Pediatrics

STOCKHOLM – Enterovirus infection appears to be strongly linked to both type 1 diabetes and islet cell autoantibodies, new research suggests.

The strength of the relationship, particularly within the first month of type 1 diabetes diagnosis, “further supports the rationale for development of enterovirus-targeted vaccines and antiviral therapy to prevent and reduce the impact of type 1 diabetes,” according to lead investigator Sonia Isaacs, MD, of the department of pediatrics and child health at the University of New South Wales, Sydney, Australia.

Enteroviruses are a large family of viruses responsible for many infections in children. These live in the intestinal tract but can cause a wide variety of illnesses. There are more than 70 different strains, which include the group A and group B coxsackieviruses, the polioviruses, hepatitis A virus, and several strains that just go by the name enterovirus. 

Dr. Isaacs presented the data, from a meta-analysis of studies using modern molecular techniques, at the annual meeting of the European Association for the Study of Diabetes.

The findings raise the question of whether people should be routinely tested for enterovirus at the time of type 1 diabetes diagnosis, she said during her presentation.

Asked by this news organization about the implications for first-degree relatives of people with type 1 diabetes, Dr. Isaacs said that they are “definitely a population to watch out for,” with regard to enteroviral infections. “Type 1 diabetes is very diverse and has different endotypes. Different environmental factors may be implicated in these different endotypes, and it may be that the enteroviruses are quite important in the first-degree relative group.”  

Asked to comment, session moderator Kamlesh Khunti, MD, PhD, told this news organization that the data were “compelling,” particularly in the short term after type 1 diabetes diagnosis. “It seems that there may be plausibility for enterovirus associated with the development of type 1 diabetes ... Are there methods by which we can reduce this risk with either antivirals or vaccinations? I think that needs to be tested.”

And in regard to first-degree relatives, “I think that’s the group to go for because the association is so highly correlated. I think that’s the group worth testing with any interventions,” said Dr. Khunti, professor of primary care diabetes and vascular medicine at the University of Leicester, England.

Link stronger a month after diagnosis, in close relatives, in Europe

The new meta-analysis is an update to a prior review published in 2011 by Dr. Isaacs’ group, which found that people with islet cell autoimmunity were more than four times as likely as were controls to have an enterovirus infection, and people with type 1 diabetes were almost 10 times as likely.

This new analysis focuses on studies using more modern molecular techniques for detecting viruses, including high throughput sequencing and single-cell technologies.

The analysis identified 60 studies with a total of 12,077 participants, of whom 900 had islet autoimmunity, 5,081 had type 1 diabetes, and 6,096 were controls. Thirty-five of the studies were from Europe, while others were from the United States, Asia, and the Middle East.

Of 16 studies examining enterovirus infection in islet autoimmunity, cases with islet autoimmunity were twice as likely to have an enterovirus infection at any time point compared to controls, a significant difference (odds ratio [OR], 2.07, P = .002.)

Among 48 studies reporting enterovirus infection in type 1 diabetes, those with type 1 diabetes were eight times as likely to have an enterovirus infection compared with controls (OR, 8.0, P < .00001).

In 25 studies including 2,977 participants with onset of type 1 diabetes within the prior month, those individuals were more than 16 times more likely to present with an enterovirus infection (OR, 16.2, P < .00001).

“The strength of this is association is greater than previously reported by both us and others,” Dr. Isaacs noted.

The association between enterovirus infection and islet autoimmunity was greater in individuals who later progressed to type 1 diabetes, with odds ratio 5.1 vs. 2.0 for those who didn’t. The association was most evident at or shortly after seroconversion (5.1), was stronger in Europe (3.2) than in other regions (1.9), and was stronger among those with a first-degree relative with type 1 diabetes (9.8) than those recruited via a high-risk human leukocyte antigen (HLA), in whom the relationship wasn’t significant.

Having multiple or consecutive enteroviral infections was also associated with islet autoimmunity (2.0).

With type 1 diabetes, the relationship with enterovirus was greater in children (9.0) than in adults (4.1), and was greater for type 1 diabetes onset within 1 year (13.8) and within 1 month (16.2) than for those with established type 1 diabetes (7.0). Here, too, the relationship was stronger in Europe (10.2) than outside Europe (7.5).

The link with type 1 diabetes and enterovirus was particularly strong for those with both a first-degree relative and a high-risk HLA (141.4).

The relationship with type 1 diabetes was significant for enterovirus species A (3.7), B (12.7) and C (13.8), including coxsackie virus genotypes, but not D.

“Future studies should focus on characterizing enterovirus genomes in at-risk cohorts rather than just the presence or absence of the virus,” Dr. Isaacs said.

However, she added, “type 1 diabetes is such a heterogenous condition, viruses may be implicated more in one type than another. It’s important that we start to look into this.”

Dr. Isaacs reports no relevant financial relationships. Dr. Khunti disclosed ties with AstraZeneca, Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Merck Sharp & Dohme, Boehringer Ingelheim, Bayer, Berlin-Chemie AG / Menarini Group, Janssen, and Napp.

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

STOCKHOLM – Enterovirus infection appears to be strongly linked to both type 1 diabetes and islet cell autoantibodies, new research suggests.

The strength of the relationship, particularly within the first month of type 1 diabetes diagnosis, “further supports the rationale for development of enterovirus-targeted vaccines and antiviral therapy to prevent and reduce the impact of type 1 diabetes,” according to lead investigator Sonia Isaacs, MD, of the department of pediatrics and child health at the University of New South Wales, Sydney, Australia.

Enteroviruses are a large family of viruses responsible for many infections in children. These live in the intestinal tract but can cause a wide variety of illnesses. There are more than 70 different strains, which include the group A and group B coxsackieviruses, the polioviruses, hepatitis A virus, and several strains that just go by the name enterovirus. 

Dr. Isaacs presented the data, from a meta-analysis of studies using modern molecular techniques, at the annual meeting of the European Association for the Study of Diabetes.

The findings raise the question of whether people should be routinely tested for enterovirus at the time of type 1 diabetes diagnosis, she said during her presentation.

Asked by this news organization about the implications for first-degree relatives of people with type 1 diabetes, Dr. Isaacs said that they are “definitely a population to watch out for,” with regard to enteroviral infections. “Type 1 diabetes is very diverse and has different endotypes. Different environmental factors may be implicated in these different endotypes, and it may be that the enteroviruses are quite important in the first-degree relative group.”  

Asked to comment, session moderator Kamlesh Khunti, MD, PhD, told this news organization that the data were “compelling,” particularly in the short term after type 1 diabetes diagnosis. “It seems that there may be plausibility for enterovirus associated with the development of type 1 diabetes ... Are there methods by which we can reduce this risk with either antivirals or vaccinations? I think that needs to be tested.”

And in regard to first-degree relatives, “I think that’s the group to go for because the association is so highly correlated. I think that’s the group worth testing with any interventions,” said Dr. Khunti, professor of primary care diabetes and vascular medicine at the University of Leicester, England.

Link stronger a month after diagnosis, in close relatives, in Europe

The new meta-analysis is an update to a prior review published in 2011 by Dr. Isaacs’ group, which found that people with islet cell autoimmunity were more than four times as likely as were controls to have an enterovirus infection, and people with type 1 diabetes were almost 10 times as likely.

This new analysis focuses on studies using more modern molecular techniques for detecting viruses, including high throughput sequencing and single-cell technologies.

The analysis identified 60 studies with a total of 12,077 participants, of whom 900 had islet autoimmunity, 5,081 had type 1 diabetes, and 6,096 were controls. Thirty-five of the studies were from Europe, while others were from the United States, Asia, and the Middle East.

Of 16 studies examining enterovirus infection in islet autoimmunity, cases with islet autoimmunity were twice as likely to have an enterovirus infection at any time point compared to controls, a significant difference (odds ratio [OR], 2.07, P = .002.)

Among 48 studies reporting enterovirus infection in type 1 diabetes, those with type 1 diabetes were eight times as likely to have an enterovirus infection compared with controls (OR, 8.0, P < .00001).

In 25 studies including 2,977 participants with onset of type 1 diabetes within the prior month, those individuals were more than 16 times more likely to present with an enterovirus infection (OR, 16.2, P < .00001).

“The strength of this is association is greater than previously reported by both us and others,” Dr. Isaacs noted.

The association between enterovirus infection and islet autoimmunity was greater in individuals who later progressed to type 1 diabetes, with odds ratio 5.1 vs. 2.0 for those who didn’t. The association was most evident at or shortly after seroconversion (5.1), was stronger in Europe (3.2) than in other regions (1.9), and was stronger among those with a first-degree relative with type 1 diabetes (9.8) than those recruited via a high-risk human leukocyte antigen (HLA), in whom the relationship wasn’t significant.

Having multiple or consecutive enteroviral infections was also associated with islet autoimmunity (2.0).

With type 1 diabetes, the relationship with enterovirus was greater in children (9.0) than in adults (4.1), and was greater for type 1 diabetes onset within 1 year (13.8) and within 1 month (16.2) than for those with established type 1 diabetes (7.0). Here, too, the relationship was stronger in Europe (10.2) than outside Europe (7.5).

The link with type 1 diabetes and enterovirus was particularly strong for those with both a first-degree relative and a high-risk HLA (141.4).

The relationship with type 1 diabetes was significant for enterovirus species A (3.7), B (12.7) and C (13.8), including coxsackie virus genotypes, but not D.

“Future studies should focus on characterizing enterovirus genomes in at-risk cohorts rather than just the presence or absence of the virus,” Dr. Isaacs said.

However, she added, “type 1 diabetes is such a heterogenous condition, viruses may be implicated more in one type than another. It’s important that we start to look into this.”

Dr. Isaacs reports no relevant financial relationships. Dr. Khunti disclosed ties with AstraZeneca, Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Merck Sharp & Dohme, Boehringer Ingelheim, Bayer, Berlin-Chemie AG / Menarini Group, Janssen, and Napp.

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

STOCKHOLM – Enterovirus infection appears to be strongly linked to both type 1 diabetes and islet cell autoantibodies, new research suggests.

The strength of the relationship, particularly within the first month of type 1 diabetes diagnosis, “further supports the rationale for development of enterovirus-targeted vaccines and antiviral therapy to prevent and reduce the impact of type 1 diabetes,” according to lead investigator Sonia Isaacs, MD, of the department of pediatrics and child health at the University of New South Wales, Sydney, Australia.

Enteroviruses are a large family of viruses responsible for many infections in children. These live in the intestinal tract but can cause a wide variety of illnesses. There are more than 70 different strains, which include the group A and group B coxsackieviruses, the polioviruses, hepatitis A virus, and several strains that just go by the name enterovirus. 

Dr. Isaacs presented the data, from a meta-analysis of studies using modern molecular techniques, at the annual meeting of the European Association for the Study of Diabetes.

The findings raise the question of whether people should be routinely tested for enterovirus at the time of type 1 diabetes diagnosis, she said during her presentation.

Asked by this news organization about the implications for first-degree relatives of people with type 1 diabetes, Dr. Isaacs said that they are “definitely a population to watch out for,” with regard to enteroviral infections. “Type 1 diabetes is very diverse and has different endotypes. Different environmental factors may be implicated in these different endotypes, and it may be that the enteroviruses are quite important in the first-degree relative group.”  

Asked to comment, session moderator Kamlesh Khunti, MD, PhD, told this news organization that the data were “compelling,” particularly in the short term after type 1 diabetes diagnosis. “It seems that there may be plausibility for enterovirus associated with the development of type 1 diabetes ... Are there methods by which we can reduce this risk with either antivirals or vaccinations? I think that needs to be tested.”

And in regard to first-degree relatives, “I think that’s the group to go for because the association is so highly correlated. I think that’s the group worth testing with any interventions,” said Dr. Khunti, professor of primary care diabetes and vascular medicine at the University of Leicester, England.

Link stronger a month after diagnosis, in close relatives, in Europe

The new meta-analysis is an update to a prior review published in 2011 by Dr. Isaacs’ group, which found that people with islet cell autoimmunity were more than four times as likely as were controls to have an enterovirus infection, and people with type 1 diabetes were almost 10 times as likely.

This new analysis focuses on studies using more modern molecular techniques for detecting viruses, including high throughput sequencing and single-cell technologies.

The analysis identified 60 studies with a total of 12,077 participants, of whom 900 had islet autoimmunity, 5,081 had type 1 diabetes, and 6,096 were controls. Thirty-five of the studies were from Europe, while others were from the United States, Asia, and the Middle East.

Of 16 studies examining enterovirus infection in islet autoimmunity, cases with islet autoimmunity were twice as likely to have an enterovirus infection at any time point compared to controls, a significant difference (odds ratio [OR], 2.07, P = .002.)

Among 48 studies reporting enterovirus infection in type 1 diabetes, those with type 1 diabetes were eight times as likely to have an enterovirus infection compared with controls (OR, 8.0, P < .00001).

In 25 studies including 2,977 participants with onset of type 1 diabetes within the prior month, those individuals were more than 16 times more likely to present with an enterovirus infection (OR, 16.2, P < .00001).

“The strength of this is association is greater than previously reported by both us and others,” Dr. Isaacs noted.

The association between enterovirus infection and islet autoimmunity was greater in individuals who later progressed to type 1 diabetes, with odds ratio 5.1 vs. 2.0 for those who didn’t. The association was most evident at or shortly after seroconversion (5.1), was stronger in Europe (3.2) than in other regions (1.9), and was stronger among those with a first-degree relative with type 1 diabetes (9.8) than those recruited via a high-risk human leukocyte antigen (HLA), in whom the relationship wasn’t significant.

Having multiple or consecutive enteroviral infections was also associated with islet autoimmunity (2.0).

With type 1 diabetes, the relationship with enterovirus was greater in children (9.0) than in adults (4.1), and was greater for type 1 diabetes onset within 1 year (13.8) and within 1 month (16.2) than for those with established type 1 diabetes (7.0). Here, too, the relationship was stronger in Europe (10.2) than outside Europe (7.5).

The link with type 1 diabetes and enterovirus was particularly strong for those with both a first-degree relative and a high-risk HLA (141.4).

The relationship with type 1 diabetes was significant for enterovirus species A (3.7), B (12.7) and C (13.8), including coxsackie virus genotypes, but not D.

“Future studies should focus on characterizing enterovirus genomes in at-risk cohorts rather than just the presence or absence of the virus,” Dr. Isaacs said.

However, she added, “type 1 diabetes is such a heterogenous condition, viruses may be implicated more in one type than another. It’s important that we start to look into this.”

Dr. Isaacs reports no relevant financial relationships. Dr. Khunti disclosed ties with AstraZeneca, Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Merck Sharp & Dohme, Boehringer Ingelheim, Bayer, Berlin-Chemie AG / Menarini Group, Janssen, and Napp.

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

The oral Janus kinase (JAK) inhibitor baricitinib appears to improve symptoms of atopic dermatitis (AD) in children aged 2 years and up, as indicated by data from the phase 3 BREEZE-AD-PEDS trial.

After 16 weeks of treatment, the primary endpoint – an Investigators Global Assessment (IGA) score of 0 or 1 with at least a 2-point improvement from baseline – was met by 41.7% of patients given 2 mg (those younger than age 10) or 4 mg of baricitinib (those aged 10-17 years), the highest dose studied in each of those two age groups.

By comparison, the primary endpoint was met in 16.4% of children in the placebo group (P < .001).

Baricitinib is approved for the treatment of AD in adults in many countries, Antonio Torrelo, MD, of the Hospital Infantil Niño Jesús, Madrid, said at the annual congress of the European Academy of Dermatology and Venereology. It was approved by the U.S. Food and Drug Administration for treating adults with severe alopecia areata in June and is under FDA review for the treatment of AD.
 

The phase 3 BREEZE-AD-PEDS trial

BREEZE-AD-PEDS was a randomized, double-blind trial that evaluated the safety and efficacy of baricitinib in 483 children and adolescents with moderate to severe AD. Participants were aged 2-17 years. Those aged 2-5 years had been diagnosed with AD for at least 6 months; if they were older, they had been diagnosed for at least 12 months.

Three dosing levels of baricitinib were tested: 121 patients were given a low dose, which was 0.5 mg/day in children aged 2 to less than 10 years and 1 mg/day in those aged 10 to less than 18 years. A medium dose – 1 mg/day in the younger children and 2 mg/day in the older children – was given to 120 children, while a high dose – 2 mg/day and 4 mg/day, respectively – was given to another 120 children.

Topical treatments were permitted, although for entry into the trial, participants had to have had an inadequate response to steroids and an inadequate or no response to topical calcineurin inhibitors. In all groups, age, gender, race, geographic region, age at diagnosis of AD, and duration of AD “were more or less similar,” Dr. Torello said.
 

Good results, but only with highest dose

The primary IGA endpoint was reached by 25.8% of children in the medium-dose group and by 18.2% in the low-dose group. Neither result was statistically significant in comparison with placebo (16.4%).

When breaking down the results between different ages, “the results in the IGA scores are consistent in both age subgroups – below 10 years and over 10 years,” Dr. Torello noted. The results are also consistent across body weights (< 20 kg, 20-60 kg, and > 60 kg), he added.

Among those treated with the high dose of baricitinib, Eczema Area and Severity Index (EASI) 75% and 95% improvement scores were reached in 52.5% and 30% of patients, respectively. Corresponding figures for the medium dose were 40% and 21.7%; for the low baricitinib dose, 32.2% and 11.6%; and for placebo, 32% and 12.3%. Again, only the results for the highest baricitinib dose were significant in comparison with placebo.

A similar pattern was seen for improvement in itch, and there was a 75% improvement in Scoring Atopic Dermatitis (SCORAD75) results.
 

Safety of baricitinib in children

The labeling for JAK inhibitors that have been approved to date, including baricitinib, include a boxed warning regarding risks for thrombosis, major adverse cardiovascular events, and all-cause mortality. The warning is based on use by patients with rheumatoid arthritis.

Dr. Torello summarized baricitinib’s safety profile in the trial as being “consistent with the well-known safety profile for baricitinib in adults with moderate to severe atopic dermatitis.”

In the study, no severe adverse effects were noted, and no new safety signals were observed, he said. The rate of any treatment-emergent effect among patients was around 50% and was similar across all baricitinib and placebo groups. Study discontinuations because of a side effect were more frequent in the placebo arm (1.6% of patients) than in the baricitinib low-, medium-, and high-dose arms (0.8%, 0%, and 0.8%, respectively).

There were no cases of deep-vein thrombosis, pulmonary embolism, or other adverse effects of special interest, including major adverse cardiovascular events, gastrointestinal perforations, and opportunistic infections, Dr. Torrelo said.

No patient experienced elevations in liver enzyme levels, although there were some cases of elevated creatinine phosphokinase levels (16% in the placebo group and 19% in the baricitinib arms altogether) that were not from muscle injury. There was a possible increase in low-density cholesterol level (3.3% of those taking placebo vs. 10.1% of baricitinib-treated patients).
 

Is there a role for baricitinib?

“Baricitinib is a potential therapeutic option with a favorable benefit-to-risk profile for children between 2 and 18 years who have moderate to severe atopic dermatitis, and candidates for systemic therapy,” Dr. Torrelo said. “No single drug is capable to treat every patient with atopic dermatitis,” he added in discussing the possible place of baricitinib in pediatric practice.

“There are patients who do not respond to dupilumab, who apparently respond later to JAK inhibitors,” he noted.

“We are trying to work phenotypically, trying to learn what kind of patients – especially children who have a more heterogeneous disease than adults – can be better treated with JAK inhibitors or dupilumab.” There may be other important considerations in choosing a treatment in children, Dr. Torrelo said, including that JAK inhibitors can be given orally, while dupilumab is administered by injection.

Asked to comment on the results, Jashin J. Wu, MD, founder and CEO of the Dermatology Research and Education Foundation in Irvine, Calif., pointed out that “only the higher dose is significantly more effective than placebo.”

In his view, “the potentially severe adverse events are not worth the risk compared to more effective agents, such as dupilumab, in this pediatric population,” added Dr. Wu, who recently authored a review of the role of JAK inhibitors in skin disease. He was not involved with the baricitinib study.

The study was funded by Eli Lilly in collaboration with Incyte. Dr. Torello has participated in advisory boards and/or has served as a principal investigator in clinical trials for AbbVie, Eli Lilly and Company, Novartis, Pfizer, Pierre Fabre, and Sanofi. Dr. Wu has been an investigator, consultant, or speaker for multiple pharmaceutical companies.

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

The oral Janus kinase (JAK) inhibitor baricitinib appears to improve symptoms of atopic dermatitis (AD) in children aged 2 years and up, as indicated by data from the phase 3 BREEZE-AD-PEDS trial.

After 16 weeks of treatment, the primary endpoint – an Investigators Global Assessment (IGA) score of 0 or 1 with at least a 2-point improvement from baseline – was met by 41.7% of patients given 2 mg (those younger than age 10) or 4 mg of baricitinib (those aged 10-17 years), the highest dose studied in each of those two age groups.

By comparison, the primary endpoint was met in 16.4% of children in the placebo group (P < .001).

Baricitinib is approved for the treatment of AD in adults in many countries, Antonio Torrelo, MD, of the Hospital Infantil Niño Jesús, Madrid, said at the annual congress of the European Academy of Dermatology and Venereology. It was approved by the U.S. Food and Drug Administration for treating adults with severe alopecia areata in June and is under FDA review for the treatment of AD.
 

The phase 3 BREEZE-AD-PEDS trial

BREEZE-AD-PEDS was a randomized, double-blind trial that evaluated the safety and efficacy of baricitinib in 483 children and adolescents with moderate to severe AD. Participants were aged 2-17 years. Those aged 2-5 years had been diagnosed with AD for at least 6 months; if they were older, they had been diagnosed for at least 12 months.

Three dosing levels of baricitinib were tested: 121 patients were given a low dose, which was 0.5 mg/day in children aged 2 to less than 10 years and 1 mg/day in those aged 10 to less than 18 years. A medium dose – 1 mg/day in the younger children and 2 mg/day in the older children – was given to 120 children, while a high dose – 2 mg/day and 4 mg/day, respectively – was given to another 120 children.

Topical treatments were permitted, although for entry into the trial, participants had to have had an inadequate response to steroids and an inadequate or no response to topical calcineurin inhibitors. In all groups, age, gender, race, geographic region, age at diagnosis of AD, and duration of AD “were more or less similar,” Dr. Torello said.
 

Good results, but only with highest dose

The primary IGA endpoint was reached by 25.8% of children in the medium-dose group and by 18.2% in the low-dose group. Neither result was statistically significant in comparison with placebo (16.4%).

When breaking down the results between different ages, “the results in the IGA scores are consistent in both age subgroups – below 10 years and over 10 years,” Dr. Torello noted. The results are also consistent across body weights (< 20 kg, 20-60 kg, and > 60 kg), he added.

Among those treated with the high dose of baricitinib, Eczema Area and Severity Index (EASI) 75% and 95% improvement scores were reached in 52.5% and 30% of patients, respectively. Corresponding figures for the medium dose were 40% and 21.7%; for the low baricitinib dose, 32.2% and 11.6%; and for placebo, 32% and 12.3%. Again, only the results for the highest baricitinib dose were significant in comparison with placebo.

A similar pattern was seen for improvement in itch, and there was a 75% improvement in Scoring Atopic Dermatitis (SCORAD75) results.
 

Safety of baricitinib in children

The labeling for JAK inhibitors that have been approved to date, including baricitinib, include a boxed warning regarding risks for thrombosis, major adverse cardiovascular events, and all-cause mortality. The warning is based on use by patients with rheumatoid arthritis.

Dr. Torello summarized baricitinib’s safety profile in the trial as being “consistent with the well-known safety profile for baricitinib in adults with moderate to severe atopic dermatitis.”

In the study, no severe adverse effects were noted, and no new safety signals were observed, he said. The rate of any treatment-emergent effect among patients was around 50% and was similar across all baricitinib and placebo groups. Study discontinuations because of a side effect were more frequent in the placebo arm (1.6% of patients) than in the baricitinib low-, medium-, and high-dose arms (0.8%, 0%, and 0.8%, respectively).

There were no cases of deep-vein thrombosis, pulmonary embolism, or other adverse effects of special interest, including major adverse cardiovascular events, gastrointestinal perforations, and opportunistic infections, Dr. Torrelo said.

No patient experienced elevations in liver enzyme levels, although there were some cases of elevated creatinine phosphokinase levels (16% in the placebo group and 19% in the baricitinib arms altogether) that were not from muscle injury. There was a possible increase in low-density cholesterol level (3.3% of those taking placebo vs. 10.1% of baricitinib-treated patients).
 

Is there a role for baricitinib?

“Baricitinib is a potential therapeutic option with a favorable benefit-to-risk profile for children between 2 and 18 years who have moderate to severe atopic dermatitis, and candidates for systemic therapy,” Dr. Torrelo said. “No single drug is capable to treat every patient with atopic dermatitis,” he added in discussing the possible place of baricitinib in pediatric practice.

“There are patients who do not respond to dupilumab, who apparently respond later to JAK inhibitors,” he noted.

“We are trying to work phenotypically, trying to learn what kind of patients – especially children who have a more heterogeneous disease than adults – can be better treated with JAK inhibitors or dupilumab.” There may be other important considerations in choosing a treatment in children, Dr. Torrelo said, including that JAK inhibitors can be given orally, while dupilumab is administered by injection.

Asked to comment on the results, Jashin J. Wu, MD, founder and CEO of the Dermatology Research and Education Foundation in Irvine, Calif., pointed out that “only the higher dose is significantly more effective than placebo.”

In his view, “the potentially severe adverse events are not worth the risk compared to more effective agents, such as dupilumab, in this pediatric population,” added Dr. Wu, who recently authored a review of the role of JAK inhibitors in skin disease. He was not involved with the baricitinib study.

The study was funded by Eli Lilly in collaboration with Incyte. Dr. Torello has participated in advisory boards and/or has served as a principal investigator in clinical trials for AbbVie, Eli Lilly and Company, Novartis, Pfizer, Pierre Fabre, and Sanofi. Dr. Wu has been an investigator, consultant, or speaker for multiple pharmaceutical companies.

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

The oral Janus kinase (JAK) inhibitor baricitinib appears to improve symptoms of atopic dermatitis (AD) in children aged 2 years and up, as indicated by data from the phase 3 BREEZE-AD-PEDS trial.

After 16 weeks of treatment, the primary endpoint – an Investigators Global Assessment (IGA) score of 0 or 1 with at least a 2-point improvement from baseline – was met by 41.7% of patients given 2 mg (those younger than age 10) or 4 mg of baricitinib (those aged 10-17 years), the highest dose studied in each of those two age groups.

By comparison, the primary endpoint was met in 16.4% of children in the placebo group (P < .001).

Baricitinib is approved for the treatment of AD in adults in many countries, Antonio Torrelo, MD, of the Hospital Infantil Niño Jesús, Madrid, said at the annual congress of the European Academy of Dermatology and Venereology. It was approved by the U.S. Food and Drug Administration for treating adults with severe alopecia areata in June and is under FDA review for the treatment of AD.
 

The phase 3 BREEZE-AD-PEDS trial

BREEZE-AD-PEDS was a randomized, double-blind trial that evaluated the safety and efficacy of baricitinib in 483 children and adolescents with moderate to severe AD. Participants were aged 2-17 years. Those aged 2-5 years had been diagnosed with AD for at least 6 months; if they were older, they had been diagnosed for at least 12 months.

Three dosing levels of baricitinib were tested: 121 patients were given a low dose, which was 0.5 mg/day in children aged 2 to less than 10 years and 1 mg/day in those aged 10 to less than 18 years. A medium dose – 1 mg/day in the younger children and 2 mg/day in the older children – was given to 120 children, while a high dose – 2 mg/day and 4 mg/day, respectively – was given to another 120 children.

Topical treatments were permitted, although for entry into the trial, participants had to have had an inadequate response to steroids and an inadequate or no response to topical calcineurin inhibitors. In all groups, age, gender, race, geographic region, age at diagnosis of AD, and duration of AD “were more or less similar,” Dr. Torello said.
 

Good results, but only with highest dose

The primary IGA endpoint was reached by 25.8% of children in the medium-dose group and by 18.2% in the low-dose group. Neither result was statistically significant in comparison with placebo (16.4%).

When breaking down the results between different ages, “the results in the IGA scores are consistent in both age subgroups – below 10 years and over 10 years,” Dr. Torello noted. The results are also consistent across body weights (< 20 kg, 20-60 kg, and > 60 kg), he added.

Among those treated with the high dose of baricitinib, Eczema Area and Severity Index (EASI) 75% and 95% improvement scores were reached in 52.5% and 30% of patients, respectively. Corresponding figures for the medium dose were 40% and 21.7%; for the low baricitinib dose, 32.2% and 11.6%; and for placebo, 32% and 12.3%. Again, only the results for the highest baricitinib dose were significant in comparison with placebo.

A similar pattern was seen for improvement in itch, and there was a 75% improvement in Scoring Atopic Dermatitis (SCORAD75) results.
 

Safety of baricitinib in children

The labeling for JAK inhibitors that have been approved to date, including baricitinib, include a boxed warning regarding risks for thrombosis, major adverse cardiovascular events, and all-cause mortality. The warning is based on use by patients with rheumatoid arthritis.

Dr. Torello summarized baricitinib’s safety profile in the trial as being “consistent with the well-known safety profile for baricitinib in adults with moderate to severe atopic dermatitis.”

In the study, no severe adverse effects were noted, and no new safety signals were observed, he said. The rate of any treatment-emergent effect among patients was around 50% and was similar across all baricitinib and placebo groups. Study discontinuations because of a side effect were more frequent in the placebo arm (1.6% of patients) than in the baricitinib low-, medium-, and high-dose arms (0.8%, 0%, and 0.8%, respectively).

There were no cases of deep-vein thrombosis, pulmonary embolism, or other adverse effects of special interest, including major adverse cardiovascular events, gastrointestinal perforations, and opportunistic infections, Dr. Torrelo said.

No patient experienced elevations in liver enzyme levels, although there were some cases of elevated creatinine phosphokinase levels (16% in the placebo group and 19% in the baricitinib arms altogether) that were not from muscle injury. There was a possible increase in low-density cholesterol level (3.3% of those taking placebo vs. 10.1% of baricitinib-treated patients).
 

Is there a role for baricitinib?

“Baricitinib is a potential therapeutic option with a favorable benefit-to-risk profile for children between 2 and 18 years who have moderate to severe atopic dermatitis, and candidates for systemic therapy,” Dr. Torrelo said. “No single drug is capable to treat every patient with atopic dermatitis,” he added in discussing the possible place of baricitinib in pediatric practice.

“There are patients who do not respond to dupilumab, who apparently respond later to JAK inhibitors,” he noted.

“We are trying to work phenotypically, trying to learn what kind of patients – especially children who have a more heterogeneous disease than adults – can be better treated with JAK inhibitors or dupilumab.” There may be other important considerations in choosing a treatment in children, Dr. Torrelo said, including that JAK inhibitors can be given orally, while dupilumab is administered by injection.

Asked to comment on the results, Jashin J. Wu, MD, founder and CEO of the Dermatology Research and Education Foundation in Irvine, Calif., pointed out that “only the higher dose is significantly more effective than placebo.”

In his view, “the potentially severe adverse events are not worth the risk compared to more effective agents, such as dupilumab, in this pediatric population,” added Dr. Wu, who recently authored a review of the role of JAK inhibitors in skin disease. He was not involved with the baricitinib study.

The study was funded by Eli Lilly in collaboration with Incyte. Dr. Torello has participated in advisory boards and/or has served as a principal investigator in clinical trials for AbbVie, Eli Lilly and Company, Novartis, Pfizer, Pierre Fabre, and Sanofi. Dr. Wu has been an investigator, consultant, or speaker for multiple pharmaceutical companies.

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

Prenatal exposure to high-dose folic acid is associated with a greater than twofold increased risk for cancer in children of mothers with epilepsy, new data from a Scandinavian registry of more than 3 million pregnancies suggests.

The increased risk for cancer did not change after considering other factors that could explain the risk, such as use of antiseizure medication (ASM).

There was no increased risk for cancer in children of mothers without epilepsy who used high-dose folic acid.

The results of this study “should be considered when the risks and benefits of folic acid supplements for women with epilepsy are discussed and before decisions about optimal dose recommendations are made,” the authors write.

“Although we believe that the association between prescription fills for high-dose folic acid and cancer in children born to mothers with epilepsy is robust, it is important to underline that these are the findings of one study only,” first author Håkon Magne Vegrim, MD, with University of Bergen (Norway) told this news organization.

The study was published online in JAMA Neurology.
 

Risks and benefits

Women with epilepsy are advised to take high doses of folic acid before and during pregnancy owing to the risk for congenital malformations associated with ASM. Whether high-dose folic acid is associated with increases in the risk for childhood cancer is unknown.

To investigate, the researchers analyzed registry data from Denmark, Norway, and Sweden for 3.3 million children followed to a median age of 7.3 years.

Among the 27,784 children born to mothers with epilepsy, 5,934 (21.4%) were exposed to high-dose folic acid (mean dose, 4.3 mg), with a cancer incidence rate of 42.5 per 100,000 person-years in 18 exposed cancer cases compared with 18.4 per 100,000 person-years in 29 unexposed cancer cases – yielding an adjusted hazard ratio of 2.7 (95% confidence interval, 1.2-6.3).

The absolute risk with exposure was 1.5% (95% CI, 0.5%-3.5%) in children of mothers with epilepsy compared with 0.6% (95% CI, 0.3%-1.1%) in children of mothers with epilepsy who were not exposed high-dose folic acid.

Prenatal exposure to high-dose folic acid was not associated with an increased risk for cancer in children of mothers without epilepsy.

In children of mothers without epilepsy, 46,646 (1.4%) were exposed to high-dose folic acid (mean dose, 2.9 mg). There were 69 exposed and 4,927 unexposed cancer cases and an aHR for cancer of 1.1 (95% CI, 0.9-1.4) and absolute risk for cancer of 0.4% (95% CI, 0.3%-0.5%).

There was no association between any specific ASM and childhood cancer.

“Removing mothers with any prescription fills for carbamazepine and valproate was not associated with the point estimate. Hence, these two ASMs were not important effect modifiers for the cancer association,” the investigators note in their study.

They also note that the most common childhood cancer types in children among mothers with epilepsy who took high-dose folic acid did not differ from the distribution in the general population.

“We need to get more knowledge about the potential mechanisms behind high-dose folic acid and childhood cancer, and it is important to identify the optimal dose to balance risks and benefits – and whether folic acid supplementation should be more individualized, based on factors like the serum level of folate and what type of antiseizure medication that is being used,” said Dr. Vegrim.
 

Practice changing?

Weighing in on the study, Elizabeth E. Gerard, MD, director of the Women with Epilepsy Program and associate professor of neurology at Northwestern University in Chicago, said, “There are known benefits of folic acid supplementation during pregnancy including a decreased risk of neural tube defects in the general population and improved neurodevelopmental outcomes in children born to mothers with and without epilepsy.”

“However, despite some expert guidelines recommending high-dose folic acid supplementation, there is a lack of certainty surrounding the ‘just right’ dose for patients with epilepsy who may become pregnant,” said Dr. Gerard, who wasn’t involved in the study.

Dr. Gerard, a member of the American Epilepsy Society, noted that other epidemiologic studies of folic acid supplementation and cancer have had “contradictory results, thus further research on this association will be needed. Additionally, differences in maternal/fetal folate metabolism and blood levels may be an important factor to study in the future.

“That said, this study definitely should cause us to pause and reevaluate the common practice of high-dose folic acid supplementation for patients with epilepsy who are considering pregnancy,” said Dr. Gerard.

The study was supported by the NordForsk Nordic Program on Health and Welfare. Dr. Vegrim and Dr. Gerard report no relevant financial relationships.

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

Prenatal exposure to high-dose folic acid is associated with a greater than twofold increased risk for cancer in children of mothers with epilepsy, new data from a Scandinavian registry of more than 3 million pregnancies suggests.

The increased risk for cancer did not change after considering other factors that could explain the risk, such as use of antiseizure medication (ASM).

There was no increased risk for cancer in children of mothers without epilepsy who used high-dose folic acid.

The results of this study “should be considered when the risks and benefits of folic acid supplements for women with epilepsy are discussed and before decisions about optimal dose recommendations are made,” the authors write.

“Although we believe that the association between prescription fills for high-dose folic acid and cancer in children born to mothers with epilepsy is robust, it is important to underline that these are the findings of one study only,” first author Håkon Magne Vegrim, MD, with University of Bergen (Norway) told this news organization.

The study was published online in JAMA Neurology.
 

Risks and benefits

Women with epilepsy are advised to take high doses of folic acid before and during pregnancy owing to the risk for congenital malformations associated with ASM. Whether high-dose folic acid is associated with increases in the risk for childhood cancer is unknown.

To investigate, the researchers analyzed registry data from Denmark, Norway, and Sweden for 3.3 million children followed to a median age of 7.3 years.

Among the 27,784 children born to mothers with epilepsy, 5,934 (21.4%) were exposed to high-dose folic acid (mean dose, 4.3 mg), with a cancer incidence rate of 42.5 per 100,000 person-years in 18 exposed cancer cases compared with 18.4 per 100,000 person-years in 29 unexposed cancer cases – yielding an adjusted hazard ratio of 2.7 (95% confidence interval, 1.2-6.3).

The absolute risk with exposure was 1.5% (95% CI, 0.5%-3.5%) in children of mothers with epilepsy compared with 0.6% (95% CI, 0.3%-1.1%) in children of mothers with epilepsy who were not exposed high-dose folic acid.

Prenatal exposure to high-dose folic acid was not associated with an increased risk for cancer in children of mothers without epilepsy.

In children of mothers without epilepsy, 46,646 (1.4%) were exposed to high-dose folic acid (mean dose, 2.9 mg). There were 69 exposed and 4,927 unexposed cancer cases and an aHR for cancer of 1.1 (95% CI, 0.9-1.4) and absolute risk for cancer of 0.4% (95% CI, 0.3%-0.5%).

There was no association between any specific ASM and childhood cancer.

“Removing mothers with any prescription fills for carbamazepine and valproate was not associated with the point estimate. Hence, these two ASMs were not important effect modifiers for the cancer association,” the investigators note in their study.

They also note that the most common childhood cancer types in children among mothers with epilepsy who took high-dose folic acid did not differ from the distribution in the general population.

“We need to get more knowledge about the potential mechanisms behind high-dose folic acid and childhood cancer, and it is important to identify the optimal dose to balance risks and benefits – and whether folic acid supplementation should be more individualized, based on factors like the serum level of folate and what type of antiseizure medication that is being used,” said Dr. Vegrim.
 

Practice changing?

Weighing in on the study, Elizabeth E. Gerard, MD, director of the Women with Epilepsy Program and associate professor of neurology at Northwestern University in Chicago, said, “There are known benefits of folic acid supplementation during pregnancy including a decreased risk of neural tube defects in the general population and improved neurodevelopmental outcomes in children born to mothers with and without epilepsy.”

“However, despite some expert guidelines recommending high-dose folic acid supplementation, there is a lack of certainty surrounding the ‘just right’ dose for patients with epilepsy who may become pregnant,” said Dr. Gerard, who wasn’t involved in the study.

Dr. Gerard, a member of the American Epilepsy Society, noted that other epidemiologic studies of folic acid supplementation and cancer have had “contradictory results, thus further research on this association will be needed. Additionally, differences in maternal/fetal folate metabolism and blood levels may be an important factor to study in the future.

“That said, this study definitely should cause us to pause and reevaluate the common practice of high-dose folic acid supplementation for patients with epilepsy who are considering pregnancy,” said Dr. Gerard.

The study was supported by the NordForsk Nordic Program on Health and Welfare. Dr. Vegrim and Dr. Gerard report no relevant financial relationships.

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

Prenatal exposure to high-dose folic acid is associated with a greater than twofold increased risk for cancer in children of mothers with epilepsy, new data from a Scandinavian registry of more than 3 million pregnancies suggests.

The increased risk for cancer did not change after considering other factors that could explain the risk, such as use of antiseizure medication (ASM).

There was no increased risk for cancer in children of mothers without epilepsy who used high-dose folic acid.

The results of this study “should be considered when the risks and benefits of folic acid supplements for women with epilepsy are discussed and before decisions about optimal dose recommendations are made,” the authors write.

“Although we believe that the association between prescription fills for high-dose folic acid and cancer in children born to mothers with epilepsy is robust, it is important to underline that these are the findings of one study only,” first author Håkon Magne Vegrim, MD, with University of Bergen (Norway) told this news organization.

The study was published online in JAMA Neurology.
 

Risks and benefits

Women with epilepsy are advised to take high doses of folic acid before and during pregnancy owing to the risk for congenital malformations associated with ASM. Whether high-dose folic acid is associated with increases in the risk for childhood cancer is unknown.

To investigate, the researchers analyzed registry data from Denmark, Norway, and Sweden for 3.3 million children followed to a median age of 7.3 years.

Among the 27,784 children born to mothers with epilepsy, 5,934 (21.4%) were exposed to high-dose folic acid (mean dose, 4.3 mg), with a cancer incidence rate of 42.5 per 100,000 person-years in 18 exposed cancer cases compared with 18.4 per 100,000 person-years in 29 unexposed cancer cases – yielding an adjusted hazard ratio of 2.7 (95% confidence interval, 1.2-6.3).

The absolute risk with exposure was 1.5% (95% CI, 0.5%-3.5%) in children of mothers with epilepsy compared with 0.6% (95% CI, 0.3%-1.1%) in children of mothers with epilepsy who were not exposed high-dose folic acid.

Prenatal exposure to high-dose folic acid was not associated with an increased risk for cancer in children of mothers without epilepsy.

In children of mothers without epilepsy, 46,646 (1.4%) were exposed to high-dose folic acid (mean dose, 2.9 mg). There were 69 exposed and 4,927 unexposed cancer cases and an aHR for cancer of 1.1 (95% CI, 0.9-1.4) and absolute risk for cancer of 0.4% (95% CI, 0.3%-0.5%).

There was no association between any specific ASM and childhood cancer.

“Removing mothers with any prescription fills for carbamazepine and valproate was not associated with the point estimate. Hence, these two ASMs were not important effect modifiers for the cancer association,” the investigators note in their study.

They also note that the most common childhood cancer types in children among mothers with epilepsy who took high-dose folic acid did not differ from the distribution in the general population.

“We need to get more knowledge about the potential mechanisms behind high-dose folic acid and childhood cancer, and it is important to identify the optimal dose to balance risks and benefits – and whether folic acid supplementation should be more individualized, based on factors like the serum level of folate and what type of antiseizure medication that is being used,” said Dr. Vegrim.
 

Practice changing?

Weighing in on the study, Elizabeth E. Gerard, MD, director of the Women with Epilepsy Program and associate professor of neurology at Northwestern University in Chicago, said, “There are known benefits of folic acid supplementation during pregnancy including a decreased risk of neural tube defects in the general population and improved neurodevelopmental outcomes in children born to mothers with and without epilepsy.”

“However, despite some expert guidelines recommending high-dose folic acid supplementation, there is a lack of certainty surrounding the ‘just right’ dose for patients with epilepsy who may become pregnant,” said Dr. Gerard, who wasn’t involved in the study.

Dr. Gerard, a member of the American Epilepsy Society, noted that other epidemiologic studies of folic acid supplementation and cancer have had “contradictory results, thus further research on this association will be needed. Additionally, differences in maternal/fetal folate metabolism and blood levels may be an important factor to study in the future.

“That said, this study definitely should cause us to pause and reevaluate the common practice of high-dose folic acid supplementation for patients with epilepsy who are considering pregnancy,” said Dr. Gerard.

The study was supported by the NordForsk Nordic Program on Health and Welfare. Dr. Vegrim and Dr. Gerard report no relevant financial relationships.

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

While great strides have been made in children’s leukemia care during the past 50 years, statistics have remained grim. For acute myeloid leukemia (AML), the most common type, 5-year survival rates were just 69% for children younger than 15 between 2009 and 2015. Patients who do survive past adolescence face high risks of future complications.

Specialists say the challenges hindering more progress include a lack of clinical research, an emphasis on competition over cooperation, and sparse insight into how best to adjust adult leukemia treatments to children. Now, a large clinical trial launched by the Leukemia & Lymphoma Society (LLS) seeks to revolutionize pediatric AML care by testing multiple experimental treatments across the globe. Its goal goes beyond simply boosting survival.

“Our project aims to find better treatments, more targeted treatments, that will leave children with fewer long-term health problems as adults. We want them to not just survive but thrive,” Gwen Nichols, MD, chief medical officer of LLS, said in an interview. “What we’ve had was not working for anybody. So we have to try a different approach.”

The LLS Pediatric Acute Leukemia (PedAL) Master Trial launched in spring of 2022. Seventy-five study locations from Nova Scotia to Hawaii are now recruiting patients up to age 22 with known or suspected relapsed/refractory AML, mixed phenotype acute leukemia, or relapsed acute lymphoblastic leukemia (ALL).

The 5-year trial expects to recruit 960 participants in the United States and Canada. Clinics in Europe, Australia, and New Zealand also are taking part.

“Pediatric oncologists should know that PedAL, for the first time, is providing a cooperative, seamless way to interrogate [the genomics of] a child’s leukemia,” hematologist/oncologist Todd Cooper, DO, section chief of pediatric oncology at Seattle Children’s Cancer and Blood Disorders Center, said in an interview. “It is also providing a seamless and efficient way for children to be assigned to clinical trials that are going to be tailored towards a particular child’s leukemia. This is something that’s never been done.”

In North America, all trial participants with relapsed AML will undergo genetic sequencing for free as part of the screening process. Clinics “can’t always access genomic screening for their patients,” Dr. Nichols said. “We’re providing that even if they don’t participate in any other part of the trial, even if they go and get another available therapy or go on a different trial. We want them to know that this is available, and they will get the results. And if they’re looking for a trial when they get those results, we have trained oncology nurses who will help them navigate and find clinical trials.”

In PedAL itself, one subtrial is now in progress: An open-label phase 3 randomized multicenter analysis of whether the oral leukemia drug venetoclax combined with the intensive infused chemotherapy treatment FLA+GO (fludarabine, high-dose cytarabine, and gemtuzumab ozogamicin) will improve overall survival compared to FLA+GO alone. Ninety-eight subjects are expected to join the 5-year subtrial.

“We expect within the next year to open three or four different subtrials of targeted therapies for specific groups of patients,” E. Anders Kolb, MD, chief of oncology and hematology at Nemours Children’s Health in Delaware and cochair of the PedAL trial, said in an interview. “Over the course of the next few years, we’re going to learn a lot about the natural history of relapsed leukemia – we don’t have a ton of data on that – and then how targeted therapies may alter some of those outcomes.”

Discussions with multiple drugmakers are in progress regarding the potential subtrials, he said.

The PedAL strategy addresses the lack of new drugs for children with AML, Seattle Children’s Dr. Cooper said. One main reason for the gap is that childhood leukemia is much less common than the adult form, he said, so a lot of drug development is geared toward adults. As a result, he said, new drugs “are geared towards adults whose leukemia is not as aggressive. Whereas in children, the acute leukemias, especially AML, are quite aggressive and need therapies that are often more intense.”

In addition, he said, “we have only recently become aware of how AML is biologically much different than in adults.”

In AML, Delaware’s Dr. Kolb explained, “there are many different phenotypes – ways that these cells can look and behave. But we treat them with a single regimen. What I like to tell families is that we’ve got a few tools in our toolbox, but they all happen to be sledgehammers. The key to the challenge in AML is that it is a molecular disease, but we’re treating it with therapies that were developed 40-50 years ago.”

In PedAL, the goal is to figure out the best ways to target therapy for the specific types that patients have. On this front, the genomic screening in the trial is crucial because it will identify which patients express certain targets and allow them to be assigned to appropriate sub-trials, Dr. Coooper said.

What’s next? “LLS has planned for this to be ongoing for the next 5 to 7 years, so that we can get a number of studies up and running,” Dr. Nichols said. “After that, those studies will continue. We will hope that most of them can be self-funded by then.”

As for cost, she noted that the PedAL trial is part of the society’s Dare to Dream Project, formerly known as the Children’s Initiative, which focuses on pediatric blood cancers. The project, with a fundraising goal of $175 million, focuses on research, patient services and survivorship.

”We have a whole range of services, travel assistance, copay programs and educational resources that doctors may want to use as a valid source of information,” she said. ‘When I was in practice, patients were always asking me, ‘Do you have anything I can read or take home to give my son something about his disease?’ LLS has good-quality, patient-level information for patients. We welcome people contacting us or going to our website and taking advantage of that for free.”

Dr. Nichols and Dr. Kolb report no disclosures. Dr. Cooper reports academic funding from LLS.

While great strides have been made in children’s leukemia care during the past 50 years, statistics have remained grim. For acute myeloid leukemia (AML), the most common type, 5-year survival rates were just 69% for children younger than 15 between 2009 and 2015. Patients who do survive past adolescence face high risks of future complications.

Specialists say the challenges hindering more progress include a lack of clinical research, an emphasis on competition over cooperation, and sparse insight into how best to adjust adult leukemia treatments to children. Now, a large clinical trial launched by the Leukemia & Lymphoma Society (LLS) seeks to revolutionize pediatric AML care by testing multiple experimental treatments across the globe. Its goal goes beyond simply boosting survival.

“Our project aims to find better treatments, more targeted treatments, that will leave children with fewer long-term health problems as adults. We want them to not just survive but thrive,” Gwen Nichols, MD, chief medical officer of LLS, said in an interview. “What we’ve had was not working for anybody. So we have to try a different approach.”

The LLS Pediatric Acute Leukemia (PedAL) Master Trial launched in spring of 2022. Seventy-five study locations from Nova Scotia to Hawaii are now recruiting patients up to age 22 with known or suspected relapsed/refractory AML, mixed phenotype acute leukemia, or relapsed acute lymphoblastic leukemia (ALL).

The 5-year trial expects to recruit 960 participants in the United States and Canada. Clinics in Europe, Australia, and New Zealand also are taking part.

“Pediatric oncologists should know that PedAL, for the first time, is providing a cooperative, seamless way to interrogate [the genomics of] a child’s leukemia,” hematologist/oncologist Todd Cooper, DO, section chief of pediatric oncology at Seattle Children’s Cancer and Blood Disorders Center, said in an interview. “It is also providing a seamless and efficient way for children to be assigned to clinical trials that are going to be tailored towards a particular child’s leukemia. This is something that’s never been done.”

In North America, all trial participants with relapsed AML will undergo genetic sequencing for free as part of the screening process. Clinics “can’t always access genomic screening for their patients,” Dr. Nichols said. “We’re providing that even if they don’t participate in any other part of the trial, even if they go and get another available therapy or go on a different trial. We want them to know that this is available, and they will get the results. And if they’re looking for a trial when they get those results, we have trained oncology nurses who will help them navigate and find clinical trials.”

In PedAL itself, one subtrial is now in progress: An open-label phase 3 randomized multicenter analysis of whether the oral leukemia drug venetoclax combined with the intensive infused chemotherapy treatment FLA+GO (fludarabine, high-dose cytarabine, and gemtuzumab ozogamicin) will improve overall survival compared to FLA+GO alone. Ninety-eight subjects are expected to join the 5-year subtrial.

“We expect within the next year to open three or four different subtrials of targeted therapies for specific groups of patients,” E. Anders Kolb, MD, chief of oncology and hematology at Nemours Children’s Health in Delaware and cochair of the PedAL trial, said in an interview. “Over the course of the next few years, we’re going to learn a lot about the natural history of relapsed leukemia – we don’t have a ton of data on that – and then how targeted therapies may alter some of those outcomes.”

Discussions with multiple drugmakers are in progress regarding the potential subtrials, he said.

The PedAL strategy addresses the lack of new drugs for children with AML, Seattle Children’s Dr. Cooper said. One main reason for the gap is that childhood leukemia is much less common than the adult form, he said, so a lot of drug development is geared toward adults. As a result, he said, new drugs “are geared towards adults whose leukemia is not as aggressive. Whereas in children, the acute leukemias, especially AML, are quite aggressive and need therapies that are often more intense.”

In addition, he said, “we have only recently become aware of how AML is biologically much different than in adults.”

In AML, Delaware’s Dr. Kolb explained, “there are many different phenotypes – ways that these cells can look and behave. But we treat them with a single regimen. What I like to tell families is that we’ve got a few tools in our toolbox, but they all happen to be sledgehammers. The key to the challenge in AML is that it is a molecular disease, but we’re treating it with therapies that were developed 40-50 years ago.”

In PedAL, the goal is to figure out the best ways to target therapy for the specific types that patients have. On this front, the genomic screening in the trial is crucial because it will identify which patients express certain targets and allow them to be assigned to appropriate sub-trials, Dr. Coooper said.

What’s next? “LLS has planned for this to be ongoing for the next 5 to 7 years, so that we can get a number of studies up and running,” Dr. Nichols said. “After that, those studies will continue. We will hope that most of them can be self-funded by then.”

As for cost, she noted that the PedAL trial is part of the society’s Dare to Dream Project, formerly known as the Children’s Initiative, which focuses on pediatric blood cancers. The project, with a fundraising goal of $175 million, focuses on research, patient services and survivorship.

”We have a whole range of services, travel assistance, copay programs and educational resources that doctors may want to use as a valid source of information,” she said. ‘When I was in practice, patients were always asking me, ‘Do you have anything I can read or take home to give my son something about his disease?’ LLS has good-quality, patient-level information for patients. We welcome people contacting us or going to our website and taking advantage of that for free.”

Dr. Nichols and Dr. Kolb report no disclosures. Dr. Cooper reports academic funding from LLS.

While great strides have been made in children’s leukemia care during the past 50 years, statistics have remained grim. For acute myeloid leukemia (AML), the most common type, 5-year survival rates were just 69% for children younger than 15 between 2009 and 2015. Patients who do survive past adolescence face high risks of future complications.

Specialists say the challenges hindering more progress include a lack of clinical research, an emphasis on competition over cooperation, and sparse insight into how best to adjust adult leukemia treatments to children. Now, a large clinical trial launched by the Leukemia & Lymphoma Society (LLS) seeks to revolutionize pediatric AML care by testing multiple experimental treatments across the globe. Its goal goes beyond simply boosting survival.

“Our project aims to find better treatments, more targeted treatments, that will leave children with fewer long-term health problems as adults. We want them to not just survive but thrive,” Gwen Nichols, MD, chief medical officer of LLS, said in an interview. “What we’ve had was not working for anybody. So we have to try a different approach.”

The LLS Pediatric Acute Leukemia (PedAL) Master Trial launched in spring of 2022. Seventy-five study locations from Nova Scotia to Hawaii are now recruiting patients up to age 22 with known or suspected relapsed/refractory AML, mixed phenotype acute leukemia, or relapsed acute lymphoblastic leukemia (ALL).

The 5-year trial expects to recruit 960 participants in the United States and Canada. Clinics in Europe, Australia, and New Zealand also are taking part.

“Pediatric oncologists should know that PedAL, for the first time, is providing a cooperative, seamless way to interrogate [the genomics of] a child’s leukemia,” hematologist/oncologist Todd Cooper, DO, section chief of pediatric oncology at Seattle Children’s Cancer and Blood Disorders Center, said in an interview. “It is also providing a seamless and efficient way for children to be assigned to clinical trials that are going to be tailored towards a particular child’s leukemia. This is something that’s never been done.”

In North America, all trial participants with relapsed AML will undergo genetic sequencing for free as part of the screening process. Clinics “can’t always access genomic screening for their patients,” Dr. Nichols said. “We’re providing that even if they don’t participate in any other part of the trial, even if they go and get another available therapy or go on a different trial. We want them to know that this is available, and they will get the results. And if they’re looking for a trial when they get those results, we have trained oncology nurses who will help them navigate and find clinical trials.”

In PedAL itself, one subtrial is now in progress: An open-label phase 3 randomized multicenter analysis of whether the oral leukemia drug venetoclax combined with the intensive infused chemotherapy treatment FLA+GO (fludarabine, high-dose cytarabine, and gemtuzumab ozogamicin) will improve overall survival compared to FLA+GO alone. Ninety-eight subjects are expected to join the 5-year subtrial.

“We expect within the next year to open three or four different subtrials of targeted therapies for specific groups of patients,” E. Anders Kolb, MD, chief of oncology and hematology at Nemours Children’s Health in Delaware and cochair of the PedAL trial, said in an interview. “Over the course of the next few years, we’re going to learn a lot about the natural history of relapsed leukemia – we don’t have a ton of data on that – and then how targeted therapies may alter some of those outcomes.”

Discussions with multiple drugmakers are in progress regarding the potential subtrials, he said.

The PedAL strategy addresses the lack of new drugs for children with AML, Seattle Children’s Dr. Cooper said. One main reason for the gap is that childhood leukemia is much less common than the adult form, he said, so a lot of drug development is geared toward adults. As a result, he said, new drugs “are geared towards adults whose leukemia is not as aggressive. Whereas in children, the acute leukemias, especially AML, are quite aggressive and need therapies that are often more intense.”

In addition, he said, “we have only recently become aware of how AML is biologically much different than in adults.”

In AML, Delaware’s Dr. Kolb explained, “there are many different phenotypes – ways that these cells can look and behave. But we treat them with a single regimen. What I like to tell families is that we’ve got a few tools in our toolbox, but they all happen to be sledgehammers. The key to the challenge in AML is that it is a molecular disease, but we’re treating it with therapies that were developed 40-50 years ago.”

In PedAL, the goal is to figure out the best ways to target therapy for the specific types that patients have. On this front, the genomic screening in the trial is crucial because it will identify which patients express certain targets and allow them to be assigned to appropriate sub-trials, Dr. Coooper said.

What’s next? “LLS has planned for this to be ongoing for the next 5 to 7 years, so that we can get a number of studies up and running,” Dr. Nichols said. “After that, those studies will continue. We will hope that most of them can be self-funded by then.”

As for cost, she noted that the PedAL trial is part of the society’s Dare to Dream Project, formerly known as the Children’s Initiative, which focuses on pediatric blood cancers. The project, with a fundraising goal of $175 million, focuses on research, patient services and survivorship.

”We have a whole range of services, travel assistance, copay programs and educational resources that doctors may want to use as a valid source of information,” she said. ‘When I was in practice, patients were always asking me, ‘Do you have anything I can read or take home to give my son something about his disease?’ LLS has good-quality, patient-level information for patients. We welcome people contacting us or going to our website and taking advantage of that for free.”

Dr. Nichols and Dr. Kolb report no disclosures. Dr. Cooper reports academic funding from LLS.

Treatment with deuruxolitinib and ritlecitinib, two investigational Janus kinase (JAK) inhibitors, resulted in substantial regrowth of scalp hair for patients with alopecia areata (AA) in separate studies reported at the annual congress of the European Academy of Dermatology and Venereology.

In the THRIVE-AA1 study, the primary endpoint of a Severity of Alopecia Tool (SALT) score of 20 or lower –which indicates that hair regrowth has occurred on at least 80% of the scalp – was achieved among patients taking deuruxolitinib, which was a significantly higher proportion than with placebo (P < .0001). Importantly, the JAK inhibitor’s effects were seen in as early as 4 weeks, and there was significant improvement in both eyelash and eyebrow hair regrowth.

In the unrelated ALLEGRO-LT study, effects from treatment with the JAK inhibitor ritlecitinib appeared to be sustained for 2 years; 69.6% of patients treated with ritlecitinib had a SALT score of 20 or lower by 24 months.

These data are “very exciting for alopecia areata because the patients selected are very severe,” observed Mahtab Samimi, MD, PhD, who cochaired the late-breaking session in which the study findings were discussed.

THRIVE-AA1 included only patients with hair loss of 50% or more. The ALLEGRO-LT study included patients with total scalp or total body hair loss (areata totalis/areata universalis) of 25%-50% at enrollment.

Moreover, “very stringent criteria” were used. SALT scores of 10 or less were evaluated in both studies, observed Dr. Samimi, professor of dermatology at the University of Tours (France).

“We can be ambitious now for our patients with alopecia areata; that’s really good news,” Dr. Samimi added.

Deuruxolitinib and the THRIVE trials

Deuruxolitinib is an oral JAK1/JAK2 inhibitor that has been tested in two similarly designed, multinational, randomized, double-blind, placebo-controlled phase 3 trials in patients with AA, THRIVE-AA1 and THRIVE-AA2.

Two doses of deuruxolitinib, 8 mg and 12 mg given twice daily, were evaluated in the trials, which altogether included just over 1,200 patients.

Results of THRIVE-AA1 have been reported by the manufacturer. Brett King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn., presented a more comprehensive review at the EADV meeting.

He reported that at 24 weeks, SALT scores of 20 or lower were achieved by 30% of adults with AA who were treated with deuruxolitinib 8 mg and by 42% of those treated with deuruxolitinib 12 mg. This primary endpoint was seen in only 1% of the placebo-treated patients.

The more stringent endpoint of having a SALT score of 10 or less, which indicates that hair regrowth has occurred over 90% of the scalp, was met by 21% of patients who received deuruxolitinib 8 mg twice a day and by 35% of those who received the 12-mg dose twice a day at 24 weeks. This endpoint was not reached by any of the placebo-treated patients.

“This is truly transformative therapy,” Dr. King said when presenting the findings. “We know that the chances of spontaneous remission when you have severe disease is next to zero,” he added.

There were reasonably high rates of patient satisfaction with the treatment, according to Dr. King. He said that 42% of those who took 8 mg twice a day and 53% of those who took 12 mg twice a day said they were “very satisfied” or “satisfied” with the degree of scalp hair regrowth achieved, compared with 5% for placebo.

Safety was as expected, and there were no signs of any blood clots, said Dr. King. Common treatment-emergent adverse events (TEAEs) that affected 5% or more of patients included acne and headache. Serious TEAEs were reported by 1.1% and 0.5% of those taking the 8-mg and 12-mg twice-daily doses, respectively, compared with 2.9% of those who received placebo.

Overall, the results look promising for deuruxolitinib, he added. He noted that almost all patients included in the trial have opted to continue in the open-label long-term safety study.

Prescribing information of the JAK inhibitors approved by the U.S. Food and Drug Administration includes a boxed warning about risk of serious infections, mortality, malignancy, major adverse cardiovascular events (MACE), and thrombosis. The warning is based on experience with another JAK inhibitor for patients with rheumatoid arthritis.
 

Ritlecitinib and the ALLEGRO studies

Interim results of the ongoing, open-label, phase 3 ALLEGRO-LT study with ritlecitinib were presented separately by Athanasios Tsianakas, MD, head of the department of dermatology at Fachklinik Bad Bentheim, Germany.

Ritlecitinib, which targets JAK3 and also the TEC family of tyrosine kinases, had met all of its endpoints in the prior ALLEGRO Phase 2b/3 study, Dr. Tsianakas said. Those included the benchmarks of a SALT score of 20 or less and a SALT score of 10 or less.

“Ritlecitinib showed a very good long-term efficacy and good safety profile in our adolescent and adult patients suffering from alopecia areata,” said Dr. Tsianakas.

A total of 447 patients were included in the trial. They were treated with 50 mg of ritlecitinib every day; some had already participated in the ALLEGRO trial, while others had been newly recruited. The latter group entered the trial after a 4-week run-in period, during which a 200-mg daily loading dose was given for 4 weeks.

Most (86%) patients had been exposed to ritlecitinib for at least 12 months; one-fifth had discontinued treatment at the data cutoff, generally because the patients no longer met the eligibility criteria for the trial.

Safety was paramount, Dr. Tsianakas highlighted. There were few adverse events that led to temporary or permanent discontinuation of the study drug. The most common TEAEs that affected 5% or more of patients included headache and acne. There were two cases of MACE (one nonfatal myocardial infarction and one nonfatal stroke).

The proportion of patients with a SALT score of 20 or less was 2.5% at 1 month, 27.9% at 3 months, 50.1% at 6 months, 59.8% at 9 months, and 65.5% at 12 months. Thereafter, there was little shift in the response. A sustained effect, in which a SALT score of 20 or less was seen out to 24 months, occurred in 69.9% of patients.

A similar pattern was seen for SALT scores of 10 or less, ranging from 16.5% at 3 months to 62.5% at 24 months.
 

Following in baricitinib’s footsteps?

This not the first time that JAK inhibitors have been shown to have beneficial effects for patients with AA. Baricitinib (Olumiant) recently became the first JAK inhibitor to be granted marketing approval for AA in the United States, largely on the basis of two pivotal phase 3 studies, BRAVE-AA1 and BRAVE-AA2.

“This is just such an incredibly exciting time,” said Dr. King. “Our discoveries in the lab are being translated into effective therapies for patients with diseases for which we’ve not previously had therapies,” he commented.

“Our concept of interferon gamma– and interleukin-15–mediated disease is probably not true for everybody,” said, Dr. King, who acknowledged that some patients with AA do not respond to JAK-inhibitor therapy or may need additional or alternative treatment.

“It’s probably not that homogeneous a disease,” he added. “It’s fascinating that the very first drugs for this disease are showing efficacy in as many patients as they are.”

The THRIVE-AAI study was funded by CONCERT Pharmaceuticals. Dr. King has served on advisory boards, has provided consulting services to, or has been a trial investigator for multiple pharmaceutical companies, including CoNCERT Pharmaceuticals. The ALLEGRO-LT study was funded by Pfizer. Dr. Tsianakas has acted as a clinical trial investigator and speaker for Pfizer.

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

Treatment with deuruxolitinib and ritlecitinib, two investigational Janus kinase (JAK) inhibitors, resulted in substantial regrowth of scalp hair for patients with alopecia areata (AA) in separate studies reported at the annual congress of the European Academy of Dermatology and Venereology.

In the THRIVE-AA1 study, the primary endpoint of a Severity of Alopecia Tool (SALT) score of 20 or lower –which indicates that hair regrowth has occurred on at least 80% of the scalp – was achieved among patients taking deuruxolitinib, which was a significantly higher proportion than with placebo (P < .0001). Importantly, the JAK inhibitor’s effects were seen in as early as 4 weeks, and there was significant improvement in both eyelash and eyebrow hair regrowth.

In the unrelated ALLEGRO-LT study, effects from treatment with the JAK inhibitor ritlecitinib appeared to be sustained for 2 years; 69.6% of patients treated with ritlecitinib had a SALT score of 20 or lower by 24 months.

These data are “very exciting for alopecia areata because the patients selected are very severe,” observed Mahtab Samimi, MD, PhD, who cochaired the late-breaking session in which the study findings were discussed.

THRIVE-AA1 included only patients with hair loss of 50% or more. The ALLEGRO-LT study included patients with total scalp or total body hair loss (areata totalis/areata universalis) of 25%-50% at enrollment.

Moreover, “very stringent criteria” were used. SALT scores of 10 or less were evaluated in both studies, observed Dr. Samimi, professor of dermatology at the University of Tours (France).

“We can be ambitious now for our patients with alopecia areata; that’s really good news,” Dr. Samimi added.

Deuruxolitinib and the THRIVE trials

Deuruxolitinib is an oral JAK1/JAK2 inhibitor that has been tested in two similarly designed, multinational, randomized, double-blind, placebo-controlled phase 3 trials in patients with AA, THRIVE-AA1 and THRIVE-AA2.

Two doses of deuruxolitinib, 8 mg and 12 mg given twice daily, were evaluated in the trials, which altogether included just over 1,200 patients.

Results of THRIVE-AA1 have been reported by the manufacturer. Brett King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn., presented a more comprehensive review at the EADV meeting.

He reported that at 24 weeks, SALT scores of 20 or lower were achieved by 30% of adults with AA who were treated with deuruxolitinib 8 mg and by 42% of those treated with deuruxolitinib 12 mg. This primary endpoint was seen in only 1% of the placebo-treated patients.

The more stringent endpoint of having a SALT score of 10 or less, which indicates that hair regrowth has occurred over 90% of the scalp, was met by 21% of patients who received deuruxolitinib 8 mg twice a day and by 35% of those who received the 12-mg dose twice a day at 24 weeks. This endpoint was not reached by any of the placebo-treated patients.

“This is truly transformative therapy,” Dr. King said when presenting the findings. “We know that the chances of spontaneous remission when you have severe disease is next to zero,” he added.

There were reasonably high rates of patient satisfaction with the treatment, according to Dr. King. He said that 42% of those who took 8 mg twice a day and 53% of those who took 12 mg twice a day said they were “very satisfied” or “satisfied” with the degree of scalp hair regrowth achieved, compared with 5% for placebo.

Safety was as expected, and there were no signs of any blood clots, said Dr. King. Common treatment-emergent adverse events (TEAEs) that affected 5% or more of patients included acne and headache. Serious TEAEs were reported by 1.1% and 0.5% of those taking the 8-mg and 12-mg twice-daily doses, respectively, compared with 2.9% of those who received placebo.

Overall, the results look promising for deuruxolitinib, he added. He noted that almost all patients included in the trial have opted to continue in the open-label long-term safety study.

Prescribing information of the JAK inhibitors approved by the U.S. Food and Drug Administration includes a boxed warning about risk of serious infections, mortality, malignancy, major adverse cardiovascular events (MACE), and thrombosis. The warning is based on experience with another JAK inhibitor for patients with rheumatoid arthritis.
 

Ritlecitinib and the ALLEGRO studies

Interim results of the ongoing, open-label, phase 3 ALLEGRO-LT study with ritlecitinib were presented separately by Athanasios Tsianakas, MD, head of the department of dermatology at Fachklinik Bad Bentheim, Germany.

Ritlecitinib, which targets JAK3 and also the TEC family of tyrosine kinases, had met all of its endpoints in the prior ALLEGRO Phase 2b/3 study, Dr. Tsianakas said. Those included the benchmarks of a SALT score of 20 or less and a SALT score of 10 or less.

“Ritlecitinib showed a very good long-term efficacy and good safety profile in our adolescent and adult patients suffering from alopecia areata,” said Dr. Tsianakas.

A total of 447 patients were included in the trial. They were treated with 50 mg of ritlecitinib every day; some had already participated in the ALLEGRO trial, while others had been newly recruited. The latter group entered the trial after a 4-week run-in period, during which a 200-mg daily loading dose was given for 4 weeks.

Most (86%) patients had been exposed to ritlecitinib for at least 12 months; one-fifth had discontinued treatment at the data cutoff, generally because the patients no longer met the eligibility criteria for the trial.

Safety was paramount, Dr. Tsianakas highlighted. There were few adverse events that led to temporary or permanent discontinuation of the study drug. The most common TEAEs that affected 5% or more of patients included headache and acne. There were two cases of MACE (one nonfatal myocardial infarction and one nonfatal stroke).

The proportion of patients with a SALT score of 20 or less was 2.5% at 1 month, 27.9% at 3 months, 50.1% at 6 months, 59.8% at 9 months, and 65.5% at 12 months. Thereafter, there was little shift in the response. A sustained effect, in which a SALT score of 20 or less was seen out to 24 months, occurred in 69.9% of patients.

A similar pattern was seen for SALT scores of 10 or less, ranging from 16.5% at 3 months to 62.5% at 24 months.
 

Following in baricitinib’s footsteps?

This not the first time that JAK inhibitors have been shown to have beneficial effects for patients with AA. Baricitinib (Olumiant) recently became the first JAK inhibitor to be granted marketing approval for AA in the United States, largely on the basis of two pivotal phase 3 studies, BRAVE-AA1 and BRAVE-AA2.

“This is just such an incredibly exciting time,” said Dr. King. “Our discoveries in the lab are being translated into effective therapies for patients with diseases for which we’ve not previously had therapies,” he commented.

“Our concept of interferon gamma– and interleukin-15–mediated disease is probably not true for everybody,” said, Dr. King, who acknowledged that some patients with AA do not respond to JAK-inhibitor therapy or may need additional or alternative treatment.

“It’s probably not that homogeneous a disease,” he added. “It’s fascinating that the very first drugs for this disease are showing efficacy in as many patients as they are.”

The THRIVE-AAI study was funded by CONCERT Pharmaceuticals. Dr. King has served on advisory boards, has provided consulting services to, or has been a trial investigator for multiple pharmaceutical companies, including CoNCERT Pharmaceuticals. The ALLEGRO-LT study was funded by Pfizer. Dr. Tsianakas has acted as a clinical trial investigator and speaker for Pfizer.

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

Treatment with deuruxolitinib and ritlecitinib, two investigational Janus kinase (JAK) inhibitors, resulted in substantial regrowth of scalp hair for patients with alopecia areata (AA) in separate studies reported at the annual congress of the European Academy of Dermatology and Venereology.

In the THRIVE-AA1 study, the primary endpoint of a Severity of Alopecia Tool (SALT) score of 20 or lower –which indicates that hair regrowth has occurred on at least 80% of the scalp – was achieved among patients taking deuruxolitinib, which was a significantly higher proportion than with placebo (P < .0001). Importantly, the JAK inhibitor’s effects were seen in as early as 4 weeks, and there was significant improvement in both eyelash and eyebrow hair regrowth.

In the unrelated ALLEGRO-LT study, effects from treatment with the JAK inhibitor ritlecitinib appeared to be sustained for 2 years; 69.6% of patients treated with ritlecitinib had a SALT score of 20 or lower by 24 months.

These data are “very exciting for alopecia areata because the patients selected are very severe,” observed Mahtab Samimi, MD, PhD, who cochaired the late-breaking session in which the study findings were discussed.

THRIVE-AA1 included only patients with hair loss of 50% or more. The ALLEGRO-LT study included patients with total scalp or total body hair loss (areata totalis/areata universalis) of 25%-50% at enrollment.

Moreover, “very stringent criteria” were used. SALT scores of 10 or less were evaluated in both studies, observed Dr. Samimi, professor of dermatology at the University of Tours (France).

“We can be ambitious now for our patients with alopecia areata; that’s really good news,” Dr. Samimi added.

Deuruxolitinib and the THRIVE trials

Deuruxolitinib is an oral JAK1/JAK2 inhibitor that has been tested in two similarly designed, multinational, randomized, double-blind, placebo-controlled phase 3 trials in patients with AA, THRIVE-AA1 and THRIVE-AA2.

Two doses of deuruxolitinib, 8 mg and 12 mg given twice daily, were evaluated in the trials, which altogether included just over 1,200 patients.

Results of THRIVE-AA1 have been reported by the manufacturer. Brett King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn., presented a more comprehensive review at the EADV meeting.

He reported that at 24 weeks, SALT scores of 20 or lower were achieved by 30% of adults with AA who were treated with deuruxolitinib 8 mg and by 42% of those treated with deuruxolitinib 12 mg. This primary endpoint was seen in only 1% of the placebo-treated patients.

The more stringent endpoint of having a SALT score of 10 or less, which indicates that hair regrowth has occurred over 90% of the scalp, was met by 21% of patients who received deuruxolitinib 8 mg twice a day and by 35% of those who received the 12-mg dose twice a day at 24 weeks. This endpoint was not reached by any of the placebo-treated patients.

“This is truly transformative therapy,” Dr. King said when presenting the findings. “We know that the chances of spontaneous remission when you have severe disease is next to zero,” he added.

There were reasonably high rates of patient satisfaction with the treatment, according to Dr. King. He said that 42% of those who took 8 mg twice a day and 53% of those who took 12 mg twice a day said they were “very satisfied” or “satisfied” with the degree of scalp hair regrowth achieved, compared with 5% for placebo.

Safety was as expected, and there were no signs of any blood clots, said Dr. King. Common treatment-emergent adverse events (TEAEs) that affected 5% or more of patients included acne and headache. Serious TEAEs were reported by 1.1% and 0.5% of those taking the 8-mg and 12-mg twice-daily doses, respectively, compared with 2.9% of those who received placebo.

Overall, the results look promising for deuruxolitinib, he added. He noted that almost all patients included in the trial have opted to continue in the open-label long-term safety study.

Prescribing information of the JAK inhibitors approved by the U.S. Food and Drug Administration includes a boxed warning about risk of serious infections, mortality, malignancy, major adverse cardiovascular events (MACE), and thrombosis. The warning is based on experience with another JAK inhibitor for patients with rheumatoid arthritis.
 

Ritlecitinib and the ALLEGRO studies

Interim results of the ongoing, open-label, phase 3 ALLEGRO-LT study with ritlecitinib were presented separately by Athanasios Tsianakas, MD, head of the department of dermatology at Fachklinik Bad Bentheim, Germany.

Ritlecitinib, which targets JAK3 and also the TEC family of tyrosine kinases, had met all of its endpoints in the prior ALLEGRO Phase 2b/3 study, Dr. Tsianakas said. Those included the benchmarks of a SALT score of 20 or less and a SALT score of 10 or less.

“Ritlecitinib showed a very good long-term efficacy and good safety profile in our adolescent and adult patients suffering from alopecia areata,” said Dr. Tsianakas.

A total of 447 patients were included in the trial. They were treated with 50 mg of ritlecitinib every day; some had already participated in the ALLEGRO trial, while others had been newly recruited. The latter group entered the trial after a 4-week run-in period, during which a 200-mg daily loading dose was given for 4 weeks.

Most (86%) patients had been exposed to ritlecitinib for at least 12 months; one-fifth had discontinued treatment at the data cutoff, generally because the patients no longer met the eligibility criteria for the trial.

Safety was paramount, Dr. Tsianakas highlighted. There were few adverse events that led to temporary or permanent discontinuation of the study drug. The most common TEAEs that affected 5% or more of patients included headache and acne. There were two cases of MACE (one nonfatal myocardial infarction and one nonfatal stroke).

The proportion of patients with a SALT score of 20 or less was 2.5% at 1 month, 27.9% at 3 months, 50.1% at 6 months, 59.8% at 9 months, and 65.5% at 12 months. Thereafter, there was little shift in the response. A sustained effect, in which a SALT score of 20 or less was seen out to 24 months, occurred in 69.9% of patients.

A similar pattern was seen for SALT scores of 10 or less, ranging from 16.5% at 3 months to 62.5% at 24 months.
 

Following in baricitinib’s footsteps?

This not the first time that JAK inhibitors have been shown to have beneficial effects for patients with AA. Baricitinib (Olumiant) recently became the first JAK inhibitor to be granted marketing approval for AA in the United States, largely on the basis of two pivotal phase 3 studies, BRAVE-AA1 and BRAVE-AA2.

“This is just such an incredibly exciting time,” said Dr. King. “Our discoveries in the lab are being translated into effective therapies for patients with diseases for which we’ve not previously had therapies,” he commented.

“Our concept of interferon gamma– and interleukin-15–mediated disease is probably not true for everybody,” said, Dr. King, who acknowledged that some patients with AA do not respond to JAK-inhibitor therapy or may need additional or alternative treatment.

“It’s probably not that homogeneous a disease,” he added. “It’s fascinating that the very first drugs for this disease are showing efficacy in as many patients as they are.”

The THRIVE-AAI study was funded by CONCERT Pharmaceuticals. Dr. King has served on advisory boards, has provided consulting services to, or has been a trial investigator for multiple pharmaceutical companies, including CoNCERT Pharmaceuticals. The ALLEGRO-LT study was funded by Pfizer. Dr. Tsianakas has acted as a clinical trial investigator and speaker for Pfizer.

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

It might be possible to develop a simple test to identify newborn children who are at risk of later developing atopic dermatitis (AD), according to findings from a Danish prospective birth cohort study.

In the study, the Barrier Dysfunction in Atopic Newborns Study (BABY), several biomarkers were found in the skin cells of newborns that were predictive not only for having AD but also for having more severe disease.

“We are able to identify predictive immune biomarkers of atopic dermatitis using a noninvasive method that was not associated with any pain,” one of the study’s investigators, Anne-Sofie Halling, MD, said at a press briefing at the annual congress of the European Academy of Dermatology and Venereology.

“Importantly, we were able to predict atopic dermatitis occurring months after [sample] collection,” said Dr. Halling, who works at Bispebjerg Hospital and is a PhD student at the University of Copenhagen.

These findings could hopefully be used to help identify children “so that preventive strategies can target these children ... and decrease the incidence of this common disease,” she added.

AD is caused “by a complex interplay between skin barrier dysfunction and immune dysregulation,” Dr. Halling said, and it is “the first step in the so-called atopic march, where children also develop food allergy, asthma, and rhinitis.” Almost all cases of AD begin during the first years of life. Approximately 15%-20% of children can be affected, she noted, emphasizing the high burden of the disease and pointing out that strategies are shifting toward trying to prevent the disease in those at risk.

Copenhagen BABY cohort

This is where the BABY study comes in, Dr. Halling said. The study enrolled 450 children at birth and followed them until age 2 years. Gene mutation testing was performed at enrollment. All children underwent skin examination, and skin samples were taken using tape strips. Tape strips were applied to the back of the hand of children born at term and between the shoulder blades on the back of children who were premature.

Skin examinations were repeated, and skin samples were obtained again at age 2 months. They were taken again only if there were any signs of AD. For those diagnosed with AD, disease severity was assessed using the Eczema Area and Severity Index (EASI) by the treating physician. Children were excluded if they had AD at the time the tape strip testing was due to be performed.
 

Comparing term and preterm children

Dr. Halling noted that analyses were performed separately for the 300 children born at term and for the 150 who were preterm.

The prevalence of AD was higher among children born at term than among the preterm children (34.6% vs. 21.2%), and the median time to onset was shorter (6 months vs. 8 months). There were also differences in the EASI scores among those who developed AD; median scores were higher in the children born at term than in the preterm children (4.1 vs. 1.6).

More children born at term than preterm children had moderate to severe AD (23.3% vs. 8%), Dr. Halling reported.
 

TARC, IL-8, and IL-18 predictive of AD

Multiple immune biomarkers were tested, including various cytokines and filaggrin degradation products. On examination of skin samples collected at birth, no particular biomarkers were found at higher levels among children who developed AD in comparison with those who did not develop AD.

With regard to biomarkers examined in skin samples at 2 months of age, however, the results were different, Dr. Halling said. One particular cytokine, thymus and activation-regulated chemokine (TARC), was seen to double the risk of AD in the first 2 years of a child’s life.

This doubled risk was seen not only among the children born at term but also among those born preterm, although the data were only significant with regard to the children born at term.

The unadjusted hazard ratios and adjusted HRs (adjusted for parental atopy and filaggrin gene mutations) in term children were 2.11 (95% confidence interval, 1.36-3.26; P = .0008) and 1.85 (95% CI, 1.18-2.89; P = .007), respectively.

For preterm children, the HRs were 2.23 (95% CI, 0.85-5.86; P = .1) and 2.60 (95% CI, 0.98-6.85; P =.05), respectively.

These findings were in line with findings of other studies, Dr. Halling said. “It is well recognized that TARC is currently the best biomarker in patients with established atopic dermatitis.” Moreover, she reported that TARC was associated with a cumulative increase in the risk for AD and that levels were found to be higher in children in whom onset occurred at a later age than among those diagnosed before 6 months of age.

“This is important, as these findings shows that TARC levels predict atopic dermatitis that occurred many months later,” Dr. Halling said.

And, in term-born children at least, TARC upped the chances that the severity of AD would be greater than had it not been present (adjusted HR, 4.65; 95% CI, 1.91-11.31; P = .0007).

Increased levels of interleukin-8 (IL-8) and IL-18 at 2 months of age were also found to be predictive of having moderate to severe AD. The risk was more than double in comparison with those in whom levels were not increased, again only in term-born children.

‘Stimulating and interesting findings’

These data are “very stimulating and interesting,” Dedee Murrell, MD, professor and head of the department of dermatology at St. George Hospital, University of New South Wales, Sydney, observed at the press briefing.

“You found this significant association mainly in the newborn children born at term, and the association in the preterm babies wasn’t as high. Is that anything to do with how they were taken care of in the hospital?” Dr. Murrell asked.

“That’s a really good question,” Dr. Halling said. “Maybe they need to be exposed for a month or two before we are actually able to identify which children will develop atopic dermatitis.”

The study was funded by the Lundbeck Foundation. Dr. Halling has acted as a consultant for Coloplast and as a speaker for Leo Pharma. Dr. Murrell has disclosed no relevant financial relationships.

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

It might be possible to develop a simple test to identify newborn children who are at risk of later developing atopic dermatitis (AD), according to findings from a Danish prospective birth cohort study.

In the study, the Barrier Dysfunction in Atopic Newborns Study (BABY), several biomarkers were found in the skin cells of newborns that were predictive not only for having AD but also for having more severe disease.

“We are able to identify predictive immune biomarkers of atopic dermatitis using a noninvasive method that was not associated with any pain,” one of the study’s investigators, Anne-Sofie Halling, MD, said at a press briefing at the annual congress of the European Academy of Dermatology and Venereology.

“Importantly, we were able to predict atopic dermatitis occurring months after [sample] collection,” said Dr. Halling, who works at Bispebjerg Hospital and is a PhD student at the University of Copenhagen.

These findings could hopefully be used to help identify children “so that preventive strategies can target these children ... and decrease the incidence of this common disease,” she added.

AD is caused “by a complex interplay between skin barrier dysfunction and immune dysregulation,” Dr. Halling said, and it is “the first step in the so-called atopic march, where children also develop food allergy, asthma, and rhinitis.” Almost all cases of AD begin during the first years of life. Approximately 15%-20% of children can be affected, she noted, emphasizing the high burden of the disease and pointing out that strategies are shifting toward trying to prevent the disease in those at risk.

Copenhagen BABY cohort

This is where the BABY study comes in, Dr. Halling said. The study enrolled 450 children at birth and followed them until age 2 years. Gene mutation testing was performed at enrollment. All children underwent skin examination, and skin samples were taken using tape strips. Tape strips were applied to the back of the hand of children born at term and between the shoulder blades on the back of children who were premature.

Skin examinations were repeated, and skin samples were obtained again at age 2 months. They were taken again only if there were any signs of AD. For those diagnosed with AD, disease severity was assessed using the Eczema Area and Severity Index (EASI) by the treating physician. Children were excluded if they had AD at the time the tape strip testing was due to be performed.
 

Comparing term and preterm children

Dr. Halling noted that analyses were performed separately for the 300 children born at term and for the 150 who were preterm.

The prevalence of AD was higher among children born at term than among the preterm children (34.6% vs. 21.2%), and the median time to onset was shorter (6 months vs. 8 months). There were also differences in the EASI scores among those who developed AD; median scores were higher in the children born at term than in the preterm children (4.1 vs. 1.6).

More children born at term than preterm children had moderate to severe AD (23.3% vs. 8%), Dr. Halling reported.
 

TARC, IL-8, and IL-18 predictive of AD

Multiple immune biomarkers were tested, including various cytokines and filaggrin degradation products. On examination of skin samples collected at birth, no particular biomarkers were found at higher levels among children who developed AD in comparison with those who did not develop AD.

With regard to biomarkers examined in skin samples at 2 months of age, however, the results were different, Dr. Halling said. One particular cytokine, thymus and activation-regulated chemokine (TARC), was seen to double the risk of AD in the first 2 years of a child’s life.

This doubled risk was seen not only among the children born at term but also among those born preterm, although the data were only significant with regard to the children born at term.

The unadjusted hazard ratios and adjusted HRs (adjusted for parental atopy and filaggrin gene mutations) in term children were 2.11 (95% confidence interval, 1.36-3.26; P = .0008) and 1.85 (95% CI, 1.18-2.89; P = .007), respectively.

For preterm children, the HRs were 2.23 (95% CI, 0.85-5.86; P = .1) and 2.60 (95% CI, 0.98-6.85; P =.05), respectively.

These findings were in line with findings of other studies, Dr. Halling said. “It is well recognized that TARC is currently the best biomarker in patients with established atopic dermatitis.” Moreover, she reported that TARC was associated with a cumulative increase in the risk for AD and that levels were found to be higher in children in whom onset occurred at a later age than among those diagnosed before 6 months of age.

“This is important, as these findings shows that TARC levels predict atopic dermatitis that occurred many months later,” Dr. Halling said.

And, in term-born children at least, TARC upped the chances that the severity of AD would be greater than had it not been present (adjusted HR, 4.65; 95% CI, 1.91-11.31; P = .0007).

Increased levels of interleukin-8 (IL-8) and IL-18 at 2 months of age were also found to be predictive of having moderate to severe AD. The risk was more than double in comparison with those in whom levels were not increased, again only in term-born children.

‘Stimulating and interesting findings’

These data are “very stimulating and interesting,” Dedee Murrell, MD, professor and head of the department of dermatology at St. George Hospital, University of New South Wales, Sydney, observed at the press briefing.

“You found this significant association mainly in the newborn children born at term, and the association in the preterm babies wasn’t as high. Is that anything to do with how they were taken care of in the hospital?” Dr. Murrell asked.

“That’s a really good question,” Dr. Halling said. “Maybe they need to be exposed for a month or two before we are actually able to identify which children will develop atopic dermatitis.”

The study was funded by the Lundbeck Foundation. Dr. Halling has acted as a consultant for Coloplast and as a speaker for Leo Pharma. Dr. Murrell has disclosed no relevant financial relationships.

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

It might be possible to develop a simple test to identify newborn children who are at risk of later developing atopic dermatitis (AD), according to findings from a Danish prospective birth cohort study.

In the study, the Barrier Dysfunction in Atopic Newborns Study (BABY), several biomarkers were found in the skin cells of newborns that were predictive not only for having AD but also for having more severe disease.

“We are able to identify predictive immune biomarkers of atopic dermatitis using a noninvasive method that was not associated with any pain,” one of the study’s investigators, Anne-Sofie Halling, MD, said at a press briefing at the annual congress of the European Academy of Dermatology and Venereology.

“Importantly, we were able to predict atopic dermatitis occurring months after [sample] collection,” said Dr. Halling, who works at Bispebjerg Hospital and is a PhD student at the University of Copenhagen.

These findings could hopefully be used to help identify children “so that preventive strategies can target these children ... and decrease the incidence of this common disease,” she added.

AD is caused “by a complex interplay between skin barrier dysfunction and immune dysregulation,” Dr. Halling said, and it is “the first step in the so-called atopic march, where children also develop food allergy, asthma, and rhinitis.” Almost all cases of AD begin during the first years of life. Approximately 15%-20% of children can be affected, she noted, emphasizing the high burden of the disease and pointing out that strategies are shifting toward trying to prevent the disease in those at risk.

Copenhagen BABY cohort

This is where the BABY study comes in, Dr. Halling said. The study enrolled 450 children at birth and followed them until age 2 years. Gene mutation testing was performed at enrollment. All children underwent skin examination, and skin samples were taken using tape strips. Tape strips were applied to the back of the hand of children born at term and between the shoulder blades on the back of children who were premature.

Skin examinations were repeated, and skin samples were obtained again at age 2 months. They were taken again only if there were any signs of AD. For those diagnosed with AD, disease severity was assessed using the Eczema Area and Severity Index (EASI) by the treating physician. Children were excluded if they had AD at the time the tape strip testing was due to be performed.
 

Comparing term and preterm children

Dr. Halling noted that analyses were performed separately for the 300 children born at term and for the 150 who were preterm.

The prevalence of AD was higher among children born at term than among the preterm children (34.6% vs. 21.2%), and the median time to onset was shorter (6 months vs. 8 months). There were also differences in the EASI scores among those who developed AD; median scores were higher in the children born at term than in the preterm children (4.1 vs. 1.6).

More children born at term than preterm children had moderate to severe AD (23.3% vs. 8%), Dr. Halling reported.
 

TARC, IL-8, and IL-18 predictive of AD

Multiple immune biomarkers were tested, including various cytokines and filaggrin degradation products. On examination of skin samples collected at birth, no particular biomarkers were found at higher levels among children who developed AD in comparison with those who did not develop AD.

With regard to biomarkers examined in skin samples at 2 months of age, however, the results were different, Dr. Halling said. One particular cytokine, thymus and activation-regulated chemokine (TARC), was seen to double the risk of AD in the first 2 years of a child’s life.

This doubled risk was seen not only among the children born at term but also among those born preterm, although the data were only significant with regard to the children born at term.

The unadjusted hazard ratios and adjusted HRs (adjusted for parental atopy and filaggrin gene mutations) in term children were 2.11 (95% confidence interval, 1.36-3.26; P = .0008) and 1.85 (95% CI, 1.18-2.89; P = .007), respectively.

For preterm children, the HRs were 2.23 (95% CI, 0.85-5.86; P = .1) and 2.60 (95% CI, 0.98-6.85; P =.05), respectively.

These findings were in line with findings of other studies, Dr. Halling said. “It is well recognized that TARC is currently the best biomarker in patients with established atopic dermatitis.” Moreover, she reported that TARC was associated with a cumulative increase in the risk for AD and that levels were found to be higher in children in whom onset occurred at a later age than among those diagnosed before 6 months of age.

“This is important, as these findings shows that TARC levels predict atopic dermatitis that occurred many months later,” Dr. Halling said.

And, in term-born children at least, TARC upped the chances that the severity of AD would be greater than had it not been present (adjusted HR, 4.65; 95% CI, 1.91-11.31; P = .0007).

Increased levels of interleukin-8 (IL-8) and IL-18 at 2 months of age were also found to be predictive of having moderate to severe AD. The risk was more than double in comparison with those in whom levels were not increased, again only in term-born children.

‘Stimulating and interesting findings’

These data are “very stimulating and interesting,” Dedee Murrell, MD, professor and head of the department of dermatology at St. George Hospital, University of New South Wales, Sydney, observed at the press briefing.

“You found this significant association mainly in the newborn children born at term, and the association in the preterm babies wasn’t as high. Is that anything to do with how they were taken care of in the hospital?” Dr. Murrell asked.

“That’s a really good question,” Dr. Halling said. “Maybe they need to be exposed for a month or two before we are actually able to identify which children will develop atopic dermatitis.”

The study was funded by the Lundbeck Foundation. Dr. Halling has acted as a consultant for Coloplast and as a speaker for Leo Pharma. Dr. Murrell has disclosed no relevant financial relationships.

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

STOCKHOLM – It remains inconclusive whether SARS-CoV-2 infection predisposes children and adolescents to a higher risk of type 1 diabetes. Data from two new studies and a recently published research letter add to the growing body of knowledge on the subject, but still can’t draw any definitive conclusions.

The latest results from a Norwegian and a Scottish study both examine incidence of type 1 diabetes in young people with a history of SARS-CoV-2 infection and were reported at the annual meeting of the European Association for the Study of Diabetes.

A 60% increased risk for type 1 diabetes at least 31 days after SARS-CoV-2 infection (adjusted hazard ratio, 1.63) was found in the Norwegian study, while in contrast, the Scottish study only found an increased risk in the first few months of the pandemic, in 2020, but importantly, no association over a much longer time period (March 2020–November 2021).

In a comment on Twitter on the two studies presented at EASD, session moderator Kamlesh Khunti, MD, professor of primary care diabetes and vascular medicine at the University of Leicester, (England), said: “In summary, two studies showing no or weak association of type 1 diabetes with COVID.”

But new data in the research letter published in JAMA Network Open, based on U.S. figures, also found an almost doubling of type 1 diabetes in children in the first few months after COVID-19 infection relative to infection with other respiratory viruses.

Lead author of the Scottish study, Helen Colhoun, PhD, honorary public health consultant at Public Health Scotland, commented: “Data in children are variable year on year, which emphasizes the need to be cautious over taking a tiny snapshot.”

Nevertheless, this is “a hugely important question and we must not drop the ball. [We must] keep looking at it and maintain scientific equipoise. ... [This] reinforces the need to carry on this analysis into the future to obtain an unequivocal picture,” she emphasized.
 

Norwegian study: If there is an association, the risk is small

German Tapia, PhD, from the Norwegian Institute of Public Health, Oslo, presented the results of a study of SARS-CoV-2 infection and subsequent risk of type 1 diabetes in 1.2 million children in Norway.

Of these, 424,354 children had been infected with SARS-CoV-2, and there were 990 incident cases of type 1 diabetes.

“What we do know about COVID-19 in children is that the symptoms are mild and only a small proportion are hospitalized with more serious symptoms. But we do not know the long-term effects of COVID-19 infection because this requires a longer follow-up period,” remarked Dr. Tapia, adding that other viral infections are thought to be linked to the development of type 1 diabetes, in particular, respiratory infections.

The data were sourced from the Norwegian Emergency Preparedness Register for COVID-19, which gathers daily data updates including infections (positive and negative results for free-of-charge testing), diagnoses (primary and secondary care), vaccinations (also free of charge), prescribed medications, and basic demographics.

“We link these data using the personal identification number that every Norwegian citizen has,” explained Dr. Tapia.

He presented results from two cohorts: firstly, results in children only, including those tested for SARS-CoV-2 infection, and secondly, a full national Norwegian population cohort.

Regarding the first cohort, those under 18 years who tested positive for SARS-CoV-2 infection, from March 2020 to March 2022, had a significantly increased risk of type 1 diabetes at least 31 days after infection, with an adjusted hazard ratio of 1.63 (95% confidence interval, 1.08-2.47; P = .02). Adjustments were made for age, sex, non-Nordic country of origin, geographic area, and socioeconomic factors.

For children who developed type 1 diabetes within 30 days of a SARS-CoV-2 infection, the HR was 1.26 (95% CI, 0.72-2.19; P = .42), which did not reach statistical significance.

“The fact that fewer people developed type 1 diabetes within 30 days is not surprising because we know that type 1 diabetes develops over a long period of time,” Dr. Tapia said.

“For this reason, we would not expect to find new cases of those people who develop type 1 diabetes within 30 days of COVID-19 infection,” he explained. In these cases, “it is most likely that they already had [type 1 diabetes], and the infection probably triggered clinical symptoms, so their type 1 diabetes was discovered.”

Turning to the full population cohort and diagnoses of type 1 diabetes over 30 days after SARS-CoV-2 infection, the Norwegian researchers found an association, with an HR of 1.57 (95% CI, 1.06-2.33; P = .03), while diagnosis of type 1 diabetes at 30 days or less generated a hazard ratio of 1.22 (95% CI, 0.72-2.19; P = .42).

“So very similar results were found, and after adjustment for confounders, results were still similar,” reported Dr. Tapia.

He also conducted a similar analysis with vaccination as an exposure but found no association between vaccination against SARS-CoV-2 and diagnosis of type 1 diabetes.

“From these results, we conclude that this suggests an increase in diagnosis of type 1 diabetes after SARS-CoV-2 infection, but it must be noted that the absolute risk of developing type 1 diabetes after infection in children is low, with most children not developing the disease,” he emphasized. “There are nearly half a million children who have been infected with SARS-CoV-2 in Norway, but only a very small proportion develop type 1 diabetes.”
 

Scottish study: No association found over longer term

Dr. Colhoun and colleagues looked at the relationship between incident type 1 diabetes and SARS-CoV-2 infection in children in Scotland using e-health record linkage.

The study involved 1.8 million people under 35 years of age and found very weak, if any, evidence of an association between incident type 1 diabetes and SARS-CoV-2.

Examining data between March 2020 and November 2021, Dr. Colhoun and colleagues identified 365,080 individuals up to age 35 with at least one detected SARS-CoV-2 infection during follow-up and 1,074 who developed type 1 diabetes.

“In children under 16 years, suspected cases of type 1 diabetes are admitted to hospital, and 97% of diagnosis dates are recorded in the Scottish Care Information – Diabetes Collaboration register [SCI-Diabetes] prior to or within 2 days of the first hospital admission for type 1 diabetes,” Dr. Colhoun said, stressing the timeliness of the data.

“We found the incidence of type 1 diabetes diagnosis increased 1.2-fold in those aged 0-14 years, but we did not find any association at an individual level of COVID-19 infection over 30 days prior to a type 1 diabetes diagnosis, in this particular dataset,” she reported. In young people aged 15-34, there was a linear increase in incident type 1 diabetes from 2015 to 2021 with no pandemic increase.

Referring to the 1.2-fold increase soon after the pandemic started, she explained that, in 0- to 14-year-olds, the increase followed a drop in the preceding months prepandemic in 2019. They also found that the seasonal pattern of type 1 diabetes diagnoses remained roughly the same across the pandemic months, with typical peaks in February and September.

In the cohort of under 35s, researchers also found a rate ratio of 2.62 (95% CI, 1.81-3.78) within a 30-day window of SARS-CoV-2 infection, but beyond 30 days, no evidence was seen of an association, with a RR of 0.86 (95% CI, 0.62-1.21; P = .40), she reported.

She explained her reasons for not considering diagnoses within 30 days of COVID-19 as causative. Echoing Dr. Tapia, Dr. Colhoun said the median time from symptom onset to diagnosis of type 1 diabetes is 25 days. “This suggests that 50% have had symptoms for over 25 days at diagnosis.”

She also stressed that when they compared the timing of SARS-CoV-2 testing with diagnosis, they found a much higher rate of COVID-19 testing around diagnosis. “This was not least because everyone admitted to hospital had to have a COVID-19 test.”
 

Latest U.S. data point to a link

Meanwhile, for the new data reported in JAMA Network Open, medical student Ellen K. Kendall of Case Western Reserve University, Cleveland, matched 571,256 pediatric patients: 285,628 with COVID-19 and 285,628 with non–COVID-19 respiratory infections.

By 6 months after COVID-19, 123 patients (0.043%) had received a new diagnosis of type 1 diabetes, but only 72 (0.025%) were diagnosed with type 1 diabetes within 6 months after non–COVID-19 respiratory infection.

At 1, 3, and 6 months after infection, risk of diagnosis of type 1 diabetes was greater among those infected with SARS-CoV-2, compared with those with non–COVID-19 respiratory infection (1 month: HR, 1.96; 3 months: HR, 2.10; and 6 months: HR, 1.83), and in subgroups of patients aged 0-9 years, a group unlikely to develop type 2 diabetes.

“In this study, new type 1 diabetes diagnoses were more likely to occur among pediatric patients with prior COVID-19 than among those with other respiratory infections (or with other encounters with health systems),” noted Ms. Kendall and coauthors. “Respiratory infections have previously been associated with onset of type 1 diabetes, but this risk was even higher among those with COVID-19 in our study, raising concern for long-term, post–COVID-19 autoimmune complications among youths.”

“The increased risk of new-onset type 1 diabetes after COVID-19 adds an important consideration for risk–benefit discussions for prevention and treatment of SARS-CoV-2 infection in pediatric populations,” they concluded.

A study from the Centers for Disease Control and Prevention published in January 2022, also concluded there was a link between COVID-19 and diabetes in children, but not with other acute respiratory infections. Children were 2.5 times more likely to be diagnosed with diabetes following a SARS-CoV-2 infection, it found.

However, the study has been criticized because it pooled all types of diabetes together and did not account for other health conditions, medications that can increase blood glucose levels, race, obesity, and other social determinants of health that might influence a child’s risk of acquiring COVID-19 or diabetes.

“I’ve no doubt that the CDC data were incorrect because the incidence rate for ... diabetes, even in those never exposed to COVID-19 infection, was 10 times the rate ever reported in the U.S.,” Dr. Colhoun said. “There’s no way these data are correct. I believe there was a confusion between incidence and prevalence of diabetes.”

“This paper caused a great deal of panic, especially among those who have a child with type 1diabetes, so we need to be very careful not to cause undue alarm until we have more definitive evidence in this arena,” she stressed.

However, she also acknowledged that the new Norwegian study was well conducted, and she has no methodological concerns about it, so “I think we just have to wait and see.”

Given the inconclusiveness on the issue, there is an ongoing CoviDiab registry collecting data on this very subject.

Dr. Tapia presented on behalf of lead author Dr. Gulseth, who has reported no relevant financial relationships. Dr. Colhoun also reported no relevant financial relationships.

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

STOCKHOLM – It remains inconclusive whether SARS-CoV-2 infection predisposes children and adolescents to a higher risk of type 1 diabetes. Data from two new studies and a recently published research letter add to the growing body of knowledge on the subject, but still can’t draw any definitive conclusions.

The latest results from a Norwegian and a Scottish study both examine incidence of type 1 diabetes in young people with a history of SARS-CoV-2 infection and were reported at the annual meeting of the European Association for the Study of Diabetes.

A 60% increased risk for type 1 diabetes at least 31 days after SARS-CoV-2 infection (adjusted hazard ratio, 1.63) was found in the Norwegian study, while in contrast, the Scottish study only found an increased risk in the first few months of the pandemic, in 2020, but importantly, no association over a much longer time period (March 2020–November 2021).

In a comment on Twitter on the two studies presented at EASD, session moderator Kamlesh Khunti, MD, professor of primary care diabetes and vascular medicine at the University of Leicester, (England), said: “In summary, two studies showing no or weak association of type 1 diabetes with COVID.”

But new data in the research letter published in JAMA Network Open, based on U.S. figures, also found an almost doubling of type 1 diabetes in children in the first few months after COVID-19 infection relative to infection with other respiratory viruses.

Lead author of the Scottish study, Helen Colhoun, PhD, honorary public health consultant at Public Health Scotland, commented: “Data in children are variable year on year, which emphasizes the need to be cautious over taking a tiny snapshot.”

Nevertheless, this is “a hugely important question and we must not drop the ball. [We must] keep looking at it and maintain scientific equipoise. ... [This] reinforces the need to carry on this analysis into the future to obtain an unequivocal picture,” she emphasized.
 

Norwegian study: If there is an association, the risk is small

German Tapia, PhD, from the Norwegian Institute of Public Health, Oslo, presented the results of a study of SARS-CoV-2 infection and subsequent risk of type 1 diabetes in 1.2 million children in Norway.

Of these, 424,354 children had been infected with SARS-CoV-2, and there were 990 incident cases of type 1 diabetes.

“What we do know about COVID-19 in children is that the symptoms are mild and only a small proportion are hospitalized with more serious symptoms. But we do not know the long-term effects of COVID-19 infection because this requires a longer follow-up period,” remarked Dr. Tapia, adding that other viral infections are thought to be linked to the development of type 1 diabetes, in particular, respiratory infections.

The data were sourced from the Norwegian Emergency Preparedness Register for COVID-19, which gathers daily data updates including infections (positive and negative results for free-of-charge testing), diagnoses (primary and secondary care), vaccinations (also free of charge), prescribed medications, and basic demographics.

“We link these data using the personal identification number that every Norwegian citizen has,” explained Dr. Tapia.

He presented results from two cohorts: firstly, results in children only, including those tested for SARS-CoV-2 infection, and secondly, a full national Norwegian population cohort.

Regarding the first cohort, those under 18 years who tested positive for SARS-CoV-2 infection, from March 2020 to March 2022, had a significantly increased risk of type 1 diabetes at least 31 days after infection, with an adjusted hazard ratio of 1.63 (95% confidence interval, 1.08-2.47; P = .02). Adjustments were made for age, sex, non-Nordic country of origin, geographic area, and socioeconomic factors.

For children who developed type 1 diabetes within 30 days of a SARS-CoV-2 infection, the HR was 1.26 (95% CI, 0.72-2.19; P = .42), which did not reach statistical significance.

“The fact that fewer people developed type 1 diabetes within 30 days is not surprising because we know that type 1 diabetes develops over a long period of time,” Dr. Tapia said.

“For this reason, we would not expect to find new cases of those people who develop type 1 diabetes within 30 days of COVID-19 infection,” he explained. In these cases, “it is most likely that they already had [type 1 diabetes], and the infection probably triggered clinical symptoms, so their type 1 diabetes was discovered.”

Turning to the full population cohort and diagnoses of type 1 diabetes over 30 days after SARS-CoV-2 infection, the Norwegian researchers found an association, with an HR of 1.57 (95% CI, 1.06-2.33; P = .03), while diagnosis of type 1 diabetes at 30 days or less generated a hazard ratio of 1.22 (95% CI, 0.72-2.19; P = .42).

“So very similar results were found, and after adjustment for confounders, results were still similar,” reported Dr. Tapia.

He also conducted a similar analysis with vaccination as an exposure but found no association between vaccination against SARS-CoV-2 and diagnosis of type 1 diabetes.

“From these results, we conclude that this suggests an increase in diagnosis of type 1 diabetes after SARS-CoV-2 infection, but it must be noted that the absolute risk of developing type 1 diabetes after infection in children is low, with most children not developing the disease,” he emphasized. “There are nearly half a million children who have been infected with SARS-CoV-2 in Norway, but only a very small proportion develop type 1 diabetes.”
 

Scottish study: No association found over longer term

Dr. Colhoun and colleagues looked at the relationship between incident type 1 diabetes and SARS-CoV-2 infection in children in Scotland using e-health record linkage.

The study involved 1.8 million people under 35 years of age and found very weak, if any, evidence of an association between incident type 1 diabetes and SARS-CoV-2.

Examining data between March 2020 and November 2021, Dr. Colhoun and colleagues identified 365,080 individuals up to age 35 with at least one detected SARS-CoV-2 infection during follow-up and 1,074 who developed type 1 diabetes.

“In children under 16 years, suspected cases of type 1 diabetes are admitted to hospital, and 97% of diagnosis dates are recorded in the Scottish Care Information – Diabetes Collaboration register [SCI-Diabetes] prior to or within 2 days of the first hospital admission for type 1 diabetes,” Dr. Colhoun said, stressing the timeliness of the data.

“We found the incidence of type 1 diabetes diagnosis increased 1.2-fold in those aged 0-14 years, but we did not find any association at an individual level of COVID-19 infection over 30 days prior to a type 1 diabetes diagnosis, in this particular dataset,” she reported. In young people aged 15-34, there was a linear increase in incident type 1 diabetes from 2015 to 2021 with no pandemic increase.

Referring to the 1.2-fold increase soon after the pandemic started, she explained that, in 0- to 14-year-olds, the increase followed a drop in the preceding months prepandemic in 2019. They also found that the seasonal pattern of type 1 diabetes diagnoses remained roughly the same across the pandemic months, with typical peaks in February and September.

In the cohort of under 35s, researchers also found a rate ratio of 2.62 (95% CI, 1.81-3.78) within a 30-day window of SARS-CoV-2 infection, but beyond 30 days, no evidence was seen of an association, with a RR of 0.86 (95% CI, 0.62-1.21; P = .40), she reported.

She explained her reasons for not considering diagnoses within 30 days of COVID-19 as causative. Echoing Dr. Tapia, Dr. Colhoun said the median time from symptom onset to diagnosis of type 1 diabetes is 25 days. “This suggests that 50% have had symptoms for over 25 days at diagnosis.”

She also stressed that when they compared the timing of SARS-CoV-2 testing with diagnosis, they found a much higher rate of COVID-19 testing around diagnosis. “This was not least because everyone admitted to hospital had to have a COVID-19 test.”
 

Latest U.S. data point to a link

Meanwhile, for the new data reported in JAMA Network Open, medical student Ellen K. Kendall of Case Western Reserve University, Cleveland, matched 571,256 pediatric patients: 285,628 with COVID-19 and 285,628 with non–COVID-19 respiratory infections.

By 6 months after COVID-19, 123 patients (0.043%) had received a new diagnosis of type 1 diabetes, but only 72 (0.025%) were diagnosed with type 1 diabetes within 6 months after non–COVID-19 respiratory infection.

At 1, 3, and 6 months after infection, risk of diagnosis of type 1 diabetes was greater among those infected with SARS-CoV-2, compared with those with non–COVID-19 respiratory infection (1 month: HR, 1.96; 3 months: HR, 2.10; and 6 months: HR, 1.83), and in subgroups of patients aged 0-9 years, a group unlikely to develop type 2 diabetes.

“In this study, new type 1 diabetes diagnoses were more likely to occur among pediatric patients with prior COVID-19 than among those with other respiratory infections (or with other encounters with health systems),” noted Ms. Kendall and coauthors. “Respiratory infections have previously been associated with onset of type 1 diabetes, but this risk was even higher among those with COVID-19 in our study, raising concern for long-term, post–COVID-19 autoimmune complications among youths.”

“The increased risk of new-onset type 1 diabetes after COVID-19 adds an important consideration for risk–benefit discussions for prevention and treatment of SARS-CoV-2 infection in pediatric populations,” they concluded.

A study from the Centers for Disease Control and Prevention published in January 2022, also concluded there was a link between COVID-19 and diabetes in children, but not with other acute respiratory infections. Children were 2.5 times more likely to be diagnosed with diabetes following a SARS-CoV-2 infection, it found.

However, the study has been criticized because it pooled all types of diabetes together and did not account for other health conditions, medications that can increase blood glucose levels, race, obesity, and other social determinants of health that might influence a child’s risk of acquiring COVID-19 or diabetes.

“I’ve no doubt that the CDC data were incorrect because the incidence rate for ... diabetes, even in those never exposed to COVID-19 infection, was 10 times the rate ever reported in the U.S.,” Dr. Colhoun said. “There’s no way these data are correct. I believe there was a confusion between incidence and prevalence of diabetes.”

“This paper caused a great deal of panic, especially among those who have a child with type 1diabetes, so we need to be very careful not to cause undue alarm until we have more definitive evidence in this arena,” she stressed.

However, she also acknowledged that the new Norwegian study was well conducted, and she has no methodological concerns about it, so “I think we just have to wait and see.”

Given the inconclusiveness on the issue, there is an ongoing CoviDiab registry collecting data on this very subject.

Dr. Tapia presented on behalf of lead author Dr. Gulseth, who has reported no relevant financial relationships. Dr. Colhoun also reported no relevant financial relationships.

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

STOCKHOLM – It remains inconclusive whether SARS-CoV-2 infection predisposes children and adolescents to a higher risk of type 1 diabetes. Data from two new studies and a recently published research letter add to the growing body of knowledge on the subject, but still can’t draw any definitive conclusions.

The latest results from a Norwegian and a Scottish study both examine incidence of type 1 diabetes in young people with a history of SARS-CoV-2 infection and were reported at the annual meeting of the European Association for the Study of Diabetes.

A 60% increased risk for type 1 diabetes at least 31 days after SARS-CoV-2 infection (adjusted hazard ratio, 1.63) was found in the Norwegian study, while in contrast, the Scottish study only found an increased risk in the first few months of the pandemic, in 2020, but importantly, no association over a much longer time period (March 2020–November 2021).

In a comment on Twitter on the two studies presented at EASD, session moderator Kamlesh Khunti, MD, professor of primary care diabetes and vascular medicine at the University of Leicester, (England), said: “In summary, two studies showing no or weak association of type 1 diabetes with COVID.”

But new data in the research letter published in JAMA Network Open, based on U.S. figures, also found an almost doubling of type 1 diabetes in children in the first few months after COVID-19 infection relative to infection with other respiratory viruses.

Lead author of the Scottish study, Helen Colhoun, PhD, honorary public health consultant at Public Health Scotland, commented: “Data in children are variable year on year, which emphasizes the need to be cautious over taking a tiny snapshot.”

Nevertheless, this is “a hugely important question and we must not drop the ball. [We must] keep looking at it and maintain scientific equipoise. ... [This] reinforces the need to carry on this analysis into the future to obtain an unequivocal picture,” she emphasized.
 

Norwegian study: If there is an association, the risk is small

German Tapia, PhD, from the Norwegian Institute of Public Health, Oslo, presented the results of a study of SARS-CoV-2 infection and subsequent risk of type 1 diabetes in 1.2 million children in Norway.

Of these, 424,354 children had been infected with SARS-CoV-2, and there were 990 incident cases of type 1 diabetes.

“What we do know about COVID-19 in children is that the symptoms are mild and only a small proportion are hospitalized with more serious symptoms. But we do not know the long-term effects of COVID-19 infection because this requires a longer follow-up period,” remarked Dr. Tapia, adding that other viral infections are thought to be linked to the development of type 1 diabetes, in particular, respiratory infections.

The data were sourced from the Norwegian Emergency Preparedness Register for COVID-19, which gathers daily data updates including infections (positive and negative results for free-of-charge testing), diagnoses (primary and secondary care), vaccinations (also free of charge), prescribed medications, and basic demographics.

“We link these data using the personal identification number that every Norwegian citizen has,” explained Dr. Tapia.

He presented results from two cohorts: firstly, results in children only, including those tested for SARS-CoV-2 infection, and secondly, a full national Norwegian population cohort.

Regarding the first cohort, those under 18 years who tested positive for SARS-CoV-2 infection, from March 2020 to March 2022, had a significantly increased risk of type 1 diabetes at least 31 days after infection, with an adjusted hazard ratio of 1.63 (95% confidence interval, 1.08-2.47; P = .02). Adjustments were made for age, sex, non-Nordic country of origin, geographic area, and socioeconomic factors.

For children who developed type 1 diabetes within 30 days of a SARS-CoV-2 infection, the HR was 1.26 (95% CI, 0.72-2.19; P = .42), which did not reach statistical significance.

“The fact that fewer people developed type 1 diabetes within 30 days is not surprising because we know that type 1 diabetes develops over a long period of time,” Dr. Tapia said.

“For this reason, we would not expect to find new cases of those people who develop type 1 diabetes within 30 days of COVID-19 infection,” he explained. In these cases, “it is most likely that they already had [type 1 diabetes], and the infection probably triggered clinical symptoms, so their type 1 diabetes was discovered.”

Turning to the full population cohort and diagnoses of type 1 diabetes over 30 days after SARS-CoV-2 infection, the Norwegian researchers found an association, with an HR of 1.57 (95% CI, 1.06-2.33; P = .03), while diagnosis of type 1 diabetes at 30 days or less generated a hazard ratio of 1.22 (95% CI, 0.72-2.19; P = .42).

“So very similar results were found, and after adjustment for confounders, results were still similar,” reported Dr. Tapia.

He also conducted a similar analysis with vaccination as an exposure but found no association between vaccination against SARS-CoV-2 and diagnosis of type 1 diabetes.

“From these results, we conclude that this suggests an increase in diagnosis of type 1 diabetes after SARS-CoV-2 infection, but it must be noted that the absolute risk of developing type 1 diabetes after infection in children is low, with most children not developing the disease,” he emphasized. “There are nearly half a million children who have been infected with SARS-CoV-2 in Norway, but only a very small proportion develop type 1 diabetes.”
 

Scottish study: No association found over longer term

Dr. Colhoun and colleagues looked at the relationship between incident type 1 diabetes and SARS-CoV-2 infection in children in Scotland using e-health record linkage.

The study involved 1.8 million people under 35 years of age and found very weak, if any, evidence of an association between incident type 1 diabetes and SARS-CoV-2.

Examining data between March 2020 and November 2021, Dr. Colhoun and colleagues identified 365,080 individuals up to age 35 with at least one detected SARS-CoV-2 infection during follow-up and 1,074 who developed type 1 diabetes.

“In children under 16 years, suspected cases of type 1 diabetes are admitted to hospital, and 97% of diagnosis dates are recorded in the Scottish Care Information – Diabetes Collaboration register [SCI-Diabetes] prior to or within 2 days of the first hospital admission for type 1 diabetes,” Dr. Colhoun said, stressing the timeliness of the data.

“We found the incidence of type 1 diabetes diagnosis increased 1.2-fold in those aged 0-14 years, but we did not find any association at an individual level of COVID-19 infection over 30 days prior to a type 1 diabetes diagnosis, in this particular dataset,” she reported. In young people aged 15-34, there was a linear increase in incident type 1 diabetes from 2015 to 2021 with no pandemic increase.

Referring to the 1.2-fold increase soon after the pandemic started, she explained that, in 0- to 14-year-olds, the increase followed a drop in the preceding months prepandemic in 2019. They also found that the seasonal pattern of type 1 diabetes diagnoses remained roughly the same across the pandemic months, with typical peaks in February and September.

In the cohort of under 35s, researchers also found a rate ratio of 2.62 (95% CI, 1.81-3.78) within a 30-day window of SARS-CoV-2 infection, but beyond 30 days, no evidence was seen of an association, with a RR of 0.86 (95% CI, 0.62-1.21; P = .40), she reported.

She explained her reasons for not considering diagnoses within 30 days of COVID-19 as causative. Echoing Dr. Tapia, Dr. Colhoun said the median time from symptom onset to diagnosis of type 1 diabetes is 25 days. “This suggests that 50% have had symptoms for over 25 days at diagnosis.”

She also stressed that when they compared the timing of SARS-CoV-2 testing with diagnosis, they found a much higher rate of COVID-19 testing around diagnosis. “This was not least because everyone admitted to hospital had to have a COVID-19 test.”
 

Latest U.S. data point to a link

Meanwhile, for the new data reported in JAMA Network Open, medical student Ellen K. Kendall of Case Western Reserve University, Cleveland, matched 571,256 pediatric patients: 285,628 with COVID-19 and 285,628 with non–COVID-19 respiratory infections.

By 6 months after COVID-19, 123 patients (0.043%) had received a new diagnosis of type 1 diabetes, but only 72 (0.025%) were diagnosed with type 1 diabetes within 6 months after non–COVID-19 respiratory infection.

At 1, 3, and 6 months after infection, risk of diagnosis of type 1 diabetes was greater among those infected with SARS-CoV-2, compared with those with non–COVID-19 respiratory infection (1 month: HR, 1.96; 3 months: HR, 2.10; and 6 months: HR, 1.83), and in subgroups of patients aged 0-9 years, a group unlikely to develop type 2 diabetes.

“In this study, new type 1 diabetes diagnoses were more likely to occur among pediatric patients with prior COVID-19 than among those with other respiratory infections (or with other encounters with health systems),” noted Ms. Kendall and coauthors. “Respiratory infections have previously been associated with onset of type 1 diabetes, but this risk was even higher among those with COVID-19 in our study, raising concern for long-term, post–COVID-19 autoimmune complications among youths.”

“The increased risk of new-onset type 1 diabetes after COVID-19 adds an important consideration for risk–benefit discussions for prevention and treatment of SARS-CoV-2 infection in pediatric populations,” they concluded.

A study from the Centers for Disease Control and Prevention published in January 2022, also concluded there was a link between COVID-19 and diabetes in children, but not with other acute respiratory infections. Children were 2.5 times more likely to be diagnosed with diabetes following a SARS-CoV-2 infection, it found.

However, the study has been criticized because it pooled all types of diabetes together and did not account for other health conditions, medications that can increase blood glucose levels, race, obesity, and other social determinants of health that might influence a child’s risk of acquiring COVID-19 or diabetes.

“I’ve no doubt that the CDC data were incorrect because the incidence rate for ... diabetes, even in those never exposed to COVID-19 infection, was 10 times the rate ever reported in the U.S.,” Dr. Colhoun said. “There’s no way these data are correct. I believe there was a confusion between incidence and prevalence of diabetes.”

“This paper caused a great deal of panic, especially among those who have a child with type 1diabetes, so we need to be very careful not to cause undue alarm until we have more definitive evidence in this arena,” she stressed.

However, she also acknowledged that the new Norwegian study was well conducted, and she has no methodological concerns about it, so “I think we just have to wait and see.”

Given the inconclusiveness on the issue, there is an ongoing CoviDiab registry collecting data on this very subject.

Dr. Tapia presented on behalf of lead author Dr. Gulseth, who has reported no relevant financial relationships. Dr. Colhoun also reported no relevant financial relationships.

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

The COVID-19 pandemic has been associated with the development of anorexia nervosa in Canadian children and adolescents, data suggest.

Preliminary results of the Canadian Paediatric Surveillance Program (CPSP) indicate that the pandemic has been a precipitating factor in the development of anorexia nervosa in almost half of children and adolescents studied. The pandemic also has precipitated hospitalizations for anorexia in more than one-third of cases.

“Data globally, and certainly our data here in Canada, have shown a real increase in health care utilization with the onset of the COVID-19 pandemic,” study author Debra Katzman, MD, professor of pediatrics at the Hospital for Sick Children in Toronto and the University of Toronto, said in an interview. “And when I talk about health care utilization, I’m talking about hospitalizations for eating disorders.”

The data were included in the 2021 results of the CPSP.
 

Focus on appearance

CPSP is a collaboration between the Public Health Agency of Canada and the Canadian Pediatric Society that consists of a network of 2,800 pediatricians and pediatric subspecialists across Canada. The latest results include surveillance studies on 14 diseases and conditions, with data collected during various periods.

From April 2020 to May 2021, researchers identified 1,800 COVID-19 cases in children and collected detailed information on 1,456 of them, including 405 cases hospitalized with pediatric inflammatory multisystem syndrome (PIMS). The median age of hospitalized cases was 3.2 years for SARS-CoV-2 infection and 5.4 years for PIMS.

Dr. Katzman and colleagues observed 118 first-time hospitalizations for anorexia nervosa between Sept. 1 and Dec. 31, 2021. More than 90% of reported cases were female, with 66% of verified cases in teens aged 14-17 years and the remainder in adolescents aged 11-13 years.

In 49% of cases, the reporting physician identified the COVID-19 pandemic as a precipitating factor in the development of anorexia nervosa. In 37% of cases, the reporting physician identified the pandemic as having precipitated the anorexia-related hospitalization.

Last year, a cross-sectional analysis of children in Canada reported that monthly hospitalizations for anorexia nervosa increased from 7.5 to 20 from March through November 2020. The monthly rate in the CPSP study was closer to 30 for first-time hospitalizations.

Dr. Katzman said that the findings about anorexia nervosa didn’t surprise her. “There was so much disruption and [so many] restrictions to young peoples’ daily routines – closures of schools and recreational activities – they lost regular connection with their peers, and they lost extracurricular and social activities,” she said. “That led to heightened anxiety and depression and really a lack of control.”

Adolescents and teens were also spending more time on social media than they were before the pandemic, she noted. “They were looking at themselves all the time, so they were getting preoccupied with their body image. There was a heightened focus on appearance, and I think that things like public-health mitigation strategies – things like hand washing, social distancing, mask wearing – may have impacted the psychological well-being of young people.”

The closure of outpatient facilities, long waiting lists to get into facilities that were opened, and “coronaphobia” about going to physicians’ offices and emergency departments compounded the problem, Dr. Katzman added.

The long-term effects of COVID and eating disorders in children are unknown, Dr. Katzman said. “This is sort of a wake-up call for the health care system that during times of stress or pandemics or crises, these kinds of things can happen, and we need to be prepared to provide the resources for vulnerable populations moving forward,” she said.
 

Heightened anxiety

Commenting on the data, Margaret Thew, APNP, director of the eating disorders program at Children’s Wisconsin in Milwaukee, said that isolation due to school closures and negative social media messages created the “perfect storm” for eating disorders in adolescents and teenagers because of higher rates of anxiety and depression. Ms. Thew was not involved in the research.

The storm is not over yet, she said. “What everyone needs to keep in mind is that we still have this very heightened state of anxiety and depression ... for adolescents, teenagers, and preteens alike,” Ms. Thew said in an interview, “and we know that many of them are not coping with their anxiety very well.”

In her experience, since the start of the pandemic, the average age of pediatric patients with eating disorders declined from 16 to 15 years, and the youngest age declined from 12 to 11 years.

Overall, the CPSP results show that children are affected by mental health issues at an earlier age than before the pandemic, said Ms. Thew. “Years ago, we wouldn’t have thought that an 8-year-old needed to be screened for some of these risk factors, but now we’re definitely getting more younger children who are struggling, and I think it’s taking too long for them to get the care they need because it’s being overlooked,” she said.

The report was funded by the Public Health Agency of Canada, Health Canada, Alberta Children’s Hospital Research Institute, Bethanys Hope Foundation, CHEO Research Institute, and Children’s Hospital Research Institute of Manitoba. Dr. Katzman and Ms. Thew have no relevant disclosures.

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

The COVID-19 pandemic has been associated with the development of anorexia nervosa in Canadian children and adolescents, data suggest.

Preliminary results of the Canadian Paediatric Surveillance Program (CPSP) indicate that the pandemic has been a precipitating factor in the development of anorexia nervosa in almost half of children and adolescents studied. The pandemic also has precipitated hospitalizations for anorexia in more than one-third of cases.

“Data globally, and certainly our data here in Canada, have shown a real increase in health care utilization with the onset of the COVID-19 pandemic,” study author Debra Katzman, MD, professor of pediatrics at the Hospital for Sick Children in Toronto and the University of Toronto, said in an interview. “And when I talk about health care utilization, I’m talking about hospitalizations for eating disorders.”

The data were included in the 2021 results of the CPSP.
 

Focus on appearance

CPSP is a collaboration between the Public Health Agency of Canada and the Canadian Pediatric Society that consists of a network of 2,800 pediatricians and pediatric subspecialists across Canada. The latest results include surveillance studies on 14 diseases and conditions, with data collected during various periods.

From April 2020 to May 2021, researchers identified 1,800 COVID-19 cases in children and collected detailed information on 1,456 of them, including 405 cases hospitalized with pediatric inflammatory multisystem syndrome (PIMS). The median age of hospitalized cases was 3.2 years for SARS-CoV-2 infection and 5.4 years for PIMS.

Dr. Katzman and colleagues observed 118 first-time hospitalizations for anorexia nervosa between Sept. 1 and Dec. 31, 2021. More than 90% of reported cases were female, with 66% of verified cases in teens aged 14-17 years and the remainder in adolescents aged 11-13 years.

In 49% of cases, the reporting physician identified the COVID-19 pandemic as a precipitating factor in the development of anorexia nervosa. In 37% of cases, the reporting physician identified the pandemic as having precipitated the anorexia-related hospitalization.

Last year, a cross-sectional analysis of children in Canada reported that monthly hospitalizations for anorexia nervosa increased from 7.5 to 20 from March through November 2020. The monthly rate in the CPSP study was closer to 30 for first-time hospitalizations.

Dr. Katzman said that the findings about anorexia nervosa didn’t surprise her. “There was so much disruption and [so many] restrictions to young peoples’ daily routines – closures of schools and recreational activities – they lost regular connection with their peers, and they lost extracurricular and social activities,” she said. “That led to heightened anxiety and depression and really a lack of control.”

Adolescents and teens were also spending more time on social media than they were before the pandemic, she noted. “They were looking at themselves all the time, so they were getting preoccupied with their body image. There was a heightened focus on appearance, and I think that things like public-health mitigation strategies – things like hand washing, social distancing, mask wearing – may have impacted the psychological well-being of young people.”

The closure of outpatient facilities, long waiting lists to get into facilities that were opened, and “coronaphobia” about going to physicians’ offices and emergency departments compounded the problem, Dr. Katzman added.

The long-term effects of COVID and eating disorders in children are unknown, Dr. Katzman said. “This is sort of a wake-up call for the health care system that during times of stress or pandemics or crises, these kinds of things can happen, and we need to be prepared to provide the resources for vulnerable populations moving forward,” she said.
 

Heightened anxiety

Commenting on the data, Margaret Thew, APNP, director of the eating disorders program at Children’s Wisconsin in Milwaukee, said that isolation due to school closures and negative social media messages created the “perfect storm” for eating disorders in adolescents and teenagers because of higher rates of anxiety and depression. Ms. Thew was not involved in the research.

The storm is not over yet, she said. “What everyone needs to keep in mind is that we still have this very heightened state of anxiety and depression ... for adolescents, teenagers, and preteens alike,” Ms. Thew said in an interview, “and we know that many of them are not coping with their anxiety very well.”

In her experience, since the start of the pandemic, the average age of pediatric patients with eating disorders declined from 16 to 15 years, and the youngest age declined from 12 to 11 years.

Overall, the CPSP results show that children are affected by mental health issues at an earlier age than before the pandemic, said Ms. Thew. “Years ago, we wouldn’t have thought that an 8-year-old needed to be screened for some of these risk factors, but now we’re definitely getting more younger children who are struggling, and I think it’s taking too long for them to get the care they need because it’s being overlooked,” she said.

The report was funded by the Public Health Agency of Canada, Health Canada, Alberta Children’s Hospital Research Institute, Bethanys Hope Foundation, CHEO Research Institute, and Children’s Hospital Research Institute of Manitoba. Dr. Katzman and Ms. Thew have no relevant disclosures.

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

The COVID-19 pandemic has been associated with the development of anorexia nervosa in Canadian children and adolescents, data suggest.

Preliminary results of the Canadian Paediatric Surveillance Program (CPSP) indicate that the pandemic has been a precipitating factor in the development of anorexia nervosa in almost half of children and adolescents studied. The pandemic also has precipitated hospitalizations for anorexia in more than one-third of cases.

“Data globally, and certainly our data here in Canada, have shown a real increase in health care utilization with the onset of the COVID-19 pandemic,” study author Debra Katzman, MD, professor of pediatrics at the Hospital for Sick Children in Toronto and the University of Toronto, said in an interview. “And when I talk about health care utilization, I’m talking about hospitalizations for eating disorders.”

The data were included in the 2021 results of the CPSP.
 

Focus on appearance

CPSP is a collaboration between the Public Health Agency of Canada and the Canadian Pediatric Society that consists of a network of 2,800 pediatricians and pediatric subspecialists across Canada. The latest results include surveillance studies on 14 diseases and conditions, with data collected during various periods.

From April 2020 to May 2021, researchers identified 1,800 COVID-19 cases in children and collected detailed information on 1,456 of them, including 405 cases hospitalized with pediatric inflammatory multisystem syndrome (PIMS). The median age of hospitalized cases was 3.2 years for SARS-CoV-2 infection and 5.4 years for PIMS.

Dr. Katzman and colleagues observed 118 first-time hospitalizations for anorexia nervosa between Sept. 1 and Dec. 31, 2021. More than 90% of reported cases were female, with 66% of verified cases in teens aged 14-17 years and the remainder in adolescents aged 11-13 years.

In 49% of cases, the reporting physician identified the COVID-19 pandemic as a precipitating factor in the development of anorexia nervosa. In 37% of cases, the reporting physician identified the pandemic as having precipitated the anorexia-related hospitalization.

Last year, a cross-sectional analysis of children in Canada reported that monthly hospitalizations for anorexia nervosa increased from 7.5 to 20 from March through November 2020. The monthly rate in the CPSP study was closer to 30 for first-time hospitalizations.

Dr. Katzman said that the findings about anorexia nervosa didn’t surprise her. “There was so much disruption and [so many] restrictions to young peoples’ daily routines – closures of schools and recreational activities – they lost regular connection with their peers, and they lost extracurricular and social activities,” she said. “That led to heightened anxiety and depression and really a lack of control.”

Adolescents and teens were also spending more time on social media than they were before the pandemic, she noted. “They were looking at themselves all the time, so they were getting preoccupied with their body image. There was a heightened focus on appearance, and I think that things like public-health mitigation strategies – things like hand washing, social distancing, mask wearing – may have impacted the psychological well-being of young people.”

The closure of outpatient facilities, long waiting lists to get into facilities that were opened, and “coronaphobia” about going to physicians’ offices and emergency departments compounded the problem, Dr. Katzman added.

The long-term effects of COVID and eating disorders in children are unknown, Dr. Katzman said. “This is sort of a wake-up call for the health care system that during times of stress or pandemics or crises, these kinds of things can happen, and we need to be prepared to provide the resources for vulnerable populations moving forward,” she said.
 

Heightened anxiety

Commenting on the data, Margaret Thew, APNP, director of the eating disorders program at Children’s Wisconsin in Milwaukee, said that isolation due to school closures and negative social media messages created the “perfect storm” for eating disorders in adolescents and teenagers because of higher rates of anxiety and depression. Ms. Thew was not involved in the research.

The storm is not over yet, she said. “What everyone needs to keep in mind is that we still have this very heightened state of anxiety and depression ... for adolescents, teenagers, and preteens alike,” Ms. Thew said in an interview, “and we know that many of them are not coping with their anxiety very well.”

In her experience, since the start of the pandemic, the average age of pediatric patients with eating disorders declined from 16 to 15 years, and the youngest age declined from 12 to 11 years.

Overall, the CPSP results show that children are affected by mental health issues at an earlier age than before the pandemic, said Ms. Thew. “Years ago, we wouldn’t have thought that an 8-year-old needed to be screened for some of these risk factors, but now we’re definitely getting more younger children who are struggling, and I think it’s taking too long for them to get the care they need because it’s being overlooked,” she said.

The report was funded by the Public Health Agency of Canada, Health Canada, Alberta Children’s Hospital Research Institute, Bethanys Hope Foundation, CHEO Research Institute, and Children’s Hospital Research Institute of Manitoba. Dr. Katzman and Ms. Thew have no relevant disclosures.

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

This transcript of Impact Factor with F. Perry Wilson has been edited for clarity.

It was 100 years ago when Leonard Thompson, age 13, received a reprieve from a death sentence. Young master Thompson had type 1 diabetes, a disease that was uniformly fatal within months of diagnosis. But he received a new treatment, insulin, from a canine pancreas. He would live 13 more years before dying at age 26 of pneumonia.

The history of type 1 diabetes since that time has been a battle on two fronts: First, the search for a cause of and cure for the disease; second, the effort to make the administration of insulin safer, more reliable, and easier.

The past 2 decades have seen a technological revolution in type 1 diabetes care, with continuous glucose monitors decreasing the need for painful finger sticks, and insulin pumps allowing for more precise titration of doses.

The dream, of course, has been to combine those two technologies, continuous glucose monitoring and insulin pumps, to create so-called closed-loop systems – basically an artificial pancreas – that would obviate the need for any intervention on the part of the patient, save the occasional refilling of an insulin reservoir.

We aren’t there yet, but we are closer than ever.

Closed-loop systems for insulin delivery, like the Tandem Control IQ system, are a marvel of technology, but they are not exactly hands-free. Users need to dial in settings for their insulin usage, count carbohydrates at meals, and inform the system that they are about to eat those meals to allow the algorithm to administer an appropriate insulin dose.

The perceived complexity of these systems may be responsible for why there are substantial disparities in the prescription of closed-loop systems. Kids of lower socioeconomic status are dramatically less likely to receive these advanced technologies. Providers may feel that patients with lower health literacy or social supports are not “ideal” for these technologies, even though they lead to demonstrably better outcomes.

That means that easier might be better. And a “bionic pancreas,” as reported in an article from The New England Journal of Medicine, is exactly that.

Broadly, it’s another closed-loop system. The bionic pancreas integrates with a continuous glucose monitor and administers insulin when needed. But the algorithm appears to be a bit smarter than what we have in existing devices. For example, patients do not need to provide any information about their usual insulin doses – just their body weight. They don’t need to count carbohydrates at meals – just to inform the device when they are eating, and whether the meal is the usual amount they eat, more, or less. The algorithm learns and adapts as it is used. Easy.

And in this randomized trial, easy does it.

A total of 219 participants were randomized in a 2:1 ratio to the bionic pancreas or usual diabetes care, though it was required that control participants use a continuous glucose monitor. Participants were as young as 6 years old and up to 79 years old; the majority were White and had a relatively high household income. The mean A1c was around 7.8% at baseline.

By the end of the study, the A1c was significantly improved in the bionic pancreas group, with a mean of 7.3% vs. 7.7% in the usual-care group.

This effect was most pronounced in those with a higher A1c at baseline.

People randomized to the bionic pancreas also spent more time in the target glucose range of 70-180 mg/dL.

All in all, the technology that makes it easy to manage your blood sugar, well, made it easy to manage your blood sugar.

But new technology is never without its hiccups. Those randomized to the bionic pancreas had a markedly higher rate of adverse events (244 events in 126 people compared with 10 events in 8 people in the usual-care group.)

This is actually a little misleading, though. The vast majority of these events were hyperglycemic episodes due to infusion set failures, which were reportable only in the bionic pancreas group. In other words, the patients in the control group who had an infusion set failure (assuming they were using an insulin pump at all) would have just called their regular doctor to get things sorted and not reported it to the study team.

Nevertheless, these adverse events – not serious, but common – highlight the fact that good software is not the only key to solving the closed-loop problem. We need good hardware too, hardware that can withstand the very active lives that children with type 1 diabetes deserve to live.

In short, the dream of a functional cure to type 1 diabetes, a true artificial pancreas, is closer than ever, but it’s still just a dream. With iterative advances like this, though, the reality may be here before you know it.

Dr. Wilson is associate professor of medicine and director of Yale University’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and on Medscape. He tweets @fperrywilson and hosts a repository of his communication work at www.methodsman.com. A version of this article first appeared on Medscape.com.

This transcript of Impact Factor with F. Perry Wilson has been edited for clarity.

It was 100 years ago when Leonard Thompson, age 13, received a reprieve from a death sentence. Young master Thompson had type 1 diabetes, a disease that was uniformly fatal within months of diagnosis. But he received a new treatment, insulin, from a canine pancreas. He would live 13 more years before dying at age 26 of pneumonia.

The history of type 1 diabetes since that time has been a battle on two fronts: First, the search for a cause of and cure for the disease; second, the effort to make the administration of insulin safer, more reliable, and easier.

The past 2 decades have seen a technological revolution in type 1 diabetes care, with continuous glucose monitors decreasing the need for painful finger sticks, and insulin pumps allowing for more precise titration of doses.

The dream, of course, has been to combine those two technologies, continuous glucose monitoring and insulin pumps, to create so-called closed-loop systems – basically an artificial pancreas – that would obviate the need for any intervention on the part of the patient, save the occasional refilling of an insulin reservoir.

We aren’t there yet, but we are closer than ever.

Closed-loop systems for insulin delivery, like the Tandem Control IQ system, are a marvel of technology, but they are not exactly hands-free. Users need to dial in settings for their insulin usage, count carbohydrates at meals, and inform the system that they are about to eat those meals to allow the algorithm to administer an appropriate insulin dose.

The perceived complexity of these systems may be responsible for why there are substantial disparities in the prescription of closed-loop systems. Kids of lower socioeconomic status are dramatically less likely to receive these advanced technologies. Providers may feel that patients with lower health literacy or social supports are not “ideal” for these technologies, even though they lead to demonstrably better outcomes.

That means that easier might be better. And a “bionic pancreas,” as reported in an article from The New England Journal of Medicine, is exactly that.

Broadly, it’s another closed-loop system. The bionic pancreas integrates with a continuous glucose monitor and administers insulin when needed. But the algorithm appears to be a bit smarter than what we have in existing devices. For example, patients do not need to provide any information about their usual insulin doses – just their body weight. They don’t need to count carbohydrates at meals – just to inform the device when they are eating, and whether the meal is the usual amount they eat, more, or less. The algorithm learns and adapts as it is used. Easy.

And in this randomized trial, easy does it.

A total of 219 participants were randomized in a 2:1 ratio to the bionic pancreas or usual diabetes care, though it was required that control participants use a continuous glucose monitor. Participants were as young as 6 years old and up to 79 years old; the majority were White and had a relatively high household income. The mean A1c was around 7.8% at baseline.

By the end of the study, the A1c was significantly improved in the bionic pancreas group, with a mean of 7.3% vs. 7.7% in the usual-care group.

This effect was most pronounced in those with a higher A1c at baseline.

People randomized to the bionic pancreas also spent more time in the target glucose range of 70-180 mg/dL.

All in all, the technology that makes it easy to manage your blood sugar, well, made it easy to manage your blood sugar.

But new technology is never without its hiccups. Those randomized to the bionic pancreas had a markedly higher rate of adverse events (244 events in 126 people compared with 10 events in 8 people in the usual-care group.)

This is actually a little misleading, though. The vast majority of these events were hyperglycemic episodes due to infusion set failures, which were reportable only in the bionic pancreas group. In other words, the patients in the control group who had an infusion set failure (assuming they were using an insulin pump at all) would have just called their regular doctor to get things sorted and not reported it to the study team.

Nevertheless, these adverse events – not serious, but common – highlight the fact that good software is not the only key to solving the closed-loop problem. We need good hardware too, hardware that can withstand the very active lives that children with type 1 diabetes deserve to live.

In short, the dream of a functional cure to type 1 diabetes, a true artificial pancreas, is closer than ever, but it’s still just a dream. With iterative advances like this, though, the reality may be here before you know it.

Dr. Wilson is associate professor of medicine and director of Yale University’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and on Medscape. He tweets @fperrywilson and hosts a repository of his communication work at www.methodsman.com. A version of this article first appeared on Medscape.com.

This transcript of Impact Factor with F. Perry Wilson has been edited for clarity.

It was 100 years ago when Leonard Thompson, age 13, received a reprieve from a death sentence. Young master Thompson had type 1 diabetes, a disease that was uniformly fatal within months of diagnosis. But he received a new treatment, insulin, from a canine pancreas. He would live 13 more years before dying at age 26 of pneumonia.

The history of type 1 diabetes since that time has been a battle on two fronts: First, the search for a cause of and cure for the disease; second, the effort to make the administration of insulin safer, more reliable, and easier.

The past 2 decades have seen a technological revolution in type 1 diabetes care, with continuous glucose monitors decreasing the need for painful finger sticks, and insulin pumps allowing for more precise titration of doses.

The dream, of course, has been to combine those two technologies, continuous glucose monitoring and insulin pumps, to create so-called closed-loop systems – basically an artificial pancreas – that would obviate the need for any intervention on the part of the patient, save the occasional refilling of an insulin reservoir.

We aren’t there yet, but we are closer than ever.

Closed-loop systems for insulin delivery, like the Tandem Control IQ system, are a marvel of technology, but they are not exactly hands-free. Users need to dial in settings for their insulin usage, count carbohydrates at meals, and inform the system that they are about to eat those meals to allow the algorithm to administer an appropriate insulin dose.

The perceived complexity of these systems may be responsible for why there are substantial disparities in the prescription of closed-loop systems. Kids of lower socioeconomic status are dramatically less likely to receive these advanced technologies. Providers may feel that patients with lower health literacy or social supports are not “ideal” for these technologies, even though they lead to demonstrably better outcomes.

That means that easier might be better. And a “bionic pancreas,” as reported in an article from The New England Journal of Medicine, is exactly that.

Broadly, it’s another closed-loop system. The bionic pancreas integrates with a continuous glucose monitor and administers insulin when needed. But the algorithm appears to be a bit smarter than what we have in existing devices. For example, patients do not need to provide any information about their usual insulin doses – just their body weight. They don’t need to count carbohydrates at meals – just to inform the device when they are eating, and whether the meal is the usual amount they eat, more, or less. The algorithm learns and adapts as it is used. Easy.

And in this randomized trial, easy does it.

A total of 219 participants were randomized in a 2:1 ratio to the bionic pancreas or usual diabetes care, though it was required that control participants use a continuous glucose monitor. Participants were as young as 6 years old and up to 79 years old; the majority were White and had a relatively high household income. The mean A1c was around 7.8% at baseline.

By the end of the study, the A1c was significantly improved in the bionic pancreas group, with a mean of 7.3% vs. 7.7% in the usual-care group.

This effect was most pronounced in those with a higher A1c at baseline.

People randomized to the bionic pancreas also spent more time in the target glucose range of 70-180 mg/dL.

All in all, the technology that makes it easy to manage your blood sugar, well, made it easy to manage your blood sugar.

But new technology is never without its hiccups. Those randomized to the bionic pancreas had a markedly higher rate of adverse events (244 events in 126 people compared with 10 events in 8 people in the usual-care group.)

This is actually a little misleading, though. The vast majority of these events were hyperglycemic episodes due to infusion set failures, which were reportable only in the bionic pancreas group. In other words, the patients in the control group who had an infusion set failure (assuming they were using an insulin pump at all) would have just called their regular doctor to get things sorted and not reported it to the study team.

Nevertheless, these adverse events – not serious, but common – highlight the fact that good software is not the only key to solving the closed-loop problem. We need good hardware too, hardware that can withstand the very active lives that children with type 1 diabetes deserve to live.

In short, the dream of a functional cure to type 1 diabetes, a true artificial pancreas, is closer than ever, but it’s still just a dream. With iterative advances like this, though, the reality may be here before you know it.

Dr. Wilson is associate professor of medicine and director of Yale University’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and on Medscape. He tweets @fperrywilson and hosts a repository of his communication work at www.methodsman.com. A version of this article first appeared on Medscape.com.

Developmental language disorder (DLD) is characterized by receptive or expressive language difficulties or both. Children with the neurodevelopmental condition “struggle to comprehend and use their native language for no obvious reason,” said the authors of a new study. This leads to problems with grammar, vocabulary, and holding conversations, and in turn an increased risk of “difficulties when learning to read, underachieving academically, being unemployed, and facing social and mental health challenges.”

The condition is common and estimated to affect 7% of children – approximately two in every classroom – but is “underrecognized” said the authors.

Saloni Krishnan, PhD, reader at Royal Holloway, University of London, who led the study as a research fellow at the University of Oxford, England, explained: “DLD is a relatively unknown and understudied condition, unlike better known neurodevelopmental conditions such as ADHD, dyslexia, or autism.”

It is suspected that children with DLD may have differences in areas of the brain involved with learning habits and rules. “Although we know that DLD does not result from gross neural lesions, we still do not have a clear picture of how brain anatomy differs in children with DLD,” the authors highlighted.
 

Language learning difficulties linked to brain differences

For their study, published in eLife, researchers used an MRI technique called multiparameter mapping (MPM) to investigate microstructural neural differences in children with DLD. The technique measures the properties of brain tissue and is particularly useful for measuring the amounts of myelin.

“Understanding the neural basis of DLD is particularly challenging given the developmental nature of the disorder, as well as the lack of animal models for understanding language,” explained the authors. However, they pointed out that MPM allows an “unparalleled in vivo method” to investigate microstructural neural changes in children with DLD.

Kate Watkins, PhD, professor of cognitive neuroscience at the University of Oxford and senior author, said: “This type of scan tells us more about the makeup or composition of the brain tissue in different areas.”

As part of the Oxford Brain Organisation in Language Development (OxBOLD) study, the researchers recruited and tested 175 children between the ages of 10 and 15 years. Subsequently, 56 children with typical language development and 33 children with DLD were scanned using MPM.

The researchers compared the two groups and found that children with DLD have less myelin in parts of the brain responsible for speaking, listening, and learning rules and habits.

Specifically, maps of magnetization transfer saturation (MTsat) – which index myelin – in children with DLD showed reductions in MTsat values in the caudate nucleus bilaterally, and in the left ventral sensorimotor cortex and Heschl’s gyrus.

“Our findings using this protocol suggest that the caudate nucleus, as well as regions in the wider speech and language network, show alterations in myelin in children with DLD,” explained the authors.

“Given myelin’s role in enabling fast and reliable communication in the brain, reduced myelin content may explain why children with DLD struggle with speech and language processing,” they highlighted.
 

Significant advance in DLD understanding

The study findings established changes in striatal and cortical myelin as a “neural basis for DLD,” explained the journal editor, who highlighted that this was a “significant advance” in the understanding of DLD. “These brain differences may explain the poorer language outcomes in this group,” the authors said.

The findings “strongly point” to a role for the striatum in the development of DLD, and this role is likely to be in the “learning of habits and sequences,” the authors said.

They pointed out, however, that myelin patterns can change over development, and that myelination can be observed after successful training. “It is important to assess whether these differences in myelin persist over development in DLD, and if they can be targeted through training using behavioral interventions,” they emphasized.

Professor Watkins commented: “The findings might help us understand the pathways involved at a biological level and ultimately allow us to explain why children with DLD have problems with language learning.”

A spokesperson for the RADLD (Raising Awareness of Developmental Language Disorder) organization, commented: “Developmental language disorder has long been understood to have a neurological basis; however, these differences in the brain development have received limited attention in research.” It added that utilizing new technology helps to better understand the “potential neurological differences” experienced by people with DLD.

More studies are needed to determine if these brain differences cause language problems and how or if experiencing language difficulties could cause these changes in the brain, explained the authors. They hoped that further research may help scientists find new treatments that target these brain differences.

Funding was provided by UK Research and Innovation, Wellcome Trust. The authors declared no competing interests.

A version of this article first appeared on MedscapeUK.

Developmental language disorder (DLD) is characterized by receptive or expressive language difficulties or both. Children with the neurodevelopmental condition “struggle to comprehend and use their native language for no obvious reason,” said the authors of a new study. This leads to problems with grammar, vocabulary, and holding conversations, and in turn an increased risk of “difficulties when learning to read, underachieving academically, being unemployed, and facing social and mental health challenges.”

The condition is common and estimated to affect 7% of children – approximately two in every classroom – but is “underrecognized” said the authors.

Saloni Krishnan, PhD, reader at Royal Holloway, University of London, who led the study as a research fellow at the University of Oxford, England, explained: “DLD is a relatively unknown and understudied condition, unlike better known neurodevelopmental conditions such as ADHD, dyslexia, or autism.”

It is suspected that children with DLD may have differences in areas of the brain involved with learning habits and rules. “Although we know that DLD does not result from gross neural lesions, we still do not have a clear picture of how brain anatomy differs in children with DLD,” the authors highlighted.
 

Language learning difficulties linked to brain differences

For their study, published in eLife, researchers used an MRI technique called multiparameter mapping (MPM) to investigate microstructural neural differences in children with DLD. The technique measures the properties of brain tissue and is particularly useful for measuring the amounts of myelin.

“Understanding the neural basis of DLD is particularly challenging given the developmental nature of the disorder, as well as the lack of animal models for understanding language,” explained the authors. However, they pointed out that MPM allows an “unparalleled in vivo method” to investigate microstructural neural changes in children with DLD.

Kate Watkins, PhD, professor of cognitive neuroscience at the University of Oxford and senior author, said: “This type of scan tells us more about the makeup or composition of the brain tissue in different areas.”

As part of the Oxford Brain Organisation in Language Development (OxBOLD) study, the researchers recruited and tested 175 children between the ages of 10 and 15 years. Subsequently, 56 children with typical language development and 33 children with DLD were scanned using MPM.

The researchers compared the two groups and found that children with DLD have less myelin in parts of the brain responsible for speaking, listening, and learning rules and habits.

Specifically, maps of magnetization transfer saturation (MTsat) – which index myelin – in children with DLD showed reductions in MTsat values in the caudate nucleus bilaterally, and in the left ventral sensorimotor cortex and Heschl’s gyrus.

“Our findings using this protocol suggest that the caudate nucleus, as well as regions in the wider speech and language network, show alterations in myelin in children with DLD,” explained the authors.

“Given myelin’s role in enabling fast and reliable communication in the brain, reduced myelin content may explain why children with DLD struggle with speech and language processing,” they highlighted.
 

Significant advance in DLD understanding

The study findings established changes in striatal and cortical myelin as a “neural basis for DLD,” explained the journal editor, who highlighted that this was a “significant advance” in the understanding of DLD. “These brain differences may explain the poorer language outcomes in this group,” the authors said.

The findings “strongly point” to a role for the striatum in the development of DLD, and this role is likely to be in the “learning of habits and sequences,” the authors said.

They pointed out, however, that myelin patterns can change over development, and that myelination can be observed after successful training. “It is important to assess whether these differences in myelin persist over development in DLD, and if they can be targeted through training using behavioral interventions,” they emphasized.

Professor Watkins commented: “The findings might help us understand the pathways involved at a biological level and ultimately allow us to explain why children with DLD have problems with language learning.”

A spokesperson for the RADLD (Raising Awareness of Developmental Language Disorder) organization, commented: “Developmental language disorder has long been understood to have a neurological basis; however, these differences in the brain development have received limited attention in research.” It added that utilizing new technology helps to better understand the “potential neurological differences” experienced by people with DLD.

More studies are needed to determine if these brain differences cause language problems and how or if experiencing language difficulties could cause these changes in the brain, explained the authors. They hoped that further research may help scientists find new treatments that target these brain differences.

Funding was provided by UK Research and Innovation, Wellcome Trust. The authors declared no competing interests.

A version of this article first appeared on MedscapeUK.

Developmental language disorder (DLD) is characterized by receptive or expressive language difficulties or both. Children with the neurodevelopmental condition “struggle to comprehend and use their native language for no obvious reason,” said the authors of a new study. This leads to problems with grammar, vocabulary, and holding conversations, and in turn an increased risk of “difficulties when learning to read, underachieving academically, being unemployed, and facing social and mental health challenges.”

The condition is common and estimated to affect 7% of children – approximately two in every classroom – but is “underrecognized” said the authors.

Saloni Krishnan, PhD, reader at Royal Holloway, University of London, who led the study as a research fellow at the University of Oxford, England, explained: “DLD is a relatively unknown and understudied condition, unlike better known neurodevelopmental conditions such as ADHD, dyslexia, or autism.”

It is suspected that children with DLD may have differences in areas of the brain involved with learning habits and rules. “Although we know that DLD does not result from gross neural lesions, we still do not have a clear picture of how brain anatomy differs in children with DLD,” the authors highlighted.
 

Language learning difficulties linked to brain differences

For their study, published in eLife, researchers used an MRI technique called multiparameter mapping (MPM) to investigate microstructural neural differences in children with DLD. The technique measures the properties of brain tissue and is particularly useful for measuring the amounts of myelin.

“Understanding the neural basis of DLD is particularly challenging given the developmental nature of the disorder, as well as the lack of animal models for understanding language,” explained the authors. However, they pointed out that MPM allows an “unparalleled in vivo method” to investigate microstructural neural changes in children with DLD.

Kate Watkins, PhD, professor of cognitive neuroscience at the University of Oxford and senior author, said: “This type of scan tells us more about the makeup or composition of the brain tissue in different areas.”

As part of the Oxford Brain Organisation in Language Development (OxBOLD) study, the researchers recruited and tested 175 children between the ages of 10 and 15 years. Subsequently, 56 children with typical language development and 33 children with DLD were scanned using MPM.

The researchers compared the two groups and found that children with DLD have less myelin in parts of the brain responsible for speaking, listening, and learning rules and habits.

Specifically, maps of magnetization transfer saturation (MTsat) – which index myelin – in children with DLD showed reductions in MTsat values in the caudate nucleus bilaterally, and in the left ventral sensorimotor cortex and Heschl’s gyrus.

“Our findings using this protocol suggest that the caudate nucleus, as well as regions in the wider speech and language network, show alterations in myelin in children with DLD,” explained the authors.

“Given myelin’s role in enabling fast and reliable communication in the brain, reduced myelin content may explain why children with DLD struggle with speech and language processing,” they highlighted.
 

Significant advance in DLD understanding

The study findings established changes in striatal and cortical myelin as a “neural basis for DLD,” explained the journal editor, who highlighted that this was a “significant advance” in the understanding of DLD. “These brain differences may explain the poorer language outcomes in this group,” the authors said.

The findings “strongly point” to a role for the striatum in the development of DLD, and this role is likely to be in the “learning of habits and sequences,” the authors said.

They pointed out, however, that myelin patterns can change over development, and that myelination can be observed after successful training. “It is important to assess whether these differences in myelin persist over development in DLD, and if they can be targeted through training using behavioral interventions,” they emphasized.

Professor Watkins commented: “The findings might help us understand the pathways involved at a biological level and ultimately allow us to explain why children with DLD have problems with language learning.”

A spokesperson for the RADLD (Raising Awareness of Developmental Language Disorder) organization, commented: “Developmental language disorder has long been understood to have a neurological basis; however, these differences in the brain development have received limited attention in research.” It added that utilizing new technology helps to better understand the “potential neurological differences” experienced by people with DLD.

More studies are needed to determine if these brain differences cause language problems and how or if experiencing language difficulties could cause these changes in the brain, explained the authors. They hoped that further research may help scientists find new treatments that target these brain differences.

Funding was provided by UK Research and Innovation, Wellcome Trust. The authors declared no competing interests.

A version of this article first appeared on MedscapeUK.