MDedge Pediatrics

PARIS – Childhood trauma affects women and men equally in terms of its impact on subsequent psychopathology, but trauma type has subsequent differential effects depending on gender, new research shows.

Investigators found childhood emotional and sexual abuse had a greater effect on women than men, whereas men were more adversely affected by emotional and physical neglect.

“Our findings indicate that exposure to childhood maltreatment increases the risk of having psychiatric symptoms in both men and women,” lead researcher Thanavadee Prachason, PhD, department of psychiatry and neuropsychology, Maastricht (the Netherlands) University Medical Center, said in a press release.

“Exposure to emotionally or sexually abusive experiences during childhood increases the risk of a variety of psychiatric symptoms, particularly in women. In contrast, a history of emotional or physical neglect in childhood increases the risk of having psychiatric symptoms more in men,” Dr. Prachason added.

The findings were presented at the European Psychiatric Association 2023 Congress.

A leading mental illness risk factor

Study presenter Laura Fusar-Poli, MD, PhD, from the department of brain and behavioral sciences, University of Pavia (Italy), said that the differential impact of trauma subtypes in men and women indicate that both gender and the type of childhood adversity experienced need to be taken into account in future studies.

Dr. Fusar-Poli began by highlighting that 13%-36% of individuals have experienced some kind of childhood trauma, with 30% exposed to at least two types of trauma.

Trauma has been identified as a risk factor for a range of mental health problems.

“It is estimated that, worldwide, around one third of all psychiatric disorders are related to childhood trauma,” senior researcher Sinan Gülöksüz, MD, PhD, also from Maastricht University Medical Center, said in the release.

Consequently, “childhood trauma is a leading preventable risk factor for mental illness,” he added.

Previous research suggests the subtype of trauma has an impact on subsequent biological changes and clinical outcomes, and that there are gender differences in the effects of childhood trauma.

To investigate, the researchers examined data from TwinssCan, a Belgian cohort of twins and siblings aged 15-35 years without a diagnosis of pervasive mental disorders.

The study included 477 females and 314 males who had completed the Childhood Trauma Questionnaire–Short Form (CTQ) and the Symptom Checklist-90 SR (SCL-90) to determine exposure to childhood adversity and levels of psychopathology, respectively.

Results showed that total CTQ scores were significantly associated with total SCL-90 scores in both men and women, as well as with each of the nine symptom domains of the SCL-90 (P < .001 for all assessments). These included psychoticism, paranoid ideation, anxiety, depression, somatization, obsessive-compulsive, interpersonal sensitivity, hostility, and phobic anxiety.

There were no significant differences in the associations with total CTQ scores between men and women.

However, when the researchers examined trauma subtypes and psychopathology, clear gender differences emerged.

Investigators found a significant association between emotional abuse on the CTQ and total SCL-90 scores in both men (P < .023) and women (P < .001), but that the association was significantly stronger in women (P = .043).

Sexual abuse was significantly associated with total SCL-90 scores in women (P < .001), while emotional neglect and physical neglect were significantly associated with psychopathology scores in men (P = .026 and P < .001, respectively).

“Physical neglect may include experiences of not having enough to eat, wearing dirty clothes, not being taken care of, and not getting taken to the doctor when the person was growing up,” said Dr. Prachason.

“Emotional neglect may include childhood experiences like not feeling loved or important, and not feeling close to the family.”

In women, emotional abuse was significantly associated with all nine symptom domains of the SCL-90, while sexual abuse was associated with seven: psychoticism, paranoid ideation, anxiety, depression, somatization, obsessive-compulsive, and hostility.

Physical neglect, in men, was significantly associated with eight of the symptom domains (all but somatization), but emotional neglect was linked only to depression, Dr. Fusar-Poli reported.

“This study showed a very important consequence of childhood trauma, and not only in people with mental disorders. I would like to underline that this is a general population, composed of adolescents and young adults, which is the age in which the majority of mental disorders starts, Dr. Fusar-Poli said in an interview.

She emphasized that psychotic disorders are only a part of the “broad range” of conditions that may be related to childhood trauma, which “can have an impact on sub-threshold symptoms that can affect functioning and quality of life in the general population.”

Addressing the differential findings in men and women, Dr. Gülöksüz noted women may be more “vulnerable to childhood trauma than men” simply because “they are exposed to more sexual and emotional abuse.”

However, he said, this is “something that we really need understand,” as there is likely an underlying mechanism, “and not only a biological mechanism but probably a societal one.”

Dr. Gülöksüz noted there could also be differences between societies in terms of the impact of childhood trauma. “Our sample was from Belgium, but what would happen if we conducted this study in Italy, or in India,” he said.

Compromised cognitive, emotional function

Commenting on the findings for this news organization, Elaine F. Walker, PhD, professor of psychology and neuroscience at Emory University in Atlanta, said stress exposure in general, including childhood trauma, “has transdiagnostic effects on vulnerability to mental disorders.”

“The effects are primarily mediated by the hypothalamic-pituitary-adrenal axis, which triggers the release of cortisol. When persistently elevated, this can result in neurobiological processes that have adverse effects on brain structure and circuitry which, in turn, compromises cognitive and emotional functioning,” said Dr. Walker, who was not associated with the study.

She noted that, “while it is possible that there are sex differences in biological sensitivity to certain subtypes of childhood trauma, it may also be the case that sex differences in the likelihood of exposure to trauma subtypes is actually the key factor.”

“At the present time, there are not specific treatment protocols aimed at addressing childhood trauma subtypes, but most experienced therapists will incorporate information about the individual’s trauma history in their treatment,” Dr. Walker added.

Also commenting on the research, Philip Gorwood, MD, PhD, head of the Clinique des Maladies Mentales et de l’Encéphale at Centre Hospitalier Sainte Anne in Paris, said the results are “important … as childhood trauma has been clearly recognized as a major risk factor for the vast majority of psychiatric disorders, but with poor knowledge of gender specificities.”

“Understanding which aspects of trauma are more damaging according to gender will facilitate research on the resilience process. Many intervention strategies will indeed benefit from a more personalized approach,” he said in a statement. Dr. Gorwood was not involved with this study.

The study authors, Dr. Gorwood, and Dr. Walker report no relevant financial relationships.

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

PARIS – Childhood trauma affects women and men equally in terms of its impact on subsequent psychopathology, but trauma type has subsequent differential effects depending on gender, new research shows.

Investigators found childhood emotional and sexual abuse had a greater effect on women than men, whereas men were more adversely affected by emotional and physical neglect.

“Our findings indicate that exposure to childhood maltreatment increases the risk of having psychiatric symptoms in both men and women,” lead researcher Thanavadee Prachason, PhD, department of psychiatry and neuropsychology, Maastricht (the Netherlands) University Medical Center, said in a press release.

“Exposure to emotionally or sexually abusive experiences during childhood increases the risk of a variety of psychiatric symptoms, particularly in women. In contrast, a history of emotional or physical neglect in childhood increases the risk of having psychiatric symptoms more in men,” Dr. Prachason added.

The findings were presented at the European Psychiatric Association 2023 Congress.

A leading mental illness risk factor

Study presenter Laura Fusar-Poli, MD, PhD, from the department of brain and behavioral sciences, University of Pavia (Italy), said that the differential impact of trauma subtypes in men and women indicate that both gender and the type of childhood adversity experienced need to be taken into account in future studies.

Dr. Fusar-Poli began by highlighting that 13%-36% of individuals have experienced some kind of childhood trauma, with 30% exposed to at least two types of trauma.

Trauma has been identified as a risk factor for a range of mental health problems.

“It is estimated that, worldwide, around one third of all psychiatric disorders are related to childhood trauma,” senior researcher Sinan Gülöksüz, MD, PhD, also from Maastricht University Medical Center, said in the release.

Consequently, “childhood trauma is a leading preventable risk factor for mental illness,” he added.

Previous research suggests the subtype of trauma has an impact on subsequent biological changes and clinical outcomes, and that there are gender differences in the effects of childhood trauma.

To investigate, the researchers examined data from TwinssCan, a Belgian cohort of twins and siblings aged 15-35 years without a diagnosis of pervasive mental disorders.

The study included 477 females and 314 males who had completed the Childhood Trauma Questionnaire–Short Form (CTQ) and the Symptom Checklist-90 SR (SCL-90) to determine exposure to childhood adversity and levels of psychopathology, respectively.

Results showed that total CTQ scores were significantly associated with total SCL-90 scores in both men and women, as well as with each of the nine symptom domains of the SCL-90 (P < .001 for all assessments). These included psychoticism, paranoid ideation, anxiety, depression, somatization, obsessive-compulsive, interpersonal sensitivity, hostility, and phobic anxiety.

There were no significant differences in the associations with total CTQ scores between men and women.

However, when the researchers examined trauma subtypes and psychopathology, clear gender differences emerged.

Investigators found a significant association between emotional abuse on the CTQ and total SCL-90 scores in both men (P < .023) and women (P < .001), but that the association was significantly stronger in women (P = .043).

Sexual abuse was significantly associated with total SCL-90 scores in women (P < .001), while emotional neglect and physical neglect were significantly associated with psychopathology scores in men (P = .026 and P < .001, respectively).

“Physical neglect may include experiences of not having enough to eat, wearing dirty clothes, not being taken care of, and not getting taken to the doctor when the person was growing up,” said Dr. Prachason.

“Emotional neglect may include childhood experiences like not feeling loved or important, and not feeling close to the family.”

In women, emotional abuse was significantly associated with all nine symptom domains of the SCL-90, while sexual abuse was associated with seven: psychoticism, paranoid ideation, anxiety, depression, somatization, obsessive-compulsive, and hostility.

Physical neglect, in men, was significantly associated with eight of the symptom domains (all but somatization), but emotional neglect was linked only to depression, Dr. Fusar-Poli reported.

“This study showed a very important consequence of childhood trauma, and not only in people with mental disorders. I would like to underline that this is a general population, composed of adolescents and young adults, which is the age in which the majority of mental disorders starts, Dr. Fusar-Poli said in an interview.

She emphasized that psychotic disorders are only a part of the “broad range” of conditions that may be related to childhood trauma, which “can have an impact on sub-threshold symptoms that can affect functioning and quality of life in the general population.”

Addressing the differential findings in men and women, Dr. Gülöksüz noted women may be more “vulnerable to childhood trauma than men” simply because “they are exposed to more sexual and emotional abuse.”

However, he said, this is “something that we really need understand,” as there is likely an underlying mechanism, “and not only a biological mechanism but probably a societal one.”

Dr. Gülöksüz noted there could also be differences between societies in terms of the impact of childhood trauma. “Our sample was from Belgium, but what would happen if we conducted this study in Italy, or in India,” he said.

Compromised cognitive, emotional function

Commenting on the findings for this news organization, Elaine F. Walker, PhD, professor of psychology and neuroscience at Emory University in Atlanta, said stress exposure in general, including childhood trauma, “has transdiagnostic effects on vulnerability to mental disorders.”

“The effects are primarily mediated by the hypothalamic-pituitary-adrenal axis, which triggers the release of cortisol. When persistently elevated, this can result in neurobiological processes that have adverse effects on brain structure and circuitry which, in turn, compromises cognitive and emotional functioning,” said Dr. Walker, who was not associated with the study.

She noted that, “while it is possible that there are sex differences in biological sensitivity to certain subtypes of childhood trauma, it may also be the case that sex differences in the likelihood of exposure to trauma subtypes is actually the key factor.”

“At the present time, there are not specific treatment protocols aimed at addressing childhood trauma subtypes, but most experienced therapists will incorporate information about the individual’s trauma history in their treatment,” Dr. Walker added.

Also commenting on the research, Philip Gorwood, MD, PhD, head of the Clinique des Maladies Mentales et de l’Encéphale at Centre Hospitalier Sainte Anne in Paris, said the results are “important … as childhood trauma has been clearly recognized as a major risk factor for the vast majority of psychiatric disorders, but with poor knowledge of gender specificities.”

“Understanding which aspects of trauma are more damaging according to gender will facilitate research on the resilience process. Many intervention strategies will indeed benefit from a more personalized approach,” he said in a statement. Dr. Gorwood was not involved with this study.

The study authors, Dr. Gorwood, and Dr. Walker report no relevant financial relationships.

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

PARIS – Childhood trauma affects women and men equally in terms of its impact on subsequent psychopathology, but trauma type has subsequent differential effects depending on gender, new research shows.

Investigators found childhood emotional and sexual abuse had a greater effect on women than men, whereas men were more adversely affected by emotional and physical neglect.

“Our findings indicate that exposure to childhood maltreatment increases the risk of having psychiatric symptoms in both men and women,” lead researcher Thanavadee Prachason, PhD, department of psychiatry and neuropsychology, Maastricht (the Netherlands) University Medical Center, said in a press release.

“Exposure to emotionally or sexually abusive experiences during childhood increases the risk of a variety of psychiatric symptoms, particularly in women. In contrast, a history of emotional or physical neglect in childhood increases the risk of having psychiatric symptoms more in men,” Dr. Prachason added.

The findings were presented at the European Psychiatric Association 2023 Congress.

A leading mental illness risk factor

Study presenter Laura Fusar-Poli, MD, PhD, from the department of brain and behavioral sciences, University of Pavia (Italy), said that the differential impact of trauma subtypes in men and women indicate that both gender and the type of childhood adversity experienced need to be taken into account in future studies.

Dr. Fusar-Poli began by highlighting that 13%-36% of individuals have experienced some kind of childhood trauma, with 30% exposed to at least two types of trauma.

Trauma has been identified as a risk factor for a range of mental health problems.

“It is estimated that, worldwide, around one third of all psychiatric disorders are related to childhood trauma,” senior researcher Sinan Gülöksüz, MD, PhD, also from Maastricht University Medical Center, said in the release.

Consequently, “childhood trauma is a leading preventable risk factor for mental illness,” he added.

Previous research suggests the subtype of trauma has an impact on subsequent biological changes and clinical outcomes, and that there are gender differences in the effects of childhood trauma.

To investigate, the researchers examined data from TwinssCan, a Belgian cohort of twins and siblings aged 15-35 years without a diagnosis of pervasive mental disorders.

The study included 477 females and 314 males who had completed the Childhood Trauma Questionnaire–Short Form (CTQ) and the Symptom Checklist-90 SR (SCL-90) to determine exposure to childhood adversity and levels of psychopathology, respectively.

Results showed that total CTQ scores were significantly associated with total SCL-90 scores in both men and women, as well as with each of the nine symptom domains of the SCL-90 (P < .001 for all assessments). These included psychoticism, paranoid ideation, anxiety, depression, somatization, obsessive-compulsive, interpersonal sensitivity, hostility, and phobic anxiety.

There were no significant differences in the associations with total CTQ scores between men and women.

However, when the researchers examined trauma subtypes and psychopathology, clear gender differences emerged.

Investigators found a significant association between emotional abuse on the CTQ and total SCL-90 scores in both men (P < .023) and women (P < .001), but that the association was significantly stronger in women (P = .043).

Sexual abuse was significantly associated with total SCL-90 scores in women (P < .001), while emotional neglect and physical neglect were significantly associated with psychopathology scores in men (P = .026 and P < .001, respectively).

“Physical neglect may include experiences of not having enough to eat, wearing dirty clothes, not being taken care of, and not getting taken to the doctor when the person was growing up,” said Dr. Prachason.

“Emotional neglect may include childhood experiences like not feeling loved or important, and not feeling close to the family.”

In women, emotional abuse was significantly associated with all nine symptom domains of the SCL-90, while sexual abuse was associated with seven: psychoticism, paranoid ideation, anxiety, depression, somatization, obsessive-compulsive, and hostility.

Physical neglect, in men, was significantly associated with eight of the symptom domains (all but somatization), but emotional neglect was linked only to depression, Dr. Fusar-Poli reported.

“This study showed a very important consequence of childhood trauma, and not only in people with mental disorders. I would like to underline that this is a general population, composed of adolescents and young adults, which is the age in which the majority of mental disorders starts, Dr. Fusar-Poli said in an interview.

She emphasized that psychotic disorders are only a part of the “broad range” of conditions that may be related to childhood trauma, which “can have an impact on sub-threshold symptoms that can affect functioning and quality of life in the general population.”

Addressing the differential findings in men and women, Dr. Gülöksüz noted women may be more “vulnerable to childhood trauma than men” simply because “they are exposed to more sexual and emotional abuse.”

However, he said, this is “something that we really need understand,” as there is likely an underlying mechanism, “and not only a biological mechanism but probably a societal one.”

Dr. Gülöksüz noted there could also be differences between societies in terms of the impact of childhood trauma. “Our sample was from Belgium, but what would happen if we conducted this study in Italy, or in India,” he said.

Compromised cognitive, emotional function

Commenting on the findings for this news organization, Elaine F. Walker, PhD, professor of psychology and neuroscience at Emory University in Atlanta, said stress exposure in general, including childhood trauma, “has transdiagnostic effects on vulnerability to mental disorders.”

“The effects are primarily mediated by the hypothalamic-pituitary-adrenal axis, which triggers the release of cortisol. When persistently elevated, this can result in neurobiological processes that have adverse effects on brain structure and circuitry which, in turn, compromises cognitive and emotional functioning,” said Dr. Walker, who was not associated with the study.

She noted that, “while it is possible that there are sex differences in biological sensitivity to certain subtypes of childhood trauma, it may also be the case that sex differences in the likelihood of exposure to trauma subtypes is actually the key factor.”

“At the present time, there are not specific treatment protocols aimed at addressing childhood trauma subtypes, but most experienced therapists will incorporate information about the individual’s trauma history in their treatment,” Dr. Walker added.

Also commenting on the research, Philip Gorwood, MD, PhD, head of the Clinique des Maladies Mentales et de l’Encéphale at Centre Hospitalier Sainte Anne in Paris, said the results are “important … as childhood trauma has been clearly recognized as a major risk factor for the vast majority of psychiatric disorders, but with poor knowledge of gender specificities.”

“Understanding which aspects of trauma are more damaging according to gender will facilitate research on the resilience process. Many intervention strategies will indeed benefit from a more personalized approach,” he said in a statement. Dr. Gorwood was not involved with this study.

The study authors, Dr. Gorwood, and Dr. Walker report no relevant financial relationships.

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

An intervention tailored for Black first-time mothers helped increase their infants’ sleep time, researchers have found, a notable result as many studies have shown Black infants get less sleep on average than White infants.

Less sleep has historically put Black children at higher risk for negative outcomes including obesity and poorer social-emotional functioning and cognitive development. These disparities persist into adulthood, the researchers note, as previous studies have shown.

Justin A. Lavner, PhD, with the department of psychology at the University of Georgia in Athens, led this post hoc secondary analysis of the Sleep SAAF (Strong African American Families) study, a randomized clinical trial of 234 participants comparing a responsive parenting (RP) intervention with a safety control group over the first 16 weeks post partum. The original analysis studied the effects of the intervention on rapid weight gain.

In the original analysis, the authors write that “From birth to 2, the prevalence of high weight for length (above the 95th percentile) is 25% higher among African American children compared to White children. From age 2 to 19, the rate of obesity is more than 50% higher among African American children compared to White children. Similar disparities persist into adulthood: rates of obesity are approximately 25% higher among African American adults compared to White adults.”

The differences in early rapid weight gain may be driving the disparities, the authors write.

Elements of the intervention

The intervention in the current analysis included materials delivered at the 3- and 8-week home visits focused on soothing and crying, feeding, and interactive play in the babies’ first months. Families were recruited from Augusta University Medical Center in Augusta, Ga., and had home visits at 1, 3, 8, and 16 weeks post partum.

Mothers got a packet of handouts and facilitators walked through the information with them. The measures involved hands-on activities, discussion, and videos, all tailored for Black families, the authors state.

Mothers were taught about responding appropriately at night when their baby cries, including giving the baby a couple of minutes to fall back to sleep independently and by using calming messages, such as shushing or white noise, before picking the baby up.
 

Babies learn to fall asleep on their own

They also learned to put infants to bed early (ideally by 8 p.m.) so the babies would be calm but awake and could learn to fall asleep on their own.

The control group’s guidance was matched for intensity and session length but focused on sleep and home safety, such as reducing the risk of sudden infant death syndrome (SIDS), keeping the baby’s sleep area close to, but away from, the mother’s bed, and preventing shaken baby syndrome.

In both groups, the 3-week visit session lasted about 90-120 minutes and the 8-week visit lasted about 45-60 minutes.
 

Longer sleep with the intervention

A total of 212 Black mothers, average age 22.7, were randomized – 108 to the RP group and 104 to the control group. Answers on questionnaires were analyzed and at 16 weeks post partum, infants in the RP group (relative to controls) had:

• Longer reported nighttime sleep (mean difference, 40 minutes [95% confidence interval, 3-77]).
• Longer total sleep duration (mean difference, 73 minutes [95% CI, 14-131]).
• Fewer nighttime wakings (mean difference, −0.4 wakings [95% CI, −0.6 to −0.1]).
• Greater likelihood of meeting guidelines of at least 12 hours of sleep per day (risk ratio, 1.4 [95% CI, 1.1 to 1.8]) than controls.

Findings were published in JAMA Network Open.

Additionally, mothers in the RP group more frequently reported they engaged in practices such as letting babies have a few minutes to fall back to sleep on their own (RR, 1.6 [95% CI, 1.0-2.6]) and being less likely to feed their infant just before the baby’s bedtime (RR, 0.5 [95% CI, 0.3-0.8]).

In an accompanying invited commentary, Sarah M. Honaker, PhD, department of pediatrics, Indiana University, Indianapolis, and Alicia Chung, EdD, Center for Early Childhood Health and Development at New York University, write that though the added average sleep duration is one of the most significant findings, there is a possibility of desirability bias because it was reported by the mothers after specific guidance by the facilitators.

“Nonetheless,” the editorialists write, “even if the true effect were half as small, this additional sleep duration could yield notable benefits in infant development if the effect persisted over time. The difference in night wakings between the intervention and control groups (1.8 vs 1.5 per night) at 16 weeks postpartum was statistically significant, though it is unclear whether this difference is clinically meaningful to families.”

They note that it is unclear from the study how the intervention was culturally adapted and how the adaptation might have affected outcomes.

Sleep intervention trials have focused on White families

The editorialists write that much is known about the benefits of behavioral sleep intervention in controlled trials and general population settings, and no adverse effects on infant attachment or cortisol levels have been linked to the interventions.

However, they add, “Unfortunately, this substantial progress in our understanding of infant BSI [behavioral sleep intervention] comes with a caveat, in that most previous studies have been performed with White families from mid-to-high socioeconomic backgrounds.”

Dr. Honaker and Dr. Chung write, “[I]t is important to note that much work remains to examine the acceptability, feasibility, and efficacy of infant BSI in other groups that have been historically marginalized.”

Dr. Lavner and colleagues point out that before their study, there had been little emphasis on interventions to encourage better sleep in general for Black infants, “as most early sleep interventions for this population have focused on SIDS prevention.”

The study by Dr. Lavner et al. was funded by the National Institutes of Health, a Harrington Faculty Fellowship from the University of Texas, and an award from the Penn State Clinical and Translational Sciences Institute supported by the National Center for Advancing Translational Sciences. Editorialist Dr. Honaker reported receiving grants from Nationwide Children’s Hospital (parent grant, Centers for Disease Control and Prevention) to evaluate the acceptability of infant behavioral sleep intervention in Black families.

An intervention tailored for Black first-time mothers helped increase their infants’ sleep time, researchers have found, a notable result as many studies have shown Black infants get less sleep on average than White infants.

Less sleep has historically put Black children at higher risk for negative outcomes including obesity and poorer social-emotional functioning and cognitive development. These disparities persist into adulthood, the researchers note, as previous studies have shown.

Justin A. Lavner, PhD, with the department of psychology at the University of Georgia in Athens, led this post hoc secondary analysis of the Sleep SAAF (Strong African American Families) study, a randomized clinical trial of 234 participants comparing a responsive parenting (RP) intervention with a safety control group over the first 16 weeks post partum. The original analysis studied the effects of the intervention on rapid weight gain.

In the original analysis, the authors write that “From birth to 2, the prevalence of high weight for length (above the 95th percentile) is 25% higher among African American children compared to White children. From age 2 to 19, the rate of obesity is more than 50% higher among African American children compared to White children. Similar disparities persist into adulthood: rates of obesity are approximately 25% higher among African American adults compared to White adults.”

The differences in early rapid weight gain may be driving the disparities, the authors write.

Elements of the intervention

The intervention in the current analysis included materials delivered at the 3- and 8-week home visits focused on soothing and crying, feeding, and interactive play in the babies’ first months. Families were recruited from Augusta University Medical Center in Augusta, Ga., and had home visits at 1, 3, 8, and 16 weeks post partum.

Mothers got a packet of handouts and facilitators walked through the information with them. The measures involved hands-on activities, discussion, and videos, all tailored for Black families, the authors state.

Mothers were taught about responding appropriately at night when their baby cries, including giving the baby a couple of minutes to fall back to sleep independently and by using calming messages, such as shushing or white noise, before picking the baby up.
 

Babies learn to fall asleep on their own

They also learned to put infants to bed early (ideally by 8 p.m.) so the babies would be calm but awake and could learn to fall asleep on their own.

The control group’s guidance was matched for intensity and session length but focused on sleep and home safety, such as reducing the risk of sudden infant death syndrome (SIDS), keeping the baby’s sleep area close to, but away from, the mother’s bed, and preventing shaken baby syndrome.

In both groups, the 3-week visit session lasted about 90-120 minutes and the 8-week visit lasted about 45-60 minutes.
 

Longer sleep with the intervention

A total of 212 Black mothers, average age 22.7, were randomized – 108 to the RP group and 104 to the control group. Answers on questionnaires were analyzed and at 16 weeks post partum, infants in the RP group (relative to controls) had:

• Longer reported nighttime sleep (mean difference, 40 minutes [95% confidence interval, 3-77]).
• Longer total sleep duration (mean difference, 73 minutes [95% CI, 14-131]).
• Fewer nighttime wakings (mean difference, −0.4 wakings [95% CI, −0.6 to −0.1]).
• Greater likelihood of meeting guidelines of at least 12 hours of sleep per day (risk ratio, 1.4 [95% CI, 1.1 to 1.8]) than controls.

Findings were published in JAMA Network Open.

Additionally, mothers in the RP group more frequently reported they engaged in practices such as letting babies have a few minutes to fall back to sleep on their own (RR, 1.6 [95% CI, 1.0-2.6]) and being less likely to feed their infant just before the baby’s bedtime (RR, 0.5 [95% CI, 0.3-0.8]).

In an accompanying invited commentary, Sarah M. Honaker, PhD, department of pediatrics, Indiana University, Indianapolis, and Alicia Chung, EdD, Center for Early Childhood Health and Development at New York University, write that though the added average sleep duration is one of the most significant findings, there is a possibility of desirability bias because it was reported by the mothers after specific guidance by the facilitators.

“Nonetheless,” the editorialists write, “even if the true effect were half as small, this additional sleep duration could yield notable benefits in infant development if the effect persisted over time. The difference in night wakings between the intervention and control groups (1.8 vs 1.5 per night) at 16 weeks postpartum was statistically significant, though it is unclear whether this difference is clinically meaningful to families.”

They note that it is unclear from the study how the intervention was culturally adapted and how the adaptation might have affected outcomes.

Sleep intervention trials have focused on White families

The editorialists write that much is known about the benefits of behavioral sleep intervention in controlled trials and general population settings, and no adverse effects on infant attachment or cortisol levels have been linked to the interventions.

However, they add, “Unfortunately, this substantial progress in our understanding of infant BSI [behavioral sleep intervention] comes with a caveat, in that most previous studies have been performed with White families from mid-to-high socioeconomic backgrounds.”

Dr. Honaker and Dr. Chung write, “[I]t is important to note that much work remains to examine the acceptability, feasibility, and efficacy of infant BSI in other groups that have been historically marginalized.”

Dr. Lavner and colleagues point out that before their study, there had been little emphasis on interventions to encourage better sleep in general for Black infants, “as most early sleep interventions for this population have focused on SIDS prevention.”

The study by Dr. Lavner et al. was funded by the National Institutes of Health, a Harrington Faculty Fellowship from the University of Texas, and an award from the Penn State Clinical and Translational Sciences Institute supported by the National Center for Advancing Translational Sciences. Editorialist Dr. Honaker reported receiving grants from Nationwide Children’s Hospital (parent grant, Centers for Disease Control and Prevention) to evaluate the acceptability of infant behavioral sleep intervention in Black families.

An intervention tailored for Black first-time mothers helped increase their infants’ sleep time, researchers have found, a notable result as many studies have shown Black infants get less sleep on average than White infants.

Less sleep has historically put Black children at higher risk for negative outcomes including obesity and poorer social-emotional functioning and cognitive development. These disparities persist into adulthood, the researchers note, as previous studies have shown.

Justin A. Lavner, PhD, with the department of psychology at the University of Georgia in Athens, led this post hoc secondary analysis of the Sleep SAAF (Strong African American Families) study, a randomized clinical trial of 234 participants comparing a responsive parenting (RP) intervention with a safety control group over the first 16 weeks post partum. The original analysis studied the effects of the intervention on rapid weight gain.

In the original analysis, the authors write that “From birth to 2, the prevalence of high weight for length (above the 95th percentile) is 25% higher among African American children compared to White children. From age 2 to 19, the rate of obesity is more than 50% higher among African American children compared to White children. Similar disparities persist into adulthood: rates of obesity are approximately 25% higher among African American adults compared to White adults.”

The differences in early rapid weight gain may be driving the disparities, the authors write.

Elements of the intervention

The intervention in the current analysis included materials delivered at the 3- and 8-week home visits focused on soothing and crying, feeding, and interactive play in the babies’ first months. Families were recruited from Augusta University Medical Center in Augusta, Ga., and had home visits at 1, 3, 8, and 16 weeks post partum.

Mothers got a packet of handouts and facilitators walked through the information with them. The measures involved hands-on activities, discussion, and videos, all tailored for Black families, the authors state.

Mothers were taught about responding appropriately at night when their baby cries, including giving the baby a couple of minutes to fall back to sleep independently and by using calming messages, such as shushing or white noise, before picking the baby up.
 

Babies learn to fall asleep on their own

They also learned to put infants to bed early (ideally by 8 p.m.) so the babies would be calm but awake and could learn to fall asleep on their own.

The control group’s guidance was matched for intensity and session length but focused on sleep and home safety, such as reducing the risk of sudden infant death syndrome (SIDS), keeping the baby’s sleep area close to, but away from, the mother’s bed, and preventing shaken baby syndrome.

In both groups, the 3-week visit session lasted about 90-120 minutes and the 8-week visit lasted about 45-60 minutes.
 

Longer sleep with the intervention

A total of 212 Black mothers, average age 22.7, were randomized – 108 to the RP group and 104 to the control group. Answers on questionnaires were analyzed and at 16 weeks post partum, infants in the RP group (relative to controls) had:

• Longer reported nighttime sleep (mean difference, 40 minutes [95% confidence interval, 3-77]).
• Longer total sleep duration (mean difference, 73 minutes [95% CI, 14-131]).
• Fewer nighttime wakings (mean difference, −0.4 wakings [95% CI, −0.6 to −0.1]).
• Greater likelihood of meeting guidelines of at least 12 hours of sleep per day (risk ratio, 1.4 [95% CI, 1.1 to 1.8]) than controls.

Findings were published in JAMA Network Open.

Additionally, mothers in the RP group more frequently reported they engaged in practices such as letting babies have a few minutes to fall back to sleep on their own (RR, 1.6 [95% CI, 1.0-2.6]) and being less likely to feed their infant just before the baby’s bedtime (RR, 0.5 [95% CI, 0.3-0.8]).

In an accompanying invited commentary, Sarah M. Honaker, PhD, department of pediatrics, Indiana University, Indianapolis, and Alicia Chung, EdD, Center for Early Childhood Health and Development at New York University, write that though the added average sleep duration is one of the most significant findings, there is a possibility of desirability bias because it was reported by the mothers after specific guidance by the facilitators.

“Nonetheless,” the editorialists write, “even if the true effect were half as small, this additional sleep duration could yield notable benefits in infant development if the effect persisted over time. The difference in night wakings between the intervention and control groups (1.8 vs 1.5 per night) at 16 weeks postpartum was statistically significant, though it is unclear whether this difference is clinically meaningful to families.”

They note that it is unclear from the study how the intervention was culturally adapted and how the adaptation might have affected outcomes.

Sleep intervention trials have focused on White families

The editorialists write that much is known about the benefits of behavioral sleep intervention in controlled trials and general population settings, and no adverse effects on infant attachment or cortisol levels have been linked to the interventions.

However, they add, “Unfortunately, this substantial progress in our understanding of infant BSI [behavioral sleep intervention] comes with a caveat, in that most previous studies have been performed with White families from mid-to-high socioeconomic backgrounds.”

Dr. Honaker and Dr. Chung write, “[I]t is important to note that much work remains to examine the acceptability, feasibility, and efficacy of infant BSI in other groups that have been historically marginalized.”

Dr. Lavner and colleagues point out that before their study, there had been little emphasis on interventions to encourage better sleep in general for Black infants, “as most early sleep interventions for this population have focused on SIDS prevention.”

The study by Dr. Lavner et al. was funded by the National Institutes of Health, a Harrington Faculty Fellowship from the University of Texas, and an award from the Penn State Clinical and Translational Sciences Institute supported by the National Center for Advancing Translational Sciences. Editorialist Dr. Honaker reported receiving grants from Nationwide Children’s Hospital (parent grant, Centers for Disease Control and Prevention) to evaluate the acceptability of infant behavioral sleep intervention in Black families.

Imaging tests may miss early signs of multiple sclerosis (MS) in children who have no symptoms of the disease, according to a recent study that points to the need for a change in diagnostic criteria for the neuromuscular condition.

The findings suggest that children, unlike adults, may not need to meet the current clinical standard criteria to be considered at risk for MS.

“This is an important study confirming that some children who have no symptoms of demyelinating disease may nonetheless have MRI findings suggestive of demyelination detected on brain imaging,” said Naila Makhani, MD, associate professor of pediatrics and of neurology at Yale University and director of the Yale Pediatric Neuroimmunology Program, New Haven, Conn. Dr. Makhani was not affiliated with the study.

Researchers reviewed the MRI scans of 38 children aged 7-17 years who had radiologically isolated syndrome (RIS), a possible precursor to MS.

Like MS, RIS is characterized by destruction of the myelin. However, RIS is generally asymptomatic.

While RIS has been linked to MS, a diagnosis of RIS does not mean someone will be diagnosed with MS. Previous studies have shown that at least 3% of MS cases begin before age 16.

The children in the study likely received an MRI because of complaints of headaches or after having been diagnosed with a concussion, according to the researchers. The participants also did not show physical symptoms for MS, nor did they meet the McDonald or Barkohf criteria, which are clinical standards used to diagnose the condition in adults and children.

Within an average of 3 years following the imaging and RIS diagnosis, almost 36% of the children experienced a clinical attack, which led to an MS diagnosis. Almost three-fourths of the children developed additional brain and spinal cord lesions in the myelin that were evident on MRI.

MS often is diagnosed after a patient has had a clinical attack, such as vision impairment, loss of balance, inflammation, or severe fatigue. Identifying the potential for the disease earlier may allow clinicians to treat sooner, according to Leslie Benson, MD, assistant director of pediatric neuroimmunology at Massachusetts General Hospital, Boston, and one of the study authors.

“The field is leaning toward [the question of], ‘Should we treat presymptomatic MS?’ ” said Dr. Benson. “If we have the opportunity to prevent disability and improve long-term outcomes with safe medications, then we would like to do so.”

The findings were published in the journal Multiple Sclerosis and Related Disorders.

According to Dr. Benson and her colleagues, adjustments to the McDonald or Barkohf criteria for children may help in the detection of RIS and may allow earlier identification of MS.

“We don’t really know when MS first starts,” Dr. Benson said. “Unless you happen to have an MRI or symptoms, there’s no way to know how long the lesions have been evolving and how long the disease progression that led to those lesions has been there.”

MRI images showing lesions in the brain stem and spinal cord of children appeared to be different from those typically seen in adults, according to Tanuja Chitnis, MD, director of the Mass General Brigham Pediatric MS Center in Boston, who is one of the study’s coauthors.

“The concern of many practitioners is whether we should be treating at the first sign of MS,” Dr. Chitnis said. “We need to understand it better in children, and in teenagers especially, when these probably start biologically.”

Dr. Benson said current criteria for diagnosing MS in children require meeting a high threshold, which may limit diagnoses to those whose condition has progressed.

“This may miss patients at risk for MS,” Dr. Benson said. “That idea of who do you diagnose RIS and what criteria work to accurately diagnose RIS is really important.”

For now, the challenge remains of investigating characteristics of patients with RIS who will later have a clinical attack.

“We need a better understanding of what criteria do need to be met and how we can best risk-stratify our patients,” Dr. Benson said. “If it is recommended to treat presymptomatic cases, that we can best stratify those at risk and not overtreat those not at risk.”

Dr. Makhani receives funding from the National Institutes of Health, the Charles H. Hood Foundation, and the Multiple Sclerosis Society.

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

Imaging tests may miss early signs of multiple sclerosis (MS) in children who have no symptoms of the disease, according to a recent study that points to the need for a change in diagnostic criteria for the neuromuscular condition.

The findings suggest that children, unlike adults, may not need to meet the current clinical standard criteria to be considered at risk for MS.

“This is an important study confirming that some children who have no symptoms of demyelinating disease may nonetheless have MRI findings suggestive of demyelination detected on brain imaging,” said Naila Makhani, MD, associate professor of pediatrics and of neurology at Yale University and director of the Yale Pediatric Neuroimmunology Program, New Haven, Conn. Dr. Makhani was not affiliated with the study.

Researchers reviewed the MRI scans of 38 children aged 7-17 years who had radiologically isolated syndrome (RIS), a possible precursor to MS.

Like MS, RIS is characterized by destruction of the myelin. However, RIS is generally asymptomatic.

While RIS has been linked to MS, a diagnosis of RIS does not mean someone will be diagnosed with MS. Previous studies have shown that at least 3% of MS cases begin before age 16.

The children in the study likely received an MRI because of complaints of headaches or after having been diagnosed with a concussion, according to the researchers. The participants also did not show physical symptoms for MS, nor did they meet the McDonald or Barkohf criteria, which are clinical standards used to diagnose the condition in adults and children.

Within an average of 3 years following the imaging and RIS diagnosis, almost 36% of the children experienced a clinical attack, which led to an MS diagnosis. Almost three-fourths of the children developed additional brain and spinal cord lesions in the myelin that were evident on MRI.

MS often is diagnosed after a patient has had a clinical attack, such as vision impairment, loss of balance, inflammation, or severe fatigue. Identifying the potential for the disease earlier may allow clinicians to treat sooner, according to Leslie Benson, MD, assistant director of pediatric neuroimmunology at Massachusetts General Hospital, Boston, and one of the study authors.

“The field is leaning toward [the question of], ‘Should we treat presymptomatic MS?’ ” said Dr. Benson. “If we have the opportunity to prevent disability and improve long-term outcomes with safe medications, then we would like to do so.”

The findings were published in the journal Multiple Sclerosis and Related Disorders.

According to Dr. Benson and her colleagues, adjustments to the McDonald or Barkohf criteria for children may help in the detection of RIS and may allow earlier identification of MS.

“We don’t really know when MS first starts,” Dr. Benson said. “Unless you happen to have an MRI or symptoms, there’s no way to know how long the lesions have been evolving and how long the disease progression that led to those lesions has been there.”

MRI images showing lesions in the brain stem and spinal cord of children appeared to be different from those typically seen in adults, according to Tanuja Chitnis, MD, director of the Mass General Brigham Pediatric MS Center in Boston, who is one of the study’s coauthors.

“The concern of many practitioners is whether we should be treating at the first sign of MS,” Dr. Chitnis said. “We need to understand it better in children, and in teenagers especially, when these probably start biologically.”

Dr. Benson said current criteria for diagnosing MS in children require meeting a high threshold, which may limit diagnoses to those whose condition has progressed.

“This may miss patients at risk for MS,” Dr. Benson said. “That idea of who do you diagnose RIS and what criteria work to accurately diagnose RIS is really important.”

For now, the challenge remains of investigating characteristics of patients with RIS who will later have a clinical attack.

“We need a better understanding of what criteria do need to be met and how we can best risk-stratify our patients,” Dr. Benson said. “If it is recommended to treat presymptomatic cases, that we can best stratify those at risk and not overtreat those not at risk.”

Dr. Makhani receives funding from the National Institutes of Health, the Charles H. Hood Foundation, and the Multiple Sclerosis Society.

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

Imaging tests may miss early signs of multiple sclerosis (MS) in children who have no symptoms of the disease, according to a recent study that points to the need for a change in diagnostic criteria for the neuromuscular condition.

The findings suggest that children, unlike adults, may not need to meet the current clinical standard criteria to be considered at risk for MS.

“This is an important study confirming that some children who have no symptoms of demyelinating disease may nonetheless have MRI findings suggestive of demyelination detected on brain imaging,” said Naila Makhani, MD, associate professor of pediatrics and of neurology at Yale University and director of the Yale Pediatric Neuroimmunology Program, New Haven, Conn. Dr. Makhani was not affiliated with the study.

Researchers reviewed the MRI scans of 38 children aged 7-17 years who had radiologically isolated syndrome (RIS), a possible precursor to MS.

Like MS, RIS is characterized by destruction of the myelin. However, RIS is generally asymptomatic.

While RIS has been linked to MS, a diagnosis of RIS does not mean someone will be diagnosed with MS. Previous studies have shown that at least 3% of MS cases begin before age 16.

The children in the study likely received an MRI because of complaints of headaches or after having been diagnosed with a concussion, according to the researchers. The participants also did not show physical symptoms for MS, nor did they meet the McDonald or Barkohf criteria, which are clinical standards used to diagnose the condition in adults and children.

Within an average of 3 years following the imaging and RIS diagnosis, almost 36% of the children experienced a clinical attack, which led to an MS diagnosis. Almost three-fourths of the children developed additional brain and spinal cord lesions in the myelin that were evident on MRI.

MS often is diagnosed after a patient has had a clinical attack, such as vision impairment, loss of balance, inflammation, or severe fatigue. Identifying the potential for the disease earlier may allow clinicians to treat sooner, according to Leslie Benson, MD, assistant director of pediatric neuroimmunology at Massachusetts General Hospital, Boston, and one of the study authors.

“The field is leaning toward [the question of], ‘Should we treat presymptomatic MS?’ ” said Dr. Benson. “If we have the opportunity to prevent disability and improve long-term outcomes with safe medications, then we would like to do so.”

The findings were published in the journal Multiple Sclerosis and Related Disorders.

According to Dr. Benson and her colleagues, adjustments to the McDonald or Barkohf criteria for children may help in the detection of RIS and may allow earlier identification of MS.

“We don’t really know when MS first starts,” Dr. Benson said. “Unless you happen to have an MRI or symptoms, there’s no way to know how long the lesions have been evolving and how long the disease progression that led to those lesions has been there.”

MRI images showing lesions in the brain stem and spinal cord of children appeared to be different from those typically seen in adults, according to Tanuja Chitnis, MD, director of the Mass General Brigham Pediatric MS Center in Boston, who is one of the study’s coauthors.

“The concern of many practitioners is whether we should be treating at the first sign of MS,” Dr. Chitnis said. “We need to understand it better in children, and in teenagers especially, when these probably start biologically.”

Dr. Benson said current criteria for diagnosing MS in children require meeting a high threshold, which may limit diagnoses to those whose condition has progressed.

“This may miss patients at risk for MS,” Dr. Benson said. “That idea of who do you diagnose RIS and what criteria work to accurately diagnose RIS is really important.”

For now, the challenge remains of investigating characteristics of patients with RIS who will later have a clinical attack.

“We need a better understanding of what criteria do need to be met and how we can best risk-stratify our patients,” Dr. Benson said. “If it is recommended to treat presymptomatic cases, that we can best stratify those at risk and not overtreat those not at risk.”

Dr. Makhani receives funding from the National Institutes of Health, the Charles H. Hood Foundation, and the Multiple Sclerosis Society.

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

Rheumatologist Marcus Snow, MD, is comfortable with prescribing biosimilars as a first-line, first-time biologic, and discussing them with patients.

“If a biosimilar is on the market, it has gone through rigorous study proving its effectiveness and equivalence to a bio-originator,” said Dr. Snow, a rheumatologist with the University of Nebraska Medical Center, Omaha, and chair of the American College of Rheumatology’s Committee on Rheumatologic Care.

The formulary makes a big difference in the conversation about options, he said. “The formularies dictate what we can prescribe. It may not be appropriate, but it is reality. The cost of biologics for a patient without insurance coverage makes it impossible to afford.”

He will often tell patients that he’ll fight any changes or formulary restrictions he does not agree with. “However, when I see patients in follow-up, even if there is no known change on the horizon, I may bring up biosimilars when we have a moment to chat about them to familiarize them with what may happen in the future.”

The need for patient education on biosimilars presents a barrier to realizing their potential to save money and expand choice, noted Cardinal Health in its 2023 biosimilars report. Of 103 rheumatologists who responded to a Cardinal Health survey, 85% agreed that patient education was important. But those conversations can take an uncomfortable turn if the patient pushes back against taking a biosimilar owing to cost or safety concerns.

It’s not uncommon for a patient to express some anxiety about biosimilars, especially if they’re doing well on a current treatment plan. Most patients do not want any changes that may lead to worsening disease control, Dr. Snow said.

Kaiser Permanente

Patients and physicians alike often don’t understand the mechanics of biosimilars. “There’s a lot of misinformation about this,” said Sameer Awsare, MD, an associate executive director for The Permanente Medical Group in Campbell, Calif. Patients should know that a biosimilar will be as clinically efficacious as the medicine they’ve been on, with the same safety profiles, said Dr. Awsare, who works with Kaiser Permanente’s pharmacy partners on biosimilars.
 

Insurance often drives the conversation

The global anti-inflammatory biologics market is anticipated to reach $150 billion by 2027, according to a recent CVS report. As of March 2023, the Food and Drug Administration had approved 40 biosimilars to 11 different reference products. There are 28 on the U.S. market and 100 more in development. Projected to save more than $180 billion over the next 5 years, they are anticipated to expand choice and drive competition.

Rheumatologists, dermatologists, and gastroenterologists are frequent prescribers, although their choices for immune-mediated inflammatory diseases are limited to tumor necrosis factor inhibitors (infliximab [Remicade] originator and adalimumab [Humira] originator) and anti-CD20 agents, such as rituximab (Rituxan) originator.

Benefit design or formulary usually dictates what medicine a patient receives. “Because of significantly higher out-of-pocket cost or formulary positioning, patients may end up with a generic or a biosimilar instead of a brand-name medicine or branded biologic,” said Robert Popovian, PharmD, MS, chief science policy officer of the Global Healthy Living Foundation.

Insurers rarely offer both Remicade and biosimilar infliximab, allowing the doctor to choose, said Miguel Regueiro, MD, chair of the Cleveland Clinic’s Digestive Disease & Surgery Institute, who prescribes infliximab biosimilars. Most often, the payer will choose the lower-cost biosimilar. “I am fine with the biosimilar, either as a new start or a switch from the reference product.”

However, the patient might feel differently. They can form an attachment to the reference medication if it has prevented severe illness. “They do not want to change, as they feel they are going on a ‘new’ medication that will not work as well,” Dr. Regueiro said.

This is where the education comes in: to reassure patients that a biosimilar will work just as well as the reference product. “For patients who have done well for years on a biologic, more time needs to be spent reassuring them and answering questions,” compared with a patient just starting on a biosimilar, he advised.

But not all physicians are quick to prescribe biosimilars.

Julie Miller Photography

Especially with psoriasis, which has so many strong options for reference drugs, a switch may be hard to justify, said dermatologist Stephanie K. Fabbro, MD, assistant professor at Northeast Ohio Medical University, Rootstown. “If I have a preference, I would rather switch a patient to a drug from a different class without a biosimilar option to reduce the possibility of pushback.”

Dr. Fabbro, part of the core faculty in the Riverside Methodist Hospital Dermatology Residency Program in Columbus, will share data from clinical trials and postmarket surveillance with patients to support her decision.
 

Conversations about cost

Patients may also push back if they don’t save money when switching to a biosimilar. “This dilemma raises the question of who is profiting when a biosimilar is dispensed,” Dr. Popovian said. Insurers and pharmacy benefit managers (PBMs) that take additional concessions from biopharmaceutical manufacturers in the form of rebates and fees will often pocket this money as profit instead of passing savings back to the patient to help reduce their out-of-pocket requirement, he added.

If an originator biologic and a biosimilar are available, “as a pharmacist, I will choose the medicine that will incur the lowest out-of-pocket cost for the patient,” Dr. Popovian said.

Discussing cost – and who dictates which biosimilar is on the formulary – is an important conversation to have with patients, said Vivek Kaul, MD, Segal-Watson Professor of Medicine at the University of Rochester (N.Y.) Medical Center.

Providing equivalent clinical efficacy while saving costs is the economic reality of biosimilars, Dr. Kaul said. Third-party payers regularly evaluate how to provide the same quality of care while saving money. Physicians and patients alike “must be mindful that as time goes on, if the science on biosimilars stays robust, if the adoption is more widespread and the cost-saving proposition turns out to be true, more formularies will be attracted to replacing the reference product with the biosimilar counterpart.”

Providers and patients can weigh the options if a formulary suddenly switches to a biosimilar, Dr. Kaul continued. “You can accept the novel product on the formulary or may have to face out-of-pocket expenses as a patient.” If providers and patients have concerns about the biosimilar, they can always appeal if there’s solid scientific evidence that supports reverting back to the reference product.

“If you think the biosimilar is equally efficacious, comes at a lower cost, and is right for the patient, then the providers should tell the patient that,” he added.

Some studies have questioned whether the biosimilars will save money, compared with the reference drug, Dr. Fabbro noted. Medicare, for example, may pay only for a certain percentage of an approved biosimilar, saddling the patient with a monthly copay costing thousands of dollars. “It is unclear whether biosimilar manufacturers will have the same level of patient support programs as the reference drug companies.”

For that reason, physicians should also inform patients about the robust patient assistance and copay assistance programs many reference drug manufacturers offer, she said.

Biosimilars 101: Familiarizing patients

Safety and ease of use are other common concerns about biosimilars. Patients may ask if the application is different, or why it’s advantageous to switch to a biosimilar, Dr. Awsare said.

Sometimes the syringe or injector for a biosimilar might look different from that of the originator drug, he said.

Anecdotally, Dr. Fabbro has heard stories of patients having injection reactions that they did not experience with the reference drug or having a disease flare-up after starting a biosimilar. 

rubberball/Getty Images

As is the case with reference products, in their conversations with patients, clinicians should address the adverse event profile of biosimilars, offering data points from published studies and clinical guidelines that support the use of these products. “There should be an emphasis on patient education around efficacy and any side effects, and how the profile of the reference product compares with a proposed biosimilar,” Dr. Kaul suggested.

When Dr. Snow discusses biosimilars and generics, “I make sure to share this in an understandable way based on the patient’s scientific background, or lack thereof,” he said. If there is enough time, he also discusses how European- and U.S.-sourced biologics are slightly different.

Pharmacists should tell patients to expect the same clinical outcomes from a biosimilar, Dr. Popovian said. However, if they have any reduction in efficacy or potential safety concerns, they should communicate with their physician or pharmacist immediately.

In Dr. Regueiro’s practice, a pharmacist specializing in inflammatory bowel disease often has a one-on-one meeting with patients to educate and answer questions. “Additionally, we provide them the Crohn’s and Colitis Foundation web link on biosimilars,” said Dr. Regueiro.
 

A village approach to education

When biosimilars first came out, there were no formal education materials, Dr. Awsare said. Kaiser Permanente decided to create its own educational materials, not just for patients but also to help educate its primary care doctors; the rheumatologists, dermatologists, and gastroenterologists using the biosimilars; the nurses infusing patients; and the pharmacists preparing the biosimilars.

The health system also has a different approach to choosing medication. Instead of having an insurance company or PBM decide what’s in the formulary, clinicians work with the pharmacists at Kaiser to look at clinical evidence and decide which biosimilar to use. Most of its plans also provide lower copays to patients when they use the biosimilar. 

This was the approach for Humira biosimilars, Dr. Awsare said. Eight will be on the market in 2023. “Our rheumatologists, dermatologists, and gastroenterologists looked at the data from Europe, looked at some real-world evidence, and then said: ‘We think this one’s going to be the best one for our patients.’ ”

Having clinicians choose the biosimilar instead of a health plan makes it a lot easier to have conversations with patients, he said. “Once we’ve moved that market share to that particular biosimilar, we give our physicians the time to have those discussions.”

Clinical pharmacists also provide educational support, offering guidance on issues such as side effects, as patients transition to the biosimilar. “We like to use the word ‘transition’ because it’s essentially the same biologic. So, you’re not actually switching,” Dr. Awsare said.

No consensus on interchangeability

Whether the conversation on interchangeability will affect patient conversations with physicians depends on who you ask.

If a biosimilar has an interchangeability designation, it means that the pharmacist can substitute it without the intervention of the clinician who prescribed the reference product. It does not relate to the quality, safety, or effectiveness of biosimilars or interchangeable biosimilar products, Dr. Popovian said.

The United States is the only country that has this designation. Even though it’s not identical to the originator drug, a biosimilar has the same clinical efficacy and safety profile. “So clinically, interchangeability is meaningless,” Dr. Awsare said.

In its report on biosimilars in the autoimmune category, CVS acknowledged that interchangeability was important but would not be a significant factor in driving adoption of biosimilars. However, in a Cardinal Health survey of 72 gastroenterologists, 38% cited the interchangeability of biosimilars as a top concern for adalimumab biosimilars, along with transitioning patients from Humira to a biosimilar (44%).

“Patient education regarding biosimilar safety, efficacy, and interchangeability appears paramount to the acceptance of these products, particularly for patients who are switched from a reference product,” Dr. Kaul noted in the Cardinal Health report.

Wherever supported by data, Dr. Kaul recommends incorporating biosimilar use and interchangeability into best practice guidelines going forward. “That will go a long way in disseminating the latest information on this topic and position this paradigm for increased adoption among providers.”

Some physicians like Dr. Snow aren’t that concerned with interchangeability. This hasn’t affected conversations with patients, he said. Multiple studies demonstrating the lack of antibody formation with multiple switches from different biosimilar drugs has eased his concern about multiple switches causing problems.

“Initially, there was a gap in demonstrating the long-term effect of multiple switches on antibody production and drug effectiveness. That gap has started to close as more data from Europe’s experience with biosimilars becomes available,” Dr. Snow said.
 

Resources for physicians, patients

The federal government has taken steps to advance biosimilars education and adoption. In 2021, President Biden signed the Advancing Education on Biosimilars Act into law, which directs the FDA to develop or improve continuing education programs that address prescribing of biosimilars and biological products.

The FDA provides educational materials on its website, including a comprehensive curriculum toolkit. The Accreditation Council for Medical Affairs has also created an online 40-hour curriculum for health care professionals called the Board-Certified Biologics and Biosimilars Specialist Program.

Dr. Fabbro recommended patients use the FDA page Biosimilar Basics for Patients to educate themselves on biosimilars. The Global Healthy Living Foundation’s podcast, Breaking Down Biosimilars, is another free resource for patients.

“While much has changed, the continued need for multistakeholder education, awareness, and dedicated research remains even more important as we expand into newer therapeutic areas and classes,” wrote the authors of the Cardinal Health report.

Help patients understand biologics and biosimilars by using AGA resources for providers and patients available at gastro.org/biosimilars.

Dr. Regueiro is on advisory boards and consults for AbbVie, Janssen, UCB, Takeda, Pfizer, Bristol-Myers Squibb, Organon, Amgen, Genentech, Gilead, Salix, Prometheus, Lilly, Celgene, TARGET PharmaSolutions, Trellis, and Boehringer Ingelheim. Dr. Fabbro is a principal investigator for Castle Biosciences, on the speakers bureau for Valchlor, and on the advisory boards of Janssen and Bristol-Myers Squibb. Dr. Popovian, Dr. Snow, Dr. Awsare, and Dr. Kaul had no disclosures.

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

Rheumatologist Marcus Snow, MD, is comfortable with prescribing biosimilars as a first-line, first-time biologic, and discussing them with patients.

“If a biosimilar is on the market, it has gone through rigorous study proving its effectiveness and equivalence to a bio-originator,” said Dr. Snow, a rheumatologist with the University of Nebraska Medical Center, Omaha, and chair of the American College of Rheumatology’s Committee on Rheumatologic Care.

The formulary makes a big difference in the conversation about options, he said. “The formularies dictate what we can prescribe. It may not be appropriate, but it is reality. The cost of biologics for a patient without insurance coverage makes it impossible to afford.”

He will often tell patients that he’ll fight any changes or formulary restrictions he does not agree with. “However, when I see patients in follow-up, even if there is no known change on the horizon, I may bring up biosimilars when we have a moment to chat about them to familiarize them with what may happen in the future.”

The need for patient education on biosimilars presents a barrier to realizing their potential to save money and expand choice, noted Cardinal Health in its 2023 biosimilars report. Of 103 rheumatologists who responded to a Cardinal Health survey, 85% agreed that patient education was important. But those conversations can take an uncomfortable turn if the patient pushes back against taking a biosimilar owing to cost or safety concerns.

It’s not uncommon for a patient to express some anxiety about biosimilars, especially if they’re doing well on a current treatment plan. Most patients do not want any changes that may lead to worsening disease control, Dr. Snow said.

Kaiser Permanente

Patients and physicians alike often don’t understand the mechanics of biosimilars. “There’s a lot of misinformation about this,” said Sameer Awsare, MD, an associate executive director for The Permanente Medical Group in Campbell, Calif. Patients should know that a biosimilar will be as clinically efficacious as the medicine they’ve been on, with the same safety profiles, said Dr. Awsare, who works with Kaiser Permanente’s pharmacy partners on biosimilars.
 

Insurance often drives the conversation

The global anti-inflammatory biologics market is anticipated to reach $150 billion by 2027, according to a recent CVS report. As of March 2023, the Food and Drug Administration had approved 40 biosimilars to 11 different reference products. There are 28 on the U.S. market and 100 more in development. Projected to save more than $180 billion over the next 5 years, they are anticipated to expand choice and drive competition.

Rheumatologists, dermatologists, and gastroenterologists are frequent prescribers, although their choices for immune-mediated inflammatory diseases are limited to tumor necrosis factor inhibitors (infliximab [Remicade] originator and adalimumab [Humira] originator) and anti-CD20 agents, such as rituximab (Rituxan) originator.

Benefit design or formulary usually dictates what medicine a patient receives. “Because of significantly higher out-of-pocket cost or formulary positioning, patients may end up with a generic or a biosimilar instead of a brand-name medicine or branded biologic,” said Robert Popovian, PharmD, MS, chief science policy officer of the Global Healthy Living Foundation.

Insurers rarely offer both Remicade and biosimilar infliximab, allowing the doctor to choose, said Miguel Regueiro, MD, chair of the Cleveland Clinic’s Digestive Disease & Surgery Institute, who prescribes infliximab biosimilars. Most often, the payer will choose the lower-cost biosimilar. “I am fine with the biosimilar, either as a new start or a switch from the reference product.”

However, the patient might feel differently. They can form an attachment to the reference medication if it has prevented severe illness. “They do not want to change, as they feel they are going on a ‘new’ medication that will not work as well,” Dr. Regueiro said.

This is where the education comes in: to reassure patients that a biosimilar will work just as well as the reference product. “For patients who have done well for years on a biologic, more time needs to be spent reassuring them and answering questions,” compared with a patient just starting on a biosimilar, he advised.

But not all physicians are quick to prescribe biosimilars.

Julie Miller Photography

Especially with psoriasis, which has so many strong options for reference drugs, a switch may be hard to justify, said dermatologist Stephanie K. Fabbro, MD, assistant professor at Northeast Ohio Medical University, Rootstown. “If I have a preference, I would rather switch a patient to a drug from a different class without a biosimilar option to reduce the possibility of pushback.”

Dr. Fabbro, part of the core faculty in the Riverside Methodist Hospital Dermatology Residency Program in Columbus, will share data from clinical trials and postmarket surveillance with patients to support her decision.
 

Conversations about cost

Patients may also push back if they don’t save money when switching to a biosimilar. “This dilemma raises the question of who is profiting when a biosimilar is dispensed,” Dr. Popovian said. Insurers and pharmacy benefit managers (PBMs) that take additional concessions from biopharmaceutical manufacturers in the form of rebates and fees will often pocket this money as profit instead of passing savings back to the patient to help reduce their out-of-pocket requirement, he added.

If an originator biologic and a biosimilar are available, “as a pharmacist, I will choose the medicine that will incur the lowest out-of-pocket cost for the patient,” Dr. Popovian said.

Discussing cost – and who dictates which biosimilar is on the formulary – is an important conversation to have with patients, said Vivek Kaul, MD, Segal-Watson Professor of Medicine at the University of Rochester (N.Y.) Medical Center.

Providing equivalent clinical efficacy while saving costs is the economic reality of biosimilars, Dr. Kaul said. Third-party payers regularly evaluate how to provide the same quality of care while saving money. Physicians and patients alike “must be mindful that as time goes on, if the science on biosimilars stays robust, if the adoption is more widespread and the cost-saving proposition turns out to be true, more formularies will be attracted to replacing the reference product with the biosimilar counterpart.”

Providers and patients can weigh the options if a formulary suddenly switches to a biosimilar, Dr. Kaul continued. “You can accept the novel product on the formulary or may have to face out-of-pocket expenses as a patient.” If providers and patients have concerns about the biosimilar, they can always appeal if there’s solid scientific evidence that supports reverting back to the reference product.

“If you think the biosimilar is equally efficacious, comes at a lower cost, and is right for the patient, then the providers should tell the patient that,” he added.

Some studies have questioned whether the biosimilars will save money, compared with the reference drug, Dr. Fabbro noted. Medicare, for example, may pay only for a certain percentage of an approved biosimilar, saddling the patient with a monthly copay costing thousands of dollars. “It is unclear whether biosimilar manufacturers will have the same level of patient support programs as the reference drug companies.”

For that reason, physicians should also inform patients about the robust patient assistance and copay assistance programs many reference drug manufacturers offer, she said.

Biosimilars 101: Familiarizing patients

Safety and ease of use are other common concerns about biosimilars. Patients may ask if the application is different, or why it’s advantageous to switch to a biosimilar, Dr. Awsare said.

Sometimes the syringe or injector for a biosimilar might look different from that of the originator drug, he said.

Anecdotally, Dr. Fabbro has heard stories of patients having injection reactions that they did not experience with the reference drug or having a disease flare-up after starting a biosimilar. 

rubberball/Getty Images

As is the case with reference products, in their conversations with patients, clinicians should address the adverse event profile of biosimilars, offering data points from published studies and clinical guidelines that support the use of these products. “There should be an emphasis on patient education around efficacy and any side effects, and how the profile of the reference product compares with a proposed biosimilar,” Dr. Kaul suggested.

When Dr. Snow discusses biosimilars and generics, “I make sure to share this in an understandable way based on the patient’s scientific background, or lack thereof,” he said. If there is enough time, he also discusses how European- and U.S.-sourced biologics are slightly different.

Pharmacists should tell patients to expect the same clinical outcomes from a biosimilar, Dr. Popovian said. However, if they have any reduction in efficacy or potential safety concerns, they should communicate with their physician or pharmacist immediately.

In Dr. Regueiro’s practice, a pharmacist specializing in inflammatory bowel disease often has a one-on-one meeting with patients to educate and answer questions. “Additionally, we provide them the Crohn’s and Colitis Foundation web link on biosimilars,” said Dr. Regueiro.
 

A village approach to education

When biosimilars first came out, there were no formal education materials, Dr. Awsare said. Kaiser Permanente decided to create its own educational materials, not just for patients but also to help educate its primary care doctors; the rheumatologists, dermatologists, and gastroenterologists using the biosimilars; the nurses infusing patients; and the pharmacists preparing the biosimilars.

The health system also has a different approach to choosing medication. Instead of having an insurance company or PBM decide what’s in the formulary, clinicians work with the pharmacists at Kaiser to look at clinical evidence and decide which biosimilar to use. Most of its plans also provide lower copays to patients when they use the biosimilar. 

This was the approach for Humira biosimilars, Dr. Awsare said. Eight will be on the market in 2023. “Our rheumatologists, dermatologists, and gastroenterologists looked at the data from Europe, looked at some real-world evidence, and then said: ‘We think this one’s going to be the best one for our patients.’ ”

Having clinicians choose the biosimilar instead of a health plan makes it a lot easier to have conversations with patients, he said. “Once we’ve moved that market share to that particular biosimilar, we give our physicians the time to have those discussions.”

Clinical pharmacists also provide educational support, offering guidance on issues such as side effects, as patients transition to the biosimilar. “We like to use the word ‘transition’ because it’s essentially the same biologic. So, you’re not actually switching,” Dr. Awsare said.

No consensus on interchangeability

Whether the conversation on interchangeability will affect patient conversations with physicians depends on who you ask.

If a biosimilar has an interchangeability designation, it means that the pharmacist can substitute it without the intervention of the clinician who prescribed the reference product. It does not relate to the quality, safety, or effectiveness of biosimilars or interchangeable biosimilar products, Dr. Popovian said.

The United States is the only country that has this designation. Even though it’s not identical to the originator drug, a biosimilar has the same clinical efficacy and safety profile. “So clinically, interchangeability is meaningless,” Dr. Awsare said.

In its report on biosimilars in the autoimmune category, CVS acknowledged that interchangeability was important but would not be a significant factor in driving adoption of biosimilars. However, in a Cardinal Health survey of 72 gastroenterologists, 38% cited the interchangeability of biosimilars as a top concern for adalimumab biosimilars, along with transitioning patients from Humira to a biosimilar (44%).

“Patient education regarding biosimilar safety, efficacy, and interchangeability appears paramount to the acceptance of these products, particularly for patients who are switched from a reference product,” Dr. Kaul noted in the Cardinal Health report.

Wherever supported by data, Dr. Kaul recommends incorporating biosimilar use and interchangeability into best practice guidelines going forward. “That will go a long way in disseminating the latest information on this topic and position this paradigm for increased adoption among providers.”

Some physicians like Dr. Snow aren’t that concerned with interchangeability. This hasn’t affected conversations with patients, he said. Multiple studies demonstrating the lack of antibody formation with multiple switches from different biosimilar drugs has eased his concern about multiple switches causing problems.

“Initially, there was a gap in demonstrating the long-term effect of multiple switches on antibody production and drug effectiveness. That gap has started to close as more data from Europe’s experience with biosimilars becomes available,” Dr. Snow said.
 

Resources for physicians, patients

The federal government has taken steps to advance biosimilars education and adoption. In 2021, President Biden signed the Advancing Education on Biosimilars Act into law, which directs the FDA to develop or improve continuing education programs that address prescribing of biosimilars and biological products.

The FDA provides educational materials on its website, including a comprehensive curriculum toolkit. The Accreditation Council for Medical Affairs has also created an online 40-hour curriculum for health care professionals called the Board-Certified Biologics and Biosimilars Specialist Program.

Dr. Fabbro recommended patients use the FDA page Biosimilar Basics for Patients to educate themselves on biosimilars. The Global Healthy Living Foundation’s podcast, Breaking Down Biosimilars, is another free resource for patients.

“While much has changed, the continued need for multistakeholder education, awareness, and dedicated research remains even more important as we expand into newer therapeutic areas and classes,” wrote the authors of the Cardinal Health report.

Help patients understand biologics and biosimilars by using AGA resources for providers and patients available at gastro.org/biosimilars.

Dr. Regueiro is on advisory boards and consults for AbbVie, Janssen, UCB, Takeda, Pfizer, Bristol-Myers Squibb, Organon, Amgen, Genentech, Gilead, Salix, Prometheus, Lilly, Celgene, TARGET PharmaSolutions, Trellis, and Boehringer Ingelheim. Dr. Fabbro is a principal investigator for Castle Biosciences, on the speakers bureau for Valchlor, and on the advisory boards of Janssen and Bristol-Myers Squibb. Dr. Popovian, Dr. Snow, Dr. Awsare, and Dr. Kaul had no disclosures.

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

Rheumatologist Marcus Snow, MD, is comfortable with prescribing biosimilars as a first-line, first-time biologic, and discussing them with patients.

“If a biosimilar is on the market, it has gone through rigorous study proving its effectiveness and equivalence to a bio-originator,” said Dr. Snow, a rheumatologist with the University of Nebraska Medical Center, Omaha, and chair of the American College of Rheumatology’s Committee on Rheumatologic Care.

The formulary makes a big difference in the conversation about options, he said. “The formularies dictate what we can prescribe. It may not be appropriate, but it is reality. The cost of biologics for a patient without insurance coverage makes it impossible to afford.”

He will often tell patients that he’ll fight any changes or formulary restrictions he does not agree with. “However, when I see patients in follow-up, even if there is no known change on the horizon, I may bring up biosimilars when we have a moment to chat about them to familiarize them with what may happen in the future.”

The need for patient education on biosimilars presents a barrier to realizing their potential to save money and expand choice, noted Cardinal Health in its 2023 biosimilars report. Of 103 rheumatologists who responded to a Cardinal Health survey, 85% agreed that patient education was important. But those conversations can take an uncomfortable turn if the patient pushes back against taking a biosimilar owing to cost or safety concerns.

It’s not uncommon for a patient to express some anxiety about biosimilars, especially if they’re doing well on a current treatment plan. Most patients do not want any changes that may lead to worsening disease control, Dr. Snow said.

Kaiser Permanente

Patients and physicians alike often don’t understand the mechanics of biosimilars. “There’s a lot of misinformation about this,” said Sameer Awsare, MD, an associate executive director for The Permanente Medical Group in Campbell, Calif. Patients should know that a biosimilar will be as clinically efficacious as the medicine they’ve been on, with the same safety profiles, said Dr. Awsare, who works with Kaiser Permanente’s pharmacy partners on biosimilars.
 

Insurance often drives the conversation

The global anti-inflammatory biologics market is anticipated to reach $150 billion by 2027, according to a recent CVS report. As of March 2023, the Food and Drug Administration had approved 40 biosimilars to 11 different reference products. There are 28 on the U.S. market and 100 more in development. Projected to save more than $180 billion over the next 5 years, they are anticipated to expand choice and drive competition.

Rheumatologists, dermatologists, and gastroenterologists are frequent prescribers, although their choices for immune-mediated inflammatory diseases are limited to tumor necrosis factor inhibitors (infliximab [Remicade] originator and adalimumab [Humira] originator) and anti-CD20 agents, such as rituximab (Rituxan) originator.

Benefit design or formulary usually dictates what medicine a patient receives. “Because of significantly higher out-of-pocket cost or formulary positioning, patients may end up with a generic or a biosimilar instead of a brand-name medicine or branded biologic,” said Robert Popovian, PharmD, MS, chief science policy officer of the Global Healthy Living Foundation.

Insurers rarely offer both Remicade and biosimilar infliximab, allowing the doctor to choose, said Miguel Regueiro, MD, chair of the Cleveland Clinic’s Digestive Disease & Surgery Institute, who prescribes infliximab biosimilars. Most often, the payer will choose the lower-cost biosimilar. “I am fine with the biosimilar, either as a new start or a switch from the reference product.”

However, the patient might feel differently. They can form an attachment to the reference medication if it has prevented severe illness. “They do not want to change, as they feel they are going on a ‘new’ medication that will not work as well,” Dr. Regueiro said.

This is where the education comes in: to reassure patients that a biosimilar will work just as well as the reference product. “For patients who have done well for years on a biologic, more time needs to be spent reassuring them and answering questions,” compared with a patient just starting on a biosimilar, he advised.

But not all physicians are quick to prescribe biosimilars.

Julie Miller Photography

Especially with psoriasis, which has so many strong options for reference drugs, a switch may be hard to justify, said dermatologist Stephanie K. Fabbro, MD, assistant professor at Northeast Ohio Medical University, Rootstown. “If I have a preference, I would rather switch a patient to a drug from a different class without a biosimilar option to reduce the possibility of pushback.”

Dr. Fabbro, part of the core faculty in the Riverside Methodist Hospital Dermatology Residency Program in Columbus, will share data from clinical trials and postmarket surveillance with patients to support her decision.
 

Conversations about cost

Patients may also push back if they don’t save money when switching to a biosimilar. “This dilemma raises the question of who is profiting when a biosimilar is dispensed,” Dr. Popovian said. Insurers and pharmacy benefit managers (PBMs) that take additional concessions from biopharmaceutical manufacturers in the form of rebates and fees will often pocket this money as profit instead of passing savings back to the patient to help reduce their out-of-pocket requirement, he added.

If an originator biologic and a biosimilar are available, “as a pharmacist, I will choose the medicine that will incur the lowest out-of-pocket cost for the patient,” Dr. Popovian said.

Discussing cost – and who dictates which biosimilar is on the formulary – is an important conversation to have with patients, said Vivek Kaul, MD, Segal-Watson Professor of Medicine at the University of Rochester (N.Y.) Medical Center.

Providing equivalent clinical efficacy while saving costs is the economic reality of biosimilars, Dr. Kaul said. Third-party payers regularly evaluate how to provide the same quality of care while saving money. Physicians and patients alike “must be mindful that as time goes on, if the science on biosimilars stays robust, if the adoption is more widespread and the cost-saving proposition turns out to be true, more formularies will be attracted to replacing the reference product with the biosimilar counterpart.”

Providers and patients can weigh the options if a formulary suddenly switches to a biosimilar, Dr. Kaul continued. “You can accept the novel product on the formulary or may have to face out-of-pocket expenses as a patient.” If providers and patients have concerns about the biosimilar, they can always appeal if there’s solid scientific evidence that supports reverting back to the reference product.

“If you think the biosimilar is equally efficacious, comes at a lower cost, and is right for the patient, then the providers should tell the patient that,” he added.

Some studies have questioned whether the biosimilars will save money, compared with the reference drug, Dr. Fabbro noted. Medicare, for example, may pay only for a certain percentage of an approved biosimilar, saddling the patient with a monthly copay costing thousands of dollars. “It is unclear whether biosimilar manufacturers will have the same level of patient support programs as the reference drug companies.”

For that reason, physicians should also inform patients about the robust patient assistance and copay assistance programs many reference drug manufacturers offer, she said.

Biosimilars 101: Familiarizing patients

Safety and ease of use are other common concerns about biosimilars. Patients may ask if the application is different, or why it’s advantageous to switch to a biosimilar, Dr. Awsare said.

Sometimes the syringe or injector for a biosimilar might look different from that of the originator drug, he said.

Anecdotally, Dr. Fabbro has heard stories of patients having injection reactions that they did not experience with the reference drug or having a disease flare-up after starting a biosimilar. 

rubberball/Getty Images

As is the case with reference products, in their conversations with patients, clinicians should address the adverse event profile of biosimilars, offering data points from published studies and clinical guidelines that support the use of these products. “There should be an emphasis on patient education around efficacy and any side effects, and how the profile of the reference product compares with a proposed biosimilar,” Dr. Kaul suggested.

When Dr. Snow discusses biosimilars and generics, “I make sure to share this in an understandable way based on the patient’s scientific background, or lack thereof,” he said. If there is enough time, he also discusses how European- and U.S.-sourced biologics are slightly different.

Pharmacists should tell patients to expect the same clinical outcomes from a biosimilar, Dr. Popovian said. However, if they have any reduction in efficacy or potential safety concerns, they should communicate with their physician or pharmacist immediately.

In Dr. Regueiro’s practice, a pharmacist specializing in inflammatory bowel disease often has a one-on-one meeting with patients to educate and answer questions. “Additionally, we provide them the Crohn’s and Colitis Foundation web link on biosimilars,” said Dr. Regueiro.
 

A village approach to education

When biosimilars first came out, there were no formal education materials, Dr. Awsare said. Kaiser Permanente decided to create its own educational materials, not just for patients but also to help educate its primary care doctors; the rheumatologists, dermatologists, and gastroenterologists using the biosimilars; the nurses infusing patients; and the pharmacists preparing the biosimilars.

The health system also has a different approach to choosing medication. Instead of having an insurance company or PBM decide what’s in the formulary, clinicians work with the pharmacists at Kaiser to look at clinical evidence and decide which biosimilar to use. Most of its plans also provide lower copays to patients when they use the biosimilar. 

This was the approach for Humira biosimilars, Dr. Awsare said. Eight will be on the market in 2023. “Our rheumatologists, dermatologists, and gastroenterologists looked at the data from Europe, looked at some real-world evidence, and then said: ‘We think this one’s going to be the best one for our patients.’ ”

Having clinicians choose the biosimilar instead of a health plan makes it a lot easier to have conversations with patients, he said. “Once we’ve moved that market share to that particular biosimilar, we give our physicians the time to have those discussions.”

Clinical pharmacists also provide educational support, offering guidance on issues such as side effects, as patients transition to the biosimilar. “We like to use the word ‘transition’ because it’s essentially the same biologic. So, you’re not actually switching,” Dr. Awsare said.

No consensus on interchangeability

Whether the conversation on interchangeability will affect patient conversations with physicians depends on who you ask.

If a biosimilar has an interchangeability designation, it means that the pharmacist can substitute it without the intervention of the clinician who prescribed the reference product. It does not relate to the quality, safety, or effectiveness of biosimilars or interchangeable biosimilar products, Dr. Popovian said.

The United States is the only country that has this designation. Even though it’s not identical to the originator drug, a biosimilar has the same clinical efficacy and safety profile. “So clinically, interchangeability is meaningless,” Dr. Awsare said.

In its report on biosimilars in the autoimmune category, CVS acknowledged that interchangeability was important but would not be a significant factor in driving adoption of biosimilars. However, in a Cardinal Health survey of 72 gastroenterologists, 38% cited the interchangeability of biosimilars as a top concern for adalimumab biosimilars, along with transitioning patients from Humira to a biosimilar (44%).

“Patient education regarding biosimilar safety, efficacy, and interchangeability appears paramount to the acceptance of these products, particularly for patients who are switched from a reference product,” Dr. Kaul noted in the Cardinal Health report.

Wherever supported by data, Dr. Kaul recommends incorporating biosimilar use and interchangeability into best practice guidelines going forward. “That will go a long way in disseminating the latest information on this topic and position this paradigm for increased adoption among providers.”

Some physicians like Dr. Snow aren’t that concerned with interchangeability. This hasn’t affected conversations with patients, he said. Multiple studies demonstrating the lack of antibody formation with multiple switches from different biosimilar drugs has eased his concern about multiple switches causing problems.

“Initially, there was a gap in demonstrating the long-term effect of multiple switches on antibody production and drug effectiveness. That gap has started to close as more data from Europe’s experience with biosimilars becomes available,” Dr. Snow said.
 

Resources for physicians, patients

The federal government has taken steps to advance biosimilars education and adoption. In 2021, President Biden signed the Advancing Education on Biosimilars Act into law, which directs the FDA to develop or improve continuing education programs that address prescribing of biosimilars and biological products.

The FDA provides educational materials on its website, including a comprehensive curriculum toolkit. The Accreditation Council for Medical Affairs has also created an online 40-hour curriculum for health care professionals called the Board-Certified Biologics and Biosimilars Specialist Program.

Dr. Fabbro recommended patients use the FDA page Biosimilar Basics for Patients to educate themselves on biosimilars. The Global Healthy Living Foundation’s podcast, Breaking Down Biosimilars, is another free resource for patients.

“While much has changed, the continued need for multistakeholder education, awareness, and dedicated research remains even more important as we expand into newer therapeutic areas and classes,” wrote the authors of the Cardinal Health report.

Help patients understand biologics and biosimilars by using AGA resources for providers and patients available at gastro.org/biosimilars.

Dr. Regueiro is on advisory boards and consults for AbbVie, Janssen, UCB, Takeda, Pfizer, Bristol-Myers Squibb, Organon, Amgen, Genentech, Gilead, Salix, Prometheus, Lilly, Celgene, TARGET PharmaSolutions, Trellis, and Boehringer Ingelheim. Dr. Fabbro is a principal investigator for Castle Biosciences, on the speakers bureau for Valchlor, and on the advisory boards of Janssen and Bristol-Myers Squibb. Dr. Popovian, Dr. Snow, Dr. Awsare, and Dr. Kaul had no disclosures.

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

Microbial biomarkers for type 1 diabetes may be present in infants as young as 12 months old, suggesting the potential to mitigate disease onset by nurturing a healthy gut microbiome early, show data from the Swedish general population.

“Our findings indicate that the gut of infants who go on to develop type 1 diabetes is notably different from healthy babies,” said Malin Bélteky, MD, from the Crown Princess Victoria’s Children’s Hospital, Linköping, Sweden, who jointly led the work, which was recently published in Diabetologia, alongside Patricia L. Milletich, PhD candidate, from the University of Florida, Gainesville.

“This discovery could be used to help identity infants at [the] highest risk of developing type 1 diabetes before or during the first stage of disease and could offer the opportunity to bolster a healthy gut microbiome to prevent the disease from becoming established,” added Dr. Bélteky.

Currently, beta-cell autoantibodies are used to predict disease, which are usually only identifiable between 9 and 36 months of age.

Marian Rewers, MD, PhD, professor of pediatrics & medicine, University of Colorado, Denver, and principal investigator of The Environmental Determinants of Diabetes in the Young (TEDDY) study, welcomed the findings, saying it is a well-designed study from a strong group of investigators.

“While the effective number of cases was very small [n = 16], the results were apparently adjusted for multiple comparisons, and significant differences were noted in the microbiome of cases versus controls at 1 year of age. This was 12 years prior to the average age of type 1 diabetes diagnosis in the cases,” he said.

“The differences in diversity and abundances of specific bacteria need to be interpreted with caution; however, the study results are consistent with several previous reports,” he noted.
 

Differences in microbial diversity and function

Data were drawn from children participating in the longitudinal, general population All Babies In Southeast Sweden (ABIS) study. Microbiota from stool samples, taken at age 1 year, were sequenced and analyzed to establish diversity, abundance, and functional status of the component bacteria. Questionnaires were completed at birth and at 1 year of age, allowing for the study of environmental factors that might influence the microbiota or type 1 diabetes risk independently. Parent diaries provided information on pregnancy, nutrition, and lifestyle factors.

Of the cohort of 167 children who developed type 1 diabetes by 2020, stool samples were available for 16 of these participants, which were compared with 268 healthy controls. The microbiomes of the 16 infants who later developed type 1 diabetes were compared with 100 iterations of 32 matched control infants (matched by geographical region, siblings at birth, residence type, duration of breastfeeding, and month of stool collection) who didn’t develop type 1 diabetes by the age of 20.

Specific bacteria found in greater abundance in children who later developed type 1 diabetes, compared with those who didn’t, included Firmicutes (Enterococcus, Gemella, and Hungatella), as well as Bacteroides (Bacteroides and Porphyromonas), known to promote inflammation and be involved in the immune response.

Bacteria with greater abundance in children who didn’t develop type 1 diabetes, compared with those who did, were Firmicutes (Anaerostipes, Flavonifractor, and Ruminococcaceae UBA1819, and Eubacterium). These species help maintain metabolic and immune health and produce butyrate, an important short-chain fatty acid that helps prevent inflammation and fuels the cells of the gut lining.

Alistipes were more abundant in infants who didn’t develop type 1 diabetes, and various abundances of Fusicatenibacter were the strongest factors for differentiating future type 1 diabetes, reported the researchers.

“Gut microbial biomarkers at 12 months would benefit the prediction opportunity well before the onset of multiple autoantibodies,” write the authors.

The youngest age at type 1 diabetes diagnosis was aged 1 year, 4 months, and the oldest was aged 21 years, 4 months. The mean age at diagnosis was 13.3 years.

The microbial differences found between infants who go on to develop type 1 diabetes and those who don’t also shed light on interactions between the developing immune system and short-chain fatty acid production and metabolism in childhood autoimmunity, write the authors.

Prior studies have found fewer short-chain fatty acid–producing microbiota in the gut of children with early-onset autoantibody development. This study confirmed these data, finding a decrease in butyrate-producing bacteria (Anaerostipes, Flavonifractor, Ruminococcaceae UBA1819, and Eubacterium) in infants who went on to develop type 1 diabetes. Likewise, a reduction in pyruvate fermentation was found in those infants with future disease.

According to coauthor Eric Triplett, PhD, from the University of Florida, Gainesville: “The autoimmune processes usually begin long before any clinical signs of disease appear, highlighting how differences in the makeup of the infant gut microbiome could shed important light on the complex interaction between the developing immune system, environmental exposures in childhood, and autoimmunity. Studies with much larger cohorts of prospectively traced individuals will be required to establish which are the strongest biomarkers and how effectively they can predict disease.”

The authors and Dr. Rewers have reported no relevant financial relationships.

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

Microbial biomarkers for type 1 diabetes may be present in infants as young as 12 months old, suggesting the potential to mitigate disease onset by nurturing a healthy gut microbiome early, show data from the Swedish general population.

“Our findings indicate that the gut of infants who go on to develop type 1 diabetes is notably different from healthy babies,” said Malin Bélteky, MD, from the Crown Princess Victoria’s Children’s Hospital, Linköping, Sweden, who jointly led the work, which was recently published in Diabetologia, alongside Patricia L. Milletich, PhD candidate, from the University of Florida, Gainesville.

“This discovery could be used to help identity infants at [the] highest risk of developing type 1 diabetes before or during the first stage of disease and could offer the opportunity to bolster a healthy gut microbiome to prevent the disease from becoming established,” added Dr. Bélteky.

Currently, beta-cell autoantibodies are used to predict disease, which are usually only identifiable between 9 and 36 months of age.

Marian Rewers, MD, PhD, professor of pediatrics & medicine, University of Colorado, Denver, and principal investigator of The Environmental Determinants of Diabetes in the Young (TEDDY) study, welcomed the findings, saying it is a well-designed study from a strong group of investigators.

“While the effective number of cases was very small [n = 16], the results were apparently adjusted for multiple comparisons, and significant differences were noted in the microbiome of cases versus controls at 1 year of age. This was 12 years prior to the average age of type 1 diabetes diagnosis in the cases,” he said.

“The differences in diversity and abundances of specific bacteria need to be interpreted with caution; however, the study results are consistent with several previous reports,” he noted.
 

Differences in microbial diversity and function

Data were drawn from children participating in the longitudinal, general population All Babies In Southeast Sweden (ABIS) study. Microbiota from stool samples, taken at age 1 year, were sequenced and analyzed to establish diversity, abundance, and functional status of the component bacteria. Questionnaires were completed at birth and at 1 year of age, allowing for the study of environmental factors that might influence the microbiota or type 1 diabetes risk independently. Parent diaries provided information on pregnancy, nutrition, and lifestyle factors.

Of the cohort of 167 children who developed type 1 diabetes by 2020, stool samples were available for 16 of these participants, which were compared with 268 healthy controls. The microbiomes of the 16 infants who later developed type 1 diabetes were compared with 100 iterations of 32 matched control infants (matched by geographical region, siblings at birth, residence type, duration of breastfeeding, and month of stool collection) who didn’t develop type 1 diabetes by the age of 20.

Specific bacteria found in greater abundance in children who later developed type 1 diabetes, compared with those who didn’t, included Firmicutes (Enterococcus, Gemella, and Hungatella), as well as Bacteroides (Bacteroides and Porphyromonas), known to promote inflammation and be involved in the immune response.

Bacteria with greater abundance in children who didn’t develop type 1 diabetes, compared with those who did, were Firmicutes (Anaerostipes, Flavonifractor, and Ruminococcaceae UBA1819, and Eubacterium). These species help maintain metabolic and immune health and produce butyrate, an important short-chain fatty acid that helps prevent inflammation and fuels the cells of the gut lining.

Alistipes were more abundant in infants who didn’t develop type 1 diabetes, and various abundances of Fusicatenibacter were the strongest factors for differentiating future type 1 diabetes, reported the researchers.

“Gut microbial biomarkers at 12 months would benefit the prediction opportunity well before the onset of multiple autoantibodies,” write the authors.

The youngest age at type 1 diabetes diagnosis was aged 1 year, 4 months, and the oldest was aged 21 years, 4 months. The mean age at diagnosis was 13.3 years.

The microbial differences found between infants who go on to develop type 1 diabetes and those who don’t also shed light on interactions between the developing immune system and short-chain fatty acid production and metabolism in childhood autoimmunity, write the authors.

Prior studies have found fewer short-chain fatty acid–producing microbiota in the gut of children with early-onset autoantibody development. This study confirmed these data, finding a decrease in butyrate-producing bacteria (Anaerostipes, Flavonifractor, Ruminococcaceae UBA1819, and Eubacterium) in infants who went on to develop type 1 diabetes. Likewise, a reduction in pyruvate fermentation was found in those infants with future disease.

According to coauthor Eric Triplett, PhD, from the University of Florida, Gainesville: “The autoimmune processes usually begin long before any clinical signs of disease appear, highlighting how differences in the makeup of the infant gut microbiome could shed important light on the complex interaction between the developing immune system, environmental exposures in childhood, and autoimmunity. Studies with much larger cohorts of prospectively traced individuals will be required to establish which are the strongest biomarkers and how effectively they can predict disease.”

The authors and Dr. Rewers have reported no relevant financial relationships.

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

Microbial biomarkers for type 1 diabetes may be present in infants as young as 12 months old, suggesting the potential to mitigate disease onset by nurturing a healthy gut microbiome early, show data from the Swedish general population.

“Our findings indicate that the gut of infants who go on to develop type 1 diabetes is notably different from healthy babies,” said Malin Bélteky, MD, from the Crown Princess Victoria’s Children’s Hospital, Linköping, Sweden, who jointly led the work, which was recently published in Diabetologia, alongside Patricia L. Milletich, PhD candidate, from the University of Florida, Gainesville.

“This discovery could be used to help identity infants at [the] highest risk of developing type 1 diabetes before or during the first stage of disease and could offer the opportunity to bolster a healthy gut microbiome to prevent the disease from becoming established,” added Dr. Bélteky.

Currently, beta-cell autoantibodies are used to predict disease, which are usually only identifiable between 9 and 36 months of age.

Marian Rewers, MD, PhD, professor of pediatrics & medicine, University of Colorado, Denver, and principal investigator of The Environmental Determinants of Diabetes in the Young (TEDDY) study, welcomed the findings, saying it is a well-designed study from a strong group of investigators.

“While the effective number of cases was very small [n = 16], the results were apparently adjusted for multiple comparisons, and significant differences were noted in the microbiome of cases versus controls at 1 year of age. This was 12 years prior to the average age of type 1 diabetes diagnosis in the cases,” he said.

“The differences in diversity and abundances of specific bacteria need to be interpreted with caution; however, the study results are consistent with several previous reports,” he noted.
 

Differences in microbial diversity and function

Data were drawn from children participating in the longitudinal, general population All Babies In Southeast Sweden (ABIS) study. Microbiota from stool samples, taken at age 1 year, were sequenced and analyzed to establish diversity, abundance, and functional status of the component bacteria. Questionnaires were completed at birth and at 1 year of age, allowing for the study of environmental factors that might influence the microbiota or type 1 diabetes risk independently. Parent diaries provided information on pregnancy, nutrition, and lifestyle factors.

Of the cohort of 167 children who developed type 1 diabetes by 2020, stool samples were available for 16 of these participants, which were compared with 268 healthy controls. The microbiomes of the 16 infants who later developed type 1 diabetes were compared with 100 iterations of 32 matched control infants (matched by geographical region, siblings at birth, residence type, duration of breastfeeding, and month of stool collection) who didn’t develop type 1 diabetes by the age of 20.

Specific bacteria found in greater abundance in children who later developed type 1 diabetes, compared with those who didn’t, included Firmicutes (Enterococcus, Gemella, and Hungatella), as well as Bacteroides (Bacteroides and Porphyromonas), known to promote inflammation and be involved in the immune response.

Bacteria with greater abundance in children who didn’t develop type 1 diabetes, compared with those who did, were Firmicutes (Anaerostipes, Flavonifractor, and Ruminococcaceae UBA1819, and Eubacterium). These species help maintain metabolic and immune health and produce butyrate, an important short-chain fatty acid that helps prevent inflammation and fuels the cells of the gut lining.

Alistipes were more abundant in infants who didn’t develop type 1 diabetes, and various abundances of Fusicatenibacter were the strongest factors for differentiating future type 1 diabetes, reported the researchers.

“Gut microbial biomarkers at 12 months would benefit the prediction opportunity well before the onset of multiple autoantibodies,” write the authors.

The youngest age at type 1 diabetes diagnosis was aged 1 year, 4 months, and the oldest was aged 21 years, 4 months. The mean age at diagnosis was 13.3 years.

The microbial differences found between infants who go on to develop type 1 diabetes and those who don’t also shed light on interactions between the developing immune system and short-chain fatty acid production and metabolism in childhood autoimmunity, write the authors.

Prior studies have found fewer short-chain fatty acid–producing microbiota in the gut of children with early-onset autoantibody development. This study confirmed these data, finding a decrease in butyrate-producing bacteria (Anaerostipes, Flavonifractor, Ruminococcaceae UBA1819, and Eubacterium) in infants who went on to develop type 1 diabetes. Likewise, a reduction in pyruvate fermentation was found in those infants with future disease.

According to coauthor Eric Triplett, PhD, from the University of Florida, Gainesville: “The autoimmune processes usually begin long before any clinical signs of disease appear, highlighting how differences in the makeup of the infant gut microbiome could shed important light on the complex interaction between the developing immune system, environmental exposures in childhood, and autoimmunity. Studies with much larger cohorts of prospectively traced individuals will be required to establish which are the strongest biomarkers and how effectively they can predict disease.”

The authors and Dr. Rewers have reported no relevant financial relationships.

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

At a joint meeting of two Food and Drug Administration advisory committees on March 29, panelists voted to modify two aspects of the iPLEDGE Risk Evaluation and Mitigation Strategy (REMS) for isotretinoin, a drug for severe, nodular acne that is highly teratogenic.

The first vote was on whether to continue the 19-day lockout period for patients who can become pregnant and do not pick up their first prescription of isotretinoin within the 7-day prescription window. Those patients currently have to wait 19 days to get their second pregnancy test and receive the medication.

Most (17) of the 22 voting members voted not to continue the 19-day period; 4 voted to keep it; and 1 abstained. But there was no consensus on when the second pregnancy test should occur if the 19-day lockout is changed.

Ken Katz, MD, MSc, a dermatologist at Kaiser Permanente in San Francisco, was among those voting not to continue the 19-day lockout.

“I think this places an unduly high burden physically and psychologically on our patients. It seems arbitrary,” he said. “Likely we will miss some pregnancies; we are missing some already. But the burden is not matched by the benefit.”

The second question concerned patients who cannot become pregnant, and it asked when REMS should require that the prescriber document counseling the patient in the iPLEDGE system. The current requirement is monthly.

Listed options and the number of votes for each were:

• Only with the first prescription as part of patient enrollment (10)
• Monthly (1)
• Every 120 days (6)
• Some other frequency (5)

For this question too, while the members largely agreed the current monthly requirement is too burdensome, there was little agreement on what the most appropriate interval should be.

Lack of data

On both questions, several advisory committee members cited a lack of data on which they could base their decision.

On the documentation question, Megha Tollefson, MD, professor of dermatology at the Mayo Clinic, Rochester, Minn., said she voted for the fourth option (some other frequency) with the thought of yearly attestation.

“As a part of this, providers have to provide monthly counseling,” Dr. Tollefson said. “This is just a documentation requirement in the iPLEDGE system. I think most prescribers do document their monthly counseling in their own medical records. I would say it would be okay not to redocument that in iPLEDGE.”

The two votes came at the end of the second day of a joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and Dermatologic and Ophthalmic Drugs Advisory Committee in which experts addressed ways to improve the iPLEDGE REMS for isotretinoin. A transition to a new platform for the iPLEDGE program caused chaos after its rollout at the end of 2021, resulting in extensive delays and denial of prescriptions.

The committees sought to balance reducing burden with maintaining safety and preventing fetal exposures to isotretinoin.

They were also tasked with discussing other REMS requirements without taking a vote on each topic.

Among those topics was whether home pregnancy tests, allowed during the COVID-19 public health emergency, should continue to be allowed. Most who spoke to the issue agreed that home tests should continue in an effort to increase access and decrease burden. Members suggested safeguards against falsified results that have been documented, including assigning names and barcodes to the test results and uploading the verification to the iPLEDGE website.

The advisory committees also discussed recommendations to encourage more participation in the iPLEDGE Pregnancy Registry.

The advisory committees’ recommendations to the FDA are nonbinding, but the FDA generally follows the recommendations of advisory panels.

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

At a joint meeting of two Food and Drug Administration advisory committees on March 29, panelists voted to modify two aspects of the iPLEDGE Risk Evaluation and Mitigation Strategy (REMS) for isotretinoin, a drug for severe, nodular acne that is highly teratogenic.

The first vote was on whether to continue the 19-day lockout period for patients who can become pregnant and do not pick up their first prescription of isotretinoin within the 7-day prescription window. Those patients currently have to wait 19 days to get their second pregnancy test and receive the medication.

Most (17) of the 22 voting members voted not to continue the 19-day period; 4 voted to keep it; and 1 abstained. But there was no consensus on when the second pregnancy test should occur if the 19-day lockout is changed.

Ken Katz, MD, MSc, a dermatologist at Kaiser Permanente in San Francisco, was among those voting not to continue the 19-day lockout.

“I think this places an unduly high burden physically and psychologically on our patients. It seems arbitrary,” he said. “Likely we will miss some pregnancies; we are missing some already. But the burden is not matched by the benefit.”

The second question concerned patients who cannot become pregnant, and it asked when REMS should require that the prescriber document counseling the patient in the iPLEDGE system. The current requirement is monthly.

Listed options and the number of votes for each were:

• Only with the first prescription as part of patient enrollment (10)
• Monthly (1)
• Every 120 days (6)
• Some other frequency (5)

For this question too, while the members largely agreed the current monthly requirement is too burdensome, there was little agreement on what the most appropriate interval should be.

Lack of data

On both questions, several advisory committee members cited a lack of data on which they could base their decision.

On the documentation question, Megha Tollefson, MD, professor of dermatology at the Mayo Clinic, Rochester, Minn., said she voted for the fourth option (some other frequency) with the thought of yearly attestation.

“As a part of this, providers have to provide monthly counseling,” Dr. Tollefson said. “This is just a documentation requirement in the iPLEDGE system. I think most prescribers do document their monthly counseling in their own medical records. I would say it would be okay not to redocument that in iPLEDGE.”

The two votes came at the end of the second day of a joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and Dermatologic and Ophthalmic Drugs Advisory Committee in which experts addressed ways to improve the iPLEDGE REMS for isotretinoin. A transition to a new platform for the iPLEDGE program caused chaos after its rollout at the end of 2021, resulting in extensive delays and denial of prescriptions.

The committees sought to balance reducing burden with maintaining safety and preventing fetal exposures to isotretinoin.

They were also tasked with discussing other REMS requirements without taking a vote on each topic.

Among those topics was whether home pregnancy tests, allowed during the COVID-19 public health emergency, should continue to be allowed. Most who spoke to the issue agreed that home tests should continue in an effort to increase access and decrease burden. Members suggested safeguards against falsified results that have been documented, including assigning names and barcodes to the test results and uploading the verification to the iPLEDGE website.

The advisory committees also discussed recommendations to encourage more participation in the iPLEDGE Pregnancy Registry.

The advisory committees’ recommendations to the FDA are nonbinding, but the FDA generally follows the recommendations of advisory panels.

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

At a joint meeting of two Food and Drug Administration advisory committees on March 29, panelists voted to modify two aspects of the iPLEDGE Risk Evaluation and Mitigation Strategy (REMS) for isotretinoin, a drug for severe, nodular acne that is highly teratogenic.

The first vote was on whether to continue the 19-day lockout period for patients who can become pregnant and do not pick up their first prescription of isotretinoin within the 7-day prescription window. Those patients currently have to wait 19 days to get their second pregnancy test and receive the medication.

Most (17) of the 22 voting members voted not to continue the 19-day period; 4 voted to keep it; and 1 abstained. But there was no consensus on when the second pregnancy test should occur if the 19-day lockout is changed.

Ken Katz, MD, MSc, a dermatologist at Kaiser Permanente in San Francisco, was among those voting not to continue the 19-day lockout.

“I think this places an unduly high burden physically and psychologically on our patients. It seems arbitrary,” he said. “Likely we will miss some pregnancies; we are missing some already. But the burden is not matched by the benefit.”

The second question concerned patients who cannot become pregnant, and it asked when REMS should require that the prescriber document counseling the patient in the iPLEDGE system. The current requirement is monthly.

Listed options and the number of votes for each were:

• Only with the first prescription as part of patient enrollment (10)
• Monthly (1)
• Every 120 days (6)
• Some other frequency (5)

For this question too, while the members largely agreed the current monthly requirement is too burdensome, there was little agreement on what the most appropriate interval should be.

Lack of data

On both questions, several advisory committee members cited a lack of data on which they could base their decision.

On the documentation question, Megha Tollefson, MD, professor of dermatology at the Mayo Clinic, Rochester, Minn., said she voted for the fourth option (some other frequency) with the thought of yearly attestation.

“As a part of this, providers have to provide monthly counseling,” Dr. Tollefson said. “This is just a documentation requirement in the iPLEDGE system. I think most prescribers do document their monthly counseling in their own medical records. I would say it would be okay not to redocument that in iPLEDGE.”

The two votes came at the end of the second day of a joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and Dermatologic and Ophthalmic Drugs Advisory Committee in which experts addressed ways to improve the iPLEDGE REMS for isotretinoin. A transition to a new platform for the iPLEDGE program caused chaos after its rollout at the end of 2021, resulting in extensive delays and denial of prescriptions.

The committees sought to balance reducing burden with maintaining safety and preventing fetal exposures to isotretinoin.

They were also tasked with discussing other REMS requirements without taking a vote on each topic.

Among those topics was whether home pregnancy tests, allowed during the COVID-19 public health emergency, should continue to be allowed. Most who spoke to the issue agreed that home tests should continue in an effort to increase access and decrease burden. Members suggested safeguards against falsified results that have been documented, including assigning names and barcodes to the test results and uploading the verification to the iPLEDGE website.

The advisory committees also discussed recommendations to encourage more participation in the iPLEDGE Pregnancy Registry.

The advisory committees’ recommendations to the FDA are nonbinding, but the FDA generally follows the recommendations of advisory panels.

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

Getting sweet on sweat

Are you the sort of person who struggles in social situations? Have the past 3 years been a secret respite from the terror and exhaustion of meeting new people? We understand your plight. People kind of suck. And you don’t have to look far to be reminded of it.

Unfortunately, on occasion we all have to interact with other human beings. If you suffer from social anxiety, this is not a fun thing to do. But new research indicates that there may be a way to alleviate the stress for those with social anxiety: armpits.

alex bracken/Unsplash

Specifically, sweat from the armpits of other people. Yes, this means a group of scientists gathered up some volunteers and collected their armpit sweat while the volunteers watched a variety of movies (horror, comedy, romance, etc.). Our condolences to the poor unpaid interns tasked with gathering the sweat.

Once they had their precious new medicine, the researchers took a group of women and administered a round of mindfulness therapy. Some of the participants then received the various sweats, while the rest were forced to smell only clean air. (The horror!) Lo and behold, the sweat groups had their anxiety scores reduced by about 40% after their therapy, compared with just 17% in the control group.

The researchers also found that the source of the sweat didn’t matter. Their study subjects responded the same to sweat excreted during a scary movie as they did to sweat from a comedy, a result that surprised the researchers. They suggested chemosignals in the sweat may affect the treatment response and advised further research. Which means more sweat collection! They plan on testing emotionally neutral movies next time, and if we can make a humble suggestion, they also should try the sweatiest movies.

Before the Food and Drug Administration can approve armpit sweat as a treatment for social anxiety, we have some advice for those shut-in introverts out there. Next time you have to interact with rabid extroverts, instead of shaking their hands, walk up to them and take a deep whiff of their armpits. Establish dominance. Someone will feel awkward, and science has proved it won’t be you.
 

The puff that vaccinates

Ever been shot with a Nerf gun or hit with a foam pool tube? More annoying than painful, right? If we asked if you’d rather get pelted with one of those than receive a traditional vaccine injection, you would choose the former. Maybe someday you actually will.

Dr. Jeremiah Gassensmith

During the boredom of the early pandemic lockdown, Jeremiah Gassensmith, PhD, of the department of chemistry and biochemistry at the University of Texas, Dallas, ordered a compressed gas–powered jet injection system to fool around with at home. Hey, who didn’t? Anyway, when it was time to go back to the lab he handed it over to one of his grad students, Yalini Wijesundara, and asked her to see what could be done with it.

In her tinkering she found that the jet injector could deliver metal-organic frameworks (MOFs) that can hold a bunch of different materials, like proteins and nucleic acids, through the skin.

Thus the “MOF-Jet” was born!

Jet injectors are nothing new, but they hurt. The MOF-Jet, however, is practically painless and cheaper than the gene guns that veterinarians use to inject biological cargo attached to the surface of a metal microparticle.

Changing the carrier gas also changes the time needed to break down the MOF and thus alters delivery of the drug inside. “If you shoot it with carbon dioxide, it will release its cargo faster within cells; if you use regular air, it will take 4 or 5 days,” Ms. Wijesundara explained in a written statement. That means the same drug could be released over different timescales without changing its formulation.

While testing on onion cells and mice, Ms. Wijesundara noted that it was as easy as “pointing and shooting” to distribute the puff of gas into the cells. A saving grace to those with needle anxiety. Not that we would know anything about needle anxiety.

More testing needs to be done before bringing this technology to human use, obviously, but we’re looking forward to saying goodbye to that dreaded prick and hello to a puff.
 

Your hippocampus is showing

Brain anatomy is one of the many, many things that’s not really our thing, but we do know a cool picture when we see one. Case in point: The image just below, which happens to be a full-scale, single-cell resolution model of the CA1 region of the hippocampus that “replicates the structure and architecture of the area, along with the position and relative connectivity of the neurons,” according to a statement from the Human Brain Project.

Dr. Michele Migliore

“We have performed a data mining operation on high resolution images of the human hippocampus, obtained from the BigBrain database. The position of individual neurons has been derived from a detailed analysis of these images,” said senior author Michele Migliore, PhD, of the Italian National Research Council’s Institute of Biophysics in Palermo.

Yes, he did say BigBrain database. BigBrain is – we checked and it’s definitely not this – a 3D model of a brain that was sectioned into 7,404 slices just 20 micrometers thick and then scanned by MRI. Digital reconstruction of those slices was done by supercomputer and the results are now available for analysis.

Dr. Migliore and his associates developed an image-processing algorithm to obtain neuronal positioning distribution and an algorithm to generate neuronal connectivity by approximating the shapes of dendrites and axons. (Our brains are starting to hurt just trying to write this.) “Some fit into narrow cones, others have a broad complex extension that can be approximated by dedicated geometrical volumes, and the connectivity to nearby neurons changes accordingly,” explained lead author Daniela Gandolfi of the University of Modena (Italy) and Reggio Emilia.

The investigators have made their dataset and the extraction methodology available on the EBRAINS platform and through the Human Brain Project and are moving on to other brain regions. And then, once everyone can find their way in and around the old gray matter, it should bring an end to conversations like this, which no doubt occur between male and female neuroscientists every day:

“Arnold, I think we’re lost.”

“Don’t worry, Bev, I know where I’m going.”

“Stop and ask this lady for directions.”

“I said I can find it.”

“Just ask her.”

“Fine. Excuse me, ma’am, can you tell us how to get to the corpora quadrigemina from here?

Getting sweet on sweat

Are you the sort of person who struggles in social situations? Have the past 3 years been a secret respite from the terror and exhaustion of meeting new people? We understand your plight. People kind of suck. And you don’t have to look far to be reminded of it.

Unfortunately, on occasion we all have to interact with other human beings. If you suffer from social anxiety, this is not a fun thing to do. But new research indicates that there may be a way to alleviate the stress for those with social anxiety: armpits.

alex bracken/Unsplash

Specifically, sweat from the armpits of other people. Yes, this means a group of scientists gathered up some volunteers and collected their armpit sweat while the volunteers watched a variety of movies (horror, comedy, romance, etc.). Our condolences to the poor unpaid interns tasked with gathering the sweat.

Once they had their precious new medicine, the researchers took a group of women and administered a round of mindfulness therapy. Some of the participants then received the various sweats, while the rest were forced to smell only clean air. (The horror!) Lo and behold, the sweat groups had their anxiety scores reduced by about 40% after their therapy, compared with just 17% in the control group.

The researchers also found that the source of the sweat didn’t matter. Their study subjects responded the same to sweat excreted during a scary movie as they did to sweat from a comedy, a result that surprised the researchers. They suggested chemosignals in the sweat may affect the treatment response and advised further research. Which means more sweat collection! They plan on testing emotionally neutral movies next time, and if we can make a humble suggestion, they also should try the sweatiest movies.

Before the Food and Drug Administration can approve armpit sweat as a treatment for social anxiety, we have some advice for those shut-in introverts out there. Next time you have to interact with rabid extroverts, instead of shaking their hands, walk up to them and take a deep whiff of their armpits. Establish dominance. Someone will feel awkward, and science has proved it won’t be you.
 

The puff that vaccinates

Ever been shot with a Nerf gun or hit with a foam pool tube? More annoying than painful, right? If we asked if you’d rather get pelted with one of those than receive a traditional vaccine injection, you would choose the former. Maybe someday you actually will.

Dr. Jeremiah Gassensmith

During the boredom of the early pandemic lockdown, Jeremiah Gassensmith, PhD, of the department of chemistry and biochemistry at the University of Texas, Dallas, ordered a compressed gas–powered jet injection system to fool around with at home. Hey, who didn’t? Anyway, when it was time to go back to the lab he handed it over to one of his grad students, Yalini Wijesundara, and asked her to see what could be done with it.

In her tinkering she found that the jet injector could deliver metal-organic frameworks (MOFs) that can hold a bunch of different materials, like proteins and nucleic acids, through the skin.

Thus the “MOF-Jet” was born!

Jet injectors are nothing new, but they hurt. The MOF-Jet, however, is practically painless and cheaper than the gene guns that veterinarians use to inject biological cargo attached to the surface of a metal microparticle.

Changing the carrier gas also changes the time needed to break down the MOF and thus alters delivery of the drug inside. “If you shoot it with carbon dioxide, it will release its cargo faster within cells; if you use regular air, it will take 4 or 5 days,” Ms. Wijesundara explained in a written statement. That means the same drug could be released over different timescales without changing its formulation.

While testing on onion cells and mice, Ms. Wijesundara noted that it was as easy as “pointing and shooting” to distribute the puff of gas into the cells. A saving grace to those with needle anxiety. Not that we would know anything about needle anxiety.

More testing needs to be done before bringing this technology to human use, obviously, but we’re looking forward to saying goodbye to that dreaded prick and hello to a puff.
 

Your hippocampus is showing

Brain anatomy is one of the many, many things that’s not really our thing, but we do know a cool picture when we see one. Case in point: The image just below, which happens to be a full-scale, single-cell resolution model of the CA1 region of the hippocampus that “replicates the structure and architecture of the area, along with the position and relative connectivity of the neurons,” according to a statement from the Human Brain Project.

Dr. Michele Migliore

“We have performed a data mining operation on high resolution images of the human hippocampus, obtained from the BigBrain database. The position of individual neurons has been derived from a detailed analysis of these images,” said senior author Michele Migliore, PhD, of the Italian National Research Council’s Institute of Biophysics in Palermo.

Yes, he did say BigBrain database. BigBrain is – we checked and it’s definitely not this – a 3D model of a brain that was sectioned into 7,404 slices just 20 micrometers thick and then scanned by MRI. Digital reconstruction of those slices was done by supercomputer and the results are now available for analysis.

Dr. Migliore and his associates developed an image-processing algorithm to obtain neuronal positioning distribution and an algorithm to generate neuronal connectivity by approximating the shapes of dendrites and axons. (Our brains are starting to hurt just trying to write this.) “Some fit into narrow cones, others have a broad complex extension that can be approximated by dedicated geometrical volumes, and the connectivity to nearby neurons changes accordingly,” explained lead author Daniela Gandolfi of the University of Modena (Italy) and Reggio Emilia.

The investigators have made their dataset and the extraction methodology available on the EBRAINS platform and through the Human Brain Project and are moving on to other brain regions. And then, once everyone can find their way in and around the old gray matter, it should bring an end to conversations like this, which no doubt occur between male and female neuroscientists every day:

“Arnold, I think we’re lost.”

“Don’t worry, Bev, I know where I’m going.”

“Stop and ask this lady for directions.”

“I said I can find it.”

“Just ask her.”

“Fine. Excuse me, ma’am, can you tell us how to get to the corpora quadrigemina from here?

Getting sweet on sweat

Are you the sort of person who struggles in social situations? Have the past 3 years been a secret respite from the terror and exhaustion of meeting new people? We understand your plight. People kind of suck. And you don’t have to look far to be reminded of it.

Unfortunately, on occasion we all have to interact with other human beings. If you suffer from social anxiety, this is not a fun thing to do. But new research indicates that there may be a way to alleviate the stress for those with social anxiety: armpits.

alex bracken/Unsplash

Specifically, sweat from the armpits of other people. Yes, this means a group of scientists gathered up some volunteers and collected their armpit sweat while the volunteers watched a variety of movies (horror, comedy, romance, etc.). Our condolences to the poor unpaid interns tasked with gathering the sweat.

Once they had their precious new medicine, the researchers took a group of women and administered a round of mindfulness therapy. Some of the participants then received the various sweats, while the rest were forced to smell only clean air. (The horror!) Lo and behold, the sweat groups had their anxiety scores reduced by about 40% after their therapy, compared with just 17% in the control group.

The researchers also found that the source of the sweat didn’t matter. Their study subjects responded the same to sweat excreted during a scary movie as they did to sweat from a comedy, a result that surprised the researchers. They suggested chemosignals in the sweat may affect the treatment response and advised further research. Which means more sweat collection! They plan on testing emotionally neutral movies next time, and if we can make a humble suggestion, they also should try the sweatiest movies.

Before the Food and Drug Administration can approve armpit sweat as a treatment for social anxiety, we have some advice for those shut-in introverts out there. Next time you have to interact with rabid extroverts, instead of shaking their hands, walk up to them and take a deep whiff of their armpits. Establish dominance. Someone will feel awkward, and science has proved it won’t be you.
 

The puff that vaccinates

Ever been shot with a Nerf gun or hit with a foam pool tube? More annoying than painful, right? If we asked if you’d rather get pelted with one of those than receive a traditional vaccine injection, you would choose the former. Maybe someday you actually will.

Dr. Jeremiah Gassensmith

During the boredom of the early pandemic lockdown, Jeremiah Gassensmith, PhD, of the department of chemistry and biochemistry at the University of Texas, Dallas, ordered a compressed gas–powered jet injection system to fool around with at home. Hey, who didn’t? Anyway, when it was time to go back to the lab he handed it over to one of his grad students, Yalini Wijesundara, and asked her to see what could be done with it.

In her tinkering she found that the jet injector could deliver metal-organic frameworks (MOFs) that can hold a bunch of different materials, like proteins and nucleic acids, through the skin.

Thus the “MOF-Jet” was born!

Jet injectors are nothing new, but they hurt. The MOF-Jet, however, is practically painless and cheaper than the gene guns that veterinarians use to inject biological cargo attached to the surface of a metal microparticle.

Changing the carrier gas also changes the time needed to break down the MOF and thus alters delivery of the drug inside. “If you shoot it with carbon dioxide, it will release its cargo faster within cells; if you use regular air, it will take 4 or 5 days,” Ms. Wijesundara explained in a written statement. That means the same drug could be released over different timescales without changing its formulation.

While testing on onion cells and mice, Ms. Wijesundara noted that it was as easy as “pointing and shooting” to distribute the puff of gas into the cells. A saving grace to those with needle anxiety. Not that we would know anything about needle anxiety.

More testing needs to be done before bringing this technology to human use, obviously, but we’re looking forward to saying goodbye to that dreaded prick and hello to a puff.
 

Your hippocampus is showing

Brain anatomy is one of the many, many things that’s not really our thing, but we do know a cool picture when we see one. Case in point: The image just below, which happens to be a full-scale, single-cell resolution model of the CA1 region of the hippocampus that “replicates the structure and architecture of the area, along with the position and relative connectivity of the neurons,” according to a statement from the Human Brain Project.

Dr. Michele Migliore

“We have performed a data mining operation on high resolution images of the human hippocampus, obtained from the BigBrain database. The position of individual neurons has been derived from a detailed analysis of these images,” said senior author Michele Migliore, PhD, of the Italian National Research Council’s Institute of Biophysics in Palermo.

Yes, he did say BigBrain database. BigBrain is – we checked and it’s definitely not this – a 3D model of a brain that was sectioned into 7,404 slices just 20 micrometers thick and then scanned by MRI. Digital reconstruction of those slices was done by supercomputer and the results are now available for analysis.

Dr. Migliore and his associates developed an image-processing algorithm to obtain neuronal positioning distribution and an algorithm to generate neuronal connectivity by approximating the shapes of dendrites and axons. (Our brains are starting to hurt just trying to write this.) “Some fit into narrow cones, others have a broad complex extension that can be approximated by dedicated geometrical volumes, and the connectivity to nearby neurons changes accordingly,” explained lead author Daniela Gandolfi of the University of Modena (Italy) and Reggio Emilia.

The investigators have made their dataset and the extraction methodology available on the EBRAINS platform and through the Human Brain Project and are moving on to other brain regions. And then, once everyone can find their way in and around the old gray matter, it should bring an end to conversations like this, which no doubt occur between male and female neuroscientists every day:

“Arnold, I think we’re lost.”

“Don’t worry, Bev, I know where I’m going.”

“Stop and ask this lady for directions.”

“I said I can find it.”

“Just ask her.”

“Fine. Excuse me, ma’am, can you tell us how to get to the corpora quadrigemina from here?

The Food and Drug Administration has approved over-the-counter sales of the overdose reversal agent Narcan (naloxone, Emergent BioSolutions). Greater access to the drug should mean more lives saved. However, it’s unclear how much the nasal spray will cost and whether pharmacies will stock the product openly on shelves. 

Currently, major pharmacy chains such as CVS and Walgreens make naloxone available without prescription, but consumers have to ask a pharmacist to dispense the drug.

“The major question is what is it going to cost,” Brian Hurley, MD, MBA, president-elect of the American Society of Addiction Medicine, said in an interview. “In order for people to access it they have to be able to afford it.”

“We won’t accomplish much if people can’t afford to buy Narcan,” said Chuck Ingoglia, president and CEO of the National Council for Mental Wellbeing, in a statement. Still, he applauded the FDA.

“No single approach will end overdose deaths but making Narcan easy to obtain and widely available likely will save countless lives annually,” he said.

“The timeline for availability and price of this OTC product is determined by the manufacturer,” the FDA said in a statement.

Commissioner Robert M. Califf, MD, called for the drug’s manufacturer to “make accessibility to the product a priority by making it available as soon as possible and at an affordable price.”

Emergent BioSolutions did not comment on cost. It said in a statement that the spray “will be available on U.S. shelves and at online retailers by the late summer,” after it has adapted Narcan for direct-to-consumer use, including more consumer-oriented packaging.

Naloxone’s cost varies, depending on geographic location and whether it is generic. According to GoodRX, a box containing two doses of generic naloxone costs $31-$100, depending on location and coupon availability.

A two-dose box of Narcan costs $135-$140. Emergent reported a 14% decline in naloxone sales in 2022 – to $373.7 million – blaming it in part on the introduction of generic formulations.

Dr. Hurley said he expects those who purchase Narcan at a drug store will primarily already be shopping there. It may or may not be those who most often experience overdose, such as people leaving incarceration or experiencing homelessness.

Having Narcan available over-the-counter “is an important supplement but it doesn’t replace the existing array of naloxone distribution programs,” Dr. Hurley said.

The FDA has encouraged naloxone manufacturers to seek OTC approval for the medication since at least 2019, when it designed a model label for a theoretical OTC product.

In November, the agency said it had determined that some naloxone products had the potential to be safe and effective for OTC use and again urged drugmakers to seek such an approval.

Emergent BioSolutions was the first to pursue OTC approval, but another manufacturer – the nonprofit Harm Reduction Therapeutics – is awaiting approval of its application to sell its spray directly to consumers.

Scott Gottlieb, MD, who was the FDA commissioner from 2017 to 2019, said in a tweet that more work needed to be done.

“This regulatory move should be followed by a strong push by elected officials to support wider deployment of Narcan, getting more doses into the hands of at risk households and frontline workers,” he tweeted.

Mr. Ingoglia said that “Narcan represents a second chance. By giving people a second chance, we also give them an opportunity to enter treatment if they so choose. You can’t recover if you’re dead, and we shouldn’t turn our backs on those who may choose a pathway to recovery that includes treatment.”
 

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

The Food and Drug Administration has approved over-the-counter sales of the overdose reversal agent Narcan (naloxone, Emergent BioSolutions). Greater access to the drug should mean more lives saved. However, it’s unclear how much the nasal spray will cost and whether pharmacies will stock the product openly on shelves. 

Currently, major pharmacy chains such as CVS and Walgreens make naloxone available without prescription, but consumers have to ask a pharmacist to dispense the drug.

“The major question is what is it going to cost,” Brian Hurley, MD, MBA, president-elect of the American Society of Addiction Medicine, said in an interview. “In order for people to access it they have to be able to afford it.”

“We won’t accomplish much if people can’t afford to buy Narcan,” said Chuck Ingoglia, president and CEO of the National Council for Mental Wellbeing, in a statement. Still, he applauded the FDA.

“No single approach will end overdose deaths but making Narcan easy to obtain and widely available likely will save countless lives annually,” he said.

“The timeline for availability and price of this OTC product is determined by the manufacturer,” the FDA said in a statement.

Commissioner Robert M. Califf, MD, called for the drug’s manufacturer to “make accessibility to the product a priority by making it available as soon as possible and at an affordable price.”

Emergent BioSolutions did not comment on cost. It said in a statement that the spray “will be available on U.S. shelves and at online retailers by the late summer,” after it has adapted Narcan for direct-to-consumer use, including more consumer-oriented packaging.

Naloxone’s cost varies, depending on geographic location and whether it is generic. According to GoodRX, a box containing two doses of generic naloxone costs $31-$100, depending on location and coupon availability.

A two-dose box of Narcan costs $135-$140. Emergent reported a 14% decline in naloxone sales in 2022 – to $373.7 million – blaming it in part on the introduction of generic formulations.

Dr. Hurley said he expects those who purchase Narcan at a drug store will primarily already be shopping there. It may or may not be those who most often experience overdose, such as people leaving incarceration or experiencing homelessness.

Having Narcan available over-the-counter “is an important supplement but it doesn’t replace the existing array of naloxone distribution programs,” Dr. Hurley said.

The FDA has encouraged naloxone manufacturers to seek OTC approval for the medication since at least 2019, when it designed a model label for a theoretical OTC product.

In November, the agency said it had determined that some naloxone products had the potential to be safe and effective for OTC use and again urged drugmakers to seek such an approval.

Emergent BioSolutions was the first to pursue OTC approval, but another manufacturer – the nonprofit Harm Reduction Therapeutics – is awaiting approval of its application to sell its spray directly to consumers.

Scott Gottlieb, MD, who was the FDA commissioner from 2017 to 2019, said in a tweet that more work needed to be done.

“This regulatory move should be followed by a strong push by elected officials to support wider deployment of Narcan, getting more doses into the hands of at risk households and frontline workers,” he tweeted.

Mr. Ingoglia said that “Narcan represents a second chance. By giving people a second chance, we also give them an opportunity to enter treatment if they so choose. You can’t recover if you’re dead, and we shouldn’t turn our backs on those who may choose a pathway to recovery that includes treatment.”
 

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

The Food and Drug Administration has approved over-the-counter sales of the overdose reversal agent Narcan (naloxone, Emergent BioSolutions). Greater access to the drug should mean more lives saved. However, it’s unclear how much the nasal spray will cost and whether pharmacies will stock the product openly on shelves. 

Currently, major pharmacy chains such as CVS and Walgreens make naloxone available without prescription, but consumers have to ask a pharmacist to dispense the drug.

“The major question is what is it going to cost,” Brian Hurley, MD, MBA, president-elect of the American Society of Addiction Medicine, said in an interview. “In order for people to access it they have to be able to afford it.”

“We won’t accomplish much if people can’t afford to buy Narcan,” said Chuck Ingoglia, president and CEO of the National Council for Mental Wellbeing, in a statement. Still, he applauded the FDA.

“No single approach will end overdose deaths but making Narcan easy to obtain and widely available likely will save countless lives annually,” he said.

“The timeline for availability and price of this OTC product is determined by the manufacturer,” the FDA said in a statement.

Commissioner Robert M. Califf, MD, called for the drug’s manufacturer to “make accessibility to the product a priority by making it available as soon as possible and at an affordable price.”

Emergent BioSolutions did not comment on cost. It said in a statement that the spray “will be available on U.S. shelves and at online retailers by the late summer,” after it has adapted Narcan for direct-to-consumer use, including more consumer-oriented packaging.

Naloxone’s cost varies, depending on geographic location and whether it is generic. According to GoodRX, a box containing two doses of generic naloxone costs $31-$100, depending on location and coupon availability.

A two-dose box of Narcan costs $135-$140. Emergent reported a 14% decline in naloxone sales in 2022 – to $373.7 million – blaming it in part on the introduction of generic formulations.

Dr. Hurley said he expects those who purchase Narcan at a drug store will primarily already be shopping there. It may or may not be those who most often experience overdose, such as people leaving incarceration or experiencing homelessness.

Having Narcan available over-the-counter “is an important supplement but it doesn’t replace the existing array of naloxone distribution programs,” Dr. Hurley said.

The FDA has encouraged naloxone manufacturers to seek OTC approval for the medication since at least 2019, when it designed a model label for a theoretical OTC product.

In November, the agency said it had determined that some naloxone products had the potential to be safe and effective for OTC use and again urged drugmakers to seek such an approval.

Emergent BioSolutions was the first to pursue OTC approval, but another manufacturer – the nonprofit Harm Reduction Therapeutics – is awaiting approval of its application to sell its spray directly to consumers.

Scott Gottlieb, MD, who was the FDA commissioner from 2017 to 2019, said in a tweet that more work needed to be done.

“This regulatory move should be followed by a strong push by elected officials to support wider deployment of Narcan, getting more doses into the hands of at risk households and frontline workers,” he tweeted.

Mr. Ingoglia said that “Narcan represents a second chance. By giving people a second chance, we also give them an opportunity to enter treatment if they so choose. You can’t recover if you’re dead, and we shouldn’t turn our backs on those who may choose a pathway to recovery that includes treatment.”
 

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

Isotretinoin, for severe, nodular acne, comes with complex safety requirements, and on March 28, two Food and Drug Administration advisory committees began a 2-day meeting examining how to relieve some of those burdens for patients, pharmacies, and prescribers.
 

Isotretinoin, previously called Accutane, is marketed as Absorica, Absorica LD, Claravis, Amnesteem, Myorisan, and Zenatane.

In a joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and Dermatologic and Ophthalmic Drugs Advisory Committee, experts addressed ways to improve the modified iPLEDGE Risk Evaluation and Mitigation Strategy (iPLEDGE REMS) for isotretinoin that caused chaos after its rollout at the end of 2021.

In January 2022, problems were multiplying with the program for clinicians, pharmacists, and patients, causing extensive delays and prescription denials. In response, the FDA said it would continue to meet with the Isotretinoin Products Manufacturers Group (IPMG) to resolve problems.

March 28 was the first day of a 2-day meeting addressing what can be done to reduce burden with the iPLEDGE REMS while maintaining safety and preventing fetal exposure to the drug.
 

Key areas of concern

The meeting focused on several key areas.

The 19-day lockout period

The lockout is a current restriction for patients who can become pregnant and do not pick up their first prescription of isotretinoin within the specified 7-day prescription window. Currently, those who miss the window must wait 19 days from the date of the first pregnancy test to take an additional pregnancy test to be eligible to receive the drug.

Lindsey Crist, PharmD, a risk management analyst for the FDA, who presented the FDA review committee’s analysis, acknowledged that the lockout period causes delays in treatment and adds frustration and costs.

She said it’s important to remember that the lockout applies only to the first prescription. “It’s intended as an additional layer of screening to detect pregnancy,” she said.

“At least 12 pregnancies have been identified during the 19-day lockout from March 2017–September of 2022,” she noted.

The FDA is looking to the advisory committee to provide recommendations on whether the lockout period should be changed.
 

Home testing

During the pandemic, iPLEDGE rules have been relaxed from having a pregnancy test done only at a Clinical Laboratory Improvement Amendments–certified laboratory and home pregnancy tests have been allowed. The question now is whether home tests should continue to be allowed.

Ms. Crist said that the FDA’s review committee recommends ending the allowance of home tests, citing insufficient data on use and the discovery of instances of falsification of pregnancy tests.

“One study at an academic medical center reviewed the medical records of 89 patients who used home pregnancy tests while taking isotretinoin during the public health emergency. It found that 15.7% submitted falsified pregnancy test results,” she said.

Ms. Crist added, however, that the review committee recommends allowing the tests to be done in a provider’s office as an alternative.

Documenting counseling patients who cannot get pregnant

Currently, this documentation must be done monthly, primarily to counsel patients against drug sharing or giving blood. Proposed changes include extending the intervals for attestation or eliminating it to reduce burden on clinicians.

IPMG representative Gregory Wedin, PharmD, pharmacovigilance and risk management director for Upsher-Smith Laboratories, said, “while we cannot support eliminating or extending the confirmation interval to a year, the [iPLEDGE] sponsors are agreeable [to] a 120-day confirmation interval.”

He said that while extending to 120 days would reduce burden on prescribers, it comes with risk in reducing oversight by a certified iPLEDGE prescriber and potentially increasing the risk for drug sharing.

“A patient may be more likely to share their drug with another person the further along with therapy they get as their condition improves,” Mr. Wedin said.

On March 29, the panel will hear more recommendations for and against modifications to iPLEDGE REMS and will vote on select modifications at the end of the meeting.

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

Isotretinoin, for severe, nodular acne, comes with complex safety requirements, and on March 28, two Food and Drug Administration advisory committees began a 2-day meeting examining how to relieve some of those burdens for patients, pharmacies, and prescribers.
 

Isotretinoin, previously called Accutane, is marketed as Absorica, Absorica LD, Claravis, Amnesteem, Myorisan, and Zenatane.

In a joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and Dermatologic and Ophthalmic Drugs Advisory Committee, experts addressed ways to improve the modified iPLEDGE Risk Evaluation and Mitigation Strategy (iPLEDGE REMS) for isotretinoin that caused chaos after its rollout at the end of 2021.

In January 2022, problems were multiplying with the program for clinicians, pharmacists, and patients, causing extensive delays and prescription denials. In response, the FDA said it would continue to meet with the Isotretinoin Products Manufacturers Group (IPMG) to resolve problems.

March 28 was the first day of a 2-day meeting addressing what can be done to reduce burden with the iPLEDGE REMS while maintaining safety and preventing fetal exposure to the drug.
 

Key areas of concern

The meeting focused on several key areas.

The 19-day lockout period

The lockout is a current restriction for patients who can become pregnant and do not pick up their first prescription of isotretinoin within the specified 7-day prescription window. Currently, those who miss the window must wait 19 days from the date of the first pregnancy test to take an additional pregnancy test to be eligible to receive the drug.

Lindsey Crist, PharmD, a risk management analyst for the FDA, who presented the FDA review committee’s analysis, acknowledged that the lockout period causes delays in treatment and adds frustration and costs.

She said it’s important to remember that the lockout applies only to the first prescription. “It’s intended as an additional layer of screening to detect pregnancy,” she said.

“At least 12 pregnancies have been identified during the 19-day lockout from March 2017–September of 2022,” she noted.

The FDA is looking to the advisory committee to provide recommendations on whether the lockout period should be changed.
 

Home testing

During the pandemic, iPLEDGE rules have been relaxed from having a pregnancy test done only at a Clinical Laboratory Improvement Amendments–certified laboratory and home pregnancy tests have been allowed. The question now is whether home tests should continue to be allowed.

Ms. Crist said that the FDA’s review committee recommends ending the allowance of home tests, citing insufficient data on use and the discovery of instances of falsification of pregnancy tests.

“One study at an academic medical center reviewed the medical records of 89 patients who used home pregnancy tests while taking isotretinoin during the public health emergency. It found that 15.7% submitted falsified pregnancy test results,” she said.

Ms. Crist added, however, that the review committee recommends allowing the tests to be done in a provider’s office as an alternative.

Documenting counseling patients who cannot get pregnant

Currently, this documentation must be done monthly, primarily to counsel patients against drug sharing or giving blood. Proposed changes include extending the intervals for attestation or eliminating it to reduce burden on clinicians.

IPMG representative Gregory Wedin, PharmD, pharmacovigilance and risk management director for Upsher-Smith Laboratories, said, “while we cannot support eliminating or extending the confirmation interval to a year, the [iPLEDGE] sponsors are agreeable [to] a 120-day confirmation interval.”

He said that while extending to 120 days would reduce burden on prescribers, it comes with risk in reducing oversight by a certified iPLEDGE prescriber and potentially increasing the risk for drug sharing.

“A patient may be more likely to share their drug with another person the further along with therapy they get as their condition improves,” Mr. Wedin said.

On March 29, the panel will hear more recommendations for and against modifications to iPLEDGE REMS and will vote on select modifications at the end of the meeting.

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

Isotretinoin, for severe, nodular acne, comes with complex safety requirements, and on March 28, two Food and Drug Administration advisory committees began a 2-day meeting examining how to relieve some of those burdens for patients, pharmacies, and prescribers.
 

Isotretinoin, previously called Accutane, is marketed as Absorica, Absorica LD, Claravis, Amnesteem, Myorisan, and Zenatane.

In a joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and Dermatologic and Ophthalmic Drugs Advisory Committee, experts addressed ways to improve the modified iPLEDGE Risk Evaluation and Mitigation Strategy (iPLEDGE REMS) for isotretinoin that caused chaos after its rollout at the end of 2021.

In January 2022, problems were multiplying with the program for clinicians, pharmacists, and patients, causing extensive delays and prescription denials. In response, the FDA said it would continue to meet with the Isotretinoin Products Manufacturers Group (IPMG) to resolve problems.

March 28 was the first day of a 2-day meeting addressing what can be done to reduce burden with the iPLEDGE REMS while maintaining safety and preventing fetal exposure to the drug.
 

Key areas of concern

The meeting focused on several key areas.

The 19-day lockout period

The lockout is a current restriction for patients who can become pregnant and do not pick up their first prescription of isotretinoin within the specified 7-day prescription window. Currently, those who miss the window must wait 19 days from the date of the first pregnancy test to take an additional pregnancy test to be eligible to receive the drug.

Lindsey Crist, PharmD, a risk management analyst for the FDA, who presented the FDA review committee’s analysis, acknowledged that the lockout period causes delays in treatment and adds frustration and costs.

She said it’s important to remember that the lockout applies only to the first prescription. “It’s intended as an additional layer of screening to detect pregnancy,” she said.

“At least 12 pregnancies have been identified during the 19-day lockout from March 2017–September of 2022,” she noted.

The FDA is looking to the advisory committee to provide recommendations on whether the lockout period should be changed.
 

Home testing

During the pandemic, iPLEDGE rules have been relaxed from having a pregnancy test done only at a Clinical Laboratory Improvement Amendments–certified laboratory and home pregnancy tests have been allowed. The question now is whether home tests should continue to be allowed.

Ms. Crist said that the FDA’s review committee recommends ending the allowance of home tests, citing insufficient data on use and the discovery of instances of falsification of pregnancy tests.

“One study at an academic medical center reviewed the medical records of 89 patients who used home pregnancy tests while taking isotretinoin during the public health emergency. It found that 15.7% submitted falsified pregnancy test results,” she said.

Ms. Crist added, however, that the review committee recommends allowing the tests to be done in a provider’s office as an alternative.

Documenting counseling patients who cannot get pregnant

Currently, this documentation must be done monthly, primarily to counsel patients against drug sharing or giving blood. Proposed changes include extending the intervals for attestation or eliminating it to reduce burden on clinicians.

IPMG representative Gregory Wedin, PharmD, pharmacovigilance and risk management director for Upsher-Smith Laboratories, said, “while we cannot support eliminating or extending the confirmation interval to a year, the [iPLEDGE] sponsors are agreeable [to] a 120-day confirmation interval.”

He said that while extending to 120 days would reduce burden on prescribers, it comes with risk in reducing oversight by a certified iPLEDGE prescriber and potentially increasing the risk for drug sharing.

“A patient may be more likely to share their drug with another person the further along with therapy they get as their condition improves,” Mr. Wedin said.

On March 29, the panel will hear more recommendations for and against modifications to iPLEDGE REMS and will vote on select modifications at the end of the meeting.

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

NEW ORLEANS – The oral Janus kinase (JAK) inhibitor ivarmacitinib, which is characterized as being highly selective for the JAK1 enzyme, is effective for the treatment of atopic dermatitis (AD), according to a phase 3 multinational trial presented as a late-breaker at the annual meeting of the American Academy of Dermatology.

Two doses were studied in the placebo-controlled trial and both demonstrated “a favorable benefit-to-risk profile in patients with moderate to severe AD,” reported Yan Zhao, MD, a clinician and researcher in the department of dermatology, Peking University People’s Hospital, Beijing.

bravo1954/E+/Getty Images

In the study, called QUARTZ3, 336 patients aged 12 and older at 51 sites in China and Canada were randomized to 4 mg once-daily ivarmacitinib, 8 mg once-daily QD ivarmacitinib, or placebo. The mean age of the population was 32 years and approximately one-third were female.

The mean duration of AD for participants was 10 years. The mean baseline Eczema Area and Severity Index (EASI) score was near 30. On the Investigator Global Assessment (IGA) tool, approximately 40% had a score of 4, which is the highest score on the scale and indicates severe disease. The remaining patients had an IGA score of 3.

The co-primary endpoints were change in IGA and EASI scores at 16 weeks, and both improved rapidly, showing statistical significance relative to placebo by 4 weeks with no plateauing effect at the end of the 16-week trial. By week 16, the proportion of patients with an EASI score of 75, signifying a 75% improvement, was 66%, 54%, and 22% for the 8-mg dose of ivarmacitinib, 4-mg dose of ivarmacitinib, and placebo groups (P < .001 versus placebo for both doses of active therapy), respectively.

The pattern of the IGA response was similar. By week 16, the proportion of patients achieving an IGA score of 0 (clear) or 1 (almost clear) was 42%, 36%, and 9% for the 8-mg dose of ivarmacitinib, 4-mg dose of ivarmacitinib, and placebo groups, respectively. The advantage of either dose over placebo was highly significant (P < .001) at 8, 12, and 16 weeks.

For the WI-NRS (Worst Itch – Numeric Rating Scale), the advantage of the 8-mg dose relative to placebo was significant (P < .001) at the 1-week evaluation. By 2 weeks, the 4-mg dose had gained the same degree of statistical significance relative to placebo. After week 4, when the maximum proportion of patients with a WI-NRS score ≤ 4 was reached (50%, 35%, and 10% in the 8-mg, 4-mg, and placebo groups), and the relative advantage of active treatment persisted until the end of the 16-week study.

Two scales were used to evaluate change in quality of life. On the DLQI (Dermatology Life Quality Index) and POEM (Patient-Oriented Eczema Measure), improvements were again rapid and sustained. By week 4, improvement with the 8-mg dose was about fourfold greater (P < .001) than improvement with placebo for DLQI and about sixfold greater (P < .001) for POEM. For the 4-mg dose, the relative differences were approximately threefold and fourfold greater, and both were significant (P <.001).

There was no further gain in these quality-of-life scales from week 4 to week 16, but the advantages relative to placebo were generally sustained, Dr. Zhao reported.

Ivarmacitinib was safe and well-tolerated, according to Dr. Zhao. The proportion of patients with a treatment-emergent adverse event that led to drug discontinuation was numerically higher (5.4%) in the placebo group than in the 8-mg (3.6%) or 4-mg group (2.7%). Rates of infection in the three groups were similar, and there were no major adverse cardiovascular events (MACE) or thromboembolism observed in any group.

Ivarmacitinib, which has about a 10-fold greater selectivity for JAK1 than JAK2 and a more than 70-fold greater selectivity for JAK1 than JAK3, is being tested for rheumatoid arthritis, inflammatory bowel disease, and alopecia areata in addition to AD, Dr. Zhao said. She also reported that an application for new drug approval has been submitted in China. Efforts to pursue regulatory approval elsewhere are anticipated.

Currently, there are three JAK inhibitors licensed for the treatment of AD in the United States. Upadacitinib (Rinvoq) and abrocitinib (Cibinqo) are also once-daily oral JAK1-selective inhibitors. Regulatory approval for AD by the Food and Drug Administration was granted to both in early 2022 and both now have an indication for moderate to severe disease in patients ages 12 years and older.

In September 2021, the first U.S. approval of a drug in this class for AD was granted for a topical formulation of ruxolitinib (Opzelura), which has selectivity for both JAK1 and JAK2. The indication is for mild to moderate AD in patients aged 12 years and older.

In the phase 3 clinical trial that led to approval of abrocitinib for AD, the comparator groups included placebo and active treatment with 300 mg dupilumab administered subcutaneously every other week. The higher of two doses of abrocitinib (100 mg) was numerically superior to dupilumab in terms of EASI 75 response at week 12 and was statistically superior for relief of itch at week 2.

Relative to the first-generation JAK inhibitor tofacitinib (Xeljanz), both of the approved oral JAK inhibitors for AD, abrocitinib and upadacitinib, have greater JAK1-selectivity. However, selectivity for all JAK inhibitors is relative rather than absolute, according to a recent review article on oral JAK inhibitors for AD. Efficacy and safety are likely determined by relative inhibition of each of the four JAK enzymes (JAK1, JAK2, JAK3, and TYK2). Although JAK1 appears to be an important target for AD treatment, the clinical significance of the degree of selectivity among oral JAK inhibitors is not yet clear.

In an interview, the senior author of that review article, Emma Guttman-Yassky, MD, PhD, emphasized this point. She said there is no evidence and no basis on which to speculate that any one drug in this class is better than another for AD. Dr. Guttman-Yassky is a professor and system chair of dermatology and immunology at the Icahn School of Medicine at Mount Sinai, New York.

“The efficacy [of ivarmacitinib] seems, in general, to be in line with other JAK inhibitors,” said Dr. Guttman-Yassky, who attended the late-breaker session during which these data were presented. Although she acknowledged that rapid control of pruritus is important clinically, she said the speed of itch relief as reported in the phase 3 ivarmacitinib trial does not distinguish it from other oral drugs in the class.

Shawn Kwatra, MD, director of the Johns Hopkins Itch Center, Johns Hopkins University, Baltimore, agreed.

“The rapid effects on itch of ivarmacitinib are consistent with those observed by the already approved JAK1-selective inhibitors abrocitinib and upadacitinib,” he said in an interview.

This suggests that head-to-head trials will be needed to draw any conclusions about the relative efficacy and safety of existing and emerging oral JAK inhibitors for AD.

Dr. Zhao has reported a financial relationship with Reistone Biopharma, which is developing ivarmacitinib and provided funding for the trial. Dr. Guttman-Yassky has reported financial relationships with more than 20 pharmaceutical companies, including companies that make JAK inhibitors. Dr. Kwatra has reported financial relationships with AbbVie, Aslan, Arcutis Biotherapeutics, Castle Biosciences, Celldex, Galderma, Genzada, Incyte, Johnson & Johnson, Leo Pharma, Novartis, Pfizer, Regeneron, and Sanofi.

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

NEW ORLEANS – The oral Janus kinase (JAK) inhibitor ivarmacitinib, which is characterized as being highly selective for the JAK1 enzyme, is effective for the treatment of atopic dermatitis (AD), according to a phase 3 multinational trial presented as a late-breaker at the annual meeting of the American Academy of Dermatology.

Two doses were studied in the placebo-controlled trial and both demonstrated “a favorable benefit-to-risk profile in patients with moderate to severe AD,” reported Yan Zhao, MD, a clinician and researcher in the department of dermatology, Peking University People’s Hospital, Beijing.

bravo1954/E+/Getty Images

In the study, called QUARTZ3, 336 patients aged 12 and older at 51 sites in China and Canada were randomized to 4 mg once-daily ivarmacitinib, 8 mg once-daily QD ivarmacitinib, or placebo. The mean age of the population was 32 years and approximately one-third were female.

The mean duration of AD for participants was 10 years. The mean baseline Eczema Area and Severity Index (EASI) score was near 30. On the Investigator Global Assessment (IGA) tool, approximately 40% had a score of 4, which is the highest score on the scale and indicates severe disease. The remaining patients had an IGA score of 3.

The co-primary endpoints were change in IGA and EASI scores at 16 weeks, and both improved rapidly, showing statistical significance relative to placebo by 4 weeks with no plateauing effect at the end of the 16-week trial. By week 16, the proportion of patients with an EASI score of 75, signifying a 75% improvement, was 66%, 54%, and 22% for the 8-mg dose of ivarmacitinib, 4-mg dose of ivarmacitinib, and placebo groups (P < .001 versus placebo for both doses of active therapy), respectively.

The pattern of the IGA response was similar. By week 16, the proportion of patients achieving an IGA score of 0 (clear) or 1 (almost clear) was 42%, 36%, and 9% for the 8-mg dose of ivarmacitinib, 4-mg dose of ivarmacitinib, and placebo groups, respectively. The advantage of either dose over placebo was highly significant (P < .001) at 8, 12, and 16 weeks.

For the WI-NRS (Worst Itch – Numeric Rating Scale), the advantage of the 8-mg dose relative to placebo was significant (P < .001) at the 1-week evaluation. By 2 weeks, the 4-mg dose had gained the same degree of statistical significance relative to placebo. After week 4, when the maximum proportion of patients with a WI-NRS score ≤ 4 was reached (50%, 35%, and 10% in the 8-mg, 4-mg, and placebo groups), and the relative advantage of active treatment persisted until the end of the 16-week study.

Two scales were used to evaluate change in quality of life. On the DLQI (Dermatology Life Quality Index) and POEM (Patient-Oriented Eczema Measure), improvements were again rapid and sustained. By week 4, improvement with the 8-mg dose was about fourfold greater (P < .001) than improvement with placebo for DLQI and about sixfold greater (P < .001) for POEM. For the 4-mg dose, the relative differences were approximately threefold and fourfold greater, and both were significant (P <.001).

There was no further gain in these quality-of-life scales from week 4 to week 16, but the advantages relative to placebo were generally sustained, Dr. Zhao reported.

Ivarmacitinib was safe and well-tolerated, according to Dr. Zhao. The proportion of patients with a treatment-emergent adverse event that led to drug discontinuation was numerically higher (5.4%) in the placebo group than in the 8-mg (3.6%) or 4-mg group (2.7%). Rates of infection in the three groups were similar, and there were no major adverse cardiovascular events (MACE) or thromboembolism observed in any group.

Ivarmacitinib, which has about a 10-fold greater selectivity for JAK1 than JAK2 and a more than 70-fold greater selectivity for JAK1 than JAK3, is being tested for rheumatoid arthritis, inflammatory bowel disease, and alopecia areata in addition to AD, Dr. Zhao said. She also reported that an application for new drug approval has been submitted in China. Efforts to pursue regulatory approval elsewhere are anticipated.

Currently, there are three JAK inhibitors licensed for the treatment of AD in the United States. Upadacitinib (Rinvoq) and abrocitinib (Cibinqo) are also once-daily oral JAK1-selective inhibitors. Regulatory approval for AD by the Food and Drug Administration was granted to both in early 2022 and both now have an indication for moderate to severe disease in patients ages 12 years and older.

In September 2021, the first U.S. approval of a drug in this class for AD was granted for a topical formulation of ruxolitinib (Opzelura), which has selectivity for both JAK1 and JAK2. The indication is for mild to moderate AD in patients aged 12 years and older.

In the phase 3 clinical trial that led to approval of abrocitinib for AD, the comparator groups included placebo and active treatment with 300 mg dupilumab administered subcutaneously every other week. The higher of two doses of abrocitinib (100 mg) was numerically superior to dupilumab in terms of EASI 75 response at week 12 and was statistically superior for relief of itch at week 2.

Relative to the first-generation JAK inhibitor tofacitinib (Xeljanz), both of the approved oral JAK inhibitors for AD, abrocitinib and upadacitinib, have greater JAK1-selectivity. However, selectivity for all JAK inhibitors is relative rather than absolute, according to a recent review article on oral JAK inhibitors for AD. Efficacy and safety are likely determined by relative inhibition of each of the four JAK enzymes (JAK1, JAK2, JAK3, and TYK2). Although JAK1 appears to be an important target for AD treatment, the clinical significance of the degree of selectivity among oral JAK inhibitors is not yet clear.

In an interview, the senior author of that review article, Emma Guttman-Yassky, MD, PhD, emphasized this point. She said there is no evidence and no basis on which to speculate that any one drug in this class is better than another for AD. Dr. Guttman-Yassky is a professor and system chair of dermatology and immunology at the Icahn School of Medicine at Mount Sinai, New York.

“The efficacy [of ivarmacitinib] seems, in general, to be in line with other JAK inhibitors,” said Dr. Guttman-Yassky, who attended the late-breaker session during which these data were presented. Although she acknowledged that rapid control of pruritus is important clinically, she said the speed of itch relief as reported in the phase 3 ivarmacitinib trial does not distinguish it from other oral drugs in the class.

Shawn Kwatra, MD, director of the Johns Hopkins Itch Center, Johns Hopkins University, Baltimore, agreed.

“The rapid effects on itch of ivarmacitinib are consistent with those observed by the already approved JAK1-selective inhibitors abrocitinib and upadacitinib,” he said in an interview.

This suggests that head-to-head trials will be needed to draw any conclusions about the relative efficacy and safety of existing and emerging oral JAK inhibitors for AD.

Dr. Zhao has reported a financial relationship with Reistone Biopharma, which is developing ivarmacitinib and provided funding for the trial. Dr. Guttman-Yassky has reported financial relationships with more than 20 pharmaceutical companies, including companies that make JAK inhibitors. Dr. Kwatra has reported financial relationships with AbbVie, Aslan, Arcutis Biotherapeutics, Castle Biosciences, Celldex, Galderma, Genzada, Incyte, Johnson & Johnson, Leo Pharma, Novartis, Pfizer, Regeneron, and Sanofi.

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

NEW ORLEANS – The oral Janus kinase (JAK) inhibitor ivarmacitinib, which is characterized as being highly selective for the JAK1 enzyme, is effective for the treatment of atopic dermatitis (AD), according to a phase 3 multinational trial presented as a late-breaker at the annual meeting of the American Academy of Dermatology.

Two doses were studied in the placebo-controlled trial and both demonstrated “a favorable benefit-to-risk profile in patients with moderate to severe AD,” reported Yan Zhao, MD, a clinician and researcher in the department of dermatology, Peking University People’s Hospital, Beijing.

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In the study, called QUARTZ3, 336 patients aged 12 and older at 51 sites in China and Canada were randomized to 4 mg once-daily ivarmacitinib, 8 mg once-daily QD ivarmacitinib, or placebo. The mean age of the population was 32 years and approximately one-third were female.

The mean duration of AD for participants was 10 years. The mean baseline Eczema Area and Severity Index (EASI) score was near 30. On the Investigator Global Assessment (IGA) tool, approximately 40% had a score of 4, which is the highest score on the scale and indicates severe disease. The remaining patients had an IGA score of 3.

The co-primary endpoints were change in IGA and EASI scores at 16 weeks, and both improved rapidly, showing statistical significance relative to placebo by 4 weeks with no plateauing effect at the end of the 16-week trial. By week 16, the proportion of patients with an EASI score of 75, signifying a 75% improvement, was 66%, 54%, and 22% for the 8-mg dose of ivarmacitinib, 4-mg dose of ivarmacitinib, and placebo groups (P < .001 versus placebo for both doses of active therapy), respectively.

The pattern of the IGA response was similar. By week 16, the proportion of patients achieving an IGA score of 0 (clear) or 1 (almost clear) was 42%, 36%, and 9% for the 8-mg dose of ivarmacitinib, 4-mg dose of ivarmacitinib, and placebo groups, respectively. The advantage of either dose over placebo was highly significant (P < .001) at 8, 12, and 16 weeks.

For the WI-NRS (Worst Itch – Numeric Rating Scale), the advantage of the 8-mg dose relative to placebo was significant (P < .001) at the 1-week evaluation. By 2 weeks, the 4-mg dose had gained the same degree of statistical significance relative to placebo. After week 4, when the maximum proportion of patients with a WI-NRS score ≤ 4 was reached (50%, 35%, and 10% in the 8-mg, 4-mg, and placebo groups), and the relative advantage of active treatment persisted until the end of the 16-week study.

Two scales were used to evaluate change in quality of life. On the DLQI (Dermatology Life Quality Index) and POEM (Patient-Oriented Eczema Measure), improvements were again rapid and sustained. By week 4, improvement with the 8-mg dose was about fourfold greater (P < .001) than improvement with placebo for DLQI and about sixfold greater (P < .001) for POEM. For the 4-mg dose, the relative differences were approximately threefold and fourfold greater, and both were significant (P <.001).

There was no further gain in these quality-of-life scales from week 4 to week 16, but the advantages relative to placebo were generally sustained, Dr. Zhao reported.

Ivarmacitinib was safe and well-tolerated, according to Dr. Zhao. The proportion of patients with a treatment-emergent adverse event that led to drug discontinuation was numerically higher (5.4%) in the placebo group than in the 8-mg (3.6%) or 4-mg group (2.7%). Rates of infection in the three groups were similar, and there were no major adverse cardiovascular events (MACE) or thromboembolism observed in any group.

Ivarmacitinib, which has about a 10-fold greater selectivity for JAK1 than JAK2 and a more than 70-fold greater selectivity for JAK1 than JAK3, is being tested for rheumatoid arthritis, inflammatory bowel disease, and alopecia areata in addition to AD, Dr. Zhao said. She also reported that an application for new drug approval has been submitted in China. Efforts to pursue regulatory approval elsewhere are anticipated.

Currently, there are three JAK inhibitors licensed for the treatment of AD in the United States. Upadacitinib (Rinvoq) and abrocitinib (Cibinqo) are also once-daily oral JAK1-selective inhibitors. Regulatory approval for AD by the Food and Drug Administration was granted to both in early 2022 and both now have an indication for moderate to severe disease in patients ages 12 years and older.

In September 2021, the first U.S. approval of a drug in this class for AD was granted for a topical formulation of ruxolitinib (Opzelura), which has selectivity for both JAK1 and JAK2. The indication is for mild to moderate AD in patients aged 12 years and older.

In the phase 3 clinical trial that led to approval of abrocitinib for AD, the comparator groups included placebo and active treatment with 300 mg dupilumab administered subcutaneously every other week. The higher of two doses of abrocitinib (100 mg) was numerically superior to dupilumab in terms of EASI 75 response at week 12 and was statistically superior for relief of itch at week 2.

Relative to the first-generation JAK inhibitor tofacitinib (Xeljanz), both of the approved oral JAK inhibitors for AD, abrocitinib and upadacitinib, have greater JAK1-selectivity. However, selectivity for all JAK inhibitors is relative rather than absolute, according to a recent review article on oral JAK inhibitors for AD. Efficacy and safety are likely determined by relative inhibition of each of the four JAK enzymes (JAK1, JAK2, JAK3, and TYK2). Although JAK1 appears to be an important target for AD treatment, the clinical significance of the degree of selectivity among oral JAK inhibitors is not yet clear.

In an interview, the senior author of that review article, Emma Guttman-Yassky, MD, PhD, emphasized this point. She said there is no evidence and no basis on which to speculate that any one drug in this class is better than another for AD. Dr. Guttman-Yassky is a professor and system chair of dermatology and immunology at the Icahn School of Medicine at Mount Sinai, New York.

“The efficacy [of ivarmacitinib] seems, in general, to be in line with other JAK inhibitors,” said Dr. Guttman-Yassky, who attended the late-breaker session during which these data were presented. Although she acknowledged that rapid control of pruritus is important clinically, she said the speed of itch relief as reported in the phase 3 ivarmacitinib trial does not distinguish it from other oral drugs in the class.

Shawn Kwatra, MD, director of the Johns Hopkins Itch Center, Johns Hopkins University, Baltimore, agreed.

“The rapid effects on itch of ivarmacitinib are consistent with those observed by the already approved JAK1-selective inhibitors abrocitinib and upadacitinib,” he said in an interview.

This suggests that head-to-head trials will be needed to draw any conclusions about the relative efficacy and safety of existing and emerging oral JAK inhibitors for AD.

Dr. Zhao has reported a financial relationship with Reistone Biopharma, which is developing ivarmacitinib and provided funding for the trial. Dr. Guttman-Yassky has reported financial relationships with more than 20 pharmaceutical companies, including companies that make JAK inhibitors. Dr. Kwatra has reported financial relationships with AbbVie, Aslan, Arcutis Biotherapeutics, Castle Biosciences, Celldex, Galderma, Genzada, Incyte, Johnson & Johnson, Leo Pharma, Novartis, Pfizer, Regeneron, and Sanofi.

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