MDedge Rheumatology

A surprising therapy is showing promise for chronic pain, vision loss, and muscle recovery, among other conditions.

It’s not a pill, an injection, or surgery.

It’s light.

Yes, light. The thing that appears when you open the curtains, flip a switch, or strike a match.

Light illuminates our world and helps us see. Early human trials suggest it may help us heal in new ways as well.

“Phototherapy is still in its infancy,” said Mohab Ibrahim, MD, PhD, a professor of anesthesiology at the University of Arizona, Tucson, who studies the effects of light on chronic pain. “There are so many questions, a lot of things we do not understand yet. But that’s where it gets interesting. What we can conclude is that different colors of light can influence different biological functions.”

This growing field goes by several names. Light therapy. Phototherapy. Photobiomodulation.

It leverages known effects of light on human health — such as skin exposure to ultraviolet light producing vitamin D or blue light’s power to regulate human body clocks — to take light as medicine in surprising new directions.
 

New Science, Old Idea

The science is young, but the concept of using light to restore health is thousands of years old.

Hippocrates prescribed sunbathing to patients at his medical center on the Greek island of Kos in 400 BC. Florence Nightingale promoted sunshine, along with fresh air, as prerequisites for recovery in hospitals during the Civil War. A Danish doctor, Niels Finsen, won the Nobel Prize in 1903 for developing ultraviolet lamps to treat a tuberculosis-related skin condition. And worried parents of the 1930s sat their babies in front of mercury arc lamps, bought at the drugstore, to discourage rickets.

Today, light therapy is widely used in medicine for newborn jaundice, psoriasis, and seasonal affective disorder and in light-activated treatments for cancers of the esophagus and lungs, as well as for actinic keratosis, a skin condition that can lead to cancer.

But researchers are finding that light may be capable of far more, particularly in conditions with few treatment options or where available drugs have unwanted side effects.
 

How Red Light Could Restore Vision

When 100 midlife and older adults, aged 53-91, with the dry form of age-related macular degeneration (AMD) were treated with an experimental red-light therapy or a sham therapy, the light treatment group showed signs of improved vision, as measured on a standard eye chart.

Volunteers received the therapy three times a week for 3-5 weeks, every 4 months for 2 years. By the study’s end, 67% of those treated with light could read an additional five letters on the chart, and 20% could read 10 or more. About 7% developed geographic atrophy — the most advanced, vision-threatening stage of dry AMD — compared with 24% in the sham group.

The study, called LIGHTSITE III, was conducted at 10 ophthalmology centers across the United States. The device they used — the Valeda Light Delivery System from medical device company LumiThera — is available in Europe and now being reviewed by the Food and Drug Administration (FDA).

courtesy LumiThera

Exposure to red light at the wavelengths used in the study likely revitalizes failing mitochondria — the power plants inside cells — so they produce more energy, the researchers say.

“This is the first therapy for dry AMD that’s actually shown a benefit in improving vision,” said study coauthor Richard Rosen, MD, chair of ophthalmology at the Icahn School of Medicine at Mount Sinai and chief of Retinal Services at the New York Eye and Ear Infirmary in New York City. “Supplements called AREDS can reduce progression, and in wet AMD we can improve vision loss with injections. But in dry AMD, none of the treatments studied in the past have improved it.”

AMD develops when the eyes can’t break down natural by-products, which glom together as clumps of protein called drusen. Drusen can lodge under the retina, eventually damaging tissue.

“Retinal epithelial cells, a single layer of cells that cares for the photoreceptors in the eyes, are there for life,” Dr. Rosen said. “They have a tremendous capacity to repair themselves, but things [such as aging and smoking] get in the way.”

“I’m proposing,” Dr. Rosen said, “that by boosting energy levels in cells [with red light], we’re improving normal repair mechanisms.”

Lab studies support this idea.

In a 2017 mouse study from the University College London Institute of Ophthalmology in England, retinal function improved by 25% in old mice exposed to red light. And a 2019 study from the Ophthalmological Research Foundation, Oviedo, Spain, found that exposure to blue light harmed the mitochondria in retina cells, while red light somewhat counteracted the losses.

If cleared by the FDA — which the company anticipated could happen in 2024 — LumiThera’s light delivery device will likely be most useful in the beginning stages of dry AMD, Dr. Rosen said. “I think treatment of early dry AMD will be huge.”

Eventually, light therapy may also be valuable in treating or managing glaucoma and diabetic retinopathy.

For now, Dr. Rosen recommended that clinicians and consumers with AMD skip over-the-counter (OTC) red-light therapy devices currently on the market.

“We don’t know what kind of light the devices produce,” he said. “The wavelengths can vary. The eyes are delicate. Experimenting on your own may be hazardous to your vision.”
 

Green Light for Pain Relief

On his way to the pharmacy to pick up pain relievers for a headache, Dr. Ibrahim passed Gene C. Reid Park in Tucson. Recalling how his brother eased headaches by sitting in his backyard, Dr. Ibrahim pulled over.

“Reid Park is probably one of the greenest areas of Tucson,” said Dr. Ibrahim, who also serves as medical director of the Comprehensive Center for Pain & Addiction at Banner-University Medical Center Phoenix in Arizona. “I spent a half hour or 40 minutes there, and my headache felt better.”

Being outdoors in a green space may be soothing for lots of reasons, like the quiet or the fresh air. But there’s also sunlight reflected off and shining through greenery. The experience inspired Dr. Ibrahim to take a closer look at the effects of green light on chronic pain.

In his 2021 study of 29 people with migraines, participants reported that, after daily exposure to green light for 10 weeks, the number of days per month when they had headaches fell from 7.9 to 2.4 for those who had episodic migraines and from 22.3 to 9.4 for those with chronic migraines. In another 2021 study, 21 people with fibromyalgia who had green light therapy for 10 weeks said their average, self-reported pain intensity fell from 8.4 to 4.9 on a 10-point scale used at the University of Arizona’s pain clinic.

Volunteers in both studies got their light therapy at home, switching on green LED lights while they listened to music, read a book, relaxed, or exercised for 1 or 2 hours daily. The lights were within their field of vision, but they did not look directly at them.

Dr. Ibrahim now has funding from the Department of Defense and Department of Veterans Affairs to find out why green light alters pain perception.

“What we know is that the visual system is connected to certain areas of the brain that also modulate pain,” he said. “We are trying to understand the connection.”

Padma Gulur, MD, a professor of anesthesiology and population health and director of Pain Management Strategy and Opioid Surveillance at Duke University, Durham, North Carolina, saw similar results in a 2023 study of 45 people with fibromyalgia. But instead of using a light source, volunteers wore glasses with clear, green, or blue lenses for 4 hours a day.

After 2 weeks, 33% in the green lens group reduced their use of opioids by 10% or more, compared with 11% in the blue lens group and 8% who wore clear lenses. Previous studies have found green light affects levels of the feel-good brain chemical serotonin and stimulates the body’s own opioid system, the authors noted.

“Green light helps your body control and reduce pain,” Dr. Gulur said. It “seems to help with pain relief by affecting the body’s natural pain management system. This effect appears to play a crucial role in antinociception — reducing the sensation of pain; antiallodynia — preventing normal, nonpainful stimuli from causing pain; and antihyperalgesia — reducing heightened sensitivity to pain.”

Light therapy could help pain patients reduce their dose of opioids or even forgo the drugs altogether, Dr. Gulur said. “It is our hope this will become a useful adjuvant therapy to manage pain.”

In the University of Arizona studies, some patients on green-light therapy stopped their medications completely. Even if they didn’t, other benefits appeared. “They had improved quality of life, decreased depression and anxiety, and improved sleep,” Dr. Ibrahim said.

But not just any green light or green-tinted glasses will work, both researchers said. “We have found there are specific frequencies of green light that give this benefit,” Dr. Gulur said. “OTC products may not be helpful for that reason.”

While Dr. Ibrahim said it could be possible for healthcare practitioners and consumers to consult his studies and put together an inexpensive green-light device at home while carefully following the protocol participants used in the studies , it would first be a good idea for patients to talk with their family doctor or a pain specialist.

“A headache is not always just a headache,” Dr. Ibrahim said. “It could be some other abnormality that needs diagnosis and treatment. If you have long-lasting pain or pain that’s getting worse, it’s always better to discuss it with your physician.”
 

Helping Muscles Recover With Red Light

Intense exercise — whether it’s a sprint at the end of a morning run, an extra set of biceps curls, or a weekend of all-day DIY home improvement projects — can temporarily damage muscle, causing soreness, inflammation, and even swelling. Phototherapy with red and near-infrared light is widely used by sports trainers, physical therapists, and athletes to aid in recovery. It may even work better than a trendy plunge in an ice bath, according to a 2019 Texas State University review.

But how does it work? Jamie Ghigiarelli, PhD, professor of Allied Health & Kinesiology at Hofstra University in Hempstead, New York, looked closely at signs of inflammation and muscle damage in 12 athletes to find out.

Study participants overtaxed their muscles with rounds of chin-ups, high-speed sprints, and repeated bench presses. Afterward, they relaxed in a full-body red-light therapy bed or in a similar bed without lights.

The results, published in 2020, showed that blood levels of creatine kinase — an enzyme that’s elevated by muscle damage — were 18% lower 1-3 days after exercising for the light-bed group than for the control group.

“Photobiomodulation seems to help with muscle recovery,” Dr. Ghigiarelli said.

Red light at wavelengths from 650 to 820 nm can enter muscle cells, where it is absorbed by mitochondria and boosts their energy production, he said. At the time of his research, some exercise science researchers and athletes thought using light therapy before an event might also increase athletic performance, but according to Dr. Ghigiarelli, that use has not panned out.

Handheld red light and near-infrared light devices for muscle recovery are widely available, but it’s important to do your homework before buying one.

“You want to choose a device with the right energy production — the right wavelength of light, the right power — to be safe and effective,” he said.

For details, he recommends consulting a 2019 paper in The Brazilian Journal of Physical Therapy called “Clinical and scientific recommendations for the use of photobiomodulation therapy in exercise performance enhancement and post-exercise recovery: Current evidence and future directions.”

The paper, from the Laboratory of Phototherapy and Innovative Technologies in Health at the Universidade Nove de Julho in Sao Paulo, Brazil, recommends that for small muscle groups like the biceps or triceps, use red-light lasers or LED devices with a wavelength of 640 nm for red light or 950 nm for infrared light, at a power of 50-200 mW per diode for single-probe device types, at a dose of 20-60 J, given 5-10 minutes after exercise.

A version of this article appeared on Medscape.com.

A surprising therapy is showing promise for chronic pain, vision loss, and muscle recovery, among other conditions.

It’s not a pill, an injection, or surgery.

It’s light.

Yes, light. The thing that appears when you open the curtains, flip a switch, or strike a match.

Light illuminates our world and helps us see. Early human trials suggest it may help us heal in new ways as well.

“Phototherapy is still in its infancy,” said Mohab Ibrahim, MD, PhD, a professor of anesthesiology at the University of Arizona, Tucson, who studies the effects of light on chronic pain. “There are so many questions, a lot of things we do not understand yet. But that’s where it gets interesting. What we can conclude is that different colors of light can influence different biological functions.”

This growing field goes by several names. Light therapy. Phototherapy. Photobiomodulation.

It leverages known effects of light on human health — such as skin exposure to ultraviolet light producing vitamin D or blue light’s power to regulate human body clocks — to take light as medicine in surprising new directions.
 

New Science, Old Idea

The science is young, but the concept of using light to restore health is thousands of years old.

Hippocrates prescribed sunbathing to patients at his medical center on the Greek island of Kos in 400 BC. Florence Nightingale promoted sunshine, along with fresh air, as prerequisites for recovery in hospitals during the Civil War. A Danish doctor, Niels Finsen, won the Nobel Prize in 1903 for developing ultraviolet lamps to treat a tuberculosis-related skin condition. And worried parents of the 1930s sat their babies in front of mercury arc lamps, bought at the drugstore, to discourage rickets.

Today, light therapy is widely used in medicine for newborn jaundice, psoriasis, and seasonal affective disorder and in light-activated treatments for cancers of the esophagus and lungs, as well as for actinic keratosis, a skin condition that can lead to cancer.

But researchers are finding that light may be capable of far more, particularly in conditions with few treatment options or where available drugs have unwanted side effects.
 

How Red Light Could Restore Vision

When 100 midlife and older adults, aged 53-91, with the dry form of age-related macular degeneration (AMD) were treated with an experimental red-light therapy or a sham therapy, the light treatment group showed signs of improved vision, as measured on a standard eye chart.

Volunteers received the therapy three times a week for 3-5 weeks, every 4 months for 2 years. By the study’s end, 67% of those treated with light could read an additional five letters on the chart, and 20% could read 10 or more. About 7% developed geographic atrophy — the most advanced, vision-threatening stage of dry AMD — compared with 24% in the sham group.

The study, called LIGHTSITE III, was conducted at 10 ophthalmology centers across the United States. The device they used — the Valeda Light Delivery System from medical device company LumiThera — is available in Europe and now being reviewed by the Food and Drug Administration (FDA).

courtesy LumiThera

Exposure to red light at the wavelengths used in the study likely revitalizes failing mitochondria — the power plants inside cells — so they produce more energy, the researchers say.

“This is the first therapy for dry AMD that’s actually shown a benefit in improving vision,” said study coauthor Richard Rosen, MD, chair of ophthalmology at the Icahn School of Medicine at Mount Sinai and chief of Retinal Services at the New York Eye and Ear Infirmary in New York City. “Supplements called AREDS can reduce progression, and in wet AMD we can improve vision loss with injections. But in dry AMD, none of the treatments studied in the past have improved it.”

AMD develops when the eyes can’t break down natural by-products, which glom together as clumps of protein called drusen. Drusen can lodge under the retina, eventually damaging tissue.

“Retinal epithelial cells, a single layer of cells that cares for the photoreceptors in the eyes, are there for life,” Dr. Rosen said. “They have a tremendous capacity to repair themselves, but things [such as aging and smoking] get in the way.”

“I’m proposing,” Dr. Rosen said, “that by boosting energy levels in cells [with red light], we’re improving normal repair mechanisms.”

Lab studies support this idea.

In a 2017 mouse study from the University College London Institute of Ophthalmology in England, retinal function improved by 25% in old mice exposed to red light. And a 2019 study from the Ophthalmological Research Foundation, Oviedo, Spain, found that exposure to blue light harmed the mitochondria in retina cells, while red light somewhat counteracted the losses.

If cleared by the FDA — which the company anticipated could happen in 2024 — LumiThera’s light delivery device will likely be most useful in the beginning stages of dry AMD, Dr. Rosen said. “I think treatment of early dry AMD will be huge.”

Eventually, light therapy may also be valuable in treating or managing glaucoma and diabetic retinopathy.

For now, Dr. Rosen recommended that clinicians and consumers with AMD skip over-the-counter (OTC) red-light therapy devices currently on the market.

“We don’t know what kind of light the devices produce,” he said. “The wavelengths can vary. The eyes are delicate. Experimenting on your own may be hazardous to your vision.”
 

Green Light for Pain Relief

On his way to the pharmacy to pick up pain relievers for a headache, Dr. Ibrahim passed Gene C. Reid Park in Tucson. Recalling how his brother eased headaches by sitting in his backyard, Dr. Ibrahim pulled over.

“Reid Park is probably one of the greenest areas of Tucson,” said Dr. Ibrahim, who also serves as medical director of the Comprehensive Center for Pain & Addiction at Banner-University Medical Center Phoenix in Arizona. “I spent a half hour or 40 minutes there, and my headache felt better.”

Being outdoors in a green space may be soothing for lots of reasons, like the quiet or the fresh air. But there’s also sunlight reflected off and shining through greenery. The experience inspired Dr. Ibrahim to take a closer look at the effects of green light on chronic pain.

In his 2021 study of 29 people with migraines, participants reported that, after daily exposure to green light for 10 weeks, the number of days per month when they had headaches fell from 7.9 to 2.4 for those who had episodic migraines and from 22.3 to 9.4 for those with chronic migraines. In another 2021 study, 21 people with fibromyalgia who had green light therapy for 10 weeks said their average, self-reported pain intensity fell from 8.4 to 4.9 on a 10-point scale used at the University of Arizona’s pain clinic.

Volunteers in both studies got their light therapy at home, switching on green LED lights while they listened to music, read a book, relaxed, or exercised for 1 or 2 hours daily. The lights were within their field of vision, but they did not look directly at them.

Dr. Ibrahim now has funding from the Department of Defense and Department of Veterans Affairs to find out why green light alters pain perception.

“What we know is that the visual system is connected to certain areas of the brain that also modulate pain,” he said. “We are trying to understand the connection.”

Padma Gulur, MD, a professor of anesthesiology and population health and director of Pain Management Strategy and Opioid Surveillance at Duke University, Durham, North Carolina, saw similar results in a 2023 study of 45 people with fibromyalgia. But instead of using a light source, volunteers wore glasses with clear, green, or blue lenses for 4 hours a day.

After 2 weeks, 33% in the green lens group reduced their use of opioids by 10% or more, compared with 11% in the blue lens group and 8% who wore clear lenses. Previous studies have found green light affects levels of the feel-good brain chemical serotonin and stimulates the body’s own opioid system, the authors noted.

“Green light helps your body control and reduce pain,” Dr. Gulur said. It “seems to help with pain relief by affecting the body’s natural pain management system. This effect appears to play a crucial role in antinociception — reducing the sensation of pain; antiallodynia — preventing normal, nonpainful stimuli from causing pain; and antihyperalgesia — reducing heightened sensitivity to pain.”

Light therapy could help pain patients reduce their dose of opioids or even forgo the drugs altogether, Dr. Gulur said. “It is our hope this will become a useful adjuvant therapy to manage pain.”

In the University of Arizona studies, some patients on green-light therapy stopped their medications completely. Even if they didn’t, other benefits appeared. “They had improved quality of life, decreased depression and anxiety, and improved sleep,” Dr. Ibrahim said.

But not just any green light or green-tinted glasses will work, both researchers said. “We have found there are specific frequencies of green light that give this benefit,” Dr. Gulur said. “OTC products may not be helpful for that reason.”

While Dr. Ibrahim said it could be possible for healthcare practitioners and consumers to consult his studies and put together an inexpensive green-light device at home while carefully following the protocol participants used in the studies , it would first be a good idea for patients to talk with their family doctor or a pain specialist.

“A headache is not always just a headache,” Dr. Ibrahim said. “It could be some other abnormality that needs diagnosis and treatment. If you have long-lasting pain or pain that’s getting worse, it’s always better to discuss it with your physician.”
 

Helping Muscles Recover With Red Light

Intense exercise — whether it’s a sprint at the end of a morning run, an extra set of biceps curls, or a weekend of all-day DIY home improvement projects — can temporarily damage muscle, causing soreness, inflammation, and even swelling. Phototherapy with red and near-infrared light is widely used by sports trainers, physical therapists, and athletes to aid in recovery. It may even work better than a trendy plunge in an ice bath, according to a 2019 Texas State University review.

But how does it work? Jamie Ghigiarelli, PhD, professor of Allied Health & Kinesiology at Hofstra University in Hempstead, New York, looked closely at signs of inflammation and muscle damage in 12 athletes to find out.

Study participants overtaxed their muscles with rounds of chin-ups, high-speed sprints, and repeated bench presses. Afterward, they relaxed in a full-body red-light therapy bed or in a similar bed without lights.

The results, published in 2020, showed that blood levels of creatine kinase — an enzyme that’s elevated by muscle damage — were 18% lower 1-3 days after exercising for the light-bed group than for the control group.

“Photobiomodulation seems to help with muscle recovery,” Dr. Ghigiarelli said.

Red light at wavelengths from 650 to 820 nm can enter muscle cells, where it is absorbed by mitochondria and boosts their energy production, he said. At the time of his research, some exercise science researchers and athletes thought using light therapy before an event might also increase athletic performance, but according to Dr. Ghigiarelli, that use has not panned out.

Handheld red light and near-infrared light devices for muscle recovery are widely available, but it’s important to do your homework before buying one.

“You want to choose a device with the right energy production — the right wavelength of light, the right power — to be safe and effective,” he said.

For details, he recommends consulting a 2019 paper in The Brazilian Journal of Physical Therapy called “Clinical and scientific recommendations for the use of photobiomodulation therapy in exercise performance enhancement and post-exercise recovery: Current evidence and future directions.”

The paper, from the Laboratory of Phototherapy and Innovative Technologies in Health at the Universidade Nove de Julho in Sao Paulo, Brazil, recommends that for small muscle groups like the biceps or triceps, use red-light lasers or LED devices with a wavelength of 640 nm for red light or 950 nm for infrared light, at a power of 50-200 mW per diode for single-probe device types, at a dose of 20-60 J, given 5-10 minutes after exercise.

A version of this article appeared on Medscape.com.

A surprising therapy is showing promise for chronic pain, vision loss, and muscle recovery, among other conditions.

It’s not a pill, an injection, or surgery.

It’s light.

Yes, light. The thing that appears when you open the curtains, flip a switch, or strike a match.

Light illuminates our world and helps us see. Early human trials suggest it may help us heal in new ways as well.

“Phototherapy is still in its infancy,” said Mohab Ibrahim, MD, PhD, a professor of anesthesiology at the University of Arizona, Tucson, who studies the effects of light on chronic pain. “There are so many questions, a lot of things we do not understand yet. But that’s where it gets interesting. What we can conclude is that different colors of light can influence different biological functions.”

This growing field goes by several names. Light therapy. Phototherapy. Photobiomodulation.

It leverages known effects of light on human health — such as skin exposure to ultraviolet light producing vitamin D or blue light’s power to regulate human body clocks — to take light as medicine in surprising new directions.
 

New Science, Old Idea

The science is young, but the concept of using light to restore health is thousands of years old.

Hippocrates prescribed sunbathing to patients at his medical center on the Greek island of Kos in 400 BC. Florence Nightingale promoted sunshine, along with fresh air, as prerequisites for recovery in hospitals during the Civil War. A Danish doctor, Niels Finsen, won the Nobel Prize in 1903 for developing ultraviolet lamps to treat a tuberculosis-related skin condition. And worried parents of the 1930s sat their babies in front of mercury arc lamps, bought at the drugstore, to discourage rickets.

Today, light therapy is widely used in medicine for newborn jaundice, psoriasis, and seasonal affective disorder and in light-activated treatments for cancers of the esophagus and lungs, as well as for actinic keratosis, a skin condition that can lead to cancer.

But researchers are finding that light may be capable of far more, particularly in conditions with few treatment options or where available drugs have unwanted side effects.
 

How Red Light Could Restore Vision

When 100 midlife and older adults, aged 53-91, with the dry form of age-related macular degeneration (AMD) were treated with an experimental red-light therapy or a sham therapy, the light treatment group showed signs of improved vision, as measured on a standard eye chart.

Volunteers received the therapy three times a week for 3-5 weeks, every 4 months for 2 years. By the study’s end, 67% of those treated with light could read an additional five letters on the chart, and 20% could read 10 or more. About 7% developed geographic atrophy — the most advanced, vision-threatening stage of dry AMD — compared with 24% in the sham group.

The study, called LIGHTSITE III, was conducted at 10 ophthalmology centers across the United States. The device they used — the Valeda Light Delivery System from medical device company LumiThera — is available in Europe and now being reviewed by the Food and Drug Administration (FDA).

courtesy LumiThera

Exposure to red light at the wavelengths used in the study likely revitalizes failing mitochondria — the power plants inside cells — so they produce more energy, the researchers say.

“This is the first therapy for dry AMD that’s actually shown a benefit in improving vision,” said study coauthor Richard Rosen, MD, chair of ophthalmology at the Icahn School of Medicine at Mount Sinai and chief of Retinal Services at the New York Eye and Ear Infirmary in New York City. “Supplements called AREDS can reduce progression, and in wet AMD we can improve vision loss with injections. But in dry AMD, none of the treatments studied in the past have improved it.”

AMD develops when the eyes can’t break down natural by-products, which glom together as clumps of protein called drusen. Drusen can lodge under the retina, eventually damaging tissue.

“Retinal epithelial cells, a single layer of cells that cares for the photoreceptors in the eyes, are there for life,” Dr. Rosen said. “They have a tremendous capacity to repair themselves, but things [such as aging and smoking] get in the way.”

“I’m proposing,” Dr. Rosen said, “that by boosting energy levels in cells [with red light], we’re improving normal repair mechanisms.”

Lab studies support this idea.

In a 2017 mouse study from the University College London Institute of Ophthalmology in England, retinal function improved by 25% in old mice exposed to red light. And a 2019 study from the Ophthalmological Research Foundation, Oviedo, Spain, found that exposure to blue light harmed the mitochondria in retina cells, while red light somewhat counteracted the losses.

If cleared by the FDA — which the company anticipated could happen in 2024 — LumiThera’s light delivery device will likely be most useful in the beginning stages of dry AMD, Dr. Rosen said. “I think treatment of early dry AMD will be huge.”

Eventually, light therapy may also be valuable in treating or managing glaucoma and diabetic retinopathy.

For now, Dr. Rosen recommended that clinicians and consumers with AMD skip over-the-counter (OTC) red-light therapy devices currently on the market.

“We don’t know what kind of light the devices produce,” he said. “The wavelengths can vary. The eyes are delicate. Experimenting on your own may be hazardous to your vision.”
 

Green Light for Pain Relief

On his way to the pharmacy to pick up pain relievers for a headache, Dr. Ibrahim passed Gene C. Reid Park in Tucson. Recalling how his brother eased headaches by sitting in his backyard, Dr. Ibrahim pulled over.

“Reid Park is probably one of the greenest areas of Tucson,” said Dr. Ibrahim, who also serves as medical director of the Comprehensive Center for Pain & Addiction at Banner-University Medical Center Phoenix in Arizona. “I spent a half hour or 40 minutes there, and my headache felt better.”

Being outdoors in a green space may be soothing for lots of reasons, like the quiet or the fresh air. But there’s also sunlight reflected off and shining through greenery. The experience inspired Dr. Ibrahim to take a closer look at the effects of green light on chronic pain.

In his 2021 study of 29 people with migraines, participants reported that, after daily exposure to green light for 10 weeks, the number of days per month when they had headaches fell from 7.9 to 2.4 for those who had episodic migraines and from 22.3 to 9.4 for those with chronic migraines. In another 2021 study, 21 people with fibromyalgia who had green light therapy for 10 weeks said their average, self-reported pain intensity fell from 8.4 to 4.9 on a 10-point scale used at the University of Arizona’s pain clinic.

Volunteers in both studies got their light therapy at home, switching on green LED lights while they listened to music, read a book, relaxed, or exercised for 1 or 2 hours daily. The lights were within their field of vision, but they did not look directly at them.

Dr. Ibrahim now has funding from the Department of Defense and Department of Veterans Affairs to find out why green light alters pain perception.

“What we know is that the visual system is connected to certain areas of the brain that also modulate pain,” he said. “We are trying to understand the connection.”

Padma Gulur, MD, a professor of anesthesiology and population health and director of Pain Management Strategy and Opioid Surveillance at Duke University, Durham, North Carolina, saw similar results in a 2023 study of 45 people with fibromyalgia. But instead of using a light source, volunteers wore glasses with clear, green, or blue lenses for 4 hours a day.

After 2 weeks, 33% in the green lens group reduced their use of opioids by 10% or more, compared with 11% in the blue lens group and 8% who wore clear lenses. Previous studies have found green light affects levels of the feel-good brain chemical serotonin and stimulates the body’s own opioid system, the authors noted.

“Green light helps your body control and reduce pain,” Dr. Gulur said. It “seems to help with pain relief by affecting the body’s natural pain management system. This effect appears to play a crucial role in antinociception — reducing the sensation of pain; antiallodynia — preventing normal, nonpainful stimuli from causing pain; and antihyperalgesia — reducing heightened sensitivity to pain.”

Light therapy could help pain patients reduce their dose of opioids or even forgo the drugs altogether, Dr. Gulur said. “It is our hope this will become a useful adjuvant therapy to manage pain.”

In the University of Arizona studies, some patients on green-light therapy stopped their medications completely. Even if they didn’t, other benefits appeared. “They had improved quality of life, decreased depression and anxiety, and improved sleep,” Dr. Ibrahim said.

But not just any green light or green-tinted glasses will work, both researchers said. “We have found there are specific frequencies of green light that give this benefit,” Dr. Gulur said. “OTC products may not be helpful for that reason.”

While Dr. Ibrahim said it could be possible for healthcare practitioners and consumers to consult his studies and put together an inexpensive green-light device at home while carefully following the protocol participants used in the studies , it would first be a good idea for patients to talk with their family doctor or a pain specialist.

“A headache is not always just a headache,” Dr. Ibrahim said. “It could be some other abnormality that needs diagnosis and treatment. If you have long-lasting pain or pain that’s getting worse, it’s always better to discuss it with your physician.”
 

Helping Muscles Recover With Red Light

Intense exercise — whether it’s a sprint at the end of a morning run, an extra set of biceps curls, or a weekend of all-day DIY home improvement projects — can temporarily damage muscle, causing soreness, inflammation, and even swelling. Phototherapy with red and near-infrared light is widely used by sports trainers, physical therapists, and athletes to aid in recovery. It may even work better than a trendy plunge in an ice bath, according to a 2019 Texas State University review.

But how does it work? Jamie Ghigiarelli, PhD, professor of Allied Health & Kinesiology at Hofstra University in Hempstead, New York, looked closely at signs of inflammation and muscle damage in 12 athletes to find out.

Study participants overtaxed their muscles with rounds of chin-ups, high-speed sprints, and repeated bench presses. Afterward, they relaxed in a full-body red-light therapy bed or in a similar bed without lights.

The results, published in 2020, showed that blood levels of creatine kinase — an enzyme that’s elevated by muscle damage — were 18% lower 1-3 days after exercising for the light-bed group than for the control group.

“Photobiomodulation seems to help with muscle recovery,” Dr. Ghigiarelli said.

Red light at wavelengths from 650 to 820 nm can enter muscle cells, where it is absorbed by mitochondria and boosts their energy production, he said. At the time of his research, some exercise science researchers and athletes thought using light therapy before an event might also increase athletic performance, but according to Dr. Ghigiarelli, that use has not panned out.

Handheld red light and near-infrared light devices for muscle recovery are widely available, but it’s important to do your homework before buying one.

“You want to choose a device with the right energy production — the right wavelength of light, the right power — to be safe and effective,” he said.

For details, he recommends consulting a 2019 paper in The Brazilian Journal of Physical Therapy called “Clinical and scientific recommendations for the use of photobiomodulation therapy in exercise performance enhancement and post-exercise recovery: Current evidence and future directions.”

The paper, from the Laboratory of Phototherapy and Innovative Technologies in Health at the Universidade Nove de Julho in Sao Paulo, Brazil, recommends that for small muscle groups like the biceps or triceps, use red-light lasers or LED devices with a wavelength of 640 nm for red light or 950 nm for infrared light, at a power of 50-200 mW per diode for single-probe device types, at a dose of 20-60 J, given 5-10 minutes after exercise.

A version of this article appeared on Medscape.com.

TOPLINE:

The maternal and neonatal outcomes in pregnant women treated with anti–interleukin (IL)-6 therapy for COVID-19 are largely favorable, with transient neonatal cytopenia observed in around one third of the babies being the only possible adverse outcome that could be related to anti–IL-6 therapy.

METHODOLOGY:

• Despite guidance, very few pregnant women with COVID-19 are offered evidence-based therapies such as anti–IL-6 due to concerns regarding fetal safety in later pregnancy.
• In this retrospective study, researchers evaluated maternal and neonatal outcomes in 25 pregnant women with COVID-19 (mean age at admission, 33 years) treated with anti–IL-6 (tocilizumab or sarilumab) at two tertiary hospitals in London.
• Most women (n = 16) received anti–IL-6 in the third trimester of pregnancy, whereas nine received it during the second trimester.
• Maternal and neonatal outcomes were assessed through medical record reviews and maternal medicine networks, with follow-up for 12 months.
• The women included in the study constituted a high-risk population with severe COVID-19; 24 required level two or three critical care. All women were receiving at least three concomitant medications due to their critical illness.

TAKEAWAY:

• Overall, 24 of 25 women treated with IL-6 receptor antibodies survived until hospital discharge.
• The sole death occurred in a woman with severe COVID-19 pneumonitis who later developed myocarditis and cardiac arrest. The physicians believed that these complications were more likely due to severe COVID-19 rather than anti–IL-6 therapy.
• All pregnancies resulted in live births; however, 16 babies had to be delivered preterm due to COVID-19 complications.
• Transient cytopenia was observed in 6 of 19 babies in whom a full blood count was performed. All the six babies were premature, with cytopenia resolving within 7 days in four babies; one baby died from complications associated with extreme prematurity.

IN PRACTICE:

“Although the authors found mild, transitory cytopenia in some (6 of 19) exposed infants, most had been delivered prematurely due to progressive COVID-19–related morbidity, and distinguishing drug effects from similar prematurity-related effects is difficult,” wrote Steven L. Clark, MD, from the Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, in an accompanying editorial.

SOURCE:

The study was led by Melanie Nana, MRCP, from the Department of Obstetric Medicine, St Thomas’ Hospital, London, England. It was published online in The Lancet Rheumatology.

LIMITATIONS:

The study was retrospective in design, which may have introduced bias. The small sample size of 25 women may have limited the generalizability of the findings. Additionally, the study did not include a control group, which made it difficult to attribute outcomes solely to anti–IL-6 therapy. The lack of long-term follow-up data on the neonates also limited the understanding of potential long-term effects.

DISCLOSURES:

This study did not receive any funding. Some authors, including the lead author, received speaker fees, grants, or consultancy fees from academic institutions or pharmaceutical companies or had other ties with various sources.

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

TOPLINE:

The maternal and neonatal outcomes in pregnant women treated with anti–interleukin (IL)-6 therapy for COVID-19 are largely favorable, with transient neonatal cytopenia observed in around one third of the babies being the only possible adverse outcome that could be related to anti–IL-6 therapy.

METHODOLOGY:

• Despite guidance, very few pregnant women with COVID-19 are offered evidence-based therapies such as anti–IL-6 due to concerns regarding fetal safety in later pregnancy.
• In this retrospective study, researchers evaluated maternal and neonatal outcomes in 25 pregnant women with COVID-19 (mean age at admission, 33 years) treated with anti–IL-6 (tocilizumab or sarilumab) at two tertiary hospitals in London.
• Most women (n = 16) received anti–IL-6 in the third trimester of pregnancy, whereas nine received it during the second trimester.
• Maternal and neonatal outcomes were assessed through medical record reviews and maternal medicine networks, with follow-up for 12 months.
• The women included in the study constituted a high-risk population with severe COVID-19; 24 required level two or three critical care. All women were receiving at least three concomitant medications due to their critical illness.

TAKEAWAY:

• Overall, 24 of 25 women treated with IL-6 receptor antibodies survived until hospital discharge.
• The sole death occurred in a woman with severe COVID-19 pneumonitis who later developed myocarditis and cardiac arrest. The physicians believed that these complications were more likely due to severe COVID-19 rather than anti–IL-6 therapy.
• All pregnancies resulted in live births; however, 16 babies had to be delivered preterm due to COVID-19 complications.
• Transient cytopenia was observed in 6 of 19 babies in whom a full blood count was performed. All the six babies were premature, with cytopenia resolving within 7 days in four babies; one baby died from complications associated with extreme prematurity.

IN PRACTICE:

“Although the authors found mild, transitory cytopenia in some (6 of 19) exposed infants, most had been delivered prematurely due to progressive COVID-19–related morbidity, and distinguishing drug effects from similar prematurity-related effects is difficult,” wrote Steven L. Clark, MD, from the Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, in an accompanying editorial.

SOURCE:

The study was led by Melanie Nana, MRCP, from the Department of Obstetric Medicine, St Thomas’ Hospital, London, England. It was published online in The Lancet Rheumatology.

LIMITATIONS:

The study was retrospective in design, which may have introduced bias. The small sample size of 25 women may have limited the generalizability of the findings. Additionally, the study did not include a control group, which made it difficult to attribute outcomes solely to anti–IL-6 therapy. The lack of long-term follow-up data on the neonates also limited the understanding of potential long-term effects.

DISCLOSURES:

This study did not receive any funding. Some authors, including the lead author, received speaker fees, grants, or consultancy fees from academic institutions or pharmaceutical companies or had other ties with various sources.

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

TOPLINE:

The maternal and neonatal outcomes in pregnant women treated with anti–interleukin (IL)-6 therapy for COVID-19 are largely favorable, with transient neonatal cytopenia observed in around one third of the babies being the only possible adverse outcome that could be related to anti–IL-6 therapy.

METHODOLOGY:

• Despite guidance, very few pregnant women with COVID-19 are offered evidence-based therapies such as anti–IL-6 due to concerns regarding fetal safety in later pregnancy.
• In this retrospective study, researchers evaluated maternal and neonatal outcomes in 25 pregnant women with COVID-19 (mean age at admission, 33 years) treated with anti–IL-6 (tocilizumab or sarilumab) at two tertiary hospitals in London.
• Most women (n = 16) received anti–IL-6 in the third trimester of pregnancy, whereas nine received it during the second trimester.
• Maternal and neonatal outcomes were assessed through medical record reviews and maternal medicine networks, with follow-up for 12 months.
• The women included in the study constituted a high-risk population with severe COVID-19; 24 required level two or three critical care. All women were receiving at least three concomitant medications due to their critical illness.

TAKEAWAY:

• Overall, 24 of 25 women treated with IL-6 receptor antibodies survived until hospital discharge.
• The sole death occurred in a woman with severe COVID-19 pneumonitis who later developed myocarditis and cardiac arrest. The physicians believed that these complications were more likely due to severe COVID-19 rather than anti–IL-6 therapy.
• All pregnancies resulted in live births; however, 16 babies had to be delivered preterm due to COVID-19 complications.
• Transient cytopenia was observed in 6 of 19 babies in whom a full blood count was performed. All the six babies were premature, with cytopenia resolving within 7 days in four babies; one baby died from complications associated with extreme prematurity.

IN PRACTICE:

“Although the authors found mild, transitory cytopenia in some (6 of 19) exposed infants, most had been delivered prematurely due to progressive COVID-19–related morbidity, and distinguishing drug effects from similar prematurity-related effects is difficult,” wrote Steven L. Clark, MD, from the Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, in an accompanying editorial.

SOURCE:

The study was led by Melanie Nana, MRCP, from the Department of Obstetric Medicine, St Thomas’ Hospital, London, England. It was published online in The Lancet Rheumatology.

LIMITATIONS:

The study was retrospective in design, which may have introduced bias. The small sample size of 25 women may have limited the generalizability of the findings. Additionally, the study did not include a control group, which made it difficult to attribute outcomes solely to anti–IL-6 therapy. The lack of long-term follow-up data on the neonates also limited the understanding of potential long-term effects.

DISCLOSURES:

This study did not receive any funding. Some authors, including the lead author, received speaker fees, grants, or consultancy fees from academic institutions or pharmaceutical companies or had other ties with various sources.

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

TOPLINE:

Upadacitinib, an oral Janus kinase (JAK) 1 inhibitor, showed an 80% complete response rate in patients with granulomatous cheilitis, with no serious adverse events, in a small retrospective case series.

METHODOLOGY:

• Granulomatous cheilitis is a rare, nonnecrotizing granulomatous inflammatory disorder characterized by intermittent or persistent swelling of the lips.
• In a retrospective case series of five patients (median age, 30 years; four women) with granulomatous cheilitis resistant to systemic treatments at a Belgian hospital between June 2023 and March 2024, all five were treated with a high dose of upadacitinib (30 mg daily).
• The primary endpoint was objective clinical improvement in lip swelling and infiltration over a median follow-up of 7.2 months.
• Three patients had concomitant dormant Crohn’s disease (CD); a secondary outcome was disease activity in these patients.

TAKEAWAY:

• Upadacitinib treatment resulted in a complete response in four patients (80%) within a median of 3.8 months and a partial response in one patient.
• CD remained dormant in the three patients with CD.
• The safety profile of upadacitinib was favorable, and no serious adverse events were reported. Two patients experienced headaches, acne, mild changes in lipids, and/or transaminitis.

IN PRACTICE:

“Upadacitinib was effective in treating patients with recalcitrant and long-lasting granulomatous cheilitis, even in cases of concomitant CD, which could substantially improve the quality of life of affected patients,” the authors wrote. More studies are needed to confirm these results in larger groups of patients over longer periods of time, “and with other JAK inhibitors.”

SOURCE:

The study was led by Axel De Greef, MD, Department of Dermatology, Cliniques universitaires Saint-Luc, Université catholique de Louvain (UCLouvain), Brussels, Belgium. It was published online in JAMA Dermatology.

LIMITATIONS:

The small sample size and short follow-up may limit the generalizability of the findings to a larger population of patients with granulomatous cheilitis.

DISCLOSURES:

The study did not report any funding sources. Some authors reported receiving nonfinancial support and personal fees from various pharmaceutical companies outside the submitted work.

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

TOPLINE:

Upadacitinib, an oral Janus kinase (JAK) 1 inhibitor, showed an 80% complete response rate in patients with granulomatous cheilitis, with no serious adverse events, in a small retrospective case series.

METHODOLOGY:

• Granulomatous cheilitis is a rare, nonnecrotizing granulomatous inflammatory disorder characterized by intermittent or persistent swelling of the lips.
• In a retrospective case series of five patients (median age, 30 years; four women) with granulomatous cheilitis resistant to systemic treatments at a Belgian hospital between June 2023 and March 2024, all five were treated with a high dose of upadacitinib (30 mg daily).
• The primary endpoint was objective clinical improvement in lip swelling and infiltration over a median follow-up of 7.2 months.
• Three patients had concomitant dormant Crohn’s disease (CD); a secondary outcome was disease activity in these patients.

TAKEAWAY:

• Upadacitinib treatment resulted in a complete response in four patients (80%) within a median of 3.8 months and a partial response in one patient.
• CD remained dormant in the three patients with CD.
• The safety profile of upadacitinib was favorable, and no serious adverse events were reported. Two patients experienced headaches, acne, mild changes in lipids, and/or transaminitis.

IN PRACTICE:

“Upadacitinib was effective in treating patients with recalcitrant and long-lasting granulomatous cheilitis, even in cases of concomitant CD, which could substantially improve the quality of life of affected patients,” the authors wrote. More studies are needed to confirm these results in larger groups of patients over longer periods of time, “and with other JAK inhibitors.”

SOURCE:

The study was led by Axel De Greef, MD, Department of Dermatology, Cliniques universitaires Saint-Luc, Université catholique de Louvain (UCLouvain), Brussels, Belgium. It was published online in JAMA Dermatology.

LIMITATIONS:

The small sample size and short follow-up may limit the generalizability of the findings to a larger population of patients with granulomatous cheilitis.

DISCLOSURES:

The study did not report any funding sources. Some authors reported receiving nonfinancial support and personal fees from various pharmaceutical companies outside the submitted work.

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

TOPLINE:

Upadacitinib, an oral Janus kinase (JAK) 1 inhibitor, showed an 80% complete response rate in patients with granulomatous cheilitis, with no serious adverse events, in a small retrospective case series.

METHODOLOGY:

• Granulomatous cheilitis is a rare, nonnecrotizing granulomatous inflammatory disorder characterized by intermittent or persistent swelling of the lips.
• In a retrospective case series of five patients (median age, 30 years; four women) with granulomatous cheilitis resistant to systemic treatments at a Belgian hospital between June 2023 and March 2024, all five were treated with a high dose of upadacitinib (30 mg daily).
• The primary endpoint was objective clinical improvement in lip swelling and infiltration over a median follow-up of 7.2 months.
• Three patients had concomitant dormant Crohn’s disease (CD); a secondary outcome was disease activity in these patients.

TAKEAWAY:

• Upadacitinib treatment resulted in a complete response in four patients (80%) within a median of 3.8 months and a partial response in one patient.
• CD remained dormant in the three patients with CD.
• The safety profile of upadacitinib was favorable, and no serious adverse events were reported. Two patients experienced headaches, acne, mild changes in lipids, and/or transaminitis.

IN PRACTICE:

“Upadacitinib was effective in treating patients with recalcitrant and long-lasting granulomatous cheilitis, even in cases of concomitant CD, which could substantially improve the quality of life of affected patients,” the authors wrote. More studies are needed to confirm these results in larger groups of patients over longer periods of time, “and with other JAK inhibitors.”

SOURCE:

The study was led by Axel De Greef, MD, Department of Dermatology, Cliniques universitaires Saint-Luc, Université catholique de Louvain (UCLouvain), Brussels, Belgium. It was published online in JAMA Dermatology.

LIMITATIONS:

The small sample size and short follow-up may limit the generalizability of the findings to a larger population of patients with granulomatous cheilitis.

DISCLOSURES:

The study did not report any funding sources. Some authors reported receiving nonfinancial support and personal fees from various pharmaceutical companies outside the submitted work.

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

TOPLINE:

Patients with alopecia areata (AA) had a higher prevalence of several psychiatric and autoimmune comorbidities at baseline and were at greater risk of developing those comorbidities after diagnosis.

METHODOLOGY:

• Researchers evaluated 63,384 patients with AA and 3,309,107 individuals without AA (aged 12-64 years) from the Merative MarketScan Research Databases.
• The matched cohorts included 16,512 patients with AA and 66,048 control individuals.
• Outcomes were the prevalence of psychiatric and autoimmune diseases at baseline and the incidence of new-onset psychiatric and autoimmune diseases during the year after diagnosis.

TAKEAWAY:

• Overall, patients with AA showed a greater prevalence of any psychiatric disease (30.9% vs 26.8%; P < .001) and any immune-mediated or autoimmune disease (16.1% vs 8.9%; P < .0001) than those with controls.
• In matched cohorts, patients with AA also showed a higher incidence of any new-onset psychiatric diseases (10.2% vs 6.8%; P < .001) or immune-mediated or autoimmune disease (6.2% vs 1.5%; P <.001) within the first 12 months of AA diagnosis than those with controls.
• Among patients with AA, the risk of developing a psychiatric comorbidity was higher (adjusted hazard ratio [aHR], 1.3; 95% CI, 1.3-1.4). The highest risks were seen for adjustment disorder (aHR, 1.5), panic disorder (aHR, 1.4), and sexual dysfunction (aHR, 1.4).
• Compared with controls, patients with AA were also at an increased risk of developing immune-mediated or autoimmune comorbidities (aHR, 2.7; 95% CI, 2.5-2.8), with the highest for systemic lupus (aHR, 5.7), atopic dermatitis (aHR, 4.3), and vitiligo (aHR, 3.8).

IN PRACTICE:

“Routine monitoring of patients with AA, especially those at risk of developing comorbidities, may permit earlier and more effective intervention,” the authors wrote.

SOURCE:

The study was led by Arash Mostaghimi, MD, MPA, MPH, Brigham and Women’s Hospital and Harvard University, Boston. It was published online on July 31, 2024, in JAMA Dermatology.

LIMITATIONS:

Causality could not be inferred because of the retrospective nature of the study. Comorbidities were solely diagnosed on the basis of diagnostic codes, and researchers did not have access to characteristics such as lab values that could have indicated any underlying comorbidity before the AA diagnosis. This study also did not account for the varying levels of severity of the disease, which may have led to an underestimation of disease burden and the risk for comorbidities.

DISCLOSURES:

AbbVie provided funding for this study. Mostaghimi disclosed receiving personal fees from Abbvie and several other companies outside of this work. The other four authors were current or former employees of Abbvie and have or may have stock and/or stock options in AbbVie.

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

TOPLINE:

Patients with alopecia areata (AA) had a higher prevalence of several psychiatric and autoimmune comorbidities at baseline and were at greater risk of developing those comorbidities after diagnosis.

METHODOLOGY:

• Researchers evaluated 63,384 patients with AA and 3,309,107 individuals without AA (aged 12-64 years) from the Merative MarketScan Research Databases.
• The matched cohorts included 16,512 patients with AA and 66,048 control individuals.
• Outcomes were the prevalence of psychiatric and autoimmune diseases at baseline and the incidence of new-onset psychiatric and autoimmune diseases during the year after diagnosis.

TAKEAWAY:

• Overall, patients with AA showed a greater prevalence of any psychiatric disease (30.9% vs 26.8%; P < .001) and any immune-mediated or autoimmune disease (16.1% vs 8.9%; P < .0001) than those with controls.
• In matched cohorts, patients with AA also showed a higher incidence of any new-onset psychiatric diseases (10.2% vs 6.8%; P < .001) or immune-mediated or autoimmune disease (6.2% vs 1.5%; P <.001) within the first 12 months of AA diagnosis than those with controls.
• Among patients with AA, the risk of developing a psychiatric comorbidity was higher (adjusted hazard ratio [aHR], 1.3; 95% CI, 1.3-1.4). The highest risks were seen for adjustment disorder (aHR, 1.5), panic disorder (aHR, 1.4), and sexual dysfunction (aHR, 1.4).
• Compared with controls, patients with AA were also at an increased risk of developing immune-mediated or autoimmune comorbidities (aHR, 2.7; 95% CI, 2.5-2.8), with the highest for systemic lupus (aHR, 5.7), atopic dermatitis (aHR, 4.3), and vitiligo (aHR, 3.8).

IN PRACTICE:

“Routine monitoring of patients with AA, especially those at risk of developing comorbidities, may permit earlier and more effective intervention,” the authors wrote.

SOURCE:

The study was led by Arash Mostaghimi, MD, MPA, MPH, Brigham and Women’s Hospital and Harvard University, Boston. It was published online on July 31, 2024, in JAMA Dermatology.

LIMITATIONS:

Causality could not be inferred because of the retrospective nature of the study. Comorbidities were solely diagnosed on the basis of diagnostic codes, and researchers did not have access to characteristics such as lab values that could have indicated any underlying comorbidity before the AA diagnosis. This study also did not account for the varying levels of severity of the disease, which may have led to an underestimation of disease burden and the risk for comorbidities.

DISCLOSURES:

AbbVie provided funding for this study. Mostaghimi disclosed receiving personal fees from Abbvie and several other companies outside of this work. The other four authors were current or former employees of Abbvie and have or may have stock and/or stock options in AbbVie.

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

TOPLINE:

Patients with alopecia areata (AA) had a higher prevalence of several psychiatric and autoimmune comorbidities at baseline and were at greater risk of developing those comorbidities after diagnosis.

METHODOLOGY:

• Researchers evaluated 63,384 patients with AA and 3,309,107 individuals without AA (aged 12-64 years) from the Merative MarketScan Research Databases.
• The matched cohorts included 16,512 patients with AA and 66,048 control individuals.
• Outcomes were the prevalence of psychiatric and autoimmune diseases at baseline and the incidence of new-onset psychiatric and autoimmune diseases during the year after diagnosis.

TAKEAWAY:

• Overall, patients with AA showed a greater prevalence of any psychiatric disease (30.9% vs 26.8%; P < .001) and any immune-mediated or autoimmune disease (16.1% vs 8.9%; P < .0001) than those with controls.
• In matched cohorts, patients with AA also showed a higher incidence of any new-onset psychiatric diseases (10.2% vs 6.8%; P < .001) or immune-mediated or autoimmune disease (6.2% vs 1.5%; P <.001) within the first 12 months of AA diagnosis than those with controls.
• Among patients with AA, the risk of developing a psychiatric comorbidity was higher (adjusted hazard ratio [aHR], 1.3; 95% CI, 1.3-1.4). The highest risks were seen for adjustment disorder (aHR, 1.5), panic disorder (aHR, 1.4), and sexual dysfunction (aHR, 1.4).
• Compared with controls, patients with AA were also at an increased risk of developing immune-mediated or autoimmune comorbidities (aHR, 2.7; 95% CI, 2.5-2.8), with the highest for systemic lupus (aHR, 5.7), atopic dermatitis (aHR, 4.3), and vitiligo (aHR, 3.8).

IN PRACTICE:

“Routine monitoring of patients with AA, especially those at risk of developing comorbidities, may permit earlier and more effective intervention,” the authors wrote.

SOURCE:

The study was led by Arash Mostaghimi, MD, MPA, MPH, Brigham and Women’s Hospital and Harvard University, Boston. It was published online on July 31, 2024, in JAMA Dermatology.

LIMITATIONS:

Causality could not be inferred because of the retrospective nature of the study. Comorbidities were solely diagnosed on the basis of diagnostic codes, and researchers did not have access to characteristics such as lab values that could have indicated any underlying comorbidity before the AA diagnosis. This study also did not account for the varying levels of severity of the disease, which may have led to an underestimation of disease burden and the risk for comorbidities.

DISCLOSURES:

AbbVie provided funding for this study. Mostaghimi disclosed receiving personal fees from Abbvie and several other companies outside of this work. The other four authors were current or former employees of Abbvie and have or may have stock and/or stock options in AbbVie.

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

VIENNA — Nipocalimab, iscalimab, and tibulizumab, but not lusvertikimab, appear to be promising new agents for Sjögren disease that warrant further investigation, suggest the results of four separate early clinical trials reported at the recent annual European Congress of Rheumatology (EULAR).

This is potentially good news for patients, as discovering new treatments that work for managing the various symptoms of Sjögren disease is a high priority, Jacques-Eric Gottenberg, MD, PhD, said when he presented the results of the phase 2 DAHLIAS study of nipocalimab during a late-breaking abstract session.

“All patients suffer from high burden of symptoms — pain, fatigue, and dryness; nearly 50% of patients have systemic complications; mortality is increased, so there is a high unmet need since no specific drug has been accepted so far,” said Dr. Gottenberg, who works at Strasbourg University Hospital in Strasbourg, France.

“The pathogenesis of the disease involves high B-cell activation, resulting in high IgG levels, and secretion of autoantibodies,” such as anti-Ro, anti-La, anti-Sjögren’s syndrome type A (anti-SSA), and anti-Sjögren’s syndrome type B antibodies, Dr. Gottenberg said.

Thus, one approach to reducing the disease burden is to try to lower circulating immunoglobulin G (IgG) levels and IgG-associated autoantibodies, which is how the monoclonal antibody nipocalimab works. Nipocalimab essentially blocks the interaction of IgG with the neonatal fragment crystallizable receptor and has already been shown to have efficacy in other autoimmune conditions such as myasthenia gravis and fetal and neonatal hemolytic disease, although not as hoped in rheumatoid arthritis.
 

The DAHLIAS Phase 2 Study

Now, results from the DAHLIAS study show that nipocalimab may also work in Sjögren disease, with significant improvement vs placebo seen in the primary endpoint of the total EULAR Sjögren’s Syndrome Disease Activity Index (clinESSDAI) at 24 weeks for one of the two doses of the drug that were tested.

The multicenter, placebo-controlled, double-blind study was conducted in 163 patients with moderate to severely active primary Sjögren disease. The latter was determined by having a clinESSDAI of 6 or higher and seropositivity for anti-Ro60, anti-Ro52, or both autoantibodies.

Dr. Gottenberg reported that the mean age of patients was 48 years; the majority (92.6%) were women and of White ethnicity (90.8%). The baseline clinESSDAI was a mean of 9.9; 98.1% had anti-Ro60, 80.6% had anti-Ro52, and 71.9% had anti-La antibodies.

In addition to standard of care, patients were randomly allocated to receive intravenous treatment every 2 weeks with nipocalimab 5 mg/kg or 15 mg/kg, or placebo.

At 24 weeks, the least squares mean (LSM) change in clinESSDAI from baseline was −3.74 for placebo, −4.08 for nipocalimab 5 mg/kg (P = not significant vs placebo), and −6.40 for nipocalimab 15 mg/kg (P = .02 vs placebo).

Nipocalimab 15 mg/kg also “demonstrated similar and consistent trends in other key efficacy endpoints,” Dr. Gottenberg said. This included improvements in the ESSDAI and EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) and composite measures such as the Sjögren’s Tool for Assessing Response (STAR), Composite of Relevant Endpoints for Sjögren’s Syndrome (CRESS), and the Disease Activity Level. There were also improvements in the unstimulated salivary flow rate.

Safety findings showed no new concerns, with adverse events reported in 62.5% of placebo-treated patients and by 79.2% and 79.6% of patients receiving nipocalimab 5 mg/kg and 15 mg/kg, respectively. Serious adverse events were reported in a respective 5.4%, 7.5%, and 7.4%, including severe infections or infections requiring intravenous anti-infectives in 1.8%, 3.8%, and 1.9% of participants, although none was thought to be related to the study treatment. No opportunistic infections or any deaths were reported.

Thomas Schindler, PhD, senior clinical scientist at F. Hoffmann-La Roche Ltd., in Basel, Switzerland, commented from the audience: “This was a very impressive set of results, and I’m very surprised that its safety profile is so benign.”

Dr. Schindler wanted to know if there were any changes in the serum albumin level and if this manifested as any laboratory abnormalities, but there were no reported cases of severe hypoalbuminemia in the study.
 

The TWINSS Phase 2 Study

Similarly hopeful results were reported for iscalimab, a fully human IgG1 anti-CD40 monoclonal antibody that is given by subcutaneous injection, during a clinical abstracts session. Xavier Mariette, MD, PhD, head of the Rheumatology Department at Bicêtre Hospital, Paris-Saclay University in Paris, France, reported updated results of the phase 2b dose-ranging TWINSS study, showing sustained benefits at 48 weeks. The primary endpoint results at 24 weeks were recently published in The Lancet.

TWINSS was set up to assess the safety and efficacy of iscalimab given every 2 weeks vs placebo in two distinct cohorts of patients with Sjögren disease — one with moderate to severe disease with both systemic and symptomatic involvement and the other with low systemic involvement but high symptom burden.

Whereas patients in the first cohort who had moderate to severe disease (n = 173) were randomly allocated to one of three doses (150, 300, and 600 mg) of iscalimab or placebo for the initial 24 weeks, those in the second cohort (n = 100) were randomly allocated to a 600-mg dose or placebo. After the double-blind period ended, patients taking iscalimab continued on the dose they were taking for another 24 weeks, with those in the placebo arms switching to the 600-mg dose in cohort 1 and the 300-mg dose in cohort 2.

Topline results for those in cohort 1 with moderate to severe Sjögren disease were that the significant improvements in ESSDAI that had been seen at week 24 were maintained in those who continued iscalimab and improved in those who had switched from placebo.

LSM change from baseline in ESSDAI vs placebo at week 24 had been −3.0, −1.4, and −2.9 for the 150-, 300-, and 600-mg doses of iscalimab, respectively. Results at week 48 were a respective −7.6, −5.7, and −7.9. The LSM change for the placebo-treated patients who had switched to the 600-mg dose was −6.7.

Dr. Mariette reported “consistent improvement” in patient-reported outcomes, including ESSPRI, the Sjögren’s Syndrome Symptom Diary, Functional Assessment of Chronic Illness Therapy-Fatigue measure, and the Impact of Dry Eye on Everyday Life instrument. There was also a significant improvement in stimulated salivary flow rates.

Similar benefits were seen in the second cohort of patients who did not have systemic involvement but had a high burden of symptoms, with improved ESSPRI scores of a LSM change from baseline vs placebo of −2.29 for patients continuing iscalimab 600 mg treatment and −1.14 for those taking the 300-mg dose after being treated with placebo. Improvements were also seen in the other patient-reported outcomes used.

Regarding safety, Dr. Mariette reported that there were “no specific issues” seen in the patients who switched from placebo to iscalimab, either at the 300-mg or 600-mg dose. Any adverse event occurred in around 80% of placebo-treated patients and roughly 90% of those given iscalimab, and serious adverse events occurred in 11.4%, 14.3%, and 11.4% pf patients treated with iscalimab 150, 300, and 600 mg, and 4.9% of those given placebo and then 600 mg iscalimab.

“The safety seems equivalent to patients having received iscalimab from the beginning of the trial,” Dr. Mariette said, adding “the risk-benefit [analysis] seems positive in patients up to week 48.”
 

Phase 1 Trial of Tibulizumab

Further positive early trial results were reported by Michael Howell, PhD, chief scientific officer for Zura Bio, a biotech company based in Henderson, Nevada. During a poster tour at EULAR 2024, Dr. Howell presented some preliminary findings from a phase 1 trial of tibulizumab, a dual antagonist of interleukin (IL)-17A and the B-cell–activating factor (BAFF) engineered by fusing elements of ixekizumab (Taltz) and tabalumab together.

“The headline result for me is that the molecule does what it’s supposed to,” Dr. Howell told this news organization. “We have potent engagement of the IL-17 and BAFF pathways, and this sets the tone for additional exploration in rheumatologic diseases where there’s known activation of those two pathways,” he said.

Dr. Howell reported that total B-cell counts and lower levels of type 1 T helper cells were seen during the trial.

Over the years, Dr. Howell, an immunologist, has been involved in the development of many therapeutics, such as risankizumab (Skyrizi) and spesolimab (Spevigo).

“When I look at the molecules and the opportunity we have to do broader antagonism of pathways in a safe aspect, this is probably one of the most exciting,” he said.

The trial he presented included 25 people with a confirmed diagnosis of Sjögren disease and anti-SSA or anti-SSB antibodies. Patients received tibulizumab or a placebo for a total of 12 weeks via a subcutaneous injection. Various doses were tested: 30 mg, 100 mg, or 300 mg every 4 weeks, or 300 mg every 2 weeks.

Serum levels of both BAFF and IL-17A increased as expected in the tibulizumab-treated patients, and Dr. Howell reported that “it’s well tolerated. There’s no adverse event profile that caused any concern.”

As a phase 1 study, it was not powered to look at efficacy, but there were positive signals, Dr. Howell said, meaning that the drug is likely to be tested further in a phase 2 trial.
 

Lusvertikimab Phase 2 Trial

During the same poster tour, the null findings of a phase 2 trial of the anti-IL-7 monoclonal antibody lusvertikimab were presented by Benjamin Fisher, MD, professor of rheumatology at Birmingham University in Birmingham, England.

Dr. Fisher told this news organization: “It’s a negative study, at least over the 3-month period that we’ve studied it.” Whether longer durations of treatment may be needed is a question that currently cannot be answered, he added.

A total of 48 patients with Sjögren disease had been included in the trial from 19 different centers in Europe, the United States, and Australia. The mean age of the participants was 53.7 years, 87% were women, and the mean duration of disease was 5.0 years. Baseline ESSDAI and ESSPRI were 12.1 and 7.0, respectively. Half were receiving other background treatment, and 72.9% were anti-Ro or anti-SSA positive.

Lusvertikimab 750 mg or a matching placebo was given via intravenous infusion at weeks 0, 2, 4, 7, and 10.

The primary endpoint was the mean change in ESSDAI from baseline to week 13, which was the same, at −3.9, in both groups. There was also no significant difference between the groups in any of the other secondary endpoints that were used, including ESSPRI, Schirmer’s test, the ocular staining score, salivary flow rate, physician and patient global assessment, assessment of fatigue, quality of life, or the composite measures STAR and CRESS.

“This isn’t going anywhere,” said Dr. Fisher, asking what was going to happen next and if this meant the end of IL-7-focused therapy.

“For years, there’s been quite a lot of interest in this,” Dr. Fisher said. Sjögren disease is characterized by a sort of focal inflammation of the saliva glands, which is composed of both T and B cells in the early stages, probably a T-cell component and a B-cell component, he explained.

“IL-7 is thought to be an important cytokine for homeostasis of the T-cell compartment, so for maintenance of T central memory and effector memory cells,” he said. “So, the idea is that, if you block IL-7, you switch off T cells, and you may rebalance the immune system towards a more regulatory phenotype. Just that it didn’t work,” Dr. Fisher said.

“There’s large unmet need,” he said. “Sjögren’s is associated with poor health-related quality of life, [and] a large part that is symptom-driven — dryness and fatigue — which we have no real interventions yet for patients; there’s no licensed therapeutics for it.”

Dr. Fisher cited ianalumab as one of the front-runners for becoming the first licensed treatment for Sjögren disease. The novel BAFF-targeting antibody is already in phase 3 trials and is also showing promise for the treatment of systemic lupus erythematosus.

“Then there are CD40-targeting drugs; the ones most advanced are dazodalibep and iscalimab.” Commenting on the potential of iscalimab, Dr. Fisher said that it “seems to work — it improves systemic disease activity; it also leads to some symptomatic improvement, which has been difficult to demonstrate in Sjögren’s.”

Dr. Fisher added that “the nipocalimab data looks interesting, as do data on TYK2 inhibition.”

The DAHLIAS study was funded by Janssen Research & Development. Dr. Gottenberg has consulted for AbbVie, Bristol Myers Squibb (BMS), Galapagos, Gilead, Janssen, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Sanofi, and UCB. The TWINSS study was funded by Novartis. Dr. Mariette has consulted for BMS, Galapagos, GlaxoSmithKline, Novartis, Pfizer, and Servier. The tibulizumab phase 1 study was funded by Eli Lilly & Company. Dr. Howell is an employee of the developer, Zura Bio. The Institut de Recherches Internationales Servier sponsored the lusvertikimab trial. Dr. Fisher has consulted for Novartis, Roche, BMS, Galapagos, Janssen, Servier, UCB, and Sanofi and received funding to his institution for collaborative research from Janssen, Celgene, Galapagos, and Servier.
 

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

VIENNA — Nipocalimab, iscalimab, and tibulizumab, but not lusvertikimab, appear to be promising new agents for Sjögren disease that warrant further investigation, suggest the results of four separate early clinical trials reported at the recent annual European Congress of Rheumatology (EULAR).

This is potentially good news for patients, as discovering new treatments that work for managing the various symptoms of Sjögren disease is a high priority, Jacques-Eric Gottenberg, MD, PhD, said when he presented the results of the phase 2 DAHLIAS study of nipocalimab during a late-breaking abstract session.

“All patients suffer from high burden of symptoms — pain, fatigue, and dryness; nearly 50% of patients have systemic complications; mortality is increased, so there is a high unmet need since no specific drug has been accepted so far,” said Dr. Gottenberg, who works at Strasbourg University Hospital in Strasbourg, France.

“The pathogenesis of the disease involves high B-cell activation, resulting in high IgG levels, and secretion of autoantibodies,” such as anti-Ro, anti-La, anti-Sjögren’s syndrome type A (anti-SSA), and anti-Sjögren’s syndrome type B antibodies, Dr. Gottenberg said.

Thus, one approach to reducing the disease burden is to try to lower circulating immunoglobulin G (IgG) levels and IgG-associated autoantibodies, which is how the monoclonal antibody nipocalimab works. Nipocalimab essentially blocks the interaction of IgG with the neonatal fragment crystallizable receptor and has already been shown to have efficacy in other autoimmune conditions such as myasthenia gravis and fetal and neonatal hemolytic disease, although not as hoped in rheumatoid arthritis.
 

The DAHLIAS Phase 2 Study

Now, results from the DAHLIAS study show that nipocalimab may also work in Sjögren disease, with significant improvement vs placebo seen in the primary endpoint of the total EULAR Sjögren’s Syndrome Disease Activity Index (clinESSDAI) at 24 weeks for one of the two doses of the drug that were tested.

The multicenter, placebo-controlled, double-blind study was conducted in 163 patients with moderate to severely active primary Sjögren disease. The latter was determined by having a clinESSDAI of 6 or higher and seropositivity for anti-Ro60, anti-Ro52, or both autoantibodies.

Dr. Gottenberg reported that the mean age of patients was 48 years; the majority (92.6%) were women and of White ethnicity (90.8%). The baseline clinESSDAI was a mean of 9.9; 98.1% had anti-Ro60, 80.6% had anti-Ro52, and 71.9% had anti-La antibodies.

In addition to standard of care, patients were randomly allocated to receive intravenous treatment every 2 weeks with nipocalimab 5 mg/kg or 15 mg/kg, or placebo.

At 24 weeks, the least squares mean (LSM) change in clinESSDAI from baseline was −3.74 for placebo, −4.08 for nipocalimab 5 mg/kg (P = not significant vs placebo), and −6.40 for nipocalimab 15 mg/kg (P = .02 vs placebo).

Nipocalimab 15 mg/kg also “demonstrated similar and consistent trends in other key efficacy endpoints,” Dr. Gottenberg said. This included improvements in the ESSDAI and EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) and composite measures such as the Sjögren’s Tool for Assessing Response (STAR), Composite of Relevant Endpoints for Sjögren’s Syndrome (CRESS), and the Disease Activity Level. There were also improvements in the unstimulated salivary flow rate.

Safety findings showed no new concerns, with adverse events reported in 62.5% of placebo-treated patients and by 79.2% and 79.6% of patients receiving nipocalimab 5 mg/kg and 15 mg/kg, respectively. Serious adverse events were reported in a respective 5.4%, 7.5%, and 7.4%, including severe infections or infections requiring intravenous anti-infectives in 1.8%, 3.8%, and 1.9% of participants, although none was thought to be related to the study treatment. No opportunistic infections or any deaths were reported.

Thomas Schindler, PhD, senior clinical scientist at F. Hoffmann-La Roche Ltd., in Basel, Switzerland, commented from the audience: “This was a very impressive set of results, and I’m very surprised that its safety profile is so benign.”

Dr. Schindler wanted to know if there were any changes in the serum albumin level and if this manifested as any laboratory abnormalities, but there were no reported cases of severe hypoalbuminemia in the study.
 

The TWINSS Phase 2 Study

Similarly hopeful results were reported for iscalimab, a fully human IgG1 anti-CD40 monoclonal antibody that is given by subcutaneous injection, during a clinical abstracts session. Xavier Mariette, MD, PhD, head of the Rheumatology Department at Bicêtre Hospital, Paris-Saclay University in Paris, France, reported updated results of the phase 2b dose-ranging TWINSS study, showing sustained benefits at 48 weeks. The primary endpoint results at 24 weeks were recently published in The Lancet.

TWINSS was set up to assess the safety and efficacy of iscalimab given every 2 weeks vs placebo in two distinct cohorts of patients with Sjögren disease — one with moderate to severe disease with both systemic and symptomatic involvement and the other with low systemic involvement but high symptom burden.

Whereas patients in the first cohort who had moderate to severe disease (n = 173) were randomly allocated to one of three doses (150, 300, and 600 mg) of iscalimab or placebo for the initial 24 weeks, those in the second cohort (n = 100) were randomly allocated to a 600-mg dose or placebo. After the double-blind period ended, patients taking iscalimab continued on the dose they were taking for another 24 weeks, with those in the placebo arms switching to the 600-mg dose in cohort 1 and the 300-mg dose in cohort 2.

Topline results for those in cohort 1 with moderate to severe Sjögren disease were that the significant improvements in ESSDAI that had been seen at week 24 were maintained in those who continued iscalimab and improved in those who had switched from placebo.

LSM change from baseline in ESSDAI vs placebo at week 24 had been −3.0, −1.4, and −2.9 for the 150-, 300-, and 600-mg doses of iscalimab, respectively. Results at week 48 were a respective −7.6, −5.7, and −7.9. The LSM change for the placebo-treated patients who had switched to the 600-mg dose was −6.7.

Dr. Mariette reported “consistent improvement” in patient-reported outcomes, including ESSPRI, the Sjögren’s Syndrome Symptom Diary, Functional Assessment of Chronic Illness Therapy-Fatigue measure, and the Impact of Dry Eye on Everyday Life instrument. There was also a significant improvement in stimulated salivary flow rates.

Similar benefits were seen in the second cohort of patients who did not have systemic involvement but had a high burden of symptoms, with improved ESSPRI scores of a LSM change from baseline vs placebo of −2.29 for patients continuing iscalimab 600 mg treatment and −1.14 for those taking the 300-mg dose after being treated with placebo. Improvements were also seen in the other patient-reported outcomes used.

Regarding safety, Dr. Mariette reported that there were “no specific issues” seen in the patients who switched from placebo to iscalimab, either at the 300-mg or 600-mg dose. Any adverse event occurred in around 80% of placebo-treated patients and roughly 90% of those given iscalimab, and serious adverse events occurred in 11.4%, 14.3%, and 11.4% pf patients treated with iscalimab 150, 300, and 600 mg, and 4.9% of those given placebo and then 600 mg iscalimab.

“The safety seems equivalent to patients having received iscalimab from the beginning of the trial,” Dr. Mariette said, adding “the risk-benefit [analysis] seems positive in patients up to week 48.”
 

Phase 1 Trial of Tibulizumab

Further positive early trial results were reported by Michael Howell, PhD, chief scientific officer for Zura Bio, a biotech company based in Henderson, Nevada. During a poster tour at EULAR 2024, Dr. Howell presented some preliminary findings from a phase 1 trial of tibulizumab, a dual antagonist of interleukin (IL)-17A and the B-cell–activating factor (BAFF) engineered by fusing elements of ixekizumab (Taltz) and tabalumab together.

“The headline result for me is that the molecule does what it’s supposed to,” Dr. Howell told this news organization. “We have potent engagement of the IL-17 and BAFF pathways, and this sets the tone for additional exploration in rheumatologic diseases where there’s known activation of those two pathways,” he said.

Dr. Howell reported that total B-cell counts and lower levels of type 1 T helper cells were seen during the trial.

Over the years, Dr. Howell, an immunologist, has been involved in the development of many therapeutics, such as risankizumab (Skyrizi) and spesolimab (Spevigo).

“When I look at the molecules and the opportunity we have to do broader antagonism of pathways in a safe aspect, this is probably one of the most exciting,” he said.

The trial he presented included 25 people with a confirmed diagnosis of Sjögren disease and anti-SSA or anti-SSB antibodies. Patients received tibulizumab or a placebo for a total of 12 weeks via a subcutaneous injection. Various doses were tested: 30 mg, 100 mg, or 300 mg every 4 weeks, or 300 mg every 2 weeks.

Serum levels of both BAFF and IL-17A increased as expected in the tibulizumab-treated patients, and Dr. Howell reported that “it’s well tolerated. There’s no adverse event profile that caused any concern.”

As a phase 1 study, it was not powered to look at efficacy, but there were positive signals, Dr. Howell said, meaning that the drug is likely to be tested further in a phase 2 trial.
 

Lusvertikimab Phase 2 Trial

During the same poster tour, the null findings of a phase 2 trial of the anti-IL-7 monoclonal antibody lusvertikimab were presented by Benjamin Fisher, MD, professor of rheumatology at Birmingham University in Birmingham, England.

Dr. Fisher told this news organization: “It’s a negative study, at least over the 3-month period that we’ve studied it.” Whether longer durations of treatment may be needed is a question that currently cannot be answered, he added.

A total of 48 patients with Sjögren disease had been included in the trial from 19 different centers in Europe, the United States, and Australia. The mean age of the participants was 53.7 years, 87% were women, and the mean duration of disease was 5.0 years. Baseline ESSDAI and ESSPRI were 12.1 and 7.0, respectively. Half were receiving other background treatment, and 72.9% were anti-Ro or anti-SSA positive.

Lusvertikimab 750 mg or a matching placebo was given via intravenous infusion at weeks 0, 2, 4, 7, and 10.

The primary endpoint was the mean change in ESSDAI from baseline to week 13, which was the same, at −3.9, in both groups. There was also no significant difference between the groups in any of the other secondary endpoints that were used, including ESSPRI, Schirmer’s test, the ocular staining score, salivary flow rate, physician and patient global assessment, assessment of fatigue, quality of life, or the composite measures STAR and CRESS.

“This isn’t going anywhere,” said Dr. Fisher, asking what was going to happen next and if this meant the end of IL-7-focused therapy.

“For years, there’s been quite a lot of interest in this,” Dr. Fisher said. Sjögren disease is characterized by a sort of focal inflammation of the saliva glands, which is composed of both T and B cells in the early stages, probably a T-cell component and a B-cell component, he explained.

“IL-7 is thought to be an important cytokine for homeostasis of the T-cell compartment, so for maintenance of T central memory and effector memory cells,” he said. “So, the idea is that, if you block IL-7, you switch off T cells, and you may rebalance the immune system towards a more regulatory phenotype. Just that it didn’t work,” Dr. Fisher said.

“There’s large unmet need,” he said. “Sjögren’s is associated with poor health-related quality of life, [and] a large part that is symptom-driven — dryness and fatigue — which we have no real interventions yet for patients; there’s no licensed therapeutics for it.”

Dr. Fisher cited ianalumab as one of the front-runners for becoming the first licensed treatment for Sjögren disease. The novel BAFF-targeting antibody is already in phase 3 trials and is also showing promise for the treatment of systemic lupus erythematosus.

“Then there are CD40-targeting drugs; the ones most advanced are dazodalibep and iscalimab.” Commenting on the potential of iscalimab, Dr. Fisher said that it “seems to work — it improves systemic disease activity; it also leads to some symptomatic improvement, which has been difficult to demonstrate in Sjögren’s.”

Dr. Fisher added that “the nipocalimab data looks interesting, as do data on TYK2 inhibition.”

The DAHLIAS study was funded by Janssen Research & Development. Dr. Gottenberg has consulted for AbbVie, Bristol Myers Squibb (BMS), Galapagos, Gilead, Janssen, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Sanofi, and UCB. The TWINSS study was funded by Novartis. Dr. Mariette has consulted for BMS, Galapagos, GlaxoSmithKline, Novartis, Pfizer, and Servier. The tibulizumab phase 1 study was funded by Eli Lilly & Company. Dr. Howell is an employee of the developer, Zura Bio. The Institut de Recherches Internationales Servier sponsored the lusvertikimab trial. Dr. Fisher has consulted for Novartis, Roche, BMS, Galapagos, Janssen, Servier, UCB, and Sanofi and received funding to his institution for collaborative research from Janssen, Celgene, Galapagos, and Servier.
 

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

VIENNA — Nipocalimab, iscalimab, and tibulizumab, but not lusvertikimab, appear to be promising new agents for Sjögren disease that warrant further investigation, suggest the results of four separate early clinical trials reported at the recent annual European Congress of Rheumatology (EULAR).

This is potentially good news for patients, as discovering new treatments that work for managing the various symptoms of Sjögren disease is a high priority, Jacques-Eric Gottenberg, MD, PhD, said when he presented the results of the phase 2 DAHLIAS study of nipocalimab during a late-breaking abstract session.

“All patients suffer from high burden of symptoms — pain, fatigue, and dryness; nearly 50% of patients have systemic complications; mortality is increased, so there is a high unmet need since no specific drug has been accepted so far,” said Dr. Gottenberg, who works at Strasbourg University Hospital in Strasbourg, France.

“The pathogenesis of the disease involves high B-cell activation, resulting in high IgG levels, and secretion of autoantibodies,” such as anti-Ro, anti-La, anti-Sjögren’s syndrome type A (anti-SSA), and anti-Sjögren’s syndrome type B antibodies, Dr. Gottenberg said.

Thus, one approach to reducing the disease burden is to try to lower circulating immunoglobulin G (IgG) levels and IgG-associated autoantibodies, which is how the monoclonal antibody nipocalimab works. Nipocalimab essentially blocks the interaction of IgG with the neonatal fragment crystallizable receptor and has already been shown to have efficacy in other autoimmune conditions such as myasthenia gravis and fetal and neonatal hemolytic disease, although not as hoped in rheumatoid arthritis.
 

The DAHLIAS Phase 2 Study

Now, results from the DAHLIAS study show that nipocalimab may also work in Sjögren disease, with significant improvement vs placebo seen in the primary endpoint of the total EULAR Sjögren’s Syndrome Disease Activity Index (clinESSDAI) at 24 weeks for one of the two doses of the drug that were tested.

The multicenter, placebo-controlled, double-blind study was conducted in 163 patients with moderate to severely active primary Sjögren disease. The latter was determined by having a clinESSDAI of 6 or higher and seropositivity for anti-Ro60, anti-Ro52, or both autoantibodies.

Dr. Gottenberg reported that the mean age of patients was 48 years; the majority (92.6%) were women and of White ethnicity (90.8%). The baseline clinESSDAI was a mean of 9.9; 98.1% had anti-Ro60, 80.6% had anti-Ro52, and 71.9% had anti-La antibodies.

In addition to standard of care, patients were randomly allocated to receive intravenous treatment every 2 weeks with nipocalimab 5 mg/kg or 15 mg/kg, or placebo.

At 24 weeks, the least squares mean (LSM) change in clinESSDAI from baseline was −3.74 for placebo, −4.08 for nipocalimab 5 mg/kg (P = not significant vs placebo), and −6.40 for nipocalimab 15 mg/kg (P = .02 vs placebo).

Nipocalimab 15 mg/kg also “demonstrated similar and consistent trends in other key efficacy endpoints,” Dr. Gottenberg said. This included improvements in the ESSDAI and EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) and composite measures such as the Sjögren’s Tool for Assessing Response (STAR), Composite of Relevant Endpoints for Sjögren’s Syndrome (CRESS), and the Disease Activity Level. There were also improvements in the unstimulated salivary flow rate.

Safety findings showed no new concerns, with adverse events reported in 62.5% of placebo-treated patients and by 79.2% and 79.6% of patients receiving nipocalimab 5 mg/kg and 15 mg/kg, respectively. Serious adverse events were reported in a respective 5.4%, 7.5%, and 7.4%, including severe infections or infections requiring intravenous anti-infectives in 1.8%, 3.8%, and 1.9% of participants, although none was thought to be related to the study treatment. No opportunistic infections or any deaths were reported.

Thomas Schindler, PhD, senior clinical scientist at F. Hoffmann-La Roche Ltd., in Basel, Switzerland, commented from the audience: “This was a very impressive set of results, and I’m very surprised that its safety profile is so benign.”

Dr. Schindler wanted to know if there were any changes in the serum albumin level and if this manifested as any laboratory abnormalities, but there were no reported cases of severe hypoalbuminemia in the study.
 

The TWINSS Phase 2 Study

Similarly hopeful results were reported for iscalimab, a fully human IgG1 anti-CD40 monoclonal antibody that is given by subcutaneous injection, during a clinical abstracts session. Xavier Mariette, MD, PhD, head of the Rheumatology Department at Bicêtre Hospital, Paris-Saclay University in Paris, France, reported updated results of the phase 2b dose-ranging TWINSS study, showing sustained benefits at 48 weeks. The primary endpoint results at 24 weeks were recently published in The Lancet.

TWINSS was set up to assess the safety and efficacy of iscalimab given every 2 weeks vs placebo in two distinct cohorts of patients with Sjögren disease — one with moderate to severe disease with both systemic and symptomatic involvement and the other with low systemic involvement but high symptom burden.

Whereas patients in the first cohort who had moderate to severe disease (n = 173) were randomly allocated to one of three doses (150, 300, and 600 mg) of iscalimab or placebo for the initial 24 weeks, those in the second cohort (n = 100) were randomly allocated to a 600-mg dose or placebo. After the double-blind period ended, patients taking iscalimab continued on the dose they were taking for another 24 weeks, with those in the placebo arms switching to the 600-mg dose in cohort 1 and the 300-mg dose in cohort 2.

Topline results for those in cohort 1 with moderate to severe Sjögren disease were that the significant improvements in ESSDAI that had been seen at week 24 were maintained in those who continued iscalimab and improved in those who had switched from placebo.

LSM change from baseline in ESSDAI vs placebo at week 24 had been −3.0, −1.4, and −2.9 for the 150-, 300-, and 600-mg doses of iscalimab, respectively. Results at week 48 were a respective −7.6, −5.7, and −7.9. The LSM change for the placebo-treated patients who had switched to the 600-mg dose was −6.7.

Dr. Mariette reported “consistent improvement” in patient-reported outcomes, including ESSPRI, the Sjögren’s Syndrome Symptom Diary, Functional Assessment of Chronic Illness Therapy-Fatigue measure, and the Impact of Dry Eye on Everyday Life instrument. There was also a significant improvement in stimulated salivary flow rates.

Similar benefits were seen in the second cohort of patients who did not have systemic involvement but had a high burden of symptoms, with improved ESSPRI scores of a LSM change from baseline vs placebo of −2.29 for patients continuing iscalimab 600 mg treatment and −1.14 for those taking the 300-mg dose after being treated with placebo. Improvements were also seen in the other patient-reported outcomes used.

Regarding safety, Dr. Mariette reported that there were “no specific issues” seen in the patients who switched from placebo to iscalimab, either at the 300-mg or 600-mg dose. Any adverse event occurred in around 80% of placebo-treated patients and roughly 90% of those given iscalimab, and serious adverse events occurred in 11.4%, 14.3%, and 11.4% pf patients treated with iscalimab 150, 300, and 600 mg, and 4.9% of those given placebo and then 600 mg iscalimab.

“The safety seems equivalent to patients having received iscalimab from the beginning of the trial,” Dr. Mariette said, adding “the risk-benefit [analysis] seems positive in patients up to week 48.”
 

Phase 1 Trial of Tibulizumab

Further positive early trial results were reported by Michael Howell, PhD, chief scientific officer for Zura Bio, a biotech company based in Henderson, Nevada. During a poster tour at EULAR 2024, Dr. Howell presented some preliminary findings from a phase 1 trial of tibulizumab, a dual antagonist of interleukin (IL)-17A and the B-cell–activating factor (BAFF) engineered by fusing elements of ixekizumab (Taltz) and tabalumab together.

“The headline result for me is that the molecule does what it’s supposed to,” Dr. Howell told this news organization. “We have potent engagement of the IL-17 and BAFF pathways, and this sets the tone for additional exploration in rheumatologic diseases where there’s known activation of those two pathways,” he said.

Dr. Howell reported that total B-cell counts and lower levels of type 1 T helper cells were seen during the trial.

Over the years, Dr. Howell, an immunologist, has been involved in the development of many therapeutics, such as risankizumab (Skyrizi) and spesolimab (Spevigo).

“When I look at the molecules and the opportunity we have to do broader antagonism of pathways in a safe aspect, this is probably one of the most exciting,” he said.

The trial he presented included 25 people with a confirmed diagnosis of Sjögren disease and anti-SSA or anti-SSB antibodies. Patients received tibulizumab or a placebo for a total of 12 weeks via a subcutaneous injection. Various doses were tested: 30 mg, 100 mg, or 300 mg every 4 weeks, or 300 mg every 2 weeks.

Serum levels of both BAFF and IL-17A increased as expected in the tibulizumab-treated patients, and Dr. Howell reported that “it’s well tolerated. There’s no adverse event profile that caused any concern.”

As a phase 1 study, it was not powered to look at efficacy, but there were positive signals, Dr. Howell said, meaning that the drug is likely to be tested further in a phase 2 trial.
 

Lusvertikimab Phase 2 Trial

During the same poster tour, the null findings of a phase 2 trial of the anti-IL-7 monoclonal antibody lusvertikimab were presented by Benjamin Fisher, MD, professor of rheumatology at Birmingham University in Birmingham, England.

Dr. Fisher told this news organization: “It’s a negative study, at least over the 3-month period that we’ve studied it.” Whether longer durations of treatment may be needed is a question that currently cannot be answered, he added.

A total of 48 patients with Sjögren disease had been included in the trial from 19 different centers in Europe, the United States, and Australia. The mean age of the participants was 53.7 years, 87% were women, and the mean duration of disease was 5.0 years. Baseline ESSDAI and ESSPRI were 12.1 and 7.0, respectively. Half were receiving other background treatment, and 72.9% were anti-Ro or anti-SSA positive.

Lusvertikimab 750 mg or a matching placebo was given via intravenous infusion at weeks 0, 2, 4, 7, and 10.

The primary endpoint was the mean change in ESSDAI from baseline to week 13, which was the same, at −3.9, in both groups. There was also no significant difference between the groups in any of the other secondary endpoints that were used, including ESSPRI, Schirmer’s test, the ocular staining score, salivary flow rate, physician and patient global assessment, assessment of fatigue, quality of life, or the composite measures STAR and CRESS.

“This isn’t going anywhere,” said Dr. Fisher, asking what was going to happen next and if this meant the end of IL-7-focused therapy.

“For years, there’s been quite a lot of interest in this,” Dr. Fisher said. Sjögren disease is characterized by a sort of focal inflammation of the saliva glands, which is composed of both T and B cells in the early stages, probably a T-cell component and a B-cell component, he explained.

“IL-7 is thought to be an important cytokine for homeostasis of the T-cell compartment, so for maintenance of T central memory and effector memory cells,” he said. “So, the idea is that, if you block IL-7, you switch off T cells, and you may rebalance the immune system towards a more regulatory phenotype. Just that it didn’t work,” Dr. Fisher said.

“There’s large unmet need,” he said. “Sjögren’s is associated with poor health-related quality of life, [and] a large part that is symptom-driven — dryness and fatigue — which we have no real interventions yet for patients; there’s no licensed therapeutics for it.”

Dr. Fisher cited ianalumab as one of the front-runners for becoming the first licensed treatment for Sjögren disease. The novel BAFF-targeting antibody is already in phase 3 trials and is also showing promise for the treatment of systemic lupus erythematosus.

“Then there are CD40-targeting drugs; the ones most advanced are dazodalibep and iscalimab.” Commenting on the potential of iscalimab, Dr. Fisher said that it “seems to work — it improves systemic disease activity; it also leads to some symptomatic improvement, which has been difficult to demonstrate in Sjögren’s.”

Dr. Fisher added that “the nipocalimab data looks interesting, as do data on TYK2 inhibition.”

The DAHLIAS study was funded by Janssen Research & Development. Dr. Gottenberg has consulted for AbbVie, Bristol Myers Squibb (BMS), Galapagos, Gilead, Janssen, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Sanofi, and UCB. The TWINSS study was funded by Novartis. Dr. Mariette has consulted for BMS, Galapagos, GlaxoSmithKline, Novartis, Pfizer, and Servier. The tibulizumab phase 1 study was funded by Eli Lilly & Company. Dr. Howell is an employee of the developer, Zura Bio. The Institut de Recherches Internationales Servier sponsored the lusvertikimab trial. Dr. Fisher has consulted for Novartis, Roche, BMS, Galapagos, Janssen, Servier, UCB, and Sanofi and received funding to his institution for collaborative research from Janssen, Celgene, Galapagos, and Servier.
 

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

Strapped for cash and searching for new profits, Tennessee-based Erlanger Health System illegally paid excessive salaries to physicians in exchange for patient referrals, the US government alleged in a federal lawsuit.

Erlanger changed its compensation model to entice revenue-generating doctors, paying some two to three times the median salary for their specialty, according to the complaint. 

The physicians in turn referred numerous patients to Erlanger, and the health system submitted claims to Medicare for the referred services in violation of the Stark Law, according to the suit, filed in US District Court for the Western District of North Carolina. 

The government’s complaint “serves as a warning” to healthcare providers who try to boost profits through improper financial arrangements with referring physicians, said Tamala E. Miles, Special Agent in Charge for the US Department of Health and Human Services (HHS) Office of Inspector General (OIG).

In a statement provided to this news organization, Erlanger denied the allegations and said it would “vigorously” defend the lawsuit. 

“Erlanger paid physicians based on amounts that outside experts advised was fair market value,” Erlanger officials said in the statement. “Erlanger did not pay for referrals. A complete picture of the facts will demonstrate that the allegations lack merit and tell a very different story than what the government now claims.”

The Erlanger case is a reminder to physicians to consult their own knowledgeable advisors when considering financial arrangements with hospitals, said William Sarraille, JD, adjunct professor for the University of Maryland Francis King Carey School of Law in Baltimore and a regulatory consultant. 

“There is a tendency by physicians when contracting ... to rely on [hospitals’] perceived compliance and legal expertise,” Mr. Sarraille told this news organization. “This case illustrates the risks in doing so. Sometimes bigger doesn’t translate into more sophisticated or more effective from a compliance perspective.” 
 

Stark Law Prohibits Kickbacks

The Stark Law prohibits hospitals from billing the Centers for Medicare & Medicaid Services (CMS) for services referred by a physician with whom the hospital has an improper financial relationship.

CMS paid Erlanger about $27.8 million for claims stemming from the improper financial arrangements, the government contends. 

“HHS-OIG will continue to investigate such deals to prevent financial arrangements that could compromise impartial medical judgment, increase healthcare costs, and erode public trust in the healthcare system,” Ms. Miles said in a statement. 
 

Suit: Health System’s Money Woes Led to Illegal Arrangements

Erlanger’s financial troubles allegedly started after a previous run-in with the US government over false claims. 

In 2005, Erlanger Health System agreed to pay the government $40 million to resolve allegations that it knowingly submitted false claims to Medicare, according to the government’s complaint. At the time, Erlanger entered into a Corporate Integrity Agreement (CIA) with the OIG that required Erlanger to put controls in place to ensure its financial relationships did not violate the Stark Law. 

Erlanger’s agreement with OIG ended in 2010. Over the next 3 years, the health system lost nearly $32 million and in fiscal year 2013, had only 65 days of cash on hand, according to the government’s lawsuit. 

Beginning in 2013, Erlanger allegedly implemented a strategy to increase profits by employing more physicians, particularly specialists from competing hospitals whose patients would need costly hospital stays, according to the complaint. 

Once hired, Erlanger’s physicians were expected to treat patients at Erlanger’s hospitals and refer them to other providers within the health system, the suit claims. Erlanger also relaxed or eliminated the oversight and controls on physician compensation put in place under the CIA. For example, Erlanger’s CEO signed some compensation contracts before its chief compliance officer could review them and no longer allowed the compliance officer to vote on whether to approve compensation arrangements, according to the complaint. 

Erlanger also changed its compensation model to include large salaries for medical director and academic positions and allegedly paid such salaries to physicians without ensuring the required work was performed. As a result, Erlanger physicians with profitable referrals were among the highest paid in the nation for their specialties, the government claims. For example, according to the complaint:

• Erlanger paid an electrophysiologist an annual clinical salary of $816,701, a medical director salary of $101,080, an academic salary of $59,322, and a productivity incentive based on work relative value units (wRVUs). The medical director and academic salaries paid were near the 90th percentile of comparable salaries in the specialty.
• The health system paid a neurosurgeon a base salary of $654,735, a productivity incentive based on wRVUs, and payments for excess call coverage ranging from $400 to $1000 per 24-hour shift. In 2016, the neurosurgeon made $500,000 in excess call payments.
• Erlanger paid a cardiothoracic surgeon a base clinical salary of $1,070,000, a sign-on bonus of $150,000, a retention bonus of $100,000 (payable in the 4th year of the contract), and a program incentive of up to $150,000 per year.

In addition, Erlanger ignored patient safety concerns about some of its high revenue-generating physicians, the government claims. 

For instance, Erlanger received multiple complaints that a cardiothoracic surgeon was misusing an expensive form of life support in which pumps and oxygenators take over heart and lung function. Overuse of the equipment prolonged patients’ hospital stays and increased the hospital fees generated by the surgeon, according to the complaint. Staff also raised concerns about the cardiothoracic surgeon’s patient outcomes. 

But Erlanger disregarded the concerns and in 2018, increased the cardiothoracic surgeon’s retention bonus from $100,000 to $250,000, the suit alleges. A year later, the health system increased his base salary from $1,070,000 to $1,195,000.

Health care compensation and billing consultants alerted Erlanger that it was overpaying salaries and handing out bonuses based on measures that overstated the work physicians were performing, but Erlanger ignored the warnings, according to the complaint. 

Administrators allegedly resisted efforts by the chief compliance officer to hire an outside consultant to review its compensation models. Erlanger fired the compliance officer in 2019. 

The former chief compliance officer and another administrator filed a whistleblower lawsuit against Erlanger in 2021. The two administrators are relators in the government’s July 2024 lawsuit. 
 

How to Protect Yourself From Illegal Hospital Deals

The Erlanger case is the latest in a series of recent complaints by the federal government involving financial arrangements between hospitals and physicians.

In December 2023, Indianapolis-based Community Health Network Inc. agreed to pay the government $345 million to resolve claims that it paid physicians above fair market value and awarded bonuses tied to referrals in violation of the Stark Law. 

Also in 2023, Saginaw, Michigan–based Covenant HealthCare and two physicians paid the government $69 million to settle allegations that administrators engaged in improper financial arrangements with referring physicians and a physician-owned investment group. In another 2023 case, Massachusetts Eye and Ear in Boston agreed to pay $5.7 million to resolve claims that some of its physician compensation plans violated the Stark Law. 

Before you enter into a financial arrangement with a hospital, it’s also important to examine what percentile the aggregate compensation would reflect, law professor Mr. Sarraille said. The Erlanger case highlights federal officials’ suspicion of compensation, in aggregate, that exceeds the 90th percentile and increased attention to compensation that exceeds the 75th percentile, he said. 

To research compensation levels, doctors can review the Medical Group Management Association’s annual compensation report or search its compensation data. 

Before signing any contracts, Mr. Sarraille suggests, physicians should also consider whether the hospital shares the same values. Ask physicians at the hospital what they have to say about the hospital’s culture, vision, and values. Have physicians left the hospital after their practices were acquired? Consider speaking with them to learn why. 

Keep in mind that a doctor’s reputation could be impacted by a compliance complaint, regardless of whether it’s directed at the hospital and not the employed physician, Mr. Sarraille said. 

“The [Erlanger] complaint focuses on the compensation of specific, named physicians saying they were wildly overcompensated,” he said. “The implication is that they sold their referral power in exchange for a pay day. It’s a bad look, no matter how the case evolves from here.” 

Physicians could also face their own liability risk under the Stark Law and False Claims Act, depending on the circumstances. In the event of related quality-of-care issues, medical liability could come into play, Mr. Sarraille noted. In such cases, plaintiffs’ attorneys may see an opportunity to boost their claims with allegations that the patient harm was a function of “chasing compensation dollars,” Mr. Sarraille said. 

“Where that happens, plaintiff lawyers see the potential for crippling punitive damages, which might not be covered by an insurer,” he said.

A version of this article appeared on Medscape.com.

Strapped for cash and searching for new profits, Tennessee-based Erlanger Health System illegally paid excessive salaries to physicians in exchange for patient referrals, the US government alleged in a federal lawsuit.

Erlanger changed its compensation model to entice revenue-generating doctors, paying some two to three times the median salary for their specialty, according to the complaint. 

The physicians in turn referred numerous patients to Erlanger, and the health system submitted claims to Medicare for the referred services in violation of the Stark Law, according to the suit, filed in US District Court for the Western District of North Carolina. 

The government’s complaint “serves as a warning” to healthcare providers who try to boost profits through improper financial arrangements with referring physicians, said Tamala E. Miles, Special Agent in Charge for the US Department of Health and Human Services (HHS) Office of Inspector General (OIG).

In a statement provided to this news organization, Erlanger denied the allegations and said it would “vigorously” defend the lawsuit. 

“Erlanger paid physicians based on amounts that outside experts advised was fair market value,” Erlanger officials said in the statement. “Erlanger did not pay for referrals. A complete picture of the facts will demonstrate that the allegations lack merit and tell a very different story than what the government now claims.”

The Erlanger case is a reminder to physicians to consult their own knowledgeable advisors when considering financial arrangements with hospitals, said William Sarraille, JD, adjunct professor for the University of Maryland Francis King Carey School of Law in Baltimore and a regulatory consultant. 

“There is a tendency by physicians when contracting ... to rely on [hospitals’] perceived compliance and legal expertise,” Mr. Sarraille told this news organization. “This case illustrates the risks in doing so. Sometimes bigger doesn’t translate into more sophisticated or more effective from a compliance perspective.” 
 

Stark Law Prohibits Kickbacks

The Stark Law prohibits hospitals from billing the Centers for Medicare & Medicaid Services (CMS) for services referred by a physician with whom the hospital has an improper financial relationship.

CMS paid Erlanger about $27.8 million for claims stemming from the improper financial arrangements, the government contends. 

“HHS-OIG will continue to investigate such deals to prevent financial arrangements that could compromise impartial medical judgment, increase healthcare costs, and erode public trust in the healthcare system,” Ms. Miles said in a statement. 
 

Suit: Health System’s Money Woes Led to Illegal Arrangements

Erlanger’s financial troubles allegedly started after a previous run-in with the US government over false claims. 

In 2005, Erlanger Health System agreed to pay the government $40 million to resolve allegations that it knowingly submitted false claims to Medicare, according to the government’s complaint. At the time, Erlanger entered into a Corporate Integrity Agreement (CIA) with the OIG that required Erlanger to put controls in place to ensure its financial relationships did not violate the Stark Law. 

Erlanger’s agreement with OIG ended in 2010. Over the next 3 years, the health system lost nearly $32 million and in fiscal year 2013, had only 65 days of cash on hand, according to the government’s lawsuit. 

Beginning in 2013, Erlanger allegedly implemented a strategy to increase profits by employing more physicians, particularly specialists from competing hospitals whose patients would need costly hospital stays, according to the complaint. 

Once hired, Erlanger’s physicians were expected to treat patients at Erlanger’s hospitals and refer them to other providers within the health system, the suit claims. Erlanger also relaxed or eliminated the oversight and controls on physician compensation put in place under the CIA. For example, Erlanger’s CEO signed some compensation contracts before its chief compliance officer could review them and no longer allowed the compliance officer to vote on whether to approve compensation arrangements, according to the complaint. 

Erlanger also changed its compensation model to include large salaries for medical director and academic positions and allegedly paid such salaries to physicians without ensuring the required work was performed. As a result, Erlanger physicians with profitable referrals were among the highest paid in the nation for their specialties, the government claims. For example, according to the complaint:

• Erlanger paid an electrophysiologist an annual clinical salary of $816,701, a medical director salary of $101,080, an academic salary of $59,322, and a productivity incentive based on work relative value units (wRVUs). The medical director and academic salaries paid were near the 90th percentile of comparable salaries in the specialty.
• The health system paid a neurosurgeon a base salary of $654,735, a productivity incentive based on wRVUs, and payments for excess call coverage ranging from $400 to $1000 per 24-hour shift. In 2016, the neurosurgeon made $500,000 in excess call payments.
• Erlanger paid a cardiothoracic surgeon a base clinical salary of $1,070,000, a sign-on bonus of $150,000, a retention bonus of $100,000 (payable in the 4th year of the contract), and a program incentive of up to $150,000 per year.

In addition, Erlanger ignored patient safety concerns about some of its high revenue-generating physicians, the government claims. 

For instance, Erlanger received multiple complaints that a cardiothoracic surgeon was misusing an expensive form of life support in which pumps and oxygenators take over heart and lung function. Overuse of the equipment prolonged patients’ hospital stays and increased the hospital fees generated by the surgeon, according to the complaint. Staff also raised concerns about the cardiothoracic surgeon’s patient outcomes. 

But Erlanger disregarded the concerns and in 2018, increased the cardiothoracic surgeon’s retention bonus from $100,000 to $250,000, the suit alleges. A year later, the health system increased his base salary from $1,070,000 to $1,195,000.

Health care compensation and billing consultants alerted Erlanger that it was overpaying salaries and handing out bonuses based on measures that overstated the work physicians were performing, but Erlanger ignored the warnings, according to the complaint. 

Administrators allegedly resisted efforts by the chief compliance officer to hire an outside consultant to review its compensation models. Erlanger fired the compliance officer in 2019. 

The former chief compliance officer and another administrator filed a whistleblower lawsuit against Erlanger in 2021. The two administrators are relators in the government’s July 2024 lawsuit. 
 

How to Protect Yourself From Illegal Hospital Deals

The Erlanger case is the latest in a series of recent complaints by the federal government involving financial arrangements between hospitals and physicians.

In December 2023, Indianapolis-based Community Health Network Inc. agreed to pay the government $345 million to resolve claims that it paid physicians above fair market value and awarded bonuses tied to referrals in violation of the Stark Law. 

Also in 2023, Saginaw, Michigan–based Covenant HealthCare and two physicians paid the government $69 million to settle allegations that administrators engaged in improper financial arrangements with referring physicians and a physician-owned investment group. In another 2023 case, Massachusetts Eye and Ear in Boston agreed to pay $5.7 million to resolve claims that some of its physician compensation plans violated the Stark Law. 

Before you enter into a financial arrangement with a hospital, it’s also important to examine what percentile the aggregate compensation would reflect, law professor Mr. Sarraille said. The Erlanger case highlights federal officials’ suspicion of compensation, in aggregate, that exceeds the 90th percentile and increased attention to compensation that exceeds the 75th percentile, he said. 

To research compensation levels, doctors can review the Medical Group Management Association’s annual compensation report or search its compensation data. 

Before signing any contracts, Mr. Sarraille suggests, physicians should also consider whether the hospital shares the same values. Ask physicians at the hospital what they have to say about the hospital’s culture, vision, and values. Have physicians left the hospital after their practices were acquired? Consider speaking with them to learn why. 

Keep in mind that a doctor’s reputation could be impacted by a compliance complaint, regardless of whether it’s directed at the hospital and not the employed physician, Mr. Sarraille said. 

“The [Erlanger] complaint focuses on the compensation of specific, named physicians saying they were wildly overcompensated,” he said. “The implication is that they sold their referral power in exchange for a pay day. It’s a bad look, no matter how the case evolves from here.” 

Physicians could also face their own liability risk under the Stark Law and False Claims Act, depending on the circumstances. In the event of related quality-of-care issues, medical liability could come into play, Mr. Sarraille noted. In such cases, plaintiffs’ attorneys may see an opportunity to boost their claims with allegations that the patient harm was a function of “chasing compensation dollars,” Mr. Sarraille said. 

“Where that happens, plaintiff lawyers see the potential for crippling punitive damages, which might not be covered by an insurer,” he said.

A version of this article appeared on Medscape.com.

Strapped for cash and searching for new profits, Tennessee-based Erlanger Health System illegally paid excessive salaries to physicians in exchange for patient referrals, the US government alleged in a federal lawsuit.

Erlanger changed its compensation model to entice revenue-generating doctors, paying some two to three times the median salary for their specialty, according to the complaint. 

The physicians in turn referred numerous patients to Erlanger, and the health system submitted claims to Medicare for the referred services in violation of the Stark Law, according to the suit, filed in US District Court for the Western District of North Carolina. 

The government’s complaint “serves as a warning” to healthcare providers who try to boost profits through improper financial arrangements with referring physicians, said Tamala E. Miles, Special Agent in Charge for the US Department of Health and Human Services (HHS) Office of Inspector General (OIG).

In a statement provided to this news organization, Erlanger denied the allegations and said it would “vigorously” defend the lawsuit. 

“Erlanger paid physicians based on amounts that outside experts advised was fair market value,” Erlanger officials said in the statement. “Erlanger did not pay for referrals. A complete picture of the facts will demonstrate that the allegations lack merit and tell a very different story than what the government now claims.”

The Erlanger case is a reminder to physicians to consult their own knowledgeable advisors when considering financial arrangements with hospitals, said William Sarraille, JD, adjunct professor for the University of Maryland Francis King Carey School of Law in Baltimore and a regulatory consultant. 

“There is a tendency by physicians when contracting ... to rely on [hospitals’] perceived compliance and legal expertise,” Mr. Sarraille told this news organization. “This case illustrates the risks in doing so. Sometimes bigger doesn’t translate into more sophisticated or more effective from a compliance perspective.” 
 

Stark Law Prohibits Kickbacks

The Stark Law prohibits hospitals from billing the Centers for Medicare & Medicaid Services (CMS) for services referred by a physician with whom the hospital has an improper financial relationship.

CMS paid Erlanger about $27.8 million for claims stemming from the improper financial arrangements, the government contends. 

“HHS-OIG will continue to investigate such deals to prevent financial arrangements that could compromise impartial medical judgment, increase healthcare costs, and erode public trust in the healthcare system,” Ms. Miles said in a statement. 
 

Suit: Health System’s Money Woes Led to Illegal Arrangements

Erlanger’s financial troubles allegedly started after a previous run-in with the US government over false claims. 

In 2005, Erlanger Health System agreed to pay the government $40 million to resolve allegations that it knowingly submitted false claims to Medicare, according to the government’s complaint. At the time, Erlanger entered into a Corporate Integrity Agreement (CIA) with the OIG that required Erlanger to put controls in place to ensure its financial relationships did not violate the Stark Law. 

Erlanger’s agreement with OIG ended in 2010. Over the next 3 years, the health system lost nearly $32 million and in fiscal year 2013, had only 65 days of cash on hand, according to the government’s lawsuit. 

Beginning in 2013, Erlanger allegedly implemented a strategy to increase profits by employing more physicians, particularly specialists from competing hospitals whose patients would need costly hospital stays, according to the complaint. 

Once hired, Erlanger’s physicians were expected to treat patients at Erlanger’s hospitals and refer them to other providers within the health system, the suit claims. Erlanger also relaxed or eliminated the oversight and controls on physician compensation put in place under the CIA. For example, Erlanger’s CEO signed some compensation contracts before its chief compliance officer could review them and no longer allowed the compliance officer to vote on whether to approve compensation arrangements, according to the complaint. 

Erlanger also changed its compensation model to include large salaries for medical director and academic positions and allegedly paid such salaries to physicians without ensuring the required work was performed. As a result, Erlanger physicians with profitable referrals were among the highest paid in the nation for their specialties, the government claims. For example, according to the complaint:

• Erlanger paid an electrophysiologist an annual clinical salary of $816,701, a medical director salary of $101,080, an academic salary of $59,322, and a productivity incentive based on work relative value units (wRVUs). The medical director and academic salaries paid were near the 90th percentile of comparable salaries in the specialty.
• The health system paid a neurosurgeon a base salary of $654,735, a productivity incentive based on wRVUs, and payments for excess call coverage ranging from $400 to $1000 per 24-hour shift. In 2016, the neurosurgeon made $500,000 in excess call payments.
• Erlanger paid a cardiothoracic surgeon a base clinical salary of $1,070,000, a sign-on bonus of $150,000, a retention bonus of $100,000 (payable in the 4th year of the contract), and a program incentive of up to $150,000 per year.

In addition, Erlanger ignored patient safety concerns about some of its high revenue-generating physicians, the government claims. 

For instance, Erlanger received multiple complaints that a cardiothoracic surgeon was misusing an expensive form of life support in which pumps and oxygenators take over heart and lung function. Overuse of the equipment prolonged patients’ hospital stays and increased the hospital fees generated by the surgeon, according to the complaint. Staff also raised concerns about the cardiothoracic surgeon’s patient outcomes. 

But Erlanger disregarded the concerns and in 2018, increased the cardiothoracic surgeon’s retention bonus from $100,000 to $250,000, the suit alleges. A year later, the health system increased his base salary from $1,070,000 to $1,195,000.

Health care compensation and billing consultants alerted Erlanger that it was overpaying salaries and handing out bonuses based on measures that overstated the work physicians were performing, but Erlanger ignored the warnings, according to the complaint. 

Administrators allegedly resisted efforts by the chief compliance officer to hire an outside consultant to review its compensation models. Erlanger fired the compliance officer in 2019. 

The former chief compliance officer and another administrator filed a whistleblower lawsuit against Erlanger in 2021. The two administrators are relators in the government’s July 2024 lawsuit. 
 

How to Protect Yourself From Illegal Hospital Deals

The Erlanger case is the latest in a series of recent complaints by the federal government involving financial arrangements between hospitals and physicians.

In December 2023, Indianapolis-based Community Health Network Inc. agreed to pay the government $345 million to resolve claims that it paid physicians above fair market value and awarded bonuses tied to referrals in violation of the Stark Law. 

Also in 2023, Saginaw, Michigan–based Covenant HealthCare and two physicians paid the government $69 million to settle allegations that administrators engaged in improper financial arrangements with referring physicians and a physician-owned investment group. In another 2023 case, Massachusetts Eye and Ear in Boston agreed to pay $5.7 million to resolve claims that some of its physician compensation plans violated the Stark Law. 

Before you enter into a financial arrangement with a hospital, it’s also important to examine what percentile the aggregate compensation would reflect, law professor Mr. Sarraille said. The Erlanger case highlights federal officials’ suspicion of compensation, in aggregate, that exceeds the 90th percentile and increased attention to compensation that exceeds the 75th percentile, he said. 

To research compensation levels, doctors can review the Medical Group Management Association’s annual compensation report or search its compensation data. 

Before signing any contracts, Mr. Sarraille suggests, physicians should also consider whether the hospital shares the same values. Ask physicians at the hospital what they have to say about the hospital’s culture, vision, and values. Have physicians left the hospital after their practices were acquired? Consider speaking with them to learn why. 

Keep in mind that a doctor’s reputation could be impacted by a compliance complaint, regardless of whether it’s directed at the hospital and not the employed physician, Mr. Sarraille said. 

“The [Erlanger] complaint focuses on the compensation of specific, named physicians saying they were wildly overcompensated,” he said. “The implication is that they sold their referral power in exchange for a pay day. It’s a bad look, no matter how the case evolves from here.” 

Physicians could also face their own liability risk under the Stark Law and False Claims Act, depending on the circumstances. In the event of related quality-of-care issues, medical liability could come into play, Mr. Sarraille noted. In such cases, plaintiffs’ attorneys may see an opportunity to boost their claims with allegations that the patient harm was a function of “chasing compensation dollars,” Mr. Sarraille said. 

“Where that happens, plaintiff lawyers see the potential for crippling punitive damages, which might not be covered by an insurer,” he said.

A version of this article appeared on Medscape.com.

TOPLINE:

Chronic exposure to air pollutants such as fine particulate matter ≤ 2.5 μm in diameter (PM_2.5), particulate matter ≤ 10 μm in diameter (PM₁₀), nitrogen dioxide (NO₂), and nitrogen oxides (NO_X) increased the risk for systemic lupus erythematosus (SLE) onset. The risk was highest among those with high genetic risk and high air-pollution exposure. 

METHODOLOGY:

• Researchers prospectively investigated the association between long-term exposure to air pollutants and incident SLE in 459,815 participants from the UK Biobank.
• A land-use regression model was used to quantify the annual average air pollution concentrations, including PM_2.5, PM₁₀, NO₂, and NO_X.
• The genetic susceptibility to lupus was assessed using polygenic risk scores (PRS), and the participants were classified into low–, intermediate–, or high–genetic-risk groups based on the tertiles of PRS.
• The joint effect of air pollutants and genetic susceptibility to lupus on the risk for incident SLE was evaluated, with the reference group consisting of participants with a low genetic risk and low exposure to air pollution.

TAKEAWAY: 

• Over a median follow-up period of 11.77 years, 399 new cases of SLE were identified.
• The odds of developing SLE were higher among participants with high genetic risk than among those with low genetic risk (hazard ratio [HR], 3.45; P < .001 for trend).
• The risk for developing SLE was even higher among participants with a high genetic risk and high exposure to PM_2.5 (adjusted HR [aHR], 4.16; 95% CI, 2.67-6.49), PM₁₀ (aHR, 5.31; 95% CI, 3.30-8.55), NO₂ (aHR, 5.61; 95% CI, 3.45-9.13), and NO_X (aHR, 4.80; 95% CI, 3.00-7.66) than among with those with a low genetic risk and low exposure to air pollutants.

IN PRACTICE:

“Findings can inform the development of stricter air quality regulations to mitigate exposure to harmful pollutants, thereby reducing the risk of SLE,” the authors wrote. 

SOURCE:

The study was led by Meiqi Xing, MASc, Huazhong University of Science and Technology, Wuhan, China. It was published online in Arthritis & Rheumatology.

LIMITATIONS:

The study participants were enrolled voluntarily, which may have led to selection bias because they might have been healthier or more health conscious. The study did not consider the specific components of air pollutants, particularly particulate matter, which may have varying effects on the incidence of SLE. Other air pollutants such as ozone, sulfur dioxide, and carbon monoxide were not included in the analysis.

DISCLOSURES:

This study did not disclose any funding source. The authors declared no conflicts of interest.

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

TOPLINE:

Chronic exposure to air pollutants such as fine particulate matter ≤ 2.5 μm in diameter (PM_2.5), particulate matter ≤ 10 μm in diameter (PM₁₀), nitrogen dioxide (NO₂), and nitrogen oxides (NO_X) increased the risk for systemic lupus erythematosus (SLE) onset. The risk was highest among those with high genetic risk and high air-pollution exposure. 

METHODOLOGY:

• Researchers prospectively investigated the association between long-term exposure to air pollutants and incident SLE in 459,815 participants from the UK Biobank.
• A land-use regression model was used to quantify the annual average air pollution concentrations, including PM_2.5, PM₁₀, NO₂, and NO_X.
• The genetic susceptibility to lupus was assessed using polygenic risk scores (PRS), and the participants were classified into low–, intermediate–, or high–genetic-risk groups based on the tertiles of PRS.
• The joint effect of air pollutants and genetic susceptibility to lupus on the risk for incident SLE was evaluated, with the reference group consisting of participants with a low genetic risk and low exposure to air pollution.

TAKEAWAY: 

• Over a median follow-up period of 11.77 years, 399 new cases of SLE were identified.
• The odds of developing SLE were higher among participants with high genetic risk than among those with low genetic risk (hazard ratio [HR], 3.45; P < .001 for trend).
• The risk for developing SLE was even higher among participants with a high genetic risk and high exposure to PM_2.5 (adjusted HR [aHR], 4.16; 95% CI, 2.67-6.49), PM₁₀ (aHR, 5.31; 95% CI, 3.30-8.55), NO₂ (aHR, 5.61; 95% CI, 3.45-9.13), and NO_X (aHR, 4.80; 95% CI, 3.00-7.66) than among with those with a low genetic risk and low exposure to air pollutants.

IN PRACTICE:

“Findings can inform the development of stricter air quality regulations to mitigate exposure to harmful pollutants, thereby reducing the risk of SLE,” the authors wrote. 

SOURCE:

The study was led by Meiqi Xing, MASc, Huazhong University of Science and Technology, Wuhan, China. It was published online in Arthritis & Rheumatology.

LIMITATIONS:

The study participants were enrolled voluntarily, which may have led to selection bias because they might have been healthier or more health conscious. The study did not consider the specific components of air pollutants, particularly particulate matter, which may have varying effects on the incidence of SLE. Other air pollutants such as ozone, sulfur dioxide, and carbon monoxide were not included in the analysis.

DISCLOSURES:

This study did not disclose any funding source. The authors declared no conflicts of interest.

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

TOPLINE:

Chronic exposure to air pollutants such as fine particulate matter ≤ 2.5 μm in diameter (PM_2.5), particulate matter ≤ 10 μm in diameter (PM₁₀), nitrogen dioxide (NO₂), and nitrogen oxides (NO_X) increased the risk for systemic lupus erythematosus (SLE) onset. The risk was highest among those with high genetic risk and high air-pollution exposure. 

METHODOLOGY:

• Researchers prospectively investigated the association between long-term exposure to air pollutants and incident SLE in 459,815 participants from the UK Biobank.
• A land-use regression model was used to quantify the annual average air pollution concentrations, including PM_2.5, PM₁₀, NO₂, and NO_X.
• The genetic susceptibility to lupus was assessed using polygenic risk scores (PRS), and the participants were classified into low–, intermediate–, or high–genetic-risk groups based on the tertiles of PRS.
• The joint effect of air pollutants and genetic susceptibility to lupus on the risk for incident SLE was evaluated, with the reference group consisting of participants with a low genetic risk and low exposure to air pollution.

TAKEAWAY: 

• Over a median follow-up period of 11.77 years, 399 new cases of SLE were identified.
• The odds of developing SLE were higher among participants with high genetic risk than among those with low genetic risk (hazard ratio [HR], 3.45; P < .001 for trend).
• The risk for developing SLE was even higher among participants with a high genetic risk and high exposure to PM_2.5 (adjusted HR [aHR], 4.16; 95% CI, 2.67-6.49), PM₁₀ (aHR, 5.31; 95% CI, 3.30-8.55), NO₂ (aHR, 5.61; 95% CI, 3.45-9.13), and NO_X (aHR, 4.80; 95% CI, 3.00-7.66) than among with those with a low genetic risk and low exposure to air pollutants.

IN PRACTICE:

“Findings can inform the development of stricter air quality regulations to mitigate exposure to harmful pollutants, thereby reducing the risk of SLE,” the authors wrote. 

SOURCE:

The study was led by Meiqi Xing, MASc, Huazhong University of Science and Technology, Wuhan, China. It was published online in Arthritis & Rheumatology.

LIMITATIONS:

The study participants were enrolled voluntarily, which may have led to selection bias because they might have been healthier or more health conscious. The study did not consider the specific components of air pollutants, particularly particulate matter, which may have varying effects on the incidence of SLE. Other air pollutants such as ozone, sulfur dioxide, and carbon monoxide were not included in the analysis.

DISCLOSURES:

This study did not disclose any funding source. The authors declared no conflicts of interest.

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

In a case that spotlights the importance of comprehensive financial controls in medical offices, a leading New York City emergency medicine physician stands accused of using his business credit card to steal nearly $1.5 million from his clinical practice and spend it on cash advances, personal travel, lavish pet services, and more.

Michael Lucchesi, MD, who had served as chairman of Emergency Medicine at SUNY Downstate Medical Center in New York City, was arraigned on July 9 and pleaded not guilty. Dr. Lucchesi’s attorney, Earl Ward, did not respond to messages from this news organization, but he told the New York Post that “the funds he used were not stolen funds.”

Dr. Lucchesi, who’s in his late 60s, faces nine counts of first- and second-degree grand larceny, first-degree falsifying business records, and third-degree criminal tax fraud. According to a press statement from the district attorney of Kings County, which encompasses the borough of Brooklyn, Dr. Lucchesi is accused of using his clinical practice’s business card for cash advances (about $115,000), high-end pet care ($176,000), personal travel ($348,000), gym membership and personal training ($109,000), catering ($52,000), tuition payments for his children ($46,000), and other expenses such as online shopping, flowers, liquor, and electronics.

Most of the alleged pet care spending — $120,000 — went to the Green Leaf Pet Resort, which has two locations in New Jersey, including one with “56 acres of nature and lots of tail wagging.” Some of the alleged spending on gym membership was at the New York Sports Clubs chain, where monthly membership tops out at $139.99.

The alleged spending occurred between 2016 and 2023 and was discovered by SUNY Downstate during an audit. Dr. Lucchesi reportedly left his position at the hospital, where he made $399,712 in 2022 as a professor, according to public records.

“As a high-ranking doctor at this vital healthcare institution, this defendant was entrusted with access to significant funds, which he allegedly exploited, stealing more than 1 million dollars to pay for a lavish lifestyle,” District Attorney Eric Gonzalez said in a statement.

SUNY Downstate is in a fight for its life amid efforts by New York Governor Kathy Hochul to shut it down. According to The New York Times, it is the only state-run hospital in New York City.

Dr. Lucchesi, who had previously served as the hospital’s chief medical officer and acting head, was released without bail. His next court date is September 25, 2024.
 

Size of Alleged Theft Is ‘Very Unusual’

David P. Weber, JD, DBA, a professor and fraud specialist at Salisbury University, Salisbury, Maryland, told this news organization that the fraudulent use of a business or purchase credit card is a form of embezzlement and “one of the most frequently seen types of frauds against organizations.”

William J. Kresse, JD, MSA, CPA/CFF, who studies fraud at Governors State University in University Park, Illinois, noted in an interview with this news organization that the high amount of alleged fraud in this case is “very unusual,” as is the period it is said to have occurred (over 6 years).

Mr. Kresse highlighted a 2024 report by the Association of Certified Fraud Examiners, which found that the median fraud loss in healthcare, on the basis of 117 cases, is $100,000. The most common form of fraud in the industry is corruption (47%), followed by billing (38%), noncash theft such as inventory (22%), and expense reimbursement (21%).

The details of the current case suggest that “SUNY Downstate had weak or insufficient internal controls to prevent this type of fraud,” Salisbury University’s Mr. Weber said. “However, research also makes clear that the tenure and position of the perpetrator play a significant role in the size of the fraud. Internal controls are supposed to apply to all employees, but the higher in the organization the perpetrator is, the easier it can be to engage in fraud.”
 

Even Small Medical Offices Can Act to Prevent Fraud

What can be done to prevent this kind of fraud? “Each employee should be required to submit actual receipts or scanned copies, and the reimbursement requests should be reviewed and inputted by a separate department or office of the organization to ensure that the expenses are legitimate,” Mr. Weber said. “In addition, all credit card statements should be available for review by the organization either simultaneously with the bill going to the employee or available for audit or review at any time without notification to the employee. Expenses that are in certain categories should be prohibited automatically and coded to the card so such a charge is rejected by the credit card bank.”

Smaller businesses — like many medical practices — may not have the manpower to handle these roles. In that case, Mr. Weber said, “The key is segregation or separation of duties. The bookkeeper cannot be the person receiving the bank statements, the payments from patients, and the invoices from vendors. There needs to be at least one other person in the loop to have some level of control.”

One strategy, he said, “is that the practice should institute a policy that only the doctor or owner of the practice can receive the mail, not the bookkeeper. Even if the practice leader does not actually review the bank statements, simply opening them before handing them off to the bookkeeper can provide a level of deterrence [since] the employee may get caught if someone else is reviewing the bank statements.”
 

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

In a case that spotlights the importance of comprehensive financial controls in medical offices, a leading New York City emergency medicine physician stands accused of using his business credit card to steal nearly $1.5 million from his clinical practice and spend it on cash advances, personal travel, lavish pet services, and more.

Michael Lucchesi, MD, who had served as chairman of Emergency Medicine at SUNY Downstate Medical Center in New York City, was arraigned on July 9 and pleaded not guilty. Dr. Lucchesi’s attorney, Earl Ward, did not respond to messages from this news organization, but he told the New York Post that “the funds he used were not stolen funds.”

Dr. Lucchesi, who’s in his late 60s, faces nine counts of first- and second-degree grand larceny, first-degree falsifying business records, and third-degree criminal tax fraud. According to a press statement from the district attorney of Kings County, which encompasses the borough of Brooklyn, Dr. Lucchesi is accused of using his clinical practice’s business card for cash advances (about $115,000), high-end pet care ($176,000), personal travel ($348,000), gym membership and personal training ($109,000), catering ($52,000), tuition payments for his children ($46,000), and other expenses such as online shopping, flowers, liquor, and electronics.

Most of the alleged pet care spending — $120,000 — went to the Green Leaf Pet Resort, which has two locations in New Jersey, including one with “56 acres of nature and lots of tail wagging.” Some of the alleged spending on gym membership was at the New York Sports Clubs chain, where monthly membership tops out at $139.99.

The alleged spending occurred between 2016 and 2023 and was discovered by SUNY Downstate during an audit. Dr. Lucchesi reportedly left his position at the hospital, where he made $399,712 in 2022 as a professor, according to public records.

“As a high-ranking doctor at this vital healthcare institution, this defendant was entrusted with access to significant funds, which he allegedly exploited, stealing more than 1 million dollars to pay for a lavish lifestyle,” District Attorney Eric Gonzalez said in a statement.

SUNY Downstate is in a fight for its life amid efforts by New York Governor Kathy Hochul to shut it down. According to The New York Times, it is the only state-run hospital in New York City.

Dr. Lucchesi, who had previously served as the hospital’s chief medical officer and acting head, was released without bail. His next court date is September 25, 2024.
 

Size of Alleged Theft Is ‘Very Unusual’

David P. Weber, JD, DBA, a professor and fraud specialist at Salisbury University, Salisbury, Maryland, told this news organization that the fraudulent use of a business or purchase credit card is a form of embezzlement and “one of the most frequently seen types of frauds against organizations.”

William J. Kresse, JD, MSA, CPA/CFF, who studies fraud at Governors State University in University Park, Illinois, noted in an interview with this news organization that the high amount of alleged fraud in this case is “very unusual,” as is the period it is said to have occurred (over 6 years).

Mr. Kresse highlighted a 2024 report by the Association of Certified Fraud Examiners, which found that the median fraud loss in healthcare, on the basis of 117 cases, is $100,000. The most common form of fraud in the industry is corruption (47%), followed by billing (38%), noncash theft such as inventory (22%), and expense reimbursement (21%).

The details of the current case suggest that “SUNY Downstate had weak or insufficient internal controls to prevent this type of fraud,” Salisbury University’s Mr. Weber said. “However, research also makes clear that the tenure and position of the perpetrator play a significant role in the size of the fraud. Internal controls are supposed to apply to all employees, but the higher in the organization the perpetrator is, the easier it can be to engage in fraud.”
 

Even Small Medical Offices Can Act to Prevent Fraud

What can be done to prevent this kind of fraud? “Each employee should be required to submit actual receipts or scanned copies, and the reimbursement requests should be reviewed and inputted by a separate department or office of the organization to ensure that the expenses are legitimate,” Mr. Weber said. “In addition, all credit card statements should be available for review by the organization either simultaneously with the bill going to the employee or available for audit or review at any time without notification to the employee. Expenses that are in certain categories should be prohibited automatically and coded to the card so such a charge is rejected by the credit card bank.”

Smaller businesses — like many medical practices — may not have the manpower to handle these roles. In that case, Mr. Weber said, “The key is segregation or separation of duties. The bookkeeper cannot be the person receiving the bank statements, the payments from patients, and the invoices from vendors. There needs to be at least one other person in the loop to have some level of control.”

One strategy, he said, “is that the practice should institute a policy that only the doctor or owner of the practice can receive the mail, not the bookkeeper. Even if the practice leader does not actually review the bank statements, simply opening them before handing them off to the bookkeeper can provide a level of deterrence [since] the employee may get caught if someone else is reviewing the bank statements.”
 

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

In a case that spotlights the importance of comprehensive financial controls in medical offices, a leading New York City emergency medicine physician stands accused of using his business credit card to steal nearly $1.5 million from his clinical practice and spend it on cash advances, personal travel, lavish pet services, and more.

Michael Lucchesi, MD, who had served as chairman of Emergency Medicine at SUNY Downstate Medical Center in New York City, was arraigned on July 9 and pleaded not guilty. Dr. Lucchesi’s attorney, Earl Ward, did not respond to messages from this news organization, but he told the New York Post that “the funds he used were not stolen funds.”

Dr. Lucchesi, who’s in his late 60s, faces nine counts of first- and second-degree grand larceny, first-degree falsifying business records, and third-degree criminal tax fraud. According to a press statement from the district attorney of Kings County, which encompasses the borough of Brooklyn, Dr. Lucchesi is accused of using his clinical practice’s business card for cash advances (about $115,000), high-end pet care ($176,000), personal travel ($348,000), gym membership and personal training ($109,000), catering ($52,000), tuition payments for his children ($46,000), and other expenses such as online shopping, flowers, liquor, and electronics.

Most of the alleged pet care spending — $120,000 — went to the Green Leaf Pet Resort, which has two locations in New Jersey, including one with “56 acres of nature and lots of tail wagging.” Some of the alleged spending on gym membership was at the New York Sports Clubs chain, where monthly membership tops out at $139.99.

The alleged spending occurred between 2016 and 2023 and was discovered by SUNY Downstate during an audit. Dr. Lucchesi reportedly left his position at the hospital, where he made $399,712 in 2022 as a professor, according to public records.

“As a high-ranking doctor at this vital healthcare institution, this defendant was entrusted with access to significant funds, which he allegedly exploited, stealing more than 1 million dollars to pay for a lavish lifestyle,” District Attorney Eric Gonzalez said in a statement.

SUNY Downstate is in a fight for its life amid efforts by New York Governor Kathy Hochul to shut it down. According to The New York Times, it is the only state-run hospital in New York City.

Dr. Lucchesi, who had previously served as the hospital’s chief medical officer and acting head, was released without bail. His next court date is September 25, 2024.
 

Size of Alleged Theft Is ‘Very Unusual’

David P. Weber, JD, DBA, a professor and fraud specialist at Salisbury University, Salisbury, Maryland, told this news organization that the fraudulent use of a business or purchase credit card is a form of embezzlement and “one of the most frequently seen types of frauds against organizations.”

William J. Kresse, JD, MSA, CPA/CFF, who studies fraud at Governors State University in University Park, Illinois, noted in an interview with this news organization that the high amount of alleged fraud in this case is “very unusual,” as is the period it is said to have occurred (over 6 years).

Mr. Kresse highlighted a 2024 report by the Association of Certified Fraud Examiners, which found that the median fraud loss in healthcare, on the basis of 117 cases, is $100,000. The most common form of fraud in the industry is corruption (47%), followed by billing (38%), noncash theft such as inventory (22%), and expense reimbursement (21%).

The details of the current case suggest that “SUNY Downstate had weak or insufficient internal controls to prevent this type of fraud,” Salisbury University’s Mr. Weber said. “However, research also makes clear that the tenure and position of the perpetrator play a significant role in the size of the fraud. Internal controls are supposed to apply to all employees, but the higher in the organization the perpetrator is, the easier it can be to engage in fraud.”
 

Even Small Medical Offices Can Act to Prevent Fraud

What can be done to prevent this kind of fraud? “Each employee should be required to submit actual receipts or scanned copies, and the reimbursement requests should be reviewed and inputted by a separate department or office of the organization to ensure that the expenses are legitimate,” Mr. Weber said. “In addition, all credit card statements should be available for review by the organization either simultaneously with the bill going to the employee or available for audit or review at any time without notification to the employee. Expenses that are in certain categories should be prohibited automatically and coded to the card so such a charge is rejected by the credit card bank.”

Smaller businesses — like many medical practices — may not have the manpower to handle these roles. In that case, Mr. Weber said, “The key is segregation or separation of duties. The bookkeeper cannot be the person receiving the bank statements, the payments from patients, and the invoices from vendors. There needs to be at least one other person in the loop to have some level of control.”

One strategy, he said, “is that the practice should institute a policy that only the doctor or owner of the practice can receive the mail, not the bookkeeper. Even if the practice leader does not actually review the bank statements, simply opening them before handing them off to the bookkeeper can provide a level of deterrence [since] the employee may get caught if someone else is reviewing the bank statements.”
 

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

VIENNA — It may have been a while since there have been any major breakthroughs in the treatment of systemic lupus erythematosus (SLE), but there are high hopes that this is a situation that may be about to change, experts agreed at the annual European Congress of Rheumatology.

“It’s an incredibly vivid area of development,” Laurent Arnaud, MD, PhD, professor of rheumatology at the University of Strasbourg in Strasbourg, France, said during one of the first sessions of the meeting. He reported that there were at least 17 phase 2 and 14 phase 3 trials that were expected to start within the next few years, all with investigational agents that target different immune cells or pathways that have been implicated in the pathogenesis of SLE.

Sara Freeman/Medscape Medical News

In a systematic review published last year, Dr. Arnaud and coauthors found that there were 92 investigational biologic or novel targeted agents in various phases of clinical testing. This included B-cell–targeting agents such as ianalumab, plasma cell-targeting agents such as daratumumab, and drugs with novel mechanisms of action such as KPG-818, which targets the CRL4-Cereblon (CRBN) E3 ubiquitin ligase complex. Phase 2 data on all three of these investigational agents were presented during various sessions at EULAR 2024, all with positive results, suggesting that their further development in SLE is worth pursuing.

There are of course “many more candidates in the pipeline,” Dr. Arnaud said. “I’m very happy that I think we are going to see great days for lupus right in front of our eyes.”
 

Targeting B Cells

Drugs that target B cells have been at the forefront of lupus treatment for several years, as David Isenberg, MD, professor of rheumatology at University College London, pointed out during an interview for EULAR TV.

“It’s clearly important to target the cells which are likely to be causing the problem in lupus, and in the main, that tends to be B cells,” he said.

Dr. Isenberg, who is renowned for his work with the B-cell–targeting agent rituximab, added: “But we know that obviously T cells integrate with B cells, so anything which interrupts the link between the T cell and the B cell is likely to be important.”
 

Chimeric Antigen Receptor (CAR) T-Cell Therapy ‘Revolution’

One new way of targeting B cells is with CAR T-cell therapy, which David D’Cruz , MD, PhD, a consultant rheumatologist for Guy’s and St. Thomas’ Hospital NHS Foundation Trust in London, picked as one of the “most striking” topics highlighted at EULAR 2024.

This is “truly personalized medicine,” Dr. D’Cruz said. This is an autologous therapy because a patient’s T cells are removed by leukapheresis, transfected with a CAR T vector directed against a component of the B cell, and then returned to them.

“I do feel that we’re on the cusp of a major revolution,” Dr. D’Cruz told this news organization. Not only in lupus but also in other rheumatic conditions that have proved really difficult to treat, such as systemic sclerosis and myositis, he said.

“Basically, it’s a very powerful B-cell–depleting tool, but it’s much more profound B-cell–depleting tool than, for example, rituximab or belimumab,” explained Dr. D’Cruz. “What you’re doing is reprogramming T cells to attack the B cells.”

Although rituximab and belimumab clear all the B cells in the circulation, there are still some cells left behind in the bone marrow, “and it’s very difficult to get rid of those,” Dr. D’Cruz said. “What CAR T-cell therapy appears to do is wipe out all the CD19-positive B cells everywhere, in the blood and the tissue. So you get a really profound B-cell depletion.”

Eric Morand, MBBS, PhD, head of rheumatology at Monash Health in Melbourne, Australia, told this news organization that there was obviously “a lot of buzz” about CAR T-cell therapy.

Sara Freeman/Medscape Medical News

“We’re waiting to see if the exciting data from Erlangen can be reproduced in other centers with other CAR T products to show that it is a universal effect. We haven’t seen that yet, but I think we will by next year.”

Cost and expertise are two major considerations and potential limiting factors, however, as Dr. D’Cruz and Dr. Isenberg both pointed out in separate interviews with this news organization.

Dr. D’Cruz said: “It’s very expensive, it takes a while, and it doesn’t always work is what I’m hearing. It’s usually successful, but again, a little bit depends on the technique and the people doing the process.”

Dr. Isenberg said: “CAR T-cell therapy is, I think, very exciting because it does look to be quite promising. But as it costs 350,000 euros per patient, I don’t think that it is going to be widely adopted.”

Even if it could be afforded by certain centers in the West, he added, this just would not be feasible in poorer nations. “So, we’ve got to find other effective, cheaper ways to go,” Dr. Isenberg said.

“I think there are some very interesting ideas with monoclonal antibodies which target at least two different targets — one on the B cell, one on the T cell — and that could well be the way to take this forward,” he suggested.
 

Ianalumab ‘Double Blocking’ B Cells

Another way could be to develop more potent B-cell–depleting drugs, as Nancy Agmon-Levin , MD, head of the Clinical Immunology, Angioedema and Allergy Unit, Lupus and Autoimmune Diseases Clinic, at Sheba Medical Center, Tel Aviv University in Tel Aviv, Israel, reported during one of the clinical abstract sessions at EULAR 2024.

Dr. Agmon-Levin presented data on 67 individuals with SLE who had participated in a multicenter phase 2 study of ianalumab, a fully human immunoglobulin (Ig) G1 monoclonal antibody that results in a “double blocking of the B-cell lineage.”

Ianalumab targets the B-cell–activating factor receptor (BAFFR), but what makes it distinct from other BAFF-targeting drugs is that it has had a fructose molecule removed from its Fc portion, which renders it more likely to trigger antibody-dependent cellular cytotoxicity.

“This is a B-cell depletion therapy,” Agmon-Levin said, but it also blocks BAFFR-mediated survival of B cells, so the subsequent recuperation process of BAFFR-expressing B cells is affected, leading to continued B-cell depletion.

The phase 2 study she presented consisted of an initial 28-week, double-blind period, during which time participants had been randomly allocated to receive either subcutaneous injections of ianalumab 300 mg or a matching placebo every 4 weeks. This was followed by a 24-week, open-label period where all participants were treated with ianalumab, and then an off-treatment, minimal follow-up period that lasted up to 68 weeks, with continued data collection for safety.

The primary outcome measure was a composite of meeting criteria for the SLE Responder Index 4 and a sustained reduction in corticosteroid use at 28 weeks. This was achieved in 15 of the 34 (44.1%) people treated with ianalumab vs only 3 (9.1%) of the 33 people who had been given a placebo.

Dr. Agmon-Levin reported that the effect on this outcome was sustained to the end of the open-label period, at 1 year, in 15 (45.5%) of 33 participants who had continued treatment with ianalumab and achieved in 13 (40.6%) of 32 participants who had switched from placebo to ianalumab treatment.

Moreover, longer durations of treatment were associated with a host of improved outcomes, Dr. Agmon-Levin said: “Treatment was improved along the 52 weeks, and we can see from the LLDAS [Lupus Low Disease Activity State], DORIS [Definition Of Remission In SLE], and SRI-6 and -8 that as you continue the therapy, you improve the outcomes.”

The potential benefits of ianalumab in the treatment of SLE and lupus nephritis will now be further examined in the phase 3 SIRIUS-SLE1 , SIRIUS-SLE2, and SIRIUS-LN trials, which are estimated to provide initial results in 2027 and complete in early 2029 or 2030.
 

Targeting Plasma Cells With Daratumumab

Another drug showing signs that it might be useful as a treatment for SLE is daratumumab, as Tobias Alexander, MD, of Charité — Universitätsmedizin Berlin, reported during one of the late-breaking abstract sessions at EULAR 2024.

“Daratumumab is a human, first-in-class anti-CD38 antibody that efficiently depletes plasma cells,” Dr. Alexander said. CD38 is both a receptor and an enzyme, and while it is found on the surface of most immune cells, it’s particularly expressed by plasma cells, he added.

Daratumumab is not a total newcomer, however, as it’s already approved for the treatment of multiple myeloma under the trade name Darzalex. The rationale for using it in SLE comes from two case reports, Dr. Alexander explained. The first, published in 2020 in The New England Journal of Medicine, involved two patients with severe and life-threatening lupus who were given off-label treatment for a period of 4 weeks and experienced good clinical and serologic responses. The second, published last year in Nature Medicine, involved six patients with refractory lupus nephritis, five of whom had a clinical response at 6 months.

“On this background, we conducted an investigator-initiated trial, which was an open-label, single-center, proof-of-concept study,” Dr. Alexander said. A total of 10 female patients whose ages ranged from 24 to 43 years were included in the phase 2 trial that was dubbed DARALUP. For inclusion, all had to have a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) of four or more for clinical manifestations, have been treated with at least two prior disease-modifying drugs to no avail, and be anti–double-stranded DNA (anti-dsDNA) antibody positive. Dr. Alexander reported that the median baseline SLEDAI-2K score was 12 and ranged from 8 to 20, with the number of prior therapies ranging from two to nine.

Daratumumab was given at a dose of 1800 mg via subcutaneous injection every week for 8 weeks. This is the same dose that is used to treat multiple myeloma, Dr. Alexander explained, although the dosing is not stopped. The reason for stopping after 8 weeks in the current trial was to be able to see what happened once the treatment was stopped. The follow-up was for 36 weeks.

Dr. Alexander reported that there was a “very dramatic and significant” effect on the primary endpoint of a reduction in anti-dsDNA antibody levels, decreasing from a median of 166.3 U/mL at baseline to 61.1 U/mL at week 12 (P = .002). Alongside, there was a reduction in the SLEDAI-2K score from 12 to 4 within 12 weeks, which was sustained at the 36-week follow-up assessment. Improvements in skin, joint, kidney, and level of proteinuria were also seen.

Although all patients experienced adverse events, none were serious. Infections and infestations (mostly nasopharyngitis, COVID-19, and gastroenteritis) were the most common, experienced by 80% of the participants; 70% had injection site reactions or fatigue, 60% had gastrointestinal symptoms, 50% had a fall of IgG < 5 g/L, 40% had headache, and 20% had back pain.

“This is a positive trial. I think we could demonstrate that [daratumumab] produced very strong, rapid, and durable clinical improvements,” Dr. Alexander said. “We think that targeting CD38 is relevant; plasma cells had been depleted based on the reduction of anti-dsDNA antibodies,” he added.

From the audience, however, Peter Nash, MBBS, of Griffith University in Brisbane, Australia, questioned whether the results could be attributed to “a steroid effect” because patients had been treated with oral dexamethasone throughout the study.

Dr. Alexander noted that steroid use had been part of the treatment schedule but acknowledged it was a possible confounder.

“I think we can be confident that [daratumumab] had a major effect on plasma cells decreasing…because we see that also the vaccine titers decreased,” Dr. Alexander said. “Time will tell, but even more important is the durability of the responses over time, which you don’t achieve under steroids.”
 

KPG-818’s Novel Mechanism of Action

Elsewhere at EULAR 2024, positive results of another phase 2 study involving a drug with an entirely different mechanism of action, KPG-818, were reported in a poster presentation. KPG-818 modulates CRBN, which results in the degradation of two transcription factors (Aiolos and Ikaros) that are involved in the development, maturation, and proliferation of innate and adaptive immune cells and have been linked to genetic risk in SLE, according to the poster’s authors. It is currently in development for the treatment of SLE, Behçet disease, inflammatory bowel disease, multiple myeloma, and non-Hodgkin lymphoma.

Yao Wang, MD, chief medical officer of KPG-818’s developer Kangpu Biopharmaceuticals, Hefei, China, and associates found that oral doses of 0.15 or 0.6 mg KPG-818 were “generally well-tolerated” and produced immunomodulatory changes that could be beneficial in people with SLE over a 12-week treatment period.

“Only two new agents have been approved for the treatment of SLE in the past five decades in USA and Europe,” Dr. Wang and team wrote, which highlights “a significant unmet need for more effective and safe treatment options.”

They believe that KPG-818 might well fit the bill based on the results of their study, in which 35 of 37 recruited patients completed the treatment. Compared with placebo, they observed reduced numbers of total B cells, Aiolos+ T and B cells, and increased Treg cells.

SLEDAI-2K and Cutaneous Lupus Erythematosus Disease Area and Severity Index activity scores in the 0.15-mg group were improved relative to baseline and placebo.

“The proof-of-concept findings suggest a favorable benefit/risk ratio in SLE for KPG-818,” Dr. Wang and coauthors said, supporting its further development in SLE.
 

Need for Treatments

Dr. Isenberg told this news organization that both daratumumab and KPG-818 would be welcome additions as treatment options if further trials proved their worth.

“The great frustration about lupus is that, compared to patients with rheumatoid arthritis, the choice has been so limited,” Dr. Isenberg said. Aside from rituximab (Rituxan) and belimumab (Benlysta), which are used with certain restrictions, there are no other biologic targeted treatments available in the United Kingdom. Anifrolumab (Saphnelo) has a license in the United States and some European countries but is not yet available for him to use in his practice.

Daratumumab and KPG-818 are “different types of molecules, and if they work that will be great. It would be nice to have the choice,” Dr. Isenberg said. “Whether they will be as effective as I think rituximab is, I don’t know, but these are some very encouraging results.”

Of course, these are all phase 2 trials, and the “big problem” is that such positive results do not always translate when it comes to phase 3, as Dr. D’Cruz told this news organization.

“Until a few years ago, there had been about 25 or 30 industry-led trails, and they’d all failed, except for belimumab and anifrolumab,” Dr. D’Cruz said. These drugs were found to work and be generally safe in phase 1 and 2 trials, but “when they come to phase 3, they all seem to fail, and we don’t know why.”

These are large global studies, D’Cruz added, observing that problems with patient selection, steroid use, and choice of outcome measures were possible factors for why the EXPLORER and LUNAR studies had shown no benefit for rituximab despite the drug being widely used to treat SLE.

Dr. Isenberg, who has coauthored an article on the topic of why drugs seem to fail at the final hurdle, noted: “I think it has a lot to do with the nature of the disease. It’s a complicated disease.” From having “savvy physicians doing the trials for you” to the placebo response, there are “a whole bunch or reasons why these things haven’t worked in lupus.”

Dr. Morand commented: “We’ve got many programs in phase 2 and 3, and because there’s so many, they’re all facing recruitment challenges, and as a consequence of so much activity, every program is going a little slower than hoped for.”

As for other drugs on the horizon, Dr. Morand noted: “We’re very optimistic about things like litifilimab and deucravacitinib; that’s two examples that are in phase 3. Earlier in the program of development, [there are] a huge range of targets being addressed. The future looks bright. But we might have to wait a while.”

Dr. Arnaud has consulted for AstraZeneca, AbbVie, Alpine Immune Sciences, Biogen, Bristol Myers Squibb, Boehringer Ingelheim, Chugai Pharmaceutical, GlaxoSmithKline, Grifols, Janssen, Kezar Life Sciences, LFB, Lilly, Medac, Merck, Novartis, Pfizer, Roche, and UCB. Dr. Isenberg has served as an adviser to Merck Serono, AstraZeneca, Eli Lilly, Servier, and ImmuPharma. Any honoraria received is passed on to a local arthritis charity connected to his hospital. Dr. D’Cruz has served as a consultant and advisory board member for GlaxoSmithKline and CSL Vifor. Dr. Morand has received research support, consultancy fees, or both from multiple pharmaceutical companies paid to his institution including AbbVie, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, EMD Serono, Dragonfly, Genentech, GlaxoSmithKline, Janssen, Novartis, RemeGen, Takeda, UCB, and Zenas. The ianalumab trial presented by Dr. Agmon-Levin was sponsored by Novartis Pharma; however, she reported having no conflicts of interest. The DARALUP study was an investigator-initiated trial supported by Janssen. Dr. Alexander has received consulting fees, study support, honoraria, and travel grants from various pharmaceutical companies including AbbVie, Amgen, AstraZeneca, Bayer, GlaxoSmithKline, Janssen, and Lilly. Dr. Nash has consulted for The Rheumatology Education Group Consultants. The KPG-818 study reported by Dr. Wang was sponsored by Kangpu Biopharmaceuticals.
 

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

VIENNA — It may have been a while since there have been any major breakthroughs in the treatment of systemic lupus erythematosus (SLE), but there are high hopes that this is a situation that may be about to change, experts agreed at the annual European Congress of Rheumatology.

“It’s an incredibly vivid area of development,” Laurent Arnaud, MD, PhD, professor of rheumatology at the University of Strasbourg in Strasbourg, France, said during one of the first sessions of the meeting. He reported that there were at least 17 phase 2 and 14 phase 3 trials that were expected to start within the next few years, all with investigational agents that target different immune cells or pathways that have been implicated in the pathogenesis of SLE.

Sara Freeman/Medscape Medical News

In a systematic review published last year, Dr. Arnaud and coauthors found that there were 92 investigational biologic or novel targeted agents in various phases of clinical testing. This included B-cell–targeting agents such as ianalumab, plasma cell-targeting agents such as daratumumab, and drugs with novel mechanisms of action such as KPG-818, which targets the CRL4-Cereblon (CRBN) E3 ubiquitin ligase complex. Phase 2 data on all three of these investigational agents were presented during various sessions at EULAR 2024, all with positive results, suggesting that their further development in SLE is worth pursuing.

There are of course “many more candidates in the pipeline,” Dr. Arnaud said. “I’m very happy that I think we are going to see great days for lupus right in front of our eyes.”
 

Targeting B Cells

Drugs that target B cells have been at the forefront of lupus treatment for several years, as David Isenberg, MD, professor of rheumatology at University College London, pointed out during an interview for EULAR TV.

“It’s clearly important to target the cells which are likely to be causing the problem in lupus, and in the main, that tends to be B cells,” he said.

Dr. Isenberg, who is renowned for his work with the B-cell–targeting agent rituximab, added: “But we know that obviously T cells integrate with B cells, so anything which interrupts the link between the T cell and the B cell is likely to be important.”
 

Chimeric Antigen Receptor (CAR) T-Cell Therapy ‘Revolution’

One new way of targeting B cells is with CAR T-cell therapy, which David D’Cruz , MD, PhD, a consultant rheumatologist for Guy’s and St. Thomas’ Hospital NHS Foundation Trust in London, picked as one of the “most striking” topics highlighted at EULAR 2024.

This is “truly personalized medicine,” Dr. D’Cruz said. This is an autologous therapy because a patient’s T cells are removed by leukapheresis, transfected with a CAR T vector directed against a component of the B cell, and then returned to them.

“I do feel that we’re on the cusp of a major revolution,” Dr. D’Cruz told this news organization. Not only in lupus but also in other rheumatic conditions that have proved really difficult to treat, such as systemic sclerosis and myositis, he said.

“Basically, it’s a very powerful B-cell–depleting tool, but it’s much more profound B-cell–depleting tool than, for example, rituximab or belimumab,” explained Dr. D’Cruz. “What you’re doing is reprogramming T cells to attack the B cells.”

Although rituximab and belimumab clear all the B cells in the circulation, there are still some cells left behind in the bone marrow, “and it’s very difficult to get rid of those,” Dr. D’Cruz said. “What CAR T-cell therapy appears to do is wipe out all the CD19-positive B cells everywhere, in the blood and the tissue. So you get a really profound B-cell depletion.”

Eric Morand, MBBS, PhD, head of rheumatology at Monash Health in Melbourne, Australia, told this news organization that there was obviously “a lot of buzz” about CAR T-cell therapy.

Sara Freeman/Medscape Medical News

“We’re waiting to see if the exciting data from Erlangen can be reproduced in other centers with other CAR T products to show that it is a universal effect. We haven’t seen that yet, but I think we will by next year.”

Cost and expertise are two major considerations and potential limiting factors, however, as Dr. D’Cruz and Dr. Isenberg both pointed out in separate interviews with this news organization.

Dr. D’Cruz said: “It’s very expensive, it takes a while, and it doesn’t always work is what I’m hearing. It’s usually successful, but again, a little bit depends on the technique and the people doing the process.”

Dr. Isenberg said: “CAR T-cell therapy is, I think, very exciting because it does look to be quite promising. But as it costs 350,000 euros per patient, I don’t think that it is going to be widely adopted.”

Even if it could be afforded by certain centers in the West, he added, this just would not be feasible in poorer nations. “So, we’ve got to find other effective, cheaper ways to go,” Dr. Isenberg said.

“I think there are some very interesting ideas with monoclonal antibodies which target at least two different targets — one on the B cell, one on the T cell — and that could well be the way to take this forward,” he suggested.
 

Ianalumab ‘Double Blocking’ B Cells

Another way could be to develop more potent B-cell–depleting drugs, as Nancy Agmon-Levin , MD, head of the Clinical Immunology, Angioedema and Allergy Unit, Lupus and Autoimmune Diseases Clinic, at Sheba Medical Center, Tel Aviv University in Tel Aviv, Israel, reported during one of the clinical abstract sessions at EULAR 2024.

Dr. Agmon-Levin presented data on 67 individuals with SLE who had participated in a multicenter phase 2 study of ianalumab, a fully human immunoglobulin (Ig) G1 monoclonal antibody that results in a “double blocking of the B-cell lineage.”

Ianalumab targets the B-cell–activating factor receptor (BAFFR), but what makes it distinct from other BAFF-targeting drugs is that it has had a fructose molecule removed from its Fc portion, which renders it more likely to trigger antibody-dependent cellular cytotoxicity.

“This is a B-cell depletion therapy,” Agmon-Levin said, but it also blocks BAFFR-mediated survival of B cells, so the subsequent recuperation process of BAFFR-expressing B cells is affected, leading to continued B-cell depletion.

The phase 2 study she presented consisted of an initial 28-week, double-blind period, during which time participants had been randomly allocated to receive either subcutaneous injections of ianalumab 300 mg or a matching placebo every 4 weeks. This was followed by a 24-week, open-label period where all participants were treated with ianalumab, and then an off-treatment, minimal follow-up period that lasted up to 68 weeks, with continued data collection for safety.

The primary outcome measure was a composite of meeting criteria for the SLE Responder Index 4 and a sustained reduction in corticosteroid use at 28 weeks. This was achieved in 15 of the 34 (44.1%) people treated with ianalumab vs only 3 (9.1%) of the 33 people who had been given a placebo.

Dr. Agmon-Levin reported that the effect on this outcome was sustained to the end of the open-label period, at 1 year, in 15 (45.5%) of 33 participants who had continued treatment with ianalumab and achieved in 13 (40.6%) of 32 participants who had switched from placebo to ianalumab treatment.

Moreover, longer durations of treatment were associated with a host of improved outcomes, Dr. Agmon-Levin said: “Treatment was improved along the 52 weeks, and we can see from the LLDAS [Lupus Low Disease Activity State], DORIS [Definition Of Remission In SLE], and SRI-6 and -8 that as you continue the therapy, you improve the outcomes.”

The potential benefits of ianalumab in the treatment of SLE and lupus nephritis will now be further examined in the phase 3 SIRIUS-SLE1 , SIRIUS-SLE2, and SIRIUS-LN trials, which are estimated to provide initial results in 2027 and complete in early 2029 or 2030.
 

Targeting Plasma Cells With Daratumumab

Another drug showing signs that it might be useful as a treatment for SLE is daratumumab, as Tobias Alexander, MD, of Charité — Universitätsmedizin Berlin, reported during one of the late-breaking abstract sessions at EULAR 2024.

“Daratumumab is a human, first-in-class anti-CD38 antibody that efficiently depletes plasma cells,” Dr. Alexander said. CD38 is both a receptor and an enzyme, and while it is found on the surface of most immune cells, it’s particularly expressed by plasma cells, he added.

Daratumumab is not a total newcomer, however, as it’s already approved for the treatment of multiple myeloma under the trade name Darzalex. The rationale for using it in SLE comes from two case reports, Dr. Alexander explained. The first, published in 2020 in The New England Journal of Medicine, involved two patients with severe and life-threatening lupus who were given off-label treatment for a period of 4 weeks and experienced good clinical and serologic responses. The second, published last year in Nature Medicine, involved six patients with refractory lupus nephritis, five of whom had a clinical response at 6 months.

“On this background, we conducted an investigator-initiated trial, which was an open-label, single-center, proof-of-concept study,” Dr. Alexander said. A total of 10 female patients whose ages ranged from 24 to 43 years were included in the phase 2 trial that was dubbed DARALUP. For inclusion, all had to have a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) of four or more for clinical manifestations, have been treated with at least two prior disease-modifying drugs to no avail, and be anti–double-stranded DNA (anti-dsDNA) antibody positive. Dr. Alexander reported that the median baseline SLEDAI-2K score was 12 and ranged from 8 to 20, with the number of prior therapies ranging from two to nine.

Daratumumab was given at a dose of 1800 mg via subcutaneous injection every week for 8 weeks. This is the same dose that is used to treat multiple myeloma, Dr. Alexander explained, although the dosing is not stopped. The reason for stopping after 8 weeks in the current trial was to be able to see what happened once the treatment was stopped. The follow-up was for 36 weeks.

Dr. Alexander reported that there was a “very dramatic and significant” effect on the primary endpoint of a reduction in anti-dsDNA antibody levels, decreasing from a median of 166.3 U/mL at baseline to 61.1 U/mL at week 12 (P = .002). Alongside, there was a reduction in the SLEDAI-2K score from 12 to 4 within 12 weeks, which was sustained at the 36-week follow-up assessment. Improvements in skin, joint, kidney, and level of proteinuria were also seen.

Although all patients experienced adverse events, none were serious. Infections and infestations (mostly nasopharyngitis, COVID-19, and gastroenteritis) were the most common, experienced by 80% of the participants; 70% had injection site reactions or fatigue, 60% had gastrointestinal symptoms, 50% had a fall of IgG < 5 g/L, 40% had headache, and 20% had back pain.

“This is a positive trial. I think we could demonstrate that [daratumumab] produced very strong, rapid, and durable clinical improvements,” Dr. Alexander said. “We think that targeting CD38 is relevant; plasma cells had been depleted based on the reduction of anti-dsDNA antibodies,” he added.

From the audience, however, Peter Nash, MBBS, of Griffith University in Brisbane, Australia, questioned whether the results could be attributed to “a steroid effect” because patients had been treated with oral dexamethasone throughout the study.

Dr. Alexander noted that steroid use had been part of the treatment schedule but acknowledged it was a possible confounder.

“I think we can be confident that [daratumumab] had a major effect on plasma cells decreasing…because we see that also the vaccine titers decreased,” Dr. Alexander said. “Time will tell, but even more important is the durability of the responses over time, which you don’t achieve under steroids.”
 

KPG-818’s Novel Mechanism of Action

Elsewhere at EULAR 2024, positive results of another phase 2 study involving a drug with an entirely different mechanism of action, KPG-818, were reported in a poster presentation. KPG-818 modulates CRBN, which results in the degradation of two transcription factors (Aiolos and Ikaros) that are involved in the development, maturation, and proliferation of innate and adaptive immune cells and have been linked to genetic risk in SLE, according to the poster’s authors. It is currently in development for the treatment of SLE, Behçet disease, inflammatory bowel disease, multiple myeloma, and non-Hodgkin lymphoma.

Yao Wang, MD, chief medical officer of KPG-818’s developer Kangpu Biopharmaceuticals, Hefei, China, and associates found that oral doses of 0.15 or 0.6 mg KPG-818 were “generally well-tolerated” and produced immunomodulatory changes that could be beneficial in people with SLE over a 12-week treatment period.

“Only two new agents have been approved for the treatment of SLE in the past five decades in USA and Europe,” Dr. Wang and team wrote, which highlights “a significant unmet need for more effective and safe treatment options.”

They believe that KPG-818 might well fit the bill based on the results of their study, in which 35 of 37 recruited patients completed the treatment. Compared with placebo, they observed reduced numbers of total B cells, Aiolos+ T and B cells, and increased Treg cells.

SLEDAI-2K and Cutaneous Lupus Erythematosus Disease Area and Severity Index activity scores in the 0.15-mg group were improved relative to baseline and placebo.

“The proof-of-concept findings suggest a favorable benefit/risk ratio in SLE for KPG-818,” Dr. Wang and coauthors said, supporting its further development in SLE.
 

Need for Treatments

Dr. Isenberg told this news organization that both daratumumab and KPG-818 would be welcome additions as treatment options if further trials proved their worth.

“The great frustration about lupus is that, compared to patients with rheumatoid arthritis, the choice has been so limited,” Dr. Isenberg said. Aside from rituximab (Rituxan) and belimumab (Benlysta), which are used with certain restrictions, there are no other biologic targeted treatments available in the United Kingdom. Anifrolumab (Saphnelo) has a license in the United States and some European countries but is not yet available for him to use in his practice.

Daratumumab and KPG-818 are “different types of molecules, and if they work that will be great. It would be nice to have the choice,” Dr. Isenberg said. “Whether they will be as effective as I think rituximab is, I don’t know, but these are some very encouraging results.”

Of course, these are all phase 2 trials, and the “big problem” is that such positive results do not always translate when it comes to phase 3, as Dr. D’Cruz told this news organization.

“Until a few years ago, there had been about 25 or 30 industry-led trails, and they’d all failed, except for belimumab and anifrolumab,” Dr. D’Cruz said. These drugs were found to work and be generally safe in phase 1 and 2 trials, but “when they come to phase 3, they all seem to fail, and we don’t know why.”

These are large global studies, D’Cruz added, observing that problems with patient selection, steroid use, and choice of outcome measures were possible factors for why the EXPLORER and LUNAR studies had shown no benefit for rituximab despite the drug being widely used to treat SLE.

Dr. Isenberg, who has coauthored an article on the topic of why drugs seem to fail at the final hurdle, noted: “I think it has a lot to do with the nature of the disease. It’s a complicated disease.” From having “savvy physicians doing the trials for you” to the placebo response, there are “a whole bunch or reasons why these things haven’t worked in lupus.”

Dr. Morand commented: “We’ve got many programs in phase 2 and 3, and because there’s so many, they’re all facing recruitment challenges, and as a consequence of so much activity, every program is going a little slower than hoped for.”

As for other drugs on the horizon, Dr. Morand noted: “We’re very optimistic about things like litifilimab and deucravacitinib; that’s two examples that are in phase 3. Earlier in the program of development, [there are] a huge range of targets being addressed. The future looks bright. But we might have to wait a while.”

Dr. Arnaud has consulted for AstraZeneca, AbbVie, Alpine Immune Sciences, Biogen, Bristol Myers Squibb, Boehringer Ingelheim, Chugai Pharmaceutical, GlaxoSmithKline, Grifols, Janssen, Kezar Life Sciences, LFB, Lilly, Medac, Merck, Novartis, Pfizer, Roche, and UCB. Dr. Isenberg has served as an adviser to Merck Serono, AstraZeneca, Eli Lilly, Servier, and ImmuPharma. Any honoraria received is passed on to a local arthritis charity connected to his hospital. Dr. D’Cruz has served as a consultant and advisory board member for GlaxoSmithKline and CSL Vifor. Dr. Morand has received research support, consultancy fees, or both from multiple pharmaceutical companies paid to his institution including AbbVie, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, EMD Serono, Dragonfly, Genentech, GlaxoSmithKline, Janssen, Novartis, RemeGen, Takeda, UCB, and Zenas. The ianalumab trial presented by Dr. Agmon-Levin was sponsored by Novartis Pharma; however, she reported having no conflicts of interest. The DARALUP study was an investigator-initiated trial supported by Janssen. Dr. Alexander has received consulting fees, study support, honoraria, and travel grants from various pharmaceutical companies including AbbVie, Amgen, AstraZeneca, Bayer, GlaxoSmithKline, Janssen, and Lilly. Dr. Nash has consulted for The Rheumatology Education Group Consultants. The KPG-818 study reported by Dr. Wang was sponsored by Kangpu Biopharmaceuticals.
 

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

VIENNA — It may have been a while since there have been any major breakthroughs in the treatment of systemic lupus erythematosus (SLE), but there are high hopes that this is a situation that may be about to change, experts agreed at the annual European Congress of Rheumatology.

“It’s an incredibly vivid area of development,” Laurent Arnaud, MD, PhD, professor of rheumatology at the University of Strasbourg in Strasbourg, France, said during one of the first sessions of the meeting. He reported that there were at least 17 phase 2 and 14 phase 3 trials that were expected to start within the next few years, all with investigational agents that target different immune cells or pathways that have been implicated in the pathogenesis of SLE.

Sara Freeman/Medscape Medical News

In a systematic review published last year, Dr. Arnaud and coauthors found that there were 92 investigational biologic or novel targeted agents in various phases of clinical testing. This included B-cell–targeting agents such as ianalumab, plasma cell-targeting agents such as daratumumab, and drugs with novel mechanisms of action such as KPG-818, which targets the CRL4-Cereblon (CRBN) E3 ubiquitin ligase complex. Phase 2 data on all three of these investigational agents were presented during various sessions at EULAR 2024, all with positive results, suggesting that their further development in SLE is worth pursuing.

There are of course “many more candidates in the pipeline,” Dr. Arnaud said. “I’m very happy that I think we are going to see great days for lupus right in front of our eyes.”
 

Targeting B Cells

Drugs that target B cells have been at the forefront of lupus treatment for several years, as David Isenberg, MD, professor of rheumatology at University College London, pointed out during an interview for EULAR TV.

“It’s clearly important to target the cells which are likely to be causing the problem in lupus, and in the main, that tends to be B cells,” he said.

Dr. Isenberg, who is renowned for his work with the B-cell–targeting agent rituximab, added: “But we know that obviously T cells integrate with B cells, so anything which interrupts the link between the T cell and the B cell is likely to be important.”
 

Chimeric Antigen Receptor (CAR) T-Cell Therapy ‘Revolution’

One new way of targeting B cells is with CAR T-cell therapy, which David D’Cruz , MD, PhD, a consultant rheumatologist for Guy’s and St. Thomas’ Hospital NHS Foundation Trust in London, picked as one of the “most striking” topics highlighted at EULAR 2024.

This is “truly personalized medicine,” Dr. D’Cruz said. This is an autologous therapy because a patient’s T cells are removed by leukapheresis, transfected with a CAR T vector directed against a component of the B cell, and then returned to them.

“I do feel that we’re on the cusp of a major revolution,” Dr. D’Cruz told this news organization. Not only in lupus but also in other rheumatic conditions that have proved really difficult to treat, such as systemic sclerosis and myositis, he said.

“Basically, it’s a very powerful B-cell–depleting tool, but it’s much more profound B-cell–depleting tool than, for example, rituximab or belimumab,” explained Dr. D’Cruz. “What you’re doing is reprogramming T cells to attack the B cells.”

Although rituximab and belimumab clear all the B cells in the circulation, there are still some cells left behind in the bone marrow, “and it’s very difficult to get rid of those,” Dr. D’Cruz said. “What CAR T-cell therapy appears to do is wipe out all the CD19-positive B cells everywhere, in the blood and the tissue. So you get a really profound B-cell depletion.”

Eric Morand, MBBS, PhD, head of rheumatology at Monash Health in Melbourne, Australia, told this news organization that there was obviously “a lot of buzz” about CAR T-cell therapy.

Sara Freeman/Medscape Medical News

“We’re waiting to see if the exciting data from Erlangen can be reproduced in other centers with other CAR T products to show that it is a universal effect. We haven’t seen that yet, but I think we will by next year.”

Cost and expertise are two major considerations and potential limiting factors, however, as Dr. D’Cruz and Dr. Isenberg both pointed out in separate interviews with this news organization.

Dr. D’Cruz said: “It’s very expensive, it takes a while, and it doesn’t always work is what I’m hearing. It’s usually successful, but again, a little bit depends on the technique and the people doing the process.”

Dr. Isenberg said: “CAR T-cell therapy is, I think, very exciting because it does look to be quite promising. But as it costs 350,000 euros per patient, I don’t think that it is going to be widely adopted.”

Even if it could be afforded by certain centers in the West, he added, this just would not be feasible in poorer nations. “So, we’ve got to find other effective, cheaper ways to go,” Dr. Isenberg said.

“I think there are some very interesting ideas with monoclonal antibodies which target at least two different targets — one on the B cell, one on the T cell — and that could well be the way to take this forward,” he suggested.
 

Ianalumab ‘Double Blocking’ B Cells

Another way could be to develop more potent B-cell–depleting drugs, as Nancy Agmon-Levin , MD, head of the Clinical Immunology, Angioedema and Allergy Unit, Lupus and Autoimmune Diseases Clinic, at Sheba Medical Center, Tel Aviv University in Tel Aviv, Israel, reported during one of the clinical abstract sessions at EULAR 2024.

Dr. Agmon-Levin presented data on 67 individuals with SLE who had participated in a multicenter phase 2 study of ianalumab, a fully human immunoglobulin (Ig) G1 monoclonal antibody that results in a “double blocking of the B-cell lineage.”

Ianalumab targets the B-cell–activating factor receptor (BAFFR), but what makes it distinct from other BAFF-targeting drugs is that it has had a fructose molecule removed from its Fc portion, which renders it more likely to trigger antibody-dependent cellular cytotoxicity.

“This is a B-cell depletion therapy,” Agmon-Levin said, but it also blocks BAFFR-mediated survival of B cells, so the subsequent recuperation process of BAFFR-expressing B cells is affected, leading to continued B-cell depletion.

The phase 2 study she presented consisted of an initial 28-week, double-blind period, during which time participants had been randomly allocated to receive either subcutaneous injections of ianalumab 300 mg or a matching placebo every 4 weeks. This was followed by a 24-week, open-label period where all participants were treated with ianalumab, and then an off-treatment, minimal follow-up period that lasted up to 68 weeks, with continued data collection for safety.

The primary outcome measure was a composite of meeting criteria for the SLE Responder Index 4 and a sustained reduction in corticosteroid use at 28 weeks. This was achieved in 15 of the 34 (44.1%) people treated with ianalumab vs only 3 (9.1%) of the 33 people who had been given a placebo.

Dr. Agmon-Levin reported that the effect on this outcome was sustained to the end of the open-label period, at 1 year, in 15 (45.5%) of 33 participants who had continued treatment with ianalumab and achieved in 13 (40.6%) of 32 participants who had switched from placebo to ianalumab treatment.

Moreover, longer durations of treatment were associated with a host of improved outcomes, Dr. Agmon-Levin said: “Treatment was improved along the 52 weeks, and we can see from the LLDAS [Lupus Low Disease Activity State], DORIS [Definition Of Remission In SLE], and SRI-6 and -8 that as you continue the therapy, you improve the outcomes.”

The potential benefits of ianalumab in the treatment of SLE and lupus nephritis will now be further examined in the phase 3 SIRIUS-SLE1 , SIRIUS-SLE2, and SIRIUS-LN trials, which are estimated to provide initial results in 2027 and complete in early 2029 or 2030.
 

Targeting Plasma Cells With Daratumumab

Another drug showing signs that it might be useful as a treatment for SLE is daratumumab, as Tobias Alexander, MD, of Charité — Universitätsmedizin Berlin, reported during one of the late-breaking abstract sessions at EULAR 2024.

“Daratumumab is a human, first-in-class anti-CD38 antibody that efficiently depletes plasma cells,” Dr. Alexander said. CD38 is both a receptor and an enzyme, and while it is found on the surface of most immune cells, it’s particularly expressed by plasma cells, he added.

Daratumumab is not a total newcomer, however, as it’s already approved for the treatment of multiple myeloma under the trade name Darzalex. The rationale for using it in SLE comes from two case reports, Dr. Alexander explained. The first, published in 2020 in The New England Journal of Medicine, involved two patients with severe and life-threatening lupus who were given off-label treatment for a period of 4 weeks and experienced good clinical and serologic responses. The second, published last year in Nature Medicine, involved six patients with refractory lupus nephritis, five of whom had a clinical response at 6 months.

“On this background, we conducted an investigator-initiated trial, which was an open-label, single-center, proof-of-concept study,” Dr. Alexander said. A total of 10 female patients whose ages ranged from 24 to 43 years were included in the phase 2 trial that was dubbed DARALUP. For inclusion, all had to have a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) of four or more for clinical manifestations, have been treated with at least two prior disease-modifying drugs to no avail, and be anti–double-stranded DNA (anti-dsDNA) antibody positive. Dr. Alexander reported that the median baseline SLEDAI-2K score was 12 and ranged from 8 to 20, with the number of prior therapies ranging from two to nine.

Daratumumab was given at a dose of 1800 mg via subcutaneous injection every week for 8 weeks. This is the same dose that is used to treat multiple myeloma, Dr. Alexander explained, although the dosing is not stopped. The reason for stopping after 8 weeks in the current trial was to be able to see what happened once the treatment was stopped. The follow-up was for 36 weeks.

Dr. Alexander reported that there was a “very dramatic and significant” effect on the primary endpoint of a reduction in anti-dsDNA antibody levels, decreasing from a median of 166.3 U/mL at baseline to 61.1 U/mL at week 12 (P = .002). Alongside, there was a reduction in the SLEDAI-2K score from 12 to 4 within 12 weeks, which was sustained at the 36-week follow-up assessment. Improvements in skin, joint, kidney, and level of proteinuria were also seen.

Although all patients experienced adverse events, none were serious. Infections and infestations (mostly nasopharyngitis, COVID-19, and gastroenteritis) were the most common, experienced by 80% of the participants; 70% had injection site reactions or fatigue, 60% had gastrointestinal symptoms, 50% had a fall of IgG < 5 g/L, 40% had headache, and 20% had back pain.

“This is a positive trial. I think we could demonstrate that [daratumumab] produced very strong, rapid, and durable clinical improvements,” Dr. Alexander said. “We think that targeting CD38 is relevant; plasma cells had been depleted based on the reduction of anti-dsDNA antibodies,” he added.

From the audience, however, Peter Nash, MBBS, of Griffith University in Brisbane, Australia, questioned whether the results could be attributed to “a steroid effect” because patients had been treated with oral dexamethasone throughout the study.

Dr. Alexander noted that steroid use had been part of the treatment schedule but acknowledged it was a possible confounder.

“I think we can be confident that [daratumumab] had a major effect on plasma cells decreasing…because we see that also the vaccine titers decreased,” Dr. Alexander said. “Time will tell, but even more important is the durability of the responses over time, which you don’t achieve under steroids.”
 

KPG-818’s Novel Mechanism of Action

Elsewhere at EULAR 2024, positive results of another phase 2 study involving a drug with an entirely different mechanism of action, KPG-818, were reported in a poster presentation. KPG-818 modulates CRBN, which results in the degradation of two transcription factors (Aiolos and Ikaros) that are involved in the development, maturation, and proliferation of innate and adaptive immune cells and have been linked to genetic risk in SLE, according to the poster’s authors. It is currently in development for the treatment of SLE, Behçet disease, inflammatory bowel disease, multiple myeloma, and non-Hodgkin lymphoma.

Yao Wang, MD, chief medical officer of KPG-818’s developer Kangpu Biopharmaceuticals, Hefei, China, and associates found that oral doses of 0.15 or 0.6 mg KPG-818 were “generally well-tolerated” and produced immunomodulatory changes that could be beneficial in people with SLE over a 12-week treatment period.

“Only two new agents have been approved for the treatment of SLE in the past five decades in USA and Europe,” Dr. Wang and team wrote, which highlights “a significant unmet need for more effective and safe treatment options.”

They believe that KPG-818 might well fit the bill based on the results of their study, in which 35 of 37 recruited patients completed the treatment. Compared with placebo, they observed reduced numbers of total B cells, Aiolos+ T and B cells, and increased Treg cells.

SLEDAI-2K and Cutaneous Lupus Erythematosus Disease Area and Severity Index activity scores in the 0.15-mg group were improved relative to baseline and placebo.

“The proof-of-concept findings suggest a favorable benefit/risk ratio in SLE for KPG-818,” Dr. Wang and coauthors said, supporting its further development in SLE.
 

Need for Treatments

Dr. Isenberg told this news organization that both daratumumab and KPG-818 would be welcome additions as treatment options if further trials proved their worth.

“The great frustration about lupus is that, compared to patients with rheumatoid arthritis, the choice has been so limited,” Dr. Isenberg said. Aside from rituximab (Rituxan) and belimumab (Benlysta), which are used with certain restrictions, there are no other biologic targeted treatments available in the United Kingdom. Anifrolumab (Saphnelo) has a license in the United States and some European countries but is not yet available for him to use in his practice.

Daratumumab and KPG-818 are “different types of molecules, and if they work that will be great. It would be nice to have the choice,” Dr. Isenberg said. “Whether they will be as effective as I think rituximab is, I don’t know, but these are some very encouraging results.”

Of course, these are all phase 2 trials, and the “big problem” is that such positive results do not always translate when it comes to phase 3, as Dr. D’Cruz told this news organization.

“Until a few years ago, there had been about 25 or 30 industry-led trails, and they’d all failed, except for belimumab and anifrolumab,” Dr. D’Cruz said. These drugs were found to work and be generally safe in phase 1 and 2 trials, but “when they come to phase 3, they all seem to fail, and we don’t know why.”

These are large global studies, D’Cruz added, observing that problems with patient selection, steroid use, and choice of outcome measures were possible factors for why the EXPLORER and LUNAR studies had shown no benefit for rituximab despite the drug being widely used to treat SLE.

Dr. Isenberg, who has coauthored an article on the topic of why drugs seem to fail at the final hurdle, noted: “I think it has a lot to do with the nature of the disease. It’s a complicated disease.” From having “savvy physicians doing the trials for you” to the placebo response, there are “a whole bunch or reasons why these things haven’t worked in lupus.”

Dr. Morand commented: “We’ve got many programs in phase 2 and 3, and because there’s so many, they’re all facing recruitment challenges, and as a consequence of so much activity, every program is going a little slower than hoped for.”

As for other drugs on the horizon, Dr. Morand noted: “We’re very optimistic about things like litifilimab and deucravacitinib; that’s two examples that are in phase 3. Earlier in the program of development, [there are] a huge range of targets being addressed. The future looks bright. But we might have to wait a while.”

Dr. Arnaud has consulted for AstraZeneca, AbbVie, Alpine Immune Sciences, Biogen, Bristol Myers Squibb, Boehringer Ingelheim, Chugai Pharmaceutical, GlaxoSmithKline, Grifols, Janssen, Kezar Life Sciences, LFB, Lilly, Medac, Merck, Novartis, Pfizer, Roche, and UCB. Dr. Isenberg has served as an adviser to Merck Serono, AstraZeneca, Eli Lilly, Servier, and ImmuPharma. Any honoraria received is passed on to a local arthritis charity connected to his hospital. Dr. D’Cruz has served as a consultant and advisory board member for GlaxoSmithKline and CSL Vifor. Dr. Morand has received research support, consultancy fees, or both from multiple pharmaceutical companies paid to his institution including AbbVie, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, EMD Serono, Dragonfly, Genentech, GlaxoSmithKline, Janssen, Novartis, RemeGen, Takeda, UCB, and Zenas. The ianalumab trial presented by Dr. Agmon-Levin was sponsored by Novartis Pharma; however, she reported having no conflicts of interest. The DARALUP study was an investigator-initiated trial supported by Janssen. Dr. Alexander has received consulting fees, study support, honoraria, and travel grants from various pharmaceutical companies including AbbVie, Amgen, AstraZeneca, Bayer, GlaxoSmithKline, Janssen, and Lilly. Dr. Nash has consulted for The Rheumatology Education Group Consultants. The KPG-818 study reported by Dr. Wang was sponsored by Kangpu Biopharmaceuticals.
 

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

TOPLINE:

Since 2014, opioid use for autoimmune rheumatic diseases decreased by 15% annually while other management modalities increased or stabilized.

METHODOLOGY:

• Researchers analyzed de-identified US claims data from the MarketScan Database from 2007-2021.
• The study included nearly 142,000 patients with autoimmune rheumatic diseases: 10,927 with ankylosing spondylitis (AS); 21,438 with psoriatic arthritis (PsA); 71,393 with rheumatoid arthritis (RA); 16,718 with Sjögren disease; 18,018 with systemic lupus erythematosus; and 3468 with systemic sclerosis.
• Primary outcome was opioid use annual trends, with secondary outcomes including trends in the use of anticonvulsants, antidepressants, skeletal muscle relaxants, nonsteroidal anti-inflammatory drugs (NSAIDs), topical pain medications, and physical or occupational therapy.

TAKEAWAY:

• The incidence of opioid use increased annually by 4% until 2014 and decreased annually by 15% after 2014.
• NSAID use increased 2% annually until 2014, then declined by 5% afterward.
• The proportion of patients utilizing physical therapy or anticonvulsants doubled from 2008 to 2020.
• NSAID prescriptions were highest in AS, PsA, and RA, while they were lowest in Sjögren disease and systemic sclerosis.

IN PRACTICE:

“Our work, along with the published literature, highlights the need for future studies to evaluate the effectiveness of pain management modality changes over time and to understand the possible effects that changes have had on outcomes such as quality of life, disability, health status, and function,” wrote the authors of the study. 

SOURCE:

The study was led by Titilola Falasinnu, PhD, Stanford University School of Medicine, Stanford, California. It was published online in The Lancet Rheumatology. 

LIMITATIONS:

The study relied on administrative claims data, which did not contain information on use of over-the-counter medications like NSAIDs and topical analgesics. The study did not include the duration of pain treatment modalities, making it difficult to differentiate between acute and chronic use. The analysis did not include race or ethnicity, which is important for understanding pain outcomes across different sociodemographic groups.

DISCLOSURES:

The study was supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. 

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

TOPLINE:

Since 2014, opioid use for autoimmune rheumatic diseases decreased by 15% annually while other management modalities increased or stabilized.

METHODOLOGY:

• Researchers analyzed de-identified US claims data from the MarketScan Database from 2007-2021.
• The study included nearly 142,000 patients with autoimmune rheumatic diseases: 10,927 with ankylosing spondylitis (AS); 21,438 with psoriatic arthritis (PsA); 71,393 with rheumatoid arthritis (RA); 16,718 with Sjögren disease; 18,018 with systemic lupus erythematosus; and 3468 with systemic sclerosis.
• Primary outcome was opioid use annual trends, with secondary outcomes including trends in the use of anticonvulsants, antidepressants, skeletal muscle relaxants, nonsteroidal anti-inflammatory drugs (NSAIDs), topical pain medications, and physical or occupational therapy.

TAKEAWAY:

• The incidence of opioid use increased annually by 4% until 2014 and decreased annually by 15% after 2014.
• NSAID use increased 2% annually until 2014, then declined by 5% afterward.
• The proportion of patients utilizing physical therapy or anticonvulsants doubled from 2008 to 2020.
• NSAID prescriptions were highest in AS, PsA, and RA, while they were lowest in Sjögren disease and systemic sclerosis.

IN PRACTICE:

“Our work, along with the published literature, highlights the need for future studies to evaluate the effectiveness of pain management modality changes over time and to understand the possible effects that changes have had on outcomes such as quality of life, disability, health status, and function,” wrote the authors of the study. 

SOURCE:

The study was led by Titilola Falasinnu, PhD, Stanford University School of Medicine, Stanford, California. It was published online in The Lancet Rheumatology. 

LIMITATIONS:

The study relied on administrative claims data, which did not contain information on use of over-the-counter medications like NSAIDs and topical analgesics. The study did not include the duration of pain treatment modalities, making it difficult to differentiate between acute and chronic use. The analysis did not include race or ethnicity, which is important for understanding pain outcomes across different sociodemographic groups.

DISCLOSURES:

The study was supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. 

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

TOPLINE:

Since 2014, opioid use for autoimmune rheumatic diseases decreased by 15% annually while other management modalities increased or stabilized.

METHODOLOGY:

• Researchers analyzed de-identified US claims data from the MarketScan Database from 2007-2021.
• The study included nearly 142,000 patients with autoimmune rheumatic diseases: 10,927 with ankylosing spondylitis (AS); 21,438 with psoriatic arthritis (PsA); 71,393 with rheumatoid arthritis (RA); 16,718 with Sjögren disease; 18,018 with systemic lupus erythematosus; and 3468 with systemic sclerosis.
• Primary outcome was opioid use annual trends, with secondary outcomes including trends in the use of anticonvulsants, antidepressants, skeletal muscle relaxants, nonsteroidal anti-inflammatory drugs (NSAIDs), topical pain medications, and physical or occupational therapy.

TAKEAWAY:

• The incidence of opioid use increased annually by 4% until 2014 and decreased annually by 15% after 2014.
• NSAID use increased 2% annually until 2014, then declined by 5% afterward.
• The proportion of patients utilizing physical therapy or anticonvulsants doubled from 2008 to 2020.
• NSAID prescriptions were highest in AS, PsA, and RA, while they were lowest in Sjögren disease and systemic sclerosis.

IN PRACTICE:

“Our work, along with the published literature, highlights the need for future studies to evaluate the effectiveness of pain management modality changes over time and to understand the possible effects that changes have had on outcomes such as quality of life, disability, health status, and function,” wrote the authors of the study. 

SOURCE:

The study was led by Titilola Falasinnu, PhD, Stanford University School of Medicine, Stanford, California. It was published online in The Lancet Rheumatology. 

LIMITATIONS:

The study relied on administrative claims data, which did not contain information on use of over-the-counter medications like NSAIDs and topical analgesics. The study did not include the duration of pain treatment modalities, making it difficult to differentiate between acute and chronic use. The analysis did not include race or ethnicity, which is important for understanding pain outcomes across different sociodemographic groups.

DISCLOSURES:

The study was supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. 

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