This transcript has been edited for clarity. 

Lawyers have the saying, “Bad facts make for bad cases; bad cases make for bad laws.” What we’re seeing, I fear, all too often in discussions about reproductive rights, reproductive behavior, and attempts to regulate and legislate with respect to abortion and contraception are many bad facts.

I do think it’s important that science and medicine speak up in local settings and every opportunity they have, not so much to say what government should do or to say whether they think a particular law is good or bad, but certainly to get the facts straight in their role as doctors, sometimes as scientists, and as caregivers.

Bad facts are making many bad policies in the reproductive behavior space. For example, there are many people, mainly on the conservative side, who are saying things like intrauterine devices, emergency contraception, and even birth control cause abortions. That is simply not true.

There are interventions that prevent fertilization from occurring. There are also interventions that prevent implantation from occurring. Neither of those are abortions. If an embryo has not implanted into a womb, it is not, by any biological definition, a pregnancy. 

In situations where a barrier method or something else prevents sperm and egg from meeting or if there is an agent that prevents an egg from implanting, these are facts that legislators, the public, and even your patients need to understand if they’re going to make sound policy about access to methods used to control reproduction.

Similarly, you can see debates about whether embryos are deserving of rights. An Alabama court has ruled that embryos are tiny children. A court can say what it wishes in terms of legal status, but it shouldn’t be deviating from the facts. 

The facts are clear. Embryos outside of a uterus implanted are not babies. They are not children. At most, an embryo in a dish might be considered, let’s say, a possible person. Once it implants in a uterus, it may become a potential person because it then still has a failure rate, postimplantation, of not becoming a baby that’s very high. Approximately 40%-50% of such embryos are genetically flawed and aren’t going to be able to turn into a child.

The notion that every embryo, whether it’s stored in a tank or sitting in a dish, is somehow a tiny child, factually is just not true. You can’t make good policy if you ignore the facts. People may wish to protect embryos. They may wish to restrict in vitro fertilization. They may wish to have people implant any embryo that is created and mandate that it has to happen because they don’t want any tiny children not to be brought to term.

Factually, they’re operating outside the realm of what biology and medicine know. There’s no tiny baby, no homunculus, or no preformed baby inside an embryo. An egg that simply fails to implant is not technically even a pregnancy. 

I think all of us have an obligation when we’re in disputes, wherever they occur, whether we’re fighting about laws, having an argument with the neighbors, or speaking to younger high school students or even patients, we need to try to make clear the facts about what we know about eggs, how birth control works, and embryos and their failure rate. 

We also have to be clear about the significance of saying the facts have to guide public policy. I think the facts should, but unfortunately, I don’t think that’s always been true in recent years. As efforts heat up to intervene more with things like contraception, getting the facts straight becomes even more important and more of a duty for those who know best.

Dr. Caplan is director, Division of Medical Ethics, New York University Langone Medical Center, New York. He served as a director, officer, partner, employee, adviser, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position). He is a contributing author and adviser for Medscape.

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

This transcript has been edited for clarity. 

Lawyers have the saying, “Bad facts make for bad cases; bad cases make for bad laws.” What we’re seeing, I fear, all too often in discussions about reproductive rights, reproductive behavior, and attempts to regulate and legislate with respect to abortion and contraception are many bad facts.

I do think it’s important that science and medicine speak up in local settings and every opportunity they have, not so much to say what government should do or to say whether they think a particular law is good or bad, but certainly to get the facts straight in their role as doctors, sometimes as scientists, and as caregivers.

Bad facts are making many bad policies in the reproductive behavior space. For example, there are many people, mainly on the conservative side, who are saying things like intrauterine devices, emergency contraception, and even birth control cause abortions. That is simply not true.

There are interventions that prevent fertilization from occurring. There are also interventions that prevent implantation from occurring. Neither of those are abortions. If an embryo has not implanted into a womb, it is not, by any biological definition, a pregnancy. 

In situations where a barrier method or something else prevents sperm and egg from meeting or if there is an agent that prevents an egg from implanting, these are facts that legislators, the public, and even your patients need to understand if they’re going to make sound policy about access to methods used to control reproduction.

Similarly, you can see debates about whether embryos are deserving of rights. An Alabama court has ruled that embryos are tiny children. A court can say what it wishes in terms of legal status, but it shouldn’t be deviating from the facts. 

The facts are clear. Embryos outside of a uterus implanted are not babies. They are not children. At most, an embryo in a dish might be considered, let’s say, a possible person. Once it implants in a uterus, it may become a potential person because it then still has a failure rate, postimplantation, of not becoming a baby that’s very high. Approximately 40%-50% of such embryos are genetically flawed and aren’t going to be able to turn into a child.

The notion that every embryo, whether it’s stored in a tank or sitting in a dish, is somehow a tiny child, factually is just not true. You can’t make good policy if you ignore the facts. People may wish to protect embryos. They may wish to restrict in vitro fertilization. They may wish to have people implant any embryo that is created and mandate that it has to happen because they don’t want any tiny children not to be brought to term.

Factually, they’re operating outside the realm of what biology and medicine know. There’s no tiny baby, no homunculus, or no preformed baby inside an embryo. An egg that simply fails to implant is not technically even a pregnancy. 

I think all of us have an obligation when we’re in disputes, wherever they occur, whether we’re fighting about laws, having an argument with the neighbors, or speaking to younger high school students or even patients, we need to try to make clear the facts about what we know about eggs, how birth control works, and embryos and their failure rate. 

We also have to be clear about the significance of saying the facts have to guide public policy. I think the facts should, but unfortunately, I don’t think that’s always been true in recent years. As efforts heat up to intervene more with things like contraception, getting the facts straight becomes even more important and more of a duty for those who know best.

Dr. Caplan is director, Division of Medical Ethics, New York University Langone Medical Center, New York. He served as a director, officer, partner, employee, adviser, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position). He is a contributing author and adviser for Medscape.

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

This transcript has been edited for clarity. 

Lawyers have the saying, “Bad facts make for bad cases; bad cases make for bad laws.” What we’re seeing, I fear, all too often in discussions about reproductive rights, reproductive behavior, and attempts to regulate and legislate with respect to abortion and contraception are many bad facts.

I do think it’s important that science and medicine speak up in local settings and every opportunity they have, not so much to say what government should do or to say whether they think a particular law is good or bad, but certainly to get the facts straight in their role as doctors, sometimes as scientists, and as caregivers.

Bad facts are making many bad policies in the reproductive behavior space. For example, there are many people, mainly on the conservative side, who are saying things like intrauterine devices, emergency contraception, and even birth control cause abortions. That is simply not true.

There are interventions that prevent fertilization from occurring. There are also interventions that prevent implantation from occurring. Neither of those are abortions. If an embryo has not implanted into a womb, it is not, by any biological definition, a pregnancy. 

In situations where a barrier method or something else prevents sperm and egg from meeting or if there is an agent that prevents an egg from implanting, these are facts that legislators, the public, and even your patients need to understand if they’re going to make sound policy about access to methods used to control reproduction.

Similarly, you can see debates about whether embryos are deserving of rights. An Alabama court has ruled that embryos are tiny children. A court can say what it wishes in terms of legal status, but it shouldn’t be deviating from the facts. 

The facts are clear. Embryos outside of a uterus implanted are not babies. They are not children. At most, an embryo in a dish might be considered, let’s say, a possible person. Once it implants in a uterus, it may become a potential person because it then still has a failure rate, postimplantation, of not becoming a baby that’s very high. Approximately 40%-50% of such embryos are genetically flawed and aren’t going to be able to turn into a child.

The notion that every embryo, whether it’s stored in a tank or sitting in a dish, is somehow a tiny child, factually is just not true. You can’t make good policy if you ignore the facts. People may wish to protect embryos. They may wish to restrict in vitro fertilization. They may wish to have people implant any embryo that is created and mandate that it has to happen because they don’t want any tiny children not to be brought to term.

Factually, they’re operating outside the realm of what biology and medicine know. There’s no tiny baby, no homunculus, or no preformed baby inside an embryo. An egg that simply fails to implant is not technically even a pregnancy. 

I think all of us have an obligation when we’re in disputes, wherever they occur, whether we’re fighting about laws, having an argument with the neighbors, or speaking to younger high school students or even patients, we need to try to make clear the facts about what we know about eggs, how birth control works, and embryos and their failure rate. 

We also have to be clear about the significance of saying the facts have to guide public policy. I think the facts should, but unfortunately, I don’t think that’s always been true in recent years. As efforts heat up to intervene more with things like contraception, getting the facts straight becomes even more important and more of a duty for those who know best.

Dr. Caplan is director, Division of Medical Ethics, New York University Langone Medical Center, New York. He served as a director, officer, partner, employee, adviser, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position). He is a contributing author and adviser for Medscape.

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

Most young people, ages 10-24 years old, who die by suicide have no previously documented mental health diagnosis, according to a large analysis of Centers for Disease Control and Prevention data.

Sofia Chaudhary, MD, with the Department of Pediatrics and Emergency Medicine at Emory University School of Medicine in Atlanta, Georgia, and colleagues, analyzed data from the National Violent Death Reporting System and found in the cross-sectional study of 40, 618 youths that 24,192 (59.6%) had no such diagnosis previously. Findings were published online in JAMA Network Open.
 

Gaps by Race, Sex and Age

The odds of having a mental health diagnosis before death by suicide differed by race and sex. Compared with White youths, the odds were lower among youths who were American Indian or Alaska Native (adjusted odds ratio [aOR], 0.45; Asian, Native Hawaiian, or Other Pacific Islander (aOR, 0.58); and Black youths (aOR, 0.62). And more than half of female youths who died by suicide had a mental health diagnosis (4429 youths [52.4%]), compared with 11,994 male youths (37.3%).

The researchers also found wide gaps by age, specifically lower odds of having a mental health diagnosis before suicide in children ages 10-14 compared with those 20-24.

“This finding is particularly notable because suicide rates have risen to become the second leading cause of death in youths aged 10 to 14 years,” the authors wrote. “Suicide prevention strategies for young children in primary care and community settings should focus on fostering resilience, promoting peer and family connectedness, and empowering children with strategies to cope with stress and adversity.”

Youths who died by firearm suicide, the most common mechanism, had the lowest rate of diagnosis. “Similar to a prior study, we found that decedents without a documented mental health diagnosis were far more likely to utilize a firearm than those with a documented mental health diagnosis,” the authors wrote. 

In an invited commentary, Lisa M. Horowitz, PhD, MPH, with the Office of the Clinical Director, Intramural Research Program, National Institute of Mental Health, in Bethesda, Maryland, and colleagues wrote that the data show that identifying youth early who have mental disorders or are at-risk for suicide “is more the exception than the rule” in the United States.

The editorialists highlight that the study showed that about one-quarter of youths who have attempted suicide and nearly one-half of youths with depressed mood had no documented mental health diagnosis. Decedents were categorized with depressed mood if they were perceived by themselves or others as depressed at the time of death.
 

Intervention Recommendations

The study authors point to the high number of youth firearm suicide (the method used by nearly half of those who died — 19,027 (46.8%) and recommended interventions. “Suicide prevention strategies are needed for the estimated 22.6 million US children living in households with firearms, of whom 4.5 million are exposed to firearms stored loaded and unlocked,” they wrote.

A mental health diagnosis was documented for only 6308 of 19,027 youths who died by firearms (33.2%).

They noted that research has shown that more than 75% of guns used in youth suicide are owned by a family member, most commonly parents, and the presence of a firearm in the home is linked with a higher risk of youth suicide.

They wrote that the risk can be mitigated by storing all guns locked and unloaded, with ammunition stored and locked in a separate location.

The editorialists said the study highlights the need for action in several primary areas. “Suicide prevention strategies should not solely rely on a history of mental illness to identify at-risk youths, and universal suicide risk screening in healthcare settings deserves greater consideration,” they wrote.

Equitable access to care is essential to youth suicide risk detection. Interventions such as lethal means safety counseling, safety planning, and a helpline number, such as 988, should be accessible to every family and healthcare clinician.

Community-level interventions are critical, including school-based suicide prevention programs, as well as population-based training for families on the safe storage of lethal means at home.

“Every trusted adult working with children and adolescents can and should be trained to recognize the warning signs of suicide risk and help young people develop the coping strategies needed to manage difficult life experiences so that suicide is never an option,” Dr. Horowitz and colleagues wrote.

A coauthor of the study, Jennifer A. Hoffmann, MD, reports receiving grants from Children’s Research Fund Junior Board outside the submitted work. Another coauthor, Joel Fein, MD, reports fees for a patent owned by Children’s Hospital of Philadelphia licensed to Potential for the Behavioral Health Screen-Emergency Department. Among the editorialists, Jeffrey A. Bridge, PhD, reported grants from the National Institute of Mental Health, Patient Centered Outcomes Research Institute, and Centers for Disease Control and Prevention; and being a member of the Scientific Advisory Board of Clarigent Health and the Scientific Council of the American Foundation for Suicide Prevention outside the submitted work.

Most young people, ages 10-24 years old, who die by suicide have no previously documented mental health diagnosis, according to a large analysis of Centers for Disease Control and Prevention data.

Sofia Chaudhary, MD, with the Department of Pediatrics and Emergency Medicine at Emory University School of Medicine in Atlanta, Georgia, and colleagues, analyzed data from the National Violent Death Reporting System and found in the cross-sectional study of 40, 618 youths that 24,192 (59.6%) had no such diagnosis previously. Findings were published online in JAMA Network Open.
 

Gaps by Race, Sex and Age

The odds of having a mental health diagnosis before death by suicide differed by race and sex. Compared with White youths, the odds were lower among youths who were American Indian or Alaska Native (adjusted odds ratio [aOR], 0.45; Asian, Native Hawaiian, or Other Pacific Islander (aOR, 0.58); and Black youths (aOR, 0.62). And more than half of female youths who died by suicide had a mental health diagnosis (4429 youths [52.4%]), compared with 11,994 male youths (37.3%).

The researchers also found wide gaps by age, specifically lower odds of having a mental health diagnosis before suicide in children ages 10-14 compared with those 20-24.

“This finding is particularly notable because suicide rates have risen to become the second leading cause of death in youths aged 10 to 14 years,” the authors wrote. “Suicide prevention strategies for young children in primary care and community settings should focus on fostering resilience, promoting peer and family connectedness, and empowering children with strategies to cope with stress and adversity.”

Youths who died by firearm suicide, the most common mechanism, had the lowest rate of diagnosis. “Similar to a prior study, we found that decedents without a documented mental health diagnosis were far more likely to utilize a firearm than those with a documented mental health diagnosis,” the authors wrote. 

In an invited commentary, Lisa M. Horowitz, PhD, MPH, with the Office of the Clinical Director, Intramural Research Program, National Institute of Mental Health, in Bethesda, Maryland, and colleagues wrote that the data show that identifying youth early who have mental disorders or are at-risk for suicide “is more the exception than the rule” in the United States.

The editorialists highlight that the study showed that about one-quarter of youths who have attempted suicide and nearly one-half of youths with depressed mood had no documented mental health diagnosis. Decedents were categorized with depressed mood if they were perceived by themselves or others as depressed at the time of death.
 

Intervention Recommendations

The study authors point to the high number of youth firearm suicide (the method used by nearly half of those who died — 19,027 (46.8%) and recommended interventions. “Suicide prevention strategies are needed for the estimated 22.6 million US children living in households with firearms, of whom 4.5 million are exposed to firearms stored loaded and unlocked,” they wrote.

A mental health diagnosis was documented for only 6308 of 19,027 youths who died by firearms (33.2%).

They noted that research has shown that more than 75% of guns used in youth suicide are owned by a family member, most commonly parents, and the presence of a firearm in the home is linked with a higher risk of youth suicide.

They wrote that the risk can be mitigated by storing all guns locked and unloaded, with ammunition stored and locked in a separate location.

The editorialists said the study highlights the need for action in several primary areas. “Suicide prevention strategies should not solely rely on a history of mental illness to identify at-risk youths, and universal suicide risk screening in healthcare settings deserves greater consideration,” they wrote.

Equitable access to care is essential to youth suicide risk detection. Interventions such as lethal means safety counseling, safety planning, and a helpline number, such as 988, should be accessible to every family and healthcare clinician.

Community-level interventions are critical, including school-based suicide prevention programs, as well as population-based training for families on the safe storage of lethal means at home.

“Every trusted adult working with children and adolescents can and should be trained to recognize the warning signs of suicide risk and help young people develop the coping strategies needed to manage difficult life experiences so that suicide is never an option,” Dr. Horowitz and colleagues wrote.

A coauthor of the study, Jennifer A. Hoffmann, MD, reports receiving grants from Children’s Research Fund Junior Board outside the submitted work. Another coauthor, Joel Fein, MD, reports fees for a patent owned by Children’s Hospital of Philadelphia licensed to Potential for the Behavioral Health Screen-Emergency Department. Among the editorialists, Jeffrey A. Bridge, PhD, reported grants from the National Institute of Mental Health, Patient Centered Outcomes Research Institute, and Centers for Disease Control and Prevention; and being a member of the Scientific Advisory Board of Clarigent Health and the Scientific Council of the American Foundation for Suicide Prevention outside the submitted work.

Most young people, ages 10-24 years old, who die by suicide have no previously documented mental health diagnosis, according to a large analysis of Centers for Disease Control and Prevention data.

Sofia Chaudhary, MD, with the Department of Pediatrics and Emergency Medicine at Emory University School of Medicine in Atlanta, Georgia, and colleagues, analyzed data from the National Violent Death Reporting System and found in the cross-sectional study of 40, 618 youths that 24,192 (59.6%) had no such diagnosis previously. Findings were published online in JAMA Network Open.
 

Gaps by Race, Sex and Age

The odds of having a mental health diagnosis before death by suicide differed by race and sex. Compared with White youths, the odds were lower among youths who were American Indian or Alaska Native (adjusted odds ratio [aOR], 0.45; Asian, Native Hawaiian, or Other Pacific Islander (aOR, 0.58); and Black youths (aOR, 0.62). And more than half of female youths who died by suicide had a mental health diagnosis (4429 youths [52.4%]), compared with 11,994 male youths (37.3%).

The researchers also found wide gaps by age, specifically lower odds of having a mental health diagnosis before suicide in children ages 10-14 compared with those 20-24.

“This finding is particularly notable because suicide rates have risen to become the second leading cause of death in youths aged 10 to 14 years,” the authors wrote. “Suicide prevention strategies for young children in primary care and community settings should focus on fostering resilience, promoting peer and family connectedness, and empowering children with strategies to cope with stress and adversity.”

Youths who died by firearm suicide, the most common mechanism, had the lowest rate of diagnosis. “Similar to a prior study, we found that decedents without a documented mental health diagnosis were far more likely to utilize a firearm than those with a documented mental health diagnosis,” the authors wrote. 

In an invited commentary, Lisa M. Horowitz, PhD, MPH, with the Office of the Clinical Director, Intramural Research Program, National Institute of Mental Health, in Bethesda, Maryland, and colleagues wrote that the data show that identifying youth early who have mental disorders or are at-risk for suicide “is more the exception than the rule” in the United States.

The editorialists highlight that the study showed that about one-quarter of youths who have attempted suicide and nearly one-half of youths with depressed mood had no documented mental health diagnosis. Decedents were categorized with depressed mood if they were perceived by themselves or others as depressed at the time of death.
 

Intervention Recommendations

The study authors point to the high number of youth firearm suicide (the method used by nearly half of those who died — 19,027 (46.8%) and recommended interventions. “Suicide prevention strategies are needed for the estimated 22.6 million US children living in households with firearms, of whom 4.5 million are exposed to firearms stored loaded and unlocked,” they wrote.

A mental health diagnosis was documented for only 6308 of 19,027 youths who died by firearms (33.2%).

They noted that research has shown that more than 75% of guns used in youth suicide are owned by a family member, most commonly parents, and the presence of a firearm in the home is linked with a higher risk of youth suicide.

They wrote that the risk can be mitigated by storing all guns locked and unloaded, with ammunition stored and locked in a separate location.

The editorialists said the study highlights the need for action in several primary areas. “Suicide prevention strategies should not solely rely on a history of mental illness to identify at-risk youths, and universal suicide risk screening in healthcare settings deserves greater consideration,” they wrote.

Equitable access to care is essential to youth suicide risk detection. Interventions such as lethal means safety counseling, safety planning, and a helpline number, such as 988, should be accessible to every family and healthcare clinician.

Community-level interventions are critical, including school-based suicide prevention programs, as well as population-based training for families on the safe storage of lethal means at home.

“Every trusted adult working with children and adolescents can and should be trained to recognize the warning signs of suicide risk and help young people develop the coping strategies needed to manage difficult life experiences so that suicide is never an option,” Dr. Horowitz and colleagues wrote.

A coauthor of the study, Jennifer A. Hoffmann, MD, reports receiving grants from Children’s Research Fund Junior Board outside the submitted work. Another coauthor, Joel Fein, MD, reports fees for a patent owned by Children’s Hospital of Philadelphia licensed to Potential for the Behavioral Health Screen-Emergency Department. Among the editorialists, Jeffrey A. Bridge, PhD, reported grants from the National Institute of Mental Health, Patient Centered Outcomes Research Institute, and Centers for Disease Control and Prevention; and being a member of the Scientific Advisory Board of Clarigent Health and the Scientific Council of the American Foundation for Suicide Prevention outside the submitted work.

While there may be some lactation consultants who disagree, in my experience counseling women attempting to breastfeed is more art than science. Well before the American Academy of Pediatrics (AAP) began to offer mini courses on breastfeeding for practitioners I was left to help new mothers based on watching my wife nurse our three children and what scraps of common sense I could sweep up off the floor.

Using my own benchmarks of success I would say I did a decent job with dyads who sought my help. I began by accepting that even under optimal conditions, not every woman and/or child can successfully breastfeed. None of the infants died or was hospitalized with dehydration. A few may have required some additional phototherapy, but they all completed infancy in good shape. On the maternal side I am sure there were a few mothers who had lingering feelings of inadequacy because they had “failed” at breastfeeding. But, for the most part, I think I succeeded in helping new mothers remain as mentally healthy as they could be given the rigors of motherhood. At least I gave it my best shot.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

While there may be some lactation consultants who disagree, in my experience counseling women attempting to breastfeed is more art than science. Well before the American Academy of Pediatrics (AAP) began to offer mini courses on breastfeeding for practitioners I was left to help new mothers based on watching my wife nurse our three children and what scraps of common sense I could sweep up off the floor.

Using my own benchmarks of success I would say I did a decent job with dyads who sought my help. I began by accepting that even under optimal conditions, not every woman and/or child can successfully breastfeed. None of the infants died or was hospitalized with dehydration. A few may have required some additional phototherapy, but they all completed infancy in good shape. On the maternal side I am sure there were a few mothers who had lingering feelings of inadequacy because they had “failed” at breastfeeding. But, for the most part, I think I succeeded in helping new mothers remain as mentally healthy as they could be given the rigors of motherhood. At least I gave it my best shot.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

While there may be some lactation consultants who disagree, in my experience counseling women attempting to breastfeed is more art than science. Well before the American Academy of Pediatrics (AAP) began to offer mini courses on breastfeeding for practitioners I was left to help new mothers based on watching my wife nurse our three children and what scraps of common sense I could sweep up off the floor.

Using my own benchmarks of success I would say I did a decent job with dyads who sought my help. I began by accepting that even under optimal conditions, not every woman and/or child can successfully breastfeed. None of the infants died or was hospitalized with dehydration. A few may have required some additional phototherapy, but they all completed infancy in good shape. On the maternal side I am sure there were a few mothers who had lingering feelings of inadequacy because they had “failed” at breastfeeding. But, for the most part, I think I succeeded in helping new mothers remain as mentally healthy as they could be given the rigors of motherhood. At least I gave it my best shot.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

The ability of advanced diffusion MRI (dMRI) techniques to detect microstructural neurological changes in military patients with remote mild traumatic brain injury (mTBI) supports wider adoption of these techniques, according to authors of a recent study. In particular, they said, using neurite orientation dispersion and density imaging (NODDI) to monitor long-term mTBI impact on brain regions related to cognitive and emotional processing can help clinicians assess recovery, predict progression, and optimize treatment.

“Currently,” said co-senior study author Ping-Hong Yeh, PhD, “there is a lack of minimally invasive, quantitative diagnostic biomarkers for monitoring progression or recovery after mild TBI. However, mild TBI can be quite disabling, with many patients reporting symptoms months or even years after injury. This is the most difficult part to diagnose.” Dr. Yeh is a researcher at the National Intrepid Center of Excellence (NICoE) at Walter Reed National Military Medical Center, Bethesda, Maryland.

The NICoE, a Department of Defense organization and the senior member of Defense Intrepid Network for Traumatic Brain Injury and Brain Health, is among several centers charged with improving support for injured service members’ recovery, rehabilitation, and reintegration into their communities. The overarching goal, said Dr. Yeh, is to enable community neurologists to refer service members and veterans to these centers for treatment and advanced imaging when needed.
 

Invisible Wounds

Limitations of conventional MRI and CT make it tough to discern which patients with mTBI will return to baseline functioning, and which will develop long-term complications. Addressing the silent or invisible wounds of mTBI will require improved diagnostic, prognostic, and therapeutic tools, he said.

For their study, published in JAMA Network Open, Dr. Yeh and colleagues compared diffusion tensor imaging (DTI) and NODDI data from 65 male service members with remote (more than 2 years old) mTBI against scans of 33 noninjured controls matched for age, sex, and active-duty status.

“Although DTI is very sensitive in detecting microstructural changes in mild TBI,” he said, “it is not specific to the underlying pathophysiological changes.”

Conversely, NODDI uses biophysical modeling of intracellular diffusion, extracellular diffusion, and free water to help physicians to understand subtle pathophysiological changes with greater sensitivity and specificity than does DTI. “This will allow us to correlate symptoms with brain structural changes, making the invisible wound visible.”

In the study, the greatest differences between injured and control patients appeared in the following NODDI metrics (P <.001 in all analyses):

• Intracellular volume fraction (ICVF) of the right corticospinal tract (CST)
• Orientation dispersion index (ODI) of the left posterior thalamic radiation (PTR)
• ODI of the left uncinate fasciculus (UNC)

Regarding patient-reported neurobehavioral symptoms, Neurobehavioral Symptom Inventory cognitive subscores were associated with fractional anisotropy of the left UNC. In addition, PTSD Checklist–Civilian version total scores and avoidance subscores corresponded, respectively, with isotropic volume fraction (ISOVF) of the genu of corpus callosum and with ODI of the left fornix and stria terminalis.
 

Next Steps

Presently, Dr. Yeh said, conventional MRI and CT usually cannot differentiate between axonal injury, axonal inflammation (which develops during the chronic phase of mTBI), and demyelination. “But newer biophysical modeling, such as NODDI, will allow us to tell the difference.” Along with providing prognostic information, he said, such technology can guide appropriate treatment, such as anti-inflammatory agents for chronic inflammation.

Most community neurologists refer patients with persistent mTBI symptoms in the absence of red flags using CT and conventional MRI for advanced neuroimaging, said Dr. Yeh. But because few community neurologists are familiar with NODDI, he said, broadening its reach will require educating these providers. Additional steps that Dr. Yeh said could occur over the next decade or more include boosting advanced dMRI sensitivity levels through improved hardware, software, and diagnostic tools.

“We need to make these techniques clinically feasible,” he added. Currently, protocols that allow advanced dMRI scans in about 10 minutes can be achievable.

The investments required to implement advanced dMRI techniques will be substantial. A state-of-the-art 3T MRI scanner that can support NODDI and DTI can easily cost $1 million, said Dr. Yeh. Factor in additional equipment options and construction costs, he added, and the total price tag can easily exceed $2 million. But rather than replacing all existing MRI systems, said Dr. Yeh, AI one day may help translate high-gradient capability even to widely used lower-field MRI scanners operating at 0.5T.

Streamlining systems that incorporate disparate scanners with different acquisition parameters will require standardized data acquisition and sharing parameters. Along with helping to evaluate new techniques as they become available, data harmonization and sharing can facilitate a shift from research comparisons between large groups to comparing a single patient against many others — a move that Dr. Yeh said must occur for advanced dMRI techniques to achieve clinical relevance.

In addition, experts will need to revise clinical guidelines for use of new technologies as their availability grows. “Improper use of these techniques will not only increase health costs, but also probably result in adverse health results.” Such guidelines could be very useful in evaluating the suitability and quality of referrals for diagnostic images, Dr. Yeh said.

Dr. Yeh reports no relevant financial interests. The project was partially funded by the US Army Medical Research and Materiel Command.

The ability of advanced diffusion MRI (dMRI) techniques to detect microstructural neurological changes in military patients with remote mild traumatic brain injury (mTBI) supports wider adoption of these techniques, according to authors of a recent study. In particular, they said, using neurite orientation dispersion and density imaging (NODDI) to monitor long-term mTBI impact on brain regions related to cognitive and emotional processing can help clinicians assess recovery, predict progression, and optimize treatment.

“Currently,” said co-senior study author Ping-Hong Yeh, PhD, “there is a lack of minimally invasive, quantitative diagnostic biomarkers for monitoring progression or recovery after mild TBI. However, mild TBI can be quite disabling, with many patients reporting symptoms months or even years after injury. This is the most difficult part to diagnose.” Dr. Yeh is a researcher at the National Intrepid Center of Excellence (NICoE) at Walter Reed National Military Medical Center, Bethesda, Maryland.

The NICoE, a Department of Defense organization and the senior member of Defense Intrepid Network for Traumatic Brain Injury and Brain Health, is among several centers charged with improving support for injured service members’ recovery, rehabilitation, and reintegration into their communities. The overarching goal, said Dr. Yeh, is to enable community neurologists to refer service members and veterans to these centers for treatment and advanced imaging when needed.
 

Invisible Wounds

Limitations of conventional MRI and CT make it tough to discern which patients with mTBI will return to baseline functioning, and which will develop long-term complications. Addressing the silent or invisible wounds of mTBI will require improved diagnostic, prognostic, and therapeutic tools, he said.

For their study, published in JAMA Network Open, Dr. Yeh and colleagues compared diffusion tensor imaging (DTI) and NODDI data from 65 male service members with remote (more than 2 years old) mTBI against scans of 33 noninjured controls matched for age, sex, and active-duty status.

“Although DTI is very sensitive in detecting microstructural changes in mild TBI,” he said, “it is not specific to the underlying pathophysiological changes.”

Conversely, NODDI uses biophysical modeling of intracellular diffusion, extracellular diffusion, and free water to help physicians to understand subtle pathophysiological changes with greater sensitivity and specificity than does DTI. “This will allow us to correlate symptoms with brain structural changes, making the invisible wound visible.”

In the study, the greatest differences between injured and control patients appeared in the following NODDI metrics (P <.001 in all analyses):

• Intracellular volume fraction (ICVF) of the right corticospinal tract (CST)
• Orientation dispersion index (ODI) of the left posterior thalamic radiation (PTR)
• ODI of the left uncinate fasciculus (UNC)

Regarding patient-reported neurobehavioral symptoms, Neurobehavioral Symptom Inventory cognitive subscores were associated with fractional anisotropy of the left UNC. In addition, PTSD Checklist–Civilian version total scores and avoidance subscores corresponded, respectively, with isotropic volume fraction (ISOVF) of the genu of corpus callosum and with ODI of the left fornix and stria terminalis.
 

Next Steps

Presently, Dr. Yeh said, conventional MRI and CT usually cannot differentiate between axonal injury, axonal inflammation (which develops during the chronic phase of mTBI), and demyelination. “But newer biophysical modeling, such as NODDI, will allow us to tell the difference.” Along with providing prognostic information, he said, such technology can guide appropriate treatment, such as anti-inflammatory agents for chronic inflammation.

Most community neurologists refer patients with persistent mTBI symptoms in the absence of red flags using CT and conventional MRI for advanced neuroimaging, said Dr. Yeh. But because few community neurologists are familiar with NODDI, he said, broadening its reach will require educating these providers. Additional steps that Dr. Yeh said could occur over the next decade or more include boosting advanced dMRI sensitivity levels through improved hardware, software, and diagnostic tools.

“We need to make these techniques clinically feasible,” he added. Currently, protocols that allow advanced dMRI scans in about 10 minutes can be achievable.

The investments required to implement advanced dMRI techniques will be substantial. A state-of-the-art 3T MRI scanner that can support NODDI and DTI can easily cost $1 million, said Dr. Yeh. Factor in additional equipment options and construction costs, he added, and the total price tag can easily exceed $2 million. But rather than replacing all existing MRI systems, said Dr. Yeh, AI one day may help translate high-gradient capability even to widely used lower-field MRI scanners operating at 0.5T.

Streamlining systems that incorporate disparate scanners with different acquisition parameters will require standardized data acquisition and sharing parameters. Along with helping to evaluate new techniques as they become available, data harmonization and sharing can facilitate a shift from research comparisons between large groups to comparing a single patient against many others — a move that Dr. Yeh said must occur for advanced dMRI techniques to achieve clinical relevance.

In addition, experts will need to revise clinical guidelines for use of new technologies as their availability grows. “Improper use of these techniques will not only increase health costs, but also probably result in adverse health results.” Such guidelines could be very useful in evaluating the suitability and quality of referrals for diagnostic images, Dr. Yeh said.

Dr. Yeh reports no relevant financial interests. The project was partially funded by the US Army Medical Research and Materiel Command.

The ability of advanced diffusion MRI (dMRI) techniques to detect microstructural neurological changes in military patients with remote mild traumatic brain injury (mTBI) supports wider adoption of these techniques, according to authors of a recent study. In particular, they said, using neurite orientation dispersion and density imaging (NODDI) to monitor long-term mTBI impact on brain regions related to cognitive and emotional processing can help clinicians assess recovery, predict progression, and optimize treatment.

“Currently,” said co-senior study author Ping-Hong Yeh, PhD, “there is a lack of minimally invasive, quantitative diagnostic biomarkers for monitoring progression or recovery after mild TBI. However, mild TBI can be quite disabling, with many patients reporting symptoms months or even years after injury. This is the most difficult part to diagnose.” Dr. Yeh is a researcher at the National Intrepid Center of Excellence (NICoE) at Walter Reed National Military Medical Center, Bethesda, Maryland.

The NICoE, a Department of Defense organization and the senior member of Defense Intrepid Network for Traumatic Brain Injury and Brain Health, is among several centers charged with improving support for injured service members’ recovery, rehabilitation, and reintegration into their communities. The overarching goal, said Dr. Yeh, is to enable community neurologists to refer service members and veterans to these centers for treatment and advanced imaging when needed.
 

Invisible Wounds

Limitations of conventional MRI and CT make it tough to discern which patients with mTBI will return to baseline functioning, and which will develop long-term complications. Addressing the silent or invisible wounds of mTBI will require improved diagnostic, prognostic, and therapeutic tools, he said.

For their study, published in JAMA Network Open, Dr. Yeh and colleagues compared diffusion tensor imaging (DTI) and NODDI data from 65 male service members with remote (more than 2 years old) mTBI against scans of 33 noninjured controls matched for age, sex, and active-duty status.

“Although DTI is very sensitive in detecting microstructural changes in mild TBI,” he said, “it is not specific to the underlying pathophysiological changes.”

Conversely, NODDI uses biophysical modeling of intracellular diffusion, extracellular diffusion, and free water to help physicians to understand subtle pathophysiological changes with greater sensitivity and specificity than does DTI. “This will allow us to correlate symptoms with brain structural changes, making the invisible wound visible.”

In the study, the greatest differences between injured and control patients appeared in the following NODDI metrics (P <.001 in all analyses):

• Intracellular volume fraction (ICVF) of the right corticospinal tract (CST)
• Orientation dispersion index (ODI) of the left posterior thalamic radiation (PTR)
• ODI of the left uncinate fasciculus (UNC)

Regarding patient-reported neurobehavioral symptoms, Neurobehavioral Symptom Inventory cognitive subscores were associated with fractional anisotropy of the left UNC. In addition, PTSD Checklist–Civilian version total scores and avoidance subscores corresponded, respectively, with isotropic volume fraction (ISOVF) of the genu of corpus callosum and with ODI of the left fornix and stria terminalis.
 

Next Steps

Presently, Dr. Yeh said, conventional MRI and CT usually cannot differentiate between axonal injury, axonal inflammation (which develops during the chronic phase of mTBI), and demyelination. “But newer biophysical modeling, such as NODDI, will allow us to tell the difference.” Along with providing prognostic information, he said, such technology can guide appropriate treatment, such as anti-inflammatory agents for chronic inflammation.

Most community neurologists refer patients with persistent mTBI symptoms in the absence of red flags using CT and conventional MRI for advanced neuroimaging, said Dr. Yeh. But because few community neurologists are familiar with NODDI, he said, broadening its reach will require educating these providers. Additional steps that Dr. Yeh said could occur over the next decade or more include boosting advanced dMRI sensitivity levels through improved hardware, software, and diagnostic tools.

“We need to make these techniques clinically feasible,” he added. Currently, protocols that allow advanced dMRI scans in about 10 minutes can be achievable.

The investments required to implement advanced dMRI techniques will be substantial. A state-of-the-art 3T MRI scanner that can support NODDI and DTI can easily cost $1 million, said Dr. Yeh. Factor in additional equipment options and construction costs, he added, and the total price tag can easily exceed $2 million. But rather than replacing all existing MRI systems, said Dr. Yeh, AI one day may help translate high-gradient capability even to widely used lower-field MRI scanners operating at 0.5T.

Streamlining systems that incorporate disparate scanners with different acquisition parameters will require standardized data acquisition and sharing parameters. Along with helping to evaluate new techniques as they become available, data harmonization and sharing can facilitate a shift from research comparisons between large groups to comparing a single patient against many others — a move that Dr. Yeh said must occur for advanced dMRI techniques to achieve clinical relevance.

In addition, experts will need to revise clinical guidelines for use of new technologies as their availability grows. “Improper use of these techniques will not only increase health costs, but also probably result in adverse health results.” Such guidelines could be very useful in evaluating the suitability and quality of referrals for diagnostic images, Dr. Yeh said.

Dr. Yeh reports no relevant financial interests. The project was partially funded by the US Army Medical Research and Materiel Command.

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.

TOPLINE:

Tirbanibulin ointment 1% shows good safety and tolerability in the treatment of actinic keratosis (AK) in fields of up to 100 cm2 on the face and scalp.

METHODOLOGY:

• This phase 3 multicenter, single-arm trial evaluated the safety and tolerability of tirbanibulin ointment 1% in 105 adults with 4-12 clinically typical, visible, and discrete AKs on the face or balding scalp from June to December 2022 in the United States. (In June 2024, the Food and Drug Administration approved a supplemental new drug application for tirbanibulin 1%, a microtubule inhibitor, allowing the expansion of the surface area treated for AKs of the face or scalp from 25 cm² to 100 cm².)
• Participants applied tirbanibulin ointment 1% once daily for 5 days over a treatment field of about 100 cm² on the face or balding scalp. A total of 102 patients completed the study.
• Safety and tolerability were evaluated with reports of treatment-emergent adverse events (TEAEs) and a composite score of six local tolerability signs on days 5, 8, 15, and 29, and on completion of the evaluation period on day 57.

TAKEAWAY:

• The most common local effects of treatment were erythema (96.1% of patients) and flaking or scaling (84.4%), with severe cases reported in 5.8% and 8.7% of the patients, respectively.
• The mean maximum local tolerability composite score was 4.1 out of 18, which peaked around day 8 and returned to baseline by day 29.
• TEAEs considered related to the treatment were reported in 18.1% of patients; the most frequent were application site pruritus (10.5%) and application site pain (8.6%). No adverse events led to the discontinuation of treatment.
• The mean percent reduction in the lesion count from baseline was 77.8% at day 57, with a mean lesion count of 1.8 at the end of the study.

IN PRACTICE:

In this study, “local tolerability and safety profiles were well characterized in patients with 4-12 clinically typical, visible, and discrete AK lesions in a field of 100 cm² and were consistent with those previously reported in patients with AK treated in pivotal trials with tirbanibulin over a smaller field (25 cm²),” the authors wrote.

SOURCE:

The study, led by Neal Bhatia, MD, of Therapeutics Clinical Research, San Diego, was published online in JAAD International.

LIMITATIONS:

The study was limited by the lack of a placebo group and the absence of long-term follow-up. 

DISCLOSURES:

This study was funded by Almirall. Five authors reported being employees of Almirall. Other authors declared having ties with various other sources, including Almirall.

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:

Tirbanibulin ointment 1% shows good safety and tolerability in the treatment of actinic keratosis (AK) in fields of up to 100 cm2 on the face and scalp.

METHODOLOGY:

• This phase 3 multicenter, single-arm trial evaluated the safety and tolerability of tirbanibulin ointment 1% in 105 adults with 4-12 clinically typical, visible, and discrete AKs on the face or balding scalp from June to December 2022 in the United States. (In June 2024, the Food and Drug Administration approved a supplemental new drug application for tirbanibulin 1%, a microtubule inhibitor, allowing the expansion of the surface area treated for AKs of the face or scalp from 25 cm² to 100 cm².)
• Participants applied tirbanibulin ointment 1% once daily for 5 days over a treatment field of about 100 cm² on the face or balding scalp. A total of 102 patients completed the study.
• Safety and tolerability were evaluated with reports of treatment-emergent adverse events (TEAEs) and a composite score of six local tolerability signs on days 5, 8, 15, and 29, and on completion of the evaluation period on day 57.

TAKEAWAY:

• The most common local effects of treatment were erythema (96.1% of patients) and flaking or scaling (84.4%), with severe cases reported in 5.8% and 8.7% of the patients, respectively.
• The mean maximum local tolerability composite score was 4.1 out of 18, which peaked around day 8 and returned to baseline by day 29.
• TEAEs considered related to the treatment were reported in 18.1% of patients; the most frequent were application site pruritus (10.5%) and application site pain (8.6%). No adverse events led to the discontinuation of treatment.
• The mean percent reduction in the lesion count from baseline was 77.8% at day 57, with a mean lesion count of 1.8 at the end of the study.

IN PRACTICE:

In this study, “local tolerability and safety profiles were well characterized in patients with 4-12 clinically typical, visible, and discrete AK lesions in a field of 100 cm² and were consistent with those previously reported in patients with AK treated in pivotal trials with tirbanibulin over a smaller field (25 cm²),” the authors wrote.

SOURCE:

The study, led by Neal Bhatia, MD, of Therapeutics Clinical Research, San Diego, was published online in JAAD International.

LIMITATIONS:

The study was limited by the lack of a placebo group and the absence of long-term follow-up. 

DISCLOSURES:

This study was funded by Almirall. Five authors reported being employees of Almirall. Other authors declared having ties with various other sources, including Almirall.

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:

Tirbanibulin ointment 1% shows good safety and tolerability in the treatment of actinic keratosis (AK) in fields of up to 100 cm2 on the face and scalp.

METHODOLOGY:

• This phase 3 multicenter, single-arm trial evaluated the safety and tolerability of tirbanibulin ointment 1% in 105 adults with 4-12 clinically typical, visible, and discrete AKs on the face or balding scalp from June to December 2022 in the United States. (In June 2024, the Food and Drug Administration approved a supplemental new drug application for tirbanibulin 1%, a microtubule inhibitor, allowing the expansion of the surface area treated for AKs of the face or scalp from 25 cm² to 100 cm².)
• Participants applied tirbanibulin ointment 1% once daily for 5 days over a treatment field of about 100 cm² on the face or balding scalp. A total of 102 patients completed the study.
• Safety and tolerability were evaluated with reports of treatment-emergent adverse events (TEAEs) and a composite score of six local tolerability signs on days 5, 8, 15, and 29, and on completion of the evaluation period on day 57.

TAKEAWAY:

• The most common local effects of treatment were erythema (96.1% of patients) and flaking or scaling (84.4%), with severe cases reported in 5.8% and 8.7% of the patients, respectively.
• The mean maximum local tolerability composite score was 4.1 out of 18, which peaked around day 8 and returned to baseline by day 29.
• TEAEs considered related to the treatment were reported in 18.1% of patients; the most frequent were application site pruritus (10.5%) and application site pain (8.6%). No adverse events led to the discontinuation of treatment.
• The mean percent reduction in the lesion count from baseline was 77.8% at day 57, with a mean lesion count of 1.8 at the end of the study.

IN PRACTICE:

In this study, “local tolerability and safety profiles were well characterized in patients with 4-12 clinically typical, visible, and discrete AK lesions in a field of 100 cm² and were consistent with those previously reported in patients with AK treated in pivotal trials with tirbanibulin over a smaller field (25 cm²),” the authors wrote.

SOURCE:

The study, led by Neal Bhatia, MD, of Therapeutics Clinical Research, San Diego, was published online in JAAD International.

LIMITATIONS:

The study was limited by the lack of a placebo group and the absence of long-term follow-up. 

DISCLOSURES:

This study was funded by Almirall. Five authors reported being employees of Almirall. Other authors declared having ties with various other sources, including Almirall.

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.

The prevalence of dermatologic conditions affecting children in refugee camps remains unclear because of the limited data on the topic, a literature review showed. However, likely culprits include infectious diseases with cutaneous manifestations, such as pediculosis, tinea capitis, and scabies.

“Current data indicates that one in two refugees are children,” one of the study investigators, Mehar Maju, MPH, a fourth-year student at of the University of Washington School of Medicine, Seattle, said in an interview following the annual meeting of the Society for Pediatric Dermatology, where the results were presented during a poster session.

Courtesy of Gary White, MD

“The number of refugees continues to rise to unprecedented levels every year,” and climate change continues to drive increases in migration, “impacting those residing in camps,” she said. “As we continue to think about what this means for best supporting those residing in camps, I think it’s also important to consider how to best support refugees, specifically children, when they arrive in the United States. Part of this is to know what conditions are most prevalent and what type of social support this vulnerable population needs.”

To identify the common dermatologic conditions among children living in refugee camps, Ms. Maju and fellow fourth-year University of Washington medical student Nadia Siddiqui searched PubMed and Google Scholar for studies that were published in English and reported on the skin disease prevalence and management for refugees who are children. Key search terms used included “refugees,” “children,” “dermatology,” and “skin disease.” Of approximately 105 potential studies identified, 19 underwent analysis. Of these, only five were included in the final review. 

One of the five studies was conducted in rural Nyala, Sudan. The study found that 88.8% of those living in orphanages and refugee camps were reported to have a skin disorder, commonly fungal or bacterial infections and dermatitis. In a separate case series, researchers found that cutaneous leishmaniasis was rising among Syrian refugee children. 

A study that looked at morbidity and disease burden in mainland Greece refugee camps found that the skin was the second-most common site of communicable diseases among children, behind those of the respiratory tract. In another study that investigated the health of children in Australian immigration detention centers, complaints related to skin conditions were significantly elevated among children who were detained offshore, compared with those who were detained onshore.

Finally, in a study of 125 children between the ages of 1 and 15 years at a Sierra Leone–based displacement camp, the prevalence of scabies was 77% among those aged < 5 years and peaked to 86% among those aged 5-9 years. 

“It was surprising to see the limited information about dermatologic diseases impacting children in refugee camps,” Ms. Maju said. “I expected that there would be more information on the specific proportion of diseases beyond those of infectious etiology. For example, I had believed that we would have more information on the prevalence of atopic dermatitis, vitiligo, and other more chronic skin diseases.” 

She acknowledged certain limitations of the analysis, mainly the lack of published information on the skin health of pediatric refugees. “A study that evaluates the health status and dermatologic prevalence of disease among children residing in camps and those newly arrived in the United States from camps would provide unprecedented insight into this topic,” Ms. Maju said. “The results could guide public health efforts in improving care delivery and preparedness in camps and clinicians serving this particular population when they arrive in the United States.”

She and Ms. Siddiqui reported having no relevant disclosures.

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

The prevalence of dermatologic conditions affecting children in refugee camps remains unclear because of the limited data on the topic, a literature review showed. However, likely culprits include infectious diseases with cutaneous manifestations, such as pediculosis, tinea capitis, and scabies.

“Current data indicates that one in two refugees are children,” one of the study investigators, Mehar Maju, MPH, a fourth-year student at of the University of Washington School of Medicine, Seattle, said in an interview following the annual meeting of the Society for Pediatric Dermatology, where the results were presented during a poster session.

Courtesy of Gary White, MD

“The number of refugees continues to rise to unprecedented levels every year,” and climate change continues to drive increases in migration, “impacting those residing in camps,” she said. “As we continue to think about what this means for best supporting those residing in camps, I think it’s also important to consider how to best support refugees, specifically children, when they arrive in the United States. Part of this is to know what conditions are most prevalent and what type of social support this vulnerable population needs.”

To identify the common dermatologic conditions among children living in refugee camps, Ms. Maju and fellow fourth-year University of Washington medical student Nadia Siddiqui searched PubMed and Google Scholar for studies that were published in English and reported on the skin disease prevalence and management for refugees who are children. Key search terms used included “refugees,” “children,” “dermatology,” and “skin disease.” Of approximately 105 potential studies identified, 19 underwent analysis. Of these, only five were included in the final review. 

One of the five studies was conducted in rural Nyala, Sudan. The study found that 88.8% of those living in orphanages and refugee camps were reported to have a skin disorder, commonly fungal or bacterial infections and dermatitis. In a separate case series, researchers found that cutaneous leishmaniasis was rising among Syrian refugee children. 

A study that looked at morbidity and disease burden in mainland Greece refugee camps found that the skin was the second-most common site of communicable diseases among children, behind those of the respiratory tract. In another study that investigated the health of children in Australian immigration detention centers, complaints related to skin conditions were significantly elevated among children who were detained offshore, compared with those who were detained onshore.

Finally, in a study of 125 children between the ages of 1 and 15 years at a Sierra Leone–based displacement camp, the prevalence of scabies was 77% among those aged < 5 years and peaked to 86% among those aged 5-9 years. 

“It was surprising to see the limited information about dermatologic diseases impacting children in refugee camps,” Ms. Maju said. “I expected that there would be more information on the specific proportion of diseases beyond those of infectious etiology. For example, I had believed that we would have more information on the prevalence of atopic dermatitis, vitiligo, and other more chronic skin diseases.” 

She acknowledged certain limitations of the analysis, mainly the lack of published information on the skin health of pediatric refugees. “A study that evaluates the health status and dermatologic prevalence of disease among children residing in camps and those newly arrived in the United States from camps would provide unprecedented insight into this topic,” Ms. Maju said. “The results could guide public health efforts in improving care delivery and preparedness in camps and clinicians serving this particular population when they arrive in the United States.”

She and Ms. Siddiqui reported having no relevant disclosures.

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

The prevalence of dermatologic conditions affecting children in refugee camps remains unclear because of the limited data on the topic, a literature review showed. However, likely culprits include infectious diseases with cutaneous manifestations, such as pediculosis, tinea capitis, and scabies.

“Current data indicates that one in two refugees are children,” one of the study investigators, Mehar Maju, MPH, a fourth-year student at of the University of Washington School of Medicine, Seattle, said in an interview following the annual meeting of the Society for Pediatric Dermatology, where the results were presented during a poster session.

Courtesy of Gary White, MD

“The number of refugees continues to rise to unprecedented levels every year,” and climate change continues to drive increases in migration, “impacting those residing in camps,” she said. “As we continue to think about what this means for best supporting those residing in camps, I think it’s also important to consider how to best support refugees, specifically children, when they arrive in the United States. Part of this is to know what conditions are most prevalent and what type of social support this vulnerable population needs.”

To identify the common dermatologic conditions among children living in refugee camps, Ms. Maju and fellow fourth-year University of Washington medical student Nadia Siddiqui searched PubMed and Google Scholar for studies that were published in English and reported on the skin disease prevalence and management for refugees who are children. Key search terms used included “refugees,” “children,” “dermatology,” and “skin disease.” Of approximately 105 potential studies identified, 19 underwent analysis. Of these, only five were included in the final review. 

One of the five studies was conducted in rural Nyala, Sudan. The study found that 88.8% of those living in orphanages and refugee camps were reported to have a skin disorder, commonly fungal or bacterial infections and dermatitis. In a separate case series, researchers found that cutaneous leishmaniasis was rising among Syrian refugee children. 

A study that looked at morbidity and disease burden in mainland Greece refugee camps found that the skin was the second-most common site of communicable diseases among children, behind those of the respiratory tract. In another study that investigated the health of children in Australian immigration detention centers, complaints related to skin conditions were significantly elevated among children who were detained offshore, compared with those who were detained onshore.

Finally, in a study of 125 children between the ages of 1 and 15 years at a Sierra Leone–based displacement camp, the prevalence of scabies was 77% among those aged < 5 years and peaked to 86% among those aged 5-9 years. 

“It was surprising to see the limited information about dermatologic diseases impacting children in refugee camps,” Ms. Maju said. “I expected that there would be more information on the specific proportion of diseases beyond those of infectious etiology. For example, I had believed that we would have more information on the prevalence of atopic dermatitis, vitiligo, and other more chronic skin diseases.” 

She acknowledged certain limitations of the analysis, mainly the lack of published information on the skin health of pediatric refugees. “A study that evaluates the health status and dermatologic prevalence of disease among children residing in camps and those newly arrived in the United States from camps would provide unprecedented insight into this topic,” Ms. Maju said. “The results could guide public health efforts in improving care delivery and preparedness in camps and clinicians serving this particular population when they arrive in the United States.”

She and Ms. Siddiqui reported having no relevant disclosures.

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

To the Editor:

Syringoma is a relatively common benign adnexal neoplasm originating in the ducts of eccrine sweat glands. It can be divided into 4 variants based on clinical features: localized; familial; Down syndrome associated; and generalized, which includes multiple syringomas and eruptive syringoma (ES).¹ Eruptive syringoma is a rare variant of generalized syringoma that was first described by Jacquet and Darier² in 1887. Clinically, ES lesions manifest as multiple nonfused, flesh-colored to reddish-brown papules that are located most commonly on the anterior trunk during childhood or adolescence. Eruptive syringoma can be missed easily or misdiagnosed clinically. We present 3 rare cases of ES.

A 28-year-old man presented with multiple asymptomatic papules on the trunk and upper arms of 20 years’ duration (patient 1). He had been diagnosed with Darier disease 3 years prior to the current presentation and was treated with oral and topical retinoic acid without a response. After 3 months of oral treatment, the retinoic acid was stopped due to elevated liver enzymes. Physical examination at the current presentation revealed multiple smooth, firm, nonfused, 1- to 4-mm, reddish to dark red papules on the neck, chest, abdomen, and flexural surfaces of the upper arms (Figure 1A). Dermoscopy of the arm lesions showed light brown pigment networks and yellowish-white unstructured areas surrounded by linear vessels on a pink background under polarized light (Figure 1B). Histopathologic examination of a lesion on the left arm revealed epithelial cords, ducts, and cystic structures within the superficial and mid dermis. The ducts were lined by 2 rows of epithelial cells with a characteristic tadpolelike pattern and filled with eosinophilic amorphous substances (Figure 1C).

A 43-year-old man who was otherwise healthy presented with brownish flat-topped papules on the chest and abdomen of 19 years’ duration (Figure 3A)(patient 3). The lesions had remained stable and did not progress. He denied any treatment. Dermoscopy of the chest lesions showed a light brown pigment network as well as dotted and linear vessels on a pale yellow background (Figure 3B).

All 3 patients demonstrated classic histopathologic features of syringoma, and none had a family history of similar skin lesions. The clinical and dermoscopic findings along with the histopathology in all 3 patients were consistent with ES. In patient 1, three sessions of electrocautery treatments on both upper arms were performed with settings of short-fire mode (1–3 V) at 4- to 8-week intervals. After treatment, the lesions subsided but recurred 7 months later. Five months after recurrence, the rash gradually increased on the trunk and upper arms. In patient 2, two sessions of CO₂ laser treatments on the trunk were performed with settings of modulated pulse mode (1–2 W) at 4- to 8-week intervals. The lesions disappeared after treatment but recurred 6 months later. At 1-year follow-up after recurrence, the rash had increased slightly. Neither patient 1 nor patient 2 developed hyperpigmentation or scarring during the 1-year follow-up period after their respective treatments. Patient 3 opted not to undergo treatment after being informed that the lesions were benign, and his condition stabilized at 1-year follow-up.

The pathogenesis of ES is unclear, but it may be affected by hormones, autoimmune status, immunosuppression (eg, liver and kidney transplantation), and medications (eg, hypersensitivity, phototoxicity, and antiepileptic medications).^3-6 Guitart et al⁷ hypothesized that ES may be a hyperplastic response of the eccrine duct to an inflammatory reaction, such as trauma from waxing or chronic scratching. It also has been associated with systemic conditions such as Nicolau-Balus syndrome (syringomas, milia, and atrophoderma vermiculata) and Down syndrome.^8,9 The lesions manifest symmetrically and are characterized by flesh-colored to reddish-brown, shiny, or flat-topped papules; however, ES also can manifest as hyperpigmentation, erythema, positive Darier sign, or pseudokoebnerization.¹⁰ The lesions typically are located on the eyelids, neck, anterior chest, upper abdomen, upper arms, axillae, and genital region, and they rarely involve the palms, soles, and mucous membranes. Eruptive syringoma commonly is asymptomatic and in rare cases gradually subsides.¹¹

Sometimes the lesions of ES are atypical and clinically resemble Darier disease, Fox-Fordyce disease, lichen planus, mastocytosis, granuloma annulare, trichoepithelioma, and sarcoidosis. Additionally, Marfan syndrome and Ehlers-Danlos syndrome should be ruled out when lesions involve the eyelids.¹¹ The differential diagnosis in our patients included Darier disease and Fox-Fordyce disease, which can be differentiated from ES via noninvasive dermoscopy and pathologic biopsy. In most patients with ES, dermoscopic findings include reticular brown lines or fine pigment networks as well as dotted and linear or reticular vessels. Tiny whitish dots, multifocal hypopigmented areas, and glittering yellow-whitish round structures are dermoscopic hallmarks of the vulvar variant of ES.^12-14 Histopathology of ES has shown epithelial cords, ducts, and cystic structures within the dermis. The ducts are lined by 2 rows of epithelial cells with a characteristic comma-shaped/tadpolelike pattern and are filled with eosinophilic amorphous substances. The dermoscopic features of Darier disease differ from ES in that Darier disease usually manifests as a comedolike opening with a central polygonal yellowish-brownish structure surrounded by a whitish halo on a pink background.¹⁵Histopathology of Darier disease has shown acantholysis above the basal layer of the epidermis and dyskeratotic keratinocytes. Dermoscopic findings in Fox-Fordyce disease include typical light brown to dark brown, folliculocentric, structureless areas with loss of dermatoglyphics. Some of the lesions also show hyperkeratotic follicular plugging.¹⁶ Histopathology of Fox-Fordyce disease includes infundibulum dilation, hyperkeratosis, plugging, acanthosis, a lymphohistiocytic infiltrate, and a perifollicular foam cell infiltrate.¹⁷Eruptive syringoma is a benign condition that generally requires no treatment. The goal of treatment is to improve cosmesis and primarily includes physical and chemical therapies such as surgical resection, cryosurgery, electrodesiccation, CO₂ laser (alone and in combination with trichloroacetic acid¹⁰), argon laser, fractional photothermolysis, dermabrasion, and chemical peeling. However, because ES involves deeper areas of the dermis, some treatments may cause hyperpigmentation, scar formation, or recurrence of the lesions and may be less effective for lesions on the eyelids, which may remain untreated. Systemic therapy consists of oral retinoic acid or tranilast.¹⁸The use of topical retinoic acid and atropine also have been reported,¹⁹ but their efficacy remains uncertain. The lesions in patient 1 did not resolve after receiving oral and topical retinoic acid. Although ES lesions may decrease in size or subside without inter­vention in rare cases, the disease was not self-limiting in our patients.

To the Editor:

Syringoma is a relatively common benign adnexal neoplasm originating in the ducts of eccrine sweat glands. It can be divided into 4 variants based on clinical features: localized; familial; Down syndrome associated; and generalized, which includes multiple syringomas and eruptive syringoma (ES).¹ Eruptive syringoma is a rare variant of generalized syringoma that was first described by Jacquet and Darier² in 1887. Clinically, ES lesions manifest as multiple nonfused, flesh-colored to reddish-brown papules that are located most commonly on the anterior trunk during childhood or adolescence. Eruptive syringoma can be missed easily or misdiagnosed clinically. We present 3 rare cases of ES.

A 28-year-old man presented with multiple asymptomatic papules on the trunk and upper arms of 20 years’ duration (patient 1). He had been diagnosed with Darier disease 3 years prior to the current presentation and was treated with oral and topical retinoic acid without a response. After 3 months of oral treatment, the retinoic acid was stopped due to elevated liver enzymes. Physical examination at the current presentation revealed multiple smooth, firm, nonfused, 1- to 4-mm, reddish to dark red papules on the neck, chest, abdomen, and flexural surfaces of the upper arms (Figure 1A). Dermoscopy of the arm lesions showed light brown pigment networks and yellowish-white unstructured areas surrounded by linear vessels on a pink background under polarized light (Figure 1B). Histopathologic examination of a lesion on the left arm revealed epithelial cords, ducts, and cystic structures within the superficial and mid dermis. The ducts were lined by 2 rows of epithelial cells with a characteristic tadpolelike pattern and filled with eosinophilic amorphous substances (Figure 1C).

A 43-year-old man who was otherwise healthy presented with brownish flat-topped papules on the chest and abdomen of 19 years’ duration (Figure 3A)(patient 3). The lesions had remained stable and did not progress. He denied any treatment. Dermoscopy of the chest lesions showed a light brown pigment network as well as dotted and linear vessels on a pale yellow background (Figure 3B).

All 3 patients demonstrated classic histopathologic features of syringoma, and none had a family history of similar skin lesions. The clinical and dermoscopic findings along with the histopathology in all 3 patients were consistent with ES. In patient 1, three sessions of electrocautery treatments on both upper arms were performed with settings of short-fire mode (1–3 V) at 4- to 8-week intervals. After treatment, the lesions subsided but recurred 7 months later. Five months after recurrence, the rash gradually increased on the trunk and upper arms. In patient 2, two sessions of CO₂ laser treatments on the trunk were performed with settings of modulated pulse mode (1–2 W) at 4- to 8-week intervals. The lesions disappeared after treatment but recurred 6 months later. At 1-year follow-up after recurrence, the rash had increased slightly. Neither patient 1 nor patient 2 developed hyperpigmentation or scarring during the 1-year follow-up period after their respective treatments. Patient 3 opted not to undergo treatment after being informed that the lesions were benign, and his condition stabilized at 1-year follow-up.

The pathogenesis of ES is unclear, but it may be affected by hormones, autoimmune status, immunosuppression (eg, liver and kidney transplantation), and medications (eg, hypersensitivity, phototoxicity, and antiepileptic medications).^3-6 Guitart et al⁷ hypothesized that ES may be a hyperplastic response of the eccrine duct to an inflammatory reaction, such as trauma from waxing or chronic scratching. It also has been associated with systemic conditions such as Nicolau-Balus syndrome (syringomas, milia, and atrophoderma vermiculata) and Down syndrome.^8,9 The lesions manifest symmetrically and are characterized by flesh-colored to reddish-brown, shiny, or flat-topped papules; however, ES also can manifest as hyperpigmentation, erythema, positive Darier sign, or pseudokoebnerization.¹⁰ The lesions typically are located on the eyelids, neck, anterior chest, upper abdomen, upper arms, axillae, and genital region, and they rarely involve the palms, soles, and mucous membranes. Eruptive syringoma commonly is asymptomatic and in rare cases gradually subsides.¹¹

Sometimes the lesions of ES are atypical and clinically resemble Darier disease, Fox-Fordyce disease, lichen planus, mastocytosis, granuloma annulare, trichoepithelioma, and sarcoidosis. Additionally, Marfan syndrome and Ehlers-Danlos syndrome should be ruled out when lesions involve the eyelids.¹¹ The differential diagnosis in our patients included Darier disease and Fox-Fordyce disease, which can be differentiated from ES via noninvasive dermoscopy and pathologic biopsy. In most patients with ES, dermoscopic findings include reticular brown lines or fine pigment networks as well as dotted and linear or reticular vessels. Tiny whitish dots, multifocal hypopigmented areas, and glittering yellow-whitish round structures are dermoscopic hallmarks of the vulvar variant of ES.^12-14 Histopathology of ES has shown epithelial cords, ducts, and cystic structures within the dermis. The ducts are lined by 2 rows of epithelial cells with a characteristic comma-shaped/tadpolelike pattern and are filled with eosinophilic amorphous substances. The dermoscopic features of Darier disease differ from ES in that Darier disease usually manifests as a comedolike opening with a central polygonal yellowish-brownish structure surrounded by a whitish halo on a pink background.¹⁵Histopathology of Darier disease has shown acantholysis above the basal layer of the epidermis and dyskeratotic keratinocytes. Dermoscopic findings in Fox-Fordyce disease include typical light brown to dark brown, folliculocentric, structureless areas with loss of dermatoglyphics. Some of the lesions also show hyperkeratotic follicular plugging.¹⁶ Histopathology of Fox-Fordyce disease includes infundibulum dilation, hyperkeratosis, plugging, acanthosis, a lymphohistiocytic infiltrate, and a perifollicular foam cell infiltrate.¹⁷Eruptive syringoma is a benign condition that generally requires no treatment. The goal of treatment is to improve cosmesis and primarily includes physical and chemical therapies such as surgical resection, cryosurgery, electrodesiccation, CO₂ laser (alone and in combination with trichloroacetic acid¹⁰), argon laser, fractional photothermolysis, dermabrasion, and chemical peeling. However, because ES involves deeper areas of the dermis, some treatments may cause hyperpigmentation, scar formation, or recurrence of the lesions and may be less effective for lesions on the eyelids, which may remain untreated. Systemic therapy consists of oral retinoic acid or tranilast.¹⁸The use of topical retinoic acid and atropine also have been reported,¹⁹ but their efficacy remains uncertain. The lesions in patient 1 did not resolve after receiving oral and topical retinoic acid. Although ES lesions may decrease in size or subside without inter­vention in rare cases, the disease was not self-limiting in our patients.

To the Editor:

Syringoma is a relatively common benign adnexal neoplasm originating in the ducts of eccrine sweat glands. It can be divided into 4 variants based on clinical features: localized; familial; Down syndrome associated; and generalized, which includes multiple syringomas and eruptive syringoma (ES).¹ Eruptive syringoma is a rare variant of generalized syringoma that was first described by Jacquet and Darier² in 1887. Clinically, ES lesions manifest as multiple nonfused, flesh-colored to reddish-brown papules that are located most commonly on the anterior trunk during childhood or adolescence. Eruptive syringoma can be missed easily or misdiagnosed clinically. We present 3 rare cases of ES.

A 28-year-old man presented with multiple asymptomatic papules on the trunk and upper arms of 20 years’ duration (patient 1). He had been diagnosed with Darier disease 3 years prior to the current presentation and was treated with oral and topical retinoic acid without a response. After 3 months of oral treatment, the retinoic acid was stopped due to elevated liver enzymes. Physical examination at the current presentation revealed multiple smooth, firm, nonfused, 1- to 4-mm, reddish to dark red papules on the neck, chest, abdomen, and flexural surfaces of the upper arms (Figure 1A). Dermoscopy of the arm lesions showed light brown pigment networks and yellowish-white unstructured areas surrounded by linear vessels on a pink background under polarized light (Figure 1B). Histopathologic examination of a lesion on the left arm revealed epithelial cords, ducts, and cystic structures within the superficial and mid dermis. The ducts were lined by 2 rows of epithelial cells with a characteristic tadpolelike pattern and filled with eosinophilic amorphous substances (Figure 1C).

A 43-year-old man who was otherwise healthy presented with brownish flat-topped papules on the chest and abdomen of 19 years’ duration (Figure 3A)(patient 3). The lesions had remained stable and did not progress. He denied any treatment. Dermoscopy of the chest lesions showed a light brown pigment network as well as dotted and linear vessels on a pale yellow background (Figure 3B).

All 3 patients demonstrated classic histopathologic features of syringoma, and none had a family history of similar skin lesions. The clinical and dermoscopic findings along with the histopathology in all 3 patients were consistent with ES. In patient 1, three sessions of electrocautery treatments on both upper arms were performed with settings of short-fire mode (1–3 V) at 4- to 8-week intervals. After treatment, the lesions subsided but recurred 7 months later. Five months after recurrence, the rash gradually increased on the trunk and upper arms. In patient 2, two sessions of CO₂ laser treatments on the trunk were performed with settings of modulated pulse mode (1–2 W) at 4- to 8-week intervals. The lesions disappeared after treatment but recurred 6 months later. At 1-year follow-up after recurrence, the rash had increased slightly. Neither patient 1 nor patient 2 developed hyperpigmentation or scarring during the 1-year follow-up period after their respective treatments. Patient 3 opted not to undergo treatment after being informed that the lesions were benign, and his condition stabilized at 1-year follow-up.

The pathogenesis of ES is unclear, but it may be affected by hormones, autoimmune status, immunosuppression (eg, liver and kidney transplantation), and medications (eg, hypersensitivity, phototoxicity, and antiepileptic medications).^3-6 Guitart et al⁷ hypothesized that ES may be a hyperplastic response of the eccrine duct to an inflammatory reaction, such as trauma from waxing or chronic scratching. It also has been associated with systemic conditions such as Nicolau-Balus syndrome (syringomas, milia, and atrophoderma vermiculata) and Down syndrome.^8,9 The lesions manifest symmetrically and are characterized by flesh-colored to reddish-brown, shiny, or flat-topped papules; however, ES also can manifest as hyperpigmentation, erythema, positive Darier sign, or pseudokoebnerization.¹⁰ The lesions typically are located on the eyelids, neck, anterior chest, upper abdomen, upper arms, axillae, and genital region, and they rarely involve the palms, soles, and mucous membranes. Eruptive syringoma commonly is asymptomatic and in rare cases gradually subsides.¹¹

Sometimes the lesions of ES are atypical and clinically resemble Darier disease, Fox-Fordyce disease, lichen planus, mastocytosis, granuloma annulare, trichoepithelioma, and sarcoidosis. Additionally, Marfan syndrome and Ehlers-Danlos syndrome should be ruled out when lesions involve the eyelids.¹¹ The differential diagnosis in our patients included Darier disease and Fox-Fordyce disease, which can be differentiated from ES via noninvasive dermoscopy and pathologic biopsy. In most patients with ES, dermoscopic findings include reticular brown lines or fine pigment networks as well as dotted and linear or reticular vessels. Tiny whitish dots, multifocal hypopigmented areas, and glittering yellow-whitish round structures are dermoscopic hallmarks of the vulvar variant of ES.^12-14 Histopathology of ES has shown epithelial cords, ducts, and cystic structures within the dermis. The ducts are lined by 2 rows of epithelial cells with a characteristic comma-shaped/tadpolelike pattern and are filled with eosinophilic amorphous substances. The dermoscopic features of Darier disease differ from ES in that Darier disease usually manifests as a comedolike opening with a central polygonal yellowish-brownish structure surrounded by a whitish halo on a pink background.¹⁵Histopathology of Darier disease has shown acantholysis above the basal layer of the epidermis and dyskeratotic keratinocytes. Dermoscopic findings in Fox-Fordyce disease include typical light brown to dark brown, folliculocentric, structureless areas with loss of dermatoglyphics. Some of the lesions also show hyperkeratotic follicular plugging.¹⁶ Histopathology of Fox-Fordyce disease includes infundibulum dilation, hyperkeratosis, plugging, acanthosis, a lymphohistiocytic infiltrate, and a perifollicular foam cell infiltrate.¹⁷Eruptive syringoma is a benign condition that generally requires no treatment. The goal of treatment is to improve cosmesis and primarily includes physical and chemical therapies such as surgical resection, cryosurgery, electrodesiccation, CO₂ laser (alone and in combination with trichloroacetic acid¹⁰), argon laser, fractional photothermolysis, dermabrasion, and chemical peeling. However, because ES involves deeper areas of the dermis, some treatments may cause hyperpigmentation, scar formation, or recurrence of the lesions and may be less effective for lesions on the eyelids, which may remain untreated. Systemic therapy consists of oral retinoic acid or tranilast.¹⁸The use of topical retinoic acid and atropine also have been reported,¹⁹ but their efficacy remains uncertain. The lesions in patient 1 did not resolve after receiving oral and topical retinoic acid. Although ES lesions may decrease in size or subside without inter­vention in rare cases, the disease was not self-limiting in our patients.

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.