Feature

Geographic spread of the ticks that most often cause Lyme disease in the United States and a rise in incidence of bites, resulting in 476,000 new US cases a year, have increased the chances that physicians who have never encountered a patient with Lyme disease will see their first cases.

“It’s increasing in areas where it was not seen before,” Steven E. Schutzer, MD, with the Department of Medicine, Rutgers New Jersey Medical School, Newark, said in an interview. Dr. Schutzer coauthored a report on diagnosing and treating Lyme disease with Patricia K. Coyle, MD, Department of Neurology, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York.

The report, a Curbside Consult published in New England Journal of Medicine Evidence, comes amid high season for Lyme disease. Bites from an ixodid (hard shield) tick — almost always the source of the disease in the United States — are most common from April through October.

Identifying the Bite

About 70%-90% of the time, Lyme disease will be signaled by erythema migrans (EM) or lesion expanding from the tick bite site, the authors wrote. The “classic” presentation looks like a bullseye, but most of the time the skin will show a variation of that, the authors noted.

“The presence of EM is considered the best clinical diagnostic marker for Lyme disease,” they wrote.

Other dermatologic conditions, however, can complicate diagnosis: “EM mimickers include contact dermatitis, other arthropod bites, fixed drug eruptions, granuloma annulare, cellulitis, dermatophytosis, and systemic lupus erythematosus,” they wrote.
 

Testing Steps

“The current recommendation is to do two-step testing almost simultaneously,” Dr. Schutzer said in an interview. The first, he said, is an ELISA (enzyme-linked immunosorbent assay)-type test and the second one, used for years, has been a pictoral view of a Western immunoblot showing which antigens of the Lyme bacteria, Borrelia burgdorferi, the antibodies are reacting to.

However, the pictoral view is subjective and some of the antigens could be cross-reactive. So the U.S. Food and Drug Administration (FDA) “has been allowing newer substitutes like a second ELISA-like assay that often uses more recombinant, less cross-reactive antigen targets,” he said. The authors advised that, “The second-tier test should not be performed alone without the first tier.”

Dr. Schutzer advised physicians to check with the lab they plan to use before sending samples.

“If you’re a practicing physician and you know you’re using a particular laboratory, you should familiarize yourself with them, talking to one of the clinical pathologists involved in advance to know what the limitations are.” Take the time to talk with the person overseeing the test and get tips on how they want the sample transported and how the cases should be reported, he said.

If the patient has neurological symptoms, he said, before treating talk with a neurologist who can advise whether, for instance, a spinal tap is in order or whether an emergency department visit is appropriate.

“If you just start proceeding you may mess up the diagnostic signs that could show up in a lab test. Don’t be hesitant to ask for extra input from colleagues,” Dr. Schutzer said.
 

Suspicion in Endemic Areas

On Long Island, New York, where Lyme disease is endemic, internist Ian Storch, DO, said he sees “a few cases a season.

“We have a lot of people over the summer going to the Hamptons and areas out east for the weekend and tick bites are not uncommon,” he said. “People panic.”

He said one thing it’s important to tell patients is that the tick has to be on the skin for 48-72 hours to transmit the disease. If individuals were in a wooded area and were fine before they got there and the tick was attached for less than 2 days, “they’re usually fine.”

Another issue, Dr. Storch said, is patients sometimes want to get tested for Lyme disease immediately after a tick bite. But the antibody test doesn’t turn positive for weeks, he noted, and you can get a false-negative result. “If you’re worried and you really want to test, you need to wait 6 weeks to do the blood test.”

In his region, he said that although a tick bite is a red flag, he may also suspect Lyme disease when a patient presents with otherwise unexplained joint pain, weakness, lethargy, or fever. “In our area, those are things that would make you test for Lyme.”

He also urged consideration of Lyme in this new age of long COVID. Weakness, fatigue, and lethargy are also classic symptoms of long COVID, he noted. “Keep Lyme disease in your differential because there is a lot of overlap with chronic Lyme disease,” Dr. Storch said.

Discerning Lyme from Southern Tick–Associated Rash Illness

Bonnie M. Word, MD, director of the Houston Travel Medicine Clinic in Texas, where Lyme disease is not endemic, said Lyme disease “will not and should not be on the initial differential diagnosis for those residing in nonendemic areas unless a history of travel to an endemic area is obtained.”

She noted the typical EM rash may not be as distinct or easy to discern on black and brown skin. In addition, she said, EM may have many variations in presentation, such as a crusted center or faint borders, which could lead to a delay in diagnosis and treatment. She suggested consulting the CDC guidance on Lyme disease rashes.

Another challenge in diagnosis, she said, is the patient who presents with what appears to be a classic EM lesion but does not live in a Lyme-endemic area. In Texas, Southern Tick–Associated Rash Illness (STARI) may present with a similar lesion, she said.

“It is transmitted by the Lone Star Tick, which is found in the southeast and south-central US,” Dr. Word said. “However, its habitat is moving northward and westerly,” she said.

Adding Lyme disease to the differential diagnosis is reasonable, she said, if a patient presents with neurologic symptoms “such as a facial palsy, meningitis, radiculitis, and carditis if in addition to their symptoms there is evidence of an epidemiologic link to a Lyme-endemic region.”

She noted that a detailed travel history is important as “Lyme is also endemic in Eastern Canada, Europe, states of the former Soviet Union, China, Mongolia, and Japan.”

Primary care physicians play a critical role in evaluating, diagnosing, and treating most cases of early Lyme disease, thus limiting the number of people who will develop disseminated or late Lyme disease, she said. “The two latter manifestations are most often treated by infectious disease, neurology, or rheumatology specialists.”

Treatment* 

Treatment is tailored to the clinical situation, Dr. Schutzer and Dr. Coyle write. A watch-and-wait approach may be appropriate in an asymptomatic but concerned person, even in an endemic area if the person has no known tick bite and no EM lesion.

If there is high risk of an infected ixodid tick bite in a high-incidence area and the tick was attached for at least 36 hours but less than 72 hours, one dose of doxycycline has been recommended as prophylaxis.

When a diagnosis of early nondisseminated Lyme disease is made after observation  of an EM lesion, oral antibiotics are typically used to treat for 10 to 14 days. Suggested oral antibiotics and doses are 100 mg of doxycycline twice a day, 500 mg of amoxicillin three times a day, or 500 mg of cefuroxime twice a day, the authors write.

Dr. Schutzer said he hopes the paper serves as a refresher for those physicians who regularly see Lyme disease cases and also helps those newly included in the disease’s spreading regions.

“The earlier you diagnose it, the earlier you can treat it and the better the chance for a favorable outcome,” he said.

Dr. Schutzer, Dr. Coyle, Dr. Storch, and Dr. Word reported no relevant financial relationships.

*This story was updated on August, 2, 2024.

Geographic spread of the ticks that most often cause Lyme disease in the United States and a rise in incidence of bites, resulting in 476,000 new US cases a year, have increased the chances that physicians who have never encountered a patient with Lyme disease will see their first cases.

“It’s increasing in areas where it was not seen before,” Steven E. Schutzer, MD, with the Department of Medicine, Rutgers New Jersey Medical School, Newark, said in an interview. Dr. Schutzer coauthored a report on diagnosing and treating Lyme disease with Patricia K. Coyle, MD, Department of Neurology, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York.

The report, a Curbside Consult published in New England Journal of Medicine Evidence, comes amid high season for Lyme disease. Bites from an ixodid (hard shield) tick — almost always the source of the disease in the United States — are most common from April through October.

Identifying the Bite

About 70%-90% of the time, Lyme disease will be signaled by erythema migrans (EM) or lesion expanding from the tick bite site, the authors wrote. The “classic” presentation looks like a bullseye, but most of the time the skin will show a variation of that, the authors noted.

“The presence of EM is considered the best clinical diagnostic marker for Lyme disease,” they wrote.

Other dermatologic conditions, however, can complicate diagnosis: “EM mimickers include contact dermatitis, other arthropod bites, fixed drug eruptions, granuloma annulare, cellulitis, dermatophytosis, and systemic lupus erythematosus,” they wrote.
 

Testing Steps

“The current recommendation is to do two-step testing almost simultaneously,” Dr. Schutzer said in an interview. The first, he said, is an ELISA (enzyme-linked immunosorbent assay)-type test and the second one, used for years, has been a pictoral view of a Western immunoblot showing which antigens of the Lyme bacteria, Borrelia burgdorferi, the antibodies are reacting to.

However, the pictoral view is subjective and some of the antigens could be cross-reactive. So the U.S. Food and Drug Administration (FDA) “has been allowing newer substitutes like a second ELISA-like assay that often uses more recombinant, less cross-reactive antigen targets,” he said. The authors advised that, “The second-tier test should not be performed alone without the first tier.”

Dr. Schutzer advised physicians to check with the lab they plan to use before sending samples.

“If you’re a practicing physician and you know you’re using a particular laboratory, you should familiarize yourself with them, talking to one of the clinical pathologists involved in advance to know what the limitations are.” Take the time to talk with the person overseeing the test and get tips on how they want the sample transported and how the cases should be reported, he said.

If the patient has neurological symptoms, he said, before treating talk with a neurologist who can advise whether, for instance, a spinal tap is in order or whether an emergency department visit is appropriate.

“If you just start proceeding you may mess up the diagnostic signs that could show up in a lab test. Don’t be hesitant to ask for extra input from colleagues,” Dr. Schutzer said.
 

Suspicion in Endemic Areas

On Long Island, New York, where Lyme disease is endemic, internist Ian Storch, DO, said he sees “a few cases a season.

“We have a lot of people over the summer going to the Hamptons and areas out east for the weekend and tick bites are not uncommon,” he said. “People panic.”

He said one thing it’s important to tell patients is that the tick has to be on the skin for 48-72 hours to transmit the disease. If individuals were in a wooded area and were fine before they got there and the tick was attached for less than 2 days, “they’re usually fine.”

Another issue, Dr. Storch said, is patients sometimes want to get tested for Lyme disease immediately after a tick bite. But the antibody test doesn’t turn positive for weeks, he noted, and you can get a false-negative result. “If you’re worried and you really want to test, you need to wait 6 weeks to do the blood test.”

In his region, he said that although a tick bite is a red flag, he may also suspect Lyme disease when a patient presents with otherwise unexplained joint pain, weakness, lethargy, or fever. “In our area, those are things that would make you test for Lyme.”

He also urged consideration of Lyme in this new age of long COVID. Weakness, fatigue, and lethargy are also classic symptoms of long COVID, he noted. “Keep Lyme disease in your differential because there is a lot of overlap with chronic Lyme disease,” Dr. Storch said.

Discerning Lyme from Southern Tick–Associated Rash Illness

Bonnie M. Word, MD, director of the Houston Travel Medicine Clinic in Texas, where Lyme disease is not endemic, said Lyme disease “will not and should not be on the initial differential diagnosis for those residing in nonendemic areas unless a history of travel to an endemic area is obtained.”

She noted the typical EM rash may not be as distinct or easy to discern on black and brown skin. In addition, she said, EM may have many variations in presentation, such as a crusted center or faint borders, which could lead to a delay in diagnosis and treatment. She suggested consulting the CDC guidance on Lyme disease rashes.

Another challenge in diagnosis, she said, is the patient who presents with what appears to be a classic EM lesion but does not live in a Lyme-endemic area. In Texas, Southern Tick–Associated Rash Illness (STARI) may present with a similar lesion, she said.

“It is transmitted by the Lone Star Tick, which is found in the southeast and south-central US,” Dr. Word said. “However, its habitat is moving northward and westerly,” she said.

Adding Lyme disease to the differential diagnosis is reasonable, she said, if a patient presents with neurologic symptoms “such as a facial palsy, meningitis, radiculitis, and carditis if in addition to their symptoms there is evidence of an epidemiologic link to a Lyme-endemic region.”

She noted that a detailed travel history is important as “Lyme is also endemic in Eastern Canada, Europe, states of the former Soviet Union, China, Mongolia, and Japan.”

Primary care physicians play a critical role in evaluating, diagnosing, and treating most cases of early Lyme disease, thus limiting the number of people who will develop disseminated or late Lyme disease, she said. “The two latter manifestations are most often treated by infectious disease, neurology, or rheumatology specialists.”

Treatment* 

Treatment is tailored to the clinical situation, Dr. Schutzer and Dr. Coyle write. A watch-and-wait approach may be appropriate in an asymptomatic but concerned person, even in an endemic area if the person has no known tick bite and no EM lesion.

If there is high risk of an infected ixodid tick bite in a high-incidence area and the tick was attached for at least 36 hours but less than 72 hours, one dose of doxycycline has been recommended as prophylaxis.

When a diagnosis of early nondisseminated Lyme disease is made after observation  of an EM lesion, oral antibiotics are typically used to treat for 10 to 14 days. Suggested oral antibiotics and doses are 100 mg of doxycycline twice a day, 500 mg of amoxicillin three times a day, or 500 mg of cefuroxime twice a day, the authors write.

Dr. Schutzer said he hopes the paper serves as a refresher for those physicians who regularly see Lyme disease cases and also helps those newly included in the disease’s spreading regions.

“The earlier you diagnose it, the earlier you can treat it and the better the chance for a favorable outcome,” he said.

Dr. Schutzer, Dr. Coyle, Dr. Storch, and Dr. Word reported no relevant financial relationships.

*This story was updated on August, 2, 2024.

Geographic spread of the ticks that most often cause Lyme disease in the United States and a rise in incidence of bites, resulting in 476,000 new US cases a year, have increased the chances that physicians who have never encountered a patient with Lyme disease will see their first cases.

“It’s increasing in areas where it was not seen before,” Steven E. Schutzer, MD, with the Department of Medicine, Rutgers New Jersey Medical School, Newark, said in an interview. Dr. Schutzer coauthored a report on diagnosing and treating Lyme disease with Patricia K. Coyle, MD, Department of Neurology, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York.

The report, a Curbside Consult published in New England Journal of Medicine Evidence, comes amid high season for Lyme disease. Bites from an ixodid (hard shield) tick — almost always the source of the disease in the United States — are most common from April through October.

Identifying the Bite

About 70%-90% of the time, Lyme disease will be signaled by erythema migrans (EM) or lesion expanding from the tick bite site, the authors wrote. The “classic” presentation looks like a bullseye, but most of the time the skin will show a variation of that, the authors noted.

“The presence of EM is considered the best clinical diagnostic marker for Lyme disease,” they wrote.

Other dermatologic conditions, however, can complicate diagnosis: “EM mimickers include contact dermatitis, other arthropod bites, fixed drug eruptions, granuloma annulare, cellulitis, dermatophytosis, and systemic lupus erythematosus,” they wrote.
 

Testing Steps

“The current recommendation is to do two-step testing almost simultaneously,” Dr. Schutzer said in an interview. The first, he said, is an ELISA (enzyme-linked immunosorbent assay)-type test and the second one, used for years, has been a pictoral view of a Western immunoblot showing which antigens of the Lyme bacteria, Borrelia burgdorferi, the antibodies are reacting to.

However, the pictoral view is subjective and some of the antigens could be cross-reactive. So the U.S. Food and Drug Administration (FDA) “has been allowing newer substitutes like a second ELISA-like assay that often uses more recombinant, less cross-reactive antigen targets,” he said. The authors advised that, “The second-tier test should not be performed alone without the first tier.”

Dr. Schutzer advised physicians to check with the lab they plan to use before sending samples.

“If you’re a practicing physician and you know you’re using a particular laboratory, you should familiarize yourself with them, talking to one of the clinical pathologists involved in advance to know what the limitations are.” Take the time to talk with the person overseeing the test and get tips on how they want the sample transported and how the cases should be reported, he said.

If the patient has neurological symptoms, he said, before treating talk with a neurologist who can advise whether, for instance, a spinal tap is in order or whether an emergency department visit is appropriate.

“If you just start proceeding you may mess up the diagnostic signs that could show up in a lab test. Don’t be hesitant to ask for extra input from colleagues,” Dr. Schutzer said.
 

Suspicion in Endemic Areas

On Long Island, New York, where Lyme disease is endemic, internist Ian Storch, DO, said he sees “a few cases a season.

“We have a lot of people over the summer going to the Hamptons and areas out east for the weekend and tick bites are not uncommon,” he said. “People panic.”

He said one thing it’s important to tell patients is that the tick has to be on the skin for 48-72 hours to transmit the disease. If individuals were in a wooded area and were fine before they got there and the tick was attached for less than 2 days, “they’re usually fine.”

Another issue, Dr. Storch said, is patients sometimes want to get tested for Lyme disease immediately after a tick bite. But the antibody test doesn’t turn positive for weeks, he noted, and you can get a false-negative result. “If you’re worried and you really want to test, you need to wait 6 weeks to do the blood test.”

In his region, he said that although a tick bite is a red flag, he may also suspect Lyme disease when a patient presents with otherwise unexplained joint pain, weakness, lethargy, or fever. “In our area, those are things that would make you test for Lyme.”

He also urged consideration of Lyme in this new age of long COVID. Weakness, fatigue, and lethargy are also classic symptoms of long COVID, he noted. “Keep Lyme disease in your differential because there is a lot of overlap with chronic Lyme disease,” Dr. Storch said.

Discerning Lyme from Southern Tick–Associated Rash Illness

Bonnie M. Word, MD, director of the Houston Travel Medicine Clinic in Texas, where Lyme disease is not endemic, said Lyme disease “will not and should not be on the initial differential diagnosis for those residing in nonendemic areas unless a history of travel to an endemic area is obtained.”

She noted the typical EM rash may not be as distinct or easy to discern on black and brown skin. In addition, she said, EM may have many variations in presentation, such as a crusted center or faint borders, which could lead to a delay in diagnosis and treatment. She suggested consulting the CDC guidance on Lyme disease rashes.

Another challenge in diagnosis, she said, is the patient who presents with what appears to be a classic EM lesion but does not live in a Lyme-endemic area. In Texas, Southern Tick–Associated Rash Illness (STARI) may present with a similar lesion, she said.

“It is transmitted by the Lone Star Tick, which is found in the southeast and south-central US,” Dr. Word said. “However, its habitat is moving northward and westerly,” she said.

Adding Lyme disease to the differential diagnosis is reasonable, she said, if a patient presents with neurologic symptoms “such as a facial palsy, meningitis, radiculitis, and carditis if in addition to their symptoms there is evidence of an epidemiologic link to a Lyme-endemic region.”

She noted that a detailed travel history is important as “Lyme is also endemic in Eastern Canada, Europe, states of the former Soviet Union, China, Mongolia, and Japan.”

Primary care physicians play a critical role in evaluating, diagnosing, and treating most cases of early Lyme disease, thus limiting the number of people who will develop disseminated or late Lyme disease, she said. “The two latter manifestations are most often treated by infectious disease, neurology, or rheumatology specialists.”

Treatment* 

Treatment is tailored to the clinical situation, Dr. Schutzer and Dr. Coyle write. A watch-and-wait approach may be appropriate in an asymptomatic but concerned person, even in an endemic area if the person has no known tick bite and no EM lesion.

If there is high risk of an infected ixodid tick bite in a high-incidence area and the tick was attached for at least 36 hours but less than 72 hours, one dose of doxycycline has been recommended as prophylaxis.

When a diagnosis of early nondisseminated Lyme disease is made after observation  of an EM lesion, oral antibiotics are typically used to treat for 10 to 14 days. Suggested oral antibiotics and doses are 100 mg of doxycycline twice a day, 500 mg of amoxicillin three times a day, or 500 mg of cefuroxime twice a day, the authors write.

Dr. Schutzer said he hopes the paper serves as a refresher for those physicians who regularly see Lyme disease cases and also helps those newly included in the disease’s spreading regions.

“The earlier you diagnose it, the earlier you can treat it and the better the chance for a favorable outcome,” he said.

Dr. Schutzer, Dr. Coyle, Dr. Storch, and Dr. Word reported no relevant financial relationships.

*This story was updated on August, 2, 2024.

When Bristeria Clark went into labor with her son in 2015, her contractions were steady at first. Then, they stalled. Her cervix stopped dilating. After a few hours, doctors at Phoebe Putney Memorial Hospital in Albany, Georgia, prepped Ms. Clark for an emergency cesarean section.

It wasn’t the vaginal birth Ms. Clark had hoped for during her pregnancy.

“I was freaking out. That was my first child. Like, of course you don’t plan that,” she said. “I just remember the gas pulling up to my face and I ended up going to sleep.”

She remembered feeling a rush of relief when she woke to see that her baby boy was healthy.

Ms. Clark, a 33-year-old nursing student who also works full-time in county government, had another C-section when her second child was born in 2020. This time, the cesarean was planned.

Ms. Clark said she’s grateful the physicians and nurses who delivered both her babies were kind and caring during her labor and delivery. But looking back, she said, she wishes she had had a doula for one-on-one support through pregnancy, childbirth, and the postpartum period. Now she wants to give other women the option she didn’t have.

Ms. Clark is a member of Morehouse School of Medicine’s first class of rural doulas, called Perinatal Patient Navigators.

The program recently graduated a dozen participants, all Black women from southwestern Georgia. They have completed more than 5 months of training and are scheduled to begin working with pregnant and postpartum patients this year.

“We’re developing a workforce that’s going to be providing the support that Black women and birthing people need,” Natalie Hernandez-Green, an associate professor of obstetrics and gynecology at Morehouse School of Medicine, Atlanta, Georgia, said at the doula commencement ceremony in Albany, Georgia.

Albany is Morehouse School of Medicine’s second Perinatal Patient Navigator program site. The first has been up and running in Atlanta since training began in the fall of 2022.

Georgia has one of the highest rates of maternal mortality in the country, according to an analysis by KFF, a health information nonprofit that includes KFF Health News. And Black Georgians are more than twice as likely as White Georgians to die of causes related to pregnancy.

“It doesn’t matter whether you’re rich or poor. Black women are dying at [an] alarming rate from pregnancy-related complications,” said Dr. Hernandez-Green, who is also executive director of the Center for Maternal Health Equity at Morehouse School of Medicine. “And we’re about to change that, one person at a time.”

The presence of a doula, along with regular nursing care, is associated with improved labor and delivery outcomes, reduced stress, and higher rates of patient satisfaction, according to the American College of Obstetricians and Gynecologists.

Multiple studies also link doulas to fewer expensive childbirth interventions, including cesarean births.

Doulas are not medical professionals. They are trained to offer education about the pregnancy and postpartum periods, to guide patients through the healthcare system, and to provide emotional and physical support before, during, and after childbirth.

Morehouse School of Medicine’s program is among a growing number of similar efforts being introduced across the country as more communities look to doulas to help address maternal mortality and poor maternal health outcomes, particularly for Black women and other women of color.

Now that she has graduated, Ms. Clark said she’s looking forward to helping other women in her community as a doula. “To be that person that would be there for my clients, treat them like a sister or like a mother, in a sense of just treating them with utmost respect,” she said. “The ultimate goal is to make them feel comfortable and let them know ‘I’m here to support you.’ ” Her training has inspired her to become an advocate for maternal health issues in southwestern Georgia.

Grants fund Morehouse School of Medicine’s doula program, which costs $350,000 a year to operate. Graduates are given a $2,000 training stipend and the program places five graduates with healthcare providers in southwestern Georgia. Grant money also pays the doulas’ salaries for 1 year. 

“It’s not sustainable if you’re chasing the next grant to fund it,” said Rachel Hardeman, a professor of health and racial equity at the University of Minnesota School of Public Health.

Thirteen states cover doulas through Medicaid, according to the Georgetown University Center for Children and Families.

Dr. Hardeman and others have found that when Medicaid programs cover doula care, states save millions of dollars in healthcare costs. “We were able to calculate the return on investment if Medicaid decided to reimburse doulas for pregnant people who are Medicaid beneficiaries,” she said.

That’s because doulas can help reduce the number of expensive medical interventions during and after birth, and improving delivery outcomes, including reduced cesarean sections.

Doulas can even reduce the likelihood of preterm birth. 

“An infant that is born at a very, very early gestational age is going to require a great deal of resources and interventions to ensure that they survive and then continue to thrive,” Dr. Hardeman said.

There is growing demand for doula services in Georgia, said Fowzio Jama, director of research for Healthy Mothers, Healthy Babies Coalition of Georgia. Her group recently completed a pilot study that offered doula services to about 170 Georgians covered under Medicaid. “We had a wait-list of over 200 clients and we wanted to give them the support that they needed, but we just couldn’t with the given resources that we had,” Ms. Jama said.

Doula services can cost hundreds or thousands of dollars out-of-pocket, making it too expensive for many low-income people, rural communities, and communities of color, many of which suffer from shortages in maternity care, according to the March of Dimes.

The Healthy Mothers, Healthy Babies study found that matching high-risk patients with doulas — particularly doulas from similar racial and ethnic backgrounds — had a positive effect on patients. 

“There was a reduced use of pitocin to induce labor. We saw fewer requests for pain medication. And with our infants, only 6% were low birth weight,” Ms. Jama said.

Still, she and others acknowledge that doulas alone can’t fix the problem of high maternal mortality and morbidity rates.

States, including Georgia, need to do more to bring comprehensive maternity care to communities that need more options, Dr. Hardeman said.

“I think it’s important to understand that doulas are not going to save us, and we should not put that expectation on them. Doulas are a tool,” she said. “They are a piece of the puzzle that is helping to impact a really, really complex issue.”

In the meantime, Joan Anderson, 55, said she’s excited to get to work supporting patients, especially from rural areas around Albany.

“I feel like I’m equipped to go out and be that voice, be that person that our community needs so bad,” said Ms. Anderson, a graduate of the Morehouse School of Medicine doula program. “I am encouraged to know that I will be joining in that mission, that fight for us, as far as maternal health is concerned.”

Ms. Anderson said that someday she wants to open a birthing center to provide maternity care. “We do not have one here in southwest Georgia at all,” Ms. Anderson said.

In addition to providing support during and after childbirth, Ms. Anderson and her fellow graduates are trained to assess their patients’ needs and connect them to services such as food assistance, mental health care, transportation to prenatal appointments, and breastfeeding assistance.

Their work is likely to have ripple effects across a largely rural corner of Georgia, said Sherrell Byrd, who co-founded and directs SOWEGA Rising, a nonprofit organization in southwestern Georgia.

“So many of the graduates are part of church networks, they are part of community organizations, some of them are our government workers. They’re very connected,” Ms. Byrd said. “And I think that connectedness is what’s going to help them be successful moving forward.”

This reporting is part of a fellowship with the Association of Health Care Journalists supported by The Commonwealth Fund. It comes from a partnership that includes WABE, NPR, and KFF Health News.

A version of this article first appeared on KFF Health News.

When Bristeria Clark went into labor with her son in 2015, her contractions were steady at first. Then, they stalled. Her cervix stopped dilating. After a few hours, doctors at Phoebe Putney Memorial Hospital in Albany, Georgia, prepped Ms. Clark for an emergency cesarean section.

It wasn’t the vaginal birth Ms. Clark had hoped for during her pregnancy.

“I was freaking out. That was my first child. Like, of course you don’t plan that,” she said. “I just remember the gas pulling up to my face and I ended up going to sleep.”

She remembered feeling a rush of relief when she woke to see that her baby boy was healthy.

Ms. Clark, a 33-year-old nursing student who also works full-time in county government, had another C-section when her second child was born in 2020. This time, the cesarean was planned.

Ms. Clark said she’s grateful the physicians and nurses who delivered both her babies were kind and caring during her labor and delivery. But looking back, she said, she wishes she had had a doula for one-on-one support through pregnancy, childbirth, and the postpartum period. Now she wants to give other women the option she didn’t have.

Ms. Clark is a member of Morehouse School of Medicine’s first class of rural doulas, called Perinatal Patient Navigators.

The program recently graduated a dozen participants, all Black women from southwestern Georgia. They have completed more than 5 months of training and are scheduled to begin working with pregnant and postpartum patients this year.

“We’re developing a workforce that’s going to be providing the support that Black women and birthing people need,” Natalie Hernandez-Green, an associate professor of obstetrics and gynecology at Morehouse School of Medicine, Atlanta, Georgia, said at the doula commencement ceremony in Albany, Georgia.

Albany is Morehouse School of Medicine’s second Perinatal Patient Navigator program site. The first has been up and running in Atlanta since training began in the fall of 2022.

Georgia has one of the highest rates of maternal mortality in the country, according to an analysis by KFF, a health information nonprofit that includes KFF Health News. And Black Georgians are more than twice as likely as White Georgians to die of causes related to pregnancy.

“It doesn’t matter whether you’re rich or poor. Black women are dying at [an] alarming rate from pregnancy-related complications,” said Dr. Hernandez-Green, who is also executive director of the Center for Maternal Health Equity at Morehouse School of Medicine. “And we’re about to change that, one person at a time.”

The presence of a doula, along with regular nursing care, is associated with improved labor and delivery outcomes, reduced stress, and higher rates of patient satisfaction, according to the American College of Obstetricians and Gynecologists.

Multiple studies also link doulas to fewer expensive childbirth interventions, including cesarean births.

Doulas are not medical professionals. They are trained to offer education about the pregnancy and postpartum periods, to guide patients through the healthcare system, and to provide emotional and physical support before, during, and after childbirth.

Morehouse School of Medicine’s program is among a growing number of similar efforts being introduced across the country as more communities look to doulas to help address maternal mortality and poor maternal health outcomes, particularly for Black women and other women of color.

Now that she has graduated, Ms. Clark said she’s looking forward to helping other women in her community as a doula. “To be that person that would be there for my clients, treat them like a sister or like a mother, in a sense of just treating them with utmost respect,” she said. “The ultimate goal is to make them feel comfortable and let them know ‘I’m here to support you.’ ” Her training has inspired her to become an advocate for maternal health issues in southwestern Georgia.

Grants fund Morehouse School of Medicine’s doula program, which costs $350,000 a year to operate. Graduates are given a $2,000 training stipend and the program places five graduates with healthcare providers in southwestern Georgia. Grant money also pays the doulas’ salaries for 1 year. 

“It’s not sustainable if you’re chasing the next grant to fund it,” said Rachel Hardeman, a professor of health and racial equity at the University of Minnesota School of Public Health.

Thirteen states cover doulas through Medicaid, according to the Georgetown University Center for Children and Families.

Dr. Hardeman and others have found that when Medicaid programs cover doula care, states save millions of dollars in healthcare costs. “We were able to calculate the return on investment if Medicaid decided to reimburse doulas for pregnant people who are Medicaid beneficiaries,” she said.

That’s because doulas can help reduce the number of expensive medical interventions during and after birth, and improving delivery outcomes, including reduced cesarean sections.

Doulas can even reduce the likelihood of preterm birth. 

“An infant that is born at a very, very early gestational age is going to require a great deal of resources and interventions to ensure that they survive and then continue to thrive,” Dr. Hardeman said.

There is growing demand for doula services in Georgia, said Fowzio Jama, director of research for Healthy Mothers, Healthy Babies Coalition of Georgia. Her group recently completed a pilot study that offered doula services to about 170 Georgians covered under Medicaid. “We had a wait-list of over 200 clients and we wanted to give them the support that they needed, but we just couldn’t with the given resources that we had,” Ms. Jama said.

Doula services can cost hundreds or thousands of dollars out-of-pocket, making it too expensive for many low-income people, rural communities, and communities of color, many of which suffer from shortages in maternity care, according to the March of Dimes.

The Healthy Mothers, Healthy Babies study found that matching high-risk patients with doulas — particularly doulas from similar racial and ethnic backgrounds — had a positive effect on patients. 

“There was a reduced use of pitocin to induce labor. We saw fewer requests for pain medication. And with our infants, only 6% were low birth weight,” Ms. Jama said.

Still, she and others acknowledge that doulas alone can’t fix the problem of high maternal mortality and morbidity rates.

States, including Georgia, need to do more to bring comprehensive maternity care to communities that need more options, Dr. Hardeman said.

“I think it’s important to understand that doulas are not going to save us, and we should not put that expectation on them. Doulas are a tool,” she said. “They are a piece of the puzzle that is helping to impact a really, really complex issue.”

In the meantime, Joan Anderson, 55, said she’s excited to get to work supporting patients, especially from rural areas around Albany.

“I feel like I’m equipped to go out and be that voice, be that person that our community needs so bad,” said Ms. Anderson, a graduate of the Morehouse School of Medicine doula program. “I am encouraged to know that I will be joining in that mission, that fight for us, as far as maternal health is concerned.”

Ms. Anderson said that someday she wants to open a birthing center to provide maternity care. “We do not have one here in southwest Georgia at all,” Ms. Anderson said.

In addition to providing support during and after childbirth, Ms. Anderson and her fellow graduates are trained to assess their patients’ needs and connect them to services such as food assistance, mental health care, transportation to prenatal appointments, and breastfeeding assistance.

Their work is likely to have ripple effects across a largely rural corner of Georgia, said Sherrell Byrd, who co-founded and directs SOWEGA Rising, a nonprofit organization in southwestern Georgia.

“So many of the graduates are part of church networks, they are part of community organizations, some of them are our government workers. They’re very connected,” Ms. Byrd said. “And I think that connectedness is what’s going to help them be successful moving forward.”

This reporting is part of a fellowship with the Association of Health Care Journalists supported by The Commonwealth Fund. It comes from a partnership that includes WABE, NPR, and KFF Health News.

A version of this article first appeared on KFF Health News.

When Bristeria Clark went into labor with her son in 2015, her contractions were steady at first. Then, they stalled. Her cervix stopped dilating. After a few hours, doctors at Phoebe Putney Memorial Hospital in Albany, Georgia, prepped Ms. Clark for an emergency cesarean section.

It wasn’t the vaginal birth Ms. Clark had hoped for during her pregnancy.

“I was freaking out. That was my first child. Like, of course you don’t plan that,” she said. “I just remember the gas pulling up to my face and I ended up going to sleep.”

She remembered feeling a rush of relief when she woke to see that her baby boy was healthy.

Ms. Clark, a 33-year-old nursing student who also works full-time in county government, had another C-section when her second child was born in 2020. This time, the cesarean was planned.

Ms. Clark said she’s grateful the physicians and nurses who delivered both her babies were kind and caring during her labor and delivery. But looking back, she said, she wishes she had had a doula for one-on-one support through pregnancy, childbirth, and the postpartum period. Now she wants to give other women the option she didn’t have.

Ms. Clark is a member of Morehouse School of Medicine’s first class of rural doulas, called Perinatal Patient Navigators.

The program recently graduated a dozen participants, all Black women from southwestern Georgia. They have completed more than 5 months of training and are scheduled to begin working with pregnant and postpartum patients this year.

“We’re developing a workforce that’s going to be providing the support that Black women and birthing people need,” Natalie Hernandez-Green, an associate professor of obstetrics and gynecology at Morehouse School of Medicine, Atlanta, Georgia, said at the doula commencement ceremony in Albany, Georgia.

Albany is Morehouse School of Medicine’s second Perinatal Patient Navigator program site. The first has been up and running in Atlanta since training began in the fall of 2022.

Georgia has one of the highest rates of maternal mortality in the country, according to an analysis by KFF, a health information nonprofit that includes KFF Health News. And Black Georgians are more than twice as likely as White Georgians to die of causes related to pregnancy.

“It doesn’t matter whether you’re rich or poor. Black women are dying at [an] alarming rate from pregnancy-related complications,” said Dr. Hernandez-Green, who is also executive director of the Center for Maternal Health Equity at Morehouse School of Medicine. “And we’re about to change that, one person at a time.”

The presence of a doula, along with regular nursing care, is associated with improved labor and delivery outcomes, reduced stress, and higher rates of patient satisfaction, according to the American College of Obstetricians and Gynecologists.

Multiple studies also link doulas to fewer expensive childbirth interventions, including cesarean births.

Doulas are not medical professionals. They are trained to offer education about the pregnancy and postpartum periods, to guide patients through the healthcare system, and to provide emotional and physical support before, during, and after childbirth.

Morehouse School of Medicine’s program is among a growing number of similar efforts being introduced across the country as more communities look to doulas to help address maternal mortality and poor maternal health outcomes, particularly for Black women and other women of color.

Now that she has graduated, Ms. Clark said she’s looking forward to helping other women in her community as a doula. “To be that person that would be there for my clients, treat them like a sister or like a mother, in a sense of just treating them with utmost respect,” she said. “The ultimate goal is to make them feel comfortable and let them know ‘I’m here to support you.’ ” Her training has inspired her to become an advocate for maternal health issues in southwestern Georgia.

Grants fund Morehouse School of Medicine’s doula program, which costs $350,000 a year to operate. Graduates are given a $2,000 training stipend and the program places five graduates with healthcare providers in southwestern Georgia. Grant money also pays the doulas’ salaries for 1 year. 

“It’s not sustainable if you’re chasing the next grant to fund it,” said Rachel Hardeman, a professor of health and racial equity at the University of Minnesota School of Public Health.

Thirteen states cover doulas through Medicaid, according to the Georgetown University Center for Children and Families.

Dr. Hardeman and others have found that when Medicaid programs cover doula care, states save millions of dollars in healthcare costs. “We were able to calculate the return on investment if Medicaid decided to reimburse doulas for pregnant people who are Medicaid beneficiaries,” she said.

That’s because doulas can help reduce the number of expensive medical interventions during and after birth, and improving delivery outcomes, including reduced cesarean sections.

Doulas can even reduce the likelihood of preterm birth. 

“An infant that is born at a very, very early gestational age is going to require a great deal of resources and interventions to ensure that they survive and then continue to thrive,” Dr. Hardeman said.

There is growing demand for doula services in Georgia, said Fowzio Jama, director of research for Healthy Mothers, Healthy Babies Coalition of Georgia. Her group recently completed a pilot study that offered doula services to about 170 Georgians covered under Medicaid. “We had a wait-list of over 200 clients and we wanted to give them the support that they needed, but we just couldn’t with the given resources that we had,” Ms. Jama said.

Doula services can cost hundreds or thousands of dollars out-of-pocket, making it too expensive for many low-income people, rural communities, and communities of color, many of which suffer from shortages in maternity care, according to the March of Dimes.

The Healthy Mothers, Healthy Babies study found that matching high-risk patients with doulas — particularly doulas from similar racial and ethnic backgrounds — had a positive effect on patients. 

“There was a reduced use of pitocin to induce labor. We saw fewer requests for pain medication. And with our infants, only 6% were low birth weight,” Ms. Jama said.

Still, she and others acknowledge that doulas alone can’t fix the problem of high maternal mortality and morbidity rates.

States, including Georgia, need to do more to bring comprehensive maternity care to communities that need more options, Dr. Hardeman said.

“I think it’s important to understand that doulas are not going to save us, and we should not put that expectation on them. Doulas are a tool,” she said. “They are a piece of the puzzle that is helping to impact a really, really complex issue.”

In the meantime, Joan Anderson, 55, said she’s excited to get to work supporting patients, especially from rural areas around Albany.

“I feel like I’m equipped to go out and be that voice, be that person that our community needs so bad,” said Ms. Anderson, a graduate of the Morehouse School of Medicine doula program. “I am encouraged to know that I will be joining in that mission, that fight for us, as far as maternal health is concerned.”

Ms. Anderson said that someday she wants to open a birthing center to provide maternity care. “We do not have one here in southwest Georgia at all,” Ms. Anderson said.

In addition to providing support during and after childbirth, Ms. Anderson and her fellow graduates are trained to assess their patients’ needs and connect them to services such as food assistance, mental health care, transportation to prenatal appointments, and breastfeeding assistance.

Their work is likely to have ripple effects across a largely rural corner of Georgia, said Sherrell Byrd, who co-founded and directs SOWEGA Rising, a nonprofit organization in southwestern Georgia.

“So many of the graduates are part of church networks, they are part of community organizations, some of them are our government workers. They’re very connected,” Ms. Byrd said. “And I think that connectedness is what’s going to help them be successful moving forward.”

This reporting is part of a fellowship with the Association of Health Care Journalists supported by The Commonwealth Fund. It comes from a partnership that includes WABE, NPR, and KFF Health News.

A version of this article first appeared on KFF Health News.

A breakthrough in medical testing now allows for colorectal cancer screening with just a simple blood test, promising a more accessible and less invasive way to catch the disease early. 

The FDA on July 29 approved the test, called Shield, which can accurately detect tumors in the colon or rectum about 87% of the time when the cancer is in treatable early stages. The approval was announced July 29 by the test’s maker, Guardant Health, and comes just months after promising clinical trial results were published in The New England Journal of Medicine.

Colorectal cancer is among the most common types of cancer diagnosed in the United States each year, along with being one of the leading causes of cancer deaths. The condition is treatable in early stages, but about 1 in 3 people don’t stay up to date on regular screenings, which should begin at age 45.

The simplicity of a blood test could make it more likely for people to be screened for and, ultimately, survive the disease. Other primary screening options include feces-based tests or colonoscopy. The 5-year survival rate for colorectal cancer is 64%.

While highly accurate at detecting DNA shed by tumors during treatable stages of colorectal cancer, the Shield test was not as effective at detecting precancerous areas of tissue, which are typically removed after being detected.

In its news release, Guardant Health officials said they anticipate the test to be covered under Medicare. The out-of-pocket cost for people whose insurance does not cover the test has not yet been announced. The test is expected to be available by next week, The New York Times reported.

If someone’s Shield test comes back positive, the person would then get more tests to confirm the result. Shield was shown in trials to have a 10% false positive rate.

“I was in for a routine physical, and my doctor asked when I had my last colonoscopy,” said John Gormly, a 77-year-old business executive in Newport Beach, California, according to a Guardant Health news release. “I said it’s been a long time, so he offered to give me the Shield blood test. A few days later, the result came back positive, so he referred me for a colonoscopy. It turned out I had stage II colon cancer. The tumor was removed, and I recovered very quickly. Thank God I had taken that blood test.”
 

A version of this article appeared on WebMD.com.

A breakthrough in medical testing now allows for colorectal cancer screening with just a simple blood test, promising a more accessible and less invasive way to catch the disease early. 

The FDA on July 29 approved the test, called Shield, which can accurately detect tumors in the colon or rectum about 87% of the time when the cancer is in treatable early stages. The approval was announced July 29 by the test’s maker, Guardant Health, and comes just months after promising clinical trial results were published in The New England Journal of Medicine.

Colorectal cancer is among the most common types of cancer diagnosed in the United States each year, along with being one of the leading causes of cancer deaths. The condition is treatable in early stages, but about 1 in 3 people don’t stay up to date on regular screenings, which should begin at age 45.

The simplicity of a blood test could make it more likely for people to be screened for and, ultimately, survive the disease. Other primary screening options include feces-based tests or colonoscopy. The 5-year survival rate for colorectal cancer is 64%.

While highly accurate at detecting DNA shed by tumors during treatable stages of colorectal cancer, the Shield test was not as effective at detecting precancerous areas of tissue, which are typically removed after being detected.

In its news release, Guardant Health officials said they anticipate the test to be covered under Medicare. The out-of-pocket cost for people whose insurance does not cover the test has not yet been announced. The test is expected to be available by next week, The New York Times reported.

If someone’s Shield test comes back positive, the person would then get more tests to confirm the result. Shield was shown in trials to have a 10% false positive rate.

“I was in for a routine physical, and my doctor asked when I had my last colonoscopy,” said John Gormly, a 77-year-old business executive in Newport Beach, California, according to a Guardant Health news release. “I said it’s been a long time, so he offered to give me the Shield blood test. A few days later, the result came back positive, so he referred me for a colonoscopy. It turned out I had stage II colon cancer. The tumor was removed, and I recovered very quickly. Thank God I had taken that blood test.”
 

A version of this article appeared on WebMD.com.

A breakthrough in medical testing now allows for colorectal cancer screening with just a simple blood test, promising a more accessible and less invasive way to catch the disease early. 

The FDA on July 29 approved the test, called Shield, which can accurately detect tumors in the colon or rectum about 87% of the time when the cancer is in treatable early stages. The approval was announced July 29 by the test’s maker, Guardant Health, and comes just months after promising clinical trial results were published in The New England Journal of Medicine.

Colorectal cancer is among the most common types of cancer diagnosed in the United States each year, along with being one of the leading causes of cancer deaths. The condition is treatable in early stages, but about 1 in 3 people don’t stay up to date on regular screenings, which should begin at age 45.

The simplicity of a blood test could make it more likely for people to be screened for and, ultimately, survive the disease. Other primary screening options include feces-based tests or colonoscopy. The 5-year survival rate for colorectal cancer is 64%.

While highly accurate at detecting DNA shed by tumors during treatable stages of colorectal cancer, the Shield test was not as effective at detecting precancerous areas of tissue, which are typically removed after being detected.

In its news release, Guardant Health officials said they anticipate the test to be covered under Medicare. The out-of-pocket cost for people whose insurance does not cover the test has not yet been announced. The test is expected to be available by next week, The New York Times reported.

If someone’s Shield test comes back positive, the person would then get more tests to confirm the result. Shield was shown in trials to have a 10% false positive rate.

“I was in for a routine physical, and my doctor asked when I had my last colonoscopy,” said John Gormly, a 77-year-old business executive in Newport Beach, California, according to a Guardant Health news release. “I said it’s been a long time, so he offered to give me the Shield blood test. A few days later, the result came back positive, so he referred me for a colonoscopy. It turned out I had stage II colon cancer. The tumor was removed, and I recovered very quickly. Thank God I had taken that blood test.”
 

A version of this article appeared on WebMD.com.

AstraZeneca was taken to task July 25 by the US Food and Drug Administration’s (FDA’s) Oncology Drug Advisory Committee (ODAC) for failing to heed an agency request about the design of a durvalumab (Imfinzi) trial for non–small cell lung cancer (NSCLC).

The trial in question, AEGEAN, investigated perioperative durvalumab for resectable NSCLC tumors across 802 patients. Patients without EGFR or ALK mutations were randomly assigned to receive durvalumab before surgery alongside platinum-containing chemotherapy and after surgery for a year as monotherapy or to receive chemotherapy and surgery alone. 

Patients receiving durvalumab demonstrated better event-free survival at 1 year (73.4% vs 64.5% without durvalumab) and a better pathologic complete response rate (17.2% vs 4.3% without). Currently, AstraZeneca is seeking to add the indication for durvalumab to those the agent already has. 

However, at the July 25 ODAC meeting, the committee explained that the AEGEAN trial design makes it impossible to tell whether patients benefited from durvalumab before surgery, after it, or at both points. 

Mounting evidence, including from AstraZeneca’s own studies, suggests that the benefit of immune checkpoint inhibitors, such as durvalumab, comes before surgery. That means prescribing durvalumab after surgery could be exposing patients to serious side effects and financial toxicity, with potentially no clinical benefit, “magnifying the risk of potential overtreatment,” the committee cautioned. 

When AEGEAN was being designed in 2018, FDA requested that AstraZeneca address the uncertainty surrounding when to use durvalumab by including separate neoadjuvant and adjuvant arms, or at least an arm where patients were treated with neoadjuvant durvalumab alone to compare with treatment both before and after surgery. 

The company didn’t follow through and, during the July 25 meeting, the committee wanted answers. “Why did you not comply with this?” asked ODAC committee acting chair Daniel Spratt, MD, a radiation oncologist at Case Western Reserve University in Cleveland, Ohio. 

AstraZeneca personnel explained that doing so would have required many more subjects, made the trial more expensive, and added about 2 years to AEGEAN.

One speaker noted that the company, which makes more than $4 billion a year on durvalumab, would have taken about 2 days to recoup that added cost. Others wondered whether the motive was to sell durvalumab for as long as possible across a patient’s course of treatment. 

Perhaps the biggest reason the company ignored the request is that “it wasn’t our understanding at that time that this was a barrier to approval,” an AstraZeneca regulatory affairs specialist said. 

To this end, the agency asked its advisory panel to vote on whether it should require — instead of simply request, as it did with AstraZeneca — companies to prove that patients need immunotherapy both before and after surgery in resectable NSCLC.

The 11-member panel voted unanimously that it should make this a requirement, and several members said it should do so in other cancers as well.

However, when the agency asked whether durvalumab’s resectable NSCLC approval should be delayed until AstraZeneca conducts a trial to answer the neoadjuvant vs adjuvant question, the panel members didn’t think so. 

The consensus was that because AEGEAN showed a decent benefit, patients and physicians should have it as an option, and approval shouldn’t be delayed. The panel said that the bigger question about the benefit of maintenance therapy should be left to future studies. 

FDA usually follows the advice of its advisory panels.
 

A version of this article appeared on Medscape.com.

AstraZeneca was taken to task July 25 by the US Food and Drug Administration’s (FDA’s) Oncology Drug Advisory Committee (ODAC) for failing to heed an agency request about the design of a durvalumab (Imfinzi) trial for non–small cell lung cancer (NSCLC).

The trial in question, AEGEAN, investigated perioperative durvalumab for resectable NSCLC tumors across 802 patients. Patients without EGFR or ALK mutations were randomly assigned to receive durvalumab before surgery alongside platinum-containing chemotherapy and after surgery for a year as monotherapy or to receive chemotherapy and surgery alone. 

Patients receiving durvalumab demonstrated better event-free survival at 1 year (73.4% vs 64.5% without durvalumab) and a better pathologic complete response rate (17.2% vs 4.3% without). Currently, AstraZeneca is seeking to add the indication for durvalumab to those the agent already has. 

However, at the July 25 ODAC meeting, the committee explained that the AEGEAN trial design makes it impossible to tell whether patients benefited from durvalumab before surgery, after it, or at both points. 

Mounting evidence, including from AstraZeneca’s own studies, suggests that the benefit of immune checkpoint inhibitors, such as durvalumab, comes before surgery. That means prescribing durvalumab after surgery could be exposing patients to serious side effects and financial toxicity, with potentially no clinical benefit, “magnifying the risk of potential overtreatment,” the committee cautioned. 

When AEGEAN was being designed in 2018, FDA requested that AstraZeneca address the uncertainty surrounding when to use durvalumab by including separate neoadjuvant and adjuvant arms, or at least an arm where patients were treated with neoadjuvant durvalumab alone to compare with treatment both before and after surgery. 

The company didn’t follow through and, during the July 25 meeting, the committee wanted answers. “Why did you not comply with this?” asked ODAC committee acting chair Daniel Spratt, MD, a radiation oncologist at Case Western Reserve University in Cleveland, Ohio. 

AstraZeneca personnel explained that doing so would have required many more subjects, made the trial more expensive, and added about 2 years to AEGEAN.

One speaker noted that the company, which makes more than $4 billion a year on durvalumab, would have taken about 2 days to recoup that added cost. Others wondered whether the motive was to sell durvalumab for as long as possible across a patient’s course of treatment. 

Perhaps the biggest reason the company ignored the request is that “it wasn’t our understanding at that time that this was a barrier to approval,” an AstraZeneca regulatory affairs specialist said. 

To this end, the agency asked its advisory panel to vote on whether it should require — instead of simply request, as it did with AstraZeneca — companies to prove that patients need immunotherapy both before and after surgery in resectable NSCLC.

The 11-member panel voted unanimously that it should make this a requirement, and several members said it should do so in other cancers as well.

However, when the agency asked whether durvalumab’s resectable NSCLC approval should be delayed until AstraZeneca conducts a trial to answer the neoadjuvant vs adjuvant question, the panel members didn’t think so. 

The consensus was that because AEGEAN showed a decent benefit, patients and physicians should have it as an option, and approval shouldn’t be delayed. The panel said that the bigger question about the benefit of maintenance therapy should be left to future studies. 

FDA usually follows the advice of its advisory panels.
 

A version of this article appeared on Medscape.com.

AstraZeneca was taken to task July 25 by the US Food and Drug Administration’s (FDA’s) Oncology Drug Advisory Committee (ODAC) for failing to heed an agency request about the design of a durvalumab (Imfinzi) trial for non–small cell lung cancer (NSCLC).

The trial in question, AEGEAN, investigated perioperative durvalumab for resectable NSCLC tumors across 802 patients. Patients without EGFR or ALK mutations were randomly assigned to receive durvalumab before surgery alongside platinum-containing chemotherapy and after surgery for a year as monotherapy or to receive chemotherapy and surgery alone. 

Patients receiving durvalumab demonstrated better event-free survival at 1 year (73.4% vs 64.5% without durvalumab) and a better pathologic complete response rate (17.2% vs 4.3% without). Currently, AstraZeneca is seeking to add the indication for durvalumab to those the agent already has. 

However, at the July 25 ODAC meeting, the committee explained that the AEGEAN trial design makes it impossible to tell whether patients benefited from durvalumab before surgery, after it, or at both points. 

Mounting evidence, including from AstraZeneca’s own studies, suggests that the benefit of immune checkpoint inhibitors, such as durvalumab, comes before surgery. That means prescribing durvalumab after surgery could be exposing patients to serious side effects and financial toxicity, with potentially no clinical benefit, “magnifying the risk of potential overtreatment,” the committee cautioned. 

When AEGEAN was being designed in 2018, FDA requested that AstraZeneca address the uncertainty surrounding when to use durvalumab by including separate neoadjuvant and adjuvant arms, or at least an arm where patients were treated with neoadjuvant durvalumab alone to compare with treatment both before and after surgery. 

The company didn’t follow through and, during the July 25 meeting, the committee wanted answers. “Why did you not comply with this?” asked ODAC committee acting chair Daniel Spratt, MD, a radiation oncologist at Case Western Reserve University in Cleveland, Ohio. 

AstraZeneca personnel explained that doing so would have required many more subjects, made the trial more expensive, and added about 2 years to AEGEAN.

One speaker noted that the company, which makes more than $4 billion a year on durvalumab, would have taken about 2 days to recoup that added cost. Others wondered whether the motive was to sell durvalumab for as long as possible across a patient’s course of treatment. 

Perhaps the biggest reason the company ignored the request is that “it wasn’t our understanding at that time that this was a barrier to approval,” an AstraZeneca regulatory affairs specialist said. 

To this end, the agency asked its advisory panel to vote on whether it should require — instead of simply request, as it did with AstraZeneca — companies to prove that patients need immunotherapy both before and after surgery in resectable NSCLC.

The 11-member panel voted unanimously that it should make this a requirement, and several members said it should do so in other cancers as well.

However, when the agency asked whether durvalumab’s resectable NSCLC approval should be delayed until AstraZeneca conducts a trial to answer the neoadjuvant vs adjuvant question, the panel members didn’t think so. 

The consensus was that because AEGEAN showed a decent benefit, patients and physicians should have it as an option, and approval shouldn’t be delayed. The panel said that the bigger question about the benefit of maintenance therapy should be left to future studies. 

FDA usually follows the advice of its advisory panels.
 

A version of this article appeared on Medscape.com.

Arisa E. Ortiz, MD, began her term as president of the American Society for Laser Medicine and Surgery (ASLMS) during the organization’s annual meeting in April 2024.

After earning her medical degree from Albany Medical College, Albany, New York, Dr. Ortiz, a native of Los Angeles, completed her dermatology residency training at the University of California, Irvine, and the university’s Beckman Laser Institute. Next, she completed a laser and cosmetic dermatology fellowship at Massachusetts General Hospital, Harvard Medical School, and the Wellman Center for Photomedicine, all in Boston, and acquired additional fellowship training in Mohs micrographic surgery at the University of California, San Diego (UCSD). Dr. Ortiz is currently director of laser and cosmetic dermatology and a clinical professor of dermatology at UCSD.

Dr. Arisa E. Ortiz

She has authored more than 60 publications on new innovations in cutaneous surgery and is a frequent speaker at meetings of the American Academy of Dermatology, the American Society for Dermatologic Surgery (ASDS), and ASLMS, and she cochairs the annual Masters of Aesthetics Symposium in San Diego. Dr. Ortiz has received several awards, including the 2024 Castle Connolly Top Doctor Award and the Exceptional Women in Medicine Award; Newsweek America’s Best Dermatologists; the ASLMS Dr. Horace Furumoto Young Investigator Award, the ASLMS Best of Session Award for Cutaneous Applications, and the ASDS President’s Outstanding Service Award. Her primary research focuses on the laser treatment of nonmelanoma skin cancer.

In an interview, Dr. Ortiz spoke about her goals as ASLMS president and other topics related to dermatology.

Who inspired you most to become a doctor?

I’ve wanted to become a doctor for as long as I can remember. My fascination with science and the idea of helping people improve their health were driving forces. However, my biggest influence early on was my uncle, who was a pediatrician. His dedication and passion for medicine deeply inspired me and solidified my desire to pursue a career in healthcare.


I understand that a bout with chickenpox as a teenager influenced your decision to specialize in dermatology.

It’s an interesting and somewhat humorous story. When I was 18, I contracted chickenpox and ended up with scars on my face. It was a tough experience as a teenager, but it’s fascinating how such events can shape your life. In my quest for help, I opened the Yellow Pages and randomly chose a dermatologist nearby, who turned out to be Gary Lask, MD, director of lasers at UCLA [University of California, Los Angeles]. During our visit, I mentioned that I was premed, and he encouraged me to consider dermatology. About 6 years later, as a second-year medical student, I realized my passion for dermatology. I reached out to Dr. Lask and told him: “You were right. I want to be a dermatologist. Now, you have to help me get in!” Today, he remains my mentor, and I am deeply grateful for his guidance and support on this journey.



One of the initiatives for your term as ASLMS president includes a focus on safety standards for lasers and energy-based devices. Why is this important now?

courtesy Dr. Arisa E. Ortiz

Working at the university, I frequently encounter severe complications arising from the improper use of lasers and energy-based devices. As these procedures gain popularity, more providers are offering them, yet often without adequate training. As the world’s premier laser society, it is our duty to ensure patient safety. In the ever-evolving field of laser medicine, it is crucial that we continually strive to enhance the regulation of laser usage, ensuring that patients receive the highest standard of care with minimal risk.



One of the suggestions you have for the safety initiative is to offer a rigorous laser safety certification course with continuing education opportunities as a way foster a culture of heightened safety standards. Please explain what would be included in such a course and how it would align with current efforts to report adverse events such as the ASDS-Northwestern University Cutaneous Procedures Adverse Events Reporting (CAPER) registry and the Food and Drug Administration’s MedWatch Program.

A laser safety certification task force has been established to determine the best approach for developing a comprehensive course. The task force aims to assess the necessity of a formal safety certification in our industry, identify the resources needed to support such a certification, establish general safety protocols to form the content foundation, address potential legal concerns, and outline the process for formal certification program recognition. This exploratory work is expected to conclude by the end of the year. The proposed course may include modules on the fundamentals of laser physics, safe operation techniques, patient selection and management, and emergency protocols. Continuing education opportunities would be considered to keep practitioners updated on the latest advancements and safety protocols in laser medicine, thereby fostering a culture of heightened safety standards.



Another initiative for your term is the rollout of a tattoo removal program for former gang members based on the UCSD Clean Slate Tattoo Removal Program. Please tell us more about your vision for this national program.

UCSD Dermatology, in collaboration with UCSD Global Health, has been involved in the Clean Slate Tattoo Removal Program for the past decade. This initiative supports and rehabilitates former gang members by offering laser tattoo removal, helping them reintegrate into society. My vision is to equip our members with the necessary protocols to implement this outreach initiative in their own communities. By providing opportunities for reform and growth, we aim to foster safer and more inclusive communities nationwide.



You were one of the first clinicians to use a laser to treat basal cell carcinoma (BCC). Who are the ideal candidates for this procedure? Is the technique ready for wide clinical adoption? If not, what kind of studies are needed to make it so?

My research passion lies in optimizing laser treatments for BCC. During my fellowship with R. Rox Anderson, MD, and Mathew Avram, MD, at the MGH Wellman Center for Photomedicine, we conducted a pilot study using the 1064-nm Nd:YAG laser, achieving a 92% clearance rate after one treatment. Inspired by these results, we conducted a larger multicenter study, which demonstrated a 90% clearance rate after a single treatment. I now incorporate this technique into my daily practice. The ideal candidates for this procedure are patients with BCC that do not meet the Mohs Appropriate Use Criteria, such as those with nodular or superficial BCC subtypes on the body, individuals who are poor surgical candidates, or those who are surgically exhausted. However, I do not recommend this treatment for patients who are primarily concerned about facial scarring, particularly younger individuals; in such cases, Mohs surgery still remains the preferred option. While I believe this technique is ready for broader clinical adoption, it requires an understanding of laser endpoints. We are also exploring antibody-targeted gold nanorods to enhance the selectivity and standardization of the treatment.



Who inspires you most in your work today?

My patients are my greatest inspiration. Their trust and dedication motivate me to stay at the forefront of dermatologic advancements, ensuring I provide the most cutting-edge and safe treatments possible. Their commitment drives my relentless pursuit of continuous learning and innovation in the field.

What’s the best advice you can give to female dermatologists seeking leadership positions at the local, state, or national level?

My best advice is to have the courage to ask for what you seek. Societies are always looking for members who are eager to participate and contribute. If you express your interest in becoming more involved, there is likely a position available for you. The more you are willing to contribute to a society, the more likely you will be noticed and excel into higher leadership positions. Take initiative, show your commitment, and don’t hesitate to step forward when opportunities arise.



What’s the one tried-and-true laser- or energy-based procedure that you consider a “must” for your dermatology practice? And why?

Determining a single “must-have” laser- or energy-based procedure is a challenging question as it greatly depends on the specific needs of your patient population. However, one of the most common concerns among patients involves issues like redness and pigmentation. Therefore, having a versatile laser or an intense pulsed light device that effectively targets both red and brown pigmentation is indispensable for most practices.



In your view, what are the top three trends in aesthetic dermatology?

Over the years, I have observed several key trends in aesthetic dermatology:

• Minimally invasive procedures. There is a growing preference for less invasive treatments. Patients increasingly desire minimal downtime while still achieving significant results.
• Advancements in laser and energy-based devices for darker skin. There have been substantial advancements in technologies that are safer and more effective for darker skin tones. These developments play a crucial role in addressing diverse patient needs and providing inclusive dermatologic care.
• Natural aesthetic. I am hopeful that the trend toward an overdone appearance is fading. There seems to be a shift back towards a more natural and conservative aesthetic, emphasizing subtle enhancements over dramatic changes.

What development in dermatology are you most excited about in the next 5 years?

I am most excited to see how artificial intelligence and robotics play a role in energy-based devices.

Dr. Ortiz disclosed having financial relationships with several pharmaceutical and device companies. She is also cochair of the MOAS.

Arisa E. Ortiz, MD, began her term as president of the American Society for Laser Medicine and Surgery (ASLMS) during the organization’s annual meeting in April 2024.

After earning her medical degree from Albany Medical College, Albany, New York, Dr. Ortiz, a native of Los Angeles, completed her dermatology residency training at the University of California, Irvine, and the university’s Beckman Laser Institute. Next, she completed a laser and cosmetic dermatology fellowship at Massachusetts General Hospital, Harvard Medical School, and the Wellman Center for Photomedicine, all in Boston, and acquired additional fellowship training in Mohs micrographic surgery at the University of California, San Diego (UCSD). Dr. Ortiz is currently director of laser and cosmetic dermatology and a clinical professor of dermatology at UCSD.

Dr. Arisa E. Ortiz

She has authored more than 60 publications on new innovations in cutaneous surgery and is a frequent speaker at meetings of the American Academy of Dermatology, the American Society for Dermatologic Surgery (ASDS), and ASLMS, and she cochairs the annual Masters of Aesthetics Symposium in San Diego. Dr. Ortiz has received several awards, including the 2024 Castle Connolly Top Doctor Award and the Exceptional Women in Medicine Award; Newsweek America’s Best Dermatologists; the ASLMS Dr. Horace Furumoto Young Investigator Award, the ASLMS Best of Session Award for Cutaneous Applications, and the ASDS President’s Outstanding Service Award. Her primary research focuses on the laser treatment of nonmelanoma skin cancer.

In an interview, Dr. Ortiz spoke about her goals as ASLMS president and other topics related to dermatology.

Who inspired you most to become a doctor?

I’ve wanted to become a doctor for as long as I can remember. My fascination with science and the idea of helping people improve their health were driving forces. However, my biggest influence early on was my uncle, who was a pediatrician. His dedication and passion for medicine deeply inspired me and solidified my desire to pursue a career in healthcare.


I understand that a bout with chickenpox as a teenager influenced your decision to specialize in dermatology.

It’s an interesting and somewhat humorous story. When I was 18, I contracted chickenpox and ended up with scars on my face. It was a tough experience as a teenager, but it’s fascinating how such events can shape your life. In my quest for help, I opened the Yellow Pages and randomly chose a dermatologist nearby, who turned out to be Gary Lask, MD, director of lasers at UCLA [University of California, Los Angeles]. During our visit, I mentioned that I was premed, and he encouraged me to consider dermatology. About 6 years later, as a second-year medical student, I realized my passion for dermatology. I reached out to Dr. Lask and told him: “You were right. I want to be a dermatologist. Now, you have to help me get in!” Today, he remains my mentor, and I am deeply grateful for his guidance and support on this journey.



One of the initiatives for your term as ASLMS president includes a focus on safety standards for lasers and energy-based devices. Why is this important now?

courtesy Dr. Arisa E. Ortiz

Working at the university, I frequently encounter severe complications arising from the improper use of lasers and energy-based devices. As these procedures gain popularity, more providers are offering them, yet often without adequate training. As the world’s premier laser society, it is our duty to ensure patient safety. In the ever-evolving field of laser medicine, it is crucial that we continually strive to enhance the regulation of laser usage, ensuring that patients receive the highest standard of care with minimal risk.



One of the suggestions you have for the safety initiative is to offer a rigorous laser safety certification course with continuing education opportunities as a way foster a culture of heightened safety standards. Please explain what would be included in such a course and how it would align with current efforts to report adverse events such as the ASDS-Northwestern University Cutaneous Procedures Adverse Events Reporting (CAPER) registry and the Food and Drug Administration’s MedWatch Program.

A laser safety certification task force has been established to determine the best approach for developing a comprehensive course. The task force aims to assess the necessity of a formal safety certification in our industry, identify the resources needed to support such a certification, establish general safety protocols to form the content foundation, address potential legal concerns, and outline the process for formal certification program recognition. This exploratory work is expected to conclude by the end of the year. The proposed course may include modules on the fundamentals of laser physics, safe operation techniques, patient selection and management, and emergency protocols. Continuing education opportunities would be considered to keep practitioners updated on the latest advancements and safety protocols in laser medicine, thereby fostering a culture of heightened safety standards.



Another initiative for your term is the rollout of a tattoo removal program for former gang members based on the UCSD Clean Slate Tattoo Removal Program. Please tell us more about your vision for this national program.

UCSD Dermatology, in collaboration with UCSD Global Health, has been involved in the Clean Slate Tattoo Removal Program for the past decade. This initiative supports and rehabilitates former gang members by offering laser tattoo removal, helping them reintegrate into society. My vision is to equip our members with the necessary protocols to implement this outreach initiative in their own communities. By providing opportunities for reform and growth, we aim to foster safer and more inclusive communities nationwide.



You were one of the first clinicians to use a laser to treat basal cell carcinoma (BCC). Who are the ideal candidates for this procedure? Is the technique ready for wide clinical adoption? If not, what kind of studies are needed to make it so?

My research passion lies in optimizing laser treatments for BCC. During my fellowship with R. Rox Anderson, MD, and Mathew Avram, MD, at the MGH Wellman Center for Photomedicine, we conducted a pilot study using the 1064-nm Nd:YAG laser, achieving a 92% clearance rate after one treatment. Inspired by these results, we conducted a larger multicenter study, which demonstrated a 90% clearance rate after a single treatment. I now incorporate this technique into my daily practice. The ideal candidates for this procedure are patients with BCC that do not meet the Mohs Appropriate Use Criteria, such as those with nodular or superficial BCC subtypes on the body, individuals who are poor surgical candidates, or those who are surgically exhausted. However, I do not recommend this treatment for patients who are primarily concerned about facial scarring, particularly younger individuals; in such cases, Mohs surgery still remains the preferred option. While I believe this technique is ready for broader clinical adoption, it requires an understanding of laser endpoints. We are also exploring antibody-targeted gold nanorods to enhance the selectivity and standardization of the treatment.



Who inspires you most in your work today?

My patients are my greatest inspiration. Their trust and dedication motivate me to stay at the forefront of dermatologic advancements, ensuring I provide the most cutting-edge and safe treatments possible. Their commitment drives my relentless pursuit of continuous learning and innovation in the field.

What’s the best advice you can give to female dermatologists seeking leadership positions at the local, state, or national level?

My best advice is to have the courage to ask for what you seek. Societies are always looking for members who are eager to participate and contribute. If you express your interest in becoming more involved, there is likely a position available for you. The more you are willing to contribute to a society, the more likely you will be noticed and excel into higher leadership positions. Take initiative, show your commitment, and don’t hesitate to step forward when opportunities arise.



What’s the one tried-and-true laser- or energy-based procedure that you consider a “must” for your dermatology practice? And why?

Determining a single “must-have” laser- or energy-based procedure is a challenging question as it greatly depends on the specific needs of your patient population. However, one of the most common concerns among patients involves issues like redness and pigmentation. Therefore, having a versatile laser or an intense pulsed light device that effectively targets both red and brown pigmentation is indispensable for most practices.



In your view, what are the top three trends in aesthetic dermatology?

Over the years, I have observed several key trends in aesthetic dermatology:

• Minimally invasive procedures. There is a growing preference for less invasive treatments. Patients increasingly desire minimal downtime while still achieving significant results.
• Advancements in laser and energy-based devices for darker skin. There have been substantial advancements in technologies that are safer and more effective for darker skin tones. These developments play a crucial role in addressing diverse patient needs and providing inclusive dermatologic care.
• Natural aesthetic. I am hopeful that the trend toward an overdone appearance is fading. There seems to be a shift back towards a more natural and conservative aesthetic, emphasizing subtle enhancements over dramatic changes.

What development in dermatology are you most excited about in the next 5 years?

I am most excited to see how artificial intelligence and robotics play a role in energy-based devices.

Dr. Ortiz disclosed having financial relationships with several pharmaceutical and device companies. She is also cochair of the MOAS.

Arisa E. Ortiz, MD, began her term as president of the American Society for Laser Medicine and Surgery (ASLMS) during the organization’s annual meeting in April 2024.

After earning her medical degree from Albany Medical College, Albany, New York, Dr. Ortiz, a native of Los Angeles, completed her dermatology residency training at the University of California, Irvine, and the university’s Beckman Laser Institute. Next, she completed a laser and cosmetic dermatology fellowship at Massachusetts General Hospital, Harvard Medical School, and the Wellman Center for Photomedicine, all in Boston, and acquired additional fellowship training in Mohs micrographic surgery at the University of California, San Diego (UCSD). Dr. Ortiz is currently director of laser and cosmetic dermatology and a clinical professor of dermatology at UCSD.

Dr. Arisa E. Ortiz

She has authored more than 60 publications on new innovations in cutaneous surgery and is a frequent speaker at meetings of the American Academy of Dermatology, the American Society for Dermatologic Surgery (ASDS), and ASLMS, and she cochairs the annual Masters of Aesthetics Symposium in San Diego. Dr. Ortiz has received several awards, including the 2024 Castle Connolly Top Doctor Award and the Exceptional Women in Medicine Award; Newsweek America’s Best Dermatologists; the ASLMS Dr. Horace Furumoto Young Investigator Award, the ASLMS Best of Session Award for Cutaneous Applications, and the ASDS President’s Outstanding Service Award. Her primary research focuses on the laser treatment of nonmelanoma skin cancer.

In an interview, Dr. Ortiz spoke about her goals as ASLMS president and other topics related to dermatology.

Who inspired you most to become a doctor?

I’ve wanted to become a doctor for as long as I can remember. My fascination with science and the idea of helping people improve their health were driving forces. However, my biggest influence early on was my uncle, who was a pediatrician. His dedication and passion for medicine deeply inspired me and solidified my desire to pursue a career in healthcare.


I understand that a bout with chickenpox as a teenager influenced your decision to specialize in dermatology.

It’s an interesting and somewhat humorous story. When I was 18, I contracted chickenpox and ended up with scars on my face. It was a tough experience as a teenager, but it’s fascinating how such events can shape your life. In my quest for help, I opened the Yellow Pages and randomly chose a dermatologist nearby, who turned out to be Gary Lask, MD, director of lasers at UCLA [University of California, Los Angeles]. During our visit, I mentioned that I was premed, and he encouraged me to consider dermatology. About 6 years later, as a second-year medical student, I realized my passion for dermatology. I reached out to Dr. Lask and told him: “You were right. I want to be a dermatologist. Now, you have to help me get in!” Today, he remains my mentor, and I am deeply grateful for his guidance and support on this journey.



One of the initiatives for your term as ASLMS president includes a focus on safety standards for lasers and energy-based devices. Why is this important now?

courtesy Dr. Arisa E. Ortiz

Working at the university, I frequently encounter severe complications arising from the improper use of lasers and energy-based devices. As these procedures gain popularity, more providers are offering them, yet often without adequate training. As the world’s premier laser society, it is our duty to ensure patient safety. In the ever-evolving field of laser medicine, it is crucial that we continually strive to enhance the regulation of laser usage, ensuring that patients receive the highest standard of care with minimal risk.



One of the suggestions you have for the safety initiative is to offer a rigorous laser safety certification course with continuing education opportunities as a way foster a culture of heightened safety standards. Please explain what would be included in such a course and how it would align with current efforts to report adverse events such as the ASDS-Northwestern University Cutaneous Procedures Adverse Events Reporting (CAPER) registry and the Food and Drug Administration’s MedWatch Program.

A laser safety certification task force has been established to determine the best approach for developing a comprehensive course. The task force aims to assess the necessity of a formal safety certification in our industry, identify the resources needed to support such a certification, establish general safety protocols to form the content foundation, address potential legal concerns, and outline the process for formal certification program recognition. This exploratory work is expected to conclude by the end of the year. The proposed course may include modules on the fundamentals of laser physics, safe operation techniques, patient selection and management, and emergency protocols. Continuing education opportunities would be considered to keep practitioners updated on the latest advancements and safety protocols in laser medicine, thereby fostering a culture of heightened safety standards.



Another initiative for your term is the rollout of a tattoo removal program for former gang members based on the UCSD Clean Slate Tattoo Removal Program. Please tell us more about your vision for this national program.

UCSD Dermatology, in collaboration with UCSD Global Health, has been involved in the Clean Slate Tattoo Removal Program for the past decade. This initiative supports and rehabilitates former gang members by offering laser tattoo removal, helping them reintegrate into society. My vision is to equip our members with the necessary protocols to implement this outreach initiative in their own communities. By providing opportunities for reform and growth, we aim to foster safer and more inclusive communities nationwide.



You were one of the first clinicians to use a laser to treat basal cell carcinoma (BCC). Who are the ideal candidates for this procedure? Is the technique ready for wide clinical adoption? If not, what kind of studies are needed to make it so?

My research passion lies in optimizing laser treatments for BCC. During my fellowship with R. Rox Anderson, MD, and Mathew Avram, MD, at the MGH Wellman Center for Photomedicine, we conducted a pilot study using the 1064-nm Nd:YAG laser, achieving a 92% clearance rate after one treatment. Inspired by these results, we conducted a larger multicenter study, which demonstrated a 90% clearance rate after a single treatment. I now incorporate this technique into my daily practice. The ideal candidates for this procedure are patients with BCC that do not meet the Mohs Appropriate Use Criteria, such as those with nodular or superficial BCC subtypes on the body, individuals who are poor surgical candidates, or those who are surgically exhausted. However, I do not recommend this treatment for patients who are primarily concerned about facial scarring, particularly younger individuals; in such cases, Mohs surgery still remains the preferred option. While I believe this technique is ready for broader clinical adoption, it requires an understanding of laser endpoints. We are also exploring antibody-targeted gold nanorods to enhance the selectivity and standardization of the treatment.



Who inspires you most in your work today?

My patients are my greatest inspiration. Their trust and dedication motivate me to stay at the forefront of dermatologic advancements, ensuring I provide the most cutting-edge and safe treatments possible. Their commitment drives my relentless pursuit of continuous learning and innovation in the field.

What’s the best advice you can give to female dermatologists seeking leadership positions at the local, state, or national level?

My best advice is to have the courage to ask for what you seek. Societies are always looking for members who are eager to participate and contribute. If you express your interest in becoming more involved, there is likely a position available for you. The more you are willing to contribute to a society, the more likely you will be noticed and excel into higher leadership positions. Take initiative, show your commitment, and don’t hesitate to step forward when opportunities arise.



What’s the one tried-and-true laser- or energy-based procedure that you consider a “must” for your dermatology practice? And why?

Determining a single “must-have” laser- or energy-based procedure is a challenging question as it greatly depends on the specific needs of your patient population. However, one of the most common concerns among patients involves issues like redness and pigmentation. Therefore, having a versatile laser or an intense pulsed light device that effectively targets both red and brown pigmentation is indispensable for most practices.



In your view, what are the top three trends in aesthetic dermatology?

Over the years, I have observed several key trends in aesthetic dermatology:

• Minimally invasive procedures. There is a growing preference for less invasive treatments. Patients increasingly desire minimal downtime while still achieving significant results.
• Advancements in laser and energy-based devices for darker skin. There have been substantial advancements in technologies that are safer and more effective for darker skin tones. These developments play a crucial role in addressing diverse patient needs and providing inclusive dermatologic care.
• Natural aesthetic. I am hopeful that the trend toward an overdone appearance is fading. There seems to be a shift back towards a more natural and conservative aesthetic, emphasizing subtle enhancements over dramatic changes.

What development in dermatology are you most excited about in the next 5 years?

I am most excited to see how artificial intelligence and robotics play a role in energy-based devices.

Dr. Ortiz disclosed having financial relationships with several pharmaceutical and device companies. She is also cochair of the MOAS.

On World Brain Day (July 22, 2024), the German Society of Neurology (DGN) and the German Brain Foundation pointed out that too much sugar can harm the brain. The current results of the Global Burden of Diseases study shows that stroke and dementia are among the top 10 causes of death. A healthy, active lifestyle with sufficient exercise and sleep, along with the avoidance of harmful substances like alcohol, nicotine, or excessive sugar, protects the brain.

“Of course, the dose makes the poison as the brain, being the body’s powerhouse, needs glucose to function,” said Frank Erbguth, MD, PhD, president of the German Brain Foundation, in a press release from DGN and the German Brain Foundation. “However, with a permanent increase in blood sugar levels due to too many, too lavish meals and constant snacking on the side, we overload the system and fuel the development of neurologic diseases, particularly dementia and stroke.”

The per capita consumption of sugar was 33.2 kg in 2021/2022, which is almost twice the recommended amount. The German Nutrition Society recommends that no more than 10% of energy come from sugar. With a goal of 2000 kilocalories, that’s 50 g per day, or 18 kg per year. This total includes not only added sugar but also naturally occurring sugar, such as in fruits, honey, or juices.
 

What’s the Mechanism?

High blood sugar levels damage brain blood vessels and promote deposits on the vessel walls, thus reducing blood flow and nutrient supply to brain cells. This process can cause various limitations, as well as vascular dementia.

In Germany, around 250,000 people are diagnosed with dementia annually, and 15%-25% have vascular dementia. That proportion represents between 40,000 and 60,000 new cases each year.

In addition, glycosaminoglycans, which are complex sugar molecules, can directly impair cognition. They affect the function of synapses between nerve cells and, thus, affect neuronal plasticity. Experimental data presented at the 2023 American Chemical Society Congress have shown this phenomenon.

Twenty years ago, a study provided evidence that a diet high in fat and sugar disrupts neuronal plasticity and can impair the function of the hippocampus in the long term. A recent meta-analysis confirms these findings: Although mental performance improves at 2-12 hours after sugar consumption, sustained sugar intake can permanently damage cognitive function.

Diabetes mellitus can indirectly cause brain damage. Since the 1990s, it has been known that patients with type 2 diabetes have a significantly higher risk for dementia. It is suspected that glucose metabolism is also disrupted in neurons, thus contributing to the development of Alzheimer’s disease. Insulin also plays a role in the formation of Alzheimer’s plaques.

The Max Planck Institute for Metabolism Research demonstrated in 2023 that regular consumption of high-sugar and high-fat foods can change the brain. This leads to an increased craving for high-sugar and high-fat foods, which in turn promotes the development of obesity and type 2 diabetes.
 

Reduce Sugar Consumption

DGN and the German Brain Foundation advise minimizing sugar consumption. This process is often challenging, as even a small dose of sugar can trigger the gut to send signals to the brain via the vagus nerve, thus causing a strong craving for more sugar. “This could be the reason why some people quickly eat a whole chocolate bar after just one piece,” said Dr. Erbguth. In addition, dopamine, a “feel-good hormone,” is released in the brain when consuming sugar, thus leading to a desire for more.

“It is wise to break free from this cycle by largely avoiding sugar,” said Peter Berlit, MD, secretary general and spokesperson for DGN. “The effort is worth it, as 40% of all dementia cases and 90% of all strokes are preventable, with many of them linked to industrial sugar,” said Dr. Berlit. DGN and the German Brain Foundation support the call for a tax on particularly sugary beverages. They also pointed out that foods like yogurt or tomato ketchup contain sugar, and alcohol can also significantly raise blood sugar levels.

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

On World Brain Day (July 22, 2024), the German Society of Neurology (DGN) and the German Brain Foundation pointed out that too much sugar can harm the brain. The current results of the Global Burden of Diseases study shows that stroke and dementia are among the top 10 causes of death. A healthy, active lifestyle with sufficient exercise and sleep, along with the avoidance of harmful substances like alcohol, nicotine, or excessive sugar, protects the brain.

“Of course, the dose makes the poison as the brain, being the body’s powerhouse, needs glucose to function,” said Frank Erbguth, MD, PhD, president of the German Brain Foundation, in a press release from DGN and the German Brain Foundation. “However, with a permanent increase in blood sugar levels due to too many, too lavish meals and constant snacking on the side, we overload the system and fuel the development of neurologic diseases, particularly dementia and stroke.”

The per capita consumption of sugar was 33.2 kg in 2021/2022, which is almost twice the recommended amount. The German Nutrition Society recommends that no more than 10% of energy come from sugar. With a goal of 2000 kilocalories, that’s 50 g per day, or 18 kg per year. This total includes not only added sugar but also naturally occurring sugar, such as in fruits, honey, or juices.
 

What’s the Mechanism?

High blood sugar levels damage brain blood vessels and promote deposits on the vessel walls, thus reducing blood flow and nutrient supply to brain cells. This process can cause various limitations, as well as vascular dementia.

In Germany, around 250,000 people are diagnosed with dementia annually, and 15%-25% have vascular dementia. That proportion represents between 40,000 and 60,000 new cases each year.

In addition, glycosaminoglycans, which are complex sugar molecules, can directly impair cognition. They affect the function of synapses between nerve cells and, thus, affect neuronal plasticity. Experimental data presented at the 2023 American Chemical Society Congress have shown this phenomenon.

Twenty years ago, a study provided evidence that a diet high in fat and sugar disrupts neuronal plasticity and can impair the function of the hippocampus in the long term. A recent meta-analysis confirms these findings: Although mental performance improves at 2-12 hours after sugar consumption, sustained sugar intake can permanently damage cognitive function.

Diabetes mellitus can indirectly cause brain damage. Since the 1990s, it has been known that patients with type 2 diabetes have a significantly higher risk for dementia. It is suspected that glucose metabolism is also disrupted in neurons, thus contributing to the development of Alzheimer’s disease. Insulin also plays a role in the formation of Alzheimer’s plaques.

The Max Planck Institute for Metabolism Research demonstrated in 2023 that regular consumption of high-sugar and high-fat foods can change the brain. This leads to an increased craving for high-sugar and high-fat foods, which in turn promotes the development of obesity and type 2 diabetes.
 

Reduce Sugar Consumption

DGN and the German Brain Foundation advise minimizing sugar consumption. This process is often challenging, as even a small dose of sugar can trigger the gut to send signals to the brain via the vagus nerve, thus causing a strong craving for more sugar. “This could be the reason why some people quickly eat a whole chocolate bar after just one piece,” said Dr. Erbguth. In addition, dopamine, a “feel-good hormone,” is released in the brain when consuming sugar, thus leading to a desire for more.

“It is wise to break free from this cycle by largely avoiding sugar,” said Peter Berlit, MD, secretary general and spokesperson for DGN. “The effort is worth it, as 40% of all dementia cases and 90% of all strokes are preventable, with many of them linked to industrial sugar,” said Dr. Berlit. DGN and the German Brain Foundation support the call for a tax on particularly sugary beverages. They also pointed out that foods like yogurt or tomato ketchup contain sugar, and alcohol can also significantly raise blood sugar levels.

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

On World Brain Day (July 22, 2024), the German Society of Neurology (DGN) and the German Brain Foundation pointed out that too much sugar can harm the brain. The current results of the Global Burden of Diseases study shows that stroke and dementia are among the top 10 causes of death. A healthy, active lifestyle with sufficient exercise and sleep, along with the avoidance of harmful substances like alcohol, nicotine, or excessive sugar, protects the brain.

“Of course, the dose makes the poison as the brain, being the body’s powerhouse, needs glucose to function,” said Frank Erbguth, MD, PhD, president of the German Brain Foundation, in a press release from DGN and the German Brain Foundation. “However, with a permanent increase in blood sugar levels due to too many, too lavish meals and constant snacking on the side, we overload the system and fuel the development of neurologic diseases, particularly dementia and stroke.”

The per capita consumption of sugar was 33.2 kg in 2021/2022, which is almost twice the recommended amount. The German Nutrition Society recommends that no more than 10% of energy come from sugar. With a goal of 2000 kilocalories, that’s 50 g per day, or 18 kg per year. This total includes not only added sugar but also naturally occurring sugar, such as in fruits, honey, or juices.
 

What’s the Mechanism?

High blood sugar levels damage brain blood vessels and promote deposits on the vessel walls, thus reducing blood flow and nutrient supply to brain cells. This process can cause various limitations, as well as vascular dementia.

In Germany, around 250,000 people are diagnosed with dementia annually, and 15%-25% have vascular dementia. That proportion represents between 40,000 and 60,000 new cases each year.

In addition, glycosaminoglycans, which are complex sugar molecules, can directly impair cognition. They affect the function of synapses between nerve cells and, thus, affect neuronal plasticity. Experimental data presented at the 2023 American Chemical Society Congress have shown this phenomenon.

Twenty years ago, a study provided evidence that a diet high in fat and sugar disrupts neuronal plasticity and can impair the function of the hippocampus in the long term. A recent meta-analysis confirms these findings: Although mental performance improves at 2-12 hours after sugar consumption, sustained sugar intake can permanently damage cognitive function.

Diabetes mellitus can indirectly cause brain damage. Since the 1990s, it has been known that patients with type 2 diabetes have a significantly higher risk for dementia. It is suspected that glucose metabolism is also disrupted in neurons, thus contributing to the development of Alzheimer’s disease. Insulin also plays a role in the formation of Alzheimer’s plaques.

The Max Planck Institute for Metabolism Research demonstrated in 2023 that regular consumption of high-sugar and high-fat foods can change the brain. This leads to an increased craving for high-sugar and high-fat foods, which in turn promotes the development of obesity and type 2 diabetes.
 

Reduce Sugar Consumption

DGN and the German Brain Foundation advise minimizing sugar consumption. This process is often challenging, as even a small dose of sugar can trigger the gut to send signals to the brain via the vagus nerve, thus causing a strong craving for more sugar. “This could be the reason why some people quickly eat a whole chocolate bar after just one piece,” said Dr. Erbguth. In addition, dopamine, a “feel-good hormone,” is released in the brain when consuming sugar, thus leading to a desire for more.

“It is wise to break free from this cycle by largely avoiding sugar,” said Peter Berlit, MD, secretary general and spokesperson for DGN. “The effort is worth it, as 40% of all dementia cases and 90% of all strokes are preventable, with many of them linked to industrial sugar,” said Dr. Berlit. DGN and the German Brain Foundation support the call for a tax on particularly sugary beverages. They also pointed out that foods like yogurt or tomato ketchup contain sugar, and alcohol can also significantly raise blood sugar levels.

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

Lauren Opladen remembers the agonizing wait all too well.

At age 17, struggling with paralyzing depression after losing her brother to suicide and her father to amyotrophic lateral sclerosis, her teacher suggested she seek help.

So, she did. But she had to spend 3 days inside an emergency department at the University of Rochester Medical Center in Rochester, New York, where the Comprehensive Psychiatric Emergency Program (CPEP) provides immediate care for youth and adults experiencing psychiatric emergencies.

“We were sleeping on a couch just waiting for all these services, when that’s precious time wasted,” Ms. Opladen said.

Ms. Opladen made it through that dark period, and 5 years later, she is a registered nurse at the same hospital. Every day she walks past a new facility she wishes had existed during her troubled teenage years: An urgent care center for children and adolescents experiencing mental health crises.

Brighter Days Pediatric Mental Health Urgent Care Center, Rochester, New York, opened in July as a walk-in clinic offering rapid assessment, crisis intervention, and short-term stabilization, provides referrals to counseling or psychiatric care. Children and adolescents at immediate risk of harming themselves or others, or who need inpatient care, are sent to CPEP or another emergency department in the area.

Similar walk-in facilities linking youth to longer-term services are popping up in nearly a dozen states, including New York, Ohio, Massachusetts, and Wisconsin. The emerging model of care may offer a crucial bridge between traditional outpatient services and emergency room (ER) visits for some young people experiencing mental health crises.

“We’ve seen a significant increase in the number of children and adolescents presenting to emergency departments with mental health concerns,” said Michael A. Scharf, MD, chief of the Division of Child and Adolescent Psychiatry at the University of Rochester Medical Center, who oversees operations at Brighter Days. “These urgent care centers provide a more appropriate setting for many of these cases, offering specialized care without the often overwhelming environment of an ER.”

The urgency of addressing youth behavioral health has become increasingly apparent. The most recent data from the US Centers for Disease Control and Prevention showed that over a 6-month period in 2020, during the early months of the COVID-19 pandemic, visits to the emergency department for mental health problems spiked 24% among children aged 5-11 years and 31% among 12-17-year-olds compared with the same period in 2019. Between March 2021 and February 2022, such emergency visits rose by 22% for teen girls, while falling by 15% for boys ages 5-12 years and 9% for older boys. Most visits occur during the school year.

But staffing shortages and limited physical space are taxing the capacity of the healthcare system to screen, diagnose, and manage these patients, according to a 2023 report published in Pediatrics.
 

Urgent Care: A Misnomer?

Some in the mental health community said the label “urgent” in these centers’ titles is misleading. Brighter Days and similar facilities do not conduct involuntary holds, administer medication, or handle serious cases like psychotic episodes.

David Mathison, MD, senior vice president of clinic operations at PM Pediatrics, a chain of pediatric urgent care clinics in Maryland, said patients and their families may mistakenly believe the centers will address mental health problems quickly.

“It’s really not urgent behavioral health. It’s really just another access point to get behavioral health,” Dr. Mathison said. “Crises in pediatrics are so much more complex” than physical injuries or acute infections, which are the bread and butter of urgent care centers.

“An urgent care center almost implies you’re going to come in for a solution to a simple problem, and it’s going to be done relatively quickly on demand, and it’s just not what the behavioral health centers do,” he said.

Dr. Mathison, who also serves on the executive committee for the section on urgent care at the American Academy of Pediatrics, likened the centers to in-person versions of crisis center hotlines, which offer virtual counseling and talk therapy and may refer individuals to specialists who can provide clinical care over the long term.

Instead, Brighter Days and other centers provide crisis de-escalation for individuals experiencing an exacerbation of a diagnosed mental illness, such a manic episode from bipolar disorder.

“Most places aren’t just going to change their therapy without either contacting their psychiatrist or having psychiatrists on staff,” Dr. Mathison said.

Other challenges at Brighter Days and similar centers include staffing with appropriately trained mental health professionals, given the nationwide shortage of child and adolescent psychiatrists, Dr. Scharf said.

The number of child and adolescent psychiatrists per 100,000 children varies significantly across states. Nationally, the average stands at 14 psychiatrists per 100,000 children, but ranges from as low as 4 to 65, according to the American Academy of Child & Adolescent Psychiatry.

For now, Dr. Scharf said, patients who visit Brighter Days are billed as if they are having a routine pediatric office visit as opposed to a pricier trip to the emergency department. And the center accepts all individuals, regardless of their insurance status.

Ms. Opladen said the urgent care center represents a significant improvement over her experience at the emergency department’s psychiatric triage.

“I saw how awful it was and just the environment,” she said. “The first thing I thought was, what do I need to do to get out of here?”

She said the pediatric mental health urgent care centers are “the complete opposite.” Like Brighter Days, these centers are designed to look more like a pediatrician’s office, with bright welcoming colors and games and toys.

“It’s separated from everything else. There’s a welcome, relaxed space,” she said. “The welcoming feel is just a whole different environment, and that’s really how it should be.”
 

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

Lauren Opladen remembers the agonizing wait all too well.

At age 17, struggling with paralyzing depression after losing her brother to suicide and her father to amyotrophic lateral sclerosis, her teacher suggested she seek help.

So, she did. But she had to spend 3 days inside an emergency department at the University of Rochester Medical Center in Rochester, New York, where the Comprehensive Psychiatric Emergency Program (CPEP) provides immediate care for youth and adults experiencing psychiatric emergencies.

“We were sleeping on a couch just waiting for all these services, when that’s precious time wasted,” Ms. Opladen said.

Ms. Opladen made it through that dark period, and 5 years later, she is a registered nurse at the same hospital. Every day she walks past a new facility she wishes had existed during her troubled teenage years: An urgent care center for children and adolescents experiencing mental health crises.

Brighter Days Pediatric Mental Health Urgent Care Center, Rochester, New York, opened in July as a walk-in clinic offering rapid assessment, crisis intervention, and short-term stabilization, provides referrals to counseling or psychiatric care. Children and adolescents at immediate risk of harming themselves or others, or who need inpatient care, are sent to CPEP or another emergency department in the area.

Similar walk-in facilities linking youth to longer-term services are popping up in nearly a dozen states, including New York, Ohio, Massachusetts, and Wisconsin. The emerging model of care may offer a crucial bridge between traditional outpatient services and emergency room (ER) visits for some young people experiencing mental health crises.

“We’ve seen a significant increase in the number of children and adolescents presenting to emergency departments with mental health concerns,” said Michael A. Scharf, MD, chief of the Division of Child and Adolescent Psychiatry at the University of Rochester Medical Center, who oversees operations at Brighter Days. “These urgent care centers provide a more appropriate setting for many of these cases, offering specialized care without the often overwhelming environment of an ER.”

The urgency of addressing youth behavioral health has become increasingly apparent. The most recent data from the US Centers for Disease Control and Prevention showed that over a 6-month period in 2020, during the early months of the COVID-19 pandemic, visits to the emergency department for mental health problems spiked 24% among children aged 5-11 years and 31% among 12-17-year-olds compared with the same period in 2019. Between March 2021 and February 2022, such emergency visits rose by 22% for teen girls, while falling by 15% for boys ages 5-12 years and 9% for older boys. Most visits occur during the school year.

But staffing shortages and limited physical space are taxing the capacity of the healthcare system to screen, diagnose, and manage these patients, according to a 2023 report published in Pediatrics.
 

Urgent Care: A Misnomer?

Some in the mental health community said the label “urgent” in these centers’ titles is misleading. Brighter Days and similar facilities do not conduct involuntary holds, administer medication, or handle serious cases like psychotic episodes.

David Mathison, MD, senior vice president of clinic operations at PM Pediatrics, a chain of pediatric urgent care clinics in Maryland, said patients and their families may mistakenly believe the centers will address mental health problems quickly.

“It’s really not urgent behavioral health. It’s really just another access point to get behavioral health,” Dr. Mathison said. “Crises in pediatrics are so much more complex” than physical injuries or acute infections, which are the bread and butter of urgent care centers.

“An urgent care center almost implies you’re going to come in for a solution to a simple problem, and it’s going to be done relatively quickly on demand, and it’s just not what the behavioral health centers do,” he said.

Dr. Mathison, who also serves on the executive committee for the section on urgent care at the American Academy of Pediatrics, likened the centers to in-person versions of crisis center hotlines, which offer virtual counseling and talk therapy and may refer individuals to specialists who can provide clinical care over the long term.

Instead, Brighter Days and other centers provide crisis de-escalation for individuals experiencing an exacerbation of a diagnosed mental illness, such a manic episode from bipolar disorder.

“Most places aren’t just going to change their therapy without either contacting their psychiatrist or having psychiatrists on staff,” Dr. Mathison said.

Other challenges at Brighter Days and similar centers include staffing with appropriately trained mental health professionals, given the nationwide shortage of child and adolescent psychiatrists, Dr. Scharf said.

The number of child and adolescent psychiatrists per 100,000 children varies significantly across states. Nationally, the average stands at 14 psychiatrists per 100,000 children, but ranges from as low as 4 to 65, according to the American Academy of Child & Adolescent Psychiatry.

For now, Dr. Scharf said, patients who visit Brighter Days are billed as if they are having a routine pediatric office visit as opposed to a pricier trip to the emergency department. And the center accepts all individuals, regardless of their insurance status.

Ms. Opladen said the urgent care center represents a significant improvement over her experience at the emergency department’s psychiatric triage.

“I saw how awful it was and just the environment,” she said. “The first thing I thought was, what do I need to do to get out of here?”

She said the pediatric mental health urgent care centers are “the complete opposite.” Like Brighter Days, these centers are designed to look more like a pediatrician’s office, with bright welcoming colors and games and toys.

“It’s separated from everything else. There’s a welcome, relaxed space,” she said. “The welcoming feel is just a whole different environment, and that’s really how it should be.”
 

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

Lauren Opladen remembers the agonizing wait all too well.

At age 17, struggling with paralyzing depression after losing her brother to suicide and her father to amyotrophic lateral sclerosis, her teacher suggested she seek help.

So, she did. But she had to spend 3 days inside an emergency department at the University of Rochester Medical Center in Rochester, New York, where the Comprehensive Psychiatric Emergency Program (CPEP) provides immediate care for youth and adults experiencing psychiatric emergencies.

“We were sleeping on a couch just waiting for all these services, when that’s precious time wasted,” Ms. Opladen said.

Ms. Opladen made it through that dark period, and 5 years later, she is a registered nurse at the same hospital. Every day she walks past a new facility she wishes had existed during her troubled teenage years: An urgent care center for children and adolescents experiencing mental health crises.

Brighter Days Pediatric Mental Health Urgent Care Center, Rochester, New York, opened in July as a walk-in clinic offering rapid assessment, crisis intervention, and short-term stabilization, provides referrals to counseling or psychiatric care. Children and adolescents at immediate risk of harming themselves or others, or who need inpatient care, are sent to CPEP or another emergency department in the area.

Similar walk-in facilities linking youth to longer-term services are popping up in nearly a dozen states, including New York, Ohio, Massachusetts, and Wisconsin. The emerging model of care may offer a crucial bridge between traditional outpatient services and emergency room (ER) visits for some young people experiencing mental health crises.

“We’ve seen a significant increase in the number of children and adolescents presenting to emergency departments with mental health concerns,” said Michael A. Scharf, MD, chief of the Division of Child and Adolescent Psychiatry at the University of Rochester Medical Center, who oversees operations at Brighter Days. “These urgent care centers provide a more appropriate setting for many of these cases, offering specialized care without the often overwhelming environment of an ER.”

The urgency of addressing youth behavioral health has become increasingly apparent. The most recent data from the US Centers for Disease Control and Prevention showed that over a 6-month period in 2020, during the early months of the COVID-19 pandemic, visits to the emergency department for mental health problems spiked 24% among children aged 5-11 years and 31% among 12-17-year-olds compared with the same period in 2019. Between March 2021 and February 2022, such emergency visits rose by 22% for teen girls, while falling by 15% for boys ages 5-12 years and 9% for older boys. Most visits occur during the school year.

But staffing shortages and limited physical space are taxing the capacity of the healthcare system to screen, diagnose, and manage these patients, according to a 2023 report published in Pediatrics.
 

Urgent Care: A Misnomer?

Some in the mental health community said the label “urgent” in these centers’ titles is misleading. Brighter Days and similar facilities do not conduct involuntary holds, administer medication, or handle serious cases like psychotic episodes.

David Mathison, MD, senior vice president of clinic operations at PM Pediatrics, a chain of pediatric urgent care clinics in Maryland, said patients and their families may mistakenly believe the centers will address mental health problems quickly.

“It’s really not urgent behavioral health. It’s really just another access point to get behavioral health,” Dr. Mathison said. “Crises in pediatrics are so much more complex” than physical injuries or acute infections, which are the bread and butter of urgent care centers.

“An urgent care center almost implies you’re going to come in for a solution to a simple problem, and it’s going to be done relatively quickly on demand, and it’s just not what the behavioral health centers do,” he said.

Dr. Mathison, who also serves on the executive committee for the section on urgent care at the American Academy of Pediatrics, likened the centers to in-person versions of crisis center hotlines, which offer virtual counseling and talk therapy and may refer individuals to specialists who can provide clinical care over the long term.

Instead, Brighter Days and other centers provide crisis de-escalation for individuals experiencing an exacerbation of a diagnosed mental illness, such a manic episode from bipolar disorder.

“Most places aren’t just going to change their therapy without either contacting their psychiatrist or having psychiatrists on staff,” Dr. Mathison said.

Other challenges at Brighter Days and similar centers include staffing with appropriately trained mental health professionals, given the nationwide shortage of child and adolescent psychiatrists, Dr. Scharf said.

The number of child and adolescent psychiatrists per 100,000 children varies significantly across states. Nationally, the average stands at 14 psychiatrists per 100,000 children, but ranges from as low as 4 to 65, according to the American Academy of Child & Adolescent Psychiatry.

For now, Dr. Scharf said, patients who visit Brighter Days are billed as if they are having a routine pediatric office visit as opposed to a pricier trip to the emergency department. And the center accepts all individuals, regardless of their insurance status.

Ms. Opladen said the urgent care center represents a significant improvement over her experience at the emergency department’s psychiatric triage.

“I saw how awful it was and just the environment,” she said. “The first thing I thought was, what do I need to do to get out of here?”

She said the pediatric mental health urgent care centers are “the complete opposite.” Like Brighter Days, these centers are designed to look more like a pediatrician’s office, with bright welcoming colors and games and toys.

“It’s separated from everything else. There’s a welcome, relaxed space,” she said. “The welcoming feel is just a whole different environment, and that’s really how it should be.”
 

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

Now, 75 years after the first presentations were made on the “sensational” effects of cortisone in the treatment of rheumatoid arthritis (RA), glucocorticoids (GCs) are still highly relevant and widely used in the management of RA and other immune-mediated inflammatory diseases.

“It makes me smile because this is such an old drug, and we need it still so much. It still hasn’t been replaced,” Josef S. Smolen, MD, observed at annual European Congress of Rheumatology.

At low doses, GCs are highly effective as anti-inflammatory and anti-destructive agents in RA and many other diseases, said Dr. Smolen, a rheumatologist and immunologist and professor emeritus at the Medical University of Vienna, Austria.

But even after all this time, the mechanisms that lead to efficacy vs toxicity have yet to be clarified. “Such separation may provide further insights into future treatment options,” said Dr. Smolen.

Sara Freeman/MDedge News

Societies Agree: Discontinue as Fast as Possible

GCs have been associated with a long list of adverse events, most notably Cushing syndrome, hypertension, cardiovascular disease, osteoporosis, myopathy, peptic ulcer, adrenal insufficiency (AI), infections, mood disorders, ophthalmologic disorders such as cataracts, skin disorders, menstrual septic necrosis, and pancreatitis.

Dose matters, Dr. Smolen said, citing studies that found that cumulative GC doses of 1000 or 1100 mg increase risks. One study by German researchers found that doses above 10 mg/d significantly raised the hazard ratio for death.

Because high disease activity is also associated with an equally high mortality risk, “we have to balance this out: Active disease vs glucocorticoid use, especially in countries that have less access to modern therapies than we have in the more affluent Western regions,” Dr. Smolen said.

Rheumatology societies generally agree that clinicians should try to minimize GC use or eventually discontinue the therapy.

The American College of Rheumatology recommends not using GCs as part of the first-line treatment of RA. “And if you want to use [them], you should do that for less than 3 months, taper and discontinue as fast as possible, and use the lowest dose possible,” Dr. Adami said.

EULAR’s recommendation is more nuanced in that it allows for a lower dose but gives physicians more choice in how they want to handle GCs, Dr. Adami said. The task force added that all patients should try to taper down or discontinue as fast as possible, he said.

For GCs in the management of systemic lupus erythematosus, a EULAR task force recommended that the type and severity of organ involvement should determine dose, with a long-term goal of maintaining the dose < 5 mg/d or possibly withdrawing it.

EULAR also recommends GC bridging when initiating or changing conventional synthetic (cs) DMARDs. This effectively dismisses the use of GCs when using biologic DMARDs or targeted synthetic DMARDs. As a bridging therapy, EULAR recommends either a single parenteral dose of GC or a predefined tapering or discontinuation scheme within 3 months, when starting an oral GC.
 

Low-Dose Approach Gains Ground

While saying he’d be the first physician to eliminate GCs whenever possible, Dr. Buttgereit made the case before the EULAR Congress that GCs in low doses could still play a role in treatment.

Many physicians believe that very low doses between 2 and 4 mg/d are a realistic therapy option for RA, he said, adding that a mean daily usage < 5 mg could be used over a longer period with relatively low risk.

Several studies he coauthored tested the 5-mg approach. The GLORIA trial compared 5 mg/d prednisolone and placebo in 451 patients aged 65 years and older with active RA over the course of 2 years. The researchers found that patients on prednisolone had a mean Disease Activity Score in 28 joints (DAS28) that was 0.37 points lower and mean joint damage score that was 1.7 points lower than those of patients on placebo, suggesting that the GC had long-term benefits in these patients with RA.

The tradeoff was a 24% increase in the risk of having at least one adverse event of special interest, but most of these events were non-severe infections, Dr. Buttgereit said.

Another study, the SEMIRA trial, assigned 128 patients to a continued regimen of prednisone 5 mg/d for 24 weeks. Another group of 131 patients received a tapered-prednisone regimen. All patients received tocilizumab 162 mg with or without csDMARDs, maintained at stable doses.

Patients in the first cohort achieved superior disease activity control than those in the tapered regimen group. “The side effects showed that in the tapering prednisone group, there were more treatment-emergent adverse effects in this double-blind trial as compared to the continued prednisone group,” Dr. Buttgereit said.

One limitation of the SEMIRA trial was that it studied the effect of tocilizumab as a GC-sparing agent, and it didn’t consider using a tumor necrosis factor or Janus kinase (JAK) inhibitor, which might have a more potent effect on pain and GC dose reduction, Dr. Adami said. “Why do we need to use glucocorticoids if we know they might be detrimental, if we know there might be some other option in our armamentarium?”

Other studies have shown that low-dose GC protocols can be used with standard treatment, according to Sebastian E. Sattui, MD, assistant professor of medicine and director of the Vasculitis Center at the University of Pittsburgh School of Medicine.

“Examples of this are the LoVAS and PEXIVAS studies for antineutrophil cytoplasmic antibody-associated [ANCA] vasculitis. This has been highlighted in existing treatment recommendations for ANCA vasculitis and systemic lupus erythematosus nephritis,” Dr. Sattui said.

Debating the Toxicity Threshold

Are low GC dosages significantly associated with adverse events like mortality, cardiovascular, or diabetes risk? It depends on who you ask.

Much of the toxicity data on GCs come from inadequately powered or controlled studies and often refer to doses that currently are considered too high, Dr. Buttgereit said. His presentation highlighted a study from Hong Kong, a time-varying analysis of GC dose and incident risk for major adverse cardiovascular events (MACE) in more than 12,000 patients with RA. Researchers found that GC regimens ≥ 5 mg/d significantly increased the risk for MACE. Comparatively, doses below this threshold did not confer excessive risk, he said.

Low-dose GCs are lesser toxic than high-dose GCs, noted Joan Merrill, MD, a professor with the Arthritis and Clinical Immunology Research Program at The University of Oklahoma Health Sciences Center, Oklahoma City. “There may be less weight gain, less chance of acne, and less risk for all the slower, more organ-threatening side effects.”

Bianca Nogrady/MDedge News

Tapering Options Across Diseases

Rheumatologists in the field continue to navigate GC-tapering options and treatment combinations that reduce the cumulative use of GCs over time, finding their own solutions based on the conditions they treat.

In his EULAR presentation, Dr. Buttgereit suggested that current therapeutic approaches for RA may be too narrow when they don’t consider the possibility of including very low doses of GCs.

For RA, “why shouldn’t we not do a combination of something like methotrexate plus a JAK inhibitor or a biological,” plus a very low dose of GCs < 5 mg/d, he asked.

However, Dr. Adami said he generally avoids GCs if RA disease activity is not severe (based on DAS28) and if the patient has a visual analog scale pain score < 7. “Nonetheless, even in patients with more severe disease, I would avoid GCs for more than 3 months. Usually, 1 month of steroids, tapered rapidly and discontinued.”

All patients should receive an appropriate treat-to-target strategy with csDMARDs and biologics if needed, he added.

A patient coming to clinic with difficult-to-treat RA who chronically uses GCs deserves special attention. The priority is bone protection with an anti-osteoporosis medication. “I found that JAK inhibitors, in some cases, help with the discontinuation of steroids, especially in those with residual pain. Therefore, I would think of switching medication,” Dr. Adami said.

For polymyalgia rheumatica, most clinicians will likely try to taper GCs around 52 weeks, similar to ACR/EULAR guidelines, according to Robert F. Spiera, MD, director of the Scleroderma and Vasculitis Program at Hospital for Special Surgery, New York City.

Hospital for Special Surgery

What to Consider for AI Symptoms

Clinicians also need to address AI in patients who are coming off GCs, Dr. Sattui said. He advised that symptoms suggestive of AI, including malaise, fatigue, nausea, and muscle and/or joint pain, should guide testing.

Even in the absence of symptoms, clinicians should consider assessing patients who have been on high doses for prolonged periods or obese or older adults who might be at a high risk for AI. “Signs to consider include weight loss, hypotension, or orthostatism,” he said.

Differentiating between AI symptoms and symptoms from the underlying disease can be a challenge. This requires a physical exam and workup, including morning serum cortisol. Collaboration with endocrinology colleagues and other treating providers is important, as well as patient education of symptoms and monitoring for possible adjustments in treating AI and other acute diseases, he said.

Dr. Smolen received research grants from AbbVie, AstraZeneca, Galapagos, and Eli Lilly. Dr. Adami received speaker fees and/or was a consultant for Galapagos, Theramex, Amgen, Eli Lilly, UCB, Fresenius Kabi, Bristol Myers Squibb, Abiogen, and Pfizer. Dr. Buttgereit’s disclosures included AbbVie, AstraZeneca, Grünenthal, Horizon Therapeutics, Mundipharma, Pfizer, and Roche. Dr. Merrill had no relevant disclosures. Dr. Spiera has been a consultant for Roche-Genentech, GlaxoSmithKline, Sanofi, ChemoCentryx, Novartis, Galderma, Cytori, AstraZeneca, Amgen, and AbbVie and received research grant support from GlaxoSmithKline, Roche-Genentech, AstraZeneca, Bristol Myers Squibb, Kadmon, Boehringer Ingelheim, Cytori, ChemoCentryx, Corbus, Novartis, Amgen, and AbbVie. Dr. Sattui reported receiving research support from AstraZeneca and GlaxoSmithKline (clinical trials), receiving consulting fees from Sanofi (funds toward research support), serving on advisory boards for Sanofi and Amgen (funds toward research support), and receiving speaker fees from Fresenius Kabi (funds toward research support).
 

A version of this article appeared on Medscape.com.

Now, 75 years after the first presentations were made on the “sensational” effects of cortisone in the treatment of rheumatoid arthritis (RA), glucocorticoids (GCs) are still highly relevant and widely used in the management of RA and other immune-mediated inflammatory diseases.

“It makes me smile because this is such an old drug, and we need it still so much. It still hasn’t been replaced,” Josef S. Smolen, MD, observed at annual European Congress of Rheumatology.

At low doses, GCs are highly effective as anti-inflammatory and anti-destructive agents in RA and many other diseases, said Dr. Smolen, a rheumatologist and immunologist and professor emeritus at the Medical University of Vienna, Austria.

But even after all this time, the mechanisms that lead to efficacy vs toxicity have yet to be clarified. “Such separation may provide further insights into future treatment options,” said Dr. Smolen.

Sara Freeman/MDedge News

Societies Agree: Discontinue as Fast as Possible

GCs have been associated with a long list of adverse events, most notably Cushing syndrome, hypertension, cardiovascular disease, osteoporosis, myopathy, peptic ulcer, adrenal insufficiency (AI), infections, mood disorders, ophthalmologic disorders such as cataracts, skin disorders, menstrual septic necrosis, and pancreatitis.

Dose matters, Dr. Smolen said, citing studies that found that cumulative GC doses of 1000 or 1100 mg increase risks. One study by German researchers found that doses above 10 mg/d significantly raised the hazard ratio for death.

Because high disease activity is also associated with an equally high mortality risk, “we have to balance this out: Active disease vs glucocorticoid use, especially in countries that have less access to modern therapies than we have in the more affluent Western regions,” Dr. Smolen said.

Rheumatology societies generally agree that clinicians should try to minimize GC use or eventually discontinue the therapy.

The American College of Rheumatology recommends not using GCs as part of the first-line treatment of RA. “And if you want to use [them], you should do that for less than 3 months, taper and discontinue as fast as possible, and use the lowest dose possible,” Dr. Adami said.

EULAR’s recommendation is more nuanced in that it allows for a lower dose but gives physicians more choice in how they want to handle GCs, Dr. Adami said. The task force added that all patients should try to taper down or discontinue as fast as possible, he said.

For GCs in the management of systemic lupus erythematosus, a EULAR task force recommended that the type and severity of organ involvement should determine dose, with a long-term goal of maintaining the dose < 5 mg/d or possibly withdrawing it.

EULAR also recommends GC bridging when initiating or changing conventional synthetic (cs) DMARDs. This effectively dismisses the use of GCs when using biologic DMARDs or targeted synthetic DMARDs. As a bridging therapy, EULAR recommends either a single parenteral dose of GC or a predefined tapering or discontinuation scheme within 3 months, when starting an oral GC.
 

Low-Dose Approach Gains Ground

While saying he’d be the first physician to eliminate GCs whenever possible, Dr. Buttgereit made the case before the EULAR Congress that GCs in low doses could still play a role in treatment.

Many physicians believe that very low doses between 2 and 4 mg/d are a realistic therapy option for RA, he said, adding that a mean daily usage < 5 mg could be used over a longer period with relatively low risk.

Several studies he coauthored tested the 5-mg approach. The GLORIA trial compared 5 mg/d prednisolone and placebo in 451 patients aged 65 years and older with active RA over the course of 2 years. The researchers found that patients on prednisolone had a mean Disease Activity Score in 28 joints (DAS28) that was 0.37 points lower and mean joint damage score that was 1.7 points lower than those of patients on placebo, suggesting that the GC had long-term benefits in these patients with RA.

The tradeoff was a 24% increase in the risk of having at least one adverse event of special interest, but most of these events were non-severe infections, Dr. Buttgereit said.

Another study, the SEMIRA trial, assigned 128 patients to a continued regimen of prednisone 5 mg/d for 24 weeks. Another group of 131 patients received a tapered-prednisone regimen. All patients received tocilizumab 162 mg with or without csDMARDs, maintained at stable doses.

Patients in the first cohort achieved superior disease activity control than those in the tapered regimen group. “The side effects showed that in the tapering prednisone group, there were more treatment-emergent adverse effects in this double-blind trial as compared to the continued prednisone group,” Dr. Buttgereit said.

One limitation of the SEMIRA trial was that it studied the effect of tocilizumab as a GC-sparing agent, and it didn’t consider using a tumor necrosis factor or Janus kinase (JAK) inhibitor, which might have a more potent effect on pain and GC dose reduction, Dr. Adami said. “Why do we need to use glucocorticoids if we know they might be detrimental, if we know there might be some other option in our armamentarium?”

Other studies have shown that low-dose GC protocols can be used with standard treatment, according to Sebastian E. Sattui, MD, assistant professor of medicine and director of the Vasculitis Center at the University of Pittsburgh School of Medicine.

“Examples of this are the LoVAS and PEXIVAS studies for antineutrophil cytoplasmic antibody-associated [ANCA] vasculitis. This has been highlighted in existing treatment recommendations for ANCA vasculitis and systemic lupus erythematosus nephritis,” Dr. Sattui said.

Debating the Toxicity Threshold

Are low GC dosages significantly associated with adverse events like mortality, cardiovascular, or diabetes risk? It depends on who you ask.

Much of the toxicity data on GCs come from inadequately powered or controlled studies and often refer to doses that currently are considered too high, Dr. Buttgereit said. His presentation highlighted a study from Hong Kong, a time-varying analysis of GC dose and incident risk for major adverse cardiovascular events (MACE) in more than 12,000 patients with RA. Researchers found that GC regimens ≥ 5 mg/d significantly increased the risk for MACE. Comparatively, doses below this threshold did not confer excessive risk, he said.

Low-dose GCs are lesser toxic than high-dose GCs, noted Joan Merrill, MD, a professor with the Arthritis and Clinical Immunology Research Program at The University of Oklahoma Health Sciences Center, Oklahoma City. “There may be less weight gain, less chance of acne, and less risk for all the slower, more organ-threatening side effects.”

Bianca Nogrady/MDedge News

Tapering Options Across Diseases

Rheumatologists in the field continue to navigate GC-tapering options and treatment combinations that reduce the cumulative use of GCs over time, finding their own solutions based on the conditions they treat.

In his EULAR presentation, Dr. Buttgereit suggested that current therapeutic approaches for RA may be too narrow when they don’t consider the possibility of including very low doses of GCs.

For RA, “why shouldn’t we not do a combination of something like methotrexate plus a JAK inhibitor or a biological,” plus a very low dose of GCs < 5 mg/d, he asked.

However, Dr. Adami said he generally avoids GCs if RA disease activity is not severe (based on DAS28) and if the patient has a visual analog scale pain score < 7. “Nonetheless, even in patients with more severe disease, I would avoid GCs for more than 3 months. Usually, 1 month of steroids, tapered rapidly and discontinued.”

All patients should receive an appropriate treat-to-target strategy with csDMARDs and biologics if needed, he added.

A patient coming to clinic with difficult-to-treat RA who chronically uses GCs deserves special attention. The priority is bone protection with an anti-osteoporosis medication. “I found that JAK inhibitors, in some cases, help with the discontinuation of steroids, especially in those with residual pain. Therefore, I would think of switching medication,” Dr. Adami said.

For polymyalgia rheumatica, most clinicians will likely try to taper GCs around 52 weeks, similar to ACR/EULAR guidelines, according to Robert F. Spiera, MD, director of the Scleroderma and Vasculitis Program at Hospital for Special Surgery, New York City.

Hospital for Special Surgery

What to Consider for AI Symptoms

Clinicians also need to address AI in patients who are coming off GCs, Dr. Sattui said. He advised that symptoms suggestive of AI, including malaise, fatigue, nausea, and muscle and/or joint pain, should guide testing.

Even in the absence of symptoms, clinicians should consider assessing patients who have been on high doses for prolonged periods or obese or older adults who might be at a high risk for AI. “Signs to consider include weight loss, hypotension, or orthostatism,” he said.

Differentiating between AI symptoms and symptoms from the underlying disease can be a challenge. This requires a physical exam and workup, including morning serum cortisol. Collaboration with endocrinology colleagues and other treating providers is important, as well as patient education of symptoms and monitoring for possible adjustments in treating AI and other acute diseases, he said.

Dr. Smolen received research grants from AbbVie, AstraZeneca, Galapagos, and Eli Lilly. Dr. Adami received speaker fees and/or was a consultant for Galapagos, Theramex, Amgen, Eli Lilly, UCB, Fresenius Kabi, Bristol Myers Squibb, Abiogen, and Pfizer. Dr. Buttgereit’s disclosures included AbbVie, AstraZeneca, Grünenthal, Horizon Therapeutics, Mundipharma, Pfizer, and Roche. Dr. Merrill had no relevant disclosures. Dr. Spiera has been a consultant for Roche-Genentech, GlaxoSmithKline, Sanofi, ChemoCentryx, Novartis, Galderma, Cytori, AstraZeneca, Amgen, and AbbVie and received research grant support from GlaxoSmithKline, Roche-Genentech, AstraZeneca, Bristol Myers Squibb, Kadmon, Boehringer Ingelheim, Cytori, ChemoCentryx, Corbus, Novartis, Amgen, and AbbVie. Dr. Sattui reported receiving research support from AstraZeneca and GlaxoSmithKline (clinical trials), receiving consulting fees from Sanofi (funds toward research support), serving on advisory boards for Sanofi and Amgen (funds toward research support), and receiving speaker fees from Fresenius Kabi (funds toward research support).
 

A version of this article appeared on Medscape.com.

Now, 75 years after the first presentations were made on the “sensational” effects of cortisone in the treatment of rheumatoid arthritis (RA), glucocorticoids (GCs) are still highly relevant and widely used in the management of RA and other immune-mediated inflammatory diseases.

“It makes me smile because this is such an old drug, and we need it still so much. It still hasn’t been replaced,” Josef S. Smolen, MD, observed at annual European Congress of Rheumatology.

At low doses, GCs are highly effective as anti-inflammatory and anti-destructive agents in RA and many other diseases, said Dr. Smolen, a rheumatologist and immunologist and professor emeritus at the Medical University of Vienna, Austria.

But even after all this time, the mechanisms that lead to efficacy vs toxicity have yet to be clarified. “Such separation may provide further insights into future treatment options,” said Dr. Smolen.

Sara Freeman/MDedge News

Societies Agree: Discontinue as Fast as Possible

GCs have been associated with a long list of adverse events, most notably Cushing syndrome, hypertension, cardiovascular disease, osteoporosis, myopathy, peptic ulcer, adrenal insufficiency (AI), infections, mood disorders, ophthalmologic disorders such as cataracts, skin disorders, menstrual septic necrosis, and pancreatitis.

Dose matters, Dr. Smolen said, citing studies that found that cumulative GC doses of 1000 or 1100 mg increase risks. One study by German researchers found that doses above 10 mg/d significantly raised the hazard ratio for death.

Because high disease activity is also associated with an equally high mortality risk, “we have to balance this out: Active disease vs glucocorticoid use, especially in countries that have less access to modern therapies than we have in the more affluent Western regions,” Dr. Smolen said.

Rheumatology societies generally agree that clinicians should try to minimize GC use or eventually discontinue the therapy.

The American College of Rheumatology recommends not using GCs as part of the first-line treatment of RA. “And if you want to use [them], you should do that for less than 3 months, taper and discontinue as fast as possible, and use the lowest dose possible,” Dr. Adami said.

EULAR’s recommendation is more nuanced in that it allows for a lower dose but gives physicians more choice in how they want to handle GCs, Dr. Adami said. The task force added that all patients should try to taper down or discontinue as fast as possible, he said.

For GCs in the management of systemic lupus erythematosus, a EULAR task force recommended that the type and severity of organ involvement should determine dose, with a long-term goal of maintaining the dose < 5 mg/d or possibly withdrawing it.

EULAR also recommends GC bridging when initiating or changing conventional synthetic (cs) DMARDs. This effectively dismisses the use of GCs when using biologic DMARDs or targeted synthetic DMARDs. As a bridging therapy, EULAR recommends either a single parenteral dose of GC or a predefined tapering or discontinuation scheme within 3 months, when starting an oral GC.
 

Low-Dose Approach Gains Ground

While saying he’d be the first physician to eliminate GCs whenever possible, Dr. Buttgereit made the case before the EULAR Congress that GCs in low doses could still play a role in treatment.

Many physicians believe that very low doses between 2 and 4 mg/d are a realistic therapy option for RA, he said, adding that a mean daily usage < 5 mg could be used over a longer period with relatively low risk.

Several studies he coauthored tested the 5-mg approach. The GLORIA trial compared 5 mg/d prednisolone and placebo in 451 patients aged 65 years and older with active RA over the course of 2 years. The researchers found that patients on prednisolone had a mean Disease Activity Score in 28 joints (DAS28) that was 0.37 points lower and mean joint damage score that was 1.7 points lower than those of patients on placebo, suggesting that the GC had long-term benefits in these patients with RA.

The tradeoff was a 24% increase in the risk of having at least one adverse event of special interest, but most of these events were non-severe infections, Dr. Buttgereit said.

Another study, the SEMIRA trial, assigned 128 patients to a continued regimen of prednisone 5 mg/d for 24 weeks. Another group of 131 patients received a tapered-prednisone regimen. All patients received tocilizumab 162 mg with or without csDMARDs, maintained at stable doses.

Patients in the first cohort achieved superior disease activity control than those in the tapered regimen group. “The side effects showed that in the tapering prednisone group, there were more treatment-emergent adverse effects in this double-blind trial as compared to the continued prednisone group,” Dr. Buttgereit said.

One limitation of the SEMIRA trial was that it studied the effect of tocilizumab as a GC-sparing agent, and it didn’t consider using a tumor necrosis factor or Janus kinase (JAK) inhibitor, which might have a more potent effect on pain and GC dose reduction, Dr. Adami said. “Why do we need to use glucocorticoids if we know they might be detrimental, if we know there might be some other option in our armamentarium?”

Other studies have shown that low-dose GC protocols can be used with standard treatment, according to Sebastian E. Sattui, MD, assistant professor of medicine and director of the Vasculitis Center at the University of Pittsburgh School of Medicine.

“Examples of this are the LoVAS and PEXIVAS studies for antineutrophil cytoplasmic antibody-associated [ANCA] vasculitis. This has been highlighted in existing treatment recommendations for ANCA vasculitis and systemic lupus erythematosus nephritis,” Dr. Sattui said.

Debating the Toxicity Threshold

Are low GC dosages significantly associated with adverse events like mortality, cardiovascular, or diabetes risk? It depends on who you ask.

Much of the toxicity data on GCs come from inadequately powered or controlled studies and often refer to doses that currently are considered too high, Dr. Buttgereit said. His presentation highlighted a study from Hong Kong, a time-varying analysis of GC dose and incident risk for major adverse cardiovascular events (MACE) in more than 12,000 patients with RA. Researchers found that GC regimens ≥ 5 mg/d significantly increased the risk for MACE. Comparatively, doses below this threshold did not confer excessive risk, he said.

Low-dose GCs are lesser toxic than high-dose GCs, noted Joan Merrill, MD, a professor with the Arthritis and Clinical Immunology Research Program at The University of Oklahoma Health Sciences Center, Oklahoma City. “There may be less weight gain, less chance of acne, and less risk for all the slower, more organ-threatening side effects.”

Bianca Nogrady/MDedge News

Tapering Options Across Diseases

Rheumatologists in the field continue to navigate GC-tapering options and treatment combinations that reduce the cumulative use of GCs over time, finding their own solutions based on the conditions they treat.

In his EULAR presentation, Dr. Buttgereit suggested that current therapeutic approaches for RA may be too narrow when they don’t consider the possibility of including very low doses of GCs.

For RA, “why shouldn’t we not do a combination of something like methotrexate plus a JAK inhibitor or a biological,” plus a very low dose of GCs < 5 mg/d, he asked.

However, Dr. Adami said he generally avoids GCs if RA disease activity is not severe (based on DAS28) and if the patient has a visual analog scale pain score < 7. “Nonetheless, even in patients with more severe disease, I would avoid GCs for more than 3 months. Usually, 1 month of steroids, tapered rapidly and discontinued.”

All patients should receive an appropriate treat-to-target strategy with csDMARDs and biologics if needed, he added.

A patient coming to clinic with difficult-to-treat RA who chronically uses GCs deserves special attention. The priority is bone protection with an anti-osteoporosis medication. “I found that JAK inhibitors, in some cases, help with the discontinuation of steroids, especially in those with residual pain. Therefore, I would think of switching medication,” Dr. Adami said.

For polymyalgia rheumatica, most clinicians will likely try to taper GCs around 52 weeks, similar to ACR/EULAR guidelines, according to Robert F. Spiera, MD, director of the Scleroderma and Vasculitis Program at Hospital for Special Surgery, New York City.

Hospital for Special Surgery

What to Consider for AI Symptoms

Clinicians also need to address AI in patients who are coming off GCs, Dr. Sattui said. He advised that symptoms suggestive of AI, including malaise, fatigue, nausea, and muscle and/or joint pain, should guide testing.

Even in the absence of symptoms, clinicians should consider assessing patients who have been on high doses for prolonged periods or obese or older adults who might be at a high risk for AI. “Signs to consider include weight loss, hypotension, or orthostatism,” he said.

Differentiating between AI symptoms and symptoms from the underlying disease can be a challenge. This requires a physical exam and workup, including morning serum cortisol. Collaboration with endocrinology colleagues and other treating providers is important, as well as patient education of symptoms and monitoring for possible adjustments in treating AI and other acute diseases, he said.

Dr. Smolen received research grants from AbbVie, AstraZeneca, Galapagos, and Eli Lilly. Dr. Adami received speaker fees and/or was a consultant for Galapagos, Theramex, Amgen, Eli Lilly, UCB, Fresenius Kabi, Bristol Myers Squibb, Abiogen, and Pfizer. Dr. Buttgereit’s disclosures included AbbVie, AstraZeneca, Grünenthal, Horizon Therapeutics, Mundipharma, Pfizer, and Roche. Dr. Merrill had no relevant disclosures. Dr. Spiera has been a consultant for Roche-Genentech, GlaxoSmithKline, Sanofi, ChemoCentryx, Novartis, Galderma, Cytori, AstraZeneca, Amgen, and AbbVie and received research grant support from GlaxoSmithKline, Roche-Genentech, AstraZeneca, Bristol Myers Squibb, Kadmon, Boehringer Ingelheim, Cytori, ChemoCentryx, Corbus, Novartis, Amgen, and AbbVie. Dr. Sattui reported receiving research support from AstraZeneca and GlaxoSmithKline (clinical trials), receiving consulting fees from Sanofi (funds toward research support), serving on advisory boards for Sanofi and Amgen (funds toward research support), and receiving speaker fees from Fresenius Kabi (funds toward research support).
 

A version of this article appeared on Medscape.com.

New treatment strategies in clinical trials show promise in reducing the tapering time of glucocorticoids (GCs) or possibly even replacing the use of GCs. Selective GC receptor agonists and modulators and GC plus hydroxysteroid dehydrogenase inhibitor combination therapy are some of the approaches under consideration.

“There is growing observational data that confirms the GC-sparing effect seen in some of these clinical trials in real-world data,” said Sebastian E. Sattui, MD, assistant professor of medicine and director of the Vasculitis Center at the University of Pittsburgh Medical Center, Pittsburgh.

GC minimization is an important goal, “and the data emerging from these trials should be reassuring for rheumatology providers,” Dr. Sattui said.

HSD-1 Inhibitors Under Study

11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1) is a tissue-specific intracellular modulator of GC action that’s been trialed for a number of rheumatic conditions. “HSD-1 deficiency or inhibition has been consistently associated with reduced GC side effects in mouse and human,” wrote the authors of a study testing the coadministration of HSD-1 inhibitor SPI-62 (clofutriben) with prednisolone in patients with polymyalgia rheumatica (PMR) to measure its impact on efficacy and toxicity.

Lead study author David Katz, PhD, chief scientific officer at Sparrow Pharmaceuticals, presented results at the at the annual European Congress of Rheumatology.

GCs are often the first-line therapy with PMR. However, it’s very difficult for patients to stop taking GCs once they start taking them. The study included patients with PMR who were taking 10 mg/d prednisolone and didn’t require a dose increase. For the study, they continued prednisolone without dose reduction for 4 weeks, receiving either SPI-62 6 mg/d or a matching placebo for 2 weeks.

During SPI-62 treatment, researchers in sequential cohorts maintained daily prednisolone doses at 10 mg, adjusted to 15 mg or adjusted to 20 mg.

A 10-mg dose of prednisolone combined with 6 mg of SPI-62 demonstrated less efficacy compared with placebo but improved upon prednisolone toxicities such as bone formation and resorption biomarkers, lipidemia, and insulin resistance. Doubling the dose to 20 mg prednisolone combined with SPI-62 achieved similar efficacy and maintained improvement of prednisolone toxicity markers.

“In patients with PMR, when we double the dose of prednisolone during coadministration with a potent HSD-1 inhibitor, we are able to have similar stability of symptoms, physical function, and systemic inflammation. At the same time, we are able to show improvements on biomarkers of bone turnover and insulin resistance,” Dr. Katz informed the EULAR 2024 audience.

An ongoing phase 2 clinical trial is testing SPI-62 in patients with endogenous Cushing syndrome. “It’s a longer-term trial, so we’re able to see at least an individual patient’s more clinical outcomes such as reversal of Cushing’s-associated myopathy and the ability of patients to discontinue all of their antidiabetic medications and yet still have good glycemic control,” he said.

Another research team from the United Kingdom explored whether AZD4017, an inhibitor of human 11ß-HSD1, could mitigate GC effects. The researchers randomly assigned 32 healthy male volunteers to AZD4017 or placebo, along with prednisolone. They reported a worsening of hepatic insulin sensitivity in the placebo group but not in the AZD4017 group, and protective effects of AZD4017 on markers of lipid metabolism and bone turnover, as well as lowered nighttime blood pressure. The results signified that coadministration of AZD4017 with prednisolone in men could be a way to reduce GC side effects.

In a Japanese phase 1/2 study, 11ß-HSD1 inhibitor S-707106 proved useful as an insulin sensitizer and antisarcopenic and anti-obesity medication in 16 patients with Cushing syndrome and autonomous cortisol secretion.
 

Novel Antitumor Necrosis Factor (TNF) Antibody Plus GC Receptor Modulator Conjugate

A novel antibody-drug conjugate comprising the anti-TNF monoclonal antibody adalimumab (ABBV-3373) linked to a GC receptor modulator shows promise as a GC alternative.

A notable 2022 study authored by Frank Buttgereit, MD, and other researchers assessed its safety and efficacy in a randomized, double-blind, active-controlled, proof-of-concept trial.

ABBV-3373 “was designed to potentially allow precise targeting of activated immune cells while significantly dampening inflammation and minimizing the systemic side effects associated with glucocorticoids,” according to AbbVie, its manufacturer.

A total of 48 adults with moderate to severe rheumatoid arthritis receiving background methotrexate were randomized to receive either ABBV-3373 (n = 31) or adalimumab (n = 17). The novel drug at 12 weeks showed a −2.65 reduction in the Disease Activity Score in 28 joints using C-reactive protein, compared with −2.13 for adalimumab. Researchers also predicted ABBV-3373 to be more effective than adalimumab based on in-trial and historical adalimumab data.

“We have great expectations for this molecule,” said Giovanni Adami, MD, PhD, a rheumatologist at the University of Verona, Verona, Italy, who has coauthored several studies on the use of GCs. Plans are underway for a phase 3 study with ABBV-3373.
 

C5a and Interleukin (IL)-6 Receptor Inhibitors as GC-Sparing Drugs

Investigators in a 2021 paper explored whether the C5a receptor inhibitor avacopan could effectively treat patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis without the need for daily GCs, following treatment with either cyclophosphamide or rituximab. They randomized 331 patients to receive avacopan or prednisone given on a tapering schedule for 20 weeks (60 mg/d tapered to discontinuation by week 21). “Avacopan was noninferior but not superior to prednisone taper with respect to remission at week 26 and was superior to prednisone taper with respect to sustained remission at week 52,” the investigators summarized.

A longer trial should test avacopan’s safety and durability in patients with ANCA-associated vasculitis, they recommended.

Sarilumab, a human monoclonal antibody that binds IL-6 receptor alpha and blocks the IL-6 pathway, yielded good results in the phase 3 SAPHYR trial as an alternative for patients with PMR who relapse while tapering prednisone therapy.

Researchers in the SAPHYR trial randomly assigned 118 patients 1:1 to receive a twice-monthly subcutaneous injection of sarilumab over 52 weeks plus a 14-week prednisone taper or placebo plus a 52-week prednisone taper. Patients in each group received a tapered GC dose initially at 15 mg/d for 2 weeks in a blinded fashion to control for disease at baseline.

Sarilumab effectively sustained remission in patients, significantly reducing the GC dose compared with placebo.

Disease flare after clinical remission took place in 57% of patients in the placebo group, vs 24% in the sarilumab group. “The placebo-treated patients had a fairly traditional 52-week GC taper. The patients treated with sarilumab had a very rapid GC taper,” said lead study author Robert Spiera, MD, director of the Scleroderma, Vasculitis and Myositis Center at the Hospital for Special Surgery, New York City.

In his own practice, Dr. Spiera often treats his patients with new-onset PMR with a fairly rapid GC taper, akin to what was used in SAPHYR, recognizing that a portion of these patients can be successfully treated with a relatively brief course of GCs, although the majority will need to have “rescue” therapy for flares with that approach.

Hospital for Special Surgery

A version of this article appeared on Medscape.com.

New treatment strategies in clinical trials show promise in reducing the tapering time of glucocorticoids (GCs) or possibly even replacing the use of GCs. Selective GC receptor agonists and modulators and GC plus hydroxysteroid dehydrogenase inhibitor combination therapy are some of the approaches under consideration.

“There is growing observational data that confirms the GC-sparing effect seen in some of these clinical trials in real-world data,” said Sebastian E. Sattui, MD, assistant professor of medicine and director of the Vasculitis Center at the University of Pittsburgh Medical Center, Pittsburgh.

GC minimization is an important goal, “and the data emerging from these trials should be reassuring for rheumatology providers,” Dr. Sattui said.

HSD-1 Inhibitors Under Study

11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1) is a tissue-specific intracellular modulator of GC action that’s been trialed for a number of rheumatic conditions. “HSD-1 deficiency or inhibition has been consistently associated with reduced GC side effects in mouse and human,” wrote the authors of a study testing the coadministration of HSD-1 inhibitor SPI-62 (clofutriben) with prednisolone in patients with polymyalgia rheumatica (PMR) to measure its impact on efficacy and toxicity.

Lead study author David Katz, PhD, chief scientific officer at Sparrow Pharmaceuticals, presented results at the at the annual European Congress of Rheumatology.

GCs are often the first-line therapy with PMR. However, it’s very difficult for patients to stop taking GCs once they start taking them. The study included patients with PMR who were taking 10 mg/d prednisolone and didn’t require a dose increase. For the study, they continued prednisolone without dose reduction for 4 weeks, receiving either SPI-62 6 mg/d or a matching placebo for 2 weeks.

During SPI-62 treatment, researchers in sequential cohorts maintained daily prednisolone doses at 10 mg, adjusted to 15 mg or adjusted to 20 mg.

A 10-mg dose of prednisolone combined with 6 mg of SPI-62 demonstrated less efficacy compared with placebo but improved upon prednisolone toxicities such as bone formation and resorption biomarkers, lipidemia, and insulin resistance. Doubling the dose to 20 mg prednisolone combined with SPI-62 achieved similar efficacy and maintained improvement of prednisolone toxicity markers.

“In patients with PMR, when we double the dose of prednisolone during coadministration with a potent HSD-1 inhibitor, we are able to have similar stability of symptoms, physical function, and systemic inflammation. At the same time, we are able to show improvements on biomarkers of bone turnover and insulin resistance,” Dr. Katz informed the EULAR 2024 audience.

An ongoing phase 2 clinical trial is testing SPI-62 in patients with endogenous Cushing syndrome. “It’s a longer-term trial, so we’re able to see at least an individual patient’s more clinical outcomes such as reversal of Cushing’s-associated myopathy and the ability of patients to discontinue all of their antidiabetic medications and yet still have good glycemic control,” he said.

Another research team from the United Kingdom explored whether AZD4017, an inhibitor of human 11ß-HSD1, could mitigate GC effects. The researchers randomly assigned 32 healthy male volunteers to AZD4017 or placebo, along with prednisolone. They reported a worsening of hepatic insulin sensitivity in the placebo group but not in the AZD4017 group, and protective effects of AZD4017 on markers of lipid metabolism and bone turnover, as well as lowered nighttime blood pressure. The results signified that coadministration of AZD4017 with prednisolone in men could be a way to reduce GC side effects.

In a Japanese phase 1/2 study, 11ß-HSD1 inhibitor S-707106 proved useful as an insulin sensitizer and antisarcopenic and anti-obesity medication in 16 patients with Cushing syndrome and autonomous cortisol secretion.
 

Novel Antitumor Necrosis Factor (TNF) Antibody Plus GC Receptor Modulator Conjugate

A novel antibody-drug conjugate comprising the anti-TNF monoclonal antibody adalimumab (ABBV-3373) linked to a GC receptor modulator shows promise as a GC alternative.

A notable 2022 study authored by Frank Buttgereit, MD, and other researchers assessed its safety and efficacy in a randomized, double-blind, active-controlled, proof-of-concept trial.

ABBV-3373 “was designed to potentially allow precise targeting of activated immune cells while significantly dampening inflammation and minimizing the systemic side effects associated with glucocorticoids,” according to AbbVie, its manufacturer.

A total of 48 adults with moderate to severe rheumatoid arthritis receiving background methotrexate were randomized to receive either ABBV-3373 (n = 31) or adalimumab (n = 17). The novel drug at 12 weeks showed a −2.65 reduction in the Disease Activity Score in 28 joints using C-reactive protein, compared with −2.13 for adalimumab. Researchers also predicted ABBV-3373 to be more effective than adalimumab based on in-trial and historical adalimumab data.

“We have great expectations for this molecule,” said Giovanni Adami, MD, PhD, a rheumatologist at the University of Verona, Verona, Italy, who has coauthored several studies on the use of GCs. Plans are underway for a phase 3 study with ABBV-3373.
 

C5a and Interleukin (IL)-6 Receptor Inhibitors as GC-Sparing Drugs

Investigators in a 2021 paper explored whether the C5a receptor inhibitor avacopan could effectively treat patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis without the need for daily GCs, following treatment with either cyclophosphamide or rituximab. They randomized 331 patients to receive avacopan or prednisone given on a tapering schedule for 20 weeks (60 mg/d tapered to discontinuation by week 21). “Avacopan was noninferior but not superior to prednisone taper with respect to remission at week 26 and was superior to prednisone taper with respect to sustained remission at week 52,” the investigators summarized.

A longer trial should test avacopan’s safety and durability in patients with ANCA-associated vasculitis, they recommended.

Sarilumab, a human monoclonal antibody that binds IL-6 receptor alpha and blocks the IL-6 pathway, yielded good results in the phase 3 SAPHYR trial as an alternative for patients with PMR who relapse while tapering prednisone therapy.

Researchers in the SAPHYR trial randomly assigned 118 patients 1:1 to receive a twice-monthly subcutaneous injection of sarilumab over 52 weeks plus a 14-week prednisone taper or placebo plus a 52-week prednisone taper. Patients in each group received a tapered GC dose initially at 15 mg/d for 2 weeks in a blinded fashion to control for disease at baseline.

Sarilumab effectively sustained remission in patients, significantly reducing the GC dose compared with placebo.

Disease flare after clinical remission took place in 57% of patients in the placebo group, vs 24% in the sarilumab group. “The placebo-treated patients had a fairly traditional 52-week GC taper. The patients treated with sarilumab had a very rapid GC taper,” said lead study author Robert Spiera, MD, director of the Scleroderma, Vasculitis and Myositis Center at the Hospital for Special Surgery, New York City.

In his own practice, Dr. Spiera often treats his patients with new-onset PMR with a fairly rapid GC taper, akin to what was used in SAPHYR, recognizing that a portion of these patients can be successfully treated with a relatively brief course of GCs, although the majority will need to have “rescue” therapy for flares with that approach.

Hospital for Special Surgery

A version of this article appeared on Medscape.com.

New treatment strategies in clinical trials show promise in reducing the tapering time of glucocorticoids (GCs) or possibly even replacing the use of GCs. Selective GC receptor agonists and modulators and GC plus hydroxysteroid dehydrogenase inhibitor combination therapy are some of the approaches under consideration.

“There is growing observational data that confirms the GC-sparing effect seen in some of these clinical trials in real-world data,” said Sebastian E. Sattui, MD, assistant professor of medicine and director of the Vasculitis Center at the University of Pittsburgh Medical Center, Pittsburgh.

GC minimization is an important goal, “and the data emerging from these trials should be reassuring for rheumatology providers,” Dr. Sattui said.

HSD-1 Inhibitors Under Study

11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1) is a tissue-specific intracellular modulator of GC action that’s been trialed for a number of rheumatic conditions. “HSD-1 deficiency or inhibition has been consistently associated with reduced GC side effects in mouse and human,” wrote the authors of a study testing the coadministration of HSD-1 inhibitor SPI-62 (clofutriben) with prednisolone in patients with polymyalgia rheumatica (PMR) to measure its impact on efficacy and toxicity.

Lead study author David Katz, PhD, chief scientific officer at Sparrow Pharmaceuticals, presented results at the at the annual European Congress of Rheumatology.

GCs are often the first-line therapy with PMR. However, it’s very difficult for patients to stop taking GCs once they start taking them. The study included patients with PMR who were taking 10 mg/d prednisolone and didn’t require a dose increase. For the study, they continued prednisolone without dose reduction for 4 weeks, receiving either SPI-62 6 mg/d or a matching placebo for 2 weeks.

During SPI-62 treatment, researchers in sequential cohorts maintained daily prednisolone doses at 10 mg, adjusted to 15 mg or adjusted to 20 mg.

A 10-mg dose of prednisolone combined with 6 mg of SPI-62 demonstrated less efficacy compared with placebo but improved upon prednisolone toxicities such as bone formation and resorption biomarkers, lipidemia, and insulin resistance. Doubling the dose to 20 mg prednisolone combined with SPI-62 achieved similar efficacy and maintained improvement of prednisolone toxicity markers.

“In patients with PMR, when we double the dose of prednisolone during coadministration with a potent HSD-1 inhibitor, we are able to have similar stability of symptoms, physical function, and systemic inflammation. At the same time, we are able to show improvements on biomarkers of bone turnover and insulin resistance,” Dr. Katz informed the EULAR 2024 audience.

An ongoing phase 2 clinical trial is testing SPI-62 in patients with endogenous Cushing syndrome. “It’s a longer-term trial, so we’re able to see at least an individual patient’s more clinical outcomes such as reversal of Cushing’s-associated myopathy and the ability of patients to discontinue all of their antidiabetic medications and yet still have good glycemic control,” he said.

Another research team from the United Kingdom explored whether AZD4017, an inhibitor of human 11ß-HSD1, could mitigate GC effects. The researchers randomly assigned 32 healthy male volunteers to AZD4017 or placebo, along with prednisolone. They reported a worsening of hepatic insulin sensitivity in the placebo group but not in the AZD4017 group, and protective effects of AZD4017 on markers of lipid metabolism and bone turnover, as well as lowered nighttime blood pressure. The results signified that coadministration of AZD4017 with prednisolone in men could be a way to reduce GC side effects.

In a Japanese phase 1/2 study, 11ß-HSD1 inhibitor S-707106 proved useful as an insulin sensitizer and antisarcopenic and anti-obesity medication in 16 patients with Cushing syndrome and autonomous cortisol secretion.
 

Novel Antitumor Necrosis Factor (TNF) Antibody Plus GC Receptor Modulator Conjugate

A novel antibody-drug conjugate comprising the anti-TNF monoclonal antibody adalimumab (ABBV-3373) linked to a GC receptor modulator shows promise as a GC alternative.

A notable 2022 study authored by Frank Buttgereit, MD, and other researchers assessed its safety and efficacy in a randomized, double-blind, active-controlled, proof-of-concept trial.

ABBV-3373 “was designed to potentially allow precise targeting of activated immune cells while significantly dampening inflammation and minimizing the systemic side effects associated with glucocorticoids,” according to AbbVie, its manufacturer.

A total of 48 adults with moderate to severe rheumatoid arthritis receiving background methotrexate were randomized to receive either ABBV-3373 (n = 31) or adalimumab (n = 17). The novel drug at 12 weeks showed a −2.65 reduction in the Disease Activity Score in 28 joints using C-reactive protein, compared with −2.13 for adalimumab. Researchers also predicted ABBV-3373 to be more effective than adalimumab based on in-trial and historical adalimumab data.

“We have great expectations for this molecule,” said Giovanni Adami, MD, PhD, a rheumatologist at the University of Verona, Verona, Italy, who has coauthored several studies on the use of GCs. Plans are underway for a phase 3 study with ABBV-3373.
 

C5a and Interleukin (IL)-6 Receptor Inhibitors as GC-Sparing Drugs

Investigators in a 2021 paper explored whether the C5a receptor inhibitor avacopan could effectively treat patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis without the need for daily GCs, following treatment with either cyclophosphamide or rituximab. They randomized 331 patients to receive avacopan or prednisone given on a tapering schedule for 20 weeks (60 mg/d tapered to discontinuation by week 21). “Avacopan was noninferior but not superior to prednisone taper with respect to remission at week 26 and was superior to prednisone taper with respect to sustained remission at week 52,” the investigators summarized.

A longer trial should test avacopan’s safety and durability in patients with ANCA-associated vasculitis, they recommended.

Sarilumab, a human monoclonal antibody that binds IL-6 receptor alpha and blocks the IL-6 pathway, yielded good results in the phase 3 SAPHYR trial as an alternative for patients with PMR who relapse while tapering prednisone therapy.

Researchers in the SAPHYR trial randomly assigned 118 patients 1:1 to receive a twice-monthly subcutaneous injection of sarilumab over 52 weeks plus a 14-week prednisone taper or placebo plus a 52-week prednisone taper. Patients in each group received a tapered GC dose initially at 15 mg/d for 2 weeks in a blinded fashion to control for disease at baseline.

Sarilumab effectively sustained remission in patients, significantly reducing the GC dose compared with placebo.

Disease flare after clinical remission took place in 57% of patients in the placebo group, vs 24% in the sarilumab group. “The placebo-treated patients had a fairly traditional 52-week GC taper. The patients treated with sarilumab had a very rapid GC taper,” said lead study author Robert Spiera, MD, director of the Scleroderma, Vasculitis and Myositis Center at the Hospital for Special Surgery, New York City.

In his own practice, Dr. Spiera often treats his patients with new-onset PMR with a fairly rapid GC taper, akin to what was used in SAPHYR, recognizing that a portion of these patients can be successfully treated with a relatively brief course of GCs, although the majority will need to have “rescue” therapy for flares with that approach.

Hospital for Special Surgery

A version of this article appeared on Medscape.com.

The health consequences of excess visceral fat tissue are well known. But there is another type of fat accumulation in the body that increases the risk for type 2 diabetes and cardiovascular diseases. In Molecular Aspects of Medicine, researchers warned that the dangers arising from intramuscular fat tissue are often underestimated.

“Everyone knows the dangers of abdominal fat or that the deposition of fat in the coronary arteries can cause a heart attack,” said lead author Osvaldo Contreras, PhD, from the School of Clinical Medicine at the University of New South Wales in Sydney, Australia. “But hardly anyone has ever heard of fat accumulation in skeletal muscles, even though they are associated with a whole range of life-threatening diseases.” 

“The work emphasizes that muscles are not only good for standing, walking, or lifting a box. They are metabolically active, produce hormones, communicate in the body, and can positively or negatively affect a person’s health,” Yurdagül Zopf, MD, PhD, professor of integrative medicine specializing in nutritional medicine and director of the Hector Center for Nutrition, Exercise, and Sports at the University Hospital Erlangen, Erlangen, Germany, said in an interview.
 

Associated With Diseases

Increased intramuscular fat is found in various conditions where muscle mass is increasingly lost and replaced by fat and connective tissue. Intramuscular fat has been observed, for example, in patients with chronic muscle diseases, sarcopenia, hormonal disorders, and metabolic diseases such as insulin resistance and type 2 diabetes, as well as in patients with cardiovascular problems such as hypertension and heart failure.

Fat accumulation in the muscles, like all fat deposits in the body, can result from an unhealthy lifestyle with excessive calorie intake and, especially, lack of exercise. “If the body has more energy available than it can use, it will initially store it as subcutaneous fat,” said Dr. Zopf. “Once these storage capacities are depleted, more and more visceral fat is deposited, and then more and more fat is stored in the organs and the muscles.”

Movement plays a particularly important role in intramuscular fat. “We know that the less physically active someone is, the higher the risk that fat will be stored in the muscles,” said Dr. Zopf.
 

Arising From Injuries

Unlike other fat tissues in the body, intramuscular fat can also accumulate in higher amounts when there are injuries to the muscles. The group led by Dr. Contreras and lead author Marcelo Flores-Opazo from the Universidad de O’Higgins in Rancagua, Chile, emphasized the role of fibroadipogenic progenitor (FAP) cells in their review. “FAPs play a crucial role in preserving and repairing muscle tissue injuries. They can differentiate into fibroblasts and adipocytes and are responsible for depositing fat and connective tissue in response to muscle injuries.”

Studies suggest that exercise can prevent FAPs from differentiating into fat and connective tissue cells. Metformin can achieve a similar effect in vitro. Dr. Contreras and colleagues hope that drug-based ways to reduce muscle fat will emerge in the future.

But how do you determine whether a patient has too much intramuscular fat? Although MRI and CT can be used for quantification, these are not routine examinations. There is currently no simple way to determine the fat content in muscles, according to the authors. The study authors hope that advances in molecular testing, imaging, and biopsies will improve diagnostic capabilities in the future.
 

Training Crucial

Until then, Dr. Contreras and colleagues advise close monitoring of one’s body weight and the maintenance of a healthy lifestyle. Excessive fat accumulation in the muscles can be prevented and reversed through adequate exercise and healthy nutrition, they emphasized. 

The important message is that these measures are possible. “With healthy nutrition and exercise, excess fat can be reduced. We have observed a reduction in muscle fat in obese individuals with just two sessions of 15-minute high-intensity workouts per week,” Dr. Zopf reported, citing her own research. The more obese a person is and the higher the inflammation in the body, the more likely additional medication may be needed.

Dr. Zopf also pointed out a peculiarity of intramuscular fat tissue. “Muscle fat can only be trained off.” A fatty liver or too much fat under the skin can be combated well with a diet, but muscles are different. “For that, you have to exercise to counteract the inflammatory cascade in the muscles.”

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

The health consequences of excess visceral fat tissue are well known. But there is another type of fat accumulation in the body that increases the risk for type 2 diabetes and cardiovascular diseases. In Molecular Aspects of Medicine, researchers warned that the dangers arising from intramuscular fat tissue are often underestimated.

“Everyone knows the dangers of abdominal fat or that the deposition of fat in the coronary arteries can cause a heart attack,” said lead author Osvaldo Contreras, PhD, from the School of Clinical Medicine at the University of New South Wales in Sydney, Australia. “But hardly anyone has ever heard of fat accumulation in skeletal muscles, even though they are associated with a whole range of life-threatening diseases.” 

“The work emphasizes that muscles are not only good for standing, walking, or lifting a box. They are metabolically active, produce hormones, communicate in the body, and can positively or negatively affect a person’s health,” Yurdagül Zopf, MD, PhD, professor of integrative medicine specializing in nutritional medicine and director of the Hector Center for Nutrition, Exercise, and Sports at the University Hospital Erlangen, Erlangen, Germany, said in an interview.
 

Associated With Diseases

Increased intramuscular fat is found in various conditions where muscle mass is increasingly lost and replaced by fat and connective tissue. Intramuscular fat has been observed, for example, in patients with chronic muscle diseases, sarcopenia, hormonal disorders, and metabolic diseases such as insulin resistance and type 2 diabetes, as well as in patients with cardiovascular problems such as hypertension and heart failure.

Fat accumulation in the muscles, like all fat deposits in the body, can result from an unhealthy lifestyle with excessive calorie intake and, especially, lack of exercise. “If the body has more energy available than it can use, it will initially store it as subcutaneous fat,” said Dr. Zopf. “Once these storage capacities are depleted, more and more visceral fat is deposited, and then more and more fat is stored in the organs and the muscles.”

Movement plays a particularly important role in intramuscular fat. “We know that the less physically active someone is, the higher the risk that fat will be stored in the muscles,” said Dr. Zopf.
 

Arising From Injuries

Unlike other fat tissues in the body, intramuscular fat can also accumulate in higher amounts when there are injuries to the muscles. The group led by Dr. Contreras and lead author Marcelo Flores-Opazo from the Universidad de O’Higgins in Rancagua, Chile, emphasized the role of fibroadipogenic progenitor (FAP) cells in their review. “FAPs play a crucial role in preserving and repairing muscle tissue injuries. They can differentiate into fibroblasts and adipocytes and are responsible for depositing fat and connective tissue in response to muscle injuries.”

Studies suggest that exercise can prevent FAPs from differentiating into fat and connective tissue cells. Metformin can achieve a similar effect in vitro. Dr. Contreras and colleagues hope that drug-based ways to reduce muscle fat will emerge in the future.

But how do you determine whether a patient has too much intramuscular fat? Although MRI and CT can be used for quantification, these are not routine examinations. There is currently no simple way to determine the fat content in muscles, according to the authors. The study authors hope that advances in molecular testing, imaging, and biopsies will improve diagnostic capabilities in the future.
 

Training Crucial

Until then, Dr. Contreras and colleagues advise close monitoring of one’s body weight and the maintenance of a healthy lifestyle. Excessive fat accumulation in the muscles can be prevented and reversed through adequate exercise and healthy nutrition, they emphasized. 

The important message is that these measures are possible. “With healthy nutrition and exercise, excess fat can be reduced. We have observed a reduction in muscle fat in obese individuals with just two sessions of 15-minute high-intensity workouts per week,” Dr. Zopf reported, citing her own research. The more obese a person is and the higher the inflammation in the body, the more likely additional medication may be needed.

Dr. Zopf also pointed out a peculiarity of intramuscular fat tissue. “Muscle fat can only be trained off.” A fatty liver or too much fat under the skin can be combated well with a diet, but muscles are different. “For that, you have to exercise to counteract the inflammatory cascade in the muscles.”

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

The health consequences of excess visceral fat tissue are well known. But there is another type of fat accumulation in the body that increases the risk for type 2 diabetes and cardiovascular diseases. In Molecular Aspects of Medicine, researchers warned that the dangers arising from intramuscular fat tissue are often underestimated.

“Everyone knows the dangers of abdominal fat or that the deposition of fat in the coronary arteries can cause a heart attack,” said lead author Osvaldo Contreras, PhD, from the School of Clinical Medicine at the University of New South Wales in Sydney, Australia. “But hardly anyone has ever heard of fat accumulation in skeletal muscles, even though they are associated with a whole range of life-threatening diseases.” 

“The work emphasizes that muscles are not only good for standing, walking, or lifting a box. They are metabolically active, produce hormones, communicate in the body, and can positively or negatively affect a person’s health,” Yurdagül Zopf, MD, PhD, professor of integrative medicine specializing in nutritional medicine and director of the Hector Center for Nutrition, Exercise, and Sports at the University Hospital Erlangen, Erlangen, Germany, said in an interview.
 

Associated With Diseases

Increased intramuscular fat is found in various conditions where muscle mass is increasingly lost and replaced by fat and connective tissue. Intramuscular fat has been observed, for example, in patients with chronic muscle diseases, sarcopenia, hormonal disorders, and metabolic diseases such as insulin resistance and type 2 diabetes, as well as in patients with cardiovascular problems such as hypertension and heart failure.

Fat accumulation in the muscles, like all fat deposits in the body, can result from an unhealthy lifestyle with excessive calorie intake and, especially, lack of exercise. “If the body has more energy available than it can use, it will initially store it as subcutaneous fat,” said Dr. Zopf. “Once these storage capacities are depleted, more and more visceral fat is deposited, and then more and more fat is stored in the organs and the muscles.”

Movement plays a particularly important role in intramuscular fat. “We know that the less physically active someone is, the higher the risk that fat will be stored in the muscles,” said Dr. Zopf.
 

Arising From Injuries

Unlike other fat tissues in the body, intramuscular fat can also accumulate in higher amounts when there are injuries to the muscles. The group led by Dr. Contreras and lead author Marcelo Flores-Opazo from the Universidad de O’Higgins in Rancagua, Chile, emphasized the role of fibroadipogenic progenitor (FAP) cells in their review. “FAPs play a crucial role in preserving and repairing muscle tissue injuries. They can differentiate into fibroblasts and adipocytes and are responsible for depositing fat and connective tissue in response to muscle injuries.”

Studies suggest that exercise can prevent FAPs from differentiating into fat and connective tissue cells. Metformin can achieve a similar effect in vitro. Dr. Contreras and colleagues hope that drug-based ways to reduce muscle fat will emerge in the future.

But how do you determine whether a patient has too much intramuscular fat? Although MRI and CT can be used for quantification, these are not routine examinations. There is currently no simple way to determine the fat content in muscles, according to the authors. The study authors hope that advances in molecular testing, imaging, and biopsies will improve diagnostic capabilities in the future.
 

Training Crucial

Until then, Dr. Contreras and colleagues advise close monitoring of one’s body weight and the maintenance of a healthy lifestyle. Excessive fat accumulation in the muscles can be prevented and reversed through adequate exercise and healthy nutrition, they emphasized. 

The important message is that these measures are possible. “With healthy nutrition and exercise, excess fat can be reduced. We have observed a reduction in muscle fat in obese individuals with just two sessions of 15-minute high-intensity workouts per week,” Dr. Zopf reported, citing her own research. The more obese a person is and the higher the inflammation in the body, the more likely additional medication may be needed.

Dr. Zopf also pointed out a peculiarity of intramuscular fat tissue. “Muscle fat can only be trained off.” A fatty liver or too much fat under the skin can be combated well with a diet, but muscles are different. “For that, you have to exercise to counteract the inflammatory cascade in the muscles.”

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