Pediatrics

AMSTERDAM — Children with short stature related to severe atopic dermatitis not only can have their condition effectively treated with 16 weeks of dupilumab but also may experience improved growth, bringing them back toward standard height curves, revealed a post hoc trial analysis.

The research was presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

The trial included a “rigorously selected … well-characterized, well-studied” population of children aged 6-11 years, said presenter Alan D. Irvine, MD, DSc, professor of dermatology, Trinity College Dublin, Ireland.

It showed that “severe atopic dermatitis does cause restriction of growth, as well as a higher weight, and therefore obviously a higher BMI [body mass index].”

He continued, however, that children at the lower percentiles of height receiving prompt treatment with dupilumab (Dupixent) “were able to rapidly move through the centiles over the 16 weeks of the study, and that may be the window for catch-up growth … when children are growing rapidly.”

Anna Yasmine Kirkorian, MD, chief of dermatology, Children’s National Hospital, Washington, DC, who was not involved in the study, said that she was “surprised” at the degree of growth achieved over the study period, as height is not something that jumps up “overnight.”

“On the other hand, it fits with my experience with children who’ve had the brakes on all of their life due to inflammation, whether it be height, going to school, sleeping — everything is sort of put on pause by this terrible inflammatory process,” she said.

“When you take the brakes off, they get to be who they are going to be,” Kirkorian added. “So I was surprised by the speed of it, but not by the fact that height was acquired.”

Her belief is that in the pre-dupilumab era, severe atopic dermatitis was often insufficiently controlled, so children were “smaller than you would predict from parental height,” and the treatment is “allowing them to reach their genetic potential.”
 

Post Hoc Analysis 

In his presentation, Irvine emphasized that it has been clearly demonstrated that adolescents with moderate and severe atopic dermatitis have a significantly higher likelihood of being below the 25th percentile of height on growth reference charts.

Such children are also at a higher risk of having low bone mineral density and low serum alkaline phosphatase (ALP) levels . While data presented at the EADV 2023 Congress showed that dupilumab significantly increased serum levels of bone ALP compared with placebo, the underlying mechanism remains unclear.

For the current analysis, Irvine and colleagues determined that the proportion of children aged 6-11 years with severe atopic dermatitis and lower stature reach a ≥ 5 centile improvement in height following 16 weeks of dupilumab treatment.

They examined data from the LIBERTY AD PEDS trial, in which patients aged 6-11 years with severe atopic dermatitis were randomized to 300 mg dupilumab every 4 weeks or placebo along with a mild or moderately potent topical corticosteroid. The study found that, overall, dupilumab was associated with significant improvements in signs, symptoms, and quality of life compared with placebo.

Height measures at baseline revealed that “more boys and more girls were below the 50th centile than you would predict for a healthy, normal control population,” Irvine said. “If we look at weight, we see the opposite,” he continued, “with a disproportionate number of boys and girls who are above the 50th centile for weight at baseline.”

Consequently, “we’re seeing these children who are shorter and heavier than the predicted healthy weight range and, as a result, obviously have higher BMI,” Irvine noted, with 67% girls and 62% boys found to have a higher BMI than normal for their age.

After 16 weeks of treatment with dupilumab, there was a much greater gain in height than that seen among those on placebo, with the most pronounced effect seen in children who had the lowest height at baseline. Indeed, among children in the lowest 25% height percentile at baseline, 30.6% on dupilumab vs 11.9% on placebo experienced an increase in height of 5 centiles or more(P < .05).

“This reflects what we see in clinical practice,” Irvine said. “Children often grow dramatically on treatment for atopic dermatitis.”

Among patients with a baseline height below the 30th percentile, 31.9% treated with dupilumab vs 11.1% treated with placebo gained at least 5 centiles in height. The figures for children below the 40th height percentile at baseline were 31.3% vs 15.5% (P < .05 for both).

Although there remained a marked difference in the proportion of children below the 50th height percentile at baseline gaining 5 centiles or more in height, at 29.0% with dupilumab versus 15.7% with placebo, it was no longer significant.

“So the effect of catch-up growth, or growth through the centiles, is most marked in those who are in the 40th centile or below,” Irvine said, indicating that the “more growth restricted kids have much more potential to catch up.”
 

‘Convincing’ Data

Overall, Kirkorian said in the interview, the data are “convincing” and support her view that severe atopic dermatitis is a “terrible chronic disease that we really underappreciate.” Atopic dermatitis, she added, “should get the respect that any severe chronic illness would have, whether that be arthritis, diabetes, or cardiac disease, because it is a systemic disorder that … profoundly affects quality of life, every minute of every day.”

However, “we don’t get all the referrals we should, until the child has suffered for years and years, and the family has suffered,” as there is a bias that it can be outgrown — although not everybody does — and it “doesn’t look as conspicuous as other chronic skin disorders,” such as psoriasis.

“Now with this study,” Kirkorian said, “it gives us a really compelling point to make to parents, to the community, and to insurers that not only are we affecting the quality of life from the itch standpoint [with dupilumab] but we may have long profound effects on growth and bone health.”

The research was sponsored by Sanofi and Regeneron Pharmaceuticals. Irvine declared relationships with AbbVie, Arena Pharmaceuticals, BenevolentAI, Chugai Pharmaceutical, Dermavant, Eli Lily, Genentech, LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, Regeneron, Sanofi, UCB, DS Biopharma, and Inflazome. Kirkorian declared relationships with Dermavant, Verrica Pharmaceuticals, Pfizer, and Incyte.
 

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

AMSTERDAM — Children with short stature related to severe atopic dermatitis not only can have their condition effectively treated with 16 weeks of dupilumab but also may experience improved growth, bringing them back toward standard height curves, revealed a post hoc trial analysis.

The research was presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

The trial included a “rigorously selected … well-characterized, well-studied” population of children aged 6-11 years, said presenter Alan D. Irvine, MD, DSc, professor of dermatology, Trinity College Dublin, Ireland.

It showed that “severe atopic dermatitis does cause restriction of growth, as well as a higher weight, and therefore obviously a higher BMI [body mass index].”

He continued, however, that children at the lower percentiles of height receiving prompt treatment with dupilumab (Dupixent) “were able to rapidly move through the centiles over the 16 weeks of the study, and that may be the window for catch-up growth … when children are growing rapidly.”

Anna Yasmine Kirkorian, MD, chief of dermatology, Children’s National Hospital, Washington, DC, who was not involved in the study, said that she was “surprised” at the degree of growth achieved over the study period, as height is not something that jumps up “overnight.”

“On the other hand, it fits with my experience with children who’ve had the brakes on all of their life due to inflammation, whether it be height, going to school, sleeping — everything is sort of put on pause by this terrible inflammatory process,” she said.

“When you take the brakes off, they get to be who they are going to be,” Kirkorian added. “So I was surprised by the speed of it, but not by the fact that height was acquired.”

Her belief is that in the pre-dupilumab era, severe atopic dermatitis was often insufficiently controlled, so children were “smaller than you would predict from parental height,” and the treatment is “allowing them to reach their genetic potential.”
 

Post Hoc Analysis 

In his presentation, Irvine emphasized that it has been clearly demonstrated that adolescents with moderate and severe atopic dermatitis have a significantly higher likelihood of being below the 25th percentile of height on growth reference charts.

Such children are also at a higher risk of having low bone mineral density and low serum alkaline phosphatase (ALP) levels . While data presented at the EADV 2023 Congress showed that dupilumab significantly increased serum levels of bone ALP compared with placebo, the underlying mechanism remains unclear.

For the current analysis, Irvine and colleagues determined that the proportion of children aged 6-11 years with severe atopic dermatitis and lower stature reach a ≥ 5 centile improvement in height following 16 weeks of dupilumab treatment.

They examined data from the LIBERTY AD PEDS trial, in which patients aged 6-11 years with severe atopic dermatitis were randomized to 300 mg dupilumab every 4 weeks or placebo along with a mild or moderately potent topical corticosteroid. The study found that, overall, dupilumab was associated with significant improvements in signs, symptoms, and quality of life compared with placebo.

Height measures at baseline revealed that “more boys and more girls were below the 50th centile than you would predict for a healthy, normal control population,” Irvine said. “If we look at weight, we see the opposite,” he continued, “with a disproportionate number of boys and girls who are above the 50th centile for weight at baseline.”

Consequently, “we’re seeing these children who are shorter and heavier than the predicted healthy weight range and, as a result, obviously have higher BMI,” Irvine noted, with 67% girls and 62% boys found to have a higher BMI than normal for their age.

After 16 weeks of treatment with dupilumab, there was a much greater gain in height than that seen among those on placebo, with the most pronounced effect seen in children who had the lowest height at baseline. Indeed, among children in the lowest 25% height percentile at baseline, 30.6% on dupilumab vs 11.9% on placebo experienced an increase in height of 5 centiles or more(P < .05).

“This reflects what we see in clinical practice,” Irvine said. “Children often grow dramatically on treatment for atopic dermatitis.”

Among patients with a baseline height below the 30th percentile, 31.9% treated with dupilumab vs 11.1% treated with placebo gained at least 5 centiles in height. The figures for children below the 40th height percentile at baseline were 31.3% vs 15.5% (P < .05 for both).

Although there remained a marked difference in the proportion of children below the 50th height percentile at baseline gaining 5 centiles or more in height, at 29.0% with dupilumab versus 15.7% with placebo, it was no longer significant.

“So the effect of catch-up growth, or growth through the centiles, is most marked in those who are in the 40th centile or below,” Irvine said, indicating that the “more growth restricted kids have much more potential to catch up.”
 

‘Convincing’ Data

Overall, Kirkorian said in the interview, the data are “convincing” and support her view that severe atopic dermatitis is a “terrible chronic disease that we really underappreciate.” Atopic dermatitis, she added, “should get the respect that any severe chronic illness would have, whether that be arthritis, diabetes, or cardiac disease, because it is a systemic disorder that … profoundly affects quality of life, every minute of every day.”

However, “we don’t get all the referrals we should, until the child has suffered for years and years, and the family has suffered,” as there is a bias that it can be outgrown — although not everybody does — and it “doesn’t look as conspicuous as other chronic skin disorders,” such as psoriasis.

“Now with this study,” Kirkorian said, “it gives us a really compelling point to make to parents, to the community, and to insurers that not only are we affecting the quality of life from the itch standpoint [with dupilumab] but we may have long profound effects on growth and bone health.”

The research was sponsored by Sanofi and Regeneron Pharmaceuticals. Irvine declared relationships with AbbVie, Arena Pharmaceuticals, BenevolentAI, Chugai Pharmaceutical, Dermavant, Eli Lily, Genentech, LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, Regeneron, Sanofi, UCB, DS Biopharma, and Inflazome. Kirkorian declared relationships with Dermavant, Verrica Pharmaceuticals, Pfizer, and Incyte.
 

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

AMSTERDAM — Children with short stature related to severe atopic dermatitis not only can have their condition effectively treated with 16 weeks of dupilumab but also may experience improved growth, bringing them back toward standard height curves, revealed a post hoc trial analysis.

The research was presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

The trial included a “rigorously selected … well-characterized, well-studied” population of children aged 6-11 years, said presenter Alan D. Irvine, MD, DSc, professor of dermatology, Trinity College Dublin, Ireland.

It showed that “severe atopic dermatitis does cause restriction of growth, as well as a higher weight, and therefore obviously a higher BMI [body mass index].”

He continued, however, that children at the lower percentiles of height receiving prompt treatment with dupilumab (Dupixent) “were able to rapidly move through the centiles over the 16 weeks of the study, and that may be the window for catch-up growth … when children are growing rapidly.”

Anna Yasmine Kirkorian, MD, chief of dermatology, Children’s National Hospital, Washington, DC, who was not involved in the study, said that she was “surprised” at the degree of growth achieved over the study period, as height is not something that jumps up “overnight.”

“On the other hand, it fits with my experience with children who’ve had the brakes on all of their life due to inflammation, whether it be height, going to school, sleeping — everything is sort of put on pause by this terrible inflammatory process,” she said.

“When you take the brakes off, they get to be who they are going to be,” Kirkorian added. “So I was surprised by the speed of it, but not by the fact that height was acquired.”

Her belief is that in the pre-dupilumab era, severe atopic dermatitis was often insufficiently controlled, so children were “smaller than you would predict from parental height,” and the treatment is “allowing them to reach their genetic potential.”
 

Post Hoc Analysis 

In his presentation, Irvine emphasized that it has been clearly demonstrated that adolescents with moderate and severe atopic dermatitis have a significantly higher likelihood of being below the 25th percentile of height on growth reference charts.

Such children are also at a higher risk of having low bone mineral density and low serum alkaline phosphatase (ALP) levels . While data presented at the EADV 2023 Congress showed that dupilumab significantly increased serum levels of bone ALP compared with placebo, the underlying mechanism remains unclear.

For the current analysis, Irvine and colleagues determined that the proportion of children aged 6-11 years with severe atopic dermatitis and lower stature reach a ≥ 5 centile improvement in height following 16 weeks of dupilumab treatment.

They examined data from the LIBERTY AD PEDS trial, in which patients aged 6-11 years with severe atopic dermatitis were randomized to 300 mg dupilumab every 4 weeks or placebo along with a mild or moderately potent topical corticosteroid. The study found that, overall, dupilumab was associated with significant improvements in signs, symptoms, and quality of life compared with placebo.

Height measures at baseline revealed that “more boys and more girls were below the 50th centile than you would predict for a healthy, normal control population,” Irvine said. “If we look at weight, we see the opposite,” he continued, “with a disproportionate number of boys and girls who are above the 50th centile for weight at baseline.”

Consequently, “we’re seeing these children who are shorter and heavier than the predicted healthy weight range and, as a result, obviously have higher BMI,” Irvine noted, with 67% girls and 62% boys found to have a higher BMI than normal for their age.

After 16 weeks of treatment with dupilumab, there was a much greater gain in height than that seen among those on placebo, with the most pronounced effect seen in children who had the lowest height at baseline. Indeed, among children in the lowest 25% height percentile at baseline, 30.6% on dupilumab vs 11.9% on placebo experienced an increase in height of 5 centiles or more(P < .05).

“This reflects what we see in clinical practice,” Irvine said. “Children often grow dramatically on treatment for atopic dermatitis.”

Among patients with a baseline height below the 30th percentile, 31.9% treated with dupilumab vs 11.1% treated with placebo gained at least 5 centiles in height. The figures for children below the 40th height percentile at baseline were 31.3% vs 15.5% (P < .05 for both).

Although there remained a marked difference in the proportion of children below the 50th height percentile at baseline gaining 5 centiles or more in height, at 29.0% with dupilumab versus 15.7% with placebo, it was no longer significant.

“So the effect of catch-up growth, or growth through the centiles, is most marked in those who are in the 40th centile or below,” Irvine said, indicating that the “more growth restricted kids have much more potential to catch up.”
 

‘Convincing’ Data

Overall, Kirkorian said in the interview, the data are “convincing” and support her view that severe atopic dermatitis is a “terrible chronic disease that we really underappreciate.” Atopic dermatitis, she added, “should get the respect that any severe chronic illness would have, whether that be arthritis, diabetes, or cardiac disease, because it is a systemic disorder that … profoundly affects quality of life, every minute of every day.”

However, “we don’t get all the referrals we should, until the child has suffered for years and years, and the family has suffered,” as there is a bias that it can be outgrown — although not everybody does — and it “doesn’t look as conspicuous as other chronic skin disorders,” such as psoriasis.

“Now with this study,” Kirkorian said, “it gives us a really compelling point to make to parents, to the community, and to insurers that not only are we affecting the quality of life from the itch standpoint [with dupilumab] but we may have long profound effects on growth and bone health.”

The research was sponsored by Sanofi and Regeneron Pharmaceuticals. Irvine declared relationships with AbbVie, Arena Pharmaceuticals, BenevolentAI, Chugai Pharmaceutical, Dermavant, Eli Lily, Genentech, LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, Regeneron, Sanofi, UCB, DS Biopharma, and Inflazome. Kirkorian declared relationships with Dermavant, Verrica Pharmaceuticals, Pfizer, and Incyte.
 

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

The monoclonal antibody nemolizumab offers long-term efficacy and safety, as well as quality-of-life benefits, in the management of adolescents and adults with moderate to severe atopic dermatitis (AD), revealed an interim analysis of the ARCADIA open-label extension study.

The research was presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

The results showed nemolizumab was associated with “ongoing clinically meaningful improvements in itch, skin lesions, and sleep disturbance,” said study presenter Diamant Thaçi, MD, PhD, of the Comprehensive Center for Inflammation Medicine, University of Lü̈beck in Germany.

Moreover, “patient-reported outcomes, including quality of life ... continued to improve over 56 weeks of treatment.” In addition, Thaçi added, the “safety data support the long-term use of nemolizumab for the treatment of adolescent and adult patients with moderate to severe atopic dermatitis.”

He explained that interleukin (IL) 31 is a key neuroimmune cytokine in AD, triggering itch, skin barrier disruption, and exacerbation of inflammation via its receptor. Nemolizumab inhibits IL-31 receptor binding and was shown in the ARCADIA 1 and ARCADIA 2 trials to provide, along with background topical corticosteroids, clinically meaningful improvements in itch, skin lesions, and sleep for up to weeks 48 of follow-up in adolescents and adults with moderate to severe AD.

The current open-label long-term extension study involved patients who were enrolled in both ARCADIA 1 and 2 trials, as well as those from four phase 2 and 2b studies, a phase 3b study, and adolescents who had not been included in a trial but who met the criteria for the extension study. All patients, whether they started on placebo plus background topical corticosteroids in a prior study, were treated with nemolizumab 30 mg subcutaneously every 4 weeks along with topical corticosteroids.

The interim analysis included all efficacy and safety data up to the cutoff of September 30, 2022, on 723 patients who had completed 56 weeks of treatment among the 1751 patients initially enrolled in the extension study.

The results showed that, regardless of whether patients were nemolizumab naive at enrollment or had previously taken the drug, there were increases in the proportion of patients with an Investigator Global Assessment (IGA) score of 0/1 and an Eczema Area and Severity Index (EASI) score of at least 75 (EASI-75) over the 56 weeks of the study.

In those naive to nemolizumab, the increase in the proportion with an IGA score of 0/1 increased from 17.7% at baseline to 49.0% at 56 weeks, while the proportion with an EASI-75 increased from 24.0% to 78.7%.

The increase in the proportion of patients with an IGA score 0/1 among those who had previously received nemolizumab increased from 28.5% at baseline to 47.1% at 56 weeks. The proportion with an EASI-75 was 38.1% at baseline, rising to 73.0% at 56 weeks.

Increases in the proportion of patients with an EASI score of at least 50 and at least 90 were also seen with nemolizumab, as were increases in the proportion of patients with an improvement of at least four points on the SCORing Atopic Dermatitis Pruritus visual analogue scale and Sleep loss scores.

Similarly, the proportion of patients with a reduction in Dermatology Life Quality Index of at least four points increased over the study period.

Regarding safety, Thaçi said, there appeared to be fewer adverse events than had been previously reported with nemolizumab. “We don’t see any signs of conjunctivitis,” he continued, or significant risk of infection apart from for COVID-19, but he pointed out that the study was conducted during the pandemic, which was “a very difficult time.”

The most common treatment-related adverse events were, aside from COVID-19, nasopharyngitis in about 10%-11% of patients, upper respiratory tract infection in about 6% to almost 7%, and headache in about 5%.

Among the adverse events of special interest, newly diagnosed asthma or worsening of asthma occurred in 4.7%-4.8% of patients, while peripheral edema was seen in 0.8%-1.7%.

“Besides this, the study results are really looking very good,” he said, adding: “It means, in a long-term study, we can say today that nemolizumab has revealed the [same] safety profile that was shown in the ARCADIA 1 and 2 trials.”

Alan D. Irvine, MD, DSc, professor of dermatology, Trinity College Dublin in Ireland, who was not involved in the study, underlined that the current interim assessment does not represent the complete dataset and is based on observed cases rather than a more rigorous methodology, such as net reclassification improvement analysis.

“So it makes it a little harder to interpret when you don’t know how many people are dropping out and why they’re dropping out,” he told this news organization. “That said, those who remain on drug out to 56 weeks do experience ongoing improvement in disease control.”

Consequently, “the most reliable message you can take from this interim analysis of long-term data is that there were no new safety signals,” and nemolizumab looks “safe and well-tolerated.”

Where nemolizumab would fit into the treatment pathway for moderate to severe AD remains an open question, Irvine said, although he believes that IL-13 pathway inhibitors such as dupilumab, tralokinumab, and lebrikizumab “will remain the treatment of choice for the immediate future due to prescriber familiarity and good efficacy data.”

However, for patients who are unsuitable for IL-13 inhibitors and/or Janus kinase inhibitors such as abrocitinib and upadacitinib, nemolizumab “could be an interesting alternative.”

“That’s probably where it is going to start,” Irvine said, “and then obviously that will change over time and as the data mature and prescribers become more familiar with the drug in the real world.”

Nemolizumab (Nemluvio) is approved for treating prurigo nodularis (PN) in the United States and in Japan and is under Food and Drug Administration review for treating AD. It is also under review for PN and AD in Europe, Canada, the United Kingdom, and several other countries, according to Galderma. It is also approved for treating pruritus associated with AD in pediatric, adolescent, and adult patients in Japan.

The study was funded by Galderma. Thaçi declared relationships with AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Galderma, Janssen-Cilag, Kyowa Kirin, LEO Pharma, L’Oréal, Eli Lilly, Novartis, Pfizer, Regeneron, Sanofi, Target RWE, and UCB. Irvine declared relationships with AbbVie, Arena Pharmaceuticals, BenevolentAl, Chugai Pharmaceutical, Dermavant, Eli Lily, Genentech, LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, Regeneron, Sanofi, UCB, DS Biopharma, and Inflazome.

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

The monoclonal antibody nemolizumab offers long-term efficacy and safety, as well as quality-of-life benefits, in the management of adolescents and adults with moderate to severe atopic dermatitis (AD), revealed an interim analysis of the ARCADIA open-label extension study.

The research was presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

The results showed nemolizumab was associated with “ongoing clinically meaningful improvements in itch, skin lesions, and sleep disturbance,” said study presenter Diamant Thaçi, MD, PhD, of the Comprehensive Center for Inflammation Medicine, University of Lü̈beck in Germany.

Moreover, “patient-reported outcomes, including quality of life ... continued to improve over 56 weeks of treatment.” In addition, Thaçi added, the “safety data support the long-term use of nemolizumab for the treatment of adolescent and adult patients with moderate to severe atopic dermatitis.”

He explained that interleukin (IL) 31 is a key neuroimmune cytokine in AD, triggering itch, skin barrier disruption, and exacerbation of inflammation via its receptor. Nemolizumab inhibits IL-31 receptor binding and was shown in the ARCADIA 1 and ARCADIA 2 trials to provide, along with background topical corticosteroids, clinically meaningful improvements in itch, skin lesions, and sleep for up to weeks 48 of follow-up in adolescents and adults with moderate to severe AD.

The current open-label long-term extension study involved patients who were enrolled in both ARCADIA 1 and 2 trials, as well as those from four phase 2 and 2b studies, a phase 3b study, and adolescents who had not been included in a trial but who met the criteria for the extension study. All patients, whether they started on placebo plus background topical corticosteroids in a prior study, were treated with nemolizumab 30 mg subcutaneously every 4 weeks along with topical corticosteroids.

The interim analysis included all efficacy and safety data up to the cutoff of September 30, 2022, on 723 patients who had completed 56 weeks of treatment among the 1751 patients initially enrolled in the extension study.

The results showed that, regardless of whether patients were nemolizumab naive at enrollment or had previously taken the drug, there were increases in the proportion of patients with an Investigator Global Assessment (IGA) score of 0/1 and an Eczema Area and Severity Index (EASI) score of at least 75 (EASI-75) over the 56 weeks of the study.

In those naive to nemolizumab, the increase in the proportion with an IGA score of 0/1 increased from 17.7% at baseline to 49.0% at 56 weeks, while the proportion with an EASI-75 increased from 24.0% to 78.7%.

The increase in the proportion of patients with an IGA score 0/1 among those who had previously received nemolizumab increased from 28.5% at baseline to 47.1% at 56 weeks. The proportion with an EASI-75 was 38.1% at baseline, rising to 73.0% at 56 weeks.

Increases in the proportion of patients with an EASI score of at least 50 and at least 90 were also seen with nemolizumab, as were increases in the proportion of patients with an improvement of at least four points on the SCORing Atopic Dermatitis Pruritus visual analogue scale and Sleep loss scores.

Similarly, the proportion of patients with a reduction in Dermatology Life Quality Index of at least four points increased over the study period.

Regarding safety, Thaçi said, there appeared to be fewer adverse events than had been previously reported with nemolizumab. “We don’t see any signs of conjunctivitis,” he continued, or significant risk of infection apart from for COVID-19, but he pointed out that the study was conducted during the pandemic, which was “a very difficult time.”

The most common treatment-related adverse events were, aside from COVID-19, nasopharyngitis in about 10%-11% of patients, upper respiratory tract infection in about 6% to almost 7%, and headache in about 5%.

Among the adverse events of special interest, newly diagnosed asthma or worsening of asthma occurred in 4.7%-4.8% of patients, while peripheral edema was seen in 0.8%-1.7%.

“Besides this, the study results are really looking very good,” he said, adding: “It means, in a long-term study, we can say today that nemolizumab has revealed the [same] safety profile that was shown in the ARCADIA 1 and 2 trials.”

Alan D. Irvine, MD, DSc, professor of dermatology, Trinity College Dublin in Ireland, who was not involved in the study, underlined that the current interim assessment does not represent the complete dataset and is based on observed cases rather than a more rigorous methodology, such as net reclassification improvement analysis.

“So it makes it a little harder to interpret when you don’t know how many people are dropping out and why they’re dropping out,” he told this news organization. “That said, those who remain on drug out to 56 weeks do experience ongoing improvement in disease control.”

Consequently, “the most reliable message you can take from this interim analysis of long-term data is that there were no new safety signals,” and nemolizumab looks “safe and well-tolerated.”

Where nemolizumab would fit into the treatment pathway for moderate to severe AD remains an open question, Irvine said, although he believes that IL-13 pathway inhibitors such as dupilumab, tralokinumab, and lebrikizumab “will remain the treatment of choice for the immediate future due to prescriber familiarity and good efficacy data.”

However, for patients who are unsuitable for IL-13 inhibitors and/or Janus kinase inhibitors such as abrocitinib and upadacitinib, nemolizumab “could be an interesting alternative.”

“That’s probably where it is going to start,” Irvine said, “and then obviously that will change over time and as the data mature and prescribers become more familiar with the drug in the real world.”

Nemolizumab (Nemluvio) is approved for treating prurigo nodularis (PN) in the United States and in Japan and is under Food and Drug Administration review for treating AD. It is also under review for PN and AD in Europe, Canada, the United Kingdom, and several other countries, according to Galderma. It is also approved for treating pruritus associated with AD in pediatric, adolescent, and adult patients in Japan.

The study was funded by Galderma. Thaçi declared relationships with AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Galderma, Janssen-Cilag, Kyowa Kirin, LEO Pharma, L’Oréal, Eli Lilly, Novartis, Pfizer, Regeneron, Sanofi, Target RWE, and UCB. Irvine declared relationships with AbbVie, Arena Pharmaceuticals, BenevolentAl, Chugai Pharmaceutical, Dermavant, Eli Lily, Genentech, LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, Regeneron, Sanofi, UCB, DS Biopharma, and Inflazome.

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

The monoclonal antibody nemolizumab offers long-term efficacy and safety, as well as quality-of-life benefits, in the management of adolescents and adults with moderate to severe atopic dermatitis (AD), revealed an interim analysis of the ARCADIA open-label extension study.

The research was presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

The results showed nemolizumab was associated with “ongoing clinically meaningful improvements in itch, skin lesions, and sleep disturbance,” said study presenter Diamant Thaçi, MD, PhD, of the Comprehensive Center for Inflammation Medicine, University of Lü̈beck in Germany.

Moreover, “patient-reported outcomes, including quality of life ... continued to improve over 56 weeks of treatment.” In addition, Thaçi added, the “safety data support the long-term use of nemolizumab for the treatment of adolescent and adult patients with moderate to severe atopic dermatitis.”

He explained that interleukin (IL) 31 is a key neuroimmune cytokine in AD, triggering itch, skin barrier disruption, and exacerbation of inflammation via its receptor. Nemolizumab inhibits IL-31 receptor binding and was shown in the ARCADIA 1 and ARCADIA 2 trials to provide, along with background topical corticosteroids, clinically meaningful improvements in itch, skin lesions, and sleep for up to weeks 48 of follow-up in adolescents and adults with moderate to severe AD.

The current open-label long-term extension study involved patients who were enrolled in both ARCADIA 1 and 2 trials, as well as those from four phase 2 and 2b studies, a phase 3b study, and adolescents who had not been included in a trial but who met the criteria for the extension study. All patients, whether they started on placebo plus background topical corticosteroids in a prior study, were treated with nemolizumab 30 mg subcutaneously every 4 weeks along with topical corticosteroids.

The interim analysis included all efficacy and safety data up to the cutoff of September 30, 2022, on 723 patients who had completed 56 weeks of treatment among the 1751 patients initially enrolled in the extension study.

The results showed that, regardless of whether patients were nemolizumab naive at enrollment or had previously taken the drug, there were increases in the proportion of patients with an Investigator Global Assessment (IGA) score of 0/1 and an Eczema Area and Severity Index (EASI) score of at least 75 (EASI-75) over the 56 weeks of the study.

In those naive to nemolizumab, the increase in the proportion with an IGA score of 0/1 increased from 17.7% at baseline to 49.0% at 56 weeks, while the proportion with an EASI-75 increased from 24.0% to 78.7%.

The increase in the proportion of patients with an IGA score 0/1 among those who had previously received nemolizumab increased from 28.5% at baseline to 47.1% at 56 weeks. The proportion with an EASI-75 was 38.1% at baseline, rising to 73.0% at 56 weeks.

Increases in the proportion of patients with an EASI score of at least 50 and at least 90 were also seen with nemolizumab, as were increases in the proportion of patients with an improvement of at least four points on the SCORing Atopic Dermatitis Pruritus visual analogue scale and Sleep loss scores.

Similarly, the proportion of patients with a reduction in Dermatology Life Quality Index of at least four points increased over the study period.

Regarding safety, Thaçi said, there appeared to be fewer adverse events than had been previously reported with nemolizumab. “We don’t see any signs of conjunctivitis,” he continued, or significant risk of infection apart from for COVID-19, but he pointed out that the study was conducted during the pandemic, which was “a very difficult time.”

The most common treatment-related adverse events were, aside from COVID-19, nasopharyngitis in about 10%-11% of patients, upper respiratory tract infection in about 6% to almost 7%, and headache in about 5%.

Among the adverse events of special interest, newly diagnosed asthma or worsening of asthma occurred in 4.7%-4.8% of patients, while peripheral edema was seen in 0.8%-1.7%.

“Besides this, the study results are really looking very good,” he said, adding: “It means, in a long-term study, we can say today that nemolizumab has revealed the [same] safety profile that was shown in the ARCADIA 1 and 2 trials.”

Alan D. Irvine, MD, DSc, professor of dermatology, Trinity College Dublin in Ireland, who was not involved in the study, underlined that the current interim assessment does not represent the complete dataset and is based on observed cases rather than a more rigorous methodology, such as net reclassification improvement analysis.

“So it makes it a little harder to interpret when you don’t know how many people are dropping out and why they’re dropping out,” he told this news organization. “That said, those who remain on drug out to 56 weeks do experience ongoing improvement in disease control.”

Consequently, “the most reliable message you can take from this interim analysis of long-term data is that there were no new safety signals,” and nemolizumab looks “safe and well-tolerated.”

Where nemolizumab would fit into the treatment pathway for moderate to severe AD remains an open question, Irvine said, although he believes that IL-13 pathway inhibitors such as dupilumab, tralokinumab, and lebrikizumab “will remain the treatment of choice for the immediate future due to prescriber familiarity and good efficacy data.”

However, for patients who are unsuitable for IL-13 inhibitors and/or Janus kinase inhibitors such as abrocitinib and upadacitinib, nemolizumab “could be an interesting alternative.”

“That’s probably where it is going to start,” Irvine said, “and then obviously that will change over time and as the data mature and prescribers become more familiar with the drug in the real world.”

Nemolizumab (Nemluvio) is approved for treating prurigo nodularis (PN) in the United States and in Japan and is under Food and Drug Administration review for treating AD. It is also under review for PN and AD in Europe, Canada, the United Kingdom, and several other countries, according to Galderma. It is also approved for treating pruritus associated with AD in pediatric, adolescent, and adult patients in Japan.

The study was funded by Galderma. Thaçi declared relationships with AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Galderma, Janssen-Cilag, Kyowa Kirin, LEO Pharma, L’Oréal, Eli Lilly, Novartis, Pfizer, Regeneron, Sanofi, Target RWE, and UCB. Irvine declared relationships with AbbVie, Arena Pharmaceuticals, BenevolentAl, Chugai Pharmaceutical, Dermavant, Eli Lily, Genentech, LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, Regeneron, Sanofi, UCB, DS Biopharma, and Inflazome.

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

Podcasts, websites, and large “Parenting” sections in bookstores testify to the large demand for parent guidance and support, but also to the fact that there is no one universally accepted guidebook, such as Benjamin Spock provided for parents almost 80 years ago with Baby and Child Care. The Positive Parenting Program — “Triple P” — is a curriculum for parents that focuses on five areas of parental competence and can be applied at different levels of intensity to address different needs, from preventing common problems and promoting healthy development to addressing substantial child behavioral problems.

We will describe the basic components of this curriculum so that you may determine whether it might be useful to the families in your practice. Then we will expand upon the domains that have proven essential for parents to nurture healthy development in their children. Even if you do not have the time or resources to provide the full Triple P curriculum, you can offer these principles directly to parents and decide when to refer them to access more formal parent training and coaching.

Triple P was developed by psychologist Matthew Sanders, to “promote positive, caring relationships between parents and their children and to help parents develop effective management strategies for dealing with a variety of childhood behavior problems and common developmental issues” as his doctoral project in Australia in the 1980s. Research in the 1990s suggested substantial efficacy, and it was packaged for broader adoption in the early 2000s. It is a tiered approach, meaning there is content for universal education (level 1), up through more intensive, specialized, and individualized content to be delivered in group or individual settings focused on building specific skills or addressing select problems. It was originally developed for the parents of 0- to 11-year-old children, with additional curricula for parents of teenagers created later. It always is delivered to parents only, through a mix of video and reading, or in-person groups or individual coaching. While the universal education resources are available for free to families of children under 12 in Australia, resources and training are available for a fee in the United states (triplep.net). Research has demonstrated considerable efficacy at reducing some of the common behavioral problems of childhood, improving parental confidence and family harmony, and decreasing rates of parental depression. It has even demonstrated efficacy in reducing the incidence of child maltreatment.

• 1. Creating a safe and engaging environment for children
• 2. Providing a positive learning environment for children
• 3. Assertive discipline
• 4. Having realistic expectations
• 5. Parental self-care.

The educational materials and more intensive parent trainings are all focused on developing knowledge and skills in the parents that will promote a positive relationship with their children, teach the children new skills while encouraging desirable behaviors, and managing problematic behaviors. The training happens with written or video scenarios, up through individualized skill coaching with homework and direct feedback from trained clinicians. While information about the universally helpful knowledge and skills can be found online or accessed through some local programs in the United States, the higher levels of intervention are less consistently available. You should explore what is available in your community, but even if you don’t have the resources for your own training, you are already offering parent guidance at every visit.

Practical Strategies

Below are practical strategies to offer parents the knowledge and support that are essential to “positive parenting,” so they may nurture their children’s healthiest development.

Attunement: Attunement is simply a parent’s ability to know who their child is and where their child is at any given time. This covers an appreciation of the child’s temperament, style, interests, strengths, and vulnerabilities. Where their child is at includes being able to read that particular child’s cues: Are they hungry? Sleepy? Sick? Frustrated? Parents are the experts on their children, but their children are also always changing. You can help the parents in your practice be intentional about being attuned to their children, so they can always be deepening their understanding of who their children are (becoming) and where they are at in any given moment. This requires protecting regular, unstructured time when they can give their children their full attention: reading, doing an art project, practicing music, or basketball. Schedules are often packed with work and school, driving between many structured activities. Reassure the parents in your practice that time spent in play is just as important. When a parent is present, attentive, and curious, asking questions, learning about the child’s thoughts, feelings and ideas, they are doing some of the most essential (and delightful) work of raising children.

Positive Environment: A “positive environment” is child-centered, with access to age-appropriate activities of a wide range. Offering first-time parents written resources about child development and age-appropriate games, books, and activities is an easy way to support positive parenting. A positive environment also has structure and routines, so children can play and explore with the comfort of knowing what to expect and what is expected of them. Do they have a regular bedtime and bedtime routines? Do they consistently eat dinner together and clean up as a family? Do they have reliable unstructured time together, maybe playing board games or kickball after dinner? These varying but predictable routines provide opportunities for children to practice helping, following through, sharing, and tolerating frustration or failure, and they give parents low-stakes opportunities to offer praise for their effort, compassion when they struggle, and affection for no reason at all. They lower the chances of parent-child interactions being predominantly reactive, demanding, pleading, or angry.

Effective Discipline: A positive environment includes reasonable and consistent consequences for rule breaking and poor behavior, and an essential part of predictability includes clear ground rules for what is expected of children at home, around chores, getting ready for school and bedtime, and their behavior. Parents need to agree on and children should understand what the consequences will be for breaking rules. Parents should also have a clear strategy for consistently and calmly enforcing rules. This is not easy, but is just as important as affection and play. If parents are struggling with discipline, it is worth asking for a specific example to learn about where the trouble lies. Are parents not on the same page? Are they worried about their children’s distress? Do they lose their temper and the matter escalates? Clear ground rules and a game plan can help them to stay calm instead of resorting to pleading and yelling. Speaking with them about the value of planning and communicating about these expectations and rules during a quiet time, not in the midst of conflict, might be enough to help them with effective discipline. Others may need more support. Books like 123 Magic with more detail on how to manage time outs can be helpful. For those parents who are managing greater difficulty, a referral to parent coaching (with a modality such as Triple P, Parent-Child Interaction Training or Collaborative Problem Solving) may be needed.

Parental Well-Being: Being aligned with one’s spouse (or other caregiver) in how to manage challenging child behaviors is essential to a healthy relationship, and overall well-being is an essential ingredient in creating a nurturing, positive environment at home. How is the parents’ communication with each other overall? Do they have time together that is not focused on the children? Does each parent have time for outside interests or hobbies? How about other important relationships? Do they prioritize their own sleep, regular exercise, and good nutrition? It can be powerful if they plan family activities that are centered on their own passions and interests as well as their children’s. It is powerful for parents to hear from you that when they protect some of their time and energy to simply care for their own health and well-being, they are building a positive environment for their children, both in how they will show up for their family and in what they model.
 

Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at pdnews@mdedge.com.

Suggested Reading

Sanders MR et al. The Development and Dissemination of the Triple P – Positive Parenting Program: A Multilevel Evidence-Based System of Parenting and Family Support. Prev Sci. 2002 Sep;3(3):173-89. doi: 10.1023/a:1019942516231.

Sanders MR. The Triple P System of Evidence-Based Parenting Support: Past, Present, and Future Directions. Clin Child Fam Psychol Rev. 2023 Dec;26(4):880-903. doi: 10.1007/s10567-023-00441-8.

Podcasts, websites, and large “Parenting” sections in bookstores testify to the large demand for parent guidance and support, but also to the fact that there is no one universally accepted guidebook, such as Benjamin Spock provided for parents almost 80 years ago with Baby and Child Care. The Positive Parenting Program — “Triple P” — is a curriculum for parents that focuses on five areas of parental competence and can be applied at different levels of intensity to address different needs, from preventing common problems and promoting healthy development to addressing substantial child behavioral problems.

We will describe the basic components of this curriculum so that you may determine whether it might be useful to the families in your practice. Then we will expand upon the domains that have proven essential for parents to nurture healthy development in their children. Even if you do not have the time or resources to provide the full Triple P curriculum, you can offer these principles directly to parents and decide when to refer them to access more formal parent training and coaching.

Triple P was developed by psychologist Matthew Sanders, to “promote positive, caring relationships between parents and their children and to help parents develop effective management strategies for dealing with a variety of childhood behavior problems and common developmental issues” as his doctoral project in Australia in the 1980s. Research in the 1990s suggested substantial efficacy, and it was packaged for broader adoption in the early 2000s. It is a tiered approach, meaning there is content for universal education (level 1), up through more intensive, specialized, and individualized content to be delivered in group or individual settings focused on building specific skills or addressing select problems. It was originally developed for the parents of 0- to 11-year-old children, with additional curricula for parents of teenagers created later. It always is delivered to parents only, through a mix of video and reading, or in-person groups or individual coaching. While the universal education resources are available for free to families of children under 12 in Australia, resources and training are available for a fee in the United states (triplep.net). Research has demonstrated considerable efficacy at reducing some of the common behavioral problems of childhood, improving parental confidence and family harmony, and decreasing rates of parental depression. It has even demonstrated efficacy in reducing the incidence of child maltreatment.

• 1. Creating a safe and engaging environment for children
• 2. Providing a positive learning environment for children
• 3. Assertive discipline
• 4. Having realistic expectations
• 5. Parental self-care.

The educational materials and more intensive parent trainings are all focused on developing knowledge and skills in the parents that will promote a positive relationship with their children, teach the children new skills while encouraging desirable behaviors, and managing problematic behaviors. The training happens with written or video scenarios, up through individualized skill coaching with homework and direct feedback from trained clinicians. While information about the universally helpful knowledge and skills can be found online or accessed through some local programs in the United States, the higher levels of intervention are less consistently available. You should explore what is available in your community, but even if you don’t have the resources for your own training, you are already offering parent guidance at every visit.

Practical Strategies

Below are practical strategies to offer parents the knowledge and support that are essential to “positive parenting,” so they may nurture their children’s healthiest development.

Attunement: Attunement is simply a parent’s ability to know who their child is and where their child is at any given time. This covers an appreciation of the child’s temperament, style, interests, strengths, and vulnerabilities. Where their child is at includes being able to read that particular child’s cues: Are they hungry? Sleepy? Sick? Frustrated? Parents are the experts on their children, but their children are also always changing. You can help the parents in your practice be intentional about being attuned to their children, so they can always be deepening their understanding of who their children are (becoming) and where they are at in any given moment. This requires protecting regular, unstructured time when they can give their children their full attention: reading, doing an art project, practicing music, or basketball. Schedules are often packed with work and school, driving between many structured activities. Reassure the parents in your practice that time spent in play is just as important. When a parent is present, attentive, and curious, asking questions, learning about the child’s thoughts, feelings and ideas, they are doing some of the most essential (and delightful) work of raising children.

Positive Environment: A “positive environment” is child-centered, with access to age-appropriate activities of a wide range. Offering first-time parents written resources about child development and age-appropriate games, books, and activities is an easy way to support positive parenting. A positive environment also has structure and routines, so children can play and explore with the comfort of knowing what to expect and what is expected of them. Do they have a regular bedtime and bedtime routines? Do they consistently eat dinner together and clean up as a family? Do they have reliable unstructured time together, maybe playing board games or kickball after dinner? These varying but predictable routines provide opportunities for children to practice helping, following through, sharing, and tolerating frustration or failure, and they give parents low-stakes opportunities to offer praise for their effort, compassion when they struggle, and affection for no reason at all. They lower the chances of parent-child interactions being predominantly reactive, demanding, pleading, or angry.

Effective Discipline: A positive environment includes reasonable and consistent consequences for rule breaking and poor behavior, and an essential part of predictability includes clear ground rules for what is expected of children at home, around chores, getting ready for school and bedtime, and their behavior. Parents need to agree on and children should understand what the consequences will be for breaking rules. Parents should also have a clear strategy for consistently and calmly enforcing rules. This is not easy, but is just as important as affection and play. If parents are struggling with discipline, it is worth asking for a specific example to learn about where the trouble lies. Are parents not on the same page? Are they worried about their children’s distress? Do they lose their temper and the matter escalates? Clear ground rules and a game plan can help them to stay calm instead of resorting to pleading and yelling. Speaking with them about the value of planning and communicating about these expectations and rules during a quiet time, not in the midst of conflict, might be enough to help them with effective discipline. Others may need more support. Books like 123 Magic with more detail on how to manage time outs can be helpful. For those parents who are managing greater difficulty, a referral to parent coaching (with a modality such as Triple P, Parent-Child Interaction Training or Collaborative Problem Solving) may be needed.

Parental Well-Being: Being aligned with one’s spouse (or other caregiver) in how to manage challenging child behaviors is essential to a healthy relationship, and overall well-being is an essential ingredient in creating a nurturing, positive environment at home. How is the parents’ communication with each other overall? Do they have time together that is not focused on the children? Does each parent have time for outside interests or hobbies? How about other important relationships? Do they prioritize their own sleep, regular exercise, and good nutrition? It can be powerful if they plan family activities that are centered on their own passions and interests as well as their children’s. It is powerful for parents to hear from you that when they protect some of their time and energy to simply care for their own health and well-being, they are building a positive environment for their children, both in how they will show up for their family and in what they model.
 

Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at pdnews@mdedge.com.

Suggested Reading

Sanders MR et al. The Development and Dissemination of the Triple P – Positive Parenting Program: A Multilevel Evidence-Based System of Parenting and Family Support. Prev Sci. 2002 Sep;3(3):173-89. doi: 10.1023/a:1019942516231.

Sanders MR. The Triple P System of Evidence-Based Parenting Support: Past, Present, and Future Directions. Clin Child Fam Psychol Rev. 2023 Dec;26(4):880-903. doi: 10.1007/s10567-023-00441-8.

Podcasts, websites, and large “Parenting” sections in bookstores testify to the large demand for parent guidance and support, but also to the fact that there is no one universally accepted guidebook, such as Benjamin Spock provided for parents almost 80 years ago with Baby and Child Care. The Positive Parenting Program — “Triple P” — is a curriculum for parents that focuses on five areas of parental competence and can be applied at different levels of intensity to address different needs, from preventing common problems and promoting healthy development to addressing substantial child behavioral problems.

We will describe the basic components of this curriculum so that you may determine whether it might be useful to the families in your practice. Then we will expand upon the domains that have proven essential for parents to nurture healthy development in their children. Even if you do not have the time or resources to provide the full Triple P curriculum, you can offer these principles directly to parents and decide when to refer them to access more formal parent training and coaching.

Triple P was developed by psychologist Matthew Sanders, to “promote positive, caring relationships between parents and their children and to help parents develop effective management strategies for dealing with a variety of childhood behavior problems and common developmental issues” as his doctoral project in Australia in the 1980s. Research in the 1990s suggested substantial efficacy, and it was packaged for broader adoption in the early 2000s. It is a tiered approach, meaning there is content for universal education (level 1), up through more intensive, specialized, and individualized content to be delivered in group or individual settings focused on building specific skills or addressing select problems. It was originally developed for the parents of 0- to 11-year-old children, with additional curricula for parents of teenagers created later. It always is delivered to parents only, through a mix of video and reading, or in-person groups or individual coaching. While the universal education resources are available for free to families of children under 12 in Australia, resources and training are available for a fee in the United states (triplep.net). Research has demonstrated considerable efficacy at reducing some of the common behavioral problems of childhood, improving parental confidence and family harmony, and decreasing rates of parental depression. It has even demonstrated efficacy in reducing the incidence of child maltreatment.

• 1. Creating a safe and engaging environment for children
• 2. Providing a positive learning environment for children
• 3. Assertive discipline
• 4. Having realistic expectations
• 5. Parental self-care.

The educational materials and more intensive parent trainings are all focused on developing knowledge and skills in the parents that will promote a positive relationship with their children, teach the children new skills while encouraging desirable behaviors, and managing problematic behaviors. The training happens with written or video scenarios, up through individualized skill coaching with homework and direct feedback from trained clinicians. While information about the universally helpful knowledge and skills can be found online or accessed through some local programs in the United States, the higher levels of intervention are less consistently available. You should explore what is available in your community, but even if you don’t have the resources for your own training, you are already offering parent guidance at every visit.

Practical Strategies

Below are practical strategies to offer parents the knowledge and support that are essential to “positive parenting,” so they may nurture their children’s healthiest development.

Attunement: Attunement is simply a parent’s ability to know who their child is and where their child is at any given time. This covers an appreciation of the child’s temperament, style, interests, strengths, and vulnerabilities. Where their child is at includes being able to read that particular child’s cues: Are they hungry? Sleepy? Sick? Frustrated? Parents are the experts on their children, but their children are also always changing. You can help the parents in your practice be intentional about being attuned to their children, so they can always be deepening their understanding of who their children are (becoming) and where they are at in any given moment. This requires protecting regular, unstructured time when they can give their children their full attention: reading, doing an art project, practicing music, or basketball. Schedules are often packed with work and school, driving between many structured activities. Reassure the parents in your practice that time spent in play is just as important. When a parent is present, attentive, and curious, asking questions, learning about the child’s thoughts, feelings and ideas, they are doing some of the most essential (and delightful) work of raising children.

Positive Environment: A “positive environment” is child-centered, with access to age-appropriate activities of a wide range. Offering first-time parents written resources about child development and age-appropriate games, books, and activities is an easy way to support positive parenting. A positive environment also has structure and routines, so children can play and explore with the comfort of knowing what to expect and what is expected of them. Do they have a regular bedtime and bedtime routines? Do they consistently eat dinner together and clean up as a family? Do they have reliable unstructured time together, maybe playing board games or kickball after dinner? These varying but predictable routines provide opportunities for children to practice helping, following through, sharing, and tolerating frustration or failure, and they give parents low-stakes opportunities to offer praise for their effort, compassion when they struggle, and affection for no reason at all. They lower the chances of parent-child interactions being predominantly reactive, demanding, pleading, or angry.

Effective Discipline: A positive environment includes reasonable and consistent consequences for rule breaking and poor behavior, and an essential part of predictability includes clear ground rules for what is expected of children at home, around chores, getting ready for school and bedtime, and their behavior. Parents need to agree on and children should understand what the consequences will be for breaking rules. Parents should also have a clear strategy for consistently and calmly enforcing rules. This is not easy, but is just as important as affection and play. If parents are struggling with discipline, it is worth asking for a specific example to learn about where the trouble lies. Are parents not on the same page? Are they worried about their children’s distress? Do they lose their temper and the matter escalates? Clear ground rules and a game plan can help them to stay calm instead of resorting to pleading and yelling. Speaking with them about the value of planning and communicating about these expectations and rules during a quiet time, not in the midst of conflict, might be enough to help them with effective discipline. Others may need more support. Books like 123 Magic with more detail on how to manage time outs can be helpful. For those parents who are managing greater difficulty, a referral to parent coaching (with a modality such as Triple P, Parent-Child Interaction Training or Collaborative Problem Solving) may be needed.

Parental Well-Being: Being aligned with one’s spouse (or other caregiver) in how to manage challenging child behaviors is essential to a healthy relationship, and overall well-being is an essential ingredient in creating a nurturing, positive environment at home. How is the parents’ communication with each other overall? Do they have time together that is not focused on the children? Does each parent have time for outside interests or hobbies? How about other important relationships? Do they prioritize their own sleep, regular exercise, and good nutrition? It can be powerful if they plan family activities that are centered on their own passions and interests as well as their children’s. It is powerful for parents to hear from you that when they protect some of their time and energy to simply care for their own health and well-being, they are building a positive environment for their children, both in how they will show up for their family and in what they model.
 

Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at pdnews@mdedge.com.

Suggested Reading

Sanders MR et al. The Development and Dissemination of the Triple P – Positive Parenting Program: A Multilevel Evidence-Based System of Parenting and Family Support. Prev Sci. 2002 Sep;3(3):173-89. doi: 10.1023/a:1019942516231.

Sanders MR. The Triple P System of Evidence-Based Parenting Support: Past, Present, and Future Directions. Clin Child Fam Psychol Rev. 2023 Dec;26(4):880-903. doi: 10.1007/s10567-023-00441-8.

TOPLINE:

Rituximab and cyclophosphamide are equally effective in achieving remission or low disease activity rates in childhood-onset antineutrophil cytoplasmic antibody–associated vasculitis (AAV), and those who received rituximab required a significantly lower steroid dose than those who received cyclophosphamide or a combination therapy.

METHODOLOGY:

• Researchers evaluated the efficacy of rituximab, cyclophosphamide, or a combination of both in pediatric patients diagnosed with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis.
• A total of 104 patients (median age at diagnosis, 14 years; 67% girls) were included from A Registry of Childhood Vasculitis; the majority had a diagnosis of GPA (81%) and renal involvement (87%). Overall, induction therapy involved rituximab for 43%, cyclophosphamide for 46%, and a combination of both for 11% patients.
• The primary endpoint was the rate of achieving remission (Pediatric Vasculitis Activity Score [PVAS] of 0) or low disease activity (PVAS ≤ 2) at the post-induction visit (4-6 months after diagnosis).
• The secondary endpoints were the degree of disease-related damage at 12- and 24-month visits and rates of drug-related hospitalization occurring between the diagnosis and post-induction visits.

TAKEAWAY:

• At the post-induction visit, 63% patients achieved remission or low disease activity, with the rates being similar between patients who received rituximab and those who received cyclophosphamide (64% vs 62%).
• Patients treated with rituximab required a significantly lower median steroid dose (0.13 mg/kg per day) than those treated with cyclophosphamide (0.3 mg/kg per day) or the combination therapy (0.3 mg/kg per day; P < .001) at the post-induction visit.
• Overall, 61% and 56% patients receiving rituximab and cyclophosphamide, respectively, had disease-related damage measure on the Pediatric Vasculitis Damage Index at the 12-month visit; however, the degree of damage was low.
• The percentage of patients requiring hospitalization was higher in the rituximab group than in the cyclophosphamide group (22% vs 10%), primarily stemming from drug- or infection-related causes (11% vs 2%).

IN PRACTICE:

“The results of this study may assist with current clinical decision-making with regard to the choice of induction medications in childhood-onset AAV and will complement the ongoing [Childhood Arthritis and Rheumatology Research Alliance] prospective [consensus treatment plans] study,” the authors wrote.

SOURCE:

This study was led by Samuel J. Gagne, MD, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center in Pennsylvania, and was published online in Arthritis Care & Research.

LIMITATIONS:

Study limitations included the inconsistencies in glucocorticoid dosing, which may have affected remission rates. Moreover, data on the adverse events not requiring hospitalization and long-term adverse events were not captured.

DISCLOSURES:

This study received funding through a Nationwide Children’s Hospital intramural grant award. The authors reported no potential conflicts of interest.

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

TOPLINE:

Rituximab and cyclophosphamide are equally effective in achieving remission or low disease activity rates in childhood-onset antineutrophil cytoplasmic antibody–associated vasculitis (AAV), and those who received rituximab required a significantly lower steroid dose than those who received cyclophosphamide or a combination therapy.

METHODOLOGY:

• Researchers evaluated the efficacy of rituximab, cyclophosphamide, or a combination of both in pediatric patients diagnosed with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis.
• A total of 104 patients (median age at diagnosis, 14 years; 67% girls) were included from A Registry of Childhood Vasculitis; the majority had a diagnosis of GPA (81%) and renal involvement (87%). Overall, induction therapy involved rituximab for 43%, cyclophosphamide for 46%, and a combination of both for 11% patients.
• The primary endpoint was the rate of achieving remission (Pediatric Vasculitis Activity Score [PVAS] of 0) or low disease activity (PVAS ≤ 2) at the post-induction visit (4-6 months after diagnosis).
• The secondary endpoints were the degree of disease-related damage at 12- and 24-month visits and rates of drug-related hospitalization occurring between the diagnosis and post-induction visits.

TAKEAWAY:

• At the post-induction visit, 63% patients achieved remission or low disease activity, with the rates being similar between patients who received rituximab and those who received cyclophosphamide (64% vs 62%).
• Patients treated with rituximab required a significantly lower median steroid dose (0.13 mg/kg per day) than those treated with cyclophosphamide (0.3 mg/kg per day) or the combination therapy (0.3 mg/kg per day; P < .001) at the post-induction visit.
• Overall, 61% and 56% patients receiving rituximab and cyclophosphamide, respectively, had disease-related damage measure on the Pediatric Vasculitis Damage Index at the 12-month visit; however, the degree of damage was low.
• The percentage of patients requiring hospitalization was higher in the rituximab group than in the cyclophosphamide group (22% vs 10%), primarily stemming from drug- or infection-related causes (11% vs 2%).

IN PRACTICE:

“The results of this study may assist with current clinical decision-making with regard to the choice of induction medications in childhood-onset AAV and will complement the ongoing [Childhood Arthritis and Rheumatology Research Alliance] prospective [consensus treatment plans] study,” the authors wrote.

SOURCE:

This study was led by Samuel J. Gagne, MD, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center in Pennsylvania, and was published online in Arthritis Care & Research.

LIMITATIONS:

Study limitations included the inconsistencies in glucocorticoid dosing, which may have affected remission rates. Moreover, data on the adverse events not requiring hospitalization and long-term adverse events were not captured.

DISCLOSURES:

This study received funding through a Nationwide Children’s Hospital intramural grant award. The authors reported no potential conflicts of interest.

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

TOPLINE:

Rituximab and cyclophosphamide are equally effective in achieving remission or low disease activity rates in childhood-onset antineutrophil cytoplasmic antibody–associated vasculitis (AAV), and those who received rituximab required a significantly lower steroid dose than those who received cyclophosphamide or a combination therapy.

METHODOLOGY:

• Researchers evaluated the efficacy of rituximab, cyclophosphamide, or a combination of both in pediatric patients diagnosed with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis.
• A total of 104 patients (median age at diagnosis, 14 years; 67% girls) were included from A Registry of Childhood Vasculitis; the majority had a diagnosis of GPA (81%) and renal involvement (87%). Overall, induction therapy involved rituximab for 43%, cyclophosphamide for 46%, and a combination of both for 11% patients.
• The primary endpoint was the rate of achieving remission (Pediatric Vasculitis Activity Score [PVAS] of 0) or low disease activity (PVAS ≤ 2) at the post-induction visit (4-6 months after diagnosis).
• The secondary endpoints were the degree of disease-related damage at 12- and 24-month visits and rates of drug-related hospitalization occurring between the diagnosis and post-induction visits.

TAKEAWAY:

• At the post-induction visit, 63% patients achieved remission or low disease activity, with the rates being similar between patients who received rituximab and those who received cyclophosphamide (64% vs 62%).
• Patients treated with rituximab required a significantly lower median steroid dose (0.13 mg/kg per day) than those treated with cyclophosphamide (0.3 mg/kg per day) or the combination therapy (0.3 mg/kg per day; P < .001) at the post-induction visit.
• Overall, 61% and 56% patients receiving rituximab and cyclophosphamide, respectively, had disease-related damage measure on the Pediatric Vasculitis Damage Index at the 12-month visit; however, the degree of damage was low.
• The percentage of patients requiring hospitalization was higher in the rituximab group than in the cyclophosphamide group (22% vs 10%), primarily stemming from drug- or infection-related causes (11% vs 2%).

IN PRACTICE:

“The results of this study may assist with current clinical decision-making with regard to the choice of induction medications in childhood-onset AAV and will complement the ongoing [Childhood Arthritis and Rheumatology Research Alliance] prospective [consensus treatment plans] study,” the authors wrote.

SOURCE:

This study was led by Samuel J. Gagne, MD, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center in Pennsylvania, and was published online in Arthritis Care & Research.

LIMITATIONS:

Study limitations included the inconsistencies in glucocorticoid dosing, which may have affected remission rates. Moreover, data on the adverse events not requiring hospitalization and long-term adverse events were not captured.

DISCLOSURES:

This study received funding through a Nationwide Children’s Hospital intramural grant award. The authors reported no potential conflicts of interest.

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

This summer, the US Food and Drug Administration (FDA) fast-tracked approval of the first-in-its-class nasal epinephrine (neffy). It’s a very welcome addition to our anaphylaxis treatment armamentarium. As the FDA announcement notes, patients with anaphylaxis at times “delay or avoid” anaphylaxis “treatment due to fear of injections.” Neffy was approved on the basis of pharmacokinetic studies. In healthy volunteers, neffy achieved similar serum epinephrine levels, rises in blood pressure, and pulse compared with IM epinephrine. 

The Need for Neffy

It was just a few days ago that I saw a new patient with fire ant anaphylaxis. The last time he tried to use an injectable epinephrine pen, he made two mistakes. First, he placed the wrong end against his thigh, and when it did not inject, he depressed it with his thumb — in other words, he injected his thumb with epinephrine. Of course, that cannot happen with neffy. 

I recall a few years ago, a child experienced anaphylaxis but the parent was hesitant to administer the EAI (epinephrine autoinjector). The parent drove to the emergency room but was delayed by traffic, and by the time they reached the ER, the patient had suffered a respiratory arrest and passed away. 

Patients are not the only ones who are hesitant to administer epinephrine. Some clinicians do not treat anaphylaxis appropriately. As an allergist, I see patients after-the-fact for diagnosis and management. Patients often tell me of systemic allergic reactions treated with IV antihistamines/corticosteroids and even sometimes with nebulized beta agonists, but not epinephrine. 

My opinion is that it’s not just needle phobia. As I mentioned, in my Medscape commentary “Injectable Epinephrine: An Epidemic of Misuse,” I believe it’s due to a misunderstanding of the guidelines and a sense that epinephrine is a potent medication to be used sparingly. Clinicians and patients must understand that epinephrine is a naturally occurring hormone and administration leads to serum levels seen under other natural circumstances (eg, stress — the fight-or-flight surge). The aforementioned article also includes a patient handout, “Don’t Fear Epinephrine,” which I encourage you to read and distribute. 

The potential benefits of neffy are clear: 

• It should overcome fear of injection ergo being more likely to be used, and used earlier, by both patient/family member and clinicians.
• It’s easier to carry than many larger devices (though not the AUVI-Q).
• It cannot be injected incorrectly. 
• Expiration is 8 months longer than the EAI.
• There are no pharmacist substitutions (as there is no equivalent device).

Potential Problems With Neffy and Some Suggested Solutions

As promising and beneficial as it is, I wonder about a few training issues. In the office, patients can be trained with a (reusable) injectable epinephrine trainer but not with a nasal spray device trainer in the office (an important alternative is a small model of a nose in the office for patient education). A training device should also be included in the neffy prescription, as with the EAI.
 

Neffy and Patients With Nasal Polyps or Nasal Surgery

It’s more complicated than that neffy cannot be used with patients who have had nasal polyps or nasal surgery. It’s really about how much healthy nasal mucosa is required for absorption. Nasal surgery may be simple or complex. Nasal polyps may be obstructive or resolved with nasal steroid or biologic therapy. Nasal polyps affect 2% of the population, but 35% of pediatric food allergy (FA) patients develop allergic rhinitis (AR), and these AR symptoms present even when not triggered by FA. AR is present at baseline in patients with FA. How does this influence neffy absorption? For FA patients who have anaphylactic reactions with severe nasal reactions, neffy absorption could be further compromised, something that has not been studied. 

Insurance Coverage

As we don’t yet know the comparative efficacy of neffy in anaphylactic episodes, it’s likely that patients, especially with more severe food sensitivities, will be prescribed both the nasal and IM devices. The question remains whether insurance will cover both. 

In “mild cases,” I suspect that doctors might be more inclined to prescribe neffy.
 

Conclusion

Delay in epinephrine use is frequent despite the clear indication during anaphylactic episodes, which in turn increases risk for mortality. Neffy will probably save many lives. 

Dr. Stadtmauer serves on the advisory board of Medscape. He is in private practice in New York City and is affiliated with the Mount Sinai School of Medicine. 

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

This summer, the US Food and Drug Administration (FDA) fast-tracked approval of the first-in-its-class nasal epinephrine (neffy). It’s a very welcome addition to our anaphylaxis treatment armamentarium. As the FDA announcement notes, patients with anaphylaxis at times “delay or avoid” anaphylaxis “treatment due to fear of injections.” Neffy was approved on the basis of pharmacokinetic studies. In healthy volunteers, neffy achieved similar serum epinephrine levels, rises in blood pressure, and pulse compared with IM epinephrine. 

The Need for Neffy

It was just a few days ago that I saw a new patient with fire ant anaphylaxis. The last time he tried to use an injectable epinephrine pen, he made two mistakes. First, he placed the wrong end against his thigh, and when it did not inject, he depressed it with his thumb — in other words, he injected his thumb with epinephrine. Of course, that cannot happen with neffy. 

I recall a few years ago, a child experienced anaphylaxis but the parent was hesitant to administer the EAI (epinephrine autoinjector). The parent drove to the emergency room but was delayed by traffic, and by the time they reached the ER, the patient had suffered a respiratory arrest and passed away. 

Patients are not the only ones who are hesitant to administer epinephrine. Some clinicians do not treat anaphylaxis appropriately. As an allergist, I see patients after-the-fact for diagnosis and management. Patients often tell me of systemic allergic reactions treated with IV antihistamines/corticosteroids and even sometimes with nebulized beta agonists, but not epinephrine. 

My opinion is that it’s not just needle phobia. As I mentioned, in my Medscape commentary “Injectable Epinephrine: An Epidemic of Misuse,” I believe it’s due to a misunderstanding of the guidelines and a sense that epinephrine is a potent medication to be used sparingly. Clinicians and patients must understand that epinephrine is a naturally occurring hormone and administration leads to serum levels seen under other natural circumstances (eg, stress — the fight-or-flight surge). The aforementioned article also includes a patient handout, “Don’t Fear Epinephrine,” which I encourage you to read and distribute. 

The potential benefits of neffy are clear: 

• It should overcome fear of injection ergo being more likely to be used, and used earlier, by both patient/family member and clinicians.
• It’s easier to carry than many larger devices (though not the AUVI-Q).
• It cannot be injected incorrectly. 
• Expiration is 8 months longer than the EAI.
• There are no pharmacist substitutions (as there is no equivalent device).

Potential Problems With Neffy and Some Suggested Solutions

As promising and beneficial as it is, I wonder about a few training issues. In the office, patients can be trained with a (reusable) injectable epinephrine trainer but not with a nasal spray device trainer in the office (an important alternative is a small model of a nose in the office for patient education). A training device should also be included in the neffy prescription, as with the EAI.
 

Neffy and Patients With Nasal Polyps or Nasal Surgery

It’s more complicated than that neffy cannot be used with patients who have had nasal polyps or nasal surgery. It’s really about how much healthy nasal mucosa is required for absorption. Nasal surgery may be simple or complex. Nasal polyps may be obstructive or resolved with nasal steroid or biologic therapy. Nasal polyps affect 2% of the population, but 35% of pediatric food allergy (FA) patients develop allergic rhinitis (AR), and these AR symptoms present even when not triggered by FA. AR is present at baseline in patients with FA. How does this influence neffy absorption? For FA patients who have anaphylactic reactions with severe nasal reactions, neffy absorption could be further compromised, something that has not been studied. 

Insurance Coverage

As we don’t yet know the comparative efficacy of neffy in anaphylactic episodes, it’s likely that patients, especially with more severe food sensitivities, will be prescribed both the nasal and IM devices. The question remains whether insurance will cover both. 

In “mild cases,” I suspect that doctors might be more inclined to prescribe neffy.
 

Conclusion

Delay in epinephrine use is frequent despite the clear indication during anaphylactic episodes, which in turn increases risk for mortality. Neffy will probably save many lives. 

Dr. Stadtmauer serves on the advisory board of Medscape. He is in private practice in New York City and is affiliated with the Mount Sinai School of Medicine. 

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

This summer, the US Food and Drug Administration (FDA) fast-tracked approval of the first-in-its-class nasal epinephrine (neffy). It’s a very welcome addition to our anaphylaxis treatment armamentarium. As the FDA announcement notes, patients with anaphylaxis at times “delay or avoid” anaphylaxis “treatment due to fear of injections.” Neffy was approved on the basis of pharmacokinetic studies. In healthy volunteers, neffy achieved similar serum epinephrine levels, rises in blood pressure, and pulse compared with IM epinephrine. 

The Need for Neffy

It was just a few days ago that I saw a new patient with fire ant anaphylaxis. The last time he tried to use an injectable epinephrine pen, he made two mistakes. First, he placed the wrong end against his thigh, and when it did not inject, he depressed it with his thumb — in other words, he injected his thumb with epinephrine. Of course, that cannot happen with neffy. 

I recall a few years ago, a child experienced anaphylaxis but the parent was hesitant to administer the EAI (epinephrine autoinjector). The parent drove to the emergency room but was delayed by traffic, and by the time they reached the ER, the patient had suffered a respiratory arrest and passed away. 

Patients are not the only ones who are hesitant to administer epinephrine. Some clinicians do not treat anaphylaxis appropriately. As an allergist, I see patients after-the-fact for diagnosis and management. Patients often tell me of systemic allergic reactions treated with IV antihistamines/corticosteroids and even sometimes with nebulized beta agonists, but not epinephrine. 

My opinion is that it’s not just needle phobia. As I mentioned, in my Medscape commentary “Injectable Epinephrine: An Epidemic of Misuse,” I believe it’s due to a misunderstanding of the guidelines and a sense that epinephrine is a potent medication to be used sparingly. Clinicians and patients must understand that epinephrine is a naturally occurring hormone and administration leads to serum levels seen under other natural circumstances (eg, stress — the fight-or-flight surge). The aforementioned article also includes a patient handout, “Don’t Fear Epinephrine,” which I encourage you to read and distribute. 

The potential benefits of neffy are clear: 

• It should overcome fear of injection ergo being more likely to be used, and used earlier, by both patient/family member and clinicians.
• It’s easier to carry than many larger devices (though not the AUVI-Q).
• It cannot be injected incorrectly. 
• Expiration is 8 months longer than the EAI.
• There are no pharmacist substitutions (as there is no equivalent device).

Potential Problems With Neffy and Some Suggested Solutions

As promising and beneficial as it is, I wonder about a few training issues. In the office, patients can be trained with a (reusable) injectable epinephrine trainer but not with a nasal spray device trainer in the office (an important alternative is a small model of a nose in the office for patient education). A training device should also be included in the neffy prescription, as with the EAI.
 

Neffy and Patients With Nasal Polyps or Nasal Surgery

It’s more complicated than that neffy cannot be used with patients who have had nasal polyps or nasal surgery. It’s really about how much healthy nasal mucosa is required for absorption. Nasal surgery may be simple or complex. Nasal polyps may be obstructive or resolved with nasal steroid or biologic therapy. Nasal polyps affect 2% of the population, but 35% of pediatric food allergy (FA) patients develop allergic rhinitis (AR), and these AR symptoms present even when not triggered by FA. AR is present at baseline in patients with FA. How does this influence neffy absorption? For FA patients who have anaphylactic reactions with severe nasal reactions, neffy absorption could be further compromised, something that has not been studied. 

Insurance Coverage

As we don’t yet know the comparative efficacy of neffy in anaphylactic episodes, it’s likely that patients, especially with more severe food sensitivities, will be prescribed both the nasal and IM devices. The question remains whether insurance will cover both. 

In “mild cases,” I suspect that doctors might be more inclined to prescribe neffy.
 

Conclusion

Delay in epinephrine use is frequent despite the clear indication during anaphylactic episodes, which in turn increases risk for mortality. Neffy will probably save many lives. 

Dr. Stadtmauer serves on the advisory board of Medscape. He is in private practice in New York City and is affiliated with the Mount Sinai School of Medicine. 

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

Cannabis use may lead to thinning of the cerebral cortex in adolescents, research in mice and humans suggested.

The multilevel study demonstrated that tetrahydrocannabinol (THC), an active substance in cannabis, causes shrinkage of dendritic arborization — the neurons’ network of antennae that play a critical role in communication between brain cells.

The connection between dendritic arborization and cortical thickness was hinted at in an earlier study by Tomáš Paus, MD, PhD, professor of psychiatry and addictology at the University of Montreal, Quebec, Canada, and colleagues, who found that cannabis use in early adolescence was associated with lower cortical thickness in boys with a high genetic risk for schizophrenia.

“We speculated at that time that the differences in cortical thickness might be related to differences in dendritic arborization, and our current study confirmed it,” Paus said.

That confirmation came in the mouse part of the study, when coauthor Graciela Piñeyro, MD, PhD, also of the University of Montreal, counted the dendritic branches of mice exposed to THC and compared the total with the number of dendritic branches in unexposed mice. “What surprised me was finding that THC in the mice was targeting the same type of cells and structures that Dr. Paus had predicted would be affected from the human studies,” she said. “Structurally, they were mostly the neurons that contribute to synapses in the cortex, and their branching was reduced.”

Paus explained that in humans, a decrease in input from the affected dendrites “makes it harder for the brain to learn new things, interact with people, cope with new situations, et cetera. In other words, it makes the brain more vulnerable to everything that can happen in a young person’s life.”

The study was published online on October 9 in the Journal of Neuroscience.
 

Of Mice, Men, and Cannabis

Although associations between cannabis use by teenagers and variations in brain maturation have been well studied, the cellular and molecular underpinnings of these associations were unclear, according to the authors.

To investigate further, they conducted this three-step study. First, they exposed adolescent male mice to THC or a synthetic cannabinoid (WIN 55,212-2) and assessed differentially expressed genes, spine numbers, and the extent of dendritic complexity in the frontal cortex of each mouse.

Next, using MRI, they examined differences in cortical thickness in 34 brain regions in 140 male adolescents who experimented with cannabis before age 16 years and 327 who did not.

Then, they again conducted experiments in mice and found that 13 THC-related genes correlated with variations in cortical thickness. Virtual histology revealed that these 13 genes were coexpressed with cell markers of astrocytes, microglia, and a type of pyramidal cell enriched in genes that regulate dendritic expression.

Similarly, the WIN-related genes correlated with differences in cortical thickness and showed coexpression patterns with the same three cell types.

Furthermore, the affected genes were also found in humans, particularly in the thinner cortical regions of the adolescents who experimented with cannabis.

By acting on microglia, THC seems to promote the removal of synapses and, eventually, the reduction of the dendritic tree in mice, Piñeyro explained. That’s important not only because a similar mechanism may be at work in humans but also because “we now might have a model to test different types of cannabis products to see which ones are producing the greatest effect on neurons and therefore greater removal of synapses through the microglia. This could be a way of testing drugs that are out in the street to see which would be the most or least dangerous to the synapses in the brain.”
 

‘Significant Implications’

Commenting on the study, Yasmin Hurd, PhD, Ward-Coleman chair of translational neuroscience at the Icahn School of Medicine at Mount Sinai and director of the Addiction Institute of Mount Sinai in New York City, said, “These findings are in line with previous results, so they are feasible. This study adds more depth by showing that cortical genes that were differentially altered by adolescent THC correlated with cannabis-related changes in cortical thickness based on human neuroimaging data.” Hurd did not participate in the research.

“The results emphasize that consumption of potent cannabis products during adolescence can impact cortical function, which has significant implications for decision-making and risky behavior as well. It also can increase vulnerability to psychiatric disorders such as schizophrenia.”

Although a mouse model is “not truly the same as the human condition, the fact that the animal model also showed evidence of the morphological changes indicative of reduced cortical thickness, [like] the humans, is strong,” she said.

Additional research could include women and assess potential sex differences, she added.

Ronald Ellis, MD, PhD, an investigator in the Center for Medicinal Cannabis Research at the University of California, San Diego School of Medicine, said, “The findings are plausible and extend prior work showing evidence of increased risk for psychotic disorders later in life in adolescents who use cannabis.” Ellis did not participate in the research.

“Future studies should explore how these findings might vary across different demographic groups, which could provide a more inclusive understanding of how cannabis impacts the brain,” he said. “Additionally, longitudinal studies to track changes in the brain over time could help to establish causal relationships more robustly.

“The take-home message to clinicians at this point is to discuss cannabis use history carefully and confidentially with adolescent patients to better provide advice on its potential risks,” he concluded.

Paus added that he would tell patients, “If you’re going to use cannabis, don’t start early. If you have to, then do so in moderation. And if you have family history of mental illness, be very careful.”

No funding for the study was reported. Paus, Piñeyro, Hurd, and Ellis declared having no relevant financial relationships. 
 

A version of this article appeared on Medscape.com.

Cannabis use may lead to thinning of the cerebral cortex in adolescents, research in mice and humans suggested.

The multilevel study demonstrated that tetrahydrocannabinol (THC), an active substance in cannabis, causes shrinkage of dendritic arborization — the neurons’ network of antennae that play a critical role in communication between brain cells.

The connection between dendritic arborization and cortical thickness was hinted at in an earlier study by Tomáš Paus, MD, PhD, professor of psychiatry and addictology at the University of Montreal, Quebec, Canada, and colleagues, who found that cannabis use in early adolescence was associated with lower cortical thickness in boys with a high genetic risk for schizophrenia.

“We speculated at that time that the differences in cortical thickness might be related to differences in dendritic arborization, and our current study confirmed it,” Paus said.

That confirmation came in the mouse part of the study, when coauthor Graciela Piñeyro, MD, PhD, also of the University of Montreal, counted the dendritic branches of mice exposed to THC and compared the total with the number of dendritic branches in unexposed mice. “What surprised me was finding that THC in the mice was targeting the same type of cells and structures that Dr. Paus had predicted would be affected from the human studies,” she said. “Structurally, they were mostly the neurons that contribute to synapses in the cortex, and their branching was reduced.”

Paus explained that in humans, a decrease in input from the affected dendrites “makes it harder for the brain to learn new things, interact with people, cope with new situations, et cetera. In other words, it makes the brain more vulnerable to everything that can happen in a young person’s life.”

The study was published online on October 9 in the Journal of Neuroscience.
 

Of Mice, Men, and Cannabis

Although associations between cannabis use by teenagers and variations in brain maturation have been well studied, the cellular and molecular underpinnings of these associations were unclear, according to the authors.

To investigate further, they conducted this three-step study. First, they exposed adolescent male mice to THC or a synthetic cannabinoid (WIN 55,212-2) and assessed differentially expressed genes, spine numbers, and the extent of dendritic complexity in the frontal cortex of each mouse.

Next, using MRI, they examined differences in cortical thickness in 34 brain regions in 140 male adolescents who experimented with cannabis before age 16 years and 327 who did not.

Then, they again conducted experiments in mice and found that 13 THC-related genes correlated with variations in cortical thickness. Virtual histology revealed that these 13 genes were coexpressed with cell markers of astrocytes, microglia, and a type of pyramidal cell enriched in genes that regulate dendritic expression.

Similarly, the WIN-related genes correlated with differences in cortical thickness and showed coexpression patterns with the same three cell types.

Furthermore, the affected genes were also found in humans, particularly in the thinner cortical regions of the adolescents who experimented with cannabis.

By acting on microglia, THC seems to promote the removal of synapses and, eventually, the reduction of the dendritic tree in mice, Piñeyro explained. That’s important not only because a similar mechanism may be at work in humans but also because “we now might have a model to test different types of cannabis products to see which ones are producing the greatest effect on neurons and therefore greater removal of synapses through the microglia. This could be a way of testing drugs that are out in the street to see which would be the most or least dangerous to the synapses in the brain.”
 

‘Significant Implications’

Commenting on the study, Yasmin Hurd, PhD, Ward-Coleman chair of translational neuroscience at the Icahn School of Medicine at Mount Sinai and director of the Addiction Institute of Mount Sinai in New York City, said, “These findings are in line with previous results, so they are feasible. This study adds more depth by showing that cortical genes that were differentially altered by adolescent THC correlated with cannabis-related changes in cortical thickness based on human neuroimaging data.” Hurd did not participate in the research.

“The results emphasize that consumption of potent cannabis products during adolescence can impact cortical function, which has significant implications for decision-making and risky behavior as well. It also can increase vulnerability to psychiatric disorders such as schizophrenia.”

Although a mouse model is “not truly the same as the human condition, the fact that the animal model also showed evidence of the morphological changes indicative of reduced cortical thickness, [like] the humans, is strong,” she said.

Additional research could include women and assess potential sex differences, she added.

Ronald Ellis, MD, PhD, an investigator in the Center for Medicinal Cannabis Research at the University of California, San Diego School of Medicine, said, “The findings are plausible and extend prior work showing evidence of increased risk for psychotic disorders later in life in adolescents who use cannabis.” Ellis did not participate in the research.

“Future studies should explore how these findings might vary across different demographic groups, which could provide a more inclusive understanding of how cannabis impacts the brain,” he said. “Additionally, longitudinal studies to track changes in the brain over time could help to establish causal relationships more robustly.

“The take-home message to clinicians at this point is to discuss cannabis use history carefully and confidentially with adolescent patients to better provide advice on its potential risks,” he concluded.

Paus added that he would tell patients, “If you’re going to use cannabis, don’t start early. If you have to, then do so in moderation. And if you have family history of mental illness, be very careful.”

No funding for the study was reported. Paus, Piñeyro, Hurd, and Ellis declared having no relevant financial relationships. 
 

A version of this article appeared on Medscape.com.

Cannabis use may lead to thinning of the cerebral cortex in adolescents, research in mice and humans suggested.

The multilevel study demonstrated that tetrahydrocannabinol (THC), an active substance in cannabis, causes shrinkage of dendritic arborization — the neurons’ network of antennae that play a critical role in communication between brain cells.

The connection between dendritic arborization and cortical thickness was hinted at in an earlier study by Tomáš Paus, MD, PhD, professor of psychiatry and addictology at the University of Montreal, Quebec, Canada, and colleagues, who found that cannabis use in early adolescence was associated with lower cortical thickness in boys with a high genetic risk for schizophrenia.

“We speculated at that time that the differences in cortical thickness might be related to differences in dendritic arborization, and our current study confirmed it,” Paus said.

That confirmation came in the mouse part of the study, when coauthor Graciela Piñeyro, MD, PhD, also of the University of Montreal, counted the dendritic branches of mice exposed to THC and compared the total with the number of dendritic branches in unexposed mice. “What surprised me was finding that THC in the mice was targeting the same type of cells and structures that Dr. Paus had predicted would be affected from the human studies,” she said. “Structurally, they were mostly the neurons that contribute to synapses in the cortex, and their branching was reduced.”

Paus explained that in humans, a decrease in input from the affected dendrites “makes it harder for the brain to learn new things, interact with people, cope with new situations, et cetera. In other words, it makes the brain more vulnerable to everything that can happen in a young person’s life.”

The study was published online on October 9 in the Journal of Neuroscience.
 

Of Mice, Men, and Cannabis

Although associations between cannabis use by teenagers and variations in brain maturation have been well studied, the cellular and molecular underpinnings of these associations were unclear, according to the authors.

To investigate further, they conducted this three-step study. First, they exposed adolescent male mice to THC or a synthetic cannabinoid (WIN 55,212-2) and assessed differentially expressed genes, spine numbers, and the extent of dendritic complexity in the frontal cortex of each mouse.

Next, using MRI, they examined differences in cortical thickness in 34 brain regions in 140 male adolescents who experimented with cannabis before age 16 years and 327 who did not.

Then, they again conducted experiments in mice and found that 13 THC-related genes correlated with variations in cortical thickness. Virtual histology revealed that these 13 genes were coexpressed with cell markers of astrocytes, microglia, and a type of pyramidal cell enriched in genes that regulate dendritic expression.

Similarly, the WIN-related genes correlated with differences in cortical thickness and showed coexpression patterns with the same three cell types.

Furthermore, the affected genes were also found in humans, particularly in the thinner cortical regions of the adolescents who experimented with cannabis.

By acting on microglia, THC seems to promote the removal of synapses and, eventually, the reduction of the dendritic tree in mice, Piñeyro explained. That’s important not only because a similar mechanism may be at work in humans but also because “we now might have a model to test different types of cannabis products to see which ones are producing the greatest effect on neurons and therefore greater removal of synapses through the microglia. This could be a way of testing drugs that are out in the street to see which would be the most or least dangerous to the synapses in the brain.”
 

‘Significant Implications’

Commenting on the study, Yasmin Hurd, PhD, Ward-Coleman chair of translational neuroscience at the Icahn School of Medicine at Mount Sinai and director of the Addiction Institute of Mount Sinai in New York City, said, “These findings are in line with previous results, so they are feasible. This study adds more depth by showing that cortical genes that were differentially altered by adolescent THC correlated with cannabis-related changes in cortical thickness based on human neuroimaging data.” Hurd did not participate in the research.

“The results emphasize that consumption of potent cannabis products during adolescence can impact cortical function, which has significant implications for decision-making and risky behavior as well. It also can increase vulnerability to psychiatric disorders such as schizophrenia.”

Although a mouse model is “not truly the same as the human condition, the fact that the animal model also showed evidence of the morphological changes indicative of reduced cortical thickness, [like] the humans, is strong,” she said.

Additional research could include women and assess potential sex differences, she added.

Ronald Ellis, MD, PhD, an investigator in the Center for Medicinal Cannabis Research at the University of California, San Diego School of Medicine, said, “The findings are plausible and extend prior work showing evidence of increased risk for psychotic disorders later in life in adolescents who use cannabis.” Ellis did not participate in the research.

“Future studies should explore how these findings might vary across different demographic groups, which could provide a more inclusive understanding of how cannabis impacts the brain,” he said. “Additionally, longitudinal studies to track changes in the brain over time could help to establish causal relationships more robustly.

“The take-home message to clinicians at this point is to discuss cannabis use history carefully and confidentially with adolescent patients to better provide advice on its potential risks,” he concluded.

Paus added that he would tell patients, “If you’re going to use cannabis, don’t start early. If you have to, then do so in moderation. And if you have family history of mental illness, be very careful.”

No funding for the study was reported. Paus, Piñeyro, Hurd, and Ellis declared having no relevant financial relationships. 
 

A version of this article appeared on Medscape.com.

A growing body of research suggests that clinicians can offer chimeric antigen receptor (CAR) T-cell therapy safely and effectively on an outpatient basis — a positive development as clinicians strive to expand access beyond metropolitan areas.

In one recent study, an industry-funded phase 2 trial, researchers found similar outcomes from outpatient and inpatient CAR T-cell therapy for relapsed/refractory large B-cell lymphoma with lisocabtagene maraleucel (Breyanzi). 

Another recent study reported that outpatient treatment of B cell non-Hodgkin lymphoma with tisagenlecleucel (Kymriah) had similar efficacy to inpatient treatment. Meanwhile, a 2023 review of CAR T-cell therapy in various settings found similar outcomes in outpatient and inpatient treatment. 

“The future of CAR T-cell therapy lies in balancing safety with accessibility,” said Rayne Rouce, MD, a pediatric oncologist at Texas Children’s Cancer Center in Houston, Texas, in an interview. “Expanding CAR T-cell therapy beyond large medical centers is a critical next step.” 
 

Great Outcomes, Low Access

Since 2017, the FDA has approved six CAR T-cell therapies, which target cancer by harnessing the power of a patient’s own T cells. As an Oregon Health & Sciences University/Knight Cancer Center website explains, T cells are removed from the patient’s body, “genetically modified to make the chimeric antigen receptor, or CAR, [which] protein binds to specific proteins on the surface of cancer cells.”

Modified cells are grown and then infused back into the body, where they “multiply and may be able to destroy all the cancer cells.”

As Rouce puts it, “CAR T-cells have revolutionized the treatment of relapsed or refractory blood cancers.” One or more of the therapies have been approved to treat types of lymphoblastic leukemia, B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, and multiple myeloma.

A 2023 review of clinical trial data reported complete response rates of 40%-54% in aggressive B-cell lymphoma, 67% in mantle cell lymphoma, and 69%-74% in indolent B cell lymphoma.

“Commercialization of CAR T-cell therapy brought hope that access would expand beyond the major academic medical centers with the highly specialized infrastructure and advanced laboratories required to manufacture and ultimately treat patients,” Rouce said. “However, it quickly became clear that patients who are underinsured or uninsured — or who live outside the network of the well-resourced institutions that house these therapies — are still unable to access these potentially life-saving therapies.”

A 2024 report estimated the cost of CAR T-cell therapy as $700,000-$1 million and said only a small percentage of those who could benefit from the treatment actually get it. For example, an estimated 10,000 patients with diffuse large B-cell lymphoma alone could benefit from CAR T therapy annually, but a survey of 200 US healthcare centers in 2021 found that 1900 procedures were performed overall for all indications. 
 

Distance to Treatment Is a Major Obstacle

Even if patients have insurance plans willing to cover CAR T-cell therapy, they may not be able get care. While more than 150 US centers are certified to administer the therapy, “distance to major medical centers with CAR T capabilities is a major obstacle,” Yuliya Linhares, MD, chief of lymphoma at Miami Cancer Institute in Miami, Florida, said in an interview. 

“I have had patients who chose to not proceed with CAR T therapy due to inability to travel the distance to the medical center for pre-CAR T appointments and assessments and a lack of caretakers who are available to stay nearby,” Linhares said.

Indeed, the challenges facing patients in rural and underserved urban areas can be overwhelming, Hoda Badr, PhD, professor of medicine at Baylor College of Medicine in Houston, Texas, said in an interview.

“They must take time off work, arrange accommodations near treatment sites, and manage travel costs, all of which strain limited financial resources. The inability to afford these additional expenses can lead to delays in receiving care or patients forgoing the treatment altogether,” Badr said. She added that “the psychological and social burden of being away from family and community support systems during treatment can intensify the stress of an already difficult situation.”

A statistic tells the story of the urban/community divide. CAR T-cell therapy administration at academic centers after leukapheresis — the separation and collection of white blood cells — is reported to be at around 90%, while it’s only 47% in community-based practices that have to refer patients elsewhere, Linhares noted. 
 

Researchers Explore CAR T-Cell Therapy in the Community 

Linhares is lead author of the phase 2 trial that explored administration of lisocabtagene maraleucel in 82 patients with relapsed/refractory large B-cell lymphoma. The findings were published Sept. 30 in Blood Advances.

The OUTREACH trial, funded by Juno/Bristol-Myers Squibb, treated patients in the third line and beyond at community medical centers (outpatient-monitored, 70%; inpatient-monitored, 30%). The trial didn’t require facilities to be certified by the Foundation for the Accreditation of Cellular Therapy (FACT); all had to be non-tertiary cancer centers that weren’t associated with a university. In order to administer therapy on the outpatient basis, the centers had to have phase 1 or hematopoietic stem cell transplant capabilities.

As Linhares explained, 72% of participating centers hadn’t provided CAR T-cell therapy before, and 44% did not have FACT accreditation. “About 32% of patients received CAR T at CAR T naive sites, while 70% of patients received CAR T as outpatients. Investigators had to decide whether patients qualified for the outpatient observation or had to be admitted for the inpatient observation,” she noted.
 

Community Outcomes Were Comparable to Major Trial

As for the results, grade 3 or higher adverse events occurred at a similar frequency among outpatients and inpatients at 74% and 76%, Linhares said. There were no grade 5 adverse events, and 25% of patients treated as outpatients were never hospitalized. 

Response rates were similar to those in the major TRANSCEND trial with the objective response rates rate of 80% and complete response rates of 54%.

“Overall,” Linhares said, “our study demonstrated that with the availability of standard operating procedures, specially trained staff and a multidisciplinary team trained in CAR T toxicity management, inpatient and outpatient CAR T administration is feasible at specialized community medical centers.”

In 2023, another study examined patients with B-cell non-Hodgkin lymphoma who were treated on an outpatient basis with tisagenlecleucel. Researchers reported that outpatient therapy was “feasible and associated with similar efficacy outcomes as inpatient treatment.”

And a 2023 systematic literature review identified 11 studies that reported outpatient vs inpatient outcomes in CAR T-cell therapy and found “comparable response rates (80-82% in outpatient and 72-80% in inpatient).” Costs were cheaper in the outpatient setting. 

Research findings like these are good news, Baylor College of Medicine’s Badr said. “Outpatient administration could help to scale the availability of this therapy to a broader range of healthcare settings, including those serving underserved populations. Findings indicate promising safety profiles, which is encouraging for expanding access.”
 

Not Every Patient Can Tolerate Outpatient Care

Linhares noted that the patients who received outpatient care in the lisocabtagene maraleucel study were in better shape than those in the inpatient group. Those selected for inpatient care had “higher disease risk characteristics, including high grade B cell lymphoma histology, higher disease burden, and having received bridging therapy. This points to the fact that the investigators properly selected patients who were at a higher risk of complications for inpatient observation. Additionally, some patients stayed as inpatient due to social factors, which increases length of stay independently of disease characteristics.”

Specifically, reasons for inpatient monitoring were disease characteristics (48%) including tumor burden and risk of adverse events; psychosocial factors (32%) including lack of caregiver support or transportation; COVID-19 precautions (8%); pre-infusion adverse events (8%) of fever and vasovagal reaction; and principal investigator decision (4%) due to limited hospital experience with CAR T-cell therapy.

Texas Children’s Cancer Center’s Rouce said “certain patients, particularly those with higher risk for complications or those who require intensive monitoring, may not be suited for outpatient CAR T-cell therapy. This may be due to other comorbidities or baseline factors known to predispose to CAR T-related toxicities. However, evidence-based risk mitigation algorithms may still allow closely monitored outpatient treatment, with recognition that hospital admission for incipient side effects may be necessary.”
 

What’s Next for Access to Therapy?

Rouce noted that her institution, like many others, is offering CAR T-cell therapy on an outpatient basis. “Additionally, continued scientific innovation, such as immediately available, off-the-shelf cell therapies and inducible safety switches, will ultimately improve access,” she said. 

Linhares noted a recent advance and highlighted research that’s now in progress. “CAR Ts now have an indication as a second-line therapy in relapsed/refractory large B-cell lymphoma, and there are ongoing clinical trials that will potentially move CAR Ts into the first line,” she said. “Some trials are exploring allogeneic, readily available off-the-shelf CAR T for the treatment of minimal residual disease positive large B-cell lymphoma after completion of first-line therapy.”

These potential advances “are increasing the need for CAR T-capable medical centers,” Linhares noted. “More and more medical centers with expert hematology teams are becoming CAR T-certified, with more patients having access to CAR T.”

Still, she said, “I don’t think access is nearly as good as it should be. Many patients in rural areas are still unable to get this life-saving treatment. “However, “it is very possible that other novel targeted therapies, such as bispecific antibodies, will be used in place of CAR T in areas with poor CAR T access. Bispecific antibody efficacy in various B cell lymphoma histologies are being currently explored.”

Rouce discloses relationships with Novartis and Pfizer. Linhares reports ties with Kyowa Kirin, AbbVie, ADC, BeiGene, Genentech, Gilead, GlaxoSmithKline, Seagen, and TG. Badr has no disclosures. 
 

A version of this article appeared on Medscape.com.

A growing body of research suggests that clinicians can offer chimeric antigen receptor (CAR) T-cell therapy safely and effectively on an outpatient basis — a positive development as clinicians strive to expand access beyond metropolitan areas.

In one recent study, an industry-funded phase 2 trial, researchers found similar outcomes from outpatient and inpatient CAR T-cell therapy for relapsed/refractory large B-cell lymphoma with lisocabtagene maraleucel (Breyanzi). 

Another recent study reported that outpatient treatment of B cell non-Hodgkin lymphoma with tisagenlecleucel (Kymriah) had similar efficacy to inpatient treatment. Meanwhile, a 2023 review of CAR T-cell therapy in various settings found similar outcomes in outpatient and inpatient treatment. 

“The future of CAR T-cell therapy lies in balancing safety with accessibility,” said Rayne Rouce, MD, a pediatric oncologist at Texas Children’s Cancer Center in Houston, Texas, in an interview. “Expanding CAR T-cell therapy beyond large medical centers is a critical next step.” 
 

Great Outcomes, Low Access

Since 2017, the FDA has approved six CAR T-cell therapies, which target cancer by harnessing the power of a patient’s own T cells. As an Oregon Health & Sciences University/Knight Cancer Center website explains, T cells are removed from the patient’s body, “genetically modified to make the chimeric antigen receptor, or CAR, [which] protein binds to specific proteins on the surface of cancer cells.”

Modified cells are grown and then infused back into the body, where they “multiply and may be able to destroy all the cancer cells.”

As Rouce puts it, “CAR T-cells have revolutionized the treatment of relapsed or refractory blood cancers.” One or more of the therapies have been approved to treat types of lymphoblastic leukemia, B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, and multiple myeloma.

A 2023 review of clinical trial data reported complete response rates of 40%-54% in aggressive B-cell lymphoma, 67% in mantle cell lymphoma, and 69%-74% in indolent B cell lymphoma.

“Commercialization of CAR T-cell therapy brought hope that access would expand beyond the major academic medical centers with the highly specialized infrastructure and advanced laboratories required to manufacture and ultimately treat patients,” Rouce said. “However, it quickly became clear that patients who are underinsured or uninsured — or who live outside the network of the well-resourced institutions that house these therapies — are still unable to access these potentially life-saving therapies.”

A 2024 report estimated the cost of CAR T-cell therapy as $700,000-$1 million and said only a small percentage of those who could benefit from the treatment actually get it. For example, an estimated 10,000 patients with diffuse large B-cell lymphoma alone could benefit from CAR T therapy annually, but a survey of 200 US healthcare centers in 2021 found that 1900 procedures were performed overall for all indications. 
 

Distance to Treatment Is a Major Obstacle

Even if patients have insurance plans willing to cover CAR T-cell therapy, they may not be able get care. While more than 150 US centers are certified to administer the therapy, “distance to major medical centers with CAR T capabilities is a major obstacle,” Yuliya Linhares, MD, chief of lymphoma at Miami Cancer Institute in Miami, Florida, said in an interview. 

“I have had patients who chose to not proceed with CAR T therapy due to inability to travel the distance to the medical center for pre-CAR T appointments and assessments and a lack of caretakers who are available to stay nearby,” Linhares said.

Indeed, the challenges facing patients in rural and underserved urban areas can be overwhelming, Hoda Badr, PhD, professor of medicine at Baylor College of Medicine in Houston, Texas, said in an interview.

“They must take time off work, arrange accommodations near treatment sites, and manage travel costs, all of which strain limited financial resources. The inability to afford these additional expenses can lead to delays in receiving care or patients forgoing the treatment altogether,” Badr said. She added that “the psychological and social burden of being away from family and community support systems during treatment can intensify the stress of an already difficult situation.”

A statistic tells the story of the urban/community divide. CAR T-cell therapy administration at academic centers after leukapheresis — the separation and collection of white blood cells — is reported to be at around 90%, while it’s only 47% in community-based practices that have to refer patients elsewhere, Linhares noted. 
 

Researchers Explore CAR T-Cell Therapy in the Community 

Linhares is lead author of the phase 2 trial that explored administration of lisocabtagene maraleucel in 82 patients with relapsed/refractory large B-cell lymphoma. The findings were published Sept. 30 in Blood Advances.

The OUTREACH trial, funded by Juno/Bristol-Myers Squibb, treated patients in the third line and beyond at community medical centers (outpatient-monitored, 70%; inpatient-monitored, 30%). The trial didn’t require facilities to be certified by the Foundation for the Accreditation of Cellular Therapy (FACT); all had to be non-tertiary cancer centers that weren’t associated with a university. In order to administer therapy on the outpatient basis, the centers had to have phase 1 or hematopoietic stem cell transplant capabilities.

As Linhares explained, 72% of participating centers hadn’t provided CAR T-cell therapy before, and 44% did not have FACT accreditation. “About 32% of patients received CAR T at CAR T naive sites, while 70% of patients received CAR T as outpatients. Investigators had to decide whether patients qualified for the outpatient observation or had to be admitted for the inpatient observation,” she noted.
 

Community Outcomes Were Comparable to Major Trial

As for the results, grade 3 or higher adverse events occurred at a similar frequency among outpatients and inpatients at 74% and 76%, Linhares said. There were no grade 5 adverse events, and 25% of patients treated as outpatients were never hospitalized. 

Response rates were similar to those in the major TRANSCEND trial with the objective response rates rate of 80% and complete response rates of 54%.

“Overall,” Linhares said, “our study demonstrated that with the availability of standard operating procedures, specially trained staff and a multidisciplinary team trained in CAR T toxicity management, inpatient and outpatient CAR T administration is feasible at specialized community medical centers.”

In 2023, another study examined patients with B-cell non-Hodgkin lymphoma who were treated on an outpatient basis with tisagenlecleucel. Researchers reported that outpatient therapy was “feasible and associated with similar efficacy outcomes as inpatient treatment.”

And a 2023 systematic literature review identified 11 studies that reported outpatient vs inpatient outcomes in CAR T-cell therapy and found “comparable response rates (80-82% in outpatient and 72-80% in inpatient).” Costs were cheaper in the outpatient setting. 

Research findings like these are good news, Baylor College of Medicine’s Badr said. “Outpatient administration could help to scale the availability of this therapy to a broader range of healthcare settings, including those serving underserved populations. Findings indicate promising safety profiles, which is encouraging for expanding access.”
 

Not Every Patient Can Tolerate Outpatient Care

Linhares noted that the patients who received outpatient care in the lisocabtagene maraleucel study were in better shape than those in the inpatient group. Those selected for inpatient care had “higher disease risk characteristics, including high grade B cell lymphoma histology, higher disease burden, and having received bridging therapy. This points to the fact that the investigators properly selected patients who were at a higher risk of complications for inpatient observation. Additionally, some patients stayed as inpatient due to social factors, which increases length of stay independently of disease characteristics.”

Specifically, reasons for inpatient monitoring were disease characteristics (48%) including tumor burden and risk of adverse events; psychosocial factors (32%) including lack of caregiver support or transportation; COVID-19 precautions (8%); pre-infusion adverse events (8%) of fever and vasovagal reaction; and principal investigator decision (4%) due to limited hospital experience with CAR T-cell therapy.

Texas Children’s Cancer Center’s Rouce said “certain patients, particularly those with higher risk for complications or those who require intensive monitoring, may not be suited for outpatient CAR T-cell therapy. This may be due to other comorbidities or baseline factors known to predispose to CAR T-related toxicities. However, evidence-based risk mitigation algorithms may still allow closely monitored outpatient treatment, with recognition that hospital admission for incipient side effects may be necessary.”
 

What’s Next for Access to Therapy?

Rouce noted that her institution, like many others, is offering CAR T-cell therapy on an outpatient basis. “Additionally, continued scientific innovation, such as immediately available, off-the-shelf cell therapies and inducible safety switches, will ultimately improve access,” she said. 

Linhares noted a recent advance and highlighted research that’s now in progress. “CAR Ts now have an indication as a second-line therapy in relapsed/refractory large B-cell lymphoma, and there are ongoing clinical trials that will potentially move CAR Ts into the first line,” she said. “Some trials are exploring allogeneic, readily available off-the-shelf CAR T for the treatment of minimal residual disease positive large B-cell lymphoma after completion of first-line therapy.”

These potential advances “are increasing the need for CAR T-capable medical centers,” Linhares noted. “More and more medical centers with expert hematology teams are becoming CAR T-certified, with more patients having access to CAR T.”

Still, she said, “I don’t think access is nearly as good as it should be. Many patients in rural areas are still unable to get this life-saving treatment. “However, “it is very possible that other novel targeted therapies, such as bispecific antibodies, will be used in place of CAR T in areas with poor CAR T access. Bispecific antibody efficacy in various B cell lymphoma histologies are being currently explored.”

Rouce discloses relationships with Novartis and Pfizer. Linhares reports ties with Kyowa Kirin, AbbVie, ADC, BeiGene, Genentech, Gilead, GlaxoSmithKline, Seagen, and TG. Badr has no disclosures. 
 

A version of this article appeared on Medscape.com.

A growing body of research suggests that clinicians can offer chimeric antigen receptor (CAR) T-cell therapy safely and effectively on an outpatient basis — a positive development as clinicians strive to expand access beyond metropolitan areas.

In one recent study, an industry-funded phase 2 trial, researchers found similar outcomes from outpatient and inpatient CAR T-cell therapy for relapsed/refractory large B-cell lymphoma with lisocabtagene maraleucel (Breyanzi). 

Another recent study reported that outpatient treatment of B cell non-Hodgkin lymphoma with tisagenlecleucel (Kymriah) had similar efficacy to inpatient treatment. Meanwhile, a 2023 review of CAR T-cell therapy in various settings found similar outcomes in outpatient and inpatient treatment. 

“The future of CAR T-cell therapy lies in balancing safety with accessibility,” said Rayne Rouce, MD, a pediatric oncologist at Texas Children’s Cancer Center in Houston, Texas, in an interview. “Expanding CAR T-cell therapy beyond large medical centers is a critical next step.” 
 

Great Outcomes, Low Access

Since 2017, the FDA has approved six CAR T-cell therapies, which target cancer by harnessing the power of a patient’s own T cells. As an Oregon Health & Sciences University/Knight Cancer Center website explains, T cells are removed from the patient’s body, “genetically modified to make the chimeric antigen receptor, or CAR, [which] protein binds to specific proteins on the surface of cancer cells.”

Modified cells are grown and then infused back into the body, where they “multiply and may be able to destroy all the cancer cells.”

As Rouce puts it, “CAR T-cells have revolutionized the treatment of relapsed or refractory blood cancers.” One or more of the therapies have been approved to treat types of lymphoblastic leukemia, B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, and multiple myeloma.

A 2023 review of clinical trial data reported complete response rates of 40%-54% in aggressive B-cell lymphoma, 67% in mantle cell lymphoma, and 69%-74% in indolent B cell lymphoma.

“Commercialization of CAR T-cell therapy brought hope that access would expand beyond the major academic medical centers with the highly specialized infrastructure and advanced laboratories required to manufacture and ultimately treat patients,” Rouce said. “However, it quickly became clear that patients who are underinsured or uninsured — or who live outside the network of the well-resourced institutions that house these therapies — are still unable to access these potentially life-saving therapies.”

A 2024 report estimated the cost of CAR T-cell therapy as $700,000-$1 million and said only a small percentage of those who could benefit from the treatment actually get it. For example, an estimated 10,000 patients with diffuse large B-cell lymphoma alone could benefit from CAR T therapy annually, but a survey of 200 US healthcare centers in 2021 found that 1900 procedures were performed overall for all indications. 
 

Distance to Treatment Is a Major Obstacle

Even if patients have insurance plans willing to cover CAR T-cell therapy, they may not be able get care. While more than 150 US centers are certified to administer the therapy, “distance to major medical centers with CAR T capabilities is a major obstacle,” Yuliya Linhares, MD, chief of lymphoma at Miami Cancer Institute in Miami, Florida, said in an interview. 

“I have had patients who chose to not proceed with CAR T therapy due to inability to travel the distance to the medical center for pre-CAR T appointments and assessments and a lack of caretakers who are available to stay nearby,” Linhares said.

Indeed, the challenges facing patients in rural and underserved urban areas can be overwhelming, Hoda Badr, PhD, professor of medicine at Baylor College of Medicine in Houston, Texas, said in an interview.

“They must take time off work, arrange accommodations near treatment sites, and manage travel costs, all of which strain limited financial resources. The inability to afford these additional expenses can lead to delays in receiving care or patients forgoing the treatment altogether,” Badr said. She added that “the psychological and social burden of being away from family and community support systems during treatment can intensify the stress of an already difficult situation.”

A statistic tells the story of the urban/community divide. CAR T-cell therapy administration at academic centers after leukapheresis — the separation and collection of white blood cells — is reported to be at around 90%, while it’s only 47% in community-based practices that have to refer patients elsewhere, Linhares noted. 
 

Researchers Explore CAR T-Cell Therapy in the Community 

Linhares is lead author of the phase 2 trial that explored administration of lisocabtagene maraleucel in 82 patients with relapsed/refractory large B-cell lymphoma. The findings were published Sept. 30 in Blood Advances.

The OUTREACH trial, funded by Juno/Bristol-Myers Squibb, treated patients in the third line and beyond at community medical centers (outpatient-monitored, 70%; inpatient-monitored, 30%). The trial didn’t require facilities to be certified by the Foundation for the Accreditation of Cellular Therapy (FACT); all had to be non-tertiary cancer centers that weren’t associated with a university. In order to administer therapy on the outpatient basis, the centers had to have phase 1 or hematopoietic stem cell transplant capabilities.

As Linhares explained, 72% of participating centers hadn’t provided CAR T-cell therapy before, and 44% did not have FACT accreditation. “About 32% of patients received CAR T at CAR T naive sites, while 70% of patients received CAR T as outpatients. Investigators had to decide whether patients qualified for the outpatient observation or had to be admitted for the inpatient observation,” she noted.
 

Community Outcomes Were Comparable to Major Trial

As for the results, grade 3 or higher adverse events occurred at a similar frequency among outpatients and inpatients at 74% and 76%, Linhares said. There were no grade 5 adverse events, and 25% of patients treated as outpatients were never hospitalized. 

Response rates were similar to those in the major TRANSCEND trial with the objective response rates rate of 80% and complete response rates of 54%.

“Overall,” Linhares said, “our study demonstrated that with the availability of standard operating procedures, specially trained staff and a multidisciplinary team trained in CAR T toxicity management, inpatient and outpatient CAR T administration is feasible at specialized community medical centers.”

In 2023, another study examined patients with B-cell non-Hodgkin lymphoma who were treated on an outpatient basis with tisagenlecleucel. Researchers reported that outpatient therapy was “feasible and associated with similar efficacy outcomes as inpatient treatment.”

And a 2023 systematic literature review identified 11 studies that reported outpatient vs inpatient outcomes in CAR T-cell therapy and found “comparable response rates (80-82% in outpatient and 72-80% in inpatient).” Costs were cheaper in the outpatient setting. 

Research findings like these are good news, Baylor College of Medicine’s Badr said. “Outpatient administration could help to scale the availability of this therapy to a broader range of healthcare settings, including those serving underserved populations. Findings indicate promising safety profiles, which is encouraging for expanding access.”
 

Not Every Patient Can Tolerate Outpatient Care

Linhares noted that the patients who received outpatient care in the lisocabtagene maraleucel study were in better shape than those in the inpatient group. Those selected for inpatient care had “higher disease risk characteristics, including high grade B cell lymphoma histology, higher disease burden, and having received bridging therapy. This points to the fact that the investigators properly selected patients who were at a higher risk of complications for inpatient observation. Additionally, some patients stayed as inpatient due to social factors, which increases length of stay independently of disease characteristics.”

Specifically, reasons for inpatient monitoring were disease characteristics (48%) including tumor burden and risk of adverse events; psychosocial factors (32%) including lack of caregiver support or transportation; COVID-19 precautions (8%); pre-infusion adverse events (8%) of fever and vasovagal reaction; and principal investigator decision (4%) due to limited hospital experience with CAR T-cell therapy.

Texas Children’s Cancer Center’s Rouce said “certain patients, particularly those with higher risk for complications or those who require intensive monitoring, may not be suited for outpatient CAR T-cell therapy. This may be due to other comorbidities or baseline factors known to predispose to CAR T-related toxicities. However, evidence-based risk mitigation algorithms may still allow closely monitored outpatient treatment, with recognition that hospital admission for incipient side effects may be necessary.”
 

What’s Next for Access to Therapy?

Rouce noted that her institution, like many others, is offering CAR T-cell therapy on an outpatient basis. “Additionally, continued scientific innovation, such as immediately available, off-the-shelf cell therapies and inducible safety switches, will ultimately improve access,” she said. 

Linhares noted a recent advance and highlighted research that’s now in progress. “CAR Ts now have an indication as a second-line therapy in relapsed/refractory large B-cell lymphoma, and there are ongoing clinical trials that will potentially move CAR Ts into the first line,” she said. “Some trials are exploring allogeneic, readily available off-the-shelf CAR T for the treatment of minimal residual disease positive large B-cell lymphoma after completion of first-line therapy.”

These potential advances “are increasing the need for CAR T-capable medical centers,” Linhares noted. “More and more medical centers with expert hematology teams are becoming CAR T-certified, with more patients having access to CAR T.”

Still, she said, “I don’t think access is nearly as good as it should be. Many patients in rural areas are still unable to get this life-saving treatment. “However, “it is very possible that other novel targeted therapies, such as bispecific antibodies, will be used in place of CAR T in areas with poor CAR T access. Bispecific antibody efficacy in various B cell lymphoma histologies are being currently explored.”

Rouce discloses relationships with Novartis and Pfizer. Linhares reports ties with Kyowa Kirin, AbbVie, ADC, BeiGene, Genentech, Gilead, GlaxoSmithKline, Seagen, and TG. Badr has no disclosures. 
 

A version of this article appeared on Medscape.com.

Approximately one third of parents of children with atopic dermatitis reported little or no improvement with elimination diets, and nearly 80% reintroduced the eliminated foods, based on survey data from nearly 300 parents.

Although atopic dermatitis can be associated with an increased risk for food allergies, major allergy organizations do not currently recommend elimination diets as a treatment for atopic dermatitis, said Nadia Makkoukdji, MD, a pediatrician at Jackson Memorial Hospital, Miami, in a presentation at the American College of Allergy, Asthma, and Immunology (ACAAI) Annual Scientific Meeting.

“A fear of drastic dietary changes often prevents families from seeking the care their children need,” Makkoukdji said in an interview. In the clinical setting, Makkoukdji noted that she has seen many patients who have started food elimination diets on their own or as recommended by other doctors, and that these diets can lead to dangers such as the development of immunoglobulin E–mediated food allergies on reintroduction of eliminated foods and malnutrition. They can also produce “emotional stress in children and anxiety or depression, while also adding stress to parents and the entire family.”

Makkoukdji conducted the study to explore parents’ perceptions of these diets in management of their children’s atopic dermatitis, she said.

In the study, Makkoukdji and colleagues sought to understand parents’ perceptions of the role of diet in atopic dermatitis in their children. The researchers reviewed surveys from 298 parents of children with atopic dermatitis who were seen at a single academic center. Parents completed the surveys in the emergency department or in an allergy, dermatology, and general pediatrics clinic.

Overall, 42% of parents identified food triggers for their child’s atopic dermatitis. The most commonly identified triggers were milk (32%), tree nuts/seeds/peanuts (16%), and eggs (11%).

Of the parents who reported food triggers, 23% removed the suspected trigger food from the child’s diet completely, 20% removed suspected trigger foods from their own diets while breastfeeding, and 19% changed their infant’s formula.

In the wake of the elimination diets, 38% of the parents reported no improvement in their child’s atopic dermatitis, 35% reported a 25% improvement, and 9% reported complete resolution. The majority (79%) reintroduced eliminated foods and reported no recurrence of atopic dermatitis symptoms.

The researchers were surprised by how many parents changed their child’s diet in the belief that certain foods exacerbated their child’s atopic dermatitis, “although this perception aligns with the common concern that food allergens can trigger or worsen atopic dermatitis flares,” Makkoukdji said.

The current study highlights the need for more awareness of the limited impact of dietary modifications on atopic dermatitis in the absence of confirmed food allergies, Makkoukdji said. “Our study shows that food elimination diets are still commonly being used by parents in the local Miami population.”

The findings were limited by several factors, including the use of data from a single center and the focus only on pediatric patients, but the primary goal was to assess parental perceptions of AD flares in relation to dietary choices, said Makkoukdji. “Future studies that include larger and more diverse populations would be valuable for the field.”
 

Dietary Modifications Don’t Live Up to Hype

“Food continues to be one of the most discussed aspects of atopic dermatitis,” Peter Lio, MD, clinical assistant professor of dermatology and pediatrics at Northwestern University Feinberg School of Medicine, Chicago, Illinois, said in an interview.

“Almost all of my patients and families ask about dietary modifications, even though almost all of them have experimented with it to some degree,” said Lio. In his experience, diet plays a small role, if any, in the day-to-day management of atopic dermatitis.

This lack of effect of dietary changes is often frustrating to patients because of the persistent “common wisdom” that points to diet as a root cause of atopic dermatitis, Lio said. “Many practitioners continue to recommend excluding foods such as gluten or dairy from the diet, but generally these are only of modest help,” and although patients wish that dietary changes would fix the problem, most are left wondering why these changes didn’t help them.

The current study findings “reflect my own experience after nearly 20 years of being deeply immersed in the world of atopic dermatitis,” Lio said. Although the takeaway message does not argue against eating healthy foods, some foods do seem to make AD worse in some patients and may have nonallergic pro-inflammatory effects.

“In those cases, it is reasonable to limit or avoid those foods. However, it is extremely difficult to tell what food or foods are driving flare-ups when things are out of control, so dietary modification is generally not the best place to start,” he said.

True food allergies are much more common in patients with atopic dermatitis compared with individuals without atopic dermatitis, but the current study is not addressing these types of allergies, Lio emphasized. “If someone has true allergy to peanuts, for example, they should not be eating them; we also know that they are not ‘cheating’ because these patients would not merely have an eczema flare; they would have urticaria, angioedema, or anaphylaxis. There is tremendous confusion around this point and lots of confusion around allergy testing and its limitations.”

In addition, patients with atopic dermatitis are more likely than those without atopic dermatitis to have abnormalities in the gut microbiome and gut barrier, Lio said.

Abnormalities in the gut microbiome are different from the concept of allergy and may fall into the more complex category of barrier and microbiome disruptors, he said. Therefore, “the food category may not be nearly as important as the specific preparation of the food along with the additives (such as preservatives and emulsifiers) that may actually be driving the problem.”

Although in the past many clinicians advised patients to try cutting out certain foods to see whether atopic dermatitis symptoms improved, this strategy is not without risk, said Lio. “There have been incredible advancements in understanding the role of the gut in tolerization to foods.” Recent research has shown that by eating foods regularly, particularly those such as peanuts that seem to have more allergic potential, the body becomes tolerant, and this prevents the development of true food allergies.

As for additional research, many questions remain about the effects of types of foods, processing methods, and timing of introduction of foods on atopic dermatitis, Lio noted.

“Atopic dermatitis is a systemic condition with the immune system, with the skin/gut/respiratory barriers and microbiome involved; I think we now have a broader view of how big and complex the landscape really is,” he said.

The study received no outside funding. The researchers had no financial conflicts to disclose. Lio had no disclosures relevant to elimination diets but disclosed serving on the speakers bureau for AbbVie, Arcutis Biotherapeutics, Eli Lilly, Galderma, Hyphens Pharma, Incyte, La Roche–Posay/L’Oréal, Pfizer, Pierre Fabre Dermatologie, Regeneron/Sanofi Genzyme, and Verrica Pharmaceuticals; serving on consulting/advisory boards; or having stock options for many pharmaceutical companies. Lio also disclosed a patent pending for a Theraplex product with royalties paid and is a board member and Scientific Advisory Committee member emeritus of the National Eczema Association.

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

Approximately one third of parents of children with atopic dermatitis reported little or no improvement with elimination diets, and nearly 80% reintroduced the eliminated foods, based on survey data from nearly 300 parents.

Although atopic dermatitis can be associated with an increased risk for food allergies, major allergy organizations do not currently recommend elimination diets as a treatment for atopic dermatitis, said Nadia Makkoukdji, MD, a pediatrician at Jackson Memorial Hospital, Miami, in a presentation at the American College of Allergy, Asthma, and Immunology (ACAAI) Annual Scientific Meeting.

“A fear of drastic dietary changes often prevents families from seeking the care their children need,” Makkoukdji said in an interview. In the clinical setting, Makkoukdji noted that she has seen many patients who have started food elimination diets on their own or as recommended by other doctors, and that these diets can lead to dangers such as the development of immunoglobulin E–mediated food allergies on reintroduction of eliminated foods and malnutrition. They can also produce “emotional stress in children and anxiety or depression, while also adding stress to parents and the entire family.”

Makkoukdji conducted the study to explore parents’ perceptions of these diets in management of their children’s atopic dermatitis, she said.

In the study, Makkoukdji and colleagues sought to understand parents’ perceptions of the role of diet in atopic dermatitis in their children. The researchers reviewed surveys from 298 parents of children with atopic dermatitis who were seen at a single academic center. Parents completed the surveys in the emergency department or in an allergy, dermatology, and general pediatrics clinic.

Overall, 42% of parents identified food triggers for their child’s atopic dermatitis. The most commonly identified triggers were milk (32%), tree nuts/seeds/peanuts (16%), and eggs (11%).

Of the parents who reported food triggers, 23% removed the suspected trigger food from the child’s diet completely, 20% removed suspected trigger foods from their own diets while breastfeeding, and 19% changed their infant’s formula.

In the wake of the elimination diets, 38% of the parents reported no improvement in their child’s atopic dermatitis, 35% reported a 25% improvement, and 9% reported complete resolution. The majority (79%) reintroduced eliminated foods and reported no recurrence of atopic dermatitis symptoms.

The researchers were surprised by how many parents changed their child’s diet in the belief that certain foods exacerbated their child’s atopic dermatitis, “although this perception aligns with the common concern that food allergens can trigger or worsen atopic dermatitis flares,” Makkoukdji said.

The current study highlights the need for more awareness of the limited impact of dietary modifications on atopic dermatitis in the absence of confirmed food allergies, Makkoukdji said. “Our study shows that food elimination diets are still commonly being used by parents in the local Miami population.”

The findings were limited by several factors, including the use of data from a single center and the focus only on pediatric patients, but the primary goal was to assess parental perceptions of AD flares in relation to dietary choices, said Makkoukdji. “Future studies that include larger and more diverse populations would be valuable for the field.”
 

Dietary Modifications Don’t Live Up to Hype

“Food continues to be one of the most discussed aspects of atopic dermatitis,” Peter Lio, MD, clinical assistant professor of dermatology and pediatrics at Northwestern University Feinberg School of Medicine, Chicago, Illinois, said in an interview.

“Almost all of my patients and families ask about dietary modifications, even though almost all of them have experimented with it to some degree,” said Lio. In his experience, diet plays a small role, if any, in the day-to-day management of atopic dermatitis.

This lack of effect of dietary changes is often frustrating to patients because of the persistent “common wisdom” that points to diet as a root cause of atopic dermatitis, Lio said. “Many practitioners continue to recommend excluding foods such as gluten or dairy from the diet, but generally these are only of modest help,” and although patients wish that dietary changes would fix the problem, most are left wondering why these changes didn’t help them.

The current study findings “reflect my own experience after nearly 20 years of being deeply immersed in the world of atopic dermatitis,” Lio said. Although the takeaway message does not argue against eating healthy foods, some foods do seem to make AD worse in some patients and may have nonallergic pro-inflammatory effects.

“In those cases, it is reasonable to limit or avoid those foods. However, it is extremely difficult to tell what food or foods are driving flare-ups when things are out of control, so dietary modification is generally not the best place to start,” he said.

True food allergies are much more common in patients with atopic dermatitis compared with individuals without atopic dermatitis, but the current study is not addressing these types of allergies, Lio emphasized. “If someone has true allergy to peanuts, for example, they should not be eating them; we also know that they are not ‘cheating’ because these patients would not merely have an eczema flare; they would have urticaria, angioedema, or anaphylaxis. There is tremendous confusion around this point and lots of confusion around allergy testing and its limitations.”

In addition, patients with atopic dermatitis are more likely than those without atopic dermatitis to have abnormalities in the gut microbiome and gut barrier, Lio said.

Abnormalities in the gut microbiome are different from the concept of allergy and may fall into the more complex category of barrier and microbiome disruptors, he said. Therefore, “the food category may not be nearly as important as the specific preparation of the food along with the additives (such as preservatives and emulsifiers) that may actually be driving the problem.”

Although in the past many clinicians advised patients to try cutting out certain foods to see whether atopic dermatitis symptoms improved, this strategy is not without risk, said Lio. “There have been incredible advancements in understanding the role of the gut in tolerization to foods.” Recent research has shown that by eating foods regularly, particularly those such as peanuts that seem to have more allergic potential, the body becomes tolerant, and this prevents the development of true food allergies.

As for additional research, many questions remain about the effects of types of foods, processing methods, and timing of introduction of foods on atopic dermatitis, Lio noted.

“Atopic dermatitis is a systemic condition with the immune system, with the skin/gut/respiratory barriers and microbiome involved; I think we now have a broader view of how big and complex the landscape really is,” he said.

The study received no outside funding. The researchers had no financial conflicts to disclose. Lio had no disclosures relevant to elimination diets but disclosed serving on the speakers bureau for AbbVie, Arcutis Biotherapeutics, Eli Lilly, Galderma, Hyphens Pharma, Incyte, La Roche–Posay/L’Oréal, Pfizer, Pierre Fabre Dermatologie, Regeneron/Sanofi Genzyme, and Verrica Pharmaceuticals; serving on consulting/advisory boards; or having stock options for many pharmaceutical companies. Lio also disclosed a patent pending for a Theraplex product with royalties paid and is a board member and Scientific Advisory Committee member emeritus of the National Eczema Association.

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

Approximately one third of parents of children with atopic dermatitis reported little or no improvement with elimination diets, and nearly 80% reintroduced the eliminated foods, based on survey data from nearly 300 parents.

Although atopic dermatitis can be associated with an increased risk for food allergies, major allergy organizations do not currently recommend elimination diets as a treatment for atopic dermatitis, said Nadia Makkoukdji, MD, a pediatrician at Jackson Memorial Hospital, Miami, in a presentation at the American College of Allergy, Asthma, and Immunology (ACAAI) Annual Scientific Meeting.

“A fear of drastic dietary changes often prevents families from seeking the care their children need,” Makkoukdji said in an interview. In the clinical setting, Makkoukdji noted that she has seen many patients who have started food elimination diets on their own or as recommended by other doctors, and that these diets can lead to dangers such as the development of immunoglobulin E–mediated food allergies on reintroduction of eliminated foods and malnutrition. They can also produce “emotional stress in children and anxiety or depression, while also adding stress to parents and the entire family.”

Makkoukdji conducted the study to explore parents’ perceptions of these diets in management of their children’s atopic dermatitis, she said.

In the study, Makkoukdji and colleagues sought to understand parents’ perceptions of the role of diet in atopic dermatitis in their children. The researchers reviewed surveys from 298 parents of children with atopic dermatitis who were seen at a single academic center. Parents completed the surveys in the emergency department or in an allergy, dermatology, and general pediatrics clinic.

Overall, 42% of parents identified food triggers for their child’s atopic dermatitis. The most commonly identified triggers were milk (32%), tree nuts/seeds/peanuts (16%), and eggs (11%).

Of the parents who reported food triggers, 23% removed the suspected trigger food from the child’s diet completely, 20% removed suspected trigger foods from their own diets while breastfeeding, and 19% changed their infant’s formula.

In the wake of the elimination diets, 38% of the parents reported no improvement in their child’s atopic dermatitis, 35% reported a 25% improvement, and 9% reported complete resolution. The majority (79%) reintroduced eliminated foods and reported no recurrence of atopic dermatitis symptoms.

The researchers were surprised by how many parents changed their child’s diet in the belief that certain foods exacerbated their child’s atopic dermatitis, “although this perception aligns with the common concern that food allergens can trigger or worsen atopic dermatitis flares,” Makkoukdji said.

The current study highlights the need for more awareness of the limited impact of dietary modifications on atopic dermatitis in the absence of confirmed food allergies, Makkoukdji said. “Our study shows that food elimination diets are still commonly being used by parents in the local Miami population.”

The findings were limited by several factors, including the use of data from a single center and the focus only on pediatric patients, but the primary goal was to assess parental perceptions of AD flares in relation to dietary choices, said Makkoukdji. “Future studies that include larger and more diverse populations would be valuable for the field.”
 

Dietary Modifications Don’t Live Up to Hype

“Food continues to be one of the most discussed aspects of atopic dermatitis,” Peter Lio, MD, clinical assistant professor of dermatology and pediatrics at Northwestern University Feinberg School of Medicine, Chicago, Illinois, said in an interview.

“Almost all of my patients and families ask about dietary modifications, even though almost all of them have experimented with it to some degree,” said Lio. In his experience, diet plays a small role, if any, in the day-to-day management of atopic dermatitis.

This lack of effect of dietary changes is often frustrating to patients because of the persistent “common wisdom” that points to diet as a root cause of atopic dermatitis, Lio said. “Many practitioners continue to recommend excluding foods such as gluten or dairy from the diet, but generally these are only of modest help,” and although patients wish that dietary changes would fix the problem, most are left wondering why these changes didn’t help them.

The current study findings “reflect my own experience after nearly 20 years of being deeply immersed in the world of atopic dermatitis,” Lio said. Although the takeaway message does not argue against eating healthy foods, some foods do seem to make AD worse in some patients and may have nonallergic pro-inflammatory effects.

“In those cases, it is reasonable to limit or avoid those foods. However, it is extremely difficult to tell what food or foods are driving flare-ups when things are out of control, so dietary modification is generally not the best place to start,” he said.

True food allergies are much more common in patients with atopic dermatitis compared with individuals without atopic dermatitis, but the current study is not addressing these types of allergies, Lio emphasized. “If someone has true allergy to peanuts, for example, they should not be eating them; we also know that they are not ‘cheating’ because these patients would not merely have an eczema flare; they would have urticaria, angioedema, or anaphylaxis. There is tremendous confusion around this point and lots of confusion around allergy testing and its limitations.”

In addition, patients with atopic dermatitis are more likely than those without atopic dermatitis to have abnormalities in the gut microbiome and gut barrier, Lio said.

Abnormalities in the gut microbiome are different from the concept of allergy and may fall into the more complex category of barrier and microbiome disruptors, he said. Therefore, “the food category may not be nearly as important as the specific preparation of the food along with the additives (such as preservatives and emulsifiers) that may actually be driving the problem.”

Although in the past many clinicians advised patients to try cutting out certain foods to see whether atopic dermatitis symptoms improved, this strategy is not without risk, said Lio. “There have been incredible advancements in understanding the role of the gut in tolerization to foods.” Recent research has shown that by eating foods regularly, particularly those such as peanuts that seem to have more allergic potential, the body becomes tolerant, and this prevents the development of true food allergies.

As for additional research, many questions remain about the effects of types of foods, processing methods, and timing of introduction of foods on atopic dermatitis, Lio noted.

“Atopic dermatitis is a systemic condition with the immune system, with the skin/gut/respiratory barriers and microbiome involved; I think we now have a broader view of how big and complex the landscape really is,” he said.

The study received no outside funding. The researchers had no financial conflicts to disclose. Lio had no disclosures relevant to elimination diets but disclosed serving on the speakers bureau for AbbVie, Arcutis Biotherapeutics, Eli Lilly, Galderma, Hyphens Pharma, Incyte, La Roche–Posay/L’Oréal, Pfizer, Pierre Fabre Dermatologie, Regeneron/Sanofi Genzyme, and Verrica Pharmaceuticals; serving on consulting/advisory boards; or having stock options for many pharmaceutical companies. Lio also disclosed a patent pending for a Theraplex product with royalties paid and is a board member and Scientific Advisory Committee member emeritus of the National Eczema Association.

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