Twice a month, a 40-foot-long truck transformed into a mobile clinic travels the Rio Grande Valley to provide rural Texans with women’s health care, including birth control.

The clinic, called the UniMóvil, is part of the Healthy Mujeres program at the University of Texas Rio Grande Valley School of Medicine in Edinburg.

The United States has about 3000 mobile health programs. But Saul Rivas, an ob.gyn., said he wasn’t aware of any that shared the specific mission of Healthy Mujeres when he helped launch the initiative in 2017. “Mujeres” means “women” in Spanish.

It’s now part of a small but growing number of mobile programs aimed at increasing rural access to women’s health services, including long-acting reversible contraception.

There are two kinds of these highly effective methods: intrauterine devices, known as IUDs, and hormonal implants inserted into the upper arm. These birth control options can be especially difficult to obtain — or have removed — in rural areas.

“Women who want to prevent an unintended pregnancy should have whatever works best for them,” said Kelly Conroy, senior director of mobile and maternal health programs at the University of Arkansas for Medical Sciences, Little Rock.

The school is launching a mobile women’s health and contraception program in rural parts of the state in October.

Rural areas have disproportionately fewer doctors, including ob.gyns., than urban areas. And rural providers may not be able to afford to stock long-acting birth control devices or may not be trained in administering them, program leaders say.

Mobile clinics help shrink that gap in rural care, but they can be challenging to operate, said Elizabeth Jones, a senior director at the National Family Planning & Reproductive Health Association.

Money is the greatest obstacle, Jones said. The Texas program costs up to $400,000 a year. A 2020 study of 173 mobile clinics found they cost an average of more than $630,000 a year. Mobile dental programs were the most expensive, averaging more than $1 million.

While many programs launch with the help of grants, they can be difficult to sustain, especially with over a decade of decreased or stagnant funding to Title X, a federal money stream that helps low-income people receive family planning services.

For example, a mobile contraception program serving rural Pennsylvania lasted less than 3 years before closing in 2023. It shut down after losing federal funding, said a spokesperson for the clinic that ran it.

Rural mobile programs aren’t as efficient or profitable as brick-and-mortar clinics. That’s because staff members may have to make hours-long trips to reach towns where they’ll probably see fewer patients than they would at a traditional site, Jones said.

She said organizations that can’t afford mobile programs can consider setting up “pop-up clinics” at existing health and community sites in rural areas.

Maria Briones is a patient who has benefited from the Healthy Mujeres program in southern Texas. The 41-year-old day care worker was concerned because she wasn’t getting her menstrual period with her IUD.

She considered going to Mexico to have the device removed because few doctors take her insurance on the US side of the Rio Grande Valley.

But Briones learned that the UniMóvil was visiting a small Texas city about 20 minutes from her home. She told the staff there that she doesn’t want more kids but was worried about the IUD.

Briones decided to keep the device after learning it’s safe and normal not to have periods while using an IUD. She won’t get billed for her appointment with the mobile clinic, even though the university health system doesn’t take her insurance.

“They have a lot of patience, and they answered all the questions that I had,” Briones said.

IUDs and hormonal implants are highly effective and can last up to 10 years. But they’re also expensive — devices can cost more than $1,000 without insurance — and inserting an IUD can be painful.

Patient-rights advocates are also concerned that some providers pressure people to use these devices.

They say ethical birth control programs aim to empower patients to choose the contraceptive method — if any — that is best for them, instead of promoting long-acting methods in an attempt to lower birth and poverty rates. They point to the history of eugenics-inspired sterilization and even more recent incidents.

For example, an investigation by Time magazine found doctors are more likely to push Black, Latina, young, and low-income women than other patients to use long-acting birth control — and to refuse to remove the devices.

Rivas said Healthy Mujeres staffers are trained on this issue.

“Our goal isn’t necessarily to place IUDs and implants,” he said. It’s to “provide education and help patients make the best decisions for themselves.”

David Wise, a spokesperson for the University of Arkansas for Medical Sciences, said staff members with the university’s mobile program will ask patients if they want to get pregnant in the next year, and will support their choice. The Arkansas and Texas programs also remove IUDs and hormonal arm implants if patients aren’t happy with them.

The Arkansas initiative will visit 14 rural counties with four vehicles the size of food trucks that were used in previous mobile health efforts. Staffing and equipment will be covered by a 2-year, $431,000 grant from an anonymous donor, Wise said.

In addition to contraception, faculty and medical residents staffing the vehicles will offer women’s health screenings, vaccinations, prenatal care, and testing and treatment for sexually transmitted infections.

Rivas said the Texas program was inspired by a study that found that, 6 months after giving birth, 34% of surveyed Texas mothers said long-acting contraception is their preferred birth control option — but only 13% were using that method.

“We started thinking about ways to address that gap,” Rivas said.

Healthy Mujeres, which is funded through multiple grants, started with a focus on contraception. It later expanded to services such as pregnancy ultrasounds, cervical cancer screenings, and testing for sexually transmitted infections.

While the Texas and Arkansas programs can bill insurance, they also have funding to help uninsured and underinsured patients afford their services. Both use community health workers — called promotoras in largely Spanish-speaking communities like the Rio Grande Valley — to connect patients with food, transportation, additional medical services, and other needs.

They partner with organizations that locals trust, such as food pantries and community colleges, which let the mobile units set up in their parking lots. And to further increase the availability of long-acting contraception in rural areas, the universities are training their students and local providers on how to insert, remove, and get reimbursed for the devices.

One difference between the programs is dictated by state laws. The Arkansas program can provide birth control to minors without a parent or guardian’s consent. But in Texas, most minors need consent before receiving health care, including contraception.

Advocates say these initiatives might help lower the rates of unintended and teen pregnancies in both states, which are higher than the national average.

Rivas and Conroy said their programs haven’t received much pushback. But Rivas said some churches that had asked the UniMóvil to visit their congregations changed their minds after learning the services included birth control.

Catherine Phillips, director of the Respect Life Office at Arkansas’ Catholic diocese, said the diocese supports efforts to achieve health care equity and she’s personally interested in mobile programs that visit rural areas such as where she lives.

But Phillips said the Arkansas program’s focus on birth control, especially long-acting methods, violates the teachings of the Catholic Church. Offering these services to minors without parental consent “makes it more egregious,” she said.

Jones said that, while these programs have hefty costs and other challenges, they also have benefits that can’t be measured in numbers.

“Building community trust and making an impact in the communities most impacted by health inequities — that’s invaluable,” she said.

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

Twice a month, a 40-foot-long truck transformed into a mobile clinic travels the Rio Grande Valley to provide rural Texans with women’s health care, including birth control.

The clinic, called the UniMóvil, is part of the Healthy Mujeres program at the University of Texas Rio Grande Valley School of Medicine in Edinburg.

The United States has about 3000 mobile health programs. But Saul Rivas, an ob.gyn., said he wasn’t aware of any that shared the specific mission of Healthy Mujeres when he helped launch the initiative in 2017. “Mujeres” means “women” in Spanish.

It’s now part of a small but growing number of mobile programs aimed at increasing rural access to women’s health services, including long-acting reversible contraception.

There are two kinds of these highly effective methods: intrauterine devices, known as IUDs, and hormonal implants inserted into the upper arm. These birth control options can be especially difficult to obtain — or have removed — in rural areas.

“Women who want to prevent an unintended pregnancy should have whatever works best for them,” said Kelly Conroy, senior director of mobile and maternal health programs at the University of Arkansas for Medical Sciences, Little Rock.

The school is launching a mobile women’s health and contraception program in rural parts of the state in October.

Rural areas have disproportionately fewer doctors, including ob.gyns., than urban areas. And rural providers may not be able to afford to stock long-acting birth control devices or may not be trained in administering them, program leaders say.

Mobile clinics help shrink that gap in rural care, but they can be challenging to operate, said Elizabeth Jones, a senior director at the National Family Planning & Reproductive Health Association.

Money is the greatest obstacle, Jones said. The Texas program costs up to $400,000 a year. A 2020 study of 173 mobile clinics found they cost an average of more than $630,000 a year. Mobile dental programs were the most expensive, averaging more than $1 million.

While many programs launch with the help of grants, they can be difficult to sustain, especially with over a decade of decreased or stagnant funding to Title X, a federal money stream that helps low-income people receive family planning services.

For example, a mobile contraception program serving rural Pennsylvania lasted less than 3 years before closing in 2023. It shut down after losing federal funding, said a spokesperson for the clinic that ran it.

Rural mobile programs aren’t as efficient or profitable as brick-and-mortar clinics. That’s because staff members may have to make hours-long trips to reach towns where they’ll probably see fewer patients than they would at a traditional site, Jones said.

She said organizations that can’t afford mobile programs can consider setting up “pop-up clinics” at existing health and community sites in rural areas.

Maria Briones is a patient who has benefited from the Healthy Mujeres program in southern Texas. The 41-year-old day care worker was concerned because she wasn’t getting her menstrual period with her IUD.

She considered going to Mexico to have the device removed because few doctors take her insurance on the US side of the Rio Grande Valley.

But Briones learned that the UniMóvil was visiting a small Texas city about 20 minutes from her home. She told the staff there that she doesn’t want more kids but was worried about the IUD.

Briones decided to keep the device after learning it’s safe and normal not to have periods while using an IUD. She won’t get billed for her appointment with the mobile clinic, even though the university health system doesn’t take her insurance.

“They have a lot of patience, and they answered all the questions that I had,” Briones said.

IUDs and hormonal implants are highly effective and can last up to 10 years. But they’re also expensive — devices can cost more than $1,000 without insurance — and inserting an IUD can be painful.

Patient-rights advocates are also concerned that some providers pressure people to use these devices.

They say ethical birth control programs aim to empower patients to choose the contraceptive method — if any — that is best for them, instead of promoting long-acting methods in an attempt to lower birth and poverty rates. They point to the history of eugenics-inspired sterilization and even more recent incidents.

For example, an investigation by Time magazine found doctors are more likely to push Black, Latina, young, and low-income women than other patients to use long-acting birth control — and to refuse to remove the devices.

Rivas said Healthy Mujeres staffers are trained on this issue.

“Our goal isn’t necessarily to place IUDs and implants,” he said. It’s to “provide education and help patients make the best decisions for themselves.”

David Wise, a spokesperson for the University of Arkansas for Medical Sciences, said staff members with the university’s mobile program will ask patients if they want to get pregnant in the next year, and will support their choice. The Arkansas and Texas programs also remove IUDs and hormonal arm implants if patients aren’t happy with them.

The Arkansas initiative will visit 14 rural counties with four vehicles the size of food trucks that were used in previous mobile health efforts. Staffing and equipment will be covered by a 2-year, $431,000 grant from an anonymous donor, Wise said.

In addition to contraception, faculty and medical residents staffing the vehicles will offer women’s health screenings, vaccinations, prenatal care, and testing and treatment for sexually transmitted infections.

Rivas said the Texas program was inspired by a study that found that, 6 months after giving birth, 34% of surveyed Texas mothers said long-acting contraception is their preferred birth control option — but only 13% were using that method.

“We started thinking about ways to address that gap,” Rivas said.

Healthy Mujeres, which is funded through multiple grants, started with a focus on contraception. It later expanded to services such as pregnancy ultrasounds, cervical cancer screenings, and testing for sexually transmitted infections.

While the Texas and Arkansas programs can bill insurance, they also have funding to help uninsured and underinsured patients afford their services. Both use community health workers — called promotoras in largely Spanish-speaking communities like the Rio Grande Valley — to connect patients with food, transportation, additional medical services, and other needs.

They partner with organizations that locals trust, such as food pantries and community colleges, which let the mobile units set up in their parking lots. And to further increase the availability of long-acting contraception in rural areas, the universities are training their students and local providers on how to insert, remove, and get reimbursed for the devices.

One difference between the programs is dictated by state laws. The Arkansas program can provide birth control to minors without a parent or guardian’s consent. But in Texas, most minors need consent before receiving health care, including contraception.

Advocates say these initiatives might help lower the rates of unintended and teen pregnancies in both states, which are higher than the national average.

Rivas and Conroy said their programs haven’t received much pushback. But Rivas said some churches that had asked the UniMóvil to visit their congregations changed their minds after learning the services included birth control.

Catherine Phillips, director of the Respect Life Office at Arkansas’ Catholic diocese, said the diocese supports efforts to achieve health care equity and she’s personally interested in mobile programs that visit rural areas such as where she lives.

But Phillips said the Arkansas program’s focus on birth control, especially long-acting methods, violates the teachings of the Catholic Church. Offering these services to minors without parental consent “makes it more egregious,” she said.

Jones said that, while these programs have hefty costs and other challenges, they also have benefits that can’t be measured in numbers.

“Building community trust and making an impact in the communities most impacted by health inequities — that’s invaluable,” she said.

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

Twice a month, a 40-foot-long truck transformed into a mobile clinic travels the Rio Grande Valley to provide rural Texans with women’s health care, including birth control.

The clinic, called the UniMóvil, is part of the Healthy Mujeres program at the University of Texas Rio Grande Valley School of Medicine in Edinburg.

The United States has about 3000 mobile health programs. But Saul Rivas, an ob.gyn., said he wasn’t aware of any that shared the specific mission of Healthy Mujeres when he helped launch the initiative in 2017. “Mujeres” means “women” in Spanish.

It’s now part of a small but growing number of mobile programs aimed at increasing rural access to women’s health services, including long-acting reversible contraception.

There are two kinds of these highly effective methods: intrauterine devices, known as IUDs, and hormonal implants inserted into the upper arm. These birth control options can be especially difficult to obtain — or have removed — in rural areas.

“Women who want to prevent an unintended pregnancy should have whatever works best for them,” said Kelly Conroy, senior director of mobile and maternal health programs at the University of Arkansas for Medical Sciences, Little Rock.

The school is launching a mobile women’s health and contraception program in rural parts of the state in October.

Rural areas have disproportionately fewer doctors, including ob.gyns., than urban areas. And rural providers may not be able to afford to stock long-acting birth control devices or may not be trained in administering them, program leaders say.

Mobile clinics help shrink that gap in rural care, but they can be challenging to operate, said Elizabeth Jones, a senior director at the National Family Planning & Reproductive Health Association.

Money is the greatest obstacle, Jones said. The Texas program costs up to $400,000 a year. A 2020 study of 173 mobile clinics found they cost an average of more than $630,000 a year. Mobile dental programs were the most expensive, averaging more than $1 million.

While many programs launch with the help of grants, they can be difficult to sustain, especially with over a decade of decreased or stagnant funding to Title X, a federal money stream that helps low-income people receive family planning services.

For example, a mobile contraception program serving rural Pennsylvania lasted less than 3 years before closing in 2023. It shut down after losing federal funding, said a spokesperson for the clinic that ran it.

Rural mobile programs aren’t as efficient or profitable as brick-and-mortar clinics. That’s because staff members may have to make hours-long trips to reach towns where they’ll probably see fewer patients than they would at a traditional site, Jones said.

She said organizations that can’t afford mobile programs can consider setting up “pop-up clinics” at existing health and community sites in rural areas.

Maria Briones is a patient who has benefited from the Healthy Mujeres program in southern Texas. The 41-year-old day care worker was concerned because she wasn’t getting her menstrual period with her IUD.

She considered going to Mexico to have the device removed because few doctors take her insurance on the US side of the Rio Grande Valley.

But Briones learned that the UniMóvil was visiting a small Texas city about 20 minutes from her home. She told the staff there that she doesn’t want more kids but was worried about the IUD.

Briones decided to keep the device after learning it’s safe and normal not to have periods while using an IUD. She won’t get billed for her appointment with the mobile clinic, even though the university health system doesn’t take her insurance.

“They have a lot of patience, and they answered all the questions that I had,” Briones said.

IUDs and hormonal implants are highly effective and can last up to 10 years. But they’re also expensive — devices can cost more than $1,000 without insurance — and inserting an IUD can be painful.

Patient-rights advocates are also concerned that some providers pressure people to use these devices.

They say ethical birth control programs aim to empower patients to choose the contraceptive method — if any — that is best for them, instead of promoting long-acting methods in an attempt to lower birth and poverty rates. They point to the history of eugenics-inspired sterilization and even more recent incidents.

For example, an investigation by Time magazine found doctors are more likely to push Black, Latina, young, and low-income women than other patients to use long-acting birth control — and to refuse to remove the devices.

Rivas said Healthy Mujeres staffers are trained on this issue.

“Our goal isn’t necessarily to place IUDs and implants,” he said. It’s to “provide education and help patients make the best decisions for themselves.”

David Wise, a spokesperson for the University of Arkansas for Medical Sciences, said staff members with the university’s mobile program will ask patients if they want to get pregnant in the next year, and will support their choice. The Arkansas and Texas programs also remove IUDs and hormonal arm implants if patients aren’t happy with them.

The Arkansas initiative will visit 14 rural counties with four vehicles the size of food trucks that were used in previous mobile health efforts. Staffing and equipment will be covered by a 2-year, $431,000 grant from an anonymous donor, Wise said.

In addition to contraception, faculty and medical residents staffing the vehicles will offer women’s health screenings, vaccinations, prenatal care, and testing and treatment for sexually transmitted infections.

Rivas said the Texas program was inspired by a study that found that, 6 months after giving birth, 34% of surveyed Texas mothers said long-acting contraception is their preferred birth control option — but only 13% were using that method.

“We started thinking about ways to address that gap,” Rivas said.

Healthy Mujeres, which is funded through multiple grants, started with a focus on contraception. It later expanded to services such as pregnancy ultrasounds, cervical cancer screenings, and testing for sexually transmitted infections.

While the Texas and Arkansas programs can bill insurance, they also have funding to help uninsured and underinsured patients afford their services. Both use community health workers — called promotoras in largely Spanish-speaking communities like the Rio Grande Valley — to connect patients with food, transportation, additional medical services, and other needs.

They partner with organizations that locals trust, such as food pantries and community colleges, which let the mobile units set up in their parking lots. And to further increase the availability of long-acting contraception in rural areas, the universities are training their students and local providers on how to insert, remove, and get reimbursed for the devices.

One difference between the programs is dictated by state laws. The Arkansas program can provide birth control to minors without a parent or guardian’s consent. But in Texas, most minors need consent before receiving health care, including contraception.

Advocates say these initiatives might help lower the rates of unintended and teen pregnancies in both states, which are higher than the national average.

Rivas and Conroy said their programs haven’t received much pushback. But Rivas said some churches that had asked the UniMóvil to visit their congregations changed their minds after learning the services included birth control.

Catherine Phillips, director of the Respect Life Office at Arkansas’ Catholic diocese, said the diocese supports efforts to achieve health care equity and she’s personally interested in mobile programs that visit rural areas such as where she lives.

But Phillips said the Arkansas program’s focus on birth control, especially long-acting methods, violates the teachings of the Catholic Church. Offering these services to minors without parental consent “makes it more egregious,” she said.

Jones said that, while these programs have hefty costs and other challenges, they also have benefits that can’t be measured in numbers.

“Building community trust and making an impact in the communities most impacted by health inequities — that’s invaluable,” she said.

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

TOPLINE:

BARCELONA, SPAIN — Patients who receive a diagnosis of neovascular age-related macular degeneration (nAMD) from their primary care clinician may be less likely to adhere to treatment than those who receive the diagnosis from a specialist who provides anti–vascular endothelial growth factor (anti-VEGF) therapy, according to global survey results presented at the European Society of Retina Specialists (EURETINA) 2024. Likewise, patients who self-pay for the medication or who have bilateral nAMD may be less adherent to therapy, researchers found.

METHODOLOGY:

• Researchers analyzed data from 4558 patients with nAMD who participated in the Barometer Global Survey, which involved 77 clinics in 24 countries, including Canada, Mexico, Brazil, Germany, and France.
• The survey included multiple-choice questions on personal characteristics, disease awareness, experiences with treatment, and logistical challenges with getting to appointments.
• An exploratory statistical analysis identified 19 variables that influenced patient adherence to anti-VEGF therapy.
• The researchers classified 670 patients who missed two or more appointments during a 12-month period as nonadherent.

TAKEAWAY:

• Patients with nAMD diagnosed by their family doctor or general practitioner had a threefold higher risk for nonadherence than those diagnosed by the physician treating their nAMD.
• Self-pay was associated with more than twice the odds of nonadherence compared with having insurance coverage (odds ratio [OR], 2.5).
• Compared with unilateral nAMD, bilateral nAMD was associated with higher odds of multiple missed appointments (OR, 1.7).
• Nonadherence increased with the number of anti-VEGF injections, which may show that “longer treatment durations could permit more opportunities for absenteeism,” the investigators noted.

IN PRACTICE:

“Identifying patient characteristics and challenges that may be associated with nonadherence allows clinicians to recognize patients at risk for nonadherence and provide further support before these patients begin to miss appointments,” the study authors wrote.

SOURCE:

This study was led by Laurent Kodjikian, MD, PhD, with Croix-Rousse University Hospital and the University of Lyon in France. The findings were presented in a poster at EURETINA 2024 (September 19-22).

LIMITATIONS:

The survey relied on participant responses using Likert scales and single-choice questions. Patients from the United States were not included in the study. 

DISCLOSURES:

The survey and medical writing support for the study were funded by Bayer Consumer Care. Kodjikian and co-authors disclosed consulting work for Bayer and other pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

BARCELONA, SPAIN — Patients who receive a diagnosis of neovascular age-related macular degeneration (nAMD) from their primary care clinician may be less likely to adhere to treatment than those who receive the diagnosis from a specialist who provides anti–vascular endothelial growth factor (anti-VEGF) therapy, according to global survey results presented at the European Society of Retina Specialists (EURETINA) 2024. Likewise, patients who self-pay for the medication or who have bilateral nAMD may be less adherent to therapy, researchers found.

METHODOLOGY:

• Researchers analyzed data from 4558 patients with nAMD who participated in the Barometer Global Survey, which involved 77 clinics in 24 countries, including Canada, Mexico, Brazil, Germany, and France.
• The survey included multiple-choice questions on personal characteristics, disease awareness, experiences with treatment, and logistical challenges with getting to appointments.
• An exploratory statistical analysis identified 19 variables that influenced patient adherence to anti-VEGF therapy.
• The researchers classified 670 patients who missed two or more appointments during a 12-month period as nonadherent.

TAKEAWAY:

• Patients with nAMD diagnosed by their family doctor or general practitioner had a threefold higher risk for nonadherence than those diagnosed by the physician treating their nAMD.
• Self-pay was associated with more than twice the odds of nonadherence compared with having insurance coverage (odds ratio [OR], 2.5).
• Compared with unilateral nAMD, bilateral nAMD was associated with higher odds of multiple missed appointments (OR, 1.7).
• Nonadherence increased with the number of anti-VEGF injections, which may show that “longer treatment durations could permit more opportunities for absenteeism,” the investigators noted.

IN PRACTICE:

“Identifying patient characteristics and challenges that may be associated with nonadherence allows clinicians to recognize patients at risk for nonadherence and provide further support before these patients begin to miss appointments,” the study authors wrote.

SOURCE:

This study was led by Laurent Kodjikian, MD, PhD, with Croix-Rousse University Hospital and the University of Lyon in France. The findings were presented in a poster at EURETINA 2024 (September 19-22).

LIMITATIONS:

The survey relied on participant responses using Likert scales and single-choice questions. Patients from the United States were not included in the study. 

DISCLOSURES:

The survey and medical writing support for the study were funded by Bayer Consumer Care. Kodjikian and co-authors disclosed consulting work for Bayer and other pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

BARCELONA, SPAIN — Patients who receive a diagnosis of neovascular age-related macular degeneration (nAMD) from their primary care clinician may be less likely to adhere to treatment than those who receive the diagnosis from a specialist who provides anti–vascular endothelial growth factor (anti-VEGF) therapy, according to global survey results presented at the European Society of Retina Specialists (EURETINA) 2024. Likewise, patients who self-pay for the medication or who have bilateral nAMD may be less adherent to therapy, researchers found.

METHODOLOGY:

• Researchers analyzed data from 4558 patients with nAMD who participated in the Barometer Global Survey, which involved 77 clinics in 24 countries, including Canada, Mexico, Brazil, Germany, and France.
• The survey included multiple-choice questions on personal characteristics, disease awareness, experiences with treatment, and logistical challenges with getting to appointments.
• An exploratory statistical analysis identified 19 variables that influenced patient adherence to anti-VEGF therapy.
• The researchers classified 670 patients who missed two or more appointments during a 12-month period as nonadherent.

TAKEAWAY:

• Patients with nAMD diagnosed by their family doctor or general practitioner had a threefold higher risk for nonadherence than those diagnosed by the physician treating their nAMD.
• Self-pay was associated with more than twice the odds of nonadherence compared with having insurance coverage (odds ratio [OR], 2.5).
• Compared with unilateral nAMD, bilateral nAMD was associated with higher odds of multiple missed appointments (OR, 1.7).
• Nonadherence increased with the number of anti-VEGF injections, which may show that “longer treatment durations could permit more opportunities for absenteeism,” the investigators noted.

IN PRACTICE:

“Identifying patient characteristics and challenges that may be associated with nonadherence allows clinicians to recognize patients at risk for nonadherence and provide further support before these patients begin to miss appointments,” the study authors wrote.

SOURCE:

This study was led by Laurent Kodjikian, MD, PhD, with Croix-Rousse University Hospital and the University of Lyon in France. The findings were presented in a poster at EURETINA 2024 (September 19-22).

LIMITATIONS:

The survey relied on participant responses using Likert scales and single-choice questions. Patients from the United States were not included in the study. 

DISCLOSURES:

The survey and medical writing support for the study were funded by Bayer Consumer Care. Kodjikian and co-authors disclosed consulting work for Bayer and other pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Premenstrual disorders (PMDs), including premenstrual dysphoric disorder (PMDD), adversely affect the lives of millions of women worldwide. Most girls and women — as many as 80%-90%— will experience some premenstrual discomfort such as irritability, depressed mood, food or alcohol cravings, bloating, body aches, breast pain, constipation, or fatigue.

Diagnosable menstrual disorders include, collectively, premenstrual syndrome (PMS); PMDD, formerly called late luteal phase dysphoric disorder; and premenstrual worsening of another medical condition.

The most debilitating of these is PMDD, which has an estimated prevalence of about 4%-8% in women of reproductive age, according to obstetrician/gynecologist Hoosna Haque, MD, assistant professor of medicine at Columbia University Irving Medical Center in New York City.

“It’s difficult to be sure because this condition is underreported,” said Luu D. Ireland, MD, MPH, assistant professor of obstetrics and gynecology at UMass Memorial Medical Center in Worcester, Massachusetts. “But more women are coming forward, and there’s more discussion and media coverage of this condition.”

Occurring in the same post-follicular timeframe as PMS, PMDD takes cyclical discomfort to a more intense level, with a trifecta of affective comorbidities, somatic manifestations, and behavioral changes, all of which can seriously impair daily functioning, including work, physical activities, and personal relationships. Romantic and marital relationships can be particularly impaired.

Although recent cost figures are lacking, PMDs exact a considerable economic toll with increased direct healthcare costs from doctor visits and pharmaceuticals. A 2010 study found that US women with PMS were more likely to accrue in excess of $500 in healthcare visit costs over 2 years, and the figure would likely be higher today. PMDs also increase work/school absenteeism and reduce productivity.
 

Etiology

Brain areas that regulate emotion and behavior contain receptors for estrogen, progesterone, and other sex hormones, which affect the functioning of neurotransmitter systems influencing mood and thinking. Although the precise pathophysiology remains unclear, PMDD is likely multifactorial and results in a heightened sensitivity to normal fluctuations in estrogen and progesterone during the luteal phase of the menstrual cycle and dysfunction of the serotonin and gamma-aminobutyric acid neurotransmitter systems.

Patients with PMDD have lower levels of cortisol and beta-endorphins during both the follicular and luteal phases, suggesting abnormalities in the hypothalamic-pituitary-gonadal axis (HPGA), which is consistent with dysregulation in mood disorders.
 

Risk Factors

These include family history, past traumatic events, smoking, chronic pain syndrome, and obesity. There may be a genetic component as recent studies have suggested the involvement of the gene that codes for the serotonergic 5HT1A receptor and allelic variants of ESR1 in the development of PMS/PMDD.

A particularly concerning aspect of PMDs of any sort is their possible association with a higher risk for death from non-natural causes. In a recent Swedish study, which did not distinguish between PMDs in general and PMDD in particular, patients had an almost 60% greater risk for death from non-natural causes and nearly twice the risk for death by suicide compared with women without PMDs.

Those diagnosed with a PMD at an early age showed excess mortality, and the risk for suicide was elevated regardless of age. “These findings support the need for careful follow-up for young women with PMDs and the need for suicide prevention strategies,” wrote lead author Marion Opatowski, PhD, a medical epidemiologist at Karolinska Institutet in Stockholm, Sweden. “Women with severe PMDD should definitely be monitored for suicidal thoughts or behavior and they should have an emergency outreach plan in place,” Haque added.
 

Diagnosis

Although the somatic manifestations of PMDD resemble those of PMS, they are more severe and associated psychological symptoms are greater. “In my experience, PMDD symptoms can last the whole 2 weeks of the luteal phase, whereas PMS might occur a couple of days before menstruation,” said Ireland.

Symptoms include labile mood, nervousness, hopelessness, anger and aggressiveness, as well as tension and irritability. Those affected may have suicidal thoughts or even behaviors. In addition to a lethargic loss of interest in normal activities, patients with PMDD may feel paranoid, confused, exhausted, or out of control and experience insomnia or hypersomnia. They may have trouble concentrating or remembering. Some patients with PMDD may already be prone to attention-deficit/hyperactivity disorder and non–cycle-related depression, anxiety, and panic attacks.

Diagnosis is based on the presence of any five of the typical affective, somatic, or behavioral symptoms outlined above in the week before onset of menses.

“It’s important to do a careful diagnosis for PMDD and rule out other underlying conditions such as existing depressive or anxiety disorders,” said Haque. “Symptoms tend to be more intense in periods of high hormonal fluctuation such as in the postpartum and perimenopause periods. Women with PMDD should be monitored for postpartum depression.”

PMDD is considered both a gynecologic-genitourinary disorder and an affective condition.

In 2013, it was controversially included as a depressive disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Strongly advocated by some patients, psychiatrists, and pharmaceutical companies, its inclusion was criticized by psychologists and generalists, who feared it would lead to overdiagnosis and pathologization of normal female hormonal changes. Women’s advocates protested that this inclusion would stigmatize female biology and harm their advance in society and the workplace, while some doctors continued to dismiss PMDD as not a serious concern.
 

Treatments

In its latest clinical practice guideline on PMDs, the American College of Obstetricians and Gynecologists (ACOG), for which Ireland served as the lead author, recommends that most patients with PMDD get medical treatment and outlines the following therapies, based on varying degrees of evidence strength.

Antidepressants. These may benefit patients with strong affective symptoms. Selective serotonin reuptake inhibitors such as sertraline (Zoloft), citalopram (Celexa), escitalopram (Lexapro), or fluoxetine (Prozac) are first choices.

Antidepressants may interrupt aberrant signaling in the HPGA, the circuit linking brain and ovaries and regulating the reproductive cycle. Serotonin norepinephrine reuptake inhibitor venlafaxine (Effexor) may also improve symptoms, but other types of antidepressants have not proven effective.

“The response to these well-tolerated drugs is rapid and can happen in the first 2 days,” said Ireland. The drugs may be taken either just in the luteal period or over the month, especially by patients with chronic depression or anxiety.

Hormonal therapy. ACOG recommends the use of combined oral contraceptives (COCs), gonadotropin-releasing hormone (GnRH) agonists to induce anovulation (with combined add-back hormones), progestin-only methods, and noncontraceptive continuous estrogen formulations. It notes, however, that COCs have not been more effective than placebo in reducing depressive symptom scores.

If symptoms do not improve over two to three cycles, an alternate therapy should be considered. Haque recommends an assessment after three cycles and then yearly.

Some women in her practice take both antidepressant and hormone therapy. “Unfortunately, there are no new pharmaceutical treatments on the horizon, but we have good ones already and we would love for patients to utilize them more often,” Ireland said.

Nonsteroidal anti-inflammatory drugs. Limited evidence shows these may reduce physical symptoms such as abdominal cramps, headaches, and general body aches, as well as some mood-related symptoms, which may be an indirect effect of pain alleviation.

Surgery. For women with the most severe intractable symptoms, bilateral oophorectomy with or without hysterectomy may be a last-resort option when medical management has failed. A trial period of GnRH agonist therapy (with or without adjunctive estrogen add-back treatment) is advised before surgery to predict a patient’s response to surgical management.

Acupuncture. ACOG suggests that acupuncture may help manage physical and affective premenstrual symptoms.

Diet. The usual dietary advice for premenstrual symptoms — such as consuming less caffeine, sugar, or alcohol and eating smaller, more frequent meals — is unlikely to help women with PMDD.

Exercise. Although it has not been well studied for PMDD, aerobic exercises such as walking, swimming, and biking tend to improve mood and energy levels in general. Exercise may reduce symptoms through several pathways, including effects on beta-endorphin, cortisol, and ovarian hormone levels.

Supplements. Vitamin B6, calcium and magnesium supplements, and herbal remedies are not supported by consistent or compelling evidence of efficacy. ACOG conditionally recommends calcium supplementation of 100-200 mg/d in adults to help manage physical and affective symptoms.

A small study suggested that supplemental zinc may improve both physical and psychological symptoms.

Cognitive-behavioral therapy. This treatment aims to interrupt negative and irrational thought patterns and may include awareness and education, as well as relaxation techniques, problem-solving and coping skills, and stress management. It has been associated with small to moderate improvement in anxiety and depression, said Ireland.

Peer support. Patients should consider joining a support group. The International Association for Premenstrual Disorders can help patients connect and develop coping skills.

The bottom line is that people with strong symptomatic evidence of PMDD should have medical intervention — to the benefit of their health and quality of life. Screening for PMDD should be part of women’s wellness examinations, said Ireland. “The impact of PMDD should not be minimized or dismissed,” said Haque. “And patients need to know there are very effective treatments.”

Ireland and Haque had no competing interests with regard to their comments.
 

A version of this article first appeared on Medscape.com.

Premenstrual disorders (PMDs), including premenstrual dysphoric disorder (PMDD), adversely affect the lives of millions of women worldwide. Most girls and women — as many as 80%-90%— will experience some premenstrual discomfort such as irritability, depressed mood, food or alcohol cravings, bloating, body aches, breast pain, constipation, or fatigue.

Diagnosable menstrual disorders include, collectively, premenstrual syndrome (PMS); PMDD, formerly called late luteal phase dysphoric disorder; and premenstrual worsening of another medical condition.

The most debilitating of these is PMDD, which has an estimated prevalence of about 4%-8% in women of reproductive age, according to obstetrician/gynecologist Hoosna Haque, MD, assistant professor of medicine at Columbia University Irving Medical Center in New York City.

“It’s difficult to be sure because this condition is underreported,” said Luu D. Ireland, MD, MPH, assistant professor of obstetrics and gynecology at UMass Memorial Medical Center in Worcester, Massachusetts. “But more women are coming forward, and there’s more discussion and media coverage of this condition.”

Occurring in the same post-follicular timeframe as PMS, PMDD takes cyclical discomfort to a more intense level, with a trifecta of affective comorbidities, somatic manifestations, and behavioral changes, all of which can seriously impair daily functioning, including work, physical activities, and personal relationships. Romantic and marital relationships can be particularly impaired.

Although recent cost figures are lacking, PMDs exact a considerable economic toll with increased direct healthcare costs from doctor visits and pharmaceuticals. A 2010 study found that US women with PMS were more likely to accrue in excess of $500 in healthcare visit costs over 2 years, and the figure would likely be higher today. PMDs also increase work/school absenteeism and reduce productivity.
 

Etiology

Brain areas that regulate emotion and behavior contain receptors for estrogen, progesterone, and other sex hormones, which affect the functioning of neurotransmitter systems influencing mood and thinking. Although the precise pathophysiology remains unclear, PMDD is likely multifactorial and results in a heightened sensitivity to normal fluctuations in estrogen and progesterone during the luteal phase of the menstrual cycle and dysfunction of the serotonin and gamma-aminobutyric acid neurotransmitter systems.

Patients with PMDD have lower levels of cortisol and beta-endorphins during both the follicular and luteal phases, suggesting abnormalities in the hypothalamic-pituitary-gonadal axis (HPGA), which is consistent with dysregulation in mood disorders.
 

Risk Factors

These include family history, past traumatic events, smoking, chronic pain syndrome, and obesity. There may be a genetic component as recent studies have suggested the involvement of the gene that codes for the serotonergic 5HT1A receptor and allelic variants of ESR1 in the development of PMS/PMDD.

A particularly concerning aspect of PMDs of any sort is their possible association with a higher risk for death from non-natural causes. In a recent Swedish study, which did not distinguish between PMDs in general and PMDD in particular, patients had an almost 60% greater risk for death from non-natural causes and nearly twice the risk for death by suicide compared with women without PMDs.

Those diagnosed with a PMD at an early age showed excess mortality, and the risk for suicide was elevated regardless of age. “These findings support the need for careful follow-up for young women with PMDs and the need for suicide prevention strategies,” wrote lead author Marion Opatowski, PhD, a medical epidemiologist at Karolinska Institutet in Stockholm, Sweden. “Women with severe PMDD should definitely be monitored for suicidal thoughts or behavior and they should have an emergency outreach plan in place,” Haque added.
 

Diagnosis

Although the somatic manifestations of PMDD resemble those of PMS, they are more severe and associated psychological symptoms are greater. “In my experience, PMDD symptoms can last the whole 2 weeks of the luteal phase, whereas PMS might occur a couple of days before menstruation,” said Ireland.

Symptoms include labile mood, nervousness, hopelessness, anger and aggressiveness, as well as tension and irritability. Those affected may have suicidal thoughts or even behaviors. In addition to a lethargic loss of interest in normal activities, patients with PMDD may feel paranoid, confused, exhausted, or out of control and experience insomnia or hypersomnia. They may have trouble concentrating or remembering. Some patients with PMDD may already be prone to attention-deficit/hyperactivity disorder and non–cycle-related depression, anxiety, and panic attacks.

Diagnosis is based on the presence of any five of the typical affective, somatic, or behavioral symptoms outlined above in the week before onset of menses.

“It’s important to do a careful diagnosis for PMDD and rule out other underlying conditions such as existing depressive or anxiety disorders,” said Haque. “Symptoms tend to be more intense in periods of high hormonal fluctuation such as in the postpartum and perimenopause periods. Women with PMDD should be monitored for postpartum depression.”

PMDD is considered both a gynecologic-genitourinary disorder and an affective condition.

In 2013, it was controversially included as a depressive disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Strongly advocated by some patients, psychiatrists, and pharmaceutical companies, its inclusion was criticized by psychologists and generalists, who feared it would lead to overdiagnosis and pathologization of normal female hormonal changes. Women’s advocates protested that this inclusion would stigmatize female biology and harm their advance in society and the workplace, while some doctors continued to dismiss PMDD as not a serious concern.
 

Treatments

In its latest clinical practice guideline on PMDs, the American College of Obstetricians and Gynecologists (ACOG), for which Ireland served as the lead author, recommends that most patients with PMDD get medical treatment and outlines the following therapies, based on varying degrees of evidence strength.

Antidepressants. These may benefit patients with strong affective symptoms. Selective serotonin reuptake inhibitors such as sertraline (Zoloft), citalopram (Celexa), escitalopram (Lexapro), or fluoxetine (Prozac) are first choices.

Antidepressants may interrupt aberrant signaling in the HPGA, the circuit linking brain and ovaries and regulating the reproductive cycle. Serotonin norepinephrine reuptake inhibitor venlafaxine (Effexor) may also improve symptoms, but other types of antidepressants have not proven effective.

“The response to these well-tolerated drugs is rapid and can happen in the first 2 days,” said Ireland. The drugs may be taken either just in the luteal period or over the month, especially by patients with chronic depression or anxiety.

Hormonal therapy. ACOG recommends the use of combined oral contraceptives (COCs), gonadotropin-releasing hormone (GnRH) agonists to induce anovulation (with combined add-back hormones), progestin-only methods, and noncontraceptive continuous estrogen formulations. It notes, however, that COCs have not been more effective than placebo in reducing depressive symptom scores.

If symptoms do not improve over two to three cycles, an alternate therapy should be considered. Haque recommends an assessment after three cycles and then yearly.

Some women in her practice take both antidepressant and hormone therapy. “Unfortunately, there are no new pharmaceutical treatments on the horizon, but we have good ones already and we would love for patients to utilize them more often,” Ireland said.

Nonsteroidal anti-inflammatory drugs. Limited evidence shows these may reduce physical symptoms such as abdominal cramps, headaches, and general body aches, as well as some mood-related symptoms, which may be an indirect effect of pain alleviation.

Surgery. For women with the most severe intractable symptoms, bilateral oophorectomy with or without hysterectomy may be a last-resort option when medical management has failed. A trial period of GnRH agonist therapy (with or without adjunctive estrogen add-back treatment) is advised before surgery to predict a patient’s response to surgical management.

Acupuncture. ACOG suggests that acupuncture may help manage physical and affective premenstrual symptoms.

Diet. The usual dietary advice for premenstrual symptoms — such as consuming less caffeine, sugar, or alcohol and eating smaller, more frequent meals — is unlikely to help women with PMDD.

Exercise. Although it has not been well studied for PMDD, aerobic exercises such as walking, swimming, and biking tend to improve mood and energy levels in general. Exercise may reduce symptoms through several pathways, including effects on beta-endorphin, cortisol, and ovarian hormone levels.

Supplements. Vitamin B6, calcium and magnesium supplements, and herbal remedies are not supported by consistent or compelling evidence of efficacy. ACOG conditionally recommends calcium supplementation of 100-200 mg/d in adults to help manage physical and affective symptoms.

A small study suggested that supplemental zinc may improve both physical and psychological symptoms.

Cognitive-behavioral therapy. This treatment aims to interrupt negative and irrational thought patterns and may include awareness and education, as well as relaxation techniques, problem-solving and coping skills, and stress management. It has been associated with small to moderate improvement in anxiety and depression, said Ireland.

Peer support. Patients should consider joining a support group. The International Association for Premenstrual Disorders can help patients connect and develop coping skills.

The bottom line is that people with strong symptomatic evidence of PMDD should have medical intervention — to the benefit of their health and quality of life. Screening for PMDD should be part of women’s wellness examinations, said Ireland. “The impact of PMDD should not be minimized or dismissed,” said Haque. “And patients need to know there are very effective treatments.”

Ireland and Haque had no competing interests with regard to their comments.
 

A version of this article first appeared on Medscape.com.

Premenstrual disorders (PMDs), including premenstrual dysphoric disorder (PMDD), adversely affect the lives of millions of women worldwide. Most girls and women — as many as 80%-90%— will experience some premenstrual discomfort such as irritability, depressed mood, food or alcohol cravings, bloating, body aches, breast pain, constipation, or fatigue.

Diagnosable menstrual disorders include, collectively, premenstrual syndrome (PMS); PMDD, formerly called late luteal phase dysphoric disorder; and premenstrual worsening of another medical condition.

The most debilitating of these is PMDD, which has an estimated prevalence of about 4%-8% in women of reproductive age, according to obstetrician/gynecologist Hoosna Haque, MD, assistant professor of medicine at Columbia University Irving Medical Center in New York City.

“It’s difficult to be sure because this condition is underreported,” said Luu D. Ireland, MD, MPH, assistant professor of obstetrics and gynecology at UMass Memorial Medical Center in Worcester, Massachusetts. “But more women are coming forward, and there’s more discussion and media coverage of this condition.”

Occurring in the same post-follicular timeframe as PMS, PMDD takes cyclical discomfort to a more intense level, with a trifecta of affective comorbidities, somatic manifestations, and behavioral changes, all of which can seriously impair daily functioning, including work, physical activities, and personal relationships. Romantic and marital relationships can be particularly impaired.

Although recent cost figures are lacking, PMDs exact a considerable economic toll with increased direct healthcare costs from doctor visits and pharmaceuticals. A 2010 study found that US women with PMS were more likely to accrue in excess of $500 in healthcare visit costs over 2 years, and the figure would likely be higher today. PMDs also increase work/school absenteeism and reduce productivity.
 

Etiology

Brain areas that regulate emotion and behavior contain receptors for estrogen, progesterone, and other sex hormones, which affect the functioning of neurotransmitter systems influencing mood and thinking. Although the precise pathophysiology remains unclear, PMDD is likely multifactorial and results in a heightened sensitivity to normal fluctuations in estrogen and progesterone during the luteal phase of the menstrual cycle and dysfunction of the serotonin and gamma-aminobutyric acid neurotransmitter systems.

Patients with PMDD have lower levels of cortisol and beta-endorphins during both the follicular and luteal phases, suggesting abnormalities in the hypothalamic-pituitary-gonadal axis (HPGA), which is consistent with dysregulation in mood disorders.
 

Risk Factors

These include family history, past traumatic events, smoking, chronic pain syndrome, and obesity. There may be a genetic component as recent studies have suggested the involvement of the gene that codes for the serotonergic 5HT1A receptor and allelic variants of ESR1 in the development of PMS/PMDD.

A particularly concerning aspect of PMDs of any sort is their possible association with a higher risk for death from non-natural causes. In a recent Swedish study, which did not distinguish between PMDs in general and PMDD in particular, patients had an almost 60% greater risk for death from non-natural causes and nearly twice the risk for death by suicide compared with women without PMDs.

Those diagnosed with a PMD at an early age showed excess mortality, and the risk for suicide was elevated regardless of age. “These findings support the need for careful follow-up for young women with PMDs and the need for suicide prevention strategies,” wrote lead author Marion Opatowski, PhD, a medical epidemiologist at Karolinska Institutet in Stockholm, Sweden. “Women with severe PMDD should definitely be monitored for suicidal thoughts or behavior and they should have an emergency outreach plan in place,” Haque added.
 

Diagnosis

Although the somatic manifestations of PMDD resemble those of PMS, they are more severe and associated psychological symptoms are greater. “In my experience, PMDD symptoms can last the whole 2 weeks of the luteal phase, whereas PMS might occur a couple of days before menstruation,” said Ireland.

Symptoms include labile mood, nervousness, hopelessness, anger and aggressiveness, as well as tension and irritability. Those affected may have suicidal thoughts or even behaviors. In addition to a lethargic loss of interest in normal activities, patients with PMDD may feel paranoid, confused, exhausted, or out of control and experience insomnia or hypersomnia. They may have trouble concentrating or remembering. Some patients with PMDD may already be prone to attention-deficit/hyperactivity disorder and non–cycle-related depression, anxiety, and panic attacks.

Diagnosis is based on the presence of any five of the typical affective, somatic, or behavioral symptoms outlined above in the week before onset of menses.

“It’s important to do a careful diagnosis for PMDD and rule out other underlying conditions such as existing depressive or anxiety disorders,” said Haque. “Symptoms tend to be more intense in periods of high hormonal fluctuation such as in the postpartum and perimenopause periods. Women with PMDD should be monitored for postpartum depression.”

PMDD is considered both a gynecologic-genitourinary disorder and an affective condition.

In 2013, it was controversially included as a depressive disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Strongly advocated by some patients, psychiatrists, and pharmaceutical companies, its inclusion was criticized by psychologists and generalists, who feared it would lead to overdiagnosis and pathologization of normal female hormonal changes. Women’s advocates protested that this inclusion would stigmatize female biology and harm their advance in society and the workplace, while some doctors continued to dismiss PMDD as not a serious concern.
 

Treatments

In its latest clinical practice guideline on PMDs, the American College of Obstetricians and Gynecologists (ACOG), for which Ireland served as the lead author, recommends that most patients with PMDD get medical treatment and outlines the following therapies, based on varying degrees of evidence strength.

Antidepressants. These may benefit patients with strong affective symptoms. Selective serotonin reuptake inhibitors such as sertraline (Zoloft), citalopram (Celexa), escitalopram (Lexapro), or fluoxetine (Prozac) are first choices.

Antidepressants may interrupt aberrant signaling in the HPGA, the circuit linking brain and ovaries and regulating the reproductive cycle. Serotonin norepinephrine reuptake inhibitor venlafaxine (Effexor) may also improve symptoms, but other types of antidepressants have not proven effective.

“The response to these well-tolerated drugs is rapid and can happen in the first 2 days,” said Ireland. The drugs may be taken either just in the luteal period or over the month, especially by patients with chronic depression or anxiety.

Hormonal therapy. ACOG recommends the use of combined oral contraceptives (COCs), gonadotropin-releasing hormone (GnRH) agonists to induce anovulation (with combined add-back hormones), progestin-only methods, and noncontraceptive continuous estrogen formulations. It notes, however, that COCs have not been more effective than placebo in reducing depressive symptom scores.

If symptoms do not improve over two to three cycles, an alternate therapy should be considered. Haque recommends an assessment after three cycles and then yearly.

Some women in her practice take both antidepressant and hormone therapy. “Unfortunately, there are no new pharmaceutical treatments on the horizon, but we have good ones already and we would love for patients to utilize them more often,” Ireland said.

Nonsteroidal anti-inflammatory drugs. Limited evidence shows these may reduce physical symptoms such as abdominal cramps, headaches, and general body aches, as well as some mood-related symptoms, which may be an indirect effect of pain alleviation.

Surgery. For women with the most severe intractable symptoms, bilateral oophorectomy with or without hysterectomy may be a last-resort option when medical management has failed. A trial period of GnRH agonist therapy (with or without adjunctive estrogen add-back treatment) is advised before surgery to predict a patient’s response to surgical management.

Acupuncture. ACOG suggests that acupuncture may help manage physical and affective premenstrual symptoms.

Diet. The usual dietary advice for premenstrual symptoms — such as consuming less caffeine, sugar, or alcohol and eating smaller, more frequent meals — is unlikely to help women with PMDD.

Exercise. Although it has not been well studied for PMDD, aerobic exercises such as walking, swimming, and biking tend to improve mood and energy levels in general. Exercise may reduce symptoms through several pathways, including effects on beta-endorphin, cortisol, and ovarian hormone levels.

Supplements. Vitamin B6, calcium and magnesium supplements, and herbal remedies are not supported by consistent or compelling evidence of efficacy. ACOG conditionally recommends calcium supplementation of 100-200 mg/d in adults to help manage physical and affective symptoms.

A small study suggested that supplemental zinc may improve both physical and psychological symptoms.

Cognitive-behavioral therapy. This treatment aims to interrupt negative and irrational thought patterns and may include awareness and education, as well as relaxation techniques, problem-solving and coping skills, and stress management. It has been associated with small to moderate improvement in anxiety and depression, said Ireland.

Peer support. Patients should consider joining a support group. The International Association for Premenstrual Disorders can help patients connect and develop coping skills.

The bottom line is that people with strong symptomatic evidence of PMDD should have medical intervention — to the benefit of their health and quality of life. Screening for PMDD should be part of women’s wellness examinations, said Ireland. “The impact of PMDD should not be minimized or dismissed,” said Haque. “And patients need to know there are very effective treatments.”

Ireland and Haque had no competing interests with regard to their comments.
 

A version of this article first appeared on Medscape.com.

TOPLINE:

Fetuses exposed in utero to SARS-CoV-2 are not at an increased risk for neurodevelopmental problems in early childhood.

METHODOLOGY:

• This prospective study aimed to assess whether in utero exposure to SARS-CoV-2, which causes COVID-19, is associated with abnormal neurodevelopment among children at ages 12, 18, and 24 months.
• It included 2003 pregnant individuals (mean age, 33.3 years) from the ASPIRE cohort who were enrolled before 10 weeks’ gestation and followed through 24 months post partum; 10.8% of them were exposed to SARS-CoV-2 during pregnancy, as determined via self-reported data or dried blood spot cards.
• The birth mothers were required to complete the Ages & Stages Questionnaires, Third Edition (ASQ-3), a validated screening tool for neurodevelopmental delays, at 12, 18, and 24 months postpartum.
• Neurodevelopmental outcomes were available for 1757, 1522, and 1523 children at ages 12, 18, and 24 months, respectively.
• The primary outcome was a score below the cutoff on the ASQ-3 across any of the following developmental domains: Communication, gross motor, fine motor, problem-solving, and social skills.

TAKEAWAY:

• The prevalence of abnormal ASQ-3 scores did not differ between children who were exposed to SARS-CoV-2 in utero and those who were not, at ages 12 (P = .39), 18 (P = .58), and 24 (P = .45) months.
• No association was observed between in utero exposure to SARS-CoV-2 and abnormal ASQ-3 scores among children in any of the age groups.
• The lack of an association between exposure to SARS-CoV-2 during pregnancy and abnormal neurodevelopment remained unchanged even when factors such as preterm delivery and the sex of the infant were considered.
• Supplemental analyses found no difference in risk based on the trimester of infection, presence of fever, or incidence of breakthrough infection following vaccination.

IN PRACTICE:

“In this prospective cohort study of pregnant individuals and offspring, in utero exposure to maternal SARS-CoV-2 infection was not associated with abnormal neurodevelopmental screening scores of children through age 24 months. These findings are critical considering the novelty of the SARS-CoV-2 virus to the human species, the global scale of the initial COVID-19 outbreak, the now-endemic nature of the virus indicating ongoing relevance for pregnant individuals,” the authors of the study wrote. 

“While the scientific consensus resists a link between in utero COVID-19 exposure and impaired offspring neurodevelopment, the question remains whether societal responses to the pandemic impacted developmental trajectories,” the researchers added. “Certain studies comparing infants from a pandemic cohort with historic controls have raised concerns about lower ASQ-3 scores among children living during the pandemic. Critically, socioeconomic factors influence vulnerability, not only to infection itself but also regarding the ability to deploy resources in times of stress (eg, school closures) to mitigate sources of developmental harm. Our data support this theory, with the observed independent protective association of increasing household income with childhood ASQ-3 scores. Additional research is warranted to clarify the potential impact of societal measures on early development and the differential impact of these measures on different communities.”
 

SOURCE:

The study was led by Eleni G. Jaswa, MD, MSc, of the Department of Obstetrics, Gynecology & Reproductive Sciences at the University of California, San Francisco. It was published online in JAMA Network Open.

LIMITATIONS: 

Limitations of the research included the use of self-reported data and dried blood spot cards for determining exposure to SARS-CoV-2, which may have led to misclassification. The ASQ-3 is a modestly sensitive tool for detecting developmental delays that may have affected the study’s power to detect associations. The sample size of this study, while larger than many, may still have been underpowered to detect small differences in neurodevelopmental outcomes.

DISCLOSURES:

The ASPIRE cohort was supported by research grants provided to the University of California, San Francisco, and by the Start Small Foundation, the California Breast Cancer Research Program, the COVID Catalyst Award, and other sources. Some authors reported receiving grants, royalties, and personal fees, serving on medical advisory boards, and having other ties with several institutions.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Fetuses exposed in utero to SARS-CoV-2 are not at an increased risk for neurodevelopmental problems in early childhood.

METHODOLOGY:

• This prospective study aimed to assess whether in utero exposure to SARS-CoV-2, which causes COVID-19, is associated with abnormal neurodevelopment among children at ages 12, 18, and 24 months.
• It included 2003 pregnant individuals (mean age, 33.3 years) from the ASPIRE cohort who were enrolled before 10 weeks’ gestation and followed through 24 months post partum; 10.8% of them were exposed to SARS-CoV-2 during pregnancy, as determined via self-reported data or dried blood spot cards.
• The birth mothers were required to complete the Ages & Stages Questionnaires, Third Edition (ASQ-3), a validated screening tool for neurodevelopmental delays, at 12, 18, and 24 months postpartum.
• Neurodevelopmental outcomes were available for 1757, 1522, and 1523 children at ages 12, 18, and 24 months, respectively.
• The primary outcome was a score below the cutoff on the ASQ-3 across any of the following developmental domains: Communication, gross motor, fine motor, problem-solving, and social skills.

TAKEAWAY:

• The prevalence of abnormal ASQ-3 scores did not differ between children who were exposed to SARS-CoV-2 in utero and those who were not, at ages 12 (P = .39), 18 (P = .58), and 24 (P = .45) months.
• No association was observed between in utero exposure to SARS-CoV-2 and abnormal ASQ-3 scores among children in any of the age groups.
• The lack of an association between exposure to SARS-CoV-2 during pregnancy and abnormal neurodevelopment remained unchanged even when factors such as preterm delivery and the sex of the infant were considered.
• Supplemental analyses found no difference in risk based on the trimester of infection, presence of fever, or incidence of breakthrough infection following vaccination.

IN PRACTICE:

“In this prospective cohort study of pregnant individuals and offspring, in utero exposure to maternal SARS-CoV-2 infection was not associated with abnormal neurodevelopmental screening scores of children through age 24 months. These findings are critical considering the novelty of the SARS-CoV-2 virus to the human species, the global scale of the initial COVID-19 outbreak, the now-endemic nature of the virus indicating ongoing relevance for pregnant individuals,” the authors of the study wrote. 

“While the scientific consensus resists a link between in utero COVID-19 exposure and impaired offspring neurodevelopment, the question remains whether societal responses to the pandemic impacted developmental trajectories,” the researchers added. “Certain studies comparing infants from a pandemic cohort with historic controls have raised concerns about lower ASQ-3 scores among children living during the pandemic. Critically, socioeconomic factors influence vulnerability, not only to infection itself but also regarding the ability to deploy resources in times of stress (eg, school closures) to mitigate sources of developmental harm. Our data support this theory, with the observed independent protective association of increasing household income with childhood ASQ-3 scores. Additional research is warranted to clarify the potential impact of societal measures on early development and the differential impact of these measures on different communities.”
 

SOURCE:

The study was led by Eleni G. Jaswa, MD, MSc, of the Department of Obstetrics, Gynecology & Reproductive Sciences at the University of California, San Francisco. It was published online in JAMA Network Open.

LIMITATIONS: 

Limitations of the research included the use of self-reported data and dried blood spot cards for determining exposure to SARS-CoV-2, which may have led to misclassification. The ASQ-3 is a modestly sensitive tool for detecting developmental delays that may have affected the study’s power to detect associations. The sample size of this study, while larger than many, may still have been underpowered to detect small differences in neurodevelopmental outcomes.

DISCLOSURES:

The ASPIRE cohort was supported by research grants provided to the University of California, San Francisco, and by the Start Small Foundation, the California Breast Cancer Research Program, the COVID Catalyst Award, and other sources. Some authors reported receiving grants, royalties, and personal fees, serving on medical advisory boards, and having other ties with several institutions.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Fetuses exposed in utero to SARS-CoV-2 are not at an increased risk for neurodevelopmental problems in early childhood.

METHODOLOGY:

• This prospective study aimed to assess whether in utero exposure to SARS-CoV-2, which causes COVID-19, is associated with abnormal neurodevelopment among children at ages 12, 18, and 24 months.
• It included 2003 pregnant individuals (mean age, 33.3 years) from the ASPIRE cohort who were enrolled before 10 weeks’ gestation and followed through 24 months post partum; 10.8% of them were exposed to SARS-CoV-2 during pregnancy, as determined via self-reported data or dried blood spot cards.
• The birth mothers were required to complete the Ages & Stages Questionnaires, Third Edition (ASQ-3), a validated screening tool for neurodevelopmental delays, at 12, 18, and 24 months postpartum.
• Neurodevelopmental outcomes were available for 1757, 1522, and 1523 children at ages 12, 18, and 24 months, respectively.
• The primary outcome was a score below the cutoff on the ASQ-3 across any of the following developmental domains: Communication, gross motor, fine motor, problem-solving, and social skills.

TAKEAWAY:

• The prevalence of abnormal ASQ-3 scores did not differ between children who were exposed to SARS-CoV-2 in utero and those who were not, at ages 12 (P = .39), 18 (P = .58), and 24 (P = .45) months.
• No association was observed between in utero exposure to SARS-CoV-2 and abnormal ASQ-3 scores among children in any of the age groups.
• The lack of an association between exposure to SARS-CoV-2 during pregnancy and abnormal neurodevelopment remained unchanged even when factors such as preterm delivery and the sex of the infant were considered.
• Supplemental analyses found no difference in risk based on the trimester of infection, presence of fever, or incidence of breakthrough infection following vaccination.

IN PRACTICE:

“In this prospective cohort study of pregnant individuals and offspring, in utero exposure to maternal SARS-CoV-2 infection was not associated with abnormal neurodevelopmental screening scores of children through age 24 months. These findings are critical considering the novelty of the SARS-CoV-2 virus to the human species, the global scale of the initial COVID-19 outbreak, the now-endemic nature of the virus indicating ongoing relevance for pregnant individuals,” the authors of the study wrote. 

“While the scientific consensus resists a link between in utero COVID-19 exposure and impaired offspring neurodevelopment, the question remains whether societal responses to the pandemic impacted developmental trajectories,” the researchers added. “Certain studies comparing infants from a pandemic cohort with historic controls have raised concerns about lower ASQ-3 scores among children living during the pandemic. Critically, socioeconomic factors influence vulnerability, not only to infection itself but also regarding the ability to deploy resources in times of stress (eg, school closures) to mitigate sources of developmental harm. Our data support this theory, with the observed independent protective association of increasing household income with childhood ASQ-3 scores. Additional research is warranted to clarify the potential impact of societal measures on early development and the differential impact of these measures on different communities.”
 

SOURCE:

The study was led by Eleni G. Jaswa, MD, MSc, of the Department of Obstetrics, Gynecology & Reproductive Sciences at the University of California, San Francisco. It was published online in JAMA Network Open.

LIMITATIONS: 

Limitations of the research included the use of self-reported data and dried blood spot cards for determining exposure to SARS-CoV-2, which may have led to misclassification. The ASQ-3 is a modestly sensitive tool for detecting developmental delays that may have affected the study’s power to detect associations. The sample size of this study, while larger than many, may still have been underpowered to detect small differences in neurodevelopmental outcomes.

DISCLOSURES:

The ASPIRE cohort was supported by research grants provided to the University of California, San Francisco, and by the Start Small Foundation, the California Breast Cancer Research Program, the COVID Catalyst Award, and other sources. Some authors reported receiving grants, royalties, and personal fees, serving on medical advisory boards, and having other ties with several institutions.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

SAVANNAH, GEORGIA — One patient with autoimmune myasthenia gravis (MG) has a niece with the same diagnosis, and at least one of his other close relatives may have it too. Another patient with MG lost his father and brother to complications from the disease, while a surviving brother also has it. These two cases, reported at a meeting of nerve/muscle specialists, spotlight one of the mysteries of MG: What role does heredity play in this disorder?

“Clinical familial associations — when transmission appears to be vertical, from parent to offspring — suggest that there is much yet to learn about genetic bases for autoimmunity and how certain mutations could favor selection for specific immune disorders,” said Elena Shanina, MD, PhD, a neurology professor at the University of Texas Medical Branch, Galveston, in an interview. She and colleagues presented the two case reports at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.

As Shanina noted, MG is usually sporadic without a link to heredity. However, she said, research suggests that up to 7% of patients have MG in their family history.

“There are well-described genetic causes for congenital myasthenic syndromes, in which mutations occur in genes for neuromuscular junction (NMJ) proteins affecting NMJ function. However, much less is known about genetic associations to autoimmune MG,” she said.

“More than a decade ago, differences in HLA DQ haplotype-associated presentation of AChR alpha-chain peptides were suggested to suffice in producing MG, and specific HLA DQ susceptibility links were found predisposing to MG. More recent studies have tried to identify specific genes such as CTLA4 mutations that enhance autoimmunity and neuroinflammation.”
 

Two Cases

In one of the case reports, a 75-year-old White man with hereditary coagulopathy presented with myasthenic crisis in the setting of acute pulmonary embolism. Chronic symptoms included diplopia, ptosis, and proximal muscle weakness.

A niece of the patient has been diagnosed with MG and suffers from ocular symptoms. Meanwhile, an uncle has ptosis but no diagnosis yet, and a daughter has dermatomyositis. Like MG, dermatomyositis is an autoimmune disease that causes muscle weakness.

The patient, who’s CTLA4 negative, is faring well on eculizumab after failing standard therapies, Shanina said.

In the other case, a 67-year-old Hispanic man presented with diplopia, generalized fatigue, and weakness. Like the other patient, he was seropositive for acetylcholine receptor antibodies.

This patient lost his father and brother to complications from MG. Another brother, who’s still living, also has MG.

“The patient has minimal manifestation status with disease and is currently controlled using oral immunomodulatory therapies,” Shanina said. “He is also CTLA4 negative.”
 

Genetics and Environment May Each Play a Role

Shanina called for research exploring mutations and inheritance patterns in families with MG.

“If there are genetic causes that increase autoimmunity with specific propensity for certain immune diseases, correcting those mutations could fundamentally change how we treat — and prevent — at least some autoimmune diseases,” she said. “For example, if HLA linkage is directly involved in determining susceptibility to MG, and if the presence of a specific HLA locus allele is sufficient to produce disease, HLA gene editing could be a future therapy to prevent such diseases. Likewise, monoclonal antibodies that target products of genes that increase risk for autoimmunity might be able to reduce such risks without modifying the patient’s genome.”

Henry J. Kaminski, MD, professor of neurology at George Washington University, Washington, DC, is familiar with the report’s findings. In an interview, he noted that while genetic profiles can make MG more likely, “the situation is not like Huntington’s or Alzheimer’s where there is a strong genetic risk.” 

Instead, he said, there’s “a genetic risk coupled to some environmental stimulus that leads to the development of MG, which is true for many complex autoimmune conditions.” 

While he doesn’t think the two new case reports are especially noteworthy, Kaminski said “the ability to assess genetic risk factors across patients will elucidate understanding of MG. Personalized medicine choices will likely require understanding of genetic risks.”

While understanding MG in families is “always good to know from a research perspective,” there’s no reason to launch surveillance of relatives to see if they also have the disease, he said.

Also, Kaminski cautioned that it’s important to differentiate autoimmune MG from congenital myasthenia, an even more rare genetic disorder of neuromuscular transmission. “Congenital myasthenias will not improve with immune therapy, and patients will suffer complications for no reason,” he said. “A patient who is seronegative should be assessed for congenital myasthenia with the right clinical presentation. The condition would be more likely in patients with a family history of symptoms similar to MG. It may be symptomatic at birth, but patients may present in adulthood.”

Kaminski noted that his team is collecting saliva samples from patients with MuSK-MG, a rare MG subtype linked to more severe cases, for genetic testing and genome-wide association studies.

There was no study funding, and the authors have no disclosures. Kaminski is principal investigator of a rare disease network dedicated to MG.

A version of this article first appeared on Medscape.com.

SAVANNAH, GEORGIA — One patient with autoimmune myasthenia gravis (MG) has a niece with the same diagnosis, and at least one of his other close relatives may have it too. Another patient with MG lost his father and brother to complications from the disease, while a surviving brother also has it. These two cases, reported at a meeting of nerve/muscle specialists, spotlight one of the mysteries of MG: What role does heredity play in this disorder?

“Clinical familial associations — when transmission appears to be vertical, from parent to offspring — suggest that there is much yet to learn about genetic bases for autoimmunity and how certain mutations could favor selection for specific immune disorders,” said Elena Shanina, MD, PhD, a neurology professor at the University of Texas Medical Branch, Galveston, in an interview. She and colleagues presented the two case reports at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.

As Shanina noted, MG is usually sporadic without a link to heredity. However, she said, research suggests that up to 7% of patients have MG in their family history.

“There are well-described genetic causes for congenital myasthenic syndromes, in which mutations occur in genes for neuromuscular junction (NMJ) proteins affecting NMJ function. However, much less is known about genetic associations to autoimmune MG,” she said.

“More than a decade ago, differences in HLA DQ haplotype-associated presentation of AChR alpha-chain peptides were suggested to suffice in producing MG, and specific HLA DQ susceptibility links were found predisposing to MG. More recent studies have tried to identify specific genes such as CTLA4 mutations that enhance autoimmunity and neuroinflammation.”
 

Two Cases

In one of the case reports, a 75-year-old White man with hereditary coagulopathy presented with myasthenic crisis in the setting of acute pulmonary embolism. Chronic symptoms included diplopia, ptosis, and proximal muscle weakness.

A niece of the patient has been diagnosed with MG and suffers from ocular symptoms. Meanwhile, an uncle has ptosis but no diagnosis yet, and a daughter has dermatomyositis. Like MG, dermatomyositis is an autoimmune disease that causes muscle weakness.

The patient, who’s CTLA4 negative, is faring well on eculizumab after failing standard therapies, Shanina said.

In the other case, a 67-year-old Hispanic man presented with diplopia, generalized fatigue, and weakness. Like the other patient, he was seropositive for acetylcholine receptor antibodies.

This patient lost his father and brother to complications from MG. Another brother, who’s still living, also has MG.

“The patient has minimal manifestation status with disease and is currently controlled using oral immunomodulatory therapies,” Shanina said. “He is also CTLA4 negative.”
 

Genetics and Environment May Each Play a Role

Shanina called for research exploring mutations and inheritance patterns in families with MG.

“If there are genetic causes that increase autoimmunity with specific propensity for certain immune diseases, correcting those mutations could fundamentally change how we treat — and prevent — at least some autoimmune diseases,” she said. “For example, if HLA linkage is directly involved in determining susceptibility to MG, and if the presence of a specific HLA locus allele is sufficient to produce disease, HLA gene editing could be a future therapy to prevent such diseases. Likewise, monoclonal antibodies that target products of genes that increase risk for autoimmunity might be able to reduce such risks without modifying the patient’s genome.”

Henry J. Kaminski, MD, professor of neurology at George Washington University, Washington, DC, is familiar with the report’s findings. In an interview, he noted that while genetic profiles can make MG more likely, “the situation is not like Huntington’s or Alzheimer’s where there is a strong genetic risk.” 

Instead, he said, there’s “a genetic risk coupled to some environmental stimulus that leads to the development of MG, which is true for many complex autoimmune conditions.” 

While he doesn’t think the two new case reports are especially noteworthy, Kaminski said “the ability to assess genetic risk factors across patients will elucidate understanding of MG. Personalized medicine choices will likely require understanding of genetic risks.”

While understanding MG in families is “always good to know from a research perspective,” there’s no reason to launch surveillance of relatives to see if they also have the disease, he said.

Also, Kaminski cautioned that it’s important to differentiate autoimmune MG from congenital myasthenia, an even more rare genetic disorder of neuromuscular transmission. “Congenital myasthenias will not improve with immune therapy, and patients will suffer complications for no reason,” he said. “A patient who is seronegative should be assessed for congenital myasthenia with the right clinical presentation. The condition would be more likely in patients with a family history of symptoms similar to MG. It may be symptomatic at birth, but patients may present in adulthood.”

Kaminski noted that his team is collecting saliva samples from patients with MuSK-MG, a rare MG subtype linked to more severe cases, for genetic testing and genome-wide association studies.

There was no study funding, and the authors have no disclosures. Kaminski is principal investigator of a rare disease network dedicated to MG.

A version of this article first appeared on Medscape.com.

SAVANNAH, GEORGIA — One patient with autoimmune myasthenia gravis (MG) has a niece with the same diagnosis, and at least one of his other close relatives may have it too. Another patient with MG lost his father and brother to complications from the disease, while a surviving brother also has it. These two cases, reported at a meeting of nerve/muscle specialists, spotlight one of the mysteries of MG: What role does heredity play in this disorder?

“Clinical familial associations — when transmission appears to be vertical, from parent to offspring — suggest that there is much yet to learn about genetic bases for autoimmunity and how certain mutations could favor selection for specific immune disorders,” said Elena Shanina, MD, PhD, a neurology professor at the University of Texas Medical Branch, Galveston, in an interview. She and colleagues presented the two case reports at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.

As Shanina noted, MG is usually sporadic without a link to heredity. However, she said, research suggests that up to 7% of patients have MG in their family history.

“There are well-described genetic causes for congenital myasthenic syndromes, in which mutations occur in genes for neuromuscular junction (NMJ) proteins affecting NMJ function. However, much less is known about genetic associations to autoimmune MG,” she said.

“More than a decade ago, differences in HLA DQ haplotype-associated presentation of AChR alpha-chain peptides were suggested to suffice in producing MG, and specific HLA DQ susceptibility links were found predisposing to MG. More recent studies have tried to identify specific genes such as CTLA4 mutations that enhance autoimmunity and neuroinflammation.”
 

Two Cases

In one of the case reports, a 75-year-old White man with hereditary coagulopathy presented with myasthenic crisis in the setting of acute pulmonary embolism. Chronic symptoms included diplopia, ptosis, and proximal muscle weakness.

A niece of the patient has been diagnosed with MG and suffers from ocular symptoms. Meanwhile, an uncle has ptosis but no diagnosis yet, and a daughter has dermatomyositis. Like MG, dermatomyositis is an autoimmune disease that causes muscle weakness.

The patient, who’s CTLA4 negative, is faring well on eculizumab after failing standard therapies, Shanina said.

In the other case, a 67-year-old Hispanic man presented with diplopia, generalized fatigue, and weakness. Like the other patient, he was seropositive for acetylcholine receptor antibodies.

This patient lost his father and brother to complications from MG. Another brother, who’s still living, also has MG.

“The patient has minimal manifestation status with disease and is currently controlled using oral immunomodulatory therapies,” Shanina said. “He is also CTLA4 negative.”
 

Genetics and Environment May Each Play a Role

Shanina called for research exploring mutations and inheritance patterns in families with MG.

“If there are genetic causes that increase autoimmunity with specific propensity for certain immune diseases, correcting those mutations could fundamentally change how we treat — and prevent — at least some autoimmune diseases,” she said. “For example, if HLA linkage is directly involved in determining susceptibility to MG, and if the presence of a specific HLA locus allele is sufficient to produce disease, HLA gene editing could be a future therapy to prevent such diseases. Likewise, monoclonal antibodies that target products of genes that increase risk for autoimmunity might be able to reduce such risks without modifying the patient’s genome.”

Henry J. Kaminski, MD, professor of neurology at George Washington University, Washington, DC, is familiar with the report’s findings. In an interview, he noted that while genetic profiles can make MG more likely, “the situation is not like Huntington’s or Alzheimer’s where there is a strong genetic risk.” 

Instead, he said, there’s “a genetic risk coupled to some environmental stimulus that leads to the development of MG, which is true for many complex autoimmune conditions.” 

While he doesn’t think the two new case reports are especially noteworthy, Kaminski said “the ability to assess genetic risk factors across patients will elucidate understanding of MG. Personalized medicine choices will likely require understanding of genetic risks.”

While understanding MG in families is “always good to know from a research perspective,” there’s no reason to launch surveillance of relatives to see if they also have the disease, he said.

Also, Kaminski cautioned that it’s important to differentiate autoimmune MG from congenital myasthenia, an even more rare genetic disorder of neuromuscular transmission. “Congenital myasthenias will not improve with immune therapy, and patients will suffer complications for no reason,” he said. “A patient who is seronegative should be assessed for congenital myasthenia with the right clinical presentation. The condition would be more likely in patients with a family history of symptoms similar to MG. It may be symptomatic at birth, but patients may present in adulthood.”

Kaminski noted that his team is collecting saliva samples from patients with MuSK-MG, a rare MG subtype linked to more severe cases, for genetic testing and genome-wide association studies.

There was no study funding, and the authors have no disclosures. Kaminski is principal investigator of a rare disease network dedicated to MG.

A version of this article first appeared on Medscape.com.

AMSTERDAM — Prurigo nodularis (PN), an itchy, highly symptomatic disease that can cause severe impairments in quality of life, may gain a third therapy if promising data on povorcitinib presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress are further validated.

“We now have a pipeline of clinical studies in PN. Who would have even thought that a few years ago,” said Shawn Kwatra, MD, professor and chair, Department of Dermatology, University of Maryland School of Medicine, Baltimore. That is a remarkable turn of events for a difficult disease, he added.

Dr. Kwatra

Dupilumab, a monoclonal antibody that inhibits the activity of interleukin (IL)–4 and IL-13, was the first treatment approved for PN by the Food and Drug Administration 2 years ago. Approval of nemolizumab, a monoclonal antibody that targets IL-31, a cytokine strongly implicated in the itch response, followed in August 2024. Povorcitinib, which targets Janus kinase 1 (JAK1), is on track to be the third.

New data on both nemolizumab and povorcitinib were presented in late breaking news sessions at EADV.

For povorcitinib, a JAK inhibitor, Dr. Kwatra presented extended phase 2 results through 40 weeks at a late-breaker session at the EADV meeting. They follow 16-week data from a randomized study presented earlier this year.

Of the 146 patients followed in the original 16-week randomized trial, which compared 15, 45, and 75 mg of oral povorcitinib once daily against placebo, 126 entered an extension in which all patients were treated with active therapy. In this single-blind phase, those who were responders at 16 weeks received 45 mg povorcitinib, and those who were nonresponders received 75 mg povorcitinib.

At 16 weeks, all doses were superior to placebo in achieving at least a 4-point reduction on the Itch Numerical Rating Scale (NRS4) and the Investigator Global Assessment (IGA) score 0 or 1 (clear or almost clear), as well as in a composite endpoint of both. However, even though the lowest dose of povorcitinib was active, there was a “very clear dose response” demonstrated in speed of response and proportion of responders, according to Dr. Kwatra.

On the 75-mg dose, the time to improvement was a median of 19 days, while the median times to improvement were 35 days on the 45-mg dose and 58 days on the 15-mg dose.

Among povorcitinib responders, 96% had met the NRS4 response at the time they entered the extension study. During the extension study, the proportion of responders who maintained this level of itch control hovered around 90% for the duration. The proportion was 89% at week 40.

The proportion of responders at 16 weeks achieving IGA 0/1, signifying clear or almost clear, was 93%. Again, the rate hovered around 90% for the full 40 weeks. At week 40, the proportion at this outcome was also 89%. The composite outcome among responders persisted at about 80% for most of the follow-up but fell to 63% at the last follow-up.

Among nonresponders who transitioned to 75 mg povorcitinib for the extension period, the NSR4 response rates climbed within 4 weeks to approximately 60% and reached 70% at week 40. For the endpoint of IGA 0/1, rates rose incrementally among the nonresponders over time, reaching 51% at week 40. The composite endpoint was reached at 40 weeks by 41% of nonresponders switched to 75 mg during the 24-week extension.

The results at 40 weeks were highly encouraging, according to Dr. Kwatra, who reported there were no surprises in regard to safety during the extension period. He reported some transient reductions in hemoglobin and infections that resolved, but there were no cardiac events or other more serious events that have been previously associated with JAK inhibitors during the 40-week study period.

When asked if there might be an advantage for povorcitinib relative to the monoclonal antibodies in regard to speed of onset, Dr. Kwatra said that there are no comparative data. Like previous experience with dupilumab, some patients responded rapidly with povorcitinib, but others took longer to achieve benefit.

This variability in response is consistent with the growing evidence that PN is a heterogeneous disease, according to Dr. Kwatra. With multiple up-regulated cytokines implicated in the pathogenesis of PN, he suggested that more treatment options would be useful. When it comes to the multiple molecular pathways involved in the pathogenesis of PN, he said, “patients can be at a different edge of a spectrum.”

In other evidence suggesting that more options are needed, another late-breaking news study at the 2024 EADV congress underlined the fact that PN is a chronic disease. Presented by Franz J. Legat, MD, professor of dermatology at the Medical University of Graz, Graz, Austria, the data involved a withdrawal evaluation nested in a long-term extension (LTE) of the OLYMPIA pivotal trials with nemolizumab.

After 52 weeks in the LTE, 34 patients entered the OLYMPIA DURABILITY study, in which they were randomized to withdrawal or to continue on nemolizumab on an every 4-week dosing schedule.

The relapse rate over 24 weeks was 16.7% (3 of 18 patients) in the continuous nemolizumab arm and 75% (12 of 16 patients) in the withdrawal arm. The median time to relapse was 112.5 days for those in the withdrawal arm and was not reached during follow-up in the nemolizumab arm.

Praising the patients who were willing to risk PN relapse by entering this randomized trial, Dr. Legat said that the study shows a relatively high risk for relapse within months of treatment withdrawal even after good PN control over a period of 52 weeks.

“These data clearly support continuous nemolizumab beyond 52 weeks,” he said.

Dr. Kwatra reported financial relationships with AbbVie, Arcutis, Biotherapeutics, Aslan, Celldex, Galderma, Genzada, Johnson & Johnson, Novartis, Pfizer, Regeneron, Sanofi, and Incyte, which is developing povorcitinib for PN. Dr. Legat reported financial relationships with Almirall, Celgene, Eli Lilly, Menlo Therapeutics, Novartis, Pfizer, Trevi, Vifor, and Galderma, which provided funding for the nemolizumab studies.

A version of this article appeared on Medscape.com.

AMSTERDAM — Prurigo nodularis (PN), an itchy, highly symptomatic disease that can cause severe impairments in quality of life, may gain a third therapy if promising data on povorcitinib presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress are further validated.

“We now have a pipeline of clinical studies in PN. Who would have even thought that a few years ago,” said Shawn Kwatra, MD, professor and chair, Department of Dermatology, University of Maryland School of Medicine, Baltimore. That is a remarkable turn of events for a difficult disease, he added.

Dr. Kwatra

Dupilumab, a monoclonal antibody that inhibits the activity of interleukin (IL)–4 and IL-13, was the first treatment approved for PN by the Food and Drug Administration 2 years ago. Approval of nemolizumab, a monoclonal antibody that targets IL-31, a cytokine strongly implicated in the itch response, followed in August 2024. Povorcitinib, which targets Janus kinase 1 (JAK1), is on track to be the third.

New data on both nemolizumab and povorcitinib were presented in late breaking news sessions at EADV.

For povorcitinib, a JAK inhibitor, Dr. Kwatra presented extended phase 2 results through 40 weeks at a late-breaker session at the EADV meeting. They follow 16-week data from a randomized study presented earlier this year.

Of the 146 patients followed in the original 16-week randomized trial, which compared 15, 45, and 75 mg of oral povorcitinib once daily against placebo, 126 entered an extension in which all patients were treated with active therapy. In this single-blind phase, those who were responders at 16 weeks received 45 mg povorcitinib, and those who were nonresponders received 75 mg povorcitinib.

At 16 weeks, all doses were superior to placebo in achieving at least a 4-point reduction on the Itch Numerical Rating Scale (NRS4) and the Investigator Global Assessment (IGA) score 0 or 1 (clear or almost clear), as well as in a composite endpoint of both. However, even though the lowest dose of povorcitinib was active, there was a “very clear dose response” demonstrated in speed of response and proportion of responders, according to Dr. Kwatra.

On the 75-mg dose, the time to improvement was a median of 19 days, while the median times to improvement were 35 days on the 45-mg dose and 58 days on the 15-mg dose.

Among povorcitinib responders, 96% had met the NRS4 response at the time they entered the extension study. During the extension study, the proportion of responders who maintained this level of itch control hovered around 90% for the duration. The proportion was 89% at week 40.

The proportion of responders at 16 weeks achieving IGA 0/1, signifying clear or almost clear, was 93%. Again, the rate hovered around 90% for the full 40 weeks. At week 40, the proportion at this outcome was also 89%. The composite outcome among responders persisted at about 80% for most of the follow-up but fell to 63% at the last follow-up.

Among nonresponders who transitioned to 75 mg povorcitinib for the extension period, the NSR4 response rates climbed within 4 weeks to approximately 60% and reached 70% at week 40. For the endpoint of IGA 0/1, rates rose incrementally among the nonresponders over time, reaching 51% at week 40. The composite endpoint was reached at 40 weeks by 41% of nonresponders switched to 75 mg during the 24-week extension.

The results at 40 weeks were highly encouraging, according to Dr. Kwatra, who reported there were no surprises in regard to safety during the extension period. He reported some transient reductions in hemoglobin and infections that resolved, but there were no cardiac events or other more serious events that have been previously associated with JAK inhibitors during the 40-week study period.

When asked if there might be an advantage for povorcitinib relative to the monoclonal antibodies in regard to speed of onset, Dr. Kwatra said that there are no comparative data. Like previous experience with dupilumab, some patients responded rapidly with povorcitinib, but others took longer to achieve benefit.

This variability in response is consistent with the growing evidence that PN is a heterogeneous disease, according to Dr. Kwatra. With multiple up-regulated cytokines implicated in the pathogenesis of PN, he suggested that more treatment options would be useful. When it comes to the multiple molecular pathways involved in the pathogenesis of PN, he said, “patients can be at a different edge of a spectrum.”

In other evidence suggesting that more options are needed, another late-breaking news study at the 2024 EADV congress underlined the fact that PN is a chronic disease. Presented by Franz J. Legat, MD, professor of dermatology at the Medical University of Graz, Graz, Austria, the data involved a withdrawal evaluation nested in a long-term extension (LTE) of the OLYMPIA pivotal trials with nemolizumab.

After 52 weeks in the LTE, 34 patients entered the OLYMPIA DURABILITY study, in which they were randomized to withdrawal or to continue on nemolizumab on an every 4-week dosing schedule.

The relapse rate over 24 weeks was 16.7% (3 of 18 patients) in the continuous nemolizumab arm and 75% (12 of 16 patients) in the withdrawal arm. The median time to relapse was 112.5 days for those in the withdrawal arm and was not reached during follow-up in the nemolizumab arm.

Praising the patients who were willing to risk PN relapse by entering this randomized trial, Dr. Legat said that the study shows a relatively high risk for relapse within months of treatment withdrawal even after good PN control over a period of 52 weeks.

“These data clearly support continuous nemolizumab beyond 52 weeks,” he said.

Dr. Kwatra reported financial relationships with AbbVie, Arcutis, Biotherapeutics, Aslan, Celldex, Galderma, Genzada, Johnson & Johnson, Novartis, Pfizer, Regeneron, Sanofi, and Incyte, which is developing povorcitinib for PN. Dr. Legat reported financial relationships with Almirall, Celgene, Eli Lilly, Menlo Therapeutics, Novartis, Pfizer, Trevi, Vifor, and Galderma, which provided funding for the nemolizumab studies.

A version of this article appeared on Medscape.com.

AMSTERDAM — Prurigo nodularis (PN), an itchy, highly symptomatic disease that can cause severe impairments in quality of life, may gain a third therapy if promising data on povorcitinib presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress are further validated.

“We now have a pipeline of clinical studies in PN. Who would have even thought that a few years ago,” said Shawn Kwatra, MD, professor and chair, Department of Dermatology, University of Maryland School of Medicine, Baltimore. That is a remarkable turn of events for a difficult disease, he added.

Dr. Kwatra

Dupilumab, a monoclonal antibody that inhibits the activity of interleukin (IL)–4 and IL-13, was the first treatment approved for PN by the Food and Drug Administration 2 years ago. Approval of nemolizumab, a monoclonal antibody that targets IL-31, a cytokine strongly implicated in the itch response, followed in August 2024. Povorcitinib, which targets Janus kinase 1 (JAK1), is on track to be the third.

New data on both nemolizumab and povorcitinib were presented in late breaking news sessions at EADV.

For povorcitinib, a JAK inhibitor, Dr. Kwatra presented extended phase 2 results through 40 weeks at a late-breaker session at the EADV meeting. They follow 16-week data from a randomized study presented earlier this year.

Of the 146 patients followed in the original 16-week randomized trial, which compared 15, 45, and 75 mg of oral povorcitinib once daily against placebo, 126 entered an extension in which all patients were treated with active therapy. In this single-blind phase, those who were responders at 16 weeks received 45 mg povorcitinib, and those who were nonresponders received 75 mg povorcitinib.

At 16 weeks, all doses were superior to placebo in achieving at least a 4-point reduction on the Itch Numerical Rating Scale (NRS4) and the Investigator Global Assessment (IGA) score 0 or 1 (clear or almost clear), as well as in a composite endpoint of both. However, even though the lowest dose of povorcitinib was active, there was a “very clear dose response” demonstrated in speed of response and proportion of responders, according to Dr. Kwatra.

On the 75-mg dose, the time to improvement was a median of 19 days, while the median times to improvement were 35 days on the 45-mg dose and 58 days on the 15-mg dose.

Among povorcitinib responders, 96% had met the NRS4 response at the time they entered the extension study. During the extension study, the proportion of responders who maintained this level of itch control hovered around 90% for the duration. The proportion was 89% at week 40.

The proportion of responders at 16 weeks achieving IGA 0/1, signifying clear or almost clear, was 93%. Again, the rate hovered around 90% for the full 40 weeks. At week 40, the proportion at this outcome was also 89%. The composite outcome among responders persisted at about 80% for most of the follow-up but fell to 63% at the last follow-up.

Among nonresponders who transitioned to 75 mg povorcitinib for the extension period, the NSR4 response rates climbed within 4 weeks to approximately 60% and reached 70% at week 40. For the endpoint of IGA 0/1, rates rose incrementally among the nonresponders over time, reaching 51% at week 40. The composite endpoint was reached at 40 weeks by 41% of nonresponders switched to 75 mg during the 24-week extension.

The results at 40 weeks were highly encouraging, according to Dr. Kwatra, who reported there were no surprises in regard to safety during the extension period. He reported some transient reductions in hemoglobin and infections that resolved, but there were no cardiac events or other more serious events that have been previously associated with JAK inhibitors during the 40-week study period.

When asked if there might be an advantage for povorcitinib relative to the monoclonal antibodies in regard to speed of onset, Dr. Kwatra said that there are no comparative data. Like previous experience with dupilumab, some patients responded rapidly with povorcitinib, but others took longer to achieve benefit.

This variability in response is consistent with the growing evidence that PN is a heterogeneous disease, according to Dr. Kwatra. With multiple up-regulated cytokines implicated in the pathogenesis of PN, he suggested that more treatment options would be useful. When it comes to the multiple molecular pathways involved in the pathogenesis of PN, he said, “patients can be at a different edge of a spectrum.”

In other evidence suggesting that more options are needed, another late-breaking news study at the 2024 EADV congress underlined the fact that PN is a chronic disease. Presented by Franz J. Legat, MD, professor of dermatology at the Medical University of Graz, Graz, Austria, the data involved a withdrawal evaluation nested in a long-term extension (LTE) of the OLYMPIA pivotal trials with nemolizumab.

After 52 weeks in the LTE, 34 patients entered the OLYMPIA DURABILITY study, in which they were randomized to withdrawal or to continue on nemolizumab on an every 4-week dosing schedule.

The relapse rate over 24 weeks was 16.7% (3 of 18 patients) in the continuous nemolizumab arm and 75% (12 of 16 patients) in the withdrawal arm. The median time to relapse was 112.5 days for those in the withdrawal arm and was not reached during follow-up in the nemolizumab arm.

Praising the patients who were willing to risk PN relapse by entering this randomized trial, Dr. Legat said that the study shows a relatively high risk for relapse within months of treatment withdrawal even after good PN control over a period of 52 weeks.

“These data clearly support continuous nemolizumab beyond 52 weeks,” he said.

Dr. Kwatra reported financial relationships with AbbVie, Arcutis, Biotherapeutics, Aslan, Celldex, Galderma, Genzada, Johnson & Johnson, Novartis, Pfizer, Regeneron, Sanofi, and Incyte, which is developing povorcitinib for PN. Dr. Legat reported financial relationships with Almirall, Celgene, Eli Lilly, Menlo Therapeutics, Novartis, Pfizer, Trevi, Vifor, and Galderma, which provided funding for the nemolizumab studies.

A version of this article appeared on Medscape.com.

TOPLINE:

In patients with localized prostate cancer, stereotactic body radiotherapy (SBRT) was associated with better urinary continence and sexual function, but slightly worse bowel function, compared with radical prostatectomy, according to a phase 3, open-label, randomized trial evaluating quality-of-life outcomes.

METHODOLOGY:

• Compared with prostatectomy, radiotherapy may offer better urinary and sexual outcomes but a higher risk for bowel toxicity in patients with localized prostate cancer. However, a comparison has not been performed in a randomized trial using more modern treatment options, such as SBRT.
• Researchers conducted the multicenter PACE-A trial to compare and evaluate quality-of-life outcomes among 123 patients (median age, 65.5 years) with low- to intermediate-risk localized prostate cancer who were randomly assigned to undergo either SBRT (n = 63) or radical prostatectomy (n = 60).
• Of the 123 patients, 97 (79%) had a Gleason score of 3+4 and 116 (94%) had National Comprehensive Cancer Network intermediate risk. The median follow-up was 60.7 months.
• The co–primary endpoints were urinary continence, measured by the number of absorbent urinary pads required per day, and bowel function, assessed using the Expanded Prostate Cancer Index Composite Short Form (EPIC-26).
• Secondary endpoints included erectile function (measured using the International Index of Erectile Function 5 questionnaire) , clinician-reported genitourinary and gastrointestinal toxicity, and International Prostate Symptom Score. Other patient-reported outcomes included EPIC-26 domain scores for urinary irritative/obstructive symptoms, and overall urinary, bowel, and sexual issues.

TAKEAWAY:

• At 2 years, only 6.5% (three of 46) of patients who ultimately received SBRT used one or more urinary pads daily compared with 50% (16 of 32) of patients who underwent prostatectomy (P < .001). Patients in the prostatectomy group reported worse EPIC-26 urinary incontinence domain scores (median, 77.3 vs 100; P = .003).
• Patients who underwent prostatectomy also had significantly worse sexual function scores (median, 18 vs 62.5 with SBRT; P < .001). Erectile dysfunction events of grade 2 or higher were significantly more common in patients who underwent prostatectomy (63% vs 18%).
• However, at 2 years, the bowel domain scores in the prostatectomy group were significantly higher than in the SBRT group (median, 100 vs 87.5), with a mean difference of 8.9.
• Overall, clinician-reported genitourinary and gastrointestinal toxicities were low in both treatment groups.

IN PRACTICE:

“PACE-A provides level 1 evidence of better outcomes of urinary continence and sexual function with worse bowel bother for SBRT, compared with prostatectomy,” the authors wrote, adding that the trial “provides contemporary toxicity estimates to optimize treatment decisions and maximize individual quality of life.”

SOURCE:

The study, led by Nicholas van As, of The Royal Marsden Hospital and The Institute of Cancer Research in London, was published online in European Urology.

LIMITATIONS:

The small sample size and differential dropout from allocated treatment could have introduced bias. Data completeness was another limitation.

DISCLOSURES:

The study was supported by grants from the Royal Marsden NHS Foundation Trust. Several authors reported having various ties with various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

In patients with localized prostate cancer, stereotactic body radiotherapy (SBRT) was associated with better urinary continence and sexual function, but slightly worse bowel function, compared with radical prostatectomy, according to a phase 3, open-label, randomized trial evaluating quality-of-life outcomes.

METHODOLOGY:

• Compared with prostatectomy, radiotherapy may offer better urinary and sexual outcomes but a higher risk for bowel toxicity in patients with localized prostate cancer. However, a comparison has not been performed in a randomized trial using more modern treatment options, such as SBRT.
• Researchers conducted the multicenter PACE-A trial to compare and evaluate quality-of-life outcomes among 123 patients (median age, 65.5 years) with low- to intermediate-risk localized prostate cancer who were randomly assigned to undergo either SBRT (n = 63) or radical prostatectomy (n = 60).
• Of the 123 patients, 97 (79%) had a Gleason score of 3+4 and 116 (94%) had National Comprehensive Cancer Network intermediate risk. The median follow-up was 60.7 months.
• The co–primary endpoints were urinary continence, measured by the number of absorbent urinary pads required per day, and bowel function, assessed using the Expanded Prostate Cancer Index Composite Short Form (EPIC-26).
• Secondary endpoints included erectile function (measured using the International Index of Erectile Function 5 questionnaire) , clinician-reported genitourinary and gastrointestinal toxicity, and International Prostate Symptom Score. Other patient-reported outcomes included EPIC-26 domain scores for urinary irritative/obstructive symptoms, and overall urinary, bowel, and sexual issues.

TAKEAWAY:

• At 2 years, only 6.5% (three of 46) of patients who ultimately received SBRT used one or more urinary pads daily compared with 50% (16 of 32) of patients who underwent prostatectomy (P < .001). Patients in the prostatectomy group reported worse EPIC-26 urinary incontinence domain scores (median, 77.3 vs 100; P = .003).
• Patients who underwent prostatectomy also had significantly worse sexual function scores (median, 18 vs 62.5 with SBRT; P < .001). Erectile dysfunction events of grade 2 or higher were significantly more common in patients who underwent prostatectomy (63% vs 18%).
• However, at 2 years, the bowel domain scores in the prostatectomy group were significantly higher than in the SBRT group (median, 100 vs 87.5), with a mean difference of 8.9.
• Overall, clinician-reported genitourinary and gastrointestinal toxicities were low in both treatment groups.

IN PRACTICE:

“PACE-A provides level 1 evidence of better outcomes of urinary continence and sexual function with worse bowel bother for SBRT, compared with prostatectomy,” the authors wrote, adding that the trial “provides contemporary toxicity estimates to optimize treatment decisions and maximize individual quality of life.”

SOURCE:

The study, led by Nicholas van As, of The Royal Marsden Hospital and The Institute of Cancer Research in London, was published online in European Urology.

LIMITATIONS:

The small sample size and differential dropout from allocated treatment could have introduced bias. Data completeness was another limitation.

DISCLOSURES:

The study was supported by grants from the Royal Marsden NHS Foundation Trust. Several authors reported having various ties with various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

In patients with localized prostate cancer, stereotactic body radiotherapy (SBRT) was associated with better urinary continence and sexual function, but slightly worse bowel function, compared with radical prostatectomy, according to a phase 3, open-label, randomized trial evaluating quality-of-life outcomes.

METHODOLOGY:

• Compared with prostatectomy, radiotherapy may offer better urinary and sexual outcomes but a higher risk for bowel toxicity in patients with localized prostate cancer. However, a comparison has not been performed in a randomized trial using more modern treatment options, such as SBRT.
• Researchers conducted the multicenter PACE-A trial to compare and evaluate quality-of-life outcomes among 123 patients (median age, 65.5 years) with low- to intermediate-risk localized prostate cancer who were randomly assigned to undergo either SBRT (n = 63) or radical prostatectomy (n = 60).
• Of the 123 patients, 97 (79%) had a Gleason score of 3+4 and 116 (94%) had National Comprehensive Cancer Network intermediate risk. The median follow-up was 60.7 months.
• The co–primary endpoints were urinary continence, measured by the number of absorbent urinary pads required per day, and bowel function, assessed using the Expanded Prostate Cancer Index Composite Short Form (EPIC-26).
• Secondary endpoints included erectile function (measured using the International Index of Erectile Function 5 questionnaire) , clinician-reported genitourinary and gastrointestinal toxicity, and International Prostate Symptom Score. Other patient-reported outcomes included EPIC-26 domain scores for urinary irritative/obstructive symptoms, and overall urinary, bowel, and sexual issues.

TAKEAWAY:

• At 2 years, only 6.5% (three of 46) of patients who ultimately received SBRT used one or more urinary pads daily compared with 50% (16 of 32) of patients who underwent prostatectomy (P < .001). Patients in the prostatectomy group reported worse EPIC-26 urinary incontinence domain scores (median, 77.3 vs 100; P = .003).
• Patients who underwent prostatectomy also had significantly worse sexual function scores (median, 18 vs 62.5 with SBRT; P < .001). Erectile dysfunction events of grade 2 or higher were significantly more common in patients who underwent prostatectomy (63% vs 18%).
• However, at 2 years, the bowel domain scores in the prostatectomy group were significantly higher than in the SBRT group (median, 100 vs 87.5), with a mean difference of 8.9.
• Overall, clinician-reported genitourinary and gastrointestinal toxicities were low in both treatment groups.

IN PRACTICE:

“PACE-A provides level 1 evidence of better outcomes of urinary continence and sexual function with worse bowel bother for SBRT, compared with prostatectomy,” the authors wrote, adding that the trial “provides contemporary toxicity estimates to optimize treatment decisions and maximize individual quality of life.”

SOURCE:

The study, led by Nicholas van As, of The Royal Marsden Hospital and The Institute of Cancer Research in London, was published online in European Urology.

LIMITATIONS:

The small sample size and differential dropout from allocated treatment could have introduced bias. Data completeness was another limitation.

DISCLOSURES:

The study was supported by grants from the Royal Marsden NHS Foundation Trust. Several authors reported having various ties with various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

AMSTERDAM — For patients with atopic dermatitis (AD) who responded to the anti–interleukin (IL)–13 monoclonal antibody lebrikizumab in the pivotal trials, the level of response, including 90% skin clearance, has generally remained unchanged among those followed up for an additional 2 years, according to the latest data from an extension study. 

At the end of the maintenance phase of the pivotal trials at 12 months, 84% of the patients enrolled into the extension had clear or almost clear skin, as per the Investigator Global Assessment (IGA). This overall figure as well as the proportion with even better responses have persisted unchanged, reported Diamant Thaçi, MD, PhD, professor and head of the Comprehensive Center for Inflammatory Medicine, University of Lübeck in Germany. 
 

Responses at 3 Years Maintained

“This is really quite remarkable,” Dr. Thaçi said. “Roughly all the patients maintained their response.” These results became even more remarkable when patients were assessed for their use of adjunctive therapy to control flares. 

“Over the whole follow-up, 90% had no need for topical corticosteroids or any other rescue therapy,” Dr. Thaçi reported, providing data from the ADjoin lebrikizumab extension study during a late-breaking news session at the annual meeting of the European Academy of Dermatology and Venereology. 

The patients in ADjoin were enrolled from the pivotal phase 3 ADvocate 1 and 2 trials completed almost 2 years ago and published together in March 2023. Lebrikizumab was approved in the United States in September 2024 for moderate to severe AD in patients aged ≥ 12 years, following previous approvals in Europe in 2023 and in Japan in January 2024.

In these two identical trials with a total of 564 patients, the primary endpoint was an IGA of 0 or 1, signifying clear or almost clear skin. At nearly 40%, the proportion of patients reaching this outcome at 16 weeks was about threefold greater (P < .001) on lebrikizumab than on placebo. The benefit was similar on secondary endpoints, such as 75% improvement in the Eczema Area and Severity Index (EASI75) score. 

At the end of the double-blind, placebo-controlled 16-week phase of the ADvocate 1 and 2 trials, which enrolled adults and adolescents aged ≥ 12 years, responders were enrolled into a maintenance phase in which they were rerandomized to 250 mg lebrikizumab every 2 weeks (Q2W) or every 4 weeks (Q4W). The latter is the approved maintenance dose. 

At the end of the maintenance phase, which lasted another 32 weeks (total exposure of 52 weeks for those initially randomized to lebrikizumab), patients were invited into the ADjoin extension. The only exclusions from the extension were serious adverse events related to lebrikizumab and noncompliance. 
 

Response Curves Appear as Straight Lines

Over the next 2 years of ADjoin, response curves appeared as straight lines not only for the overall response but when patients were stratified for different levels of response at the extension study entry. Specifically, 81.5% and 83.3% had an IGA score of 0 or 1 in the Q2W and Q4W arms at completion of the ADvocate 16-week double-blind phase. At 3 years, the rates were 84.0% and 82.9%, respectively. 

For the subgroup who entered ADjoin with an EASI75 or an EASI90 response, the persistence of this level of response over 2 years was similar, although there was some gain observed among those who entered the trial with an EASI75 response. 

“Not only did these patients maintain their response, but the response on average slowly improved, so that there were more patients with an EASI90 response at the 3-year timepoint,” Dr. Thaçi said.

Of the 181 patients in the ADjoin extension, 82 patients were maintained on Q2W dosing and 99 were maintained on Q4W lebrikizumab. Their mean age was about 35 years, more than half were women, and nearly 40% had severe AD at the time they enrolled in the ADvocate trials. There was essentially no difference in response rates among those in the Q2W and Q4W arms over time in ADjoin. 
 

Side Effect Profile Essentially Unchanged

The side effect and tolerability profiles, which were favorable in the original 16-week placebo-controlled study, have remained unchanged over the subsequent maintenance phase and through the additional 2 years of the ADjoin extension.

“There continued to be reports of conjunctivitis, which is very specific for anti–IL-13 therapies,” Dr. Thaçi said. However, he said that the incidence did not increase over time, and because it was easy to treat, “most patients do not discontinue lebrikizumab for this reason.” Moreover, he said the impression was that “the number of patients experiencing adverse effects has been decreasing over time.” 

Calling these long-term results “very exciting,” Dr. Thaçi called lebrikizumab “a very valuable option for long-term AD care.” 

Asked for his perspective on the results, Jonathan I. Silverberg, MD, PhD, Director of Clinical Research, Department of Dermatology, George Washington University, Washington, DC, said that it is important to study long-term efficacy, and these results are positive. Without direct comparisons to other biologics available for AD, nothing can be implied about the relative efficacy of monoclonal antibodies approved for AD. 

“These data are important both from an efficacy and safety perspective” for those advising patients who need chronic AD treatment, said Dr. Silverberg, who was the principal investigator of the ADvocate trials. 

Earlier this year, 5-year follow-up data were published for dupilumab. Of 326 patients who remained on therapy this long, 220 (67%) maintained an IGA of 0 or 1 at the end of the study. There were no unexpected adverse events, which were generally stable or declined throughout the study. 

Dr. Thaçi has financial relationships with AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Galderma, Leo Pharma, L’Oreal, Janssen-Cilag, New Bridge, Novartis, Pfizer, Regeneron, Roche, Sanofi, Sun Pharma, UCB, and Vichy. Dr. Silverberg reported financial relationships with more than 40 pharmaceutical companies including those that make drugs for AD.

A version of this article appeared on Medscape.com.

AMSTERDAM — For patients with atopic dermatitis (AD) who responded to the anti–interleukin (IL)–13 monoclonal antibody lebrikizumab in the pivotal trials, the level of response, including 90% skin clearance, has generally remained unchanged among those followed up for an additional 2 years, according to the latest data from an extension study. 

At the end of the maintenance phase of the pivotal trials at 12 months, 84% of the patients enrolled into the extension had clear or almost clear skin, as per the Investigator Global Assessment (IGA). This overall figure as well as the proportion with even better responses have persisted unchanged, reported Diamant Thaçi, MD, PhD, professor and head of the Comprehensive Center for Inflammatory Medicine, University of Lübeck in Germany. 
 

Responses at 3 Years Maintained

“This is really quite remarkable,” Dr. Thaçi said. “Roughly all the patients maintained their response.” These results became even more remarkable when patients were assessed for their use of adjunctive therapy to control flares. 

“Over the whole follow-up, 90% had no need for topical corticosteroids or any other rescue therapy,” Dr. Thaçi reported, providing data from the ADjoin lebrikizumab extension study during a late-breaking news session at the annual meeting of the European Academy of Dermatology and Venereology. 

The patients in ADjoin were enrolled from the pivotal phase 3 ADvocate 1 and 2 trials completed almost 2 years ago and published together in March 2023. Lebrikizumab was approved in the United States in September 2024 for moderate to severe AD in patients aged ≥ 12 years, following previous approvals in Europe in 2023 and in Japan in January 2024.

In these two identical trials with a total of 564 patients, the primary endpoint was an IGA of 0 or 1, signifying clear or almost clear skin. At nearly 40%, the proportion of patients reaching this outcome at 16 weeks was about threefold greater (P < .001) on lebrikizumab than on placebo. The benefit was similar on secondary endpoints, such as 75% improvement in the Eczema Area and Severity Index (EASI75) score. 

At the end of the double-blind, placebo-controlled 16-week phase of the ADvocate 1 and 2 trials, which enrolled adults and adolescents aged ≥ 12 years, responders were enrolled into a maintenance phase in which they were rerandomized to 250 mg lebrikizumab every 2 weeks (Q2W) or every 4 weeks (Q4W). The latter is the approved maintenance dose. 

At the end of the maintenance phase, which lasted another 32 weeks (total exposure of 52 weeks for those initially randomized to lebrikizumab), patients were invited into the ADjoin extension. The only exclusions from the extension were serious adverse events related to lebrikizumab and noncompliance. 
 

Response Curves Appear as Straight Lines

Over the next 2 years of ADjoin, response curves appeared as straight lines not only for the overall response but when patients were stratified for different levels of response at the extension study entry. Specifically, 81.5% and 83.3% had an IGA score of 0 or 1 in the Q2W and Q4W arms at completion of the ADvocate 16-week double-blind phase. At 3 years, the rates were 84.0% and 82.9%, respectively. 

For the subgroup who entered ADjoin with an EASI75 or an EASI90 response, the persistence of this level of response over 2 years was similar, although there was some gain observed among those who entered the trial with an EASI75 response. 

“Not only did these patients maintain their response, but the response on average slowly improved, so that there were more patients with an EASI90 response at the 3-year timepoint,” Dr. Thaçi said.

Of the 181 patients in the ADjoin extension, 82 patients were maintained on Q2W dosing and 99 were maintained on Q4W lebrikizumab. Their mean age was about 35 years, more than half were women, and nearly 40% had severe AD at the time they enrolled in the ADvocate trials. There was essentially no difference in response rates among those in the Q2W and Q4W arms over time in ADjoin. 
 

Side Effect Profile Essentially Unchanged

The side effect and tolerability profiles, which were favorable in the original 16-week placebo-controlled study, have remained unchanged over the subsequent maintenance phase and through the additional 2 years of the ADjoin extension.

“There continued to be reports of conjunctivitis, which is very specific for anti–IL-13 therapies,” Dr. Thaçi said. However, he said that the incidence did not increase over time, and because it was easy to treat, “most patients do not discontinue lebrikizumab for this reason.” Moreover, he said the impression was that “the number of patients experiencing adverse effects has been decreasing over time.” 

Calling these long-term results “very exciting,” Dr. Thaçi called lebrikizumab “a very valuable option for long-term AD care.” 

Asked for his perspective on the results, Jonathan I. Silverberg, MD, PhD, Director of Clinical Research, Department of Dermatology, George Washington University, Washington, DC, said that it is important to study long-term efficacy, and these results are positive. Without direct comparisons to other biologics available for AD, nothing can be implied about the relative efficacy of monoclonal antibodies approved for AD. 

“These data are important both from an efficacy and safety perspective” for those advising patients who need chronic AD treatment, said Dr. Silverberg, who was the principal investigator of the ADvocate trials. 

Earlier this year, 5-year follow-up data were published for dupilumab. Of 326 patients who remained on therapy this long, 220 (67%) maintained an IGA of 0 or 1 at the end of the study. There were no unexpected adverse events, which were generally stable or declined throughout the study. 

Dr. Thaçi has financial relationships with AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Galderma, Leo Pharma, L’Oreal, Janssen-Cilag, New Bridge, Novartis, Pfizer, Regeneron, Roche, Sanofi, Sun Pharma, UCB, and Vichy. Dr. Silverberg reported financial relationships with more than 40 pharmaceutical companies including those that make drugs for AD.

A version of this article appeared on Medscape.com.

AMSTERDAM — For patients with atopic dermatitis (AD) who responded to the anti–interleukin (IL)–13 monoclonal antibody lebrikizumab in the pivotal trials, the level of response, including 90% skin clearance, has generally remained unchanged among those followed up for an additional 2 years, according to the latest data from an extension study. 

At the end of the maintenance phase of the pivotal trials at 12 months, 84% of the patients enrolled into the extension had clear or almost clear skin, as per the Investigator Global Assessment (IGA). This overall figure as well as the proportion with even better responses have persisted unchanged, reported Diamant Thaçi, MD, PhD, professor and head of the Comprehensive Center for Inflammatory Medicine, University of Lübeck in Germany. 
 

Responses at 3 Years Maintained

“This is really quite remarkable,” Dr. Thaçi said. “Roughly all the patients maintained their response.” These results became even more remarkable when patients were assessed for their use of adjunctive therapy to control flares. 

“Over the whole follow-up, 90% had no need for topical corticosteroids or any other rescue therapy,” Dr. Thaçi reported, providing data from the ADjoin lebrikizumab extension study during a late-breaking news session at the annual meeting of the European Academy of Dermatology and Venereology. 

The patients in ADjoin were enrolled from the pivotal phase 3 ADvocate 1 and 2 trials completed almost 2 years ago and published together in March 2023. Lebrikizumab was approved in the United States in September 2024 for moderate to severe AD in patients aged ≥ 12 years, following previous approvals in Europe in 2023 and in Japan in January 2024.

In these two identical trials with a total of 564 patients, the primary endpoint was an IGA of 0 or 1, signifying clear or almost clear skin. At nearly 40%, the proportion of patients reaching this outcome at 16 weeks was about threefold greater (P < .001) on lebrikizumab than on placebo. The benefit was similar on secondary endpoints, such as 75% improvement in the Eczema Area and Severity Index (EASI75) score. 

At the end of the double-blind, placebo-controlled 16-week phase of the ADvocate 1 and 2 trials, which enrolled adults and adolescents aged ≥ 12 years, responders were enrolled into a maintenance phase in which they were rerandomized to 250 mg lebrikizumab every 2 weeks (Q2W) or every 4 weeks (Q4W). The latter is the approved maintenance dose. 

At the end of the maintenance phase, which lasted another 32 weeks (total exposure of 52 weeks for those initially randomized to lebrikizumab), patients were invited into the ADjoin extension. The only exclusions from the extension were serious adverse events related to lebrikizumab and noncompliance. 
 

Response Curves Appear as Straight Lines

Over the next 2 years of ADjoin, response curves appeared as straight lines not only for the overall response but when patients were stratified for different levels of response at the extension study entry. Specifically, 81.5% and 83.3% had an IGA score of 0 or 1 in the Q2W and Q4W arms at completion of the ADvocate 16-week double-blind phase. At 3 years, the rates were 84.0% and 82.9%, respectively. 

For the subgroup who entered ADjoin with an EASI75 or an EASI90 response, the persistence of this level of response over 2 years was similar, although there was some gain observed among those who entered the trial with an EASI75 response. 

“Not only did these patients maintain their response, but the response on average slowly improved, so that there were more patients with an EASI90 response at the 3-year timepoint,” Dr. Thaçi said.

Of the 181 patients in the ADjoin extension, 82 patients were maintained on Q2W dosing and 99 were maintained on Q4W lebrikizumab. Their mean age was about 35 years, more than half were women, and nearly 40% had severe AD at the time they enrolled in the ADvocate trials. There was essentially no difference in response rates among those in the Q2W and Q4W arms over time in ADjoin. 
 

Side Effect Profile Essentially Unchanged

The side effect and tolerability profiles, which were favorable in the original 16-week placebo-controlled study, have remained unchanged over the subsequent maintenance phase and through the additional 2 years of the ADjoin extension.

“There continued to be reports of conjunctivitis, which is very specific for anti–IL-13 therapies,” Dr. Thaçi said. However, he said that the incidence did not increase over time, and because it was easy to treat, “most patients do not discontinue lebrikizumab for this reason.” Moreover, he said the impression was that “the number of patients experiencing adverse effects has been decreasing over time.” 

Calling these long-term results “very exciting,” Dr. Thaçi called lebrikizumab “a very valuable option for long-term AD care.” 

Asked for his perspective on the results, Jonathan I. Silverberg, MD, PhD, Director of Clinical Research, Department of Dermatology, George Washington University, Washington, DC, said that it is important to study long-term efficacy, and these results are positive. Without direct comparisons to other biologics available for AD, nothing can be implied about the relative efficacy of monoclonal antibodies approved for AD. 

“These data are important both from an efficacy and safety perspective” for those advising patients who need chronic AD treatment, said Dr. Silverberg, who was the principal investigator of the ADvocate trials. 

Earlier this year, 5-year follow-up data were published for dupilumab. Of 326 patients who remained on therapy this long, 220 (67%) maintained an IGA of 0 or 1 at the end of the study. There were no unexpected adverse events, which were generally stable or declined throughout the study. 

Dr. Thaçi has financial relationships with AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Galderma, Leo Pharma, L’Oreal, Janssen-Cilag, New Bridge, Novartis, Pfizer, Regeneron, Roche, Sanofi, Sun Pharma, UCB, and Vichy. Dr. Silverberg reported financial relationships with more than 40 pharmaceutical companies including those that make drugs for AD.

A version of this article appeared on Medscape.com.

AMSTERDAM — For frontal fibrosing alopecia (FFA), a disease with no approved therapies, topical delgocitinib attenuated inflammation and generated hair regrowth in women in a controlled phase 2a trial.

“This is an exciting avenue for FFA if the data are recapitulated in a larger population. It could be an important new treatment option,” said Maryanne Senna, MD, director at Lahey Hospital & Medical Center’s Hair Loss Center of Excellence, Burlington, Massachusetts, and assistant dermatology professor at Harvard Medical School, Boston, Massachusetts.

In a design characterized as “exploratory,” the trial had two parts: a randomized, double-blind, vehicle-controlled intervention for 12 weeks, followed by an open-label extension of topical delgocitinib for all participants for another 12 weeks. 

The primary efficacy endpoint was change in the molecular signature of FFA inflammation at 12 weeks. Clinical improvement was monitored with both trichoscopic images capturing the numbers of hairs and follicular units at 12 weeks and clinical severity scores through week 24. In a topical cream formulation, the Janus kinase inhibitor (JAKi) delgocitinib was associated with favorable activity for both. 
 

Some Hair Regrowth for All

“At 24 weeks, all patients achieved some degree of hair regrowth and a stabilization of disease based on hairline measurements,” Senna reported in a late-breaking news session at the 2024 European Academy of Dermatology and Venereology (EADV) Congress. 

On the clinical endpoints, Senna noted an upward trajectory in clinical improvement at the completion of the study.

The 30 participants were randomly assigned in a 1:1 ratio to receive delgocitinib cream in a concentration of 20 mg/g or vehicle cream applied twice daily for 12 weeks. At the end of this double-blind period, patients on vehicle were crossed over to the active therapy, and all patients were monitored for another 12 weeks in an open-label extension. 

The change from baseline in FFA biomarkers was selected as the primary endpoint based on previous work showing up-regulation in the expression of the Th1 biomarkers CXCL9, CXCL10, and interferon gamma in lesional vs nonlesional scalp in patients with FFA. 

When biopsies at the end of 12 weeks in the double-blind phase of the study were compared with the baseline biopsies, researchers found a decrease in expression of the three local inflammation markers in all patients receiving the JAKi, but not in those receiving the vehicle cream. In this small patient sample, only the reduction in expression of CXCL9, a cytokine known for differentiation and promotion of leukocytes, reached statistical significance (P < .05).

But in an analysis involving the expression of multiple genes, “lesions treated with delgocitinib had a 4% improvement in normalization toward a nonlesional transcriptomic profile, while patients treated with vehicle had a 33% worsening,” Senna reported. The difference was highly significant (P < .001).

Furthermore, the decrease in total Lichen Planopilaris Activity Index and FFA severity scores were numerically and statistically greater (P = .023) in the active-treatment arm than in the vehicle arm by the end of the double-blind part of the trial, she said.

On trichoscopy, there was an increased number of hairs and follicular units at 12 weeks relative to baseline among those treated with topical delgocitinib but a reduction in those treated with vehicle.
 

JAKi Patients Gained Hair, Vehicle Patients Lost Hair

On the basis of hair count per square centimeter from baseline, delgocitinib-treated patients gained on average of seven hairs whereas vehicle recipients lost an average of 11 hairs at 24 weeks, Senna reported.

Patients originally treated with vehicle did improve in most outcome measures in the open-label extension of the experimental treatment after crossover, but they did not catch up to those initially randomized to delgocitinib because of further accrual of favorable changes in the active-treatment group over time.

“There were no adverse events associated with active therapy or vehicle, including application-site reactions,” Senna said. The one between-group difference was a higher rate of COVID-19, but this was greater in the control arm.

All 30 of the participants in this study were women, and all had moderate to severe disease at enrollment. The median age was 64 years. Because of the predominant population at the hair loss center, all but one of the participants were White, and one participant was Asian. 

Characterizing FFA as “devastating and disfiguring,” Senna, who specializes in the care of alopecia, noted that this a difficult disease to control with the off-label strategies that are now used. The slow progress to identify treatments for FFA is illustrated by the fact that only one other double-blind and randomized trial has ever been conducted in FFA, she said.
 

Exploratory Study Supports Anecdotal Experience

On the basis of prior anecdotal experience with JAKi treatment for FFA, Senna said, “I do think that it is possible to get largely clear skin with this therapy.” However, she is now hoping for definitive trials to better characterize the efficacy and safety of oral and topical therapies, perhaps used sequentially to maintain clinical improvement.

In light of the limited current options, Menno de Rie, MD, PhD, professor of dermatology at the University of Amsterdam in the Netherlands, called these data “very inspiring and hopeful.” He suggested the promise of this therapy was reinforced by the upward trajectory of the biomarkers and clinical improvement over the study period. 

“Any improvement in treatment options would be welcome, because we do not [have] any reliable therapies for this condition,” de Rie, who was not an investigator, said in an interview after the presentation. 

Ultimately, Senna said, once effective therapy is established, the goal will be to start as early as possible in the disease process. She noted that there is evidence that prompt therapy can reverse the disorder, not just prevent progression.

“If you can get to the hair follicles before the point of no return, there is [a] chance [of] follicular rescue,” she said.

Delgocitinib cream (Anzupgo) was approved in Europe for treating chronic hand eczema in late September and is under review for the same indication in the United States. 

Senna has financial relationships with Arena, Concert, Eli Lilly, Pfizer, and Leo Pharma, which provided funding for this study. de Rie reported no potential conflicts of interest.

A version of this article appeared on Medscape.com.

AMSTERDAM — For frontal fibrosing alopecia (FFA), a disease with no approved therapies, topical delgocitinib attenuated inflammation and generated hair regrowth in women in a controlled phase 2a trial.

“This is an exciting avenue for FFA if the data are recapitulated in a larger population. It could be an important new treatment option,” said Maryanne Senna, MD, director at Lahey Hospital & Medical Center’s Hair Loss Center of Excellence, Burlington, Massachusetts, and assistant dermatology professor at Harvard Medical School, Boston, Massachusetts.

In a design characterized as “exploratory,” the trial had two parts: a randomized, double-blind, vehicle-controlled intervention for 12 weeks, followed by an open-label extension of topical delgocitinib for all participants for another 12 weeks. 

The primary efficacy endpoint was change in the molecular signature of FFA inflammation at 12 weeks. Clinical improvement was monitored with both trichoscopic images capturing the numbers of hairs and follicular units at 12 weeks and clinical severity scores through week 24. In a topical cream formulation, the Janus kinase inhibitor (JAKi) delgocitinib was associated with favorable activity for both. 
 

Some Hair Regrowth for All

“At 24 weeks, all patients achieved some degree of hair regrowth and a stabilization of disease based on hairline measurements,” Senna reported in a late-breaking news session at the 2024 European Academy of Dermatology and Venereology (EADV) Congress. 

On the clinical endpoints, Senna noted an upward trajectory in clinical improvement at the completion of the study.

The 30 participants were randomly assigned in a 1:1 ratio to receive delgocitinib cream in a concentration of 20 mg/g or vehicle cream applied twice daily for 12 weeks. At the end of this double-blind period, patients on vehicle were crossed over to the active therapy, and all patients were monitored for another 12 weeks in an open-label extension. 

The change from baseline in FFA biomarkers was selected as the primary endpoint based on previous work showing up-regulation in the expression of the Th1 biomarkers CXCL9, CXCL10, and interferon gamma in lesional vs nonlesional scalp in patients with FFA. 

When biopsies at the end of 12 weeks in the double-blind phase of the study were compared with the baseline biopsies, researchers found a decrease in expression of the three local inflammation markers in all patients receiving the JAKi, but not in those receiving the vehicle cream. In this small patient sample, only the reduction in expression of CXCL9, a cytokine known for differentiation and promotion of leukocytes, reached statistical significance (P < .05).

But in an analysis involving the expression of multiple genes, “lesions treated with delgocitinib had a 4% improvement in normalization toward a nonlesional transcriptomic profile, while patients treated with vehicle had a 33% worsening,” Senna reported. The difference was highly significant (P < .001).

Furthermore, the decrease in total Lichen Planopilaris Activity Index and FFA severity scores were numerically and statistically greater (P = .023) in the active-treatment arm than in the vehicle arm by the end of the double-blind part of the trial, she said.

On trichoscopy, there was an increased number of hairs and follicular units at 12 weeks relative to baseline among those treated with topical delgocitinib but a reduction in those treated with vehicle.
 

JAKi Patients Gained Hair, Vehicle Patients Lost Hair

On the basis of hair count per square centimeter from baseline, delgocitinib-treated patients gained on average of seven hairs whereas vehicle recipients lost an average of 11 hairs at 24 weeks, Senna reported.

Patients originally treated with vehicle did improve in most outcome measures in the open-label extension of the experimental treatment after crossover, but they did not catch up to those initially randomized to delgocitinib because of further accrual of favorable changes in the active-treatment group over time.

“There were no adverse events associated with active therapy or vehicle, including application-site reactions,” Senna said. The one between-group difference was a higher rate of COVID-19, but this was greater in the control arm.

All 30 of the participants in this study were women, and all had moderate to severe disease at enrollment. The median age was 64 years. Because of the predominant population at the hair loss center, all but one of the participants were White, and one participant was Asian. 

Characterizing FFA as “devastating and disfiguring,” Senna, who specializes in the care of alopecia, noted that this a difficult disease to control with the off-label strategies that are now used. The slow progress to identify treatments for FFA is illustrated by the fact that only one other double-blind and randomized trial has ever been conducted in FFA, she said.
 

Exploratory Study Supports Anecdotal Experience

On the basis of prior anecdotal experience with JAKi treatment for FFA, Senna said, “I do think that it is possible to get largely clear skin with this therapy.” However, she is now hoping for definitive trials to better characterize the efficacy and safety of oral and topical therapies, perhaps used sequentially to maintain clinical improvement.

In light of the limited current options, Menno de Rie, MD, PhD, professor of dermatology at the University of Amsterdam in the Netherlands, called these data “very inspiring and hopeful.” He suggested the promise of this therapy was reinforced by the upward trajectory of the biomarkers and clinical improvement over the study period. 

“Any improvement in treatment options would be welcome, because we do not [have] any reliable therapies for this condition,” de Rie, who was not an investigator, said in an interview after the presentation. 

Ultimately, Senna said, once effective therapy is established, the goal will be to start as early as possible in the disease process. She noted that there is evidence that prompt therapy can reverse the disorder, not just prevent progression.

“If you can get to the hair follicles before the point of no return, there is [a] chance [of] follicular rescue,” she said.

Delgocitinib cream (Anzupgo) was approved in Europe for treating chronic hand eczema in late September and is under review for the same indication in the United States. 

Senna has financial relationships with Arena, Concert, Eli Lilly, Pfizer, and Leo Pharma, which provided funding for this study. de Rie reported no potential conflicts of interest.

A version of this article appeared on Medscape.com.

AMSTERDAM — For frontal fibrosing alopecia (FFA), a disease with no approved therapies, topical delgocitinib attenuated inflammation and generated hair regrowth in women in a controlled phase 2a trial.

“This is an exciting avenue for FFA if the data are recapitulated in a larger population. It could be an important new treatment option,” said Maryanne Senna, MD, director at Lahey Hospital & Medical Center’s Hair Loss Center of Excellence, Burlington, Massachusetts, and assistant dermatology professor at Harvard Medical School, Boston, Massachusetts.

In a design characterized as “exploratory,” the trial had two parts: a randomized, double-blind, vehicle-controlled intervention for 12 weeks, followed by an open-label extension of topical delgocitinib for all participants for another 12 weeks. 

The primary efficacy endpoint was change in the molecular signature of FFA inflammation at 12 weeks. Clinical improvement was monitored with both trichoscopic images capturing the numbers of hairs and follicular units at 12 weeks and clinical severity scores through week 24. In a topical cream formulation, the Janus kinase inhibitor (JAKi) delgocitinib was associated with favorable activity for both. 
 

Some Hair Regrowth for All

“At 24 weeks, all patients achieved some degree of hair regrowth and a stabilization of disease based on hairline measurements,” Senna reported in a late-breaking news session at the 2024 European Academy of Dermatology and Venereology (EADV) Congress. 

On the clinical endpoints, Senna noted an upward trajectory in clinical improvement at the completion of the study.

The 30 participants were randomly assigned in a 1:1 ratio to receive delgocitinib cream in a concentration of 20 mg/g or vehicle cream applied twice daily for 12 weeks. At the end of this double-blind period, patients on vehicle were crossed over to the active therapy, and all patients were monitored for another 12 weeks in an open-label extension. 

The change from baseline in FFA biomarkers was selected as the primary endpoint based on previous work showing up-regulation in the expression of the Th1 biomarkers CXCL9, CXCL10, and interferon gamma in lesional vs nonlesional scalp in patients with FFA. 

When biopsies at the end of 12 weeks in the double-blind phase of the study were compared with the baseline biopsies, researchers found a decrease in expression of the three local inflammation markers in all patients receiving the JAKi, but not in those receiving the vehicle cream. In this small patient sample, only the reduction in expression of CXCL9, a cytokine known for differentiation and promotion of leukocytes, reached statistical significance (P < .05).

But in an analysis involving the expression of multiple genes, “lesions treated with delgocitinib had a 4% improvement in normalization toward a nonlesional transcriptomic profile, while patients treated with vehicle had a 33% worsening,” Senna reported. The difference was highly significant (P < .001).

Furthermore, the decrease in total Lichen Planopilaris Activity Index and FFA severity scores were numerically and statistically greater (P = .023) in the active-treatment arm than in the vehicle arm by the end of the double-blind part of the trial, she said.

On trichoscopy, there was an increased number of hairs and follicular units at 12 weeks relative to baseline among those treated with topical delgocitinib but a reduction in those treated with vehicle.
 

JAKi Patients Gained Hair, Vehicle Patients Lost Hair

On the basis of hair count per square centimeter from baseline, delgocitinib-treated patients gained on average of seven hairs whereas vehicle recipients lost an average of 11 hairs at 24 weeks, Senna reported.

Patients originally treated with vehicle did improve in most outcome measures in the open-label extension of the experimental treatment after crossover, but they did not catch up to those initially randomized to delgocitinib because of further accrual of favorable changes in the active-treatment group over time.

“There were no adverse events associated with active therapy or vehicle, including application-site reactions,” Senna said. The one between-group difference was a higher rate of COVID-19, but this was greater in the control arm.

All 30 of the participants in this study were women, and all had moderate to severe disease at enrollment. The median age was 64 years. Because of the predominant population at the hair loss center, all but one of the participants were White, and one participant was Asian. 

Characterizing FFA as “devastating and disfiguring,” Senna, who specializes in the care of alopecia, noted that this a difficult disease to control with the off-label strategies that are now used. The slow progress to identify treatments for FFA is illustrated by the fact that only one other double-blind and randomized trial has ever been conducted in FFA, she said.
 

Exploratory Study Supports Anecdotal Experience

On the basis of prior anecdotal experience with JAKi treatment for FFA, Senna said, “I do think that it is possible to get largely clear skin with this therapy.” However, she is now hoping for definitive trials to better characterize the efficacy and safety of oral and topical therapies, perhaps used sequentially to maintain clinical improvement.

In light of the limited current options, Menno de Rie, MD, PhD, professor of dermatology at the University of Amsterdam in the Netherlands, called these data “very inspiring and hopeful.” He suggested the promise of this therapy was reinforced by the upward trajectory of the biomarkers and clinical improvement over the study period. 

“Any improvement in treatment options would be welcome, because we do not [have] any reliable therapies for this condition,” de Rie, who was not an investigator, said in an interview after the presentation. 

Ultimately, Senna said, once effective therapy is established, the goal will be to start as early as possible in the disease process. She noted that there is evidence that prompt therapy can reverse the disorder, not just prevent progression.

“If you can get to the hair follicles before the point of no return, there is [a] chance [of] follicular rescue,” she said.

Delgocitinib cream (Anzupgo) was approved in Europe for treating chronic hand eczema in late September and is under review for the same indication in the United States. 

Senna has financial relationships with Arena, Concert, Eli Lilly, Pfizer, and Leo Pharma, which provided funding for this study. de Rie reported no potential conflicts of interest.

A version of this article appeared on Medscape.com.

It has been 24 years since a pharmaceutical was last approved for posttraumatic stress disorder (PTSD). The condition is notoriously difficult to treat, with up to 40% patients finding no relief from symptoms through psychotherapy or current medications.

Many clinicians, advocates, and patients had pinned their hopes on the psychedelic drug midomafetamine with assisted therapy (MDMA-AT). However, in August, the US Food and Drug Administration (FDA) rejected it. At this point, it’s unclear when the therapy will be available, if ever.

“Not getting the FDA approval of any drug at this point is a setback for the field,” Lori Davis, MD, a senior research psychiatrist at the Birmingham Veterans Affairs (VA) Health Care System in Birmingham, Alabama, told Medscape Medical News.

Having an FDA-approved product would have helped increase public awareness of PTSD and driven interest in developing new therapies, said Davis, who is also adjunct professor of psychiatry at the Heersink School of Medicine, University of Alabama at Birmingham.
 

A Treatable Condition

So with MDMA-AT off the table, where does the field go next? 

A public meeting in September hosted by the Reagan-Udall Foundation for the FDA in sought to answer that question. Agency officials joined representatives from the Department of Defense (DoD) and VA, patients, advocates, and industry representatives to discuss the current treatment landscape and what can be done to accelerate development of PTSD treatment.

Despite the common belief that PTSD is intractable, it “is a treatable condition,” Paula P. Schnurr, PhD, executive director of the VA National Center for PTSD, said at the meeting.

“There are effective treatments that work well for a lot of people, although not everyone has a satisfactory response,” she added.

The most effective psychotherapies are “trauma-focused,” and include cognitive processing therapy, eye movement desensitization and reprocessing, and prolonged exposure, according to the VA National Center for PTSD.

Three drugs have been approved by the FDA for PTSD: Venlafaxine (Effexor) in 1993, sertraline (Zoloft) in 1999, and paroxetine (Paxil) in 2000.

However, as the September meeting demonstrated, more therapies are needed.

“It’s clear to FDA and the federal government at large that there is an unmet need for safe and effective therapies to treat PTSD,” Bernard Fischer, MD, deputy director of the Division of Psychiatry in the Office of New Drugs at FDA’s Center for Drug Evaluation and Research, said at the meeting.

There is no shortage of research, Fischer added. Nearly 500 trials focused on PTSD are listed on clinicaltrials.gov are recruiting participants now or plan to soon.

Unsurprisingly, one of the primary drivers of PTSD therapeutics research is the VA. About 14% of the 5.7 million veterans who received care through the VA in 2023 had a diagnosis of PTSD.

“The US military is currently losing thousands of service members each year to PTSD- related disability discharges,” US Army Maj. Aaron Wolfgang, MD, a psychiatrist at the Walter Reed National Military Medical Center, said at the meeting. Only about 12%-20% of patients achieve remission with conventional therapies, added Wolfgang, who also is an assistant professor at the Uniformed Services University.

“For these reasons, establishing better treatments for PTSD is not only a matter of humanitarianism but also a pressing matter of national security,” he said.

The VA has committed at least $230 million to more than 140 active research projects in PTSD, Miriam J. Smyth, PhD, acting director of the clinical science, research and development service at the VA, said at the Reagan-Udall meeting.

One of the VA projects is the PTSD psychopharmacology initiative, which began in 2017 and now has 14 active clinical trials, said Smyth, who is also acting director for brain behavior and mental health at the VA. The first study should be finished by 2025.

The Million Veteran Program, with more than 1 million enrollees, has led to the discovery of genes related to re-experiencing traumatic memories and has confirmed that both PTSD and traumatic brain injury are risk factors for dementia, Smyth said.

The DoD has created a novel platform that establishes a common infrastructure for testing multiple drugs, called M-PACT. The platform allows sharing of placebo data across treatment arms. Drugs cycle off the platform if evidence indicates probability of success or failure.

Four trials are actively recruiting veterans and current service members. One is looking at vilazodone, approved in 2011 for major depressive disorder. It is being compared with placebo and fluoxetine in a trial that is currently recruiting.

Another trial will study daridorexant (sold as Quviviq), an orexin receptor antagonist, against placebo. The FDA approved daridorexant in 2022 as an insomnia treatment. A core issue in PTSD is sleep disruption, noted Davis.
 

New Therapies on the Way

Separately, Davis and colleagues are also studying methylphenidate, the stimulant used for attention-deficit/hyperactivity disorder. It may help with neurocognitive complaints and reduce PTSD symptoms, said Davis.

Because it is generic, few pharmaceutical manufacturers are likely to test it for PTSD, she said. But eventually, their work may lead a company to test newer stimulants for PTSD, she said.

Another potential therapeutic, BNC210, received Fast Track designation for PTSD from the FDA in 2019. Bionomics Limited in Australia will soon launch phase 3 trials of the investigational oral drug, which is a negative allosteric modulator of the alpha-7 nicotinic acetylcholine receptor. In late July, the company announced “ favorable feedback” from the agency on its phase 2 study, which led to the decision to move forward with larger trials.

Researchers at Brigham and Women’s Hospital have just reported that they may have found a target within the brain that will allow for transcranial magnetic stimulation (TMS) to ameliorate PTSD symptoms. They published results of a mapping effort in Nature Neuroscience and reported on one patient who had improved symptoms after receiving TMS for severe PTSD.

But perhaps one of the most promising treatments is a combination of sertraline and the new psychiatric medication brexpiprazole.

Brexpiprazole was developed by Otsuka Pharmaceutical and approved in the United States in 2015 as an adjunctive therapy to antidepressants for major depressive disorder and as a treatment for schizophrenia. In 2023, the FDA approved it for Alzheimer’s-related agitation. However, according to Otsuka, its mechanism of action is unknown.

Its efficacy may be mediated through a combination of partial agonist activity at serotonin 5-HT1A and dopamine D2 receptors, antagonist activity at serotonin 5-HT2A receptors, as well as antagonism of alpha-1B/2C receptors, said the company.

“It is the combination, rather than either alone, that’s going to have that broad synergistic pharmacology that is obviously potent for ameliorating the symptoms of PTSD,” said Davis, who has received consulting fees from Otsuka. “That’s an exciting development.”

Otsuka and partner Lundbeck Pharmaceuticals reported results in May from the companies’ phase 2 and 3 randomized clinical trials. The therapy achieved a statistically significant reduction (P <.05) in PTSD symptoms compared with sertraline plus placebo. This was without any supplemental psychotherapy.

The FDA accepted the companies’ new drug application in June and is expected to make a decision on approval in February 2025.
 

The Potential of Psychedelics

Though Lykos Therapeutics may have to go back to the drawing board on its MDMA-AT, psychedelics still have potential as PTSD therapies, Smyth said, who added that the VA is continuing to encourage study of MDMA and other psychedelic agents.

The VA issued a call for proposals for research on psychedelics in January, focused on MDMA or psilocybin in combination with psychotherapy. The administration received the first wave of applications early in the summer.

Scientific peer review panels made up of research experts from within and outside the VA have reviewed the applications and funding announcements are expected this fall, Smyth said.

Wolfgang, the Army psychiatrist, said, “Under the psychedelic treatment research clinical trial award, we welcome investigators to apply to what we anticipate will usher in a new era of innovation and hope for service members and their families who need it the most.”

Psychedelic studies are also proceeding without VA funding, as they have for years, when most of the trials were backed by universities or foundations or other private money. Johns Hopkins University is recruiting for a study in which patients would receive psilocybin along with trauma-focused psychotherapy, as is Ohio State University.

London-based Compass Pathways said in May that it successfully completed a phase 2 trial of Comp360, its synthetic psilocybin, in PTSD. The company has started a phase 3 study in treatment-resistant depression but has not given any further updates on PTSD.

Davis said that she believes that the FDA’s rejection of Lykos won’t lead to a shutdown of exploration of psychedelics.

“I think it informs these designs going forward, but it doesn’t eliminate that whole field of research,” she said.

Davis reported receiving consulting fees from Boehringer Ingelheim and Otsuka and research funding from Alkermes, the Patient-Centered Outcomes Research Institute, and the VA. Schnurr, Fischer, Smyth, and Wolfgang reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

It has been 24 years since a pharmaceutical was last approved for posttraumatic stress disorder (PTSD). The condition is notoriously difficult to treat, with up to 40% patients finding no relief from symptoms through psychotherapy or current medications.

Many clinicians, advocates, and patients had pinned their hopes on the psychedelic drug midomafetamine with assisted therapy (MDMA-AT). However, in August, the US Food and Drug Administration (FDA) rejected it. At this point, it’s unclear when the therapy will be available, if ever.

“Not getting the FDA approval of any drug at this point is a setback for the field,” Lori Davis, MD, a senior research psychiatrist at the Birmingham Veterans Affairs (VA) Health Care System in Birmingham, Alabama, told Medscape Medical News.

Having an FDA-approved product would have helped increase public awareness of PTSD and driven interest in developing new therapies, said Davis, who is also adjunct professor of psychiatry at the Heersink School of Medicine, University of Alabama at Birmingham.
 

A Treatable Condition

So with MDMA-AT off the table, where does the field go next? 

A public meeting in September hosted by the Reagan-Udall Foundation for the FDA in sought to answer that question. Agency officials joined representatives from the Department of Defense (DoD) and VA, patients, advocates, and industry representatives to discuss the current treatment landscape and what can be done to accelerate development of PTSD treatment.

Despite the common belief that PTSD is intractable, it “is a treatable condition,” Paula P. Schnurr, PhD, executive director of the VA National Center for PTSD, said at the meeting.

“There are effective treatments that work well for a lot of people, although not everyone has a satisfactory response,” she added.

The most effective psychotherapies are “trauma-focused,” and include cognitive processing therapy, eye movement desensitization and reprocessing, and prolonged exposure, according to the VA National Center for PTSD.

Three drugs have been approved by the FDA for PTSD: Venlafaxine (Effexor) in 1993, sertraline (Zoloft) in 1999, and paroxetine (Paxil) in 2000.

However, as the September meeting demonstrated, more therapies are needed.

“It’s clear to FDA and the federal government at large that there is an unmet need for safe and effective therapies to treat PTSD,” Bernard Fischer, MD, deputy director of the Division of Psychiatry in the Office of New Drugs at FDA’s Center for Drug Evaluation and Research, said at the meeting.

There is no shortage of research, Fischer added. Nearly 500 trials focused on PTSD are listed on clinicaltrials.gov are recruiting participants now or plan to soon.

Unsurprisingly, one of the primary drivers of PTSD therapeutics research is the VA. About 14% of the 5.7 million veterans who received care through the VA in 2023 had a diagnosis of PTSD.

“The US military is currently losing thousands of service members each year to PTSD- related disability discharges,” US Army Maj. Aaron Wolfgang, MD, a psychiatrist at the Walter Reed National Military Medical Center, said at the meeting. Only about 12%-20% of patients achieve remission with conventional therapies, added Wolfgang, who also is an assistant professor at the Uniformed Services University.

“For these reasons, establishing better treatments for PTSD is not only a matter of humanitarianism but also a pressing matter of national security,” he said.

The VA has committed at least $230 million to more than 140 active research projects in PTSD, Miriam J. Smyth, PhD, acting director of the clinical science, research and development service at the VA, said at the Reagan-Udall meeting.

One of the VA projects is the PTSD psychopharmacology initiative, which began in 2017 and now has 14 active clinical trials, said Smyth, who is also acting director for brain behavior and mental health at the VA. The first study should be finished by 2025.

The Million Veteran Program, with more than 1 million enrollees, has led to the discovery of genes related to re-experiencing traumatic memories and has confirmed that both PTSD and traumatic brain injury are risk factors for dementia, Smyth said.

The DoD has created a novel platform that establishes a common infrastructure for testing multiple drugs, called M-PACT. The platform allows sharing of placebo data across treatment arms. Drugs cycle off the platform if evidence indicates probability of success or failure.

Four trials are actively recruiting veterans and current service members. One is looking at vilazodone, approved in 2011 for major depressive disorder. It is being compared with placebo and fluoxetine in a trial that is currently recruiting.

Another trial will study daridorexant (sold as Quviviq), an orexin receptor antagonist, against placebo. The FDA approved daridorexant in 2022 as an insomnia treatment. A core issue in PTSD is sleep disruption, noted Davis.
 

New Therapies on the Way

Separately, Davis and colleagues are also studying methylphenidate, the stimulant used for attention-deficit/hyperactivity disorder. It may help with neurocognitive complaints and reduce PTSD symptoms, said Davis.

Because it is generic, few pharmaceutical manufacturers are likely to test it for PTSD, she said. But eventually, their work may lead a company to test newer stimulants for PTSD, she said.

Another potential therapeutic, BNC210, received Fast Track designation for PTSD from the FDA in 2019. Bionomics Limited in Australia will soon launch phase 3 trials of the investigational oral drug, which is a negative allosteric modulator of the alpha-7 nicotinic acetylcholine receptor. In late July, the company announced “ favorable feedback” from the agency on its phase 2 study, which led to the decision to move forward with larger trials.

Researchers at Brigham and Women’s Hospital have just reported that they may have found a target within the brain that will allow for transcranial magnetic stimulation (TMS) to ameliorate PTSD symptoms. They published results of a mapping effort in Nature Neuroscience and reported on one patient who had improved symptoms after receiving TMS for severe PTSD.

But perhaps one of the most promising treatments is a combination of sertraline and the new psychiatric medication brexpiprazole.

Brexpiprazole was developed by Otsuka Pharmaceutical and approved in the United States in 2015 as an adjunctive therapy to antidepressants for major depressive disorder and as a treatment for schizophrenia. In 2023, the FDA approved it for Alzheimer’s-related agitation. However, according to Otsuka, its mechanism of action is unknown.

Its efficacy may be mediated through a combination of partial agonist activity at serotonin 5-HT1A and dopamine D2 receptors, antagonist activity at serotonin 5-HT2A receptors, as well as antagonism of alpha-1B/2C receptors, said the company.

“It is the combination, rather than either alone, that’s going to have that broad synergistic pharmacology that is obviously potent for ameliorating the symptoms of PTSD,” said Davis, who has received consulting fees from Otsuka. “That’s an exciting development.”

Otsuka and partner Lundbeck Pharmaceuticals reported results in May from the companies’ phase 2 and 3 randomized clinical trials. The therapy achieved a statistically significant reduction (P <.05) in PTSD symptoms compared with sertraline plus placebo. This was without any supplemental psychotherapy.

The FDA accepted the companies’ new drug application in June and is expected to make a decision on approval in February 2025.
 

The Potential of Psychedelics

Though Lykos Therapeutics may have to go back to the drawing board on its MDMA-AT, psychedelics still have potential as PTSD therapies, Smyth said, who added that the VA is continuing to encourage study of MDMA and other psychedelic agents.

The VA issued a call for proposals for research on psychedelics in January, focused on MDMA or psilocybin in combination with psychotherapy. The administration received the first wave of applications early in the summer.

Scientific peer review panels made up of research experts from within and outside the VA have reviewed the applications and funding announcements are expected this fall, Smyth said.

Wolfgang, the Army psychiatrist, said, “Under the psychedelic treatment research clinical trial award, we welcome investigators to apply to what we anticipate will usher in a new era of innovation and hope for service members and their families who need it the most.”

Psychedelic studies are also proceeding without VA funding, as they have for years, when most of the trials were backed by universities or foundations or other private money. Johns Hopkins University is recruiting for a study in which patients would receive psilocybin along with trauma-focused psychotherapy, as is Ohio State University.

London-based Compass Pathways said in May that it successfully completed a phase 2 trial of Comp360, its synthetic psilocybin, in PTSD. The company has started a phase 3 study in treatment-resistant depression but has not given any further updates on PTSD.

Davis said that she believes that the FDA’s rejection of Lykos won’t lead to a shutdown of exploration of psychedelics.

“I think it informs these designs going forward, but it doesn’t eliminate that whole field of research,” she said.

Davis reported receiving consulting fees from Boehringer Ingelheim and Otsuka and research funding from Alkermes, the Patient-Centered Outcomes Research Institute, and the VA. Schnurr, Fischer, Smyth, and Wolfgang reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

It has been 24 years since a pharmaceutical was last approved for posttraumatic stress disorder (PTSD). The condition is notoriously difficult to treat, with up to 40% patients finding no relief from symptoms through psychotherapy or current medications.

Many clinicians, advocates, and patients had pinned their hopes on the psychedelic drug midomafetamine with assisted therapy (MDMA-AT). However, in August, the US Food and Drug Administration (FDA) rejected it. At this point, it’s unclear when the therapy will be available, if ever.

“Not getting the FDA approval of any drug at this point is a setback for the field,” Lori Davis, MD, a senior research psychiatrist at the Birmingham Veterans Affairs (VA) Health Care System in Birmingham, Alabama, told Medscape Medical News.

Having an FDA-approved product would have helped increase public awareness of PTSD and driven interest in developing new therapies, said Davis, who is also adjunct professor of psychiatry at the Heersink School of Medicine, University of Alabama at Birmingham.
 

A Treatable Condition

So with MDMA-AT off the table, where does the field go next? 

A public meeting in September hosted by the Reagan-Udall Foundation for the FDA in sought to answer that question. Agency officials joined representatives from the Department of Defense (DoD) and VA, patients, advocates, and industry representatives to discuss the current treatment landscape and what can be done to accelerate development of PTSD treatment.

Despite the common belief that PTSD is intractable, it “is a treatable condition,” Paula P. Schnurr, PhD, executive director of the VA National Center for PTSD, said at the meeting.

“There are effective treatments that work well for a lot of people, although not everyone has a satisfactory response,” she added.

The most effective psychotherapies are “trauma-focused,” and include cognitive processing therapy, eye movement desensitization and reprocessing, and prolonged exposure, according to the VA National Center for PTSD.

Three drugs have been approved by the FDA for PTSD: Venlafaxine (Effexor) in 1993, sertraline (Zoloft) in 1999, and paroxetine (Paxil) in 2000.

However, as the September meeting demonstrated, more therapies are needed.

“It’s clear to FDA and the federal government at large that there is an unmet need for safe and effective therapies to treat PTSD,” Bernard Fischer, MD, deputy director of the Division of Psychiatry in the Office of New Drugs at FDA’s Center for Drug Evaluation and Research, said at the meeting.

There is no shortage of research, Fischer added. Nearly 500 trials focused on PTSD are listed on clinicaltrials.gov are recruiting participants now or plan to soon.

Unsurprisingly, one of the primary drivers of PTSD therapeutics research is the VA. About 14% of the 5.7 million veterans who received care through the VA in 2023 had a diagnosis of PTSD.

“The US military is currently losing thousands of service members each year to PTSD- related disability discharges,” US Army Maj. Aaron Wolfgang, MD, a psychiatrist at the Walter Reed National Military Medical Center, said at the meeting. Only about 12%-20% of patients achieve remission with conventional therapies, added Wolfgang, who also is an assistant professor at the Uniformed Services University.

“For these reasons, establishing better treatments for PTSD is not only a matter of humanitarianism but also a pressing matter of national security,” he said.

The VA has committed at least $230 million to more than 140 active research projects in PTSD, Miriam J. Smyth, PhD, acting director of the clinical science, research and development service at the VA, said at the Reagan-Udall meeting.

One of the VA projects is the PTSD psychopharmacology initiative, which began in 2017 and now has 14 active clinical trials, said Smyth, who is also acting director for brain behavior and mental health at the VA. The first study should be finished by 2025.

The Million Veteran Program, with more than 1 million enrollees, has led to the discovery of genes related to re-experiencing traumatic memories and has confirmed that both PTSD and traumatic brain injury are risk factors for dementia, Smyth said.

The DoD has created a novel platform that establishes a common infrastructure for testing multiple drugs, called M-PACT. The platform allows sharing of placebo data across treatment arms. Drugs cycle off the platform if evidence indicates probability of success or failure.

Four trials are actively recruiting veterans and current service members. One is looking at vilazodone, approved in 2011 for major depressive disorder. It is being compared with placebo and fluoxetine in a trial that is currently recruiting.

Another trial will study daridorexant (sold as Quviviq), an orexin receptor antagonist, against placebo. The FDA approved daridorexant in 2022 as an insomnia treatment. A core issue in PTSD is sleep disruption, noted Davis.
 

New Therapies on the Way

Separately, Davis and colleagues are also studying methylphenidate, the stimulant used for attention-deficit/hyperactivity disorder. It may help with neurocognitive complaints and reduce PTSD symptoms, said Davis.

Because it is generic, few pharmaceutical manufacturers are likely to test it for PTSD, she said. But eventually, their work may lead a company to test newer stimulants for PTSD, she said.

Another potential therapeutic, BNC210, received Fast Track designation for PTSD from the FDA in 2019. Bionomics Limited in Australia will soon launch phase 3 trials of the investigational oral drug, which is a negative allosteric modulator of the alpha-7 nicotinic acetylcholine receptor. In late July, the company announced “ favorable feedback” from the agency on its phase 2 study, which led to the decision to move forward with larger trials.

Researchers at Brigham and Women’s Hospital have just reported that they may have found a target within the brain that will allow for transcranial magnetic stimulation (TMS) to ameliorate PTSD symptoms. They published results of a mapping effort in Nature Neuroscience and reported on one patient who had improved symptoms after receiving TMS for severe PTSD.

But perhaps one of the most promising treatments is a combination of sertraline and the new psychiatric medication brexpiprazole.

Brexpiprazole was developed by Otsuka Pharmaceutical and approved in the United States in 2015 as an adjunctive therapy to antidepressants for major depressive disorder and as a treatment for schizophrenia. In 2023, the FDA approved it for Alzheimer’s-related agitation. However, according to Otsuka, its mechanism of action is unknown.

Its efficacy may be mediated through a combination of partial agonist activity at serotonin 5-HT1A and dopamine D2 receptors, antagonist activity at serotonin 5-HT2A receptors, as well as antagonism of alpha-1B/2C receptors, said the company.

“It is the combination, rather than either alone, that’s going to have that broad synergistic pharmacology that is obviously potent for ameliorating the symptoms of PTSD,” said Davis, who has received consulting fees from Otsuka. “That’s an exciting development.”

Otsuka and partner Lundbeck Pharmaceuticals reported results in May from the companies’ phase 2 and 3 randomized clinical trials. The therapy achieved a statistically significant reduction (P <.05) in PTSD symptoms compared with sertraline plus placebo. This was without any supplemental psychotherapy.

The FDA accepted the companies’ new drug application in June and is expected to make a decision on approval in February 2025.
 

The Potential of Psychedelics

Though Lykos Therapeutics may have to go back to the drawing board on its MDMA-AT, psychedelics still have potential as PTSD therapies, Smyth said, who added that the VA is continuing to encourage study of MDMA and other psychedelic agents.

The VA issued a call for proposals for research on psychedelics in January, focused on MDMA or psilocybin in combination with psychotherapy. The administration received the first wave of applications early in the summer.

Scientific peer review panels made up of research experts from within and outside the VA have reviewed the applications and funding announcements are expected this fall, Smyth said.

Wolfgang, the Army psychiatrist, said, “Under the psychedelic treatment research clinical trial award, we welcome investigators to apply to what we anticipate will usher in a new era of innovation and hope for service members and their families who need it the most.”

Psychedelic studies are also proceeding without VA funding, as they have for years, when most of the trials were backed by universities or foundations or other private money. Johns Hopkins University is recruiting for a study in which patients would receive psilocybin along with trauma-focused psychotherapy, as is Ohio State University.

London-based Compass Pathways said in May that it successfully completed a phase 2 trial of Comp360, its synthetic psilocybin, in PTSD. The company has started a phase 3 study in treatment-resistant depression but has not given any further updates on PTSD.

Davis said that she believes that the FDA’s rejection of Lykos won’t lead to a shutdown of exploration of psychedelics.

“I think it informs these designs going forward, but it doesn’t eliminate that whole field of research,” she said.

Davis reported receiving consulting fees from Boehringer Ingelheim and Otsuka and research funding from Alkermes, the Patient-Centered Outcomes Research Institute, and the VA. Schnurr, Fischer, Smyth, and Wolfgang reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.