis Mergui, MD, president of the International Federation for Colposcopy, during the press conference of the Congress of the French Society of Colposcopy and Cervico-Vaginal Pathology.
“Do I have cancer? When did I catch this papillomavirus? Is it dangerous for my partner? How do I get rid of it?” “Not everyone is equipped to answer these four questions. However, it is extremely important that healthcare professionals provide correct answers to patients so that they stop worrying,” Dr. Mergui explained.
Papillomavirus and Cancer
One of the first instincts of patients who receive a positive HPV test is to turn to the Internet. There, they read about “high-risk HPV, which is potentially oncogenic,” and become completely panicked, said Dr. Mergui.
However, among women, the probability of having a high-grade CIN3 lesion or higher on the cervix when the HPV test is positive is about 7%, according to the ATHENA study. “About 93% of patients do not have a severe lesion on the cervix. That’s why colposcopy is not performed on all patients. They need to be reassured,” said Dr. Mergui. When the papillomavirus persists, there is a risk for a cervical lesion. After 11 years, between 20% and 30% of patients develop a high-grade lesion on the cervix. However, on average, a high-risk HPV is spontaneously eliminated within 1-2 years. “After 14 months, 50% of women will test negative for their papillomavirus,” Dr. Mergui noted.
“High-risk HPV does not mean there is a lesion; it means there is a risk of developing a lesion on the cervix one day. That’s why these patients need to be monitored and explored,” he added.
In practice, when a patient aged between 30 and 65 years has a positive HPV test, cytology is performed to look for lesions. Only in the case of an abnormal smear, ASC-US, is colposcopy recommended. In the absence of a lesion, a control HPV test is conducted 1 year later to monitor virus persistence.
It should be noted that patients who have been treated for a cervical lesion have a five times higher risk of developing invasive cervical, vaginal, or vulvar cancer. Therefore, treated patients must be monitored once every 3 years for life.
Time of Infection
Many patients ask, “When did I catch this papillomavirus?” In response, Dr. Mergui first emphasized that HPV infection is common. “Between ages 15 and 30 years, most of us are infected with a high-risk HPV. When we look at the incidence between ages 15 and 25 years, every year, 20% of all young girls are infected with HPV, including 17% with high-risk HPV. The virus is usually caught within the first 5 years of sexual activity, and typically disappears after about a year,” he explained.
However, the most disturbing scenario for patients is when their last examination was negative, and there is no apparent reason for having caught the virus since then. Suspicion often falls on the partner. Once again, the gynecologist seeks to reassure.
It is possible that the last time screening was conducted, the virus was not sought (HPV test), but rather cervical lesions were sought by smear. However, a normal smear does not mean that the papillomavirus is not present. A negative cytology does not mean a negative HPV test. As we have seen, the virus is not always associated with the presence of a lesion, explained Dr. Mergui.
Also, having had a negative HPV test a few years earlier does not mean that one was not already infected. The HPV test determines the quantity of virus. Therefore, it is possible that the virus was present in small quantities that were without clinical significance (hence, a negative test). However, a few years later, the virus may have multiplied, and the HPV test became positive.
“Sometimes, the virus re-emerges 40, 50 years after infection due to age-related immune decline,” said Dr. Mergui. “So, just because the smear was negative or the HPV test was negative at the last examination does not mean that one was infected between the two.” Moreover, only 15% of couples have the same virus present on the penis or vagina, he pointed out.
Protecting One’s Partner
Once the diagnosis is made, it is often too late to protect the partner because they have already been infected. “It is certain that the partner will be infected or has already been infected because when the patient comes to you with a positive HPV test, she has already had sexual intercourse. It is worth noting that the virus can be transmitted through digital touching, and condoms are not very effective in preventing virus transmission,” said Dr. Mergui.
The speaker further clarified that the risk for men is much lower than that for women. “In women, about 40,000 lesions linked to high-risk HPV types, precancerous or cancerous, are observed every year. In men, this number is 1900. So, this represents 20 times fewer neoplastic lesions in men. The problem in men is oropharyngeal lesions, which are three times more common than in women. However, there is no screening for oropharyngeal cancer.”
So, when should the partner consult? Dr. Mergui advised consulting when there are clinically visible lesions (small warts, bumps, or ear, nose, and throat symptoms). “I do not recommend systematic examination of male or female partners,” he added.
Clearing the Virus
There are treatments for cervical lesions but not for papillomavirus infection.
“The only thing that can be suggested is quitting smoking, which increases viral clearance, thus reducing viral load. Also, the use of condoms helps improve viral clearance, but when women have a stable relationship, it seems unrealistic to think they will constantly use condoms. Finally, the prophylactic vaccine has been proposed, but it does not treat the infection. In fact, the real solution is to tell patients that they need to continue regular monitoring,” said Dr. Mergui.
“It should be noted that an ongoing study at the European level seems to show that when women who have undergone surgical treatment for a high-grade cervical lesion are vaccinated at the time of treatment or just after treatment, it reduces the risk of recurrence by 50%. So, the risk of recurrence is around 7%-8%. This strategy could be interesting, but for now, there is no official recommendation,” Dr. Mergui concluded.
This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.
Glycemic control in pregnancy: The role of CGM for T1D and T2D, and intrapartum management
WASHINGTON — Continuous glucose monitoring (CGM) is widely used during pregnancy for individuals with type 1 diabetes — with pregnancy-specific target metrics now chosen and benefits on perinatal outcomes demonstrated — but more research is needed to elucidate its role in the growing population of pregnant people with type 2 diabetes and gestational diabetes (GDM). And overall, there are still “many more questions unanswered about CGM use in pregnancy than what we have answered,” Celeste Durnwald, MD, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.
There’s much to learn about how to best interpret “the detailed and complex data that CGM provides,” and what targets in addition to time in range (TIR) are most important, said Dr. Durnwald, director of the perinatal diabetes program and associate professor of ob.gyn. at the Hospital of the University of Pennsylvania, Philadelphia, in a presentation on CGM.
Among other questions are whether fasting glucose is “as important in the era of CGM,” and whether there should be different glycemic targets for nocturnal versus daytime TIR, she said. Moreover, questions justifiably remain about whether the TIR targets for type 1 diabetes in pregnancy are indeed optimal, she said in a discussion period.
Ongoing research is looking at whether CGM can motivate and guide patients with GDM through diet and lifestyle changes such that “we can see changes in amounts of medication we use,” Dr. Durnwald noted in her presentation. “There’s a whole breadth of research looking at whether CGM can help predict diagnosis of GDM, large for gestational age, or preeclampsia, and what are the targets.”
Maternal hypoglycemia during pregnancy — a time when strict glycemic control is recommended to reduce the risk of congenital malformations and other fetal and neonatal morbidity — remains a concern in type 1 diabetes, even with widespread use of CGM in this population, said Barak Rosenn, MD, during a presentation on glycemic control in type 1 diabetes.
A pilot study of a newly designed pregnancy-specific closed-loop insulin delivery system, published last year (Diabetes Care. 2023;46:1425-31), has offered the first “really encouraging information about the ability to use our most up-to-date technology to help our type 1 patients maintain strict control and at the same time decrease their risk of severe hypoglycemia,” said Dr. Rosenn, a maternal-fetal medicine specialist at the Jersey City Medical Center, Jersey City, New Jersey.
Guidance for tight intrapartum glucose control, meanwhile, has been backed by little evidence, said Michal Fishel Bartal, MD, MS, and some recent studies and reviews have shown little to no effect of such tight control on neonatal hypoglycemia, which is the aim of the guidance.
“We need to reexamine current recommendations,” said Dr. Bartal, assistant professor in the division of maternal-fetal medicine at the University of Texas Health Science Center, Houston, during a presentation on intrapartum care. “There’s very limited evidence-based data for the way we manage people with diabetes [during labor and delivery].”
The Knowns And Unknowns of CGM in Pregnancy
The multicenter, international CONCEPTT trial (Continuous Glucose Monitoring in Pregnant Women With Type 1 Diabetes), published in 2017, was the first trial to demonstrate improvements in perinatal outcomes, and it “brought CGM to the forefront in terms of widespread use,” Dr. Durnwald said.
The trial randomized more than 300 patients with type 1 diabetes who were pregnant or planning pregnancy (both users of insulin pumps and users of multiple insulin injections) to continuous, real-time CGM in addition to finger-stick glucose monitoring, or standard finger-stick glucose tests alone. In addition to small improvements in A1c and 7% more TIR (without an increase in hypoglycemia), pregnant CGM users had reductions in large-for-gestational age (LGA) births (53% vs 69%, P = .0489), neonatal intensive care admissions lasting more than 24 hours, and severe neonatal hypoglycemia.
Numbers needed to treat to prevent adverse outcomes in the CONCEPTT trial were six for LGA, six for NICU admission, and eight for neonatal hypoglycemia.
Data from the CONCEPTT trial featured prominently in the development of consensus recommendations for CGM targets in pregnancy by an international expert panel endorsed by the American Diabetes Association. In its 2019 report, the group recommended a target range of 63-140 mg/dL for type 1 and type 2 diabetes during pregnancy (compared with 70-180 mg/dL outside of pregnancy), and a TIR > 70% for pregnant people with type 1 diabetes. (Targets for time below range and time above range are also defined for type 1.)
More data are needed, the group said, in order to recommend TIR targets for type 2 diabetes in pregnancy or GDM (Diabetes Care. 2019;42:1593-603). “Many argue,” Dr. Durnwald said, “that there could be more stringent targets for those at less risk for [maternal] hypoglycemia, especially our GDM population.”
There’s a question of whether even higher TIR would further improve perinatal outcomes, she said, “or will we reach a threshold where higher TIR doesn’t get us a [further] reduction in LGA or preeclampsia.”
And while TIR is “certainly our buzzword,” lower mean glucose levels have also been associated with a lower risk of LGA and other adverse neonatal outcomes. A 2019 retrospective study from Sweden, for instance, analyzed patterns of CGM data from 186 pregnant women with type 1 diabetes and found significant associations between elevated mean glucose levels (in the second and third trimesters) and both LGA and an adverse neonatal composite outcome (Diabetologia. 2019;62:1143-53).
Elevated TIR was also associated with LGA, but “mean glucose had the strongest association with the rate of LGA,” Dr. Durnwald said.
Similarly, a 2020 subanalysis of the CONCEPTT trial data found that a higher mean glucose at both 24 and 34 weeks of gestation was significantly associated with a greater risk of LGA (Diabetes Care. 2020;43:1178-84), and a smaller 2015 analysis of data from two randomized controlled trials of CGM in pregnant women with type 1 and type 2 diabetes found this association in trimesters 2 and 3 (Diabetes Care. 2015;38;1319-25).
The ADA’s Standards of Care in Diabetes (Diabetes Care. 2024;47:S282-S294) endorse CGM as an adjunctive tool in pregnancy — not as a replacement for all traditional blood glucose monitoring — and advise that the use of CGM-reported mean glucose is superior to the use of estimated A1c, glucose management indicator, and other calculations to estimate A1c. Changes occur in pregnancy, Dr. Durnwald pointed out. “Most experts will identify a [target] mean glucose < 120 mg/dL in those with type 1, but there’s potential to have a mean glucose closer to 100 in certainly our patients with GDM and some of our patients with type 2,” she said. To a lesser extent, researchers have also looked at the effect of CMG-reported glycemic variability on outcomes such as LGA, with at least two studies finding some association, and there has been some research on nocturnal glucose and LGA, Dr. Durnwald said. CGM “gives us the opportunity,” she said, “to think about nocturnal glucose as a possible target” for further optimizing diabetes management during pregnancy.
CGM in Type 2, GDM
CGM in type 2 diabetes in pregnancy was addressed in a recently published systematic review and meta-analysis, which found only three qualifying randomized controlled trials and concluded that CGM use was not associated with improvements in perinatal outcomes, as assessed by LGA and preeclampsia (Am J Obstet Gynecol MFM. 2023;5:100969). “It’s very limited by the small sample size and the fact that most [patients] were using intermittent CGM,” Dr. Durnwald said. “It highlights how important it is to perform larger studies with continuous CGM.”
While the 2024 ADA standards say there are insufficient data to support the use of CGM in all patients with type 2 diabetes or GDM — and that the decision should be individualized “based on treatment regimen, circumstance, preferences, and needs” — real-world access to CGM for type 2, and even a bit for GDM, is improving, she said.
Some insurers require patients to be on insulin, but the trends are such that “we certainly talk about CGM to all our patients with type 2 diabetes and even our patients with GDM,” Dr. Durnwald said in a later interview. “CGMs are being advertised so we definitely have people who ask about them upon diagnosis, and we try to make it work for them.”
Is Preventing Maternal Hypoglycemia Possible?
Advancements in technology and pharmacology aimed at optimizing glycemic control — increased adoption of CGM, the use of insulin pump therapy, and the use of more rapid insulin analogs — appear to have had little to no impact on rates of severe maternal hypoglycemia in type 1 diabetes in pregnancy, said Dr. Rosenn, referring to several published studies.
The CONCEPTT study in type 1 diabetes, for instance, “gave us the best data we have on the use of CGM,” but differences in the percentage of patients with severe hypoglycemia and the total number of severe hypoglycemia episodes were basically the same whether patients used CGM or not, he said.
Closed-loop insulin delivery systems have been found in nonpregnant patients with type 1 diabetes to “be helpful in keeping people in range and also possibly [decreasing nocturnal hypoglycemia],” but the systems are not approved for use in pregnancy. “There’s not enough data on use in pregnancy, but probably more important, the algorithms used in the closed-loop systems are not directed to the targets we consider ideal for pregnancy,” Dr. Rosenn said.
In a pilot study of a closed-loop delivery system customized for pregnancies complicated by type 1 diabetes, 10 pregnant women were recruited at 14-32 weeks and, after a 1- to 2-week run-in period using a regular CGM-augmented pump, they used the closed-loop system targeting a daytime glucose of 80-110 mg/dL and nocturnal glucose of 80-100 mg/dL.
Mean TIR (a target range of 63-140 mg/dL) increased from 65% during the run-in period to 79% on the closed-loop system, and there were significant decreases in both time above range and time in the hypoglycemic ranges of < 63 mg/dL and < 54 mg/dL. Hypoglycemic events per week (defined as < 54 mg/dL for over 15 minutes) decreased from 4 to 0.7 (Diabetes Care. 2023;46:1425-31).
The investigators are continuing their research, and there are currently two randomized controlled trials underway examining use of closed-loop systems designed for pregnancy, said Dr. Rosenn, who was involved in feasibility research leading up to the pilot study. “So I’m hopeful we’ll see some encouraging information in the future.”
Maternal hypoglycemia during pregnancy is more common in type 1 diabetes, but it also affects pregnancies complicated by type 2 diabetes and GDM. In addition to the strict glycemic control imposed to improve maternal and fetal outcomes, pregnancy itself plays a role.
Research several decades ago from the Diabetes in Pregnancy Program Project, a prospective cohort in Cincinnati which Dr. Rosenn co-led, documented impaired counterregulatory physiology in pregnancy. Even in nondiabetic patients, there are declines in secretion of glucagon and growth hormone in response to hypoglycemia, for instance. In patients with type 1 diabetes, the diminishment in counterregulatory response is more severe.
Rethinking Intrapartum Care
Guidance for tight blood glucose control during labor and delivery for insulin-treated individuals — as reflected in the American College of Obstetricians and Gynecologists Practice Bulletin No. 201 on Pregestational Diabetes and in recommendations from the United Kingdom’s National Institute for Health and Care Excellence (NICE) — is based on small case series and overall “poor-quality” evidence that more recent research has failed to back up, Dr. Bartal said.
A systematic review published in 2018, for example, concluded there is a paucity of high-quality data supporting the association of glucose during labor and delivery with neonatal hypoglycemia in pregnancies complicated by diabetes (Diabet Med. 2018;35:173-83). And in a subsequent retrospective cohort study of pregnant women with type 1/type 2/GDM and their neonates, the same investigators reported no difference in the target glucose in labor between those with and without neonatal hypotension, after adjustment for important neonatal factors such as LGA and preterm delivery (Diabet Med. 2020;37:138-46).
Also exemplifying the body of research, Dr. Bartal said, is another single-center retrospective study published in 2020 that evaluated outcomes in the years before and after the institution of a formal intrapartum insulin regimen (a standardized protocol for titration of insulin and glucose infusions) for women with pregestational or gestational diabetes. The protocol was associated with improved maternal glucose control, but an increased frequency of neonatal hypoglycemia (Obstet Gynecol. 2020;136:411-6).
Her own group at the University of Texas in Houston looked retrospectively at 233 insulin-treated pregnancies complicated by type 2 diabetes and found no significant difference in the rate of neonatal hypoglycemia between those placed on a drip and those who were not, Dr. Bartal said. Over 40% of the newborns had hypoglycemia; it occurred irrespective of the route of delivery as well (J Matern Fetal Neonatal Med. 2022;35:7445-51).
Only two published randomized controlled trials have evaluated blood sugar control in labor, she said. The first, published in 2006, compared a continuous insulin drip with a rotation of glucose and non–glucose-containing fluids in insulin-requiring diabetes and found no differences in maternal blood glucose (the primary outcome) and a similar risk of neonatal hypoglycemia (Am J Obstet Gynecol. 2006;195;1095-9).
The second RCT, published in 2019, evaluated tight versus liberalized control (60-100 mg/dL, checking every hour, versus 60-120 mg/dL, checking every 4 hours) in laboring women with GDM. The first neonatal blood glucose level was similar in both groups, while the mean neonatal blood glucose level in the first 24 hours of life was lower with tight control (54 vs 58 mg/dL, P = .49) (Obstet Gynecol. 2019;133:1171-7). Findings from a new RCT conducted at the University of Texas in Houston of usual care versus more permissive glucose control will be presented at the SMFM Pregnancy Meeting in February 2024, she said.
Neonatal hypoglycemia is associated with increased risk of NICU admission, “but it’s also associated with possible long-term developmental deficit,” Dr. Bartal said, with the risk highest in children exposed to severe, recurrent, or clinically undetected hypoglycemia. Research has documented significantly increased risks of low executive function and visual motor function, for instance, in children who experienced neonatal hypoglycemia.
The risk of neonatal hypoglycemia has been linked to a variety of factors outside of the intrapartum period such as diabetes control and weight gain during pregnancy, neonatal birth weight/LGA, neonatal adiposity, gestational age at delivery, maternal body mass index, smoking, and diabetes control prior to pregnancy, Dr. Bartal noted. Also challenging is the reality that neonatal hypoglycemia as a research outcome is not standardized; definitions have varied across studies.
Tight intrapartum control comes with “costs,” from close monitoring of labor to increased resource utilization, and it may affect the labor experience/satisfaction, Dr. Bartal said. “But furthermore,” she said, “there are studies coming out, especially in the anesthesiology journals, that show there may be possible harm,” such as the risk of maternal and neonatal hyponatremia, and maternal hypoglycemia. A 2016 editorial in Anaesthesia (2016;71:750) describes these concerns, she noted.
“I do think we need to rethink our current recommendations,” she said.
Dr. Durnwald reported serving on the Dexcom GDM advisory board and receiving funding from United Health Group and the Helmsley Charitable Trust. Dr. Bartal and Dr. Rosenn reported no conflicts of interest.
WASHINGTON — Continuous glucose monitoring (CGM) is widely used during pregnancy for individuals with type 1 diabetes — with pregnancy-specific target metrics now chosen and benefits on perinatal outcomes demonstrated — but more research is needed to elucidate its role in the growing population of pregnant people with type 2 diabetes and gestational diabetes (GDM). And overall, there are still “many more questions unanswered about CGM use in pregnancy than what we have answered,” Celeste Durnwald, MD, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.
There’s much to learn about how to best interpret “the detailed and complex data that CGM provides,” and what targets in addition to time in range (TIR) are most important, said Dr. Durnwald, director of the perinatal diabetes program and associate professor of ob.gyn. at the Hospital of the University of Pennsylvania, Philadelphia, in a presentation on CGM.
Among other questions are whether fasting glucose is “as important in the era of CGM,” and whether there should be different glycemic targets for nocturnal versus daytime TIR, she said. Moreover, questions justifiably remain about whether the TIR targets for type 1 diabetes in pregnancy are indeed optimal, she said in a discussion period.
Ongoing research is looking at whether CGM can motivate and guide patients with GDM through diet and lifestyle changes such that “we can see changes in amounts of medication we use,” Dr. Durnwald noted in her presentation. “There’s a whole breadth of research looking at whether CGM can help predict diagnosis of GDM, large for gestational age, or preeclampsia, and what are the targets.”
Maternal hypoglycemia during pregnancy — a time when strict glycemic control is recommended to reduce the risk of congenital malformations and other fetal and neonatal morbidity — remains a concern in type 1 diabetes, even with widespread use of CGM in this population, said Barak Rosenn, MD, during a presentation on glycemic control in type 1 diabetes.
A pilot study of a newly designed pregnancy-specific closed-loop insulin delivery system, published last year (Diabetes Care. 2023;46:1425-31), has offered the first “really encouraging information about the ability to use our most up-to-date technology to help our type 1 patients maintain strict control and at the same time decrease their risk of severe hypoglycemia,” said Dr. Rosenn, a maternal-fetal medicine specialist at the Jersey City Medical Center, Jersey City, New Jersey.
Guidance for tight intrapartum glucose control, meanwhile, has been backed by little evidence, said Michal Fishel Bartal, MD, MS, and some recent studies and reviews have shown little to no effect of such tight control on neonatal hypoglycemia, which is the aim of the guidance.
“We need to reexamine current recommendations,” said Dr. Bartal, assistant professor in the division of maternal-fetal medicine at the University of Texas Health Science Center, Houston, during a presentation on intrapartum care. “There’s very limited evidence-based data for the way we manage people with diabetes [during labor and delivery].”
The Knowns And Unknowns of CGM in Pregnancy
The multicenter, international CONCEPTT trial (Continuous Glucose Monitoring in Pregnant Women With Type 1 Diabetes), published in 2017, was the first trial to demonstrate improvements in perinatal outcomes, and it “brought CGM to the forefront in terms of widespread use,” Dr. Durnwald said.
The trial randomized more than 300 patients with type 1 diabetes who were pregnant or planning pregnancy (both users of insulin pumps and users of multiple insulin injections) to continuous, real-time CGM in addition to finger-stick glucose monitoring, or standard finger-stick glucose tests alone. In addition to small improvements in A1c and 7% more TIR (without an increase in hypoglycemia), pregnant CGM users had reductions in large-for-gestational age (LGA) births (53% vs 69%, P = .0489), neonatal intensive care admissions lasting more than 24 hours, and severe neonatal hypoglycemia.
Numbers needed to treat to prevent adverse outcomes in the CONCEPTT trial were six for LGA, six for NICU admission, and eight for neonatal hypoglycemia.
Data from the CONCEPTT trial featured prominently in the development of consensus recommendations for CGM targets in pregnancy by an international expert panel endorsed by the American Diabetes Association. In its 2019 report, the group recommended a target range of 63-140 mg/dL for type 1 and type 2 diabetes during pregnancy (compared with 70-180 mg/dL outside of pregnancy), and a TIR > 70% for pregnant people with type 1 diabetes. (Targets for time below range and time above range are also defined for type 1.)
More data are needed, the group said, in order to recommend TIR targets for type 2 diabetes in pregnancy or GDM (Diabetes Care. 2019;42:1593-603). “Many argue,” Dr. Durnwald said, “that there could be more stringent targets for those at less risk for [maternal] hypoglycemia, especially our GDM population.”
There’s a question of whether even higher TIR would further improve perinatal outcomes, she said, “or will we reach a threshold where higher TIR doesn’t get us a [further] reduction in LGA or preeclampsia.”
And while TIR is “certainly our buzzword,” lower mean glucose levels have also been associated with a lower risk of LGA and other adverse neonatal outcomes. A 2019 retrospective study from Sweden, for instance, analyzed patterns of CGM data from 186 pregnant women with type 1 diabetes and found significant associations between elevated mean glucose levels (in the second and third trimesters) and both LGA and an adverse neonatal composite outcome (Diabetologia. 2019;62:1143-53).
Elevated TIR was also associated with LGA, but “mean glucose had the strongest association with the rate of LGA,” Dr. Durnwald said.
Similarly, a 2020 subanalysis of the CONCEPTT trial data found that a higher mean glucose at both 24 and 34 weeks of gestation was significantly associated with a greater risk of LGA (Diabetes Care. 2020;43:1178-84), and a smaller 2015 analysis of data from two randomized controlled trials of CGM in pregnant women with type 1 and type 2 diabetes found this association in trimesters 2 and 3 (Diabetes Care. 2015;38;1319-25).
The ADA’s Standards of Care in Diabetes (Diabetes Care. 2024;47:S282-S294) endorse CGM as an adjunctive tool in pregnancy — not as a replacement for all traditional blood glucose monitoring — and advise that the use of CGM-reported mean glucose is superior to the use of estimated A1c, glucose management indicator, and other calculations to estimate A1c. Changes occur in pregnancy, Dr. Durnwald pointed out. “Most experts will identify a [target] mean glucose < 120 mg/dL in those with type 1, but there’s potential to have a mean glucose closer to 100 in certainly our patients with GDM and some of our patients with type 2,” she said. To a lesser extent, researchers have also looked at the effect of CMG-reported glycemic variability on outcomes such as LGA, with at least two studies finding some association, and there has been some research on nocturnal glucose and LGA, Dr. Durnwald said. CGM “gives us the opportunity,” she said, “to think about nocturnal glucose as a possible target” for further optimizing diabetes management during pregnancy.
CGM in Type 2, GDM
CGM in type 2 diabetes in pregnancy was addressed in a recently published systematic review and meta-analysis, which found only three qualifying randomized controlled trials and concluded that CGM use was not associated with improvements in perinatal outcomes, as assessed by LGA and preeclampsia (Am J Obstet Gynecol MFM. 2023;5:100969). “It’s very limited by the small sample size and the fact that most [patients] were using intermittent CGM,” Dr. Durnwald said. “It highlights how important it is to perform larger studies with continuous CGM.”
While the 2024 ADA standards say there are insufficient data to support the use of CGM in all patients with type 2 diabetes or GDM — and that the decision should be individualized “based on treatment regimen, circumstance, preferences, and needs” — real-world access to CGM for type 2, and even a bit for GDM, is improving, she said.
Some insurers require patients to be on insulin, but the trends are such that “we certainly talk about CGM to all our patients with type 2 diabetes and even our patients with GDM,” Dr. Durnwald said in a later interview. “CGMs are being advertised so we definitely have people who ask about them upon diagnosis, and we try to make it work for them.”
Is Preventing Maternal Hypoglycemia Possible?
Advancements in technology and pharmacology aimed at optimizing glycemic control — increased adoption of CGM, the use of insulin pump therapy, and the use of more rapid insulin analogs — appear to have had little to no impact on rates of severe maternal hypoglycemia in type 1 diabetes in pregnancy, said Dr. Rosenn, referring to several published studies.
The CONCEPTT study in type 1 diabetes, for instance, “gave us the best data we have on the use of CGM,” but differences in the percentage of patients with severe hypoglycemia and the total number of severe hypoglycemia episodes were basically the same whether patients used CGM or not, he said.
Closed-loop insulin delivery systems have been found in nonpregnant patients with type 1 diabetes to “be helpful in keeping people in range and also possibly [decreasing nocturnal hypoglycemia],” but the systems are not approved for use in pregnancy. “There’s not enough data on use in pregnancy, but probably more important, the algorithms used in the closed-loop systems are not directed to the targets we consider ideal for pregnancy,” Dr. Rosenn said.
In a pilot study of a closed-loop delivery system customized for pregnancies complicated by type 1 diabetes, 10 pregnant women were recruited at 14-32 weeks and, after a 1- to 2-week run-in period using a regular CGM-augmented pump, they used the closed-loop system targeting a daytime glucose of 80-110 mg/dL and nocturnal glucose of 80-100 mg/dL.
Mean TIR (a target range of 63-140 mg/dL) increased from 65% during the run-in period to 79% on the closed-loop system, and there were significant decreases in both time above range and time in the hypoglycemic ranges of < 63 mg/dL and < 54 mg/dL. Hypoglycemic events per week (defined as < 54 mg/dL for over 15 minutes) decreased from 4 to 0.7 (Diabetes Care. 2023;46:1425-31).
The investigators are continuing their research, and there are currently two randomized controlled trials underway examining use of closed-loop systems designed for pregnancy, said Dr. Rosenn, who was involved in feasibility research leading up to the pilot study. “So I’m hopeful we’ll see some encouraging information in the future.”
Maternal hypoglycemia during pregnancy is more common in type 1 diabetes, but it also affects pregnancies complicated by type 2 diabetes and GDM. In addition to the strict glycemic control imposed to improve maternal and fetal outcomes, pregnancy itself plays a role.
Research several decades ago from the Diabetes in Pregnancy Program Project, a prospective cohort in Cincinnati which Dr. Rosenn co-led, documented impaired counterregulatory physiology in pregnancy. Even in nondiabetic patients, there are declines in secretion of glucagon and growth hormone in response to hypoglycemia, for instance. In patients with type 1 diabetes, the diminishment in counterregulatory response is more severe.
Rethinking Intrapartum Care
Guidance for tight blood glucose control during labor and delivery for insulin-treated individuals — as reflected in the American College of Obstetricians and Gynecologists Practice Bulletin No. 201 on Pregestational Diabetes and in recommendations from the United Kingdom’s National Institute for Health and Care Excellence (NICE) — is based on small case series and overall “poor-quality” evidence that more recent research has failed to back up, Dr. Bartal said.
A systematic review published in 2018, for example, concluded there is a paucity of high-quality data supporting the association of glucose during labor and delivery with neonatal hypoglycemia in pregnancies complicated by diabetes (Diabet Med. 2018;35:173-83). And in a subsequent retrospective cohort study of pregnant women with type 1/type 2/GDM and their neonates, the same investigators reported no difference in the target glucose in labor between those with and without neonatal hypotension, after adjustment for important neonatal factors such as LGA and preterm delivery (Diabet Med. 2020;37:138-46).
Also exemplifying the body of research, Dr. Bartal said, is another single-center retrospective study published in 2020 that evaluated outcomes in the years before and after the institution of a formal intrapartum insulin regimen (a standardized protocol for titration of insulin and glucose infusions) for women with pregestational or gestational diabetes. The protocol was associated with improved maternal glucose control, but an increased frequency of neonatal hypoglycemia (Obstet Gynecol. 2020;136:411-6).
Her own group at the University of Texas in Houston looked retrospectively at 233 insulin-treated pregnancies complicated by type 2 diabetes and found no significant difference in the rate of neonatal hypoglycemia between those placed on a drip and those who were not, Dr. Bartal said. Over 40% of the newborns had hypoglycemia; it occurred irrespective of the route of delivery as well (J Matern Fetal Neonatal Med. 2022;35:7445-51).
Only two published randomized controlled trials have evaluated blood sugar control in labor, she said. The first, published in 2006, compared a continuous insulin drip with a rotation of glucose and non–glucose-containing fluids in insulin-requiring diabetes and found no differences in maternal blood glucose (the primary outcome) and a similar risk of neonatal hypoglycemia (Am J Obstet Gynecol. 2006;195;1095-9).
The second RCT, published in 2019, evaluated tight versus liberalized control (60-100 mg/dL, checking every hour, versus 60-120 mg/dL, checking every 4 hours) in laboring women with GDM. The first neonatal blood glucose level was similar in both groups, while the mean neonatal blood glucose level in the first 24 hours of life was lower with tight control (54 vs 58 mg/dL, P = .49) (Obstet Gynecol. 2019;133:1171-7). Findings from a new RCT conducted at the University of Texas in Houston of usual care versus more permissive glucose control will be presented at the SMFM Pregnancy Meeting in February 2024, she said.
Neonatal hypoglycemia is associated with increased risk of NICU admission, “but it’s also associated with possible long-term developmental deficit,” Dr. Bartal said, with the risk highest in children exposed to severe, recurrent, or clinically undetected hypoglycemia. Research has documented significantly increased risks of low executive function and visual motor function, for instance, in children who experienced neonatal hypoglycemia.
The risk of neonatal hypoglycemia has been linked to a variety of factors outside of the intrapartum period such as diabetes control and weight gain during pregnancy, neonatal birth weight/LGA, neonatal adiposity, gestational age at delivery, maternal body mass index, smoking, and diabetes control prior to pregnancy, Dr. Bartal noted. Also challenging is the reality that neonatal hypoglycemia as a research outcome is not standardized; definitions have varied across studies.
Tight intrapartum control comes with “costs,” from close monitoring of labor to increased resource utilization, and it may affect the labor experience/satisfaction, Dr. Bartal said. “But furthermore,” she said, “there are studies coming out, especially in the anesthesiology journals, that show there may be possible harm,” such as the risk of maternal and neonatal hyponatremia, and maternal hypoglycemia. A 2016 editorial in Anaesthesia (2016;71:750) describes these concerns, she noted.
“I do think we need to rethink our current recommendations,” she said.
Dr. Durnwald reported serving on the Dexcom GDM advisory board and receiving funding from United Health Group and the Helmsley Charitable Trust. Dr. Bartal and Dr. Rosenn reported no conflicts of interest.
WASHINGTON — Continuous glucose monitoring (CGM) is widely used during pregnancy for individuals with type 1 diabetes — with pregnancy-specific target metrics now chosen and benefits on perinatal outcomes demonstrated — but more research is needed to elucidate its role in the growing population of pregnant people with type 2 diabetes and gestational diabetes (GDM). And overall, there are still “many more questions unanswered about CGM use in pregnancy than what we have answered,” Celeste Durnwald, MD, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.
There’s much to learn about how to best interpret “the detailed and complex data that CGM provides,” and what targets in addition to time in range (TIR) are most important, said Dr. Durnwald, director of the perinatal diabetes program and associate professor of ob.gyn. at the Hospital of the University of Pennsylvania, Philadelphia, in a presentation on CGM.
Among other questions are whether fasting glucose is “as important in the era of CGM,” and whether there should be different glycemic targets for nocturnal versus daytime TIR, she said. Moreover, questions justifiably remain about whether the TIR targets for type 1 diabetes in pregnancy are indeed optimal, she said in a discussion period.
Ongoing research is looking at whether CGM can motivate and guide patients with GDM through diet and lifestyle changes such that “we can see changes in amounts of medication we use,” Dr. Durnwald noted in her presentation. “There’s a whole breadth of research looking at whether CGM can help predict diagnosis of GDM, large for gestational age, or preeclampsia, and what are the targets.”
Maternal hypoglycemia during pregnancy — a time when strict glycemic control is recommended to reduce the risk of congenital malformations and other fetal and neonatal morbidity — remains a concern in type 1 diabetes, even with widespread use of CGM in this population, said Barak Rosenn, MD, during a presentation on glycemic control in type 1 diabetes.
A pilot study of a newly designed pregnancy-specific closed-loop insulin delivery system, published last year (Diabetes Care. 2023;46:1425-31), has offered the first “really encouraging information about the ability to use our most up-to-date technology to help our type 1 patients maintain strict control and at the same time decrease their risk of severe hypoglycemia,” said Dr. Rosenn, a maternal-fetal medicine specialist at the Jersey City Medical Center, Jersey City, New Jersey.
Guidance for tight intrapartum glucose control, meanwhile, has been backed by little evidence, said Michal Fishel Bartal, MD, MS, and some recent studies and reviews have shown little to no effect of such tight control on neonatal hypoglycemia, which is the aim of the guidance.
“We need to reexamine current recommendations,” said Dr. Bartal, assistant professor in the division of maternal-fetal medicine at the University of Texas Health Science Center, Houston, during a presentation on intrapartum care. “There’s very limited evidence-based data for the way we manage people with diabetes [during labor and delivery].”
The Knowns And Unknowns of CGM in Pregnancy
The multicenter, international CONCEPTT trial (Continuous Glucose Monitoring in Pregnant Women With Type 1 Diabetes), published in 2017, was the first trial to demonstrate improvements in perinatal outcomes, and it “brought CGM to the forefront in terms of widespread use,” Dr. Durnwald said.
The trial randomized more than 300 patients with type 1 diabetes who were pregnant or planning pregnancy (both users of insulin pumps and users of multiple insulin injections) to continuous, real-time CGM in addition to finger-stick glucose monitoring, or standard finger-stick glucose tests alone. In addition to small improvements in A1c and 7% more TIR (without an increase in hypoglycemia), pregnant CGM users had reductions in large-for-gestational age (LGA) births (53% vs 69%, P = .0489), neonatal intensive care admissions lasting more than 24 hours, and severe neonatal hypoglycemia.
Numbers needed to treat to prevent adverse outcomes in the CONCEPTT trial were six for LGA, six for NICU admission, and eight for neonatal hypoglycemia.
Data from the CONCEPTT trial featured prominently in the development of consensus recommendations for CGM targets in pregnancy by an international expert panel endorsed by the American Diabetes Association. In its 2019 report, the group recommended a target range of 63-140 mg/dL for type 1 and type 2 diabetes during pregnancy (compared with 70-180 mg/dL outside of pregnancy), and a TIR > 70% for pregnant people with type 1 diabetes. (Targets for time below range and time above range are also defined for type 1.)
More data are needed, the group said, in order to recommend TIR targets for type 2 diabetes in pregnancy or GDM (Diabetes Care. 2019;42:1593-603). “Many argue,” Dr. Durnwald said, “that there could be more stringent targets for those at less risk for [maternal] hypoglycemia, especially our GDM population.”
There’s a question of whether even higher TIR would further improve perinatal outcomes, she said, “or will we reach a threshold where higher TIR doesn’t get us a [further] reduction in LGA or preeclampsia.”
And while TIR is “certainly our buzzword,” lower mean glucose levels have also been associated with a lower risk of LGA and other adverse neonatal outcomes. A 2019 retrospective study from Sweden, for instance, analyzed patterns of CGM data from 186 pregnant women with type 1 diabetes and found significant associations between elevated mean glucose levels (in the second and third trimesters) and both LGA and an adverse neonatal composite outcome (Diabetologia. 2019;62:1143-53).
Elevated TIR was also associated with LGA, but “mean glucose had the strongest association with the rate of LGA,” Dr. Durnwald said.
Similarly, a 2020 subanalysis of the CONCEPTT trial data found that a higher mean glucose at both 24 and 34 weeks of gestation was significantly associated with a greater risk of LGA (Diabetes Care. 2020;43:1178-84), and a smaller 2015 analysis of data from two randomized controlled trials of CGM in pregnant women with type 1 and type 2 diabetes found this association in trimesters 2 and 3 (Diabetes Care. 2015;38;1319-25).
The ADA’s Standards of Care in Diabetes (Diabetes Care. 2024;47:S282-S294) endorse CGM as an adjunctive tool in pregnancy — not as a replacement for all traditional blood glucose monitoring — and advise that the use of CGM-reported mean glucose is superior to the use of estimated A1c, glucose management indicator, and other calculations to estimate A1c. Changes occur in pregnancy, Dr. Durnwald pointed out. “Most experts will identify a [target] mean glucose < 120 mg/dL in those with type 1, but there’s potential to have a mean glucose closer to 100 in certainly our patients with GDM and some of our patients with type 2,” she said. To a lesser extent, researchers have also looked at the effect of CMG-reported glycemic variability on outcomes such as LGA, with at least two studies finding some association, and there has been some research on nocturnal glucose and LGA, Dr. Durnwald said. CGM “gives us the opportunity,” she said, “to think about nocturnal glucose as a possible target” for further optimizing diabetes management during pregnancy.
CGM in Type 2, GDM
CGM in type 2 diabetes in pregnancy was addressed in a recently published systematic review and meta-analysis, which found only three qualifying randomized controlled trials and concluded that CGM use was not associated with improvements in perinatal outcomes, as assessed by LGA and preeclampsia (Am J Obstet Gynecol MFM. 2023;5:100969). “It’s very limited by the small sample size and the fact that most [patients] were using intermittent CGM,” Dr. Durnwald said. “It highlights how important it is to perform larger studies with continuous CGM.”
While the 2024 ADA standards say there are insufficient data to support the use of CGM in all patients with type 2 diabetes or GDM — and that the decision should be individualized “based on treatment regimen, circumstance, preferences, and needs” — real-world access to CGM for type 2, and even a bit for GDM, is improving, she said.
Some insurers require patients to be on insulin, but the trends are such that “we certainly talk about CGM to all our patients with type 2 diabetes and even our patients with GDM,” Dr. Durnwald said in a later interview. “CGMs are being advertised so we definitely have people who ask about them upon diagnosis, and we try to make it work for them.”
Is Preventing Maternal Hypoglycemia Possible?
Advancements in technology and pharmacology aimed at optimizing glycemic control — increased adoption of CGM, the use of insulin pump therapy, and the use of more rapid insulin analogs — appear to have had little to no impact on rates of severe maternal hypoglycemia in type 1 diabetes in pregnancy, said Dr. Rosenn, referring to several published studies.
The CONCEPTT study in type 1 diabetes, for instance, “gave us the best data we have on the use of CGM,” but differences in the percentage of patients with severe hypoglycemia and the total number of severe hypoglycemia episodes were basically the same whether patients used CGM or not, he said.
Closed-loop insulin delivery systems have been found in nonpregnant patients with type 1 diabetes to “be helpful in keeping people in range and also possibly [decreasing nocturnal hypoglycemia],” but the systems are not approved for use in pregnancy. “There’s not enough data on use in pregnancy, but probably more important, the algorithms used in the closed-loop systems are not directed to the targets we consider ideal for pregnancy,” Dr. Rosenn said.
In a pilot study of a closed-loop delivery system customized for pregnancies complicated by type 1 diabetes, 10 pregnant women were recruited at 14-32 weeks and, after a 1- to 2-week run-in period using a regular CGM-augmented pump, they used the closed-loop system targeting a daytime glucose of 80-110 mg/dL and nocturnal glucose of 80-100 mg/dL.
Mean TIR (a target range of 63-140 mg/dL) increased from 65% during the run-in period to 79% on the closed-loop system, and there were significant decreases in both time above range and time in the hypoglycemic ranges of < 63 mg/dL and < 54 mg/dL. Hypoglycemic events per week (defined as < 54 mg/dL for over 15 minutes) decreased from 4 to 0.7 (Diabetes Care. 2023;46:1425-31).
The investigators are continuing their research, and there are currently two randomized controlled trials underway examining use of closed-loop systems designed for pregnancy, said Dr. Rosenn, who was involved in feasibility research leading up to the pilot study. “So I’m hopeful we’ll see some encouraging information in the future.”
Maternal hypoglycemia during pregnancy is more common in type 1 diabetes, but it also affects pregnancies complicated by type 2 diabetes and GDM. In addition to the strict glycemic control imposed to improve maternal and fetal outcomes, pregnancy itself plays a role.
Research several decades ago from the Diabetes in Pregnancy Program Project, a prospective cohort in Cincinnati which Dr. Rosenn co-led, documented impaired counterregulatory physiology in pregnancy. Even in nondiabetic patients, there are declines in secretion of glucagon and growth hormone in response to hypoglycemia, for instance. In patients with type 1 diabetes, the diminishment in counterregulatory response is more severe.
Rethinking Intrapartum Care
Guidance for tight blood glucose control during labor and delivery for insulin-treated individuals — as reflected in the American College of Obstetricians and Gynecologists Practice Bulletin No. 201 on Pregestational Diabetes and in recommendations from the United Kingdom’s National Institute for Health and Care Excellence (NICE) — is based on small case series and overall “poor-quality” evidence that more recent research has failed to back up, Dr. Bartal said.
A systematic review published in 2018, for example, concluded there is a paucity of high-quality data supporting the association of glucose during labor and delivery with neonatal hypoglycemia in pregnancies complicated by diabetes (Diabet Med. 2018;35:173-83). And in a subsequent retrospective cohort study of pregnant women with type 1/type 2/GDM and their neonates, the same investigators reported no difference in the target glucose in labor between those with and without neonatal hypotension, after adjustment for important neonatal factors such as LGA and preterm delivery (Diabet Med. 2020;37:138-46).
Also exemplifying the body of research, Dr. Bartal said, is another single-center retrospective study published in 2020 that evaluated outcomes in the years before and after the institution of a formal intrapartum insulin regimen (a standardized protocol for titration of insulin and glucose infusions) for women with pregestational or gestational diabetes. The protocol was associated with improved maternal glucose control, but an increased frequency of neonatal hypoglycemia (Obstet Gynecol. 2020;136:411-6).
Her own group at the University of Texas in Houston looked retrospectively at 233 insulin-treated pregnancies complicated by type 2 diabetes and found no significant difference in the rate of neonatal hypoglycemia between those placed on a drip and those who were not, Dr. Bartal said. Over 40% of the newborns had hypoglycemia; it occurred irrespective of the route of delivery as well (J Matern Fetal Neonatal Med. 2022;35:7445-51).
Only two published randomized controlled trials have evaluated blood sugar control in labor, she said. The first, published in 2006, compared a continuous insulin drip with a rotation of glucose and non–glucose-containing fluids in insulin-requiring diabetes and found no differences in maternal blood glucose (the primary outcome) and a similar risk of neonatal hypoglycemia (Am J Obstet Gynecol. 2006;195;1095-9).
The second RCT, published in 2019, evaluated tight versus liberalized control (60-100 mg/dL, checking every hour, versus 60-120 mg/dL, checking every 4 hours) in laboring women with GDM. The first neonatal blood glucose level was similar in both groups, while the mean neonatal blood glucose level in the first 24 hours of life was lower with tight control (54 vs 58 mg/dL, P = .49) (Obstet Gynecol. 2019;133:1171-7). Findings from a new RCT conducted at the University of Texas in Houston of usual care versus more permissive glucose control will be presented at the SMFM Pregnancy Meeting in February 2024, she said.
Neonatal hypoglycemia is associated with increased risk of NICU admission, “but it’s also associated with possible long-term developmental deficit,” Dr. Bartal said, with the risk highest in children exposed to severe, recurrent, or clinically undetected hypoglycemia. Research has documented significantly increased risks of low executive function and visual motor function, for instance, in children who experienced neonatal hypoglycemia.
The risk of neonatal hypoglycemia has been linked to a variety of factors outside of the intrapartum period such as diabetes control and weight gain during pregnancy, neonatal birth weight/LGA, neonatal adiposity, gestational age at delivery, maternal body mass index, smoking, and diabetes control prior to pregnancy, Dr. Bartal noted. Also challenging is the reality that neonatal hypoglycemia as a research outcome is not standardized; definitions have varied across studies.
Tight intrapartum control comes with “costs,” from close monitoring of labor to increased resource utilization, and it may affect the labor experience/satisfaction, Dr. Bartal said. “But furthermore,” she said, “there are studies coming out, especially in the anesthesiology journals, that show there may be possible harm,” such as the risk of maternal and neonatal hyponatremia, and maternal hypoglycemia. A 2016 editorial in Anaesthesia (2016;71:750) describes these concerns, she noted.
“I do think we need to rethink our current recommendations,” she said.
Dr. Durnwald reported serving on the Dexcom GDM advisory board and receiving funding from United Health Group and the Helmsley Charitable Trust. Dr. Bartal and Dr. Rosenn reported no conflicts of interest.
FROM DPSG-NA 2024
Testosterone Replacement Shows No Benefit in Diabetes Prevention
Testosterone replacement therapy in the treatment of hypogonadism showed no benefit in slowing the progression of prediabetes or diabetes, contrary to previous evidence that suggested potential improvements in insulin sensitivity and metabolism.
“The findings of this study suggest that testosterone replacement therapy alone should not be used as a therapeutic intervention to prevent or treat diabetes in men with hypogonadism,” reported the authors of research published this month in JAMA Internal Medicine.
The suggestion that testosterone replacement could prevent or slow diabetes stems from numerous studies linking testosterone deficiency to a host of adverse effects that include increases in insulin resistance and an increased risk for prediabetes and type 2 diabetes.
Furthermore, one recent uncontrolled study showed a lower rate of progression from prediabetes to diabetes in testosterone-treated vs untreated men with hypogonadism.
But with no known randomized clinical trials evaluating the effects of testosterone on diabetes in the absence of a concurrent lifestyle intervention, Shalender Bhasin, MB, of the Research Program in Men’s Health: Aging and Metabolism, at Brigham and Women’s Hospital, Harvard Medical School, Boston, and colleagues conducted a substudy of the randomized TRAVERSE trial, which was conducted at 316 sites in the United States.
“We hypothesized that testosterone replacement therapy for men with hypogonadism and prediabetes would be associated with a significantly lower rate of progression to diabetes,” they wrote.
In the study, named the TRAVERSE Diabetes Study, 5204 participants aged between 40 and 85 years with hypogonadism as well as prediabetes (n = 1175) or diabetes (n = 3880) were randomized 1:1 to receive treatment either with 1.62% testosterone gel or placebo gel.
The participants had a mean age of 63.2 years, and the mean A1c among those with prediabetes was 5.8%.
For the primary outcome, the risk for progression to diabetes did not differ significantly between the testosterone-treated and placebo groups at 6 months (0.7% vs 1.4%), 12 months (7.8% vs 10.7%), 24 months (10.1% vs 14.6%), 36 months (12.8% vs 15.8%), or 48 months (13.4% vs 15.7%; omnibus test P = .49).
There were also no significant differences in terms of glycemic remission and the changes in glucose and A1c levels between the testosterone- and placebo-treated men with prediabetes or diabetes, consistent with findings from previous smaller trials.
The authors pointed out that the participants in the TRAVERSE trial had mild to moderate testosterone deficiency, and “it is possible that greater improvements in insulin sensitivity may be observed in men with severe testosterone deficiency.”
However, they noted that most men with hypogonadism who are treated with testosterone replacement therapy have only mild testosterone deficiency.
The parent TRAVERSE study did show testosterone replacement therapy to be associated with higher incidences of venous thromboembolism, atrial fibrillation, and acute kidney injury; however, no additional between-group differences were observed based on diabetes or prediabetes status.
“The findings of this study do not support the use of testosterone replacement therapy alone to prevent or to treat diabetes in men with hypogonadism,” the authors concluded.
Study ‘Overcomes Limitations of Prior Studies’
In an editorial published concurrently with the study, Lona Mody, MD, of the Division of Geriatric and Palliative Care Medicine, University of Michigan Medical School, in Ann Arbor, and colleagues underscored that “the results of this study suggest that testosterone replacement therapy will not benefit glycemic control in men without hypogonadism despite the inappropriately high rates of use in this group.”
Further commenting, Dr. Mody elaborated on the high rates of use, noting that data have shown androgen use among men over 40 years increased more than threefold from 0.81% in 2001 to 2.91% in 2011.
“Based on sales data, testosterone prescribing has increased 100-fold from $18 million in the late 1980s to $1.8 billion over three decades,” Dr. Mody said.
She noted that while some previous research has shown a similar lack of benefits, “the current study overcomes some limitations of prior studies.”
Ultimately, the evidence indicated that “the only major indication for testosterone replacement therapy remains to treat bothersome symptoms of hypogonadism,” Dr. Mody said. “It does not appear to have metabolic benefits.”
This trial was funded by a consortium of testosterone manufacturers led by AbbVie Inc., with additional financial support provided by Endo Pharmaceuticals, Acerus Pharmaceuticals Corporation, and Upsher-Smith Laboratories, LLC.
A version of this article appeared on Medscape.com.
Testosterone replacement therapy in the treatment of hypogonadism showed no benefit in slowing the progression of prediabetes or diabetes, contrary to previous evidence that suggested potential improvements in insulin sensitivity and metabolism.
“The findings of this study suggest that testosterone replacement therapy alone should not be used as a therapeutic intervention to prevent or treat diabetes in men with hypogonadism,” reported the authors of research published this month in JAMA Internal Medicine.
The suggestion that testosterone replacement could prevent or slow diabetes stems from numerous studies linking testosterone deficiency to a host of adverse effects that include increases in insulin resistance and an increased risk for prediabetes and type 2 diabetes.
Furthermore, one recent uncontrolled study showed a lower rate of progression from prediabetes to diabetes in testosterone-treated vs untreated men with hypogonadism.
But with no known randomized clinical trials evaluating the effects of testosterone on diabetes in the absence of a concurrent lifestyle intervention, Shalender Bhasin, MB, of the Research Program in Men’s Health: Aging and Metabolism, at Brigham and Women’s Hospital, Harvard Medical School, Boston, and colleagues conducted a substudy of the randomized TRAVERSE trial, which was conducted at 316 sites in the United States.
“We hypothesized that testosterone replacement therapy for men with hypogonadism and prediabetes would be associated with a significantly lower rate of progression to diabetes,” they wrote.
In the study, named the TRAVERSE Diabetes Study, 5204 participants aged between 40 and 85 years with hypogonadism as well as prediabetes (n = 1175) or diabetes (n = 3880) were randomized 1:1 to receive treatment either with 1.62% testosterone gel or placebo gel.
The participants had a mean age of 63.2 years, and the mean A1c among those with prediabetes was 5.8%.
For the primary outcome, the risk for progression to diabetes did not differ significantly between the testosterone-treated and placebo groups at 6 months (0.7% vs 1.4%), 12 months (7.8% vs 10.7%), 24 months (10.1% vs 14.6%), 36 months (12.8% vs 15.8%), or 48 months (13.4% vs 15.7%; omnibus test P = .49).
There were also no significant differences in terms of glycemic remission and the changes in glucose and A1c levels between the testosterone- and placebo-treated men with prediabetes or diabetes, consistent with findings from previous smaller trials.
The authors pointed out that the participants in the TRAVERSE trial had mild to moderate testosterone deficiency, and “it is possible that greater improvements in insulin sensitivity may be observed in men with severe testosterone deficiency.”
However, they noted that most men with hypogonadism who are treated with testosterone replacement therapy have only mild testosterone deficiency.
The parent TRAVERSE study did show testosterone replacement therapy to be associated with higher incidences of venous thromboembolism, atrial fibrillation, and acute kidney injury; however, no additional between-group differences were observed based on diabetes or prediabetes status.
“The findings of this study do not support the use of testosterone replacement therapy alone to prevent or to treat diabetes in men with hypogonadism,” the authors concluded.
Study ‘Overcomes Limitations of Prior Studies’
In an editorial published concurrently with the study, Lona Mody, MD, of the Division of Geriatric and Palliative Care Medicine, University of Michigan Medical School, in Ann Arbor, and colleagues underscored that “the results of this study suggest that testosterone replacement therapy will not benefit glycemic control in men without hypogonadism despite the inappropriately high rates of use in this group.”
Further commenting, Dr. Mody elaborated on the high rates of use, noting that data have shown androgen use among men over 40 years increased more than threefold from 0.81% in 2001 to 2.91% in 2011.
“Based on sales data, testosterone prescribing has increased 100-fold from $18 million in the late 1980s to $1.8 billion over three decades,” Dr. Mody said.
She noted that while some previous research has shown a similar lack of benefits, “the current study overcomes some limitations of prior studies.”
Ultimately, the evidence indicated that “the only major indication for testosterone replacement therapy remains to treat bothersome symptoms of hypogonadism,” Dr. Mody said. “It does not appear to have metabolic benefits.”
This trial was funded by a consortium of testosterone manufacturers led by AbbVie Inc., with additional financial support provided by Endo Pharmaceuticals, Acerus Pharmaceuticals Corporation, and Upsher-Smith Laboratories, LLC.
A version of this article appeared on Medscape.com.
Testosterone replacement therapy in the treatment of hypogonadism showed no benefit in slowing the progression of prediabetes or diabetes, contrary to previous evidence that suggested potential improvements in insulin sensitivity and metabolism.
“The findings of this study suggest that testosterone replacement therapy alone should not be used as a therapeutic intervention to prevent or treat diabetes in men with hypogonadism,” reported the authors of research published this month in JAMA Internal Medicine.
The suggestion that testosterone replacement could prevent or slow diabetes stems from numerous studies linking testosterone deficiency to a host of adverse effects that include increases in insulin resistance and an increased risk for prediabetes and type 2 diabetes.
Furthermore, one recent uncontrolled study showed a lower rate of progression from prediabetes to diabetes in testosterone-treated vs untreated men with hypogonadism.
But with no known randomized clinical trials evaluating the effects of testosterone on diabetes in the absence of a concurrent lifestyle intervention, Shalender Bhasin, MB, of the Research Program in Men’s Health: Aging and Metabolism, at Brigham and Women’s Hospital, Harvard Medical School, Boston, and colleagues conducted a substudy of the randomized TRAVERSE trial, which was conducted at 316 sites in the United States.
“We hypothesized that testosterone replacement therapy for men with hypogonadism and prediabetes would be associated with a significantly lower rate of progression to diabetes,” they wrote.
In the study, named the TRAVERSE Diabetes Study, 5204 participants aged between 40 and 85 years with hypogonadism as well as prediabetes (n = 1175) or diabetes (n = 3880) were randomized 1:1 to receive treatment either with 1.62% testosterone gel or placebo gel.
The participants had a mean age of 63.2 years, and the mean A1c among those with prediabetes was 5.8%.
For the primary outcome, the risk for progression to diabetes did not differ significantly between the testosterone-treated and placebo groups at 6 months (0.7% vs 1.4%), 12 months (7.8% vs 10.7%), 24 months (10.1% vs 14.6%), 36 months (12.8% vs 15.8%), or 48 months (13.4% vs 15.7%; omnibus test P = .49).
There were also no significant differences in terms of glycemic remission and the changes in glucose and A1c levels between the testosterone- and placebo-treated men with prediabetes or diabetes, consistent with findings from previous smaller trials.
The authors pointed out that the participants in the TRAVERSE trial had mild to moderate testosterone deficiency, and “it is possible that greater improvements in insulin sensitivity may be observed in men with severe testosterone deficiency.”
However, they noted that most men with hypogonadism who are treated with testosterone replacement therapy have only mild testosterone deficiency.
The parent TRAVERSE study did show testosterone replacement therapy to be associated with higher incidences of venous thromboembolism, atrial fibrillation, and acute kidney injury; however, no additional between-group differences were observed based on diabetes or prediabetes status.
“The findings of this study do not support the use of testosterone replacement therapy alone to prevent or to treat diabetes in men with hypogonadism,” the authors concluded.
Study ‘Overcomes Limitations of Prior Studies’
In an editorial published concurrently with the study, Lona Mody, MD, of the Division of Geriatric and Palliative Care Medicine, University of Michigan Medical School, in Ann Arbor, and colleagues underscored that “the results of this study suggest that testosterone replacement therapy will not benefit glycemic control in men without hypogonadism despite the inappropriately high rates of use in this group.”
Further commenting, Dr. Mody elaborated on the high rates of use, noting that data have shown androgen use among men over 40 years increased more than threefold from 0.81% in 2001 to 2.91% in 2011.
“Based on sales data, testosterone prescribing has increased 100-fold from $18 million in the late 1980s to $1.8 billion over three decades,” Dr. Mody said.
She noted that while some previous research has shown a similar lack of benefits, “the current study overcomes some limitations of prior studies.”
Ultimately, the evidence indicated that “the only major indication for testosterone replacement therapy remains to treat bothersome symptoms of hypogonadism,” Dr. Mody said. “It does not appear to have metabolic benefits.”
This trial was funded by a consortium of testosterone manufacturers led by AbbVie Inc., with additional financial support provided by Endo Pharmaceuticals, Acerus Pharmaceuticals Corporation, and Upsher-Smith Laboratories, LLC.
A version of this article appeared on Medscape.com.
Survey: Dermatology Residents Shortchanged on Sensitive Skin Education
Although sensitive skin affects an estimated 40%-70% of the population, knowledge of the pathophysiology of sensitive skin is incomplete, and consensus is lacking as to the best diagnosis and treatment strategies, and the inclusion of sensitive skin education in dermatology curricula has not been examined, according to Erika T. McCormick, BS, and Adam Friedman, MD, of George Washington University, Washington, DC.
For the study, published in the Journal of Drugs in Dermatology, they developed a 26-question survey for dermatology residents that asked about sensitive skin in dermatology residency training. Participants came from the Orlando Dermatology, Aesthetic, and Surgical Conference email list.
Survey respondents included 214 residents at various levels of training at programs across the United States; 67.1% were female, 92.1% were aged 25-34 years, and 85.5% were in academic or university programs.
Overall, 99% of respondents believed that sensitive skin issues should be part of their residency training to some extent, and 84% reported experiences with patients for whom the chief presenting complaint was sensitive skin.
However, fewer than half (48%) of the residents reported specific resident education in sensitive skin, while 51% reported nonspecific education about sensitive skin education in the context of other skin diseases, and 1% reported no education about sensitive skin.
Less than one-quarter of the respondents who received any sensitive skin education reported feeling comfortable in their ability to diagnose, evaluate, and manage sensitive skin, while those with sensitive skin–specific education were significantly more likely to describe themselves as “very knowledgeable.”
As for treatment approaches, residents with specific sensitive skin education were more likely than were those without sensitive skin–specific training to ask patients about allergies and past reactions to skin products, and to counsel them about environmental triggers.
Notably, 96% of the respondents were not familiar with the Sensitive Skin (SS) Scale–10, a validated measure of sensitive skin severity.
The most common challenges in care of patients with sensitive skin were assessing improvement over time, reported by 25% of respondents, recommending products (23%), and prescribing/medical management (22%). The topics residents expressed most interest in learning about were product recommendations (78%), patient counseling (77%), reviewing research on sensitive skin (70%), diagnosing sensitive skin (67%), using the SS-10 (48%), and clinical research updates (40%).
The findings were limited by several factors including the reliance on self-reports, the researchers noted. However, the results highlight the lack of consensus in treatment of sensitive skin and the need to address this knowledge gap at the residency level, they said.
Improving Tools for Practice
“Many practice patterns and approaches are forged in the fires of training,” corresponding author Dr. Friedman, professor and chair of dermatology and residency program director at George Washington University, said in an interview. “Identifying gaps, especially for heavily prevalent issues, questions, and concerns such as sensitive skin that residents will encounter in practice is important to ensure an educated workforce,” he said.
Education on sensitive skin is lacking because, until recently, research and clinical guidance have been lacking, Dr. Friedman said. The root of the problem is that sensitive skin is mainly considered a symptom, rather than an independent condition, he explained. “Depending on the study, the prevalence of sensitive skin has been reported as high as 70%, with roughly 40% of these patients having no primary skin condition,” he said. This means sensitive skin can be both a symptom and a condition, which causes confusion for clinicians and patients, he added.
“Therefore, in order to overcome this gap, the condition itself at a minimum needs a standard definition and a way to diagnosis, which we fortunately have in the validated research tool known as the SS-10,” said Dr. Friedman.
Almost all residents surveyed in the current study had never heard of the SS-10, but more than half found it to be useful after learning of it through the study survey, he noted.
Looking ahead, greater elucidation of the pathophysiology of sensitive skin is needed to effectively pursue studies of products and treatments for these patients, but the SS-10 can be used to define and monitor the condition to evaluate improvement, he added.
The study was funded by an independent fellowship grant from Galderma. Ms. McCormick is supported by an unrestricted fellowship grant funded by Galderma. Dr. Friedman has served as a consultant for Galderma.
Although sensitive skin affects an estimated 40%-70% of the population, knowledge of the pathophysiology of sensitive skin is incomplete, and consensus is lacking as to the best diagnosis and treatment strategies, and the inclusion of sensitive skin education in dermatology curricula has not been examined, according to Erika T. McCormick, BS, and Adam Friedman, MD, of George Washington University, Washington, DC.
For the study, published in the Journal of Drugs in Dermatology, they developed a 26-question survey for dermatology residents that asked about sensitive skin in dermatology residency training. Participants came from the Orlando Dermatology, Aesthetic, and Surgical Conference email list.
Survey respondents included 214 residents at various levels of training at programs across the United States; 67.1% were female, 92.1% were aged 25-34 years, and 85.5% were in academic or university programs.
Overall, 99% of respondents believed that sensitive skin issues should be part of their residency training to some extent, and 84% reported experiences with patients for whom the chief presenting complaint was sensitive skin.
However, fewer than half (48%) of the residents reported specific resident education in sensitive skin, while 51% reported nonspecific education about sensitive skin education in the context of other skin diseases, and 1% reported no education about sensitive skin.
Less than one-quarter of the respondents who received any sensitive skin education reported feeling comfortable in their ability to diagnose, evaluate, and manage sensitive skin, while those with sensitive skin–specific education were significantly more likely to describe themselves as “very knowledgeable.”
As for treatment approaches, residents with specific sensitive skin education were more likely than were those without sensitive skin–specific training to ask patients about allergies and past reactions to skin products, and to counsel them about environmental triggers.
Notably, 96% of the respondents were not familiar with the Sensitive Skin (SS) Scale–10, a validated measure of sensitive skin severity.
The most common challenges in care of patients with sensitive skin were assessing improvement over time, reported by 25% of respondents, recommending products (23%), and prescribing/medical management (22%). The topics residents expressed most interest in learning about were product recommendations (78%), patient counseling (77%), reviewing research on sensitive skin (70%), diagnosing sensitive skin (67%), using the SS-10 (48%), and clinical research updates (40%).
The findings were limited by several factors including the reliance on self-reports, the researchers noted. However, the results highlight the lack of consensus in treatment of sensitive skin and the need to address this knowledge gap at the residency level, they said.
Improving Tools for Practice
“Many practice patterns and approaches are forged in the fires of training,” corresponding author Dr. Friedman, professor and chair of dermatology and residency program director at George Washington University, said in an interview. “Identifying gaps, especially for heavily prevalent issues, questions, and concerns such as sensitive skin that residents will encounter in practice is important to ensure an educated workforce,” he said.
Education on sensitive skin is lacking because, until recently, research and clinical guidance have been lacking, Dr. Friedman said. The root of the problem is that sensitive skin is mainly considered a symptom, rather than an independent condition, he explained. “Depending on the study, the prevalence of sensitive skin has been reported as high as 70%, with roughly 40% of these patients having no primary skin condition,” he said. This means sensitive skin can be both a symptom and a condition, which causes confusion for clinicians and patients, he added.
“Therefore, in order to overcome this gap, the condition itself at a minimum needs a standard definition and a way to diagnosis, which we fortunately have in the validated research tool known as the SS-10,” said Dr. Friedman.
Almost all residents surveyed in the current study had never heard of the SS-10, but more than half found it to be useful after learning of it through the study survey, he noted.
Looking ahead, greater elucidation of the pathophysiology of sensitive skin is needed to effectively pursue studies of products and treatments for these patients, but the SS-10 can be used to define and monitor the condition to evaluate improvement, he added.
The study was funded by an independent fellowship grant from Galderma. Ms. McCormick is supported by an unrestricted fellowship grant funded by Galderma. Dr. Friedman has served as a consultant for Galderma.
Although sensitive skin affects an estimated 40%-70% of the population, knowledge of the pathophysiology of sensitive skin is incomplete, and consensus is lacking as to the best diagnosis and treatment strategies, and the inclusion of sensitive skin education in dermatology curricula has not been examined, according to Erika T. McCormick, BS, and Adam Friedman, MD, of George Washington University, Washington, DC.
For the study, published in the Journal of Drugs in Dermatology, they developed a 26-question survey for dermatology residents that asked about sensitive skin in dermatology residency training. Participants came from the Orlando Dermatology, Aesthetic, and Surgical Conference email list.
Survey respondents included 214 residents at various levels of training at programs across the United States; 67.1% were female, 92.1% were aged 25-34 years, and 85.5% were in academic or university programs.
Overall, 99% of respondents believed that sensitive skin issues should be part of their residency training to some extent, and 84% reported experiences with patients for whom the chief presenting complaint was sensitive skin.
However, fewer than half (48%) of the residents reported specific resident education in sensitive skin, while 51% reported nonspecific education about sensitive skin education in the context of other skin diseases, and 1% reported no education about sensitive skin.
Less than one-quarter of the respondents who received any sensitive skin education reported feeling comfortable in their ability to diagnose, evaluate, and manage sensitive skin, while those with sensitive skin–specific education were significantly more likely to describe themselves as “very knowledgeable.”
As for treatment approaches, residents with specific sensitive skin education were more likely than were those without sensitive skin–specific training to ask patients about allergies and past reactions to skin products, and to counsel them about environmental triggers.
Notably, 96% of the respondents were not familiar with the Sensitive Skin (SS) Scale–10, a validated measure of sensitive skin severity.
The most common challenges in care of patients with sensitive skin were assessing improvement over time, reported by 25% of respondents, recommending products (23%), and prescribing/medical management (22%). The topics residents expressed most interest in learning about were product recommendations (78%), patient counseling (77%), reviewing research on sensitive skin (70%), diagnosing sensitive skin (67%), using the SS-10 (48%), and clinical research updates (40%).
The findings were limited by several factors including the reliance on self-reports, the researchers noted. However, the results highlight the lack of consensus in treatment of sensitive skin and the need to address this knowledge gap at the residency level, they said.
Improving Tools for Practice
“Many practice patterns and approaches are forged in the fires of training,” corresponding author Dr. Friedman, professor and chair of dermatology and residency program director at George Washington University, said in an interview. “Identifying gaps, especially for heavily prevalent issues, questions, and concerns such as sensitive skin that residents will encounter in practice is important to ensure an educated workforce,” he said.
Education on sensitive skin is lacking because, until recently, research and clinical guidance have been lacking, Dr. Friedman said. The root of the problem is that sensitive skin is mainly considered a symptom, rather than an independent condition, he explained. “Depending on the study, the prevalence of sensitive skin has been reported as high as 70%, with roughly 40% of these patients having no primary skin condition,” he said. This means sensitive skin can be both a symptom and a condition, which causes confusion for clinicians and patients, he added.
“Therefore, in order to overcome this gap, the condition itself at a minimum needs a standard definition and a way to diagnosis, which we fortunately have in the validated research tool known as the SS-10,” said Dr. Friedman.
Almost all residents surveyed in the current study had never heard of the SS-10, but more than half found it to be useful after learning of it through the study survey, he noted.
Looking ahead, greater elucidation of the pathophysiology of sensitive skin is needed to effectively pursue studies of products and treatments for these patients, but the SS-10 can be used to define and monitor the condition to evaluate improvement, he added.
The study was funded by an independent fellowship grant from Galderma. Ms. McCormick is supported by an unrestricted fellowship grant funded by Galderma. Dr. Friedman has served as a consultant for Galderma.
FROM THE JOURNAL OF DRUGS IN DERMATOLOGY
Freedom of Speech and Gender-Affirming Care
Blue Hill is a small idyllic town a little less than two and a half hours Down East the coast from where I am sitting here in Harpswell. Thanks to gentrification it tends to lean left politically, but like the rest of Maine most folks in the surrounding communities often don’t know or care much about their neighbor’s party affiliation. Its library, founded in 1796, is well funded and a source of civic pride.
One day a couple of years ago, the library director received a donated book from a patron. Although he personally didn’t agree with the book’s message, he felt it deserved a space in their collection dealing with the subject. What happened in the wake of this donation is an ugly tale. Some community members objected to the book and asked that it be removed from the shelves, or at least kept under the desk and loaned out only on request.
The objectors, many of whom knew the director, were confrontational. The collections committee unanimously supported his decision. Some committee members also received similar responses from community members. Remember, this is a small town.
A request for support sent to the American Library Association was basically ignored. Over the next 2 years things have quieted, but fractured friendships and relationships in this quiet coastal Maine town have not been repaired. However, as the librarian has observed, “intellectual freedom or the freedom of speech isn’t there just to protect the ideas that we like.”
While the title of the book may feel inflammatory to some, every publisher hopes to grab the market’s attention with a hot title. The cause of this sad situation in Blue Hill was not a white supremacist’s polemic offering specific ways to create genocide. This was a book suggesting that gender dysphoria presenting in adolescence may have multiple causes and raises concerns about the wisdom of the pace of some gender-affirming care.
Clearly the topic of gender dysphoria in adolescence has become a third rail that must be approached with caution or completely avoided. A recent opinion piece in the New York Times provides even more concerning examples of this peril. Again, the eye-catching title of the article — As Kids, They Thought They Were Trans. They No Longer Do — draws in the audience eager to read about some unfortunate individuals who have regretted their decision to transition and are now detransitioning.
If you are interested in hearing anecdotal evidence and opinions supporting the notion that there is such a thing as rapid-onset gender dysphoria, I suggest you read the entire piece. However, the article’s most troubling message for me comes when I read about the professionals who were former gender-related care providers who left the field because of “pushback, the accusations of being transphobic, from being pro-assessment and wanting a more thorough process.”
One therapist trained in gender-affirming care who began to have doubts about the model and spoke out in favor of a more measured approach was investigated by her licensing board after transgender advocates threatened to report her. Ultimately, her case was dismissed, but she continues to fear for her safety.
Gender-related healthcare is another sad example of how in this country it is the noise coming from the advocates on the extremes of the issue that is drowning out the “vast ideological middle” that is seeking civil and rational discussions.
In this situation there are those who want to make it illegal for the healthcare providers to help patients who might benefit from transitioning. On the other end of the spectrum are those advocates who are unwilling to acknowledge that there may be some adolescents with what has been called by some “rapid-onset gender dysphoria.”
The landscape on which this tragedy is being played out is changing so quickly that there will be no correct answers in the short term. There just isn’t enough data. However, there is enough anecdotal evidence from professionals who were and still are practicing gender-related care to raise a concern that something is happening in the adolescent population that suggests some individuals with gender dysphoria should be managed in a different way than the currently accepted gender-affirming model. The size of this subgroup is up for debate and we may never learn it because of reporting bias and privacy concerns.
The American Academy of Pediatrics has recently authorized a systematic review of gender-affirming care. I hope that, like the librarian in Blue Hill, it will have the courage to include all the evidence available even though, as we have seen here in Maine, some of it may spark a firestorm of vehement responses.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.
Blue Hill is a small idyllic town a little less than two and a half hours Down East the coast from where I am sitting here in Harpswell. Thanks to gentrification it tends to lean left politically, but like the rest of Maine most folks in the surrounding communities often don’t know or care much about their neighbor’s party affiliation. Its library, founded in 1796, is well funded and a source of civic pride.
One day a couple of years ago, the library director received a donated book from a patron. Although he personally didn’t agree with the book’s message, he felt it deserved a space in their collection dealing with the subject. What happened in the wake of this donation is an ugly tale. Some community members objected to the book and asked that it be removed from the shelves, or at least kept under the desk and loaned out only on request.
The objectors, many of whom knew the director, were confrontational. The collections committee unanimously supported his decision. Some committee members also received similar responses from community members. Remember, this is a small town.
A request for support sent to the American Library Association was basically ignored. Over the next 2 years things have quieted, but fractured friendships and relationships in this quiet coastal Maine town have not been repaired. However, as the librarian has observed, “intellectual freedom or the freedom of speech isn’t there just to protect the ideas that we like.”
While the title of the book may feel inflammatory to some, every publisher hopes to grab the market’s attention with a hot title. The cause of this sad situation in Blue Hill was not a white supremacist’s polemic offering specific ways to create genocide. This was a book suggesting that gender dysphoria presenting in adolescence may have multiple causes and raises concerns about the wisdom of the pace of some gender-affirming care.
Clearly the topic of gender dysphoria in adolescence has become a third rail that must be approached with caution or completely avoided. A recent opinion piece in the New York Times provides even more concerning examples of this peril. Again, the eye-catching title of the article — As Kids, They Thought They Were Trans. They No Longer Do — draws in the audience eager to read about some unfortunate individuals who have regretted their decision to transition and are now detransitioning.
If you are interested in hearing anecdotal evidence and opinions supporting the notion that there is such a thing as rapid-onset gender dysphoria, I suggest you read the entire piece. However, the article’s most troubling message for me comes when I read about the professionals who were former gender-related care providers who left the field because of “pushback, the accusations of being transphobic, from being pro-assessment and wanting a more thorough process.”
One therapist trained in gender-affirming care who began to have doubts about the model and spoke out in favor of a more measured approach was investigated by her licensing board after transgender advocates threatened to report her. Ultimately, her case was dismissed, but she continues to fear for her safety.
Gender-related healthcare is another sad example of how in this country it is the noise coming from the advocates on the extremes of the issue that is drowning out the “vast ideological middle” that is seeking civil and rational discussions.
In this situation there are those who want to make it illegal for the healthcare providers to help patients who might benefit from transitioning. On the other end of the spectrum are those advocates who are unwilling to acknowledge that there may be some adolescents with what has been called by some “rapid-onset gender dysphoria.”
The landscape on which this tragedy is being played out is changing so quickly that there will be no correct answers in the short term. There just isn’t enough data. However, there is enough anecdotal evidence from professionals who were and still are practicing gender-related care to raise a concern that something is happening in the adolescent population that suggests some individuals with gender dysphoria should be managed in a different way than the currently accepted gender-affirming model. The size of this subgroup is up for debate and we may never learn it because of reporting bias and privacy concerns.
The American Academy of Pediatrics has recently authorized a systematic review of gender-affirming care. I hope that, like the librarian in Blue Hill, it will have the courage to include all the evidence available even though, as we have seen here in Maine, some of it may spark a firestorm of vehement responses.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.
Blue Hill is a small idyllic town a little less than two and a half hours Down East the coast from where I am sitting here in Harpswell. Thanks to gentrification it tends to lean left politically, but like the rest of Maine most folks in the surrounding communities often don’t know or care much about their neighbor’s party affiliation. Its library, founded in 1796, is well funded and a source of civic pride.
One day a couple of years ago, the library director received a donated book from a patron. Although he personally didn’t agree with the book’s message, he felt it deserved a space in their collection dealing with the subject. What happened in the wake of this donation is an ugly tale. Some community members objected to the book and asked that it be removed from the shelves, or at least kept under the desk and loaned out only on request.
The objectors, many of whom knew the director, were confrontational. The collections committee unanimously supported his decision. Some committee members also received similar responses from community members. Remember, this is a small town.
A request for support sent to the American Library Association was basically ignored. Over the next 2 years things have quieted, but fractured friendships and relationships in this quiet coastal Maine town have not been repaired. However, as the librarian has observed, “intellectual freedom or the freedom of speech isn’t there just to protect the ideas that we like.”
While the title of the book may feel inflammatory to some, every publisher hopes to grab the market’s attention with a hot title. The cause of this sad situation in Blue Hill was not a white supremacist’s polemic offering specific ways to create genocide. This was a book suggesting that gender dysphoria presenting in adolescence may have multiple causes and raises concerns about the wisdom of the pace of some gender-affirming care.
Clearly the topic of gender dysphoria in adolescence has become a third rail that must be approached with caution or completely avoided. A recent opinion piece in the New York Times provides even more concerning examples of this peril. Again, the eye-catching title of the article — As Kids, They Thought They Were Trans. They No Longer Do — draws in the audience eager to read about some unfortunate individuals who have regretted their decision to transition and are now detransitioning.
If you are interested in hearing anecdotal evidence and opinions supporting the notion that there is such a thing as rapid-onset gender dysphoria, I suggest you read the entire piece. However, the article’s most troubling message for me comes when I read about the professionals who were former gender-related care providers who left the field because of “pushback, the accusations of being transphobic, from being pro-assessment and wanting a more thorough process.”
One therapist trained in gender-affirming care who began to have doubts about the model and spoke out in favor of a more measured approach was investigated by her licensing board after transgender advocates threatened to report her. Ultimately, her case was dismissed, but she continues to fear for her safety.
Gender-related healthcare is another sad example of how in this country it is the noise coming from the advocates on the extremes of the issue that is drowning out the “vast ideological middle” that is seeking civil and rational discussions.
In this situation there are those who want to make it illegal for the healthcare providers to help patients who might benefit from transitioning. On the other end of the spectrum are those advocates who are unwilling to acknowledge that there may be some adolescents with what has been called by some “rapid-onset gender dysphoria.”
The landscape on which this tragedy is being played out is changing so quickly that there will be no correct answers in the short term. There just isn’t enough data. However, there is enough anecdotal evidence from professionals who were and still are practicing gender-related care to raise a concern that something is happening in the adolescent population that suggests some individuals with gender dysphoria should be managed in a different way than the currently accepted gender-affirming model. The size of this subgroup is up for debate and we may never learn it because of reporting bias and privacy concerns.
The American Academy of Pediatrics has recently authorized a systematic review of gender-affirming care. I hope that, like the librarian in Blue Hill, it will have the courage to include all the evidence available even though, as we have seen here in Maine, some of it may spark a firestorm of vehement responses.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.
Patients With Stable Lupus May Be Safely Weaned Off MMF
Patients with quiescent systemic lupus erythematosus (SLE) who are on maintenance therapy with mycophenolate mofetil (MMF) may be able to be safely weaned off the drug with the understanding that disease flare may occur and may require restarting immunosuppressive therapy.
That’s the conclusion of investigators in a multicenter randomized trial conducted at 19 US centers and published in The Lancet Rheumatology. They found that among 100 patients with stable SLE who were on MMF for at least 2 years for renal indications or at least 1 year for nonrenal indications, MMF withdrawal was not significantly inferior to MMF maintenance in terms of clinically significant disease reactivation within at least 1 year.
“Our findings suggest that mycophenolate mofetil could be safely withdrawn in patients with stable SLE. However, larger studies with a longer follow-up are still needed,” wrote Eliza F. Chakravarty, MD, MS, from the University of Oklahoma College of Medicine in Oklahoma City, and colleagues.
“Our study was only for 60 weeks, so we don’t have long-term data on what happens when patients taper off, but my recommendation — and I think the data support this — is that even if you do have a history of lupus nephritis, if you had stable disease or very little to no activity for a year or 2, then I think it’s worth stopping the medication and following for any signs of disease flare,” Dr. Chakravarty said in an interview with this news organization.
She added that “in clinical practice, we would follow patients regularly no matter what they’re on, even if they’re in remission, looking for clinical signs or laboratory evidence of flare, and then if they look like they might be having flare, treat them accordingly.”
Toxicities a Concern
Although MMF is effective for inducing prolonged disease quiescence, it is a known teratogen and has significant toxicities, and it’s desirable to wean patients off the drug if it can be done safely, Dr. Chakravarty said.
The optimal duration of maintenance therapy with MMF is not known, however, which prompted the researchers to conduct the open-label study.
Patients aged 18-70 years who met the American College of Rheumatology (ACR) 1997 SLE criteria and had a clinical SLE Disease Activity Index (SLEDAI) score ≤ 4 at screening and who also had been on stable or tapering MMF therapy for 2 or more years for renal indications or 1 or more year for nonrenal indications were eligible. All patients were on a background regimen of hydroxychloroquine.
Patients were randomly assigned on an equal basis to either withdrawal with a 12-week taper or to continued maintenance at their baseline dose, ranging from 1 to 3 g/day for 60 weeks.
The investigators used an adaptive random-allocation strategy to ensure that the groups were balanced for study site, renal vs nonrenal disease, and baseline MMF dose (≥ 2 g/day vs < 2 g/day).
A total of 100 patients with an average age of 42 years were included in a modified intention-to-treat analysis: 49 were randomly assigned to maintenance and 51 to withdrawal.
Overall, 84% of patients were women, 40% were White, and 41% were Black. Most patients, 76%, had a history of lupus nephritis.
Significant disease reactivation, the primary endpoints, was defined as the need to increase prednisone to ≥ 15 mg/day for 4 weeks, the need for two or more short steroid bursts, or the need to resume MMF or start patients on another immunosuppressive therapy.
By week 60, 18% of patients in the withdrawal group had clinically significant disease reactivation compared with 10% of patients in the maintenance group.
“Although the differences were not significant, this study used an estimation-based design to determine estimated increases in clinically significant disease reactivation risk with 75%, 85%, and 95% confidence limits to assist clinicians and patients in making informed treatment decisions. We found a 6%-8% increase with upper 85% confidence limits of 11%-19% in clinically significant disease reactivation and flare risk following mycophenolate mofetil withdrawal,” the investigators wrote.
Rates of adverse events were similar between the groups, occurring in 90% of patients in the maintenance arm and 88% of those in the withdrawal arm. Infections occurred more frequently among patients in the maintenance group, at 64% vs 46%.
Encouraging Data
In an accompanying editorial, Noémie Jourde-Chiche, MD, PhD, from Aix-Marseille University in Marseille, France, and Laurent Chiche, MD, from Hopital Europeen de Marseille, wrote that the study data “were clearly encouraging.” They noted that the results show that it’s feasible to wean select patients off immunosuppressive therapy and keep SLE in check and that the quantified risk assessment strategy will allow shared decision-making for each patient.
“Overall, the prospect of a time-limited (versus lifelong) treatment may favor compliance, as observed in other disease fields, which might consolidate remission and reduce the risk of subsequent relapse, using sequentially treat-to-target and think-to-untreat strategies for a win-wean era in SLE,” they wrote.
“We’ve been awaiting the results of this trial for quite a while, and so it is nice to see it out,” commented Karen H. Costenbader, MD, MPH, professor of medicine at Harvard Medical School, and chair of the division of rheumatology and director of the Lupus Program at Brigham and Women’s Hospital in Boston, Massachusetts.
“It does provide some data to address a question that comes up in discussions with patients all the time: A person with lupus has been doing really well, in what we call low disease activity state or remission, but on mycophenolate, possibly for several years,” she said in a reply to a request for objective commentary.
“The question is how and when to taper and can MMF be safely discontinued,” she said. “Personally, I always review the severity of the underlying disease and indication for the MMF in the first place. Really active SLE with rapidly progressing kidney or other organ damage has to be treated with tremendous respect and no one wants to go back there. I also think about how long it has been, which other medications are still being taken (hydroxychloroquine, belimumab [Benlysta], etc.) and whether the labs and symptoms have really returned to completely normal. Then I have discussions about all this with my patient and we often try a long, slow, gingerly taper with a lot of interim monitoring.”
The study was funded by the National Institute of Allergy and Infectious Diseases and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Chakravarty and Dr. Costenbader report no relevant financial relationships. Dr. Jourde-Chiche declares personal consulting fees from Otsuka and AstraZeneca, personal speaking fees from GlaxoSmithKline and Otsuka, and personal payment for expert testimony from Otsuka. Dr. Chiche declares research grants paid to his institution from AstraZeneca and GlaxoSmithKline, personal consulting fees from Novartis and AstraZeneca, and personal speaking fees from GlaxoSmithKline and Novartis.
A version of this article appeared on Medscape.com .
Patients with quiescent systemic lupus erythematosus (SLE) who are on maintenance therapy with mycophenolate mofetil (MMF) may be able to be safely weaned off the drug with the understanding that disease flare may occur and may require restarting immunosuppressive therapy.
That’s the conclusion of investigators in a multicenter randomized trial conducted at 19 US centers and published in The Lancet Rheumatology. They found that among 100 patients with stable SLE who were on MMF for at least 2 years for renal indications or at least 1 year for nonrenal indications, MMF withdrawal was not significantly inferior to MMF maintenance in terms of clinically significant disease reactivation within at least 1 year.
“Our findings suggest that mycophenolate mofetil could be safely withdrawn in patients with stable SLE. However, larger studies with a longer follow-up are still needed,” wrote Eliza F. Chakravarty, MD, MS, from the University of Oklahoma College of Medicine in Oklahoma City, and colleagues.
“Our study was only for 60 weeks, so we don’t have long-term data on what happens when patients taper off, but my recommendation — and I think the data support this — is that even if you do have a history of lupus nephritis, if you had stable disease or very little to no activity for a year or 2, then I think it’s worth stopping the medication and following for any signs of disease flare,” Dr. Chakravarty said in an interview with this news organization.
She added that “in clinical practice, we would follow patients regularly no matter what they’re on, even if they’re in remission, looking for clinical signs or laboratory evidence of flare, and then if they look like they might be having flare, treat them accordingly.”
Toxicities a Concern
Although MMF is effective for inducing prolonged disease quiescence, it is a known teratogen and has significant toxicities, and it’s desirable to wean patients off the drug if it can be done safely, Dr. Chakravarty said.
The optimal duration of maintenance therapy with MMF is not known, however, which prompted the researchers to conduct the open-label study.
Patients aged 18-70 years who met the American College of Rheumatology (ACR) 1997 SLE criteria and had a clinical SLE Disease Activity Index (SLEDAI) score ≤ 4 at screening and who also had been on stable or tapering MMF therapy for 2 or more years for renal indications or 1 or more year for nonrenal indications were eligible. All patients were on a background regimen of hydroxychloroquine.
Patients were randomly assigned on an equal basis to either withdrawal with a 12-week taper or to continued maintenance at their baseline dose, ranging from 1 to 3 g/day for 60 weeks.
The investigators used an adaptive random-allocation strategy to ensure that the groups were balanced for study site, renal vs nonrenal disease, and baseline MMF dose (≥ 2 g/day vs < 2 g/day).
A total of 100 patients with an average age of 42 years were included in a modified intention-to-treat analysis: 49 were randomly assigned to maintenance and 51 to withdrawal.
Overall, 84% of patients were women, 40% were White, and 41% were Black. Most patients, 76%, had a history of lupus nephritis.
Significant disease reactivation, the primary endpoints, was defined as the need to increase prednisone to ≥ 15 mg/day for 4 weeks, the need for two or more short steroid bursts, or the need to resume MMF or start patients on another immunosuppressive therapy.
By week 60, 18% of patients in the withdrawal group had clinically significant disease reactivation compared with 10% of patients in the maintenance group.
“Although the differences were not significant, this study used an estimation-based design to determine estimated increases in clinically significant disease reactivation risk with 75%, 85%, and 95% confidence limits to assist clinicians and patients in making informed treatment decisions. We found a 6%-8% increase with upper 85% confidence limits of 11%-19% in clinically significant disease reactivation and flare risk following mycophenolate mofetil withdrawal,” the investigators wrote.
Rates of adverse events were similar between the groups, occurring in 90% of patients in the maintenance arm and 88% of those in the withdrawal arm. Infections occurred more frequently among patients in the maintenance group, at 64% vs 46%.
Encouraging Data
In an accompanying editorial, Noémie Jourde-Chiche, MD, PhD, from Aix-Marseille University in Marseille, France, and Laurent Chiche, MD, from Hopital Europeen de Marseille, wrote that the study data “were clearly encouraging.” They noted that the results show that it’s feasible to wean select patients off immunosuppressive therapy and keep SLE in check and that the quantified risk assessment strategy will allow shared decision-making for each patient.
“Overall, the prospect of a time-limited (versus lifelong) treatment may favor compliance, as observed in other disease fields, which might consolidate remission and reduce the risk of subsequent relapse, using sequentially treat-to-target and think-to-untreat strategies for a win-wean era in SLE,” they wrote.
“We’ve been awaiting the results of this trial for quite a while, and so it is nice to see it out,” commented Karen H. Costenbader, MD, MPH, professor of medicine at Harvard Medical School, and chair of the division of rheumatology and director of the Lupus Program at Brigham and Women’s Hospital in Boston, Massachusetts.
“It does provide some data to address a question that comes up in discussions with patients all the time: A person with lupus has been doing really well, in what we call low disease activity state or remission, but on mycophenolate, possibly for several years,” she said in a reply to a request for objective commentary.
“The question is how and when to taper and can MMF be safely discontinued,” she said. “Personally, I always review the severity of the underlying disease and indication for the MMF in the first place. Really active SLE with rapidly progressing kidney or other organ damage has to be treated with tremendous respect and no one wants to go back there. I also think about how long it has been, which other medications are still being taken (hydroxychloroquine, belimumab [Benlysta], etc.) and whether the labs and symptoms have really returned to completely normal. Then I have discussions about all this with my patient and we often try a long, slow, gingerly taper with a lot of interim monitoring.”
The study was funded by the National Institute of Allergy and Infectious Diseases and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Chakravarty and Dr. Costenbader report no relevant financial relationships. Dr. Jourde-Chiche declares personal consulting fees from Otsuka and AstraZeneca, personal speaking fees from GlaxoSmithKline and Otsuka, and personal payment for expert testimony from Otsuka. Dr. Chiche declares research grants paid to his institution from AstraZeneca and GlaxoSmithKline, personal consulting fees from Novartis and AstraZeneca, and personal speaking fees from GlaxoSmithKline and Novartis.
A version of this article appeared on Medscape.com .
Patients with quiescent systemic lupus erythematosus (SLE) who are on maintenance therapy with mycophenolate mofetil (MMF) may be able to be safely weaned off the drug with the understanding that disease flare may occur and may require restarting immunosuppressive therapy.
That’s the conclusion of investigators in a multicenter randomized trial conducted at 19 US centers and published in The Lancet Rheumatology. They found that among 100 patients with stable SLE who were on MMF for at least 2 years for renal indications or at least 1 year for nonrenal indications, MMF withdrawal was not significantly inferior to MMF maintenance in terms of clinically significant disease reactivation within at least 1 year.
“Our findings suggest that mycophenolate mofetil could be safely withdrawn in patients with stable SLE. However, larger studies with a longer follow-up are still needed,” wrote Eliza F. Chakravarty, MD, MS, from the University of Oklahoma College of Medicine in Oklahoma City, and colleagues.
“Our study was only for 60 weeks, so we don’t have long-term data on what happens when patients taper off, but my recommendation — and I think the data support this — is that even if you do have a history of lupus nephritis, if you had stable disease or very little to no activity for a year or 2, then I think it’s worth stopping the medication and following for any signs of disease flare,” Dr. Chakravarty said in an interview with this news organization.
She added that “in clinical practice, we would follow patients regularly no matter what they’re on, even if they’re in remission, looking for clinical signs or laboratory evidence of flare, and then if they look like they might be having flare, treat them accordingly.”
Toxicities a Concern
Although MMF is effective for inducing prolonged disease quiescence, it is a known teratogen and has significant toxicities, and it’s desirable to wean patients off the drug if it can be done safely, Dr. Chakravarty said.
The optimal duration of maintenance therapy with MMF is not known, however, which prompted the researchers to conduct the open-label study.
Patients aged 18-70 years who met the American College of Rheumatology (ACR) 1997 SLE criteria and had a clinical SLE Disease Activity Index (SLEDAI) score ≤ 4 at screening and who also had been on stable or tapering MMF therapy for 2 or more years for renal indications or 1 or more year for nonrenal indications were eligible. All patients were on a background regimen of hydroxychloroquine.
Patients were randomly assigned on an equal basis to either withdrawal with a 12-week taper or to continued maintenance at their baseline dose, ranging from 1 to 3 g/day for 60 weeks.
The investigators used an adaptive random-allocation strategy to ensure that the groups were balanced for study site, renal vs nonrenal disease, and baseline MMF dose (≥ 2 g/day vs < 2 g/day).
A total of 100 patients with an average age of 42 years were included in a modified intention-to-treat analysis: 49 were randomly assigned to maintenance and 51 to withdrawal.
Overall, 84% of patients were women, 40% were White, and 41% were Black. Most patients, 76%, had a history of lupus nephritis.
Significant disease reactivation, the primary endpoints, was defined as the need to increase prednisone to ≥ 15 mg/day for 4 weeks, the need for two or more short steroid bursts, or the need to resume MMF or start patients on another immunosuppressive therapy.
By week 60, 18% of patients in the withdrawal group had clinically significant disease reactivation compared with 10% of patients in the maintenance group.
“Although the differences were not significant, this study used an estimation-based design to determine estimated increases in clinically significant disease reactivation risk with 75%, 85%, and 95% confidence limits to assist clinicians and patients in making informed treatment decisions. We found a 6%-8% increase with upper 85% confidence limits of 11%-19% in clinically significant disease reactivation and flare risk following mycophenolate mofetil withdrawal,” the investigators wrote.
Rates of adverse events were similar between the groups, occurring in 90% of patients in the maintenance arm and 88% of those in the withdrawal arm. Infections occurred more frequently among patients in the maintenance group, at 64% vs 46%.
Encouraging Data
In an accompanying editorial, Noémie Jourde-Chiche, MD, PhD, from Aix-Marseille University in Marseille, France, and Laurent Chiche, MD, from Hopital Europeen de Marseille, wrote that the study data “were clearly encouraging.” They noted that the results show that it’s feasible to wean select patients off immunosuppressive therapy and keep SLE in check and that the quantified risk assessment strategy will allow shared decision-making for each patient.
“Overall, the prospect of a time-limited (versus lifelong) treatment may favor compliance, as observed in other disease fields, which might consolidate remission and reduce the risk of subsequent relapse, using sequentially treat-to-target and think-to-untreat strategies for a win-wean era in SLE,” they wrote.
“We’ve been awaiting the results of this trial for quite a while, and so it is nice to see it out,” commented Karen H. Costenbader, MD, MPH, professor of medicine at Harvard Medical School, and chair of the division of rheumatology and director of the Lupus Program at Brigham and Women’s Hospital in Boston, Massachusetts.
“It does provide some data to address a question that comes up in discussions with patients all the time: A person with lupus has been doing really well, in what we call low disease activity state or remission, but on mycophenolate, possibly for several years,” she said in a reply to a request for objective commentary.
“The question is how and when to taper and can MMF be safely discontinued,” she said. “Personally, I always review the severity of the underlying disease and indication for the MMF in the first place. Really active SLE with rapidly progressing kidney or other organ damage has to be treated with tremendous respect and no one wants to go back there. I also think about how long it has been, which other medications are still being taken (hydroxychloroquine, belimumab [Benlysta], etc.) and whether the labs and symptoms have really returned to completely normal. Then I have discussions about all this with my patient and we often try a long, slow, gingerly taper with a lot of interim monitoring.”
The study was funded by the National Institute of Allergy and Infectious Diseases and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Chakravarty and Dr. Costenbader report no relevant financial relationships. Dr. Jourde-Chiche declares personal consulting fees from Otsuka and AstraZeneca, personal speaking fees from GlaxoSmithKline and Otsuka, and personal payment for expert testimony from Otsuka. Dr. Chiche declares research grants paid to his institution from AstraZeneca and GlaxoSmithKline, personal consulting fees from Novartis and AstraZeneca, and personal speaking fees from GlaxoSmithKline and Novartis.
A version of this article appeared on Medscape.com .
FROM THE LANCET RHEUMATOLOGY