Pediatrics

To the Editor:

Blastomycosislike pyoderma (BLP), also commonly referred to as pyoderma vegetans, is a rare cutaneous bacterial infection that often mimics other fungal, inflammatory, or neoplastic disorders.¹ It is characterized by a collection of neutrophilic abscesses with pseudoepitheliomatous hyperplasia that coalesce into crusted plaques.

A 15-year-old adolescent girl with a history of type 1 diabetes mellitus was admitted for diabetic ketoacidosis. The patient presented with bilateral pretibial lesions of 6 years’ duration that developed after swimming in a pool following reported trauma to the site. These pruritic plaques had grown slowly and were occasionally tender. Of note, with episodes of hyperglycemia, the lesions developed purulent drainage.

Upon admission to the hospital and subsequent dermatology consultation, physical examination revealed the right pretibial shin had a 15×5-cm, gray-brown, hyperpigmented, verrucous, tender plaque with purulent drainage and overlying crust (Figure 1). The left pretibial shin had a similar smaller lesion (Figure 2). Laboratory test results were notable for a white blood cell count of 41.84 cells/µL (reference range, 3.8–10.5 cells/µL), blood glucose level of 586 mg/dL (reference range, 70–99 mg/dL), and hemoglobin A_1c of 11.7% (reference range, 4.0%–5.6%). A biopsy specimen from the right pretibial shin was stained with hematoxylin and eosin for dermatopathologic evaluation as well as sent for tissue culture. Tissue and wound cultures grew Staphylococcus aureus and group B Streptococcus with no fungal or acid-fast bacilli growth.

To the Editor:

Blastomycosislike pyoderma (BLP), also commonly referred to as pyoderma vegetans, is a rare cutaneous bacterial infection that often mimics other fungal, inflammatory, or neoplastic disorders.¹ It is characterized by a collection of neutrophilic abscesses with pseudoepitheliomatous hyperplasia that coalesce into crusted plaques.

A 15-year-old adolescent girl with a history of type 1 diabetes mellitus was admitted for diabetic ketoacidosis. The patient presented with bilateral pretibial lesions of 6 years’ duration that developed after swimming in a pool following reported trauma to the site. These pruritic plaques had grown slowly and were occasionally tender. Of note, with episodes of hyperglycemia, the lesions developed purulent drainage.

Upon admission to the hospital and subsequent dermatology consultation, physical examination revealed the right pretibial shin had a 15×5-cm, gray-brown, hyperpigmented, verrucous, tender plaque with purulent drainage and overlying crust (Figure 1). The left pretibial shin had a similar smaller lesion (Figure 2). Laboratory test results were notable for a white blood cell count of 41.84 cells/µL (reference range, 3.8–10.5 cells/µL), blood glucose level of 586 mg/dL (reference range, 70–99 mg/dL), and hemoglobin A_1c of 11.7% (reference range, 4.0%–5.6%). A biopsy specimen from the right pretibial shin was stained with hematoxylin and eosin for dermatopathologic evaluation as well as sent for tissue culture. Tissue and wound cultures grew Staphylococcus aureus and group B Streptococcus with no fungal or acid-fast bacilli growth.

To the Editor:

Blastomycosislike pyoderma (BLP), also commonly referred to as pyoderma vegetans, is a rare cutaneous bacterial infection that often mimics other fungal, inflammatory, or neoplastic disorders.¹ It is characterized by a collection of neutrophilic abscesses with pseudoepitheliomatous hyperplasia that coalesce into crusted plaques.

A 15-year-old adolescent girl with a history of type 1 diabetes mellitus was admitted for diabetic ketoacidosis. The patient presented with bilateral pretibial lesions of 6 years’ duration that developed after swimming in a pool following reported trauma to the site. These pruritic plaques had grown slowly and were occasionally tender. Of note, with episodes of hyperglycemia, the lesions developed purulent drainage.

Upon admission to the hospital and subsequent dermatology consultation, physical examination revealed the right pretibial shin had a 15×5-cm, gray-brown, hyperpigmented, verrucous, tender plaque with purulent drainage and overlying crust (Figure 1). The left pretibial shin had a similar smaller lesion (Figure 2). Laboratory test results were notable for a white blood cell count of 41.84 cells/µL (reference range, 3.8–10.5 cells/µL), blood glucose level of 586 mg/dL (reference range, 70–99 mg/dL), and hemoglobin A_1c of 11.7% (reference range, 4.0%–5.6%). A biopsy specimen from the right pretibial shin was stained with hematoxylin and eosin for dermatopathologic evaluation as well as sent for tissue culture. Tissue and wound cultures grew Staphylococcus aureus and group B Streptococcus with no fungal or acid-fast bacilli growth.

Pfizer’s COVID-19 vaccine for children ages 2 to 5 years old fizzled in clinical trials, the company said on Friday, signaling a further delay in getting a vaccine to preschoolers just as Omicron bears down on the U.S.

In a news release, Pfizer reported that while its 3-microgram dose – which is less than one-third of the dose given to older children – generated a protective immune response in babies and toddlers ages 6 to 24 months, it didn’t generate adequate immunity in children ages 2 to 5.

The company plans to change its clinical trial to add a third dose for younger children in hopes of improving those results. It also plans to test a third dose of its 10-microgram vaccine for children ages 5 to 12.

If the trials are successful, Pfizer said it would submit data to the FDA for an emergency use authorization (EUA) in the first half of 2022.

That pushes the timeline of getting a vaccine to younger children back by several months. In November, Anthony Fauci, MD, head of the National Institute of Allergy Infectious Diseases, predicted a vaccine would be ready for preschoolers by spring.

“On one hand, parents are understandably disappointed,” said Jill Foster, MD, a pediatric infectious disease doctor at the University of Minnesota Medical School. “On the other, it shows that the system for testing vaccines is working. Children are not little adults and have complex immune systems, so it’s not just a matter of making the dose smaller and expecting that it will work,” she said, noting that data from Moderna’s KidCOVE study in preschoolers is pending.

Until there’s a vaccine, Dr. Foster says parents should protect babies and toddlers by making sure everyone around them is vaccinated, promote the use of face masks for everyone around them and for all children over age 2, and continue to avoid crowded gatherings, particularly those that are indoors.

“Hand sanitizer is important, but this virus, especially the Omicron variant, is very easily spread through the air, so keep the air clear of virus as much as possible,” she said.

While the youngest children are still waiting for an effective vaccine, there was reassuring news Dec. 16 about the safety of Pfizer’s vaccine for school-aged kids – those ages 5 through 11.

Out of more than 7 million doses given since this vaccine was authorized for emergency use in late October, most reactions to the vaccine – including arm pain, swelling, and fatigue – have been mild and gone away quickly, without the need to miss school or see a doctor, the CDC reported to a meeting of its Advisory Committee on Immunization Practices, or ACIP.

Many experts had been waiting to see if this vaccine would cause rare cases of heart inflammation called myocarditis, as a higher dose did in teens and young adults.

The news on this front was excellent. About 6 weeks after this vaccine became available, the CDC says there have been only eight confirmed cases of myocarditis in this age group. Six more cases are under investigation.

To put this risk into context, data collected by the American Academy of Pediatrics and the Children’s Hospital Association shows that about 1% of children who test positive for COVID-19 are hospitalized for their infections, while the risk of getting a case of myocarditis after vaccination is .0002%, making it about 5,000 times more likely that a child would need to be hospitalized for COVID-19 than for myocarditis after vaccination.

John Su, MD, who is a member of the CDC’s Vaccine Safety Team, reported there had been two deaths in children after a COVID-19 vaccination. Both were girls, ages 5 and 6. Both had complicated medical histories for several medical disorders. It’s not clear their deaths were linked to the vaccine, and the causes of their deaths are still under investigation.

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

Pfizer’s COVID-19 vaccine for children ages 2 to 5 years old fizzled in clinical trials, the company said on Friday, signaling a further delay in getting a vaccine to preschoolers just as Omicron bears down on the U.S.

In a news release, Pfizer reported that while its 3-microgram dose – which is less than one-third of the dose given to older children – generated a protective immune response in babies and toddlers ages 6 to 24 months, it didn’t generate adequate immunity in children ages 2 to 5.

The company plans to change its clinical trial to add a third dose for younger children in hopes of improving those results. It also plans to test a third dose of its 10-microgram vaccine for children ages 5 to 12.

If the trials are successful, Pfizer said it would submit data to the FDA for an emergency use authorization (EUA) in the first half of 2022.

That pushes the timeline of getting a vaccine to younger children back by several months. In November, Anthony Fauci, MD, head of the National Institute of Allergy Infectious Diseases, predicted a vaccine would be ready for preschoolers by spring.

“On one hand, parents are understandably disappointed,” said Jill Foster, MD, a pediatric infectious disease doctor at the University of Minnesota Medical School. “On the other, it shows that the system for testing vaccines is working. Children are not little adults and have complex immune systems, so it’s not just a matter of making the dose smaller and expecting that it will work,” she said, noting that data from Moderna’s KidCOVE study in preschoolers is pending.

Until there’s a vaccine, Dr. Foster says parents should protect babies and toddlers by making sure everyone around them is vaccinated, promote the use of face masks for everyone around them and for all children over age 2, and continue to avoid crowded gatherings, particularly those that are indoors.

“Hand sanitizer is important, but this virus, especially the Omicron variant, is very easily spread through the air, so keep the air clear of virus as much as possible,” she said.

While the youngest children are still waiting for an effective vaccine, there was reassuring news Dec. 16 about the safety of Pfizer’s vaccine for school-aged kids – those ages 5 through 11.

Out of more than 7 million doses given since this vaccine was authorized for emergency use in late October, most reactions to the vaccine – including arm pain, swelling, and fatigue – have been mild and gone away quickly, without the need to miss school or see a doctor, the CDC reported to a meeting of its Advisory Committee on Immunization Practices, or ACIP.

Many experts had been waiting to see if this vaccine would cause rare cases of heart inflammation called myocarditis, as a higher dose did in teens and young adults.

The news on this front was excellent. About 6 weeks after this vaccine became available, the CDC says there have been only eight confirmed cases of myocarditis in this age group. Six more cases are under investigation.

To put this risk into context, data collected by the American Academy of Pediatrics and the Children’s Hospital Association shows that about 1% of children who test positive for COVID-19 are hospitalized for their infections, while the risk of getting a case of myocarditis after vaccination is .0002%, making it about 5,000 times more likely that a child would need to be hospitalized for COVID-19 than for myocarditis after vaccination.

John Su, MD, who is a member of the CDC’s Vaccine Safety Team, reported there had been two deaths in children after a COVID-19 vaccination. Both were girls, ages 5 and 6. Both had complicated medical histories for several medical disorders. It’s not clear their deaths were linked to the vaccine, and the causes of their deaths are still under investigation.

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

Pfizer’s COVID-19 vaccine for children ages 2 to 5 years old fizzled in clinical trials, the company said on Friday, signaling a further delay in getting a vaccine to preschoolers just as Omicron bears down on the U.S.

In a news release, Pfizer reported that while its 3-microgram dose – which is less than one-third of the dose given to older children – generated a protective immune response in babies and toddlers ages 6 to 24 months, it didn’t generate adequate immunity in children ages 2 to 5.

The company plans to change its clinical trial to add a third dose for younger children in hopes of improving those results. It also plans to test a third dose of its 10-microgram vaccine for children ages 5 to 12.

If the trials are successful, Pfizer said it would submit data to the FDA for an emergency use authorization (EUA) in the first half of 2022.

That pushes the timeline of getting a vaccine to younger children back by several months. In November, Anthony Fauci, MD, head of the National Institute of Allergy Infectious Diseases, predicted a vaccine would be ready for preschoolers by spring.

“On one hand, parents are understandably disappointed,” said Jill Foster, MD, a pediatric infectious disease doctor at the University of Minnesota Medical School. “On the other, it shows that the system for testing vaccines is working. Children are not little adults and have complex immune systems, so it’s not just a matter of making the dose smaller and expecting that it will work,” she said, noting that data from Moderna’s KidCOVE study in preschoolers is pending.

Until there’s a vaccine, Dr. Foster says parents should protect babies and toddlers by making sure everyone around them is vaccinated, promote the use of face masks for everyone around them and for all children over age 2, and continue to avoid crowded gatherings, particularly those that are indoors.

“Hand sanitizer is important, but this virus, especially the Omicron variant, is very easily spread through the air, so keep the air clear of virus as much as possible,” she said.

While the youngest children are still waiting for an effective vaccine, there was reassuring news Dec. 16 about the safety of Pfizer’s vaccine for school-aged kids – those ages 5 through 11.

Out of more than 7 million doses given since this vaccine was authorized for emergency use in late October, most reactions to the vaccine – including arm pain, swelling, and fatigue – have been mild and gone away quickly, without the need to miss school or see a doctor, the CDC reported to a meeting of its Advisory Committee on Immunization Practices, or ACIP.

Many experts had been waiting to see if this vaccine would cause rare cases of heart inflammation called myocarditis, as a higher dose did in teens and young adults.

The news on this front was excellent. About 6 weeks after this vaccine became available, the CDC says there have been only eight confirmed cases of myocarditis in this age group. Six more cases are under investigation.

To put this risk into context, data collected by the American Academy of Pediatrics and the Children’s Hospital Association shows that about 1% of children who test positive for COVID-19 are hospitalized for their infections, while the risk of getting a case of myocarditis after vaccination is .0002%, making it about 5,000 times more likely that a child would need to be hospitalized for COVID-19 than for myocarditis after vaccination.

John Su, MD, who is a member of the CDC’s Vaccine Safety Team, reported there had been two deaths in children after a COVID-19 vaccination. Both were girls, ages 5 and 6. Both had complicated medical histories for several medical disorders. It’s not clear their deaths were linked to the vaccine, and the causes of their deaths are still under investigation.

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

Remarkable results were reported at the annual meeting of the American Society of Hematology for the investigational drug fitusiran to prevent bleeding in hemophilia patients.

Fitusiran is a small interfering RNA molecule that blocks antithrombin production in liver cells. Instead of taking the traditional approach in hemophilia treatment of boosting the coagulation cascade by replacing what’s missing, the idea of fitusiran is to short circuit the body’s anticoagulation system by targeting antithrombin.

Patients in two trials presented at the meeting, ATLAS-A/B and ATLAS-INH, had about a 90% reduction in their annualized bleeding rates when treated with prophylactic fitusiran, with half or more having no bleeds that required treatment during the 9-month trials. The median annualized bleeding rate fell to 0, trial investigators reported at the meeting.

These findings held in both hemophilia A and B with and without inhibitors, which are antibodies formed against exogenous clotting factors, and on subanalysis of spontaneous and joint bleeding rates. Reduced bleeding was associated with substantial improvements in health-care related quality of life, particularly in the physical health domain.
 

A question about study design

An audience member at ASH noted that the trials didn’t compare fitusiran against prophylactic treatment, which is standard of care for hemophilia, but rather against episodic treatment – concentrated factors or bypassing agents in subjects with inhibitors – once subjects in the control groups started to bleed.

Still, the numbers reported in the studies “have never been achieved with standard prophylaxis in the past.” Furthermore, standard prophylaxis requires lifelong intravenous infusions, sometimes several a week, said lead ATLAS-A/B investigator Alok Srivastava, MD, a hematologist at the Christian Medical College in Vellore, India.

Fitusiran was dosed in the studies as a once-a-month 80 mg subcutaneous injection, so is much less bothersome. Also, it seems likely that some patients will only need dosing every other month. Maker Sanofi Genzyme is exploring lower and less frequent dosing to reduce thrombotic event risks that emerged in earlier studies, said Steven Pipe, MD, a pediatric hematologist at the University of Michigan, Ann Arbor, and the senior investigator on ATLAS-A/B, which assessed fitusiran in patients without inhibitors.

Serious thrombotic events occurred in two fitusiran patients in the trials, one of which led to discontinuation.
 

No pricing information

Overall, “I think [fitusiran] is a tremendous leap forward” with “the opportunity to transform the day-to-day lives of patients,” particularly those with hemophilia B, who have limited treatment options, Dr. Pipe said.

If approved for the U.S. market, fitusiran will go up against the monoclonal antibody emicizumab (Hemlibra), a subcutaneous injection dosed weekly to monthly that mimics the function of factor VIII, so it’s approved only for hemophilia A with or without inhibitors.

Several audience members at ASH noted that a major consideration for fitusiran, if approved, will be its cost. There’s no pricing information yet, but annual list price for emicizumab is reported to be in the $500,000 range.

For hemophilia A, “it will come to what proves to be the most efficacious and safe, with also consideration given to pricing,” Nigel Key, MD, a hematologist at the University of North Carolina at Chapel Hill, said in a comment.
 

Trial details

In ATLAS-A/B, 80 male patients were randomized to prophylactic fitusiran once monthly and 40 to continue with clotting factors as needed for bleeding. Just over 20% had hemophilia B, the rest hemophilia A. The mean age was 34 years, and subjects had a mean of about 12 bleeds in the 6 months leading up to the study.

Half of the fitusiran group had no treated bleeds during the study period versus only 5% in the control arm.

The five treatment emergent serious adverse events in the fitusiran arm included cholelithiasis in two subjects, plus cholecystitis, lower respiratory tract infection, and asthma in one each. Two fitusiran patients discontinued treatment because of cholecystitis and increased alanine aminotransferase.

ATLAS-INH had the same study design, and investigated patients with inhibitors; again, just over 20% had hemophilia B, the rest A. Mean age was 28 years, and patients had a mean of about 13 bleeds over the 6 months before the study. A total of 38 subjects were randomized to fitusiran, and 19 to bypassing agents as needed.

Almost 66% of fitusiran patients had no treated bleeds versus about 5% in the control arm.

none provided

There “was far less bleeding both for hemophilia A and B. It’s definitely a clinically meaningful and important” effect, said ATLAS-INH lead investigator Guy Young, MD, director of the hemostasis and thrombosis program at Children’s Hospital Los Angeles.

He said the improved quality of life with fitusiran noted in both trials was “not surprising. If you only have to dose once a month subcutaneously, and you are not bleeding, of course your quality of life is going to improve.”

Both fitusiran thrombotic events occurred in ATLAS-INH. One patient developed deep vein thrombosis, subclavian vein thrombosis, and superficial thrombophlebitis but stayed in the study. Another discontinued after developing suspected spinal vessel thrombosis. Serious adverse events among five other subjects included acute cholecystitis and hematuria.

Fitusiran was associated with liver enzyme elevations in both trials, but they were generally mild to moderate.

The studies were funded by fitusiran maker Sanofi Genzyme. Several investigators were employees. Dr. Pipe is a consultant, Dr. Srivastava is a researcher and adviser, and Dr. Young is a speaker and consultant for the company and disclosed honoraria from it. Dr. Key had no relevant disclosures.

[email protected]

Remarkable results were reported at the annual meeting of the American Society of Hematology for the investigational drug fitusiran to prevent bleeding in hemophilia patients.

Fitusiran is a small interfering RNA molecule that blocks antithrombin production in liver cells. Instead of taking the traditional approach in hemophilia treatment of boosting the coagulation cascade by replacing what’s missing, the idea of fitusiran is to short circuit the body’s anticoagulation system by targeting antithrombin.

Patients in two trials presented at the meeting, ATLAS-A/B and ATLAS-INH, had about a 90% reduction in their annualized bleeding rates when treated with prophylactic fitusiran, with half or more having no bleeds that required treatment during the 9-month trials. The median annualized bleeding rate fell to 0, trial investigators reported at the meeting.

These findings held in both hemophilia A and B with and without inhibitors, which are antibodies formed against exogenous clotting factors, and on subanalysis of spontaneous and joint bleeding rates. Reduced bleeding was associated with substantial improvements in health-care related quality of life, particularly in the physical health domain.
 

A question about study design

An audience member at ASH noted that the trials didn’t compare fitusiran against prophylactic treatment, which is standard of care for hemophilia, but rather against episodic treatment – concentrated factors or bypassing agents in subjects with inhibitors – once subjects in the control groups started to bleed.

Still, the numbers reported in the studies “have never been achieved with standard prophylaxis in the past.” Furthermore, standard prophylaxis requires lifelong intravenous infusions, sometimes several a week, said lead ATLAS-A/B investigator Alok Srivastava, MD, a hematologist at the Christian Medical College in Vellore, India.

Fitusiran was dosed in the studies as a once-a-month 80 mg subcutaneous injection, so is much less bothersome. Also, it seems likely that some patients will only need dosing every other month. Maker Sanofi Genzyme is exploring lower and less frequent dosing to reduce thrombotic event risks that emerged in earlier studies, said Steven Pipe, MD, a pediatric hematologist at the University of Michigan, Ann Arbor, and the senior investigator on ATLAS-A/B, which assessed fitusiran in patients without inhibitors.

Serious thrombotic events occurred in two fitusiran patients in the trials, one of which led to discontinuation.
 

No pricing information

Overall, “I think [fitusiran] is a tremendous leap forward” with “the opportunity to transform the day-to-day lives of patients,” particularly those with hemophilia B, who have limited treatment options, Dr. Pipe said.

If approved for the U.S. market, fitusiran will go up against the monoclonal antibody emicizumab (Hemlibra), a subcutaneous injection dosed weekly to monthly that mimics the function of factor VIII, so it’s approved only for hemophilia A with or without inhibitors.

Several audience members at ASH noted that a major consideration for fitusiran, if approved, will be its cost. There’s no pricing information yet, but annual list price for emicizumab is reported to be in the $500,000 range.

For hemophilia A, “it will come to what proves to be the most efficacious and safe, with also consideration given to pricing,” Nigel Key, MD, a hematologist at the University of North Carolina at Chapel Hill, said in a comment.
 

Trial details

In ATLAS-A/B, 80 male patients were randomized to prophylactic fitusiran once monthly and 40 to continue with clotting factors as needed for bleeding. Just over 20% had hemophilia B, the rest hemophilia A. The mean age was 34 years, and subjects had a mean of about 12 bleeds in the 6 months leading up to the study.

Half of the fitusiran group had no treated bleeds during the study period versus only 5% in the control arm.

The five treatment emergent serious adverse events in the fitusiran arm included cholelithiasis in two subjects, plus cholecystitis, lower respiratory tract infection, and asthma in one each. Two fitusiran patients discontinued treatment because of cholecystitis and increased alanine aminotransferase.

ATLAS-INH had the same study design, and investigated patients with inhibitors; again, just over 20% had hemophilia B, the rest A. Mean age was 28 years, and patients had a mean of about 13 bleeds over the 6 months before the study. A total of 38 subjects were randomized to fitusiran, and 19 to bypassing agents as needed.

Almost 66% of fitusiran patients had no treated bleeds versus about 5% in the control arm.

none provided

There “was far less bleeding both for hemophilia A and B. It’s definitely a clinically meaningful and important” effect, said ATLAS-INH lead investigator Guy Young, MD, director of the hemostasis and thrombosis program at Children’s Hospital Los Angeles.

He said the improved quality of life with fitusiran noted in both trials was “not surprising. If you only have to dose once a month subcutaneously, and you are not bleeding, of course your quality of life is going to improve.”

Both fitusiran thrombotic events occurred in ATLAS-INH. One patient developed deep vein thrombosis, subclavian vein thrombosis, and superficial thrombophlebitis but stayed in the study. Another discontinued after developing suspected spinal vessel thrombosis. Serious adverse events among five other subjects included acute cholecystitis and hematuria.

Fitusiran was associated with liver enzyme elevations in both trials, but they were generally mild to moderate.

The studies were funded by fitusiran maker Sanofi Genzyme. Several investigators were employees. Dr. Pipe is a consultant, Dr. Srivastava is a researcher and adviser, and Dr. Young is a speaker and consultant for the company and disclosed honoraria from it. Dr. Key had no relevant disclosures.

[email protected]

Remarkable results were reported at the annual meeting of the American Society of Hematology for the investigational drug fitusiran to prevent bleeding in hemophilia patients.

Fitusiran is a small interfering RNA molecule that blocks antithrombin production in liver cells. Instead of taking the traditional approach in hemophilia treatment of boosting the coagulation cascade by replacing what’s missing, the idea of fitusiran is to short circuit the body’s anticoagulation system by targeting antithrombin.

Patients in two trials presented at the meeting, ATLAS-A/B and ATLAS-INH, had about a 90% reduction in their annualized bleeding rates when treated with prophylactic fitusiran, with half or more having no bleeds that required treatment during the 9-month trials. The median annualized bleeding rate fell to 0, trial investigators reported at the meeting.

These findings held in both hemophilia A and B with and without inhibitors, which are antibodies formed against exogenous clotting factors, and on subanalysis of spontaneous and joint bleeding rates. Reduced bleeding was associated with substantial improvements in health-care related quality of life, particularly in the physical health domain.
 

A question about study design

An audience member at ASH noted that the trials didn’t compare fitusiran against prophylactic treatment, which is standard of care for hemophilia, but rather against episodic treatment – concentrated factors or bypassing agents in subjects with inhibitors – once subjects in the control groups started to bleed.

Still, the numbers reported in the studies “have never been achieved with standard prophylaxis in the past.” Furthermore, standard prophylaxis requires lifelong intravenous infusions, sometimes several a week, said lead ATLAS-A/B investigator Alok Srivastava, MD, a hematologist at the Christian Medical College in Vellore, India.

Fitusiran was dosed in the studies as a once-a-month 80 mg subcutaneous injection, so is much less bothersome. Also, it seems likely that some patients will only need dosing every other month. Maker Sanofi Genzyme is exploring lower and less frequent dosing to reduce thrombotic event risks that emerged in earlier studies, said Steven Pipe, MD, a pediatric hematologist at the University of Michigan, Ann Arbor, and the senior investigator on ATLAS-A/B, which assessed fitusiran in patients without inhibitors.

Serious thrombotic events occurred in two fitusiran patients in the trials, one of which led to discontinuation.
 

No pricing information

Overall, “I think [fitusiran] is a tremendous leap forward” with “the opportunity to transform the day-to-day lives of patients,” particularly those with hemophilia B, who have limited treatment options, Dr. Pipe said.

If approved for the U.S. market, fitusiran will go up against the monoclonal antibody emicizumab (Hemlibra), a subcutaneous injection dosed weekly to monthly that mimics the function of factor VIII, so it’s approved only for hemophilia A with or without inhibitors.

Several audience members at ASH noted that a major consideration for fitusiran, if approved, will be its cost. There’s no pricing information yet, but annual list price for emicizumab is reported to be in the $500,000 range.

For hemophilia A, “it will come to what proves to be the most efficacious and safe, with also consideration given to pricing,” Nigel Key, MD, a hematologist at the University of North Carolina at Chapel Hill, said in a comment.
 

Trial details

In ATLAS-A/B, 80 male patients were randomized to prophylactic fitusiran once monthly and 40 to continue with clotting factors as needed for bleeding. Just over 20% had hemophilia B, the rest hemophilia A. The mean age was 34 years, and subjects had a mean of about 12 bleeds in the 6 months leading up to the study.

Half of the fitusiran group had no treated bleeds during the study period versus only 5% in the control arm.

The five treatment emergent serious adverse events in the fitusiran arm included cholelithiasis in two subjects, plus cholecystitis, lower respiratory tract infection, and asthma in one each. Two fitusiran patients discontinued treatment because of cholecystitis and increased alanine aminotransferase.

ATLAS-INH had the same study design, and investigated patients with inhibitors; again, just over 20% had hemophilia B, the rest A. Mean age was 28 years, and patients had a mean of about 13 bleeds over the 6 months before the study. A total of 38 subjects were randomized to fitusiran, and 19 to bypassing agents as needed.

Almost 66% of fitusiran patients had no treated bleeds versus about 5% in the control arm.

none provided

There “was far less bleeding both for hemophilia A and B. It’s definitely a clinically meaningful and important” effect, said ATLAS-INH lead investigator Guy Young, MD, director of the hemostasis and thrombosis program at Children’s Hospital Los Angeles.

He said the improved quality of life with fitusiran noted in both trials was “not surprising. If you only have to dose once a month subcutaneously, and you are not bleeding, of course your quality of life is going to improve.”

Both fitusiran thrombotic events occurred in ATLAS-INH. One patient developed deep vein thrombosis, subclavian vein thrombosis, and superficial thrombophlebitis but stayed in the study. Another discontinued after developing suspected spinal vessel thrombosis. Serious adverse events among five other subjects included acute cholecystitis and hematuria.

Fitusiran was associated with liver enzyme elevations in both trials, but they were generally mild to moderate.

The studies were funded by fitusiran maker Sanofi Genzyme. Several investigators were employees. Dr. Pipe is a consultant, Dr. Srivastava is a researcher and adviser, and Dr. Young is a speaker and consultant for the company and disclosed honoraria from it. Dr. Key had no relevant disclosures.

[email protected]

Physicians at a Boston hospital adjusted medical management for nearly three-quarters of patients with infantile- or childhood-onset epilepsy who were diagnosed with genetic epilepsy, researchers reported at the annual meeting of the American Epilepsy Society. The findings provide new insight into the usefulness of genetic tests in children with epilepsy of unknown cause.

“Genetic testing is significantly impacting medical care in a population of individuals with infantile- or childhood-onset epilepsy. Genetic testing should be included as part of the standard evaluation of individuals with unexplained pediatric epilepsy as a means of achieving diagnostic precision and informing clinical management,” study lead author Isabel Haviland, MD, a neurologist with Boston Children’s Hospital/Harvard Medical School, said in an interview.

According to Dr. Haviland, the causes of epilepsy are unexplained in an estimated two-thirds of pediatric epilepsy cases. “Increasingly, when genetic testing is available, previously unexplained cases of pediatric epilepsy are being found to have single-gene etiologies,” she said. “Though a genetic diagnosis in this population has implications for medical care, the direct impact on medical management in a clinical setting has not been measured. We aimed to describe the impact of genetic diagnosis on medical management in a cohort of individuals with pediatric epilepsy.”

Researchers tracked 602 patients at Boston Children’s Hospital who received next-generation gene sequencing testing from 2012 to 2019. Of those, Dr. Haviland said, 152 (25%) had a positive result that indicated genetic epilepsy (46% female, median age of onset = 6 months [2-15 months]). These patients were included in the study.

“We documented an impact on medical management in nearly three-fourths of participants (72%),” Dr. Haviland said. “A genetic diagnosis affected at least one of four categories of medical management, including care coordination (48%), treatment (45%), counseling about a change in prognosis (28%), and change in diagnosis for a few individuals who had a prior established diagnosis (1%).”

As examples, she mentioned three cases:

• Testing revealed that a subject has a disease-causing genetic variant in a gene called PRRT2. “This gene is involved in the release of neurotransmitters in the brain,” Dr. Haviland said. “Thanks to his diagnosis, he was treated with the antiseizure medication oxcarbazepine, which is often effective for epilepsy caused by variants in this gene. He had excellent response to the medication and later became seizure free.”
• A subject had a variation in the SCN1A gene that causes types of epilepsy. “At the time of his diagnosis, there was a trial for a medication called fenfluramine being offered for individuals with SCN1A variants, and his family elected to participate,” she said. “This medication was later approved by the [Food and Drug Administration] for SCN1A-related epilepsy.”
• Testing identified disease-causing variant in the GRIN2A gene in another subject. “This gene is involved in brain cell communication,” Dr. Haviland said. “This individual was treated with memantine, which acts on the specific biological pathway affected by the gene. This treatment would not have been considered without the genetic diagnosis as it is currently only approved for Alzheimer’s disease.”

In addition, Dr. Haviland said, researchers found that “there was impact on medical management both in those with earlier age of epilepsy onset (under 2 years) and those with later age of onset, as well as both in those with developmental disorders (such as autism spectrum disorder, intellectual disability and developmental delay) and those with normal development.

As for the cost of genetic tests, Dr. Haviland pointed to a 2019 study that she said estimated epilepsy panel testing runs from $1,500 to $7,500, and the whole exome sequencing from $4,500 to $7,000. “Insurers sometimes cover testing, but not always,” she said. “In some cases, insurance will only cover testing if it is documented that results will directly alter medical management, which highlights the importance of our findings.”

No study funding was reported. Dr. Haviland and several other authors report no disclosures. One author reports consulting fees from Takeda, Zogenix, Marinus, and FOXG1 Research Foundation. Another author reports research support from the International Foundation for CDKL5 Research.

Physicians at a Boston hospital adjusted medical management for nearly three-quarters of patients with infantile- or childhood-onset epilepsy who were diagnosed with genetic epilepsy, researchers reported at the annual meeting of the American Epilepsy Society. The findings provide new insight into the usefulness of genetic tests in children with epilepsy of unknown cause.

“Genetic testing is significantly impacting medical care in a population of individuals with infantile- or childhood-onset epilepsy. Genetic testing should be included as part of the standard evaluation of individuals with unexplained pediatric epilepsy as a means of achieving diagnostic precision and informing clinical management,” study lead author Isabel Haviland, MD, a neurologist with Boston Children’s Hospital/Harvard Medical School, said in an interview.

According to Dr. Haviland, the causes of epilepsy are unexplained in an estimated two-thirds of pediatric epilepsy cases. “Increasingly, when genetic testing is available, previously unexplained cases of pediatric epilepsy are being found to have single-gene etiologies,” she said. “Though a genetic diagnosis in this population has implications for medical care, the direct impact on medical management in a clinical setting has not been measured. We aimed to describe the impact of genetic diagnosis on medical management in a cohort of individuals with pediatric epilepsy.”

Researchers tracked 602 patients at Boston Children’s Hospital who received next-generation gene sequencing testing from 2012 to 2019. Of those, Dr. Haviland said, 152 (25%) had a positive result that indicated genetic epilepsy (46% female, median age of onset = 6 months [2-15 months]). These patients were included in the study.

“We documented an impact on medical management in nearly three-fourths of participants (72%),” Dr. Haviland said. “A genetic diagnosis affected at least one of four categories of medical management, including care coordination (48%), treatment (45%), counseling about a change in prognosis (28%), and change in diagnosis for a few individuals who had a prior established diagnosis (1%).”

As examples, she mentioned three cases:

• Testing revealed that a subject has a disease-causing genetic variant in a gene called PRRT2. “This gene is involved in the release of neurotransmitters in the brain,” Dr. Haviland said. “Thanks to his diagnosis, he was treated with the antiseizure medication oxcarbazepine, which is often effective for epilepsy caused by variants in this gene. He had excellent response to the medication and later became seizure free.”
• A subject had a variation in the SCN1A gene that causes types of epilepsy. “At the time of his diagnosis, there was a trial for a medication called fenfluramine being offered for individuals with SCN1A variants, and his family elected to participate,” she said. “This medication was later approved by the [Food and Drug Administration] for SCN1A-related epilepsy.”
• Testing identified disease-causing variant in the GRIN2A gene in another subject. “This gene is involved in brain cell communication,” Dr. Haviland said. “This individual was treated with memantine, which acts on the specific biological pathway affected by the gene. This treatment would not have been considered without the genetic diagnosis as it is currently only approved for Alzheimer’s disease.”

In addition, Dr. Haviland said, researchers found that “there was impact on medical management both in those with earlier age of epilepsy onset (under 2 years) and those with later age of onset, as well as both in those with developmental disorders (such as autism spectrum disorder, intellectual disability and developmental delay) and those with normal development.

As for the cost of genetic tests, Dr. Haviland pointed to a 2019 study that she said estimated epilepsy panel testing runs from $1,500 to $7,500, and the whole exome sequencing from $4,500 to $7,000. “Insurers sometimes cover testing, but not always,” she said. “In some cases, insurance will only cover testing if it is documented that results will directly alter medical management, which highlights the importance of our findings.”

No study funding was reported. Dr. Haviland and several other authors report no disclosures. One author reports consulting fees from Takeda, Zogenix, Marinus, and FOXG1 Research Foundation. Another author reports research support from the International Foundation for CDKL5 Research.

Physicians at a Boston hospital adjusted medical management for nearly three-quarters of patients with infantile- or childhood-onset epilepsy who were diagnosed with genetic epilepsy, researchers reported at the annual meeting of the American Epilepsy Society. The findings provide new insight into the usefulness of genetic tests in children with epilepsy of unknown cause.

“Genetic testing is significantly impacting medical care in a population of individuals with infantile- or childhood-onset epilepsy. Genetic testing should be included as part of the standard evaluation of individuals with unexplained pediatric epilepsy as a means of achieving diagnostic precision and informing clinical management,” study lead author Isabel Haviland, MD, a neurologist with Boston Children’s Hospital/Harvard Medical School, said in an interview.

According to Dr. Haviland, the causes of epilepsy are unexplained in an estimated two-thirds of pediatric epilepsy cases. “Increasingly, when genetic testing is available, previously unexplained cases of pediatric epilepsy are being found to have single-gene etiologies,” she said. “Though a genetic diagnosis in this population has implications for medical care, the direct impact on medical management in a clinical setting has not been measured. We aimed to describe the impact of genetic diagnosis on medical management in a cohort of individuals with pediatric epilepsy.”

Researchers tracked 602 patients at Boston Children’s Hospital who received next-generation gene sequencing testing from 2012 to 2019. Of those, Dr. Haviland said, 152 (25%) had a positive result that indicated genetic epilepsy (46% female, median age of onset = 6 months [2-15 months]). These patients were included in the study.

“We documented an impact on medical management in nearly three-fourths of participants (72%),” Dr. Haviland said. “A genetic diagnosis affected at least one of four categories of medical management, including care coordination (48%), treatment (45%), counseling about a change in prognosis (28%), and change in diagnosis for a few individuals who had a prior established diagnosis (1%).”

As examples, she mentioned three cases:

• Testing revealed that a subject has a disease-causing genetic variant in a gene called PRRT2. “This gene is involved in the release of neurotransmitters in the brain,” Dr. Haviland said. “Thanks to his diagnosis, he was treated with the antiseizure medication oxcarbazepine, which is often effective for epilepsy caused by variants in this gene. He had excellent response to the medication and later became seizure free.”
• A subject had a variation in the SCN1A gene that causes types of epilepsy. “At the time of his diagnosis, there was a trial for a medication called fenfluramine being offered for individuals with SCN1A variants, and his family elected to participate,” she said. “This medication was later approved by the [Food and Drug Administration] for SCN1A-related epilepsy.”
• Testing identified disease-causing variant in the GRIN2A gene in another subject. “This gene is involved in brain cell communication,” Dr. Haviland said. “This individual was treated with memantine, which acts on the specific biological pathway affected by the gene. This treatment would not have been considered without the genetic diagnosis as it is currently only approved for Alzheimer’s disease.”

In addition, Dr. Haviland said, researchers found that “there was impact on medical management both in those with earlier age of epilepsy onset (under 2 years) and those with later age of onset, as well as both in those with developmental disorders (such as autism spectrum disorder, intellectual disability and developmental delay) and those with normal development.

As for the cost of genetic tests, Dr. Haviland pointed to a 2019 study that she said estimated epilepsy panel testing runs from $1,500 to $7,500, and the whole exome sequencing from $4,500 to $7,000. “Insurers sometimes cover testing, but not always,” she said. “In some cases, insurance will only cover testing if it is documented that results will directly alter medical management, which highlights the importance of our findings.”

No study funding was reported. Dr. Haviland and several other authors report no disclosures. One author reports consulting fees from Takeda, Zogenix, Marinus, and FOXG1 Research Foundation. Another author reports research support from the International Foundation for CDKL5 Research.

New draft guidance from the World Professional Association for Transgender Health (WPATH) is raising serious concerns among professionals caring for people with gender dysphoria, prompting claims that WPATH is an organization “captured by activists.”

LemonTreeImages/Thinkstock

Experts in adolescent and child psychology, as well as pediatric health, have expressed dismay that the WPATH Standards of Care (SOC) 8 appear to miss some of the most urgent issues in the field of transgender medicine and are considered to express a radical and unreserved leaning towards “gender-affirmation.”

The WPATH SOC 8 document is available for view and comment until Dec. 16 until 11.59 PM EST, after which time revisions will be made and the final version published. 

Despite repeated attempts by this news organization to seek clarification on certain aspects of the guidance from members of the WPATH SOC 8 committee, requests were declined “until the guidance is finalized.”

According to the WPATH website, the SOC 8 aims to provide “clinical guidance for health professionals to assist transgender and gender diverse people with safe and effective pathways” to manage their gender dysphoria and potentially transition.

Such pathways may relate to primary care, gynecologic and urologic care, reproductive options, voice and communication therapy, mental health services, and hormonal or surgical treatments, among others.

WPATH adds that it was felt necessary to revise the existing SOC 7 (published in 2012) because of recent “globally unprecedented increase and visibility of transgender and gender-diverse people seeking support and gender-affirming medical treatment.”

Gender-affirming medical treatment means different things at different ages. In the case of kids with gender dysphoria who have not yet entered puberty associated with their birth sex, this might include prescribing so-called “puberty blockers” to delay natural puberty – gonadotrophin-releasing hormone analogs that are licensed for use in precocious puberty in children. Such agents have not been licensed for use in children with gender dysphoria, however, so any use for this purpose is off-label.

Following puberty blockade – or in cases where adolescents have already undergone natural puberty – the next step is to begin cross-sex hormones. So, for a female patient who wants to transition to male (FTM), that would be lifelong testosterone, and for a male who wants to be female (MTF), it involves lifelong estrogen. Again, use of such hormones in transgender individuals is entirely off-label.

Just last month, two of America’s leading experts on transgender medicine, both psychologists – including one who is transgender – told this news organization they were concerned that the quality of the evaluations of youth with gender dysphoria are being stifled by activists who are worried that open discussions will further stigmatize trans individuals.

They subsequently wrote an op-ed on the topic entitled, “The mental health establishment is failing trans kids,” which was finally published in the Washington Post on Nov. 24, after numerous other mainstream U.S. media outlets had rejected it.
 

New SOC 8 ‘is not evidence based,’ should not be new ‘gold standard’

One expert says the draft SOC 8 lacks balance and does not address certain issues, while paying undue attention to others that detract from real questions facing the field of transgender medicine, both in the United States and around the world.

Julia Mason, MD, is a pediatrician based in Gresham, Oregon, with a special interest in children and adolescents experiencing gender dysphoria. “The SOC 8 shows us that WPATH remains captured by activists,” she asserts. 

Dr. Mason questions the integrity of WPATH based on what she has read in the draft SOC 8.

“We need a serious organization to take a sober look at the evidence, and that is why we have established the Society for Evidence-Based Gender Medicine [SEGM],” she noted. “This is what we do – we are looking at all of the evidence.”

Dr. Mason is a clinical advisor to SEGM, an organization set-up to evaluate current interventions and evidence on gender dysphoria.

The pediatrician has particular concerns regarding the child and adolescent chapters in the draft SOC 8. The adolescent chapter states: “Guidelines are meant to provide a gold standard based on the available evidence at this moment of time.”

Dr. Mason disputes this assertion. “This document should not be the new gold standard going forward, primarily because it is not evidence based.”

In an interview, Dr. Mason explained that WPATH say they used the “Delphi consensus process” to determine their recommendations, but “this process is designed for use with a panel of experts when evidence is lacking. I would say they didn’t have a panel of experts. They largely had a panel of activists, with a few experts.”

There is no mention, for example, of England’s National Institute for Health and Care Excellence (NICE) evidence reviews on puberty blockers and cross-sex hormones from earlier this year. These reviews determined that no studies have compared cross-sex hormones or puberty blockers with a control group and all follow-up periods for cross-sex hormones were relatively short.

This disappoints Dr. Mason: “These are significant; they are important documents.”

And much of the evidence quoted comes from the well-known and often-quoted “Dutch-protocol” study of 2011, in which the children studied were much younger at the time of their gender dysphoria, compared with the many adolescents who make up the current surge in presentation at gender clinics worldwide, she adds.
 

Rapid-onset GD: adolescents presenting late with little history

Dr. Mason also stresses that the SOC 8 does not address the most urgent issues in transgender medicine today, mainly because it does not address rapid-onset gender dysphoria (ROGD): “This is the dilemma of the 21st century; it’s new.”

ROGD – a term first coined in 2018 by researcher Lisa Littman, MD, MPH, now president of the Institute for Comprehensive Gender Dysphoria Research (ICGDR) – refers to the phenomena of adolescents expressing a desire to transition from their birth sex after little or no apparent previous indication.

However, the SOC 8 does make reference to aspects of adolescent development that might impact their decision-making processes around gender identity during teen years. The chapter on adolescents reads: “... adolescence is also often associated with increased risk-taking behaviors. Along with these notable changes ... individuation from parents ... [there is] often a heightened focus on peer relationships, which can be both positive and detrimental.” 

The guidance goes on to point out that “it is critical to understand how all of these aspects of development may impact the decision-making for a given young person within their specific cultural context.” 
 

Desistance and detransitioning not adequately addressed

Dr. Mason also says there is little mention “about detransitioning in this SOC [8], and ‘gender dysphoria’ and ‘trans’ are terms that are not defined.” 

Likewise, there is no mention of desistance, she highlights, which is when individuals naturally resolve their dysphoria around their birth sex as they grow older.

The most recent published data seen by this news organization relates to a study from March 2021 that showed nearly 88% of boys who struggled with gender identity in childhood (approximate mean age 8 years and follow-up at approximate mean age 20 years) desisted. It reads: “Of the 139 participants, 17 (12.2%) were classified as ‘persisters’ and the remaining 122 (87.8%) were classified as desisters.”

“Most children with gender dysphoria will desist and lose their concept of themselves as being the opposite gender,” Dr. Mason explains. “This is the safest path for a child – desistance.”

“Transition can turn a healthy young person into a lifelong medical patient and has significant health risks,” she emphasizes, stressing that transition has not been shown to decrease the probability of suicide, or attempts at suicide, despite myriad claims saying otherwise. 

“Before we were routinely transitioning kids at school, the vast majority of children grew out of their gender dysphoria. This history is not recognized at all in these SOC [8],” she maintains.

Ken Zucker, PhD, CPsych, an author of the study of desistance in boys, says the terms desistence and persistence of gender dysphoria have caused some consternation in certain circles.

An editor of the Archives of Sexual Behavior and professor in the department of psychiatry, University of Toronto, Dr. Zucker has published widely on the topic.

He told this news organization: “The terms persistence and desistance have become verboten among the WPATH cognoscenti. Perhaps the contributors to SOC 8 have come up with alternative descriptors.”  

“The term ‘desistance’ is particularly annoying to some of the gender-affirming clinicians, because they don’t believe that desistance is bona fide,” Dr. Zucker points out.

“The desistance resisters are like anti-vaxxers – nothing one can provide as evidence for the efficacy of vaccines is sufficient. There will always be a new objection.” 

Other mental health issues, in particular ADHD and autism

It is also widely acknowledged that there is a higher rate of neurodevelopmental and psychiatric diagnoses in individuals with gender dysphoria. For example, one 2020 study found that transgender people were three to six times as likely to be autistic as cisgender people (those whose gender is aligned with their birth sex). 

Statement one in the chapter on adolescents in draft WPATH SOC 8 does give a nod to this, pointing out that health professionals working with gender diverse adolescents “should receive training and develop expertise in autism spectrum disorders and other neurodiversity conditions.”

It also notes that in some cases “a more extended assessment process may be useful, such as for youth with more complex presentations (e.g., complicated mental health histories, co-occurring autism spectrum characteristics in particular) and an absence of experienced childhood gender incongruence.”

However, Dr. Mason stresses that underlying mental health issues are central to addressing how to manage a significant number of these patients.

“If a young person has ADHD or autism, they are not ready to make decisions about the rest of their life at age 18. Even a neurotypical young person is still developing their frontal cortex in their early 20s, and it takes longer for those with ADHD or on the autism spectrum.”

She firmly believes that the guidance does not give sufficient consideration to comorbidities in people over the age of 18.

According to their [SOC 8] guidelines, “once someone is 18 they are ready for anything,” says Dr. Mason.  

Offering some explanation for the increased prevalence of ADHD and autism in those with gender dysphoria, Dr. Mason notes that children can have “hyperfocus” and those with autism will fixate on a particular area of interest. “If a child is unhappy in their life, and this can be more likely if someone is neuro-atypical, then it is likely that the individual might go online and find this one solution [for example, a transgender identity] that seems to fix everything.” 

Perceptions of femininity and masculinity can also be extra challenging for a child with autism, Dr. Mason says. “It is relatively easy for an autistic girl to feel like she should be a boy because the rules of femininity are composed of nonverbal, subtle behaviors that can be difficult to pick up on,” she points out. “An autistic child who isn’t particularly good at nonverbal communication might not pick up on these and thus feel they are not very ‘female.’” 

“There’s a whole lot of grass-is-greener-type thinking. Girls think boys have an easier life, and boys think girls have an easier life. I know some detransitioners who have spoken eloquently about realizing their mistake on this,” she adds.

Other parts of the SOC 8 that Dr. Mason disagrees with include the recommendation in the adolescent chapter that 14-year-olds are mature enough to start cross-sex hormones, that is, giving testosterone to a female who wants to transition to male or estrogen to a male who wishes to transition to female. “I think that’s far too young,” she asserts.

And she points out that the document states 17-year-olds are ready for genital reassignment surgery. Again, she believes this is far too young.

“Also, the SOC 8 document does not clarify who is appropriate for surgery. Whenever surgery is discussed, it becomes very vague,” she said. 

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

New draft guidance from the World Professional Association for Transgender Health (WPATH) is raising serious concerns among professionals caring for people with gender dysphoria, prompting claims that WPATH is an organization “captured by activists.”

LemonTreeImages/Thinkstock

Experts in adolescent and child psychology, as well as pediatric health, have expressed dismay that the WPATH Standards of Care (SOC) 8 appear to miss some of the most urgent issues in the field of transgender medicine and are considered to express a radical and unreserved leaning towards “gender-affirmation.”

The WPATH SOC 8 document is available for view and comment until Dec. 16 until 11.59 PM EST, after which time revisions will be made and the final version published. 

Despite repeated attempts by this news organization to seek clarification on certain aspects of the guidance from members of the WPATH SOC 8 committee, requests were declined “until the guidance is finalized.”

According to the WPATH website, the SOC 8 aims to provide “clinical guidance for health professionals to assist transgender and gender diverse people with safe and effective pathways” to manage their gender dysphoria and potentially transition.

Such pathways may relate to primary care, gynecologic and urologic care, reproductive options, voice and communication therapy, mental health services, and hormonal or surgical treatments, among others.

WPATH adds that it was felt necessary to revise the existing SOC 7 (published in 2012) because of recent “globally unprecedented increase and visibility of transgender and gender-diverse people seeking support and gender-affirming medical treatment.”

Gender-affirming medical treatment means different things at different ages. In the case of kids with gender dysphoria who have not yet entered puberty associated with their birth sex, this might include prescribing so-called “puberty blockers” to delay natural puberty – gonadotrophin-releasing hormone analogs that are licensed for use in precocious puberty in children. Such agents have not been licensed for use in children with gender dysphoria, however, so any use for this purpose is off-label.

Following puberty blockade – or in cases where adolescents have already undergone natural puberty – the next step is to begin cross-sex hormones. So, for a female patient who wants to transition to male (FTM), that would be lifelong testosterone, and for a male who wants to be female (MTF), it involves lifelong estrogen. Again, use of such hormones in transgender individuals is entirely off-label.

Just last month, two of America’s leading experts on transgender medicine, both psychologists – including one who is transgender – told this news organization they were concerned that the quality of the evaluations of youth with gender dysphoria are being stifled by activists who are worried that open discussions will further stigmatize trans individuals.

They subsequently wrote an op-ed on the topic entitled, “The mental health establishment is failing trans kids,” which was finally published in the Washington Post on Nov. 24, after numerous other mainstream U.S. media outlets had rejected it.
 

New SOC 8 ‘is not evidence based,’ should not be new ‘gold standard’

One expert says the draft SOC 8 lacks balance and does not address certain issues, while paying undue attention to others that detract from real questions facing the field of transgender medicine, both in the United States and around the world.

Julia Mason, MD, is a pediatrician based in Gresham, Oregon, with a special interest in children and adolescents experiencing gender dysphoria. “The SOC 8 shows us that WPATH remains captured by activists,” she asserts. 

Dr. Mason questions the integrity of WPATH based on what she has read in the draft SOC 8.

“We need a serious organization to take a sober look at the evidence, and that is why we have established the Society for Evidence-Based Gender Medicine [SEGM],” she noted. “This is what we do – we are looking at all of the evidence.”

Dr. Mason is a clinical advisor to SEGM, an organization set-up to evaluate current interventions and evidence on gender dysphoria.

The pediatrician has particular concerns regarding the child and adolescent chapters in the draft SOC 8. The adolescent chapter states: “Guidelines are meant to provide a gold standard based on the available evidence at this moment of time.”

Dr. Mason disputes this assertion. “This document should not be the new gold standard going forward, primarily because it is not evidence based.”

In an interview, Dr. Mason explained that WPATH say they used the “Delphi consensus process” to determine their recommendations, but “this process is designed for use with a panel of experts when evidence is lacking. I would say they didn’t have a panel of experts. They largely had a panel of activists, with a few experts.”

There is no mention, for example, of England’s National Institute for Health and Care Excellence (NICE) evidence reviews on puberty blockers and cross-sex hormones from earlier this year. These reviews determined that no studies have compared cross-sex hormones or puberty blockers with a control group and all follow-up periods for cross-sex hormones were relatively short.

This disappoints Dr. Mason: “These are significant; they are important documents.”

And much of the evidence quoted comes from the well-known and often-quoted “Dutch-protocol” study of 2011, in which the children studied were much younger at the time of their gender dysphoria, compared with the many adolescents who make up the current surge in presentation at gender clinics worldwide, she adds.
 

Rapid-onset GD: adolescents presenting late with little history

Dr. Mason also stresses that the SOC 8 does not address the most urgent issues in transgender medicine today, mainly because it does not address rapid-onset gender dysphoria (ROGD): “This is the dilemma of the 21st century; it’s new.”

ROGD – a term first coined in 2018 by researcher Lisa Littman, MD, MPH, now president of the Institute for Comprehensive Gender Dysphoria Research (ICGDR) – refers to the phenomena of adolescents expressing a desire to transition from their birth sex after little or no apparent previous indication.

However, the SOC 8 does make reference to aspects of adolescent development that might impact their decision-making processes around gender identity during teen years. The chapter on adolescents reads: “... adolescence is also often associated with increased risk-taking behaviors. Along with these notable changes ... individuation from parents ... [there is] often a heightened focus on peer relationships, which can be both positive and detrimental.” 

The guidance goes on to point out that “it is critical to understand how all of these aspects of development may impact the decision-making for a given young person within their specific cultural context.” 
 

Desistance and detransitioning not adequately addressed

Dr. Mason also says there is little mention “about detransitioning in this SOC [8], and ‘gender dysphoria’ and ‘trans’ are terms that are not defined.” 

Likewise, there is no mention of desistance, she highlights, which is when individuals naturally resolve their dysphoria around their birth sex as they grow older.

The most recent published data seen by this news organization relates to a study from March 2021 that showed nearly 88% of boys who struggled with gender identity in childhood (approximate mean age 8 years and follow-up at approximate mean age 20 years) desisted. It reads: “Of the 139 participants, 17 (12.2%) were classified as ‘persisters’ and the remaining 122 (87.8%) were classified as desisters.”

“Most children with gender dysphoria will desist and lose their concept of themselves as being the opposite gender,” Dr. Mason explains. “This is the safest path for a child – desistance.”

“Transition can turn a healthy young person into a lifelong medical patient and has significant health risks,” she emphasizes, stressing that transition has not been shown to decrease the probability of suicide, or attempts at suicide, despite myriad claims saying otherwise. 

“Before we were routinely transitioning kids at school, the vast majority of children grew out of their gender dysphoria. This history is not recognized at all in these SOC [8],” she maintains.

Ken Zucker, PhD, CPsych, an author of the study of desistance in boys, says the terms desistence and persistence of gender dysphoria have caused some consternation in certain circles.

An editor of the Archives of Sexual Behavior and professor in the department of psychiatry, University of Toronto, Dr. Zucker has published widely on the topic.

He told this news organization: “The terms persistence and desistance have become verboten among the WPATH cognoscenti. Perhaps the contributors to SOC 8 have come up with alternative descriptors.”  

“The term ‘desistance’ is particularly annoying to some of the gender-affirming clinicians, because they don’t believe that desistance is bona fide,” Dr. Zucker points out.

“The desistance resisters are like anti-vaxxers – nothing one can provide as evidence for the efficacy of vaccines is sufficient. There will always be a new objection.” 

Other mental health issues, in particular ADHD and autism

It is also widely acknowledged that there is a higher rate of neurodevelopmental and psychiatric diagnoses in individuals with gender dysphoria. For example, one 2020 study found that transgender people were three to six times as likely to be autistic as cisgender people (those whose gender is aligned with their birth sex). 

Statement one in the chapter on adolescents in draft WPATH SOC 8 does give a nod to this, pointing out that health professionals working with gender diverse adolescents “should receive training and develop expertise in autism spectrum disorders and other neurodiversity conditions.”

It also notes that in some cases “a more extended assessment process may be useful, such as for youth with more complex presentations (e.g., complicated mental health histories, co-occurring autism spectrum characteristics in particular) and an absence of experienced childhood gender incongruence.”

However, Dr. Mason stresses that underlying mental health issues are central to addressing how to manage a significant number of these patients.

“If a young person has ADHD or autism, they are not ready to make decisions about the rest of their life at age 18. Even a neurotypical young person is still developing their frontal cortex in their early 20s, and it takes longer for those with ADHD or on the autism spectrum.”

She firmly believes that the guidance does not give sufficient consideration to comorbidities in people over the age of 18.

According to their [SOC 8] guidelines, “once someone is 18 they are ready for anything,” says Dr. Mason.  

Offering some explanation for the increased prevalence of ADHD and autism in those with gender dysphoria, Dr. Mason notes that children can have “hyperfocus” and those with autism will fixate on a particular area of interest. “If a child is unhappy in their life, and this can be more likely if someone is neuro-atypical, then it is likely that the individual might go online and find this one solution [for example, a transgender identity] that seems to fix everything.” 

Perceptions of femininity and masculinity can also be extra challenging for a child with autism, Dr. Mason says. “It is relatively easy for an autistic girl to feel like she should be a boy because the rules of femininity are composed of nonverbal, subtle behaviors that can be difficult to pick up on,” she points out. “An autistic child who isn’t particularly good at nonverbal communication might not pick up on these and thus feel they are not very ‘female.’” 

“There’s a whole lot of grass-is-greener-type thinking. Girls think boys have an easier life, and boys think girls have an easier life. I know some detransitioners who have spoken eloquently about realizing their mistake on this,” she adds.

Other parts of the SOC 8 that Dr. Mason disagrees with include the recommendation in the adolescent chapter that 14-year-olds are mature enough to start cross-sex hormones, that is, giving testosterone to a female who wants to transition to male or estrogen to a male who wishes to transition to female. “I think that’s far too young,” she asserts.

And she points out that the document states 17-year-olds are ready for genital reassignment surgery. Again, she believes this is far too young.

“Also, the SOC 8 document does not clarify who is appropriate for surgery. Whenever surgery is discussed, it becomes very vague,” she said. 

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

New draft guidance from the World Professional Association for Transgender Health (WPATH) is raising serious concerns among professionals caring for people with gender dysphoria, prompting claims that WPATH is an organization “captured by activists.”

LemonTreeImages/Thinkstock

Experts in adolescent and child psychology, as well as pediatric health, have expressed dismay that the WPATH Standards of Care (SOC) 8 appear to miss some of the most urgent issues in the field of transgender medicine and are considered to express a radical and unreserved leaning towards “gender-affirmation.”

The WPATH SOC 8 document is available for view and comment until Dec. 16 until 11.59 PM EST, after which time revisions will be made and the final version published. 

Despite repeated attempts by this news organization to seek clarification on certain aspects of the guidance from members of the WPATH SOC 8 committee, requests were declined “until the guidance is finalized.”

According to the WPATH website, the SOC 8 aims to provide “clinical guidance for health professionals to assist transgender and gender diverse people with safe and effective pathways” to manage their gender dysphoria and potentially transition.

Such pathways may relate to primary care, gynecologic and urologic care, reproductive options, voice and communication therapy, mental health services, and hormonal or surgical treatments, among others.

WPATH adds that it was felt necessary to revise the existing SOC 7 (published in 2012) because of recent “globally unprecedented increase and visibility of transgender and gender-diverse people seeking support and gender-affirming medical treatment.”

Gender-affirming medical treatment means different things at different ages. In the case of kids with gender dysphoria who have not yet entered puberty associated with their birth sex, this might include prescribing so-called “puberty blockers” to delay natural puberty – gonadotrophin-releasing hormone analogs that are licensed for use in precocious puberty in children. Such agents have not been licensed for use in children with gender dysphoria, however, so any use for this purpose is off-label.

Following puberty blockade – or in cases where adolescents have already undergone natural puberty – the next step is to begin cross-sex hormones. So, for a female patient who wants to transition to male (FTM), that would be lifelong testosterone, and for a male who wants to be female (MTF), it involves lifelong estrogen. Again, use of such hormones in transgender individuals is entirely off-label.

Just last month, two of America’s leading experts on transgender medicine, both psychologists – including one who is transgender – told this news organization they were concerned that the quality of the evaluations of youth with gender dysphoria are being stifled by activists who are worried that open discussions will further stigmatize trans individuals.

They subsequently wrote an op-ed on the topic entitled, “The mental health establishment is failing trans kids,” which was finally published in the Washington Post on Nov. 24, after numerous other mainstream U.S. media outlets had rejected it.
 

New SOC 8 ‘is not evidence based,’ should not be new ‘gold standard’

One expert says the draft SOC 8 lacks balance and does not address certain issues, while paying undue attention to others that detract from real questions facing the field of transgender medicine, both in the United States and around the world.

Julia Mason, MD, is a pediatrician based in Gresham, Oregon, with a special interest in children and adolescents experiencing gender dysphoria. “The SOC 8 shows us that WPATH remains captured by activists,” she asserts. 

Dr. Mason questions the integrity of WPATH based on what she has read in the draft SOC 8.

“We need a serious organization to take a sober look at the evidence, and that is why we have established the Society for Evidence-Based Gender Medicine [SEGM],” she noted. “This is what we do – we are looking at all of the evidence.”

Dr. Mason is a clinical advisor to SEGM, an organization set-up to evaluate current interventions and evidence on gender dysphoria.

The pediatrician has particular concerns regarding the child and adolescent chapters in the draft SOC 8. The adolescent chapter states: “Guidelines are meant to provide a gold standard based on the available evidence at this moment of time.”

Dr. Mason disputes this assertion. “This document should not be the new gold standard going forward, primarily because it is not evidence based.”

In an interview, Dr. Mason explained that WPATH say they used the “Delphi consensus process” to determine their recommendations, but “this process is designed for use with a panel of experts when evidence is lacking. I would say they didn’t have a panel of experts. They largely had a panel of activists, with a few experts.”

There is no mention, for example, of England’s National Institute for Health and Care Excellence (NICE) evidence reviews on puberty blockers and cross-sex hormones from earlier this year. These reviews determined that no studies have compared cross-sex hormones or puberty blockers with a control group and all follow-up periods for cross-sex hormones were relatively short.

This disappoints Dr. Mason: “These are significant; they are important documents.”

And much of the evidence quoted comes from the well-known and often-quoted “Dutch-protocol” study of 2011, in which the children studied were much younger at the time of their gender dysphoria, compared with the many adolescents who make up the current surge in presentation at gender clinics worldwide, she adds.
 

Rapid-onset GD: adolescents presenting late with little history

Dr. Mason also stresses that the SOC 8 does not address the most urgent issues in transgender medicine today, mainly because it does not address rapid-onset gender dysphoria (ROGD): “This is the dilemma of the 21st century; it’s new.”

ROGD – a term first coined in 2018 by researcher Lisa Littman, MD, MPH, now president of the Institute for Comprehensive Gender Dysphoria Research (ICGDR) – refers to the phenomena of adolescents expressing a desire to transition from their birth sex after little or no apparent previous indication.

However, the SOC 8 does make reference to aspects of adolescent development that might impact their decision-making processes around gender identity during teen years. The chapter on adolescents reads: “... adolescence is also often associated with increased risk-taking behaviors. Along with these notable changes ... individuation from parents ... [there is] often a heightened focus on peer relationships, which can be both positive and detrimental.” 

The guidance goes on to point out that “it is critical to understand how all of these aspects of development may impact the decision-making for a given young person within their specific cultural context.” 
 

Desistance and detransitioning not adequately addressed

Dr. Mason also says there is little mention “about detransitioning in this SOC [8], and ‘gender dysphoria’ and ‘trans’ are terms that are not defined.” 

Likewise, there is no mention of desistance, she highlights, which is when individuals naturally resolve their dysphoria around their birth sex as they grow older.

The most recent published data seen by this news organization relates to a study from March 2021 that showed nearly 88% of boys who struggled with gender identity in childhood (approximate mean age 8 years and follow-up at approximate mean age 20 years) desisted. It reads: “Of the 139 participants, 17 (12.2%) were classified as ‘persisters’ and the remaining 122 (87.8%) were classified as desisters.”

“Most children with gender dysphoria will desist and lose their concept of themselves as being the opposite gender,” Dr. Mason explains. “This is the safest path for a child – desistance.”

“Transition can turn a healthy young person into a lifelong medical patient and has significant health risks,” she emphasizes, stressing that transition has not been shown to decrease the probability of suicide, or attempts at suicide, despite myriad claims saying otherwise. 

“Before we were routinely transitioning kids at school, the vast majority of children grew out of their gender dysphoria. This history is not recognized at all in these SOC [8],” she maintains.

Ken Zucker, PhD, CPsych, an author of the study of desistance in boys, says the terms desistence and persistence of gender dysphoria have caused some consternation in certain circles.

An editor of the Archives of Sexual Behavior and professor in the department of psychiatry, University of Toronto, Dr. Zucker has published widely on the topic.

He told this news organization: “The terms persistence and desistance have become verboten among the WPATH cognoscenti. Perhaps the contributors to SOC 8 have come up with alternative descriptors.”  

“The term ‘desistance’ is particularly annoying to some of the gender-affirming clinicians, because they don’t believe that desistance is bona fide,” Dr. Zucker points out.

“The desistance resisters are like anti-vaxxers – nothing one can provide as evidence for the efficacy of vaccines is sufficient. There will always be a new objection.” 

Other mental health issues, in particular ADHD and autism

It is also widely acknowledged that there is a higher rate of neurodevelopmental and psychiatric diagnoses in individuals with gender dysphoria. For example, one 2020 study found that transgender people were three to six times as likely to be autistic as cisgender people (those whose gender is aligned with their birth sex). 

Statement one in the chapter on adolescents in draft WPATH SOC 8 does give a nod to this, pointing out that health professionals working with gender diverse adolescents “should receive training and develop expertise in autism spectrum disorders and other neurodiversity conditions.”

It also notes that in some cases “a more extended assessment process may be useful, such as for youth with more complex presentations (e.g., complicated mental health histories, co-occurring autism spectrum characteristics in particular) and an absence of experienced childhood gender incongruence.”

However, Dr. Mason stresses that underlying mental health issues are central to addressing how to manage a significant number of these patients.

“If a young person has ADHD or autism, they are not ready to make decisions about the rest of their life at age 18. Even a neurotypical young person is still developing their frontal cortex in their early 20s, and it takes longer for those with ADHD or on the autism spectrum.”

She firmly believes that the guidance does not give sufficient consideration to comorbidities in people over the age of 18.

According to their [SOC 8] guidelines, “once someone is 18 they are ready for anything,” says Dr. Mason.  

Offering some explanation for the increased prevalence of ADHD and autism in those with gender dysphoria, Dr. Mason notes that children can have “hyperfocus” and those with autism will fixate on a particular area of interest. “If a child is unhappy in their life, and this can be more likely if someone is neuro-atypical, then it is likely that the individual might go online and find this one solution [for example, a transgender identity] that seems to fix everything.” 

Perceptions of femininity and masculinity can also be extra challenging for a child with autism, Dr. Mason says. “It is relatively easy for an autistic girl to feel like she should be a boy because the rules of femininity are composed of nonverbal, subtle behaviors that can be difficult to pick up on,” she points out. “An autistic child who isn’t particularly good at nonverbal communication might not pick up on these and thus feel they are not very ‘female.’” 

“There’s a whole lot of grass-is-greener-type thinking. Girls think boys have an easier life, and boys think girls have an easier life. I know some detransitioners who have spoken eloquently about realizing their mistake on this,” she adds.

Other parts of the SOC 8 that Dr. Mason disagrees with include the recommendation in the adolescent chapter that 14-year-olds are mature enough to start cross-sex hormones, that is, giving testosterone to a female who wants to transition to male or estrogen to a male who wishes to transition to female. “I think that’s far too young,” she asserts.

And she points out that the document states 17-year-olds are ready for genital reassignment surgery. Again, she believes this is far too young.

“Also, the SOC 8 document does not clarify who is appropriate for surgery. Whenever surgery is discussed, it becomes very vague,” she said. 

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

The advisory on youth mental health from Surgeon General Vivek Murthy, MD, casts a necessary spotlight on the crisis, clinical psychiatrists say. But some think it could have produced more specifics about funding and payment parity for reimbursement.

The 53-page advisory says that about one in five U.S. children and adolescents aged 3-17 suffer from a mental, emotional, developmental, or behavioral disorder. In the decade before COVID, feelings of sadness and hopelessness, as well as suicidal behaviors, were on the rise. The pandemic has exacerbated symptoms of anxiety, depression, and other mental health issues in young people. Compared with 2019, ED visits in early 2021 for suspected suicide attempts rose 51% in adolescent girls and 4% in boys. “Depressive and anxiety symptoms doubled during the pandemic,” the advisory said.
 

Scope of the advisory

The advisory, released Dec. 7, covers all sectors and considers all social and policy factors that might be contributing to this crisis, said Jessica (Jessi) Gold, MD, MS, an assistant professor in the department of psychiatry at Washington University, St. Louis.

“It is always possible to reimagine health care to be more patient centered and mental health forward.” But changes of this magnitude take time, Dr. Gold, also director of wellness, engagement, and outreach at the university, said in an interview.

She has seen the impact of the pandemic firsthand in her clinic among students and frontline health care workers aged 18-30. People in that age group “feel everything deeply,” Dr. Gold said. Emotions tied to COVID-19 are just a part of it. Confounding factors, such as climate change, racism, and school shootings all contribute to their overall mental health.

Some children and adolescents with social anxiety have fared better during the pandemic, but those who are part of demographic groups such as racial and ethnic minorities, LGBTQ individuals, low-income youth, and those involved in juvenile justice or welfare systems face a higher risk of mental health challenges, the pandemic notwithstanding.

In her work with schools, Denese Shervington, MD, MPH, has witnessed more mental health challenges related to isolation and separation. “There’s an overall worry about the loss of what used to be, the seeming predictability and certainty of prepandemic life,” said Dr. Shervington, clinical professor of psychiatry at Tulane University, and president and CEO of the Institute for Women and Ethnic Studies, both in New Orleans.
 

A systems of care plan

The advisory lists actionable items for health care and 10 other industry sectors to improve mental health of children and young adults.

Health care organizations and professionals were advised to take the following six steps:

• Implement trauma-informed care principles and other prevention strategies. This may involve referring patients to resources such as economic and legal supports, school enrichment programs, and educating families on healthy child development in the clinic.
• Routinely screen children for mental health challenges and risk factors such as adverse childhood experiences during primary care well-visits or annual physicals, or at schools or EDs. Primary care physicians should use principles of trauma-informed care to conduct these screenings.
• Screen parents, caregivers, and other family members for depression, intimate partner violence, substance use, and other challenges. These can be done in tandem with broader assessments of social determinants of health such as food or housing insecurity.
• Combine efforts of clinical staff with trusted community partners and child welfare and juvenile justice. Hospital-based violence intervention programs, for example, identify patients at risk of repeat violent injury and refer them to hospital- and community-based resources.
• Build multidisciplinary teams, enlisting children and families to develop services that are tailored to their needs for screening and treatment. Such services should reflect cultural diversity and offered in multiple languages.
• Support the well-being of mental health workers and community leaders to foster their ability to help youth and their families.

Dr. Murthy is talking about a “systems of care” approach, in which all sectors that touch children and youth – not just health care – must work together and do their jobs effectively but collaboratively to address this public health crisis, said Aradhana (Bela) Sood MD, MSHA, FAACAP, senior professor of child mental health policy at Virginia Commonwealth University, Richmond. “An investment in infrastructure support of positive mental health in early childhood, be it in schools, communities, or family well-being will lead to a future where illness is not the result of major preventable societal factors, such as a lack of social supports and trauma.”
 

Changes will ‘take a lot of buy-in’

The recommendations are actionable in the real world – but there are a lot of them, said Dr. Gold. Dr. Murthy doesn’t specify what the plan is to accomplish these metrics or fund them, she added. He “has money and funders like foundations as steps, but foundations have also suffered in the pandemic, so it is not that simple.” Many of these changes are wide in scope and will take a lot of buy-in.

Dr. Shervington would like to have seen more of a focus on educator well-being, given that young people spend a lot of time in educational settings.

“My organization just completed a study in New Orleans that showed teachers having elevated levels of trauma-based conditions since the pandemic,” she said. Schools are indeed a key place to support holistic mental health by focusing on school climate, Dr. Sood added. “If school administrators became uniformly consistent with recognizing the importance of psychological wellness as a prerequisite of good learning, they will create environments where teachers are keenly aware of a child’s mental wellness and make reduction of bullying, wellness check-ins, [and] school-based mental health clinics a priority.

“These are ways nonmedical, community-based supports can enhance student well-being, and reduce depression and other mental health conditions,” Dr. Sood added.
 

Child psychiatrists stretched ‘even thinner’

Despite mental health parity rules, health plans have not been held accountable. That failure, combined with excessive demands for prior authorization for mental health treatments “have led to dangerous shortages of psychiatrists able to accept insurance,” said Paul S. Nestadt, MD, an assistant professor and public mental health researcher at Johns Hopkins University, Baltimore.

“This is particularly true for child psychiatrists, who are stretched even thinner than those of us in general practice,” Dr. Nestadt said.

While he doesn’t address it head on, Dr. Murthy uses classic parity language when he states that “mental health is no less important than physical health,” said Dr. Nestadt, who consulted with the surgeon general on developing this advisory. “While many of us would have liked to see parity highlighted more directly, this advisory was designed to be an overview.”
 

Highlighting social media, gun violence

Dr. Nestadt said he was pleased that the advisory emphasized the importance of restricting access to lethal means in preventing youth suicide.

“With youth suicide rates rising faster than in other age groups, and suicide mortality tied so closely to method availability, the surgeon general made the right choice in highlighting the role of guns in suicide,” he said.

The advisory also discussed the role of media and social media companies in addressing the crisis, which is important, said Dr. Gold.

“I believe very strongly that the way we talk about and portray mental health in the media matters,” she said. “I have seen it matter in the clinic with patients. They’ll wonder if someone will think they are now violent if they are diagnosed with a mental illness. Stories change the narrative.”

While the advisory isn’t perfect, the state of youth mental health “will only get worse if we don’t do something,” noted Dr. Gold. “It is critical that this is validated and discussed at the highest level and messages like Dr. Murthy’s get heard.”

Dr. Gold, Dr. Shervington, and Dr. Sood had no disclosures. Dr. Nestadt disclosed serving as a consultant to the surgeon general advisory.

The advisory on youth mental health from Surgeon General Vivek Murthy, MD, casts a necessary spotlight on the crisis, clinical psychiatrists say. But some think it could have produced more specifics about funding and payment parity for reimbursement.

The 53-page advisory says that about one in five U.S. children and adolescents aged 3-17 suffer from a mental, emotional, developmental, or behavioral disorder. In the decade before COVID, feelings of sadness and hopelessness, as well as suicidal behaviors, were on the rise. The pandemic has exacerbated symptoms of anxiety, depression, and other mental health issues in young people. Compared with 2019, ED visits in early 2021 for suspected suicide attempts rose 51% in adolescent girls and 4% in boys. “Depressive and anxiety symptoms doubled during the pandemic,” the advisory said.
 

Scope of the advisory

The advisory, released Dec. 7, covers all sectors and considers all social and policy factors that might be contributing to this crisis, said Jessica (Jessi) Gold, MD, MS, an assistant professor in the department of psychiatry at Washington University, St. Louis.

“It is always possible to reimagine health care to be more patient centered and mental health forward.” But changes of this magnitude take time, Dr. Gold, also director of wellness, engagement, and outreach at the university, said in an interview.

She has seen the impact of the pandemic firsthand in her clinic among students and frontline health care workers aged 18-30. People in that age group “feel everything deeply,” Dr. Gold said. Emotions tied to COVID-19 are just a part of it. Confounding factors, such as climate change, racism, and school shootings all contribute to their overall mental health.

Some children and adolescents with social anxiety have fared better during the pandemic, but those who are part of demographic groups such as racial and ethnic minorities, LGBTQ individuals, low-income youth, and those involved in juvenile justice or welfare systems face a higher risk of mental health challenges, the pandemic notwithstanding.

In her work with schools, Denese Shervington, MD, MPH, has witnessed more mental health challenges related to isolation and separation. “There’s an overall worry about the loss of what used to be, the seeming predictability and certainty of prepandemic life,” said Dr. Shervington, clinical professor of psychiatry at Tulane University, and president and CEO of the Institute for Women and Ethnic Studies, both in New Orleans.
 

A systems of care plan

The advisory lists actionable items for health care and 10 other industry sectors to improve mental health of children and young adults.

Health care organizations and professionals were advised to take the following six steps:

• Implement trauma-informed care principles and other prevention strategies. This may involve referring patients to resources such as economic and legal supports, school enrichment programs, and educating families on healthy child development in the clinic.
• Routinely screen children for mental health challenges and risk factors such as adverse childhood experiences during primary care well-visits or annual physicals, or at schools or EDs. Primary care physicians should use principles of trauma-informed care to conduct these screenings.
• Screen parents, caregivers, and other family members for depression, intimate partner violence, substance use, and other challenges. These can be done in tandem with broader assessments of social determinants of health such as food or housing insecurity.
• Combine efforts of clinical staff with trusted community partners and child welfare and juvenile justice. Hospital-based violence intervention programs, for example, identify patients at risk of repeat violent injury and refer them to hospital- and community-based resources.
• Build multidisciplinary teams, enlisting children and families to develop services that are tailored to their needs for screening and treatment. Such services should reflect cultural diversity and offered in multiple languages.
• Support the well-being of mental health workers and community leaders to foster their ability to help youth and their families.

Dr. Murthy is talking about a “systems of care” approach, in which all sectors that touch children and youth – not just health care – must work together and do their jobs effectively but collaboratively to address this public health crisis, said Aradhana (Bela) Sood MD, MSHA, FAACAP, senior professor of child mental health policy at Virginia Commonwealth University, Richmond. “An investment in infrastructure support of positive mental health in early childhood, be it in schools, communities, or family well-being will lead to a future where illness is not the result of major preventable societal factors, such as a lack of social supports and trauma.”
 

Changes will ‘take a lot of buy-in’

The recommendations are actionable in the real world – but there are a lot of them, said Dr. Gold. Dr. Murthy doesn’t specify what the plan is to accomplish these metrics or fund them, she added. He “has money and funders like foundations as steps, but foundations have also suffered in the pandemic, so it is not that simple.” Many of these changes are wide in scope and will take a lot of buy-in.

Dr. Shervington would like to have seen more of a focus on educator well-being, given that young people spend a lot of time in educational settings.

“My organization just completed a study in New Orleans that showed teachers having elevated levels of trauma-based conditions since the pandemic,” she said. Schools are indeed a key place to support holistic mental health by focusing on school climate, Dr. Sood added. “If school administrators became uniformly consistent with recognizing the importance of psychological wellness as a prerequisite of good learning, they will create environments where teachers are keenly aware of a child’s mental wellness and make reduction of bullying, wellness check-ins, [and] school-based mental health clinics a priority.

“These are ways nonmedical, community-based supports can enhance student well-being, and reduce depression and other mental health conditions,” Dr. Sood added.
 

Child psychiatrists stretched ‘even thinner’

Despite mental health parity rules, health plans have not been held accountable. That failure, combined with excessive demands for prior authorization for mental health treatments “have led to dangerous shortages of psychiatrists able to accept insurance,” said Paul S. Nestadt, MD, an assistant professor and public mental health researcher at Johns Hopkins University, Baltimore.

“This is particularly true for child psychiatrists, who are stretched even thinner than those of us in general practice,” Dr. Nestadt said.

While he doesn’t address it head on, Dr. Murthy uses classic parity language when he states that “mental health is no less important than physical health,” said Dr. Nestadt, who consulted with the surgeon general on developing this advisory. “While many of us would have liked to see parity highlighted more directly, this advisory was designed to be an overview.”
 

Highlighting social media, gun violence

Dr. Nestadt said he was pleased that the advisory emphasized the importance of restricting access to lethal means in preventing youth suicide.

“With youth suicide rates rising faster than in other age groups, and suicide mortality tied so closely to method availability, the surgeon general made the right choice in highlighting the role of guns in suicide,” he said.

The advisory also discussed the role of media and social media companies in addressing the crisis, which is important, said Dr. Gold.

“I believe very strongly that the way we talk about and portray mental health in the media matters,” she said. “I have seen it matter in the clinic with patients. They’ll wonder if someone will think they are now violent if they are diagnosed with a mental illness. Stories change the narrative.”

While the advisory isn’t perfect, the state of youth mental health “will only get worse if we don’t do something,” noted Dr. Gold. “It is critical that this is validated and discussed at the highest level and messages like Dr. Murthy’s get heard.”

Dr. Gold, Dr. Shervington, and Dr. Sood had no disclosures. Dr. Nestadt disclosed serving as a consultant to the surgeon general advisory.

The advisory on youth mental health from Surgeon General Vivek Murthy, MD, casts a necessary spotlight on the crisis, clinical psychiatrists say. But some think it could have produced more specifics about funding and payment parity for reimbursement.

The 53-page advisory says that about one in five U.S. children and adolescents aged 3-17 suffer from a mental, emotional, developmental, or behavioral disorder. In the decade before COVID, feelings of sadness and hopelessness, as well as suicidal behaviors, were on the rise. The pandemic has exacerbated symptoms of anxiety, depression, and other mental health issues in young people. Compared with 2019, ED visits in early 2021 for suspected suicide attempts rose 51% in adolescent girls and 4% in boys. “Depressive and anxiety symptoms doubled during the pandemic,” the advisory said.
 

Scope of the advisory

The advisory, released Dec. 7, covers all sectors and considers all social and policy factors that might be contributing to this crisis, said Jessica (Jessi) Gold, MD, MS, an assistant professor in the department of psychiatry at Washington University, St. Louis.

“It is always possible to reimagine health care to be more patient centered and mental health forward.” But changes of this magnitude take time, Dr. Gold, also director of wellness, engagement, and outreach at the university, said in an interview.

She has seen the impact of the pandemic firsthand in her clinic among students and frontline health care workers aged 18-30. People in that age group “feel everything deeply,” Dr. Gold said. Emotions tied to COVID-19 are just a part of it. Confounding factors, such as climate change, racism, and school shootings all contribute to their overall mental health.

Some children and adolescents with social anxiety have fared better during the pandemic, but those who are part of demographic groups such as racial and ethnic minorities, LGBTQ individuals, low-income youth, and those involved in juvenile justice or welfare systems face a higher risk of mental health challenges, the pandemic notwithstanding.

In her work with schools, Denese Shervington, MD, MPH, has witnessed more mental health challenges related to isolation and separation. “There’s an overall worry about the loss of what used to be, the seeming predictability and certainty of prepandemic life,” said Dr. Shervington, clinical professor of psychiatry at Tulane University, and president and CEO of the Institute for Women and Ethnic Studies, both in New Orleans.
 

A systems of care plan

The advisory lists actionable items for health care and 10 other industry sectors to improve mental health of children and young adults.

Health care organizations and professionals were advised to take the following six steps:

• Implement trauma-informed care principles and other prevention strategies. This may involve referring patients to resources such as economic and legal supports, school enrichment programs, and educating families on healthy child development in the clinic.
• Routinely screen children for mental health challenges and risk factors such as adverse childhood experiences during primary care well-visits or annual physicals, or at schools or EDs. Primary care physicians should use principles of trauma-informed care to conduct these screenings.
• Screen parents, caregivers, and other family members for depression, intimate partner violence, substance use, and other challenges. These can be done in tandem with broader assessments of social determinants of health such as food or housing insecurity.
• Combine efforts of clinical staff with trusted community partners and child welfare and juvenile justice. Hospital-based violence intervention programs, for example, identify patients at risk of repeat violent injury and refer them to hospital- and community-based resources.
• Build multidisciplinary teams, enlisting children and families to develop services that are tailored to their needs for screening and treatment. Such services should reflect cultural diversity and offered in multiple languages.
• Support the well-being of mental health workers and community leaders to foster their ability to help youth and their families.

Dr. Murthy is talking about a “systems of care” approach, in which all sectors that touch children and youth – not just health care – must work together and do their jobs effectively but collaboratively to address this public health crisis, said Aradhana (Bela) Sood MD, MSHA, FAACAP, senior professor of child mental health policy at Virginia Commonwealth University, Richmond. “An investment in infrastructure support of positive mental health in early childhood, be it in schools, communities, or family well-being will lead to a future where illness is not the result of major preventable societal factors, such as a lack of social supports and trauma.”
 

Changes will ‘take a lot of buy-in’

The recommendations are actionable in the real world – but there are a lot of them, said Dr. Gold. Dr. Murthy doesn’t specify what the plan is to accomplish these metrics or fund them, she added. He “has money and funders like foundations as steps, but foundations have also suffered in the pandemic, so it is not that simple.” Many of these changes are wide in scope and will take a lot of buy-in.

Dr. Shervington would like to have seen more of a focus on educator well-being, given that young people spend a lot of time in educational settings.

“My organization just completed a study in New Orleans that showed teachers having elevated levels of trauma-based conditions since the pandemic,” she said. Schools are indeed a key place to support holistic mental health by focusing on school climate, Dr. Sood added. “If school administrators became uniformly consistent with recognizing the importance of psychological wellness as a prerequisite of good learning, they will create environments where teachers are keenly aware of a child’s mental wellness and make reduction of bullying, wellness check-ins, [and] school-based mental health clinics a priority.

“These are ways nonmedical, community-based supports can enhance student well-being, and reduce depression and other mental health conditions,” Dr. Sood added.
 

Child psychiatrists stretched ‘even thinner’

Despite mental health parity rules, health plans have not been held accountable. That failure, combined with excessive demands for prior authorization for mental health treatments “have led to dangerous shortages of psychiatrists able to accept insurance,” said Paul S. Nestadt, MD, an assistant professor and public mental health researcher at Johns Hopkins University, Baltimore.

“This is particularly true for child psychiatrists, who are stretched even thinner than those of us in general practice,” Dr. Nestadt said.

While he doesn’t address it head on, Dr. Murthy uses classic parity language when he states that “mental health is no less important than physical health,” said Dr. Nestadt, who consulted with the surgeon general on developing this advisory. “While many of us would have liked to see parity highlighted more directly, this advisory was designed to be an overview.”
 

Highlighting social media, gun violence

Dr. Nestadt said he was pleased that the advisory emphasized the importance of restricting access to lethal means in preventing youth suicide.

“With youth suicide rates rising faster than in other age groups, and suicide mortality tied so closely to method availability, the surgeon general made the right choice in highlighting the role of guns in suicide,” he said.

The advisory also discussed the role of media and social media companies in addressing the crisis, which is important, said Dr. Gold.

“I believe very strongly that the way we talk about and portray mental health in the media matters,” she said. “I have seen it matter in the clinic with patients. They’ll wonder if someone will think they are now violent if they are diagnosed with a mental illness. Stories change the narrative.”

While the advisory isn’t perfect, the state of youth mental health “will only get worse if we don’t do something,” noted Dr. Gold. “It is critical that this is validated and discussed at the highest level and messages like Dr. Murthy’s get heard.”

Dr. Gold, Dr. Shervington, and Dr. Sood had no disclosures. Dr. Nestadt disclosed serving as a consultant to the surgeon general advisory.

ATLANTA – Virtual clinic visits have enabled sickle cell disease patients to stay alive and healthier during the COVID-19 pandemic, but concerns remain for those who lack access to specialized care centers, according to an investigator at the annual meeting of the American Society of Hematology.

During the first COVID-19 wave in the summer of 2020, Atlanta’s Grady Sickle Cell Center, the nation’s largest adult sickle cell center, recorded two deaths among the 20 COVID-19_infected patients seen there, said Fuad El Rassi, MD, of Emory University, Atlanta.

ASH

ATLANTA – Virtual clinic visits have enabled sickle cell disease patients to stay alive and healthier during the COVID-19 pandemic, but concerns remain for those who lack access to specialized care centers, according to an investigator at the annual meeting of the American Society of Hematology.

During the first COVID-19 wave in the summer of 2020, Atlanta’s Grady Sickle Cell Center, the nation’s largest adult sickle cell center, recorded two deaths among the 20 COVID-19_infected patients seen there, said Fuad El Rassi, MD, of Emory University, Atlanta.

ASH

ATLANTA – Virtual clinic visits have enabled sickle cell disease patients to stay alive and healthier during the COVID-19 pandemic, but concerns remain for those who lack access to specialized care centers, according to an investigator at the annual meeting of the American Society of Hematology.

During the first COVID-19 wave in the summer of 2020, Atlanta’s Grady Sickle Cell Center, the nation’s largest adult sickle cell center, recorded two deaths among the 20 COVID-19_infected patients seen there, said Fuad El Rassi, MD, of Emory University, Atlanta.

ASH

The Food and Drug Administration is convening an emergency meeting Dec. 16 with representatives from the American Academy of Dermatology Association (AADA) to discuss the flawed rollout of the new, gender-neutral approach to the isotretinoin risk mitigation program that launched on Dec. 13, and what can be done to fix it.

By most accounts, the rollout was disastrous, chaotic, and a failure. Dermatologists on Twitter and elsewhere are angry and frustrated, with some calling for a temporary halt to the program until the bugs can be ironed out.

On Twitter Dec. 15, the Academy posted: “Due to the unacceptable situation with #iPLEDGE, the @US_FDA has convened an emergency meeting with AADA representatives tomorrow, December 16.”

The switch to a new platform was met with frustration from physicians, pharmacists, and patients alike. The new website crashed repeatedly, with physicians and patients complaining they got locked out or bounced off the platform when they attempted to follow instructions to enter information. Calls to obtain support from a live person often required hours on hold, several said.

The new approach to the isotretinoin risk-mitigation program itself isn’t under fire. It was welcomed by dermatologists and others who had long requested the change. Instead of three risk categories (females of reproductive potential, females not of reproductive potential, and males), there are now two (those who can get pregnant and those who cannot). Advocates for the change said it will make the experience more inclusive for transgender patients. The previous categories, some contended, were a barrier to access to care.

Because isotretinoin (Absorica, Amnesteem, Claravis, others), an oral retinoid used to treat severe forms of acne, is teratogenic, with a high risk of birth defects, and has also been associated with other health issues, those who take the medication who are able to get pregnant must take contraceptive precautions. The risk evaluation and mitigation program (REMS), mandated by the FDA, stipulates that physicians, patients, and pharmacists prescribing, using, or dispensing the drug must all be registered with requirements that include the use of two forms of an effective contraceptive and regular pregnancy tests by those capable of becoming pregnant.

A day of frustration

Before navigating the new website, a new log-on name was needed, said Ilona J. Frieden, MD, chair of the AADA’s iPLEDGE Workgroup and professor of dermatology at the University of California, San Francisco. “They made you create a month-day-year date of personal significance.” When she tried to log on, she got locked out, she said in an interview.

The transition from the old website to the new, which Dr. Frieden said is now administered by a different vendor, was done quickly. The previous website shut down Dec. 10, and the new one launched Dec. 13, the first day for the new approach.

“A slower rollout would have helped,” Dr. Frieden said. While she and other dermatologists said they offered input previously on how to make the transition go more smoothly, no one seemed to want that help. “We did have a listening session with the FDA,” Dr. Frieden said. That was before the scheduled meeting of Dec. 16.

Neil S. Goldberg, MD, a dermatologist in Westchester County, New York, also was frustrated with the rollout. “The week before the transition, one of my staff had to call iPLEDGE. They had a 177-minute wait to get to a human.

“They want us to register patients online now instead of signing forms in the office, but the links to view, download, or print don’t work,” Dr. Goldberg said in an interview.

This was after receiving information from the iPLEDGE REMS program, which stated, “The iPLEDGE REMS website will be updated to a modernized platform. All program materials and educational tools will be now available to you at the click of a button.’’

Dr. Goldberg also received calls from three patients who reported that they couldn’t complete the quiz that is required of patients capable of reproducing to demonstrate their comprehension about risk. Without the completed quiz, required monthly, the prescription can’t be refilled.

“It’s chaotic,” said Howa Yeung, MD, assistant professor of dermatology at Emory University, Atlanta. “The change is sudden, it’s a major change in the workflow. The process of reverification [required] is not that hard, but a lot of people have trouble even logging into the platform.”

What would help? To have a human on the phone to help navigate the system, Dr. Yeung said.

The glitches are delaying prescriptions for established patients and new ones as well, Dr. Yeung said. Existing patients who can get pregnant have 7 days after their negative pregnancy test to get their prescription filled. “And over the weekend the website was down,” he said, so that was a 2-day delay.

“The information we have and were told to use doesn’t match what is in their database,” said Mitesh Patel, PharmD, owner of Sunshine Pharmacy in White Plains, N.Y., who said pharmacists are experiencing issues with the new platform similar to those of doctors.

Twitter users had a lot to say, as well. Jack Resneck Jr., MD, professor of dermatology at the University of California, San Francisco, tweeted: “#Accutane has basically been pulled from market by utter incompetence of @SyneosHealth hired by @US_FDA to administer risk mgmt program.”

Dr. Resneck, president-elect of the American Medical Association, noted the crashed website, help line with 6-hour hold times, and patients unable to get the drug.

Adewole Adamson, MD, a dermatologist at the University of Texas, Austin, tweeted, “Dermatologists around the US are BIG mad about the current accutane debacle brought on by @SyneosHealth and @US_FDA. What a disaster for patient care!”

Are fixes in sight?

On Tuesday, Dec. 14, AADA President Kenneth J. Tomecki, MD, issued a statement expressing disappointment about the transition.

AAD

“In advance of this transition, the AADA engaged the FDA and the iPLEDGE administrator, Syneos Health, about the numerous workflow concerns raised by dermatologists and how the impending changes would threaten patient access to necessary medication. Those concerns have become a reality across the country and we’re working to ensure patients can maintain safe and appropriate access to the treatment they need.”

The AADA, the statement continues, supports efforts to streamline the program while keeping patient safety and incorporating input from physicians.

“We are very aware of the problems with the implementation of the iPLEDGE program,” FDA spokesperson Charlie Kohler said in an email. “We are continuing to work closely with the isotretinoin manufacturers to ensure that they implement a smoothly functioning iPLEDGE REMS program and that patient care is not interrupted.”

“Syneos Health appreciates the concern about iPLEDGE,” said Gary Gatyas, a spokesperson for Syneos Health. “While Syneos Health does not maintain the iPLEDGE system or contact center, we are doing what we can to help the responsible parties with a resolution.” Meanwhile, he recommended that people contact the call center.

He did not respond immediately to questions about who is responsible for maintaining the system and call center.

Dr. Goldberg, Dr. Frieden, and Dr. Yeung have disclosed no relevant financial relationships.

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

The Food and Drug Administration is convening an emergency meeting Dec. 16 with representatives from the American Academy of Dermatology Association (AADA) to discuss the flawed rollout of the new, gender-neutral approach to the isotretinoin risk mitigation program that launched on Dec. 13, and what can be done to fix it.

By most accounts, the rollout was disastrous, chaotic, and a failure. Dermatologists on Twitter and elsewhere are angry and frustrated, with some calling for a temporary halt to the program until the bugs can be ironed out.

On Twitter Dec. 15, the Academy posted: “Due to the unacceptable situation with #iPLEDGE, the @US_FDA has convened an emergency meeting with AADA representatives tomorrow, December 16.”

The switch to a new platform was met with frustration from physicians, pharmacists, and patients alike. The new website crashed repeatedly, with physicians and patients complaining they got locked out or bounced off the platform when they attempted to follow instructions to enter information. Calls to obtain support from a live person often required hours on hold, several said.

The new approach to the isotretinoin risk-mitigation program itself isn’t under fire. It was welcomed by dermatologists and others who had long requested the change. Instead of three risk categories (females of reproductive potential, females not of reproductive potential, and males), there are now two (those who can get pregnant and those who cannot). Advocates for the change said it will make the experience more inclusive for transgender patients. The previous categories, some contended, were a barrier to access to care.

Because isotretinoin (Absorica, Amnesteem, Claravis, others), an oral retinoid used to treat severe forms of acne, is teratogenic, with a high risk of birth defects, and has also been associated with other health issues, those who take the medication who are able to get pregnant must take contraceptive precautions. The risk evaluation and mitigation program (REMS), mandated by the FDA, stipulates that physicians, patients, and pharmacists prescribing, using, or dispensing the drug must all be registered with requirements that include the use of two forms of an effective contraceptive and regular pregnancy tests by those capable of becoming pregnant.

A day of frustration

Before navigating the new website, a new log-on name was needed, said Ilona J. Frieden, MD, chair of the AADA’s iPLEDGE Workgroup and professor of dermatology at the University of California, San Francisco. “They made you create a month-day-year date of personal significance.” When she tried to log on, she got locked out, she said in an interview.

The transition from the old website to the new, which Dr. Frieden said is now administered by a different vendor, was done quickly. The previous website shut down Dec. 10, and the new one launched Dec. 13, the first day for the new approach.

“A slower rollout would have helped,” Dr. Frieden said. While she and other dermatologists said they offered input previously on how to make the transition go more smoothly, no one seemed to want that help. “We did have a listening session with the FDA,” Dr. Frieden said. That was before the scheduled meeting of Dec. 16.

Neil S. Goldberg, MD, a dermatologist in Westchester County, New York, also was frustrated with the rollout. “The week before the transition, one of my staff had to call iPLEDGE. They had a 177-minute wait to get to a human.

“They want us to register patients online now instead of signing forms in the office, but the links to view, download, or print don’t work,” Dr. Goldberg said in an interview.

This was after receiving information from the iPLEDGE REMS program, which stated, “The iPLEDGE REMS website will be updated to a modernized platform. All program materials and educational tools will be now available to you at the click of a button.’’

Dr. Goldberg also received calls from three patients who reported that they couldn’t complete the quiz that is required of patients capable of reproducing to demonstrate their comprehension about risk. Without the completed quiz, required monthly, the prescription can’t be refilled.

“It’s chaotic,” said Howa Yeung, MD, assistant professor of dermatology at Emory University, Atlanta. “The change is sudden, it’s a major change in the workflow. The process of reverification [required] is not that hard, but a lot of people have trouble even logging into the platform.”

What would help? To have a human on the phone to help navigate the system, Dr. Yeung said.

The glitches are delaying prescriptions for established patients and new ones as well, Dr. Yeung said. Existing patients who can get pregnant have 7 days after their negative pregnancy test to get their prescription filled. “And over the weekend the website was down,” he said, so that was a 2-day delay.

“The information we have and were told to use doesn’t match what is in their database,” said Mitesh Patel, PharmD, owner of Sunshine Pharmacy in White Plains, N.Y., who said pharmacists are experiencing issues with the new platform similar to those of doctors.

Twitter users had a lot to say, as well. Jack Resneck Jr., MD, professor of dermatology at the University of California, San Francisco, tweeted: “#Accutane has basically been pulled from market by utter incompetence of @SyneosHealth hired by @US_FDA to administer risk mgmt program.”

Dr. Resneck, president-elect of the American Medical Association, noted the crashed website, help line with 6-hour hold times, and patients unable to get the drug.

Adewole Adamson, MD, a dermatologist at the University of Texas, Austin, tweeted, “Dermatologists around the US are BIG mad about the current accutane debacle brought on by @SyneosHealth and @US_FDA. What a disaster for patient care!”

Are fixes in sight?

On Tuesday, Dec. 14, AADA President Kenneth J. Tomecki, MD, issued a statement expressing disappointment about the transition.

AAD

“In advance of this transition, the AADA engaged the FDA and the iPLEDGE administrator, Syneos Health, about the numerous workflow concerns raised by dermatologists and how the impending changes would threaten patient access to necessary medication. Those concerns have become a reality across the country and we’re working to ensure patients can maintain safe and appropriate access to the treatment they need.”

The AADA, the statement continues, supports efforts to streamline the program while keeping patient safety and incorporating input from physicians.

“We are very aware of the problems with the implementation of the iPLEDGE program,” FDA spokesperson Charlie Kohler said in an email. “We are continuing to work closely with the isotretinoin manufacturers to ensure that they implement a smoothly functioning iPLEDGE REMS program and that patient care is not interrupted.”

“Syneos Health appreciates the concern about iPLEDGE,” said Gary Gatyas, a spokesperson for Syneos Health. “While Syneos Health does not maintain the iPLEDGE system or contact center, we are doing what we can to help the responsible parties with a resolution.” Meanwhile, he recommended that people contact the call center.

He did not respond immediately to questions about who is responsible for maintaining the system and call center.

Dr. Goldberg, Dr. Frieden, and Dr. Yeung have disclosed no relevant financial relationships.

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

The Food and Drug Administration is convening an emergency meeting Dec. 16 with representatives from the American Academy of Dermatology Association (AADA) to discuss the flawed rollout of the new, gender-neutral approach to the isotretinoin risk mitigation program that launched on Dec. 13, and what can be done to fix it.

By most accounts, the rollout was disastrous, chaotic, and a failure. Dermatologists on Twitter and elsewhere are angry and frustrated, with some calling for a temporary halt to the program until the bugs can be ironed out.

On Twitter Dec. 15, the Academy posted: “Due to the unacceptable situation with #iPLEDGE, the @US_FDA has convened an emergency meeting with AADA representatives tomorrow, December 16.”

The switch to a new platform was met with frustration from physicians, pharmacists, and patients alike. The new website crashed repeatedly, with physicians and patients complaining they got locked out or bounced off the platform when they attempted to follow instructions to enter information. Calls to obtain support from a live person often required hours on hold, several said.

The new approach to the isotretinoin risk-mitigation program itself isn’t under fire. It was welcomed by dermatologists and others who had long requested the change. Instead of three risk categories (females of reproductive potential, females not of reproductive potential, and males), there are now two (those who can get pregnant and those who cannot). Advocates for the change said it will make the experience more inclusive for transgender patients. The previous categories, some contended, were a barrier to access to care.

Because isotretinoin (Absorica, Amnesteem, Claravis, others), an oral retinoid used to treat severe forms of acne, is teratogenic, with a high risk of birth defects, and has also been associated with other health issues, those who take the medication who are able to get pregnant must take contraceptive precautions. The risk evaluation and mitigation program (REMS), mandated by the FDA, stipulates that physicians, patients, and pharmacists prescribing, using, or dispensing the drug must all be registered with requirements that include the use of two forms of an effective contraceptive and regular pregnancy tests by those capable of becoming pregnant.

A day of frustration

Before navigating the new website, a new log-on name was needed, said Ilona J. Frieden, MD, chair of the AADA’s iPLEDGE Workgroup and professor of dermatology at the University of California, San Francisco. “They made you create a month-day-year date of personal significance.” When she tried to log on, she got locked out, she said in an interview.

The transition from the old website to the new, which Dr. Frieden said is now administered by a different vendor, was done quickly. The previous website shut down Dec. 10, and the new one launched Dec. 13, the first day for the new approach.

“A slower rollout would have helped,” Dr. Frieden said. While she and other dermatologists said they offered input previously on how to make the transition go more smoothly, no one seemed to want that help. “We did have a listening session with the FDA,” Dr. Frieden said. That was before the scheduled meeting of Dec. 16.

Neil S. Goldberg, MD, a dermatologist in Westchester County, New York, also was frustrated with the rollout. “The week before the transition, one of my staff had to call iPLEDGE. They had a 177-minute wait to get to a human.

“They want us to register patients online now instead of signing forms in the office, but the links to view, download, or print don’t work,” Dr. Goldberg said in an interview.

This was after receiving information from the iPLEDGE REMS program, which stated, “The iPLEDGE REMS website will be updated to a modernized platform. All program materials and educational tools will be now available to you at the click of a button.’’

Dr. Goldberg also received calls from three patients who reported that they couldn’t complete the quiz that is required of patients capable of reproducing to demonstrate their comprehension about risk. Without the completed quiz, required monthly, the prescription can’t be refilled.

“It’s chaotic,” said Howa Yeung, MD, assistant professor of dermatology at Emory University, Atlanta. “The change is sudden, it’s a major change in the workflow. The process of reverification [required] is not that hard, but a lot of people have trouble even logging into the platform.”

What would help? To have a human on the phone to help navigate the system, Dr. Yeung said.

The glitches are delaying prescriptions for established patients and new ones as well, Dr. Yeung said. Existing patients who can get pregnant have 7 days after their negative pregnancy test to get their prescription filled. “And over the weekend the website was down,” he said, so that was a 2-day delay.

“The information we have and were told to use doesn’t match what is in their database,” said Mitesh Patel, PharmD, owner of Sunshine Pharmacy in White Plains, N.Y., who said pharmacists are experiencing issues with the new platform similar to those of doctors.

Twitter users had a lot to say, as well. Jack Resneck Jr., MD, professor of dermatology at the University of California, San Francisco, tweeted: “#Accutane has basically been pulled from market by utter incompetence of @SyneosHealth hired by @US_FDA to administer risk mgmt program.”

Dr. Resneck, president-elect of the American Medical Association, noted the crashed website, help line with 6-hour hold times, and patients unable to get the drug.

Adewole Adamson, MD, a dermatologist at the University of Texas, Austin, tweeted, “Dermatologists around the US are BIG mad about the current accutane debacle brought on by @SyneosHealth and @US_FDA. What a disaster for patient care!”

Are fixes in sight?

On Tuesday, Dec. 14, AADA President Kenneth J. Tomecki, MD, issued a statement expressing disappointment about the transition.

AAD

“In advance of this transition, the AADA engaged the FDA and the iPLEDGE administrator, Syneos Health, about the numerous workflow concerns raised by dermatologists and how the impending changes would threaten patient access to necessary medication. Those concerns have become a reality across the country and we’re working to ensure patients can maintain safe and appropriate access to the treatment they need.”

The AADA, the statement continues, supports efforts to streamline the program while keeping patient safety and incorporating input from physicians.

“We are very aware of the problems with the implementation of the iPLEDGE program,” FDA spokesperson Charlie Kohler said in an email. “We are continuing to work closely with the isotretinoin manufacturers to ensure that they implement a smoothly functioning iPLEDGE REMS program and that patient care is not interrupted.”

“Syneos Health appreciates the concern about iPLEDGE,” said Gary Gatyas, a spokesperson for Syneos Health. “While Syneos Health does not maintain the iPLEDGE system or contact center, we are doing what we can to help the responsible parties with a resolution.” Meanwhile, he recommended that people contact the call center.

He did not respond immediately to questions about who is responsible for maintaining the system and call center.

Dr. Goldberg, Dr. Frieden, and Dr. Yeung have disclosed no relevant financial relationships.

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

Illicit drug use among U.S. teenagers dropped sharply in 2021, likely because of stay-at-home orders and other restrictions on social activities due to the COVID-19 pandemic.

The latest findings, from the Monitoring the Future survey, represent the largest 1-year decrease in overall illicit drug use reported since the survey began in 1975.

“We have never seen such dramatic decreases in drug use among teens in just a 1-year period,” Nora Volkow, MD, director of the National Institute on Drug Abuse (NIDA), said in a news release. 

“These data are unprecedented and highlight one unexpected potential consequence of the COVID-19 pandemic, which caused seismic shifts in the day-to-day lives of adolescents,” said Dr. Volkow.

The annual Monitoring the Future survey is conducted by researchers at the University of Michigan, Ann Arbor, and funded by NIDA, to assess drug and alcohol use and related attitudes among adolescent students across the United States.

This year’s self-reported survey included 32,260 students in grades 8, 10, and 12 across 319 public and private schools.

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

Illicit drug use among U.S. teenagers dropped sharply in 2021, likely because of stay-at-home orders and other restrictions on social activities due to the COVID-19 pandemic.

The latest findings, from the Monitoring the Future survey, represent the largest 1-year decrease in overall illicit drug use reported since the survey began in 1975.

“We have never seen such dramatic decreases in drug use among teens in just a 1-year period,” Nora Volkow, MD, director of the National Institute on Drug Abuse (NIDA), said in a news release. 

“These data are unprecedented and highlight one unexpected potential consequence of the COVID-19 pandemic, which caused seismic shifts in the day-to-day lives of adolescents,” said Dr. Volkow.

The annual Monitoring the Future survey is conducted by researchers at the University of Michigan, Ann Arbor, and funded by NIDA, to assess drug and alcohol use and related attitudes among adolescent students across the United States.

This year’s self-reported survey included 32,260 students in grades 8, 10, and 12 across 319 public and private schools.

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

Illicit drug use among U.S. teenagers dropped sharply in 2021, likely because of stay-at-home orders and other restrictions on social activities due to the COVID-19 pandemic.

The latest findings, from the Monitoring the Future survey, represent the largest 1-year decrease in overall illicit drug use reported since the survey began in 1975.

“We have never seen such dramatic decreases in drug use among teens in just a 1-year period,” Nora Volkow, MD, director of the National Institute on Drug Abuse (NIDA), said in a news release. 

“These data are unprecedented and highlight one unexpected potential consequence of the COVID-19 pandemic, which caused seismic shifts in the day-to-day lives of adolescents,” said Dr. Volkow.

The annual Monitoring the Future survey is conducted by researchers at the University of Michigan, Ann Arbor, and funded by NIDA, to assess drug and alcohol use and related attitudes among adolescent students across the United States.

This year’s self-reported survey included 32,260 students in grades 8, 10, and 12 across 319 public and private schools.

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

Responses to abrocitinib treatment among patients with moderate to severe atopic dermatitis (AD) showed dose-dependent consistency across age groups and was comparable in patients aged 51 years and older, results from a post hoc analysis of four trials showed.

Abrocitinib (Cibinqo) is an oral, once-daily, Janus kinase 1 selective inhibitor that has shown good efficacy and safety as monotherapy or combined with topical therapy for treatment of patients with moderate to severe AD. The agent was approved in mid-December in Europe for the treatment of moderate to severe AD in adults who are candidates for systemic therapy and is currently under review by the Food and Drug Administration.

“We know that responses to, and adverse events associated with, systemic therapies may vary among patients of different ages,” Andrew F. Alexis, MD, MPH, said during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis virtual symposium. “The efficacy and safety of abrocitinib monotherapy were previously evaluated in adolescent and adult subpopulations from controlled clinical trials in patients with moderate to severe AD. The objective of the current study was to assess the impact of age on short-term responses to abrocitinib treatment in patients with moderate to severe AD.”

Dr. Alexis, professor of clinical dermatology at Weill Cornell Medicine, New York, and colleagues performed a post hoc analysis across four randomized, double-blind studies that was stratified by age group: 12-17 years, 18-40 years, 41-50 years, and 51 years and older. Efficacy data were assessed separately for patients in the monotherapy pool and in the JADE COMPARE trial. The monotherapy pool included patients from one phase 2b study and two phase 3 studies who received abrocitinib 200 mg, abrocitinib 100 mg, or placebo monotherapy for 12 weeks (JADE-MONO-1 and JADE-MONO-2).

The JADE COMPARE pool included patients who received abrocitinib 200 mg, abrocitinib 100 mg, or placebo, plus medicated topical therapy for 16 weeks. Data from patients in all four trials were pooled for the analysis of treatment-emergent adverse events. Efficacy points analyzed were the Investigator Global Assessment (IGA) score of 0/1 (clear or almost clear), a 75% reduction from baseline in the Eczema Area and Severity Index (EASI-75), or Peak Pruritus Numeric Rating Scale score (PP-NRS4) at week 12 for the monotherapy pool and at week 16 for COMPARE.

In the monotherapy pool, the proportions of patients ages 12-17 years, 18-40 years, 41-50 years, and 51 years and older who achieved an IGA 0/1 response at 12 weeks were 31.3%, 40.2%, 43.8%, and 50.8% (abrocitinib 200 mg); 22%, 23.7%, 22.4%, and 40.8% (abrocitinib 100 mg); and 8.7%, 8%, 3.3%, and 10% (placebo).

In JADE COMPARE, the proportions of patients aged 18-40 years, 41-50 years, and 51 years and older who achieved an IGA 0/1 response were 50%, 53.2%, and 34.8% (abrocitinib 200 mg); 36.9%, 37.1%, and 26.1% (abrocitinib 100 mg); and 12%, 11.8%, and 16.7% (placebo) at 16 weeks. Similar trends were observed for EASI-75 and PP-NRS4 responses at 12 weeks.

Across all age groups, the most common treatment-emergent adverse events were infections/infestations and gastrointestinal effects; most cases were mild or moderate. Nausea was more frequent in the two younger age groups and was dose related: For abrocitinib 200 mg and abrocitinib 100 mg, respectively, the rates of nausea were 18.8% and 7.8% in patients aged 12-17 years; 17.1% and 6.4% in patients aged 18-40 years; and 7.1% and 3.3% in patients aged 51 and older.

“Efficacy responses in patients 51 years of age and older were comparable to those in other age groups,” concluded Dr. Alexis, vice chair for diversity and inclusion in the department of dermatology at Weill Cornell. “The safety profile was consistent across age ranges and was similar to that reported previously.”

The investigators found that treatment response to abrocitinib “in the absence or presence of medicated topical therapy was fairly consistent across age groups, showed similar dose-dependency, and importantly, did not show reduced efficacy in older adults as measured by lesional severity, extent, and itch at 4 months,” said Raj Chovatiya, MD, PhD, assistant professor of dermatology at Northwestern University, Chicago, who was asked to comment on the study.

“Furthermore, the safety profile was consistent across all adults, though notably, nausea was more common among younger age groups, highlighting an area of future investigation,” he added. “Overall, these data show that abrocitinib is associated with similar short-term responses across adulthood and underscore the importance of the JAK-STAT pathway in the underlying pathophysiology of AD in different age groups. It will be interesting to see how these data reflect the real-world setting with both short- and long-term outcomes in a heterogeneous patient population.”

In the interview, Dr. Chovatiya said, “the next frontier in personalized therapy for AD involves deeper clinical phenotyping of our patients and a better understanding of how efficacy and safety vary across patient groups.” For example, he noted, “AD in earlier versus later adulthood may be associated with different clinical signs, symptoms, comorbidities, and other measures of patient burden, and thus, may be associated with different treatment responses to systemic therapy.”  

Dr. Alexis disclosed that he has served as an adviser to, or has received consulting fees from, Leo, Galderma, Pfizer, Sanofi-Regeneron, Dermavant, Beiersdorf, Valeant, L’Oréal, BMS, Bausch Health, UCB, Vyne, Arcutis, Janssen, Allergan, Almirall, AbbVie, Sol-Gel, and Amgen.

Dr. Chovatiya disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for AbbVie, Arena, Arcutis, Incyte, Pfizer, Regeneron, and Sanofi-Genzyme.

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

Responses to abrocitinib treatment among patients with moderate to severe atopic dermatitis (AD) showed dose-dependent consistency across age groups and was comparable in patients aged 51 years and older, results from a post hoc analysis of four trials showed.

Abrocitinib (Cibinqo) is an oral, once-daily, Janus kinase 1 selective inhibitor that has shown good efficacy and safety as monotherapy or combined with topical therapy for treatment of patients with moderate to severe AD. The agent was approved in mid-December in Europe for the treatment of moderate to severe AD in adults who are candidates for systemic therapy and is currently under review by the Food and Drug Administration.

“We know that responses to, and adverse events associated with, systemic therapies may vary among patients of different ages,” Andrew F. Alexis, MD, MPH, said during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis virtual symposium. “The efficacy and safety of abrocitinib monotherapy were previously evaluated in adolescent and adult subpopulations from controlled clinical trials in patients with moderate to severe AD. The objective of the current study was to assess the impact of age on short-term responses to abrocitinib treatment in patients with moderate to severe AD.”

Dr. Alexis, professor of clinical dermatology at Weill Cornell Medicine, New York, and colleagues performed a post hoc analysis across four randomized, double-blind studies that was stratified by age group: 12-17 years, 18-40 years, 41-50 years, and 51 years and older. Efficacy data were assessed separately for patients in the monotherapy pool and in the JADE COMPARE trial. The monotherapy pool included patients from one phase 2b study and two phase 3 studies who received abrocitinib 200 mg, abrocitinib 100 mg, or placebo monotherapy for 12 weeks (JADE-MONO-1 and JADE-MONO-2).

The JADE COMPARE pool included patients who received abrocitinib 200 mg, abrocitinib 100 mg, or placebo, plus medicated topical therapy for 16 weeks. Data from patients in all four trials were pooled for the analysis of treatment-emergent adverse events. Efficacy points analyzed were the Investigator Global Assessment (IGA) score of 0/1 (clear or almost clear), a 75% reduction from baseline in the Eczema Area and Severity Index (EASI-75), or Peak Pruritus Numeric Rating Scale score (PP-NRS4) at week 12 for the monotherapy pool and at week 16 for COMPARE.

In the monotherapy pool, the proportions of patients ages 12-17 years, 18-40 years, 41-50 years, and 51 years and older who achieved an IGA 0/1 response at 12 weeks were 31.3%, 40.2%, 43.8%, and 50.8% (abrocitinib 200 mg); 22%, 23.7%, 22.4%, and 40.8% (abrocitinib 100 mg); and 8.7%, 8%, 3.3%, and 10% (placebo).

In JADE COMPARE, the proportions of patients aged 18-40 years, 41-50 years, and 51 years and older who achieved an IGA 0/1 response were 50%, 53.2%, and 34.8% (abrocitinib 200 mg); 36.9%, 37.1%, and 26.1% (abrocitinib 100 mg); and 12%, 11.8%, and 16.7% (placebo) at 16 weeks. Similar trends were observed for EASI-75 and PP-NRS4 responses at 12 weeks.

Across all age groups, the most common treatment-emergent adverse events were infections/infestations and gastrointestinal effects; most cases were mild or moderate. Nausea was more frequent in the two younger age groups and was dose related: For abrocitinib 200 mg and abrocitinib 100 mg, respectively, the rates of nausea were 18.8% and 7.8% in patients aged 12-17 years; 17.1% and 6.4% in patients aged 18-40 years; and 7.1% and 3.3% in patients aged 51 and older.

“Efficacy responses in patients 51 years of age and older were comparable to those in other age groups,” concluded Dr. Alexis, vice chair for diversity and inclusion in the department of dermatology at Weill Cornell. “The safety profile was consistent across age ranges and was similar to that reported previously.”

The investigators found that treatment response to abrocitinib “in the absence or presence of medicated topical therapy was fairly consistent across age groups, showed similar dose-dependency, and importantly, did not show reduced efficacy in older adults as measured by lesional severity, extent, and itch at 4 months,” said Raj Chovatiya, MD, PhD, assistant professor of dermatology at Northwestern University, Chicago, who was asked to comment on the study.

“Furthermore, the safety profile was consistent across all adults, though notably, nausea was more common among younger age groups, highlighting an area of future investigation,” he added. “Overall, these data show that abrocitinib is associated with similar short-term responses across adulthood and underscore the importance of the JAK-STAT pathway in the underlying pathophysiology of AD in different age groups. It will be interesting to see how these data reflect the real-world setting with both short- and long-term outcomes in a heterogeneous patient population.”

In the interview, Dr. Chovatiya said, “the next frontier in personalized therapy for AD involves deeper clinical phenotyping of our patients and a better understanding of how efficacy and safety vary across patient groups.” For example, he noted, “AD in earlier versus later adulthood may be associated with different clinical signs, symptoms, comorbidities, and other measures of patient burden, and thus, may be associated with different treatment responses to systemic therapy.”  

Dr. Alexis disclosed that he has served as an adviser to, or has received consulting fees from, Leo, Galderma, Pfizer, Sanofi-Regeneron, Dermavant, Beiersdorf, Valeant, L’Oréal, BMS, Bausch Health, UCB, Vyne, Arcutis, Janssen, Allergan, Almirall, AbbVie, Sol-Gel, and Amgen.

Dr. Chovatiya disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for AbbVie, Arena, Arcutis, Incyte, Pfizer, Regeneron, and Sanofi-Genzyme.

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

Responses to abrocitinib treatment among patients with moderate to severe atopic dermatitis (AD) showed dose-dependent consistency across age groups and was comparable in patients aged 51 years and older, results from a post hoc analysis of four trials showed.

Abrocitinib (Cibinqo) is an oral, once-daily, Janus kinase 1 selective inhibitor that has shown good efficacy and safety as monotherapy or combined with topical therapy for treatment of patients with moderate to severe AD. The agent was approved in mid-December in Europe for the treatment of moderate to severe AD in adults who are candidates for systemic therapy and is currently under review by the Food and Drug Administration.

“We know that responses to, and adverse events associated with, systemic therapies may vary among patients of different ages,” Andrew F. Alexis, MD, MPH, said during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis virtual symposium. “The efficacy and safety of abrocitinib monotherapy were previously evaluated in adolescent and adult subpopulations from controlled clinical trials in patients with moderate to severe AD. The objective of the current study was to assess the impact of age on short-term responses to abrocitinib treatment in patients with moderate to severe AD.”

Dr. Alexis, professor of clinical dermatology at Weill Cornell Medicine, New York, and colleagues performed a post hoc analysis across four randomized, double-blind studies that was stratified by age group: 12-17 years, 18-40 years, 41-50 years, and 51 years and older. Efficacy data were assessed separately for patients in the monotherapy pool and in the JADE COMPARE trial. The monotherapy pool included patients from one phase 2b study and two phase 3 studies who received abrocitinib 200 mg, abrocitinib 100 mg, or placebo monotherapy for 12 weeks (JADE-MONO-1 and JADE-MONO-2).

The JADE COMPARE pool included patients who received abrocitinib 200 mg, abrocitinib 100 mg, or placebo, plus medicated topical therapy for 16 weeks. Data from patients in all four trials were pooled for the analysis of treatment-emergent adverse events. Efficacy points analyzed were the Investigator Global Assessment (IGA) score of 0/1 (clear or almost clear), a 75% reduction from baseline in the Eczema Area and Severity Index (EASI-75), or Peak Pruritus Numeric Rating Scale score (PP-NRS4) at week 12 for the monotherapy pool and at week 16 for COMPARE.

In the monotherapy pool, the proportions of patients ages 12-17 years, 18-40 years, 41-50 years, and 51 years and older who achieved an IGA 0/1 response at 12 weeks were 31.3%, 40.2%, 43.8%, and 50.8% (abrocitinib 200 mg); 22%, 23.7%, 22.4%, and 40.8% (abrocitinib 100 mg); and 8.7%, 8%, 3.3%, and 10% (placebo).

In JADE COMPARE, the proportions of patients aged 18-40 years, 41-50 years, and 51 years and older who achieved an IGA 0/1 response were 50%, 53.2%, and 34.8% (abrocitinib 200 mg); 36.9%, 37.1%, and 26.1% (abrocitinib 100 mg); and 12%, 11.8%, and 16.7% (placebo) at 16 weeks. Similar trends were observed for EASI-75 and PP-NRS4 responses at 12 weeks.

Across all age groups, the most common treatment-emergent adverse events were infections/infestations and gastrointestinal effects; most cases were mild or moderate. Nausea was more frequent in the two younger age groups and was dose related: For abrocitinib 200 mg and abrocitinib 100 mg, respectively, the rates of nausea were 18.8% and 7.8% in patients aged 12-17 years; 17.1% and 6.4% in patients aged 18-40 years; and 7.1% and 3.3% in patients aged 51 and older.

“Efficacy responses in patients 51 years of age and older were comparable to those in other age groups,” concluded Dr. Alexis, vice chair for diversity and inclusion in the department of dermatology at Weill Cornell. “The safety profile was consistent across age ranges and was similar to that reported previously.”

The investigators found that treatment response to abrocitinib “in the absence or presence of medicated topical therapy was fairly consistent across age groups, showed similar dose-dependency, and importantly, did not show reduced efficacy in older adults as measured by lesional severity, extent, and itch at 4 months,” said Raj Chovatiya, MD, PhD, assistant professor of dermatology at Northwestern University, Chicago, who was asked to comment on the study.

“Furthermore, the safety profile was consistent across all adults, though notably, nausea was more common among younger age groups, highlighting an area of future investigation,” he added. “Overall, these data show that abrocitinib is associated with similar short-term responses across adulthood and underscore the importance of the JAK-STAT pathway in the underlying pathophysiology of AD in different age groups. It will be interesting to see how these data reflect the real-world setting with both short- and long-term outcomes in a heterogeneous patient population.”

In the interview, Dr. Chovatiya said, “the next frontier in personalized therapy for AD involves deeper clinical phenotyping of our patients and a better understanding of how efficacy and safety vary across patient groups.” For example, he noted, “AD in earlier versus later adulthood may be associated with different clinical signs, symptoms, comorbidities, and other measures of patient burden, and thus, may be associated with different treatment responses to systemic therapy.”  

Dr. Alexis disclosed that he has served as an adviser to, or has received consulting fees from, Leo, Galderma, Pfizer, Sanofi-Regeneron, Dermavant, Beiersdorf, Valeant, L’Oréal, BMS, Bausch Health, UCB, Vyne, Arcutis, Janssen, Allergan, Almirall, AbbVie, Sol-Gel, and Amgen.

Dr. Chovatiya disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for AbbVie, Arena, Arcutis, Incyte, Pfizer, Regeneron, and Sanofi-Genzyme.

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