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Children With Severe Atopic Dermatitis Catch Up on Growth With Dupilumab
AMSTERDAM — , 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 — , 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 — , 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.
FROM EADV 2024
Nemolizumab Benefits for Atopic Dermatitis Maintained in Long-Term Follow-Up Study
(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.
(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.
(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.
FROM EADV 2024
Lichen Planus Responds to Treatment with Topical Ruxolitinib in Phase 2 Study
both when given twice daily and as needed, according to data from a phase 2 trial.
The research, presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress, involved 64 patients older than 18 years. Ruxolitinib cream (Opzelura) is a topical formulation of a Janus kinase (JAK)1/JAK2 inhibitor, approved by the Food and Drug Administration (FDA) for treating mild to moderate atopic dermatitis and for nonsegmental vitiligo in adults and children aged 12 years or older.
Ruxolitinib cream twice daily resulted in “significant improvements in cutaneous lichen planus disease severity vs vehicle” after 16 weeks of treatment, said the study presenter, Aaron R. Mangold, MD, a dermatologist at Mayo Clinic, Scottsdale, Arizona.
Further improvements were seen during another 16 weeks of additional open-label, as-needed application, he added, and the topical treatment was “generally well tolerated.”
Consequently, “ruxolitinib cream represents a promising potential treatment for cutaneous lichen planus,” Mangold concluded.
Asked to comment on the results, Adam Friedman, MD, Professor and Chair of Dermatology, George Washington University, Washington, DC, who was not involved with the study, said that in keeping with the characterization of lichen planus using the four Ps — purple, polygonal, pruritic, papules — it is “Pretty common, Predictably disabling and disfiguring, and Passed over again and again in the drug development world.”
He said in an interview that this chronic inflammatory skin condition, which affects roughly 2% of the population, also “lacks consensus on work-up and management, likely in part owing to the absence of sizable clinical trial data.”
A recent survey conducted at a meeting indicated that dermatologists “heavily lean on topical therapies for the management of all severity levels,” noted Friedman, one of the survey authors. “Therefore, the phase 2 data presented at EADV is a welcome addition to the mix.”
Phase 2 Study Results
At the meeting, Mangold said that a previous proof-of-concept single-arm study in 12 patients suggested that topical ruxolitinib was highly effective in treating cutaneous lichen planus.
The current phase 2 trial enrolled 64 patients with predominantly cutaneous disease who had an Investigator’s Global Assessment (IGA) score of 3 or 4 and an Itch Numeric Rating Scale (NRS) score of ≥ 4. Their median age was 57 years, and 71.9% were women. Nearly 63% were White, 28.1% were Black, and 6.3% were Asian. The median duration of disease was 4.9 years, and 90.6% had received prior treatment for their lichen planus.
They were randomized to receive 1.5% ruxolitinib cream or a vehicle cream twice daily for 16 weeks, and following a primary endpoint assessment, they were transferred to an open-label extension period, during which they used ruxolitinib cream as needed for another 16 weeks. There was an additional 30-day safety follow-up period.
At week 16, significantly more patients treated with the ruxolitinib cream (50.0%) vs vehicle cream (21.9%) achieved IGA treatment success (the primary endpoint), defined as an IGA score of 0 or 1 with ≥ 2-grade improvement from baseline (odds ratio, 4.04; P = .0129).
In the open-label extension, when all patients used the active cream as needed, the proportion achieving IGA treatment success increased to 60% among the patients originally treated with ruxolitinib cream and 60.9% among those who switched from the vehicle cream.
A similar pattern was seen with Itch NRS scores. At 16 weeks, 57.7% of those treated with the ruxolitinib cream and 19.2% of those given the vehicle cream achieved an Itch NRS score of ≥ 4 (P < .01), rising to 84.2% and 73.3%, respectively, during the open-label extension.
The time to achievement of an Itch NRS of ≥ 4 was also significantly shorter with the ruxolitinib cream than with the vehicle cream (median days, 17 vs 97; hazard ratio, 2.85; P = .0008).
In both treatment groups, Skin Pain NRS scores decreased by a mean of 3.0 with ruxolitinib cream and 1.3 with the vehicle cream at week 16. By the end of the open-label extension, scores dropped by 4.3 among those who continued on active treatment and by 3.5 among those who switched from vehicle to topical ruxolitinib.
There were few treatment-emergent adverse events, with just three ruxolitinib patients affected during the randomized phase of the trial. There was one grade ≥ 3 event considered unrelated to the study drug, and no serious treatment-emergent adverse events were reported.
The most common adverse events during the randomized period were nasopharyngitis, hypertension, and contusion, all experienced by fewer than 10% of patients, whereas sinusitis, increased blood cholesterol levels, and increased blood creatine phosphokinase were most common in the open-label extension, experienced by no more than 5% of patients.
In the interview, Friedman commented that “these data provide hope that one day soon, there will be an FDA-approved, effective, and well-tolerated approach for this condition, validating the patient and supporting the dermatologist with an evidence-based option.”
The study was funded by Incyte. Mangold declared relationships with Argenx, Boehringer Ingelheim, Bristol-Myers Squibb, Clarivate, Incyte Corporation, Janssen, Nuvig Therapeutics, Pfizer, Regeneron Pharmaceuticals, Soligenix, Tourmaline Bio, AbbVie, Corbus, Eli Lilly, Kyowa, Merck, miRagen Therapeutics, Palvella Therapeutics, Priovant Therapeutics, and Adelphi Values. Friedman declared a relationship with Incyte, but it is not related to this topic.
A version of this article first appeared on Medscape.com.
both when given twice daily and as needed, according to data from a phase 2 trial.
The research, presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress, involved 64 patients older than 18 years. Ruxolitinib cream (Opzelura) is a topical formulation of a Janus kinase (JAK)1/JAK2 inhibitor, approved by the Food and Drug Administration (FDA) for treating mild to moderate atopic dermatitis and for nonsegmental vitiligo in adults and children aged 12 years or older.
Ruxolitinib cream twice daily resulted in “significant improvements in cutaneous lichen planus disease severity vs vehicle” after 16 weeks of treatment, said the study presenter, Aaron R. Mangold, MD, a dermatologist at Mayo Clinic, Scottsdale, Arizona.
Further improvements were seen during another 16 weeks of additional open-label, as-needed application, he added, and the topical treatment was “generally well tolerated.”
Consequently, “ruxolitinib cream represents a promising potential treatment for cutaneous lichen planus,” Mangold concluded.
Asked to comment on the results, Adam Friedman, MD, Professor and Chair of Dermatology, George Washington University, Washington, DC, who was not involved with the study, said that in keeping with the characterization of lichen planus using the four Ps — purple, polygonal, pruritic, papules — it is “Pretty common, Predictably disabling and disfiguring, and Passed over again and again in the drug development world.”
He said in an interview that this chronic inflammatory skin condition, which affects roughly 2% of the population, also “lacks consensus on work-up and management, likely in part owing to the absence of sizable clinical trial data.”
A recent survey conducted at a meeting indicated that dermatologists “heavily lean on topical therapies for the management of all severity levels,” noted Friedman, one of the survey authors. “Therefore, the phase 2 data presented at EADV is a welcome addition to the mix.”
Phase 2 Study Results
At the meeting, Mangold said that a previous proof-of-concept single-arm study in 12 patients suggested that topical ruxolitinib was highly effective in treating cutaneous lichen planus.
The current phase 2 trial enrolled 64 patients with predominantly cutaneous disease who had an Investigator’s Global Assessment (IGA) score of 3 or 4 and an Itch Numeric Rating Scale (NRS) score of ≥ 4. Their median age was 57 years, and 71.9% were women. Nearly 63% were White, 28.1% were Black, and 6.3% were Asian. The median duration of disease was 4.9 years, and 90.6% had received prior treatment for their lichen planus.
They were randomized to receive 1.5% ruxolitinib cream or a vehicle cream twice daily for 16 weeks, and following a primary endpoint assessment, they were transferred to an open-label extension period, during which they used ruxolitinib cream as needed for another 16 weeks. There was an additional 30-day safety follow-up period.
At week 16, significantly more patients treated with the ruxolitinib cream (50.0%) vs vehicle cream (21.9%) achieved IGA treatment success (the primary endpoint), defined as an IGA score of 0 or 1 with ≥ 2-grade improvement from baseline (odds ratio, 4.04; P = .0129).
In the open-label extension, when all patients used the active cream as needed, the proportion achieving IGA treatment success increased to 60% among the patients originally treated with ruxolitinib cream and 60.9% among those who switched from the vehicle cream.
A similar pattern was seen with Itch NRS scores. At 16 weeks, 57.7% of those treated with the ruxolitinib cream and 19.2% of those given the vehicle cream achieved an Itch NRS score of ≥ 4 (P < .01), rising to 84.2% and 73.3%, respectively, during the open-label extension.
The time to achievement of an Itch NRS of ≥ 4 was also significantly shorter with the ruxolitinib cream than with the vehicle cream (median days, 17 vs 97; hazard ratio, 2.85; P = .0008).
In both treatment groups, Skin Pain NRS scores decreased by a mean of 3.0 with ruxolitinib cream and 1.3 with the vehicle cream at week 16. By the end of the open-label extension, scores dropped by 4.3 among those who continued on active treatment and by 3.5 among those who switched from vehicle to topical ruxolitinib.
There were few treatment-emergent adverse events, with just three ruxolitinib patients affected during the randomized phase of the trial. There was one grade ≥ 3 event considered unrelated to the study drug, and no serious treatment-emergent adverse events were reported.
The most common adverse events during the randomized period were nasopharyngitis, hypertension, and contusion, all experienced by fewer than 10% of patients, whereas sinusitis, increased blood cholesterol levels, and increased blood creatine phosphokinase were most common in the open-label extension, experienced by no more than 5% of patients.
In the interview, Friedman commented that “these data provide hope that one day soon, there will be an FDA-approved, effective, and well-tolerated approach for this condition, validating the patient and supporting the dermatologist with an evidence-based option.”
The study was funded by Incyte. Mangold declared relationships with Argenx, Boehringer Ingelheim, Bristol-Myers Squibb, Clarivate, Incyte Corporation, Janssen, Nuvig Therapeutics, Pfizer, Regeneron Pharmaceuticals, Soligenix, Tourmaline Bio, AbbVie, Corbus, Eli Lilly, Kyowa, Merck, miRagen Therapeutics, Palvella Therapeutics, Priovant Therapeutics, and Adelphi Values. Friedman declared a relationship with Incyte, but it is not related to this topic.
A version of this article first appeared on Medscape.com.
both when given twice daily and as needed, according to data from a phase 2 trial.
The research, presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress, involved 64 patients older than 18 years. Ruxolitinib cream (Opzelura) is a topical formulation of a Janus kinase (JAK)1/JAK2 inhibitor, approved by the Food and Drug Administration (FDA) for treating mild to moderate atopic dermatitis and for nonsegmental vitiligo in adults and children aged 12 years or older.
Ruxolitinib cream twice daily resulted in “significant improvements in cutaneous lichen planus disease severity vs vehicle” after 16 weeks of treatment, said the study presenter, Aaron R. Mangold, MD, a dermatologist at Mayo Clinic, Scottsdale, Arizona.
Further improvements were seen during another 16 weeks of additional open-label, as-needed application, he added, and the topical treatment was “generally well tolerated.”
Consequently, “ruxolitinib cream represents a promising potential treatment for cutaneous lichen planus,” Mangold concluded.
Asked to comment on the results, Adam Friedman, MD, Professor and Chair of Dermatology, George Washington University, Washington, DC, who was not involved with the study, said that in keeping with the characterization of lichen planus using the four Ps — purple, polygonal, pruritic, papules — it is “Pretty common, Predictably disabling and disfiguring, and Passed over again and again in the drug development world.”
He said in an interview that this chronic inflammatory skin condition, which affects roughly 2% of the population, also “lacks consensus on work-up and management, likely in part owing to the absence of sizable clinical trial data.”
A recent survey conducted at a meeting indicated that dermatologists “heavily lean on topical therapies for the management of all severity levels,” noted Friedman, one of the survey authors. “Therefore, the phase 2 data presented at EADV is a welcome addition to the mix.”
Phase 2 Study Results
At the meeting, Mangold said that a previous proof-of-concept single-arm study in 12 patients suggested that topical ruxolitinib was highly effective in treating cutaneous lichen planus.
The current phase 2 trial enrolled 64 patients with predominantly cutaneous disease who had an Investigator’s Global Assessment (IGA) score of 3 or 4 and an Itch Numeric Rating Scale (NRS) score of ≥ 4. Their median age was 57 years, and 71.9% were women. Nearly 63% were White, 28.1% were Black, and 6.3% were Asian. The median duration of disease was 4.9 years, and 90.6% had received prior treatment for their lichen planus.
They were randomized to receive 1.5% ruxolitinib cream or a vehicle cream twice daily for 16 weeks, and following a primary endpoint assessment, they were transferred to an open-label extension period, during which they used ruxolitinib cream as needed for another 16 weeks. There was an additional 30-day safety follow-up period.
At week 16, significantly more patients treated with the ruxolitinib cream (50.0%) vs vehicle cream (21.9%) achieved IGA treatment success (the primary endpoint), defined as an IGA score of 0 or 1 with ≥ 2-grade improvement from baseline (odds ratio, 4.04; P = .0129).
In the open-label extension, when all patients used the active cream as needed, the proportion achieving IGA treatment success increased to 60% among the patients originally treated with ruxolitinib cream and 60.9% among those who switched from the vehicle cream.
A similar pattern was seen with Itch NRS scores. At 16 weeks, 57.7% of those treated with the ruxolitinib cream and 19.2% of those given the vehicle cream achieved an Itch NRS score of ≥ 4 (P < .01), rising to 84.2% and 73.3%, respectively, during the open-label extension.
The time to achievement of an Itch NRS of ≥ 4 was also significantly shorter with the ruxolitinib cream than with the vehicle cream (median days, 17 vs 97; hazard ratio, 2.85; P = .0008).
In both treatment groups, Skin Pain NRS scores decreased by a mean of 3.0 with ruxolitinib cream and 1.3 with the vehicle cream at week 16. By the end of the open-label extension, scores dropped by 4.3 among those who continued on active treatment and by 3.5 among those who switched from vehicle to topical ruxolitinib.
There were few treatment-emergent adverse events, with just three ruxolitinib patients affected during the randomized phase of the trial. There was one grade ≥ 3 event considered unrelated to the study drug, and no serious treatment-emergent adverse events were reported.
The most common adverse events during the randomized period were nasopharyngitis, hypertension, and contusion, all experienced by fewer than 10% of patients, whereas sinusitis, increased blood cholesterol levels, and increased blood creatine phosphokinase were most common in the open-label extension, experienced by no more than 5% of patients.
In the interview, Friedman commented that “these data provide hope that one day soon, there will be an FDA-approved, effective, and well-tolerated approach for this condition, validating the patient and supporting the dermatologist with an evidence-based option.”
The study was funded by Incyte. Mangold declared relationships with Argenx, Boehringer Ingelheim, Bristol-Myers Squibb, Clarivate, Incyte Corporation, Janssen, Nuvig Therapeutics, Pfizer, Regeneron Pharmaceuticals, Soligenix, Tourmaline Bio, AbbVie, Corbus, Eli Lilly, Kyowa, Merck, miRagen Therapeutics, Palvella Therapeutics, Priovant Therapeutics, and Adelphi Values. Friedman declared a relationship with Incyte, but it is not related to this topic.
A version of this article first appeared on Medscape.com.
FROM EADV 2024
Study Finds No Increased MACE Risk for JAK Inhibitors in Patients With Atopic Dermatitis
, suggested the results of a large, US-based, retrospective cohort study.
This holds true even in individuals aged 50 years or older, whose age puts them at increased cardiovascular (CV) risk, said Amina El Ayadi, PhD, of the University of Texas Medical Branch at Galveston. He presented the findings at the recent European Academy of Dermatology and Venereology (EADV) 2024 Congress.
Specifically, the analysis looked at treatment with the oral JAK1 inhibitors upadacitinib (Rinvoq) and abrocitinib (Cibinqo), both approved for treating AD in the United States, and found that the relative risk for MACE, such as acute myocardial infarction, cardiac arrest, stroke, or acute deep vein thrombosis, was ≤ 1.0 compared with those not treated with a JAKi.
Similarly, the relative risk for other CV safety endpoints, such as having an abnormal ECG or pericardial effusion, was also around 1.0. There was a slight increase in the relative risk for arrhythmias, peripheral edema, angina pectoris, or heart failure, but no value went > 1.6 and CIs spanned 1.0, indicating the results lack statistical significance.
Reassurance for Dermatologists?
“This suggests that oral administration of these drugs to the patient with atopic dermatitis does not increase the risk of major adverse cardiac events, and dermatologists, based on our data, can safely consider JAK inhibitors for treating moderate to severe dermatitis, even in patients with high risk for these diseases,” El Ayadi said during a late-breaking news session at the meeting.
Yolanda Gilaberte Calzada, MD, PhD, head of the Dermatology Department at Miguel Servet University Hospital in Zaragoza, Spain, who was one of the chairs for the session, said that this was “very good news for us.”
Gilaberte Calzada, president of the Spanish Academy of Dermatology and Venereology, asked if there were any data on the duration of treatment with the two JAKis included in the analysis. El Ayadi said that this was something that would be looked at in future data analyses.
Gilaberte Calzada also observed that because the CIs were wide, with more time, “we will have more defined data.”
Analyses Overview
For the two analyses — one in the overall population of patients with AD and the other in those aged 50 years or older — electronic medical record (EMR) data from the TriNetX Research Network were used. This is a global, federated health research network that contains EMRs for more than 275 million patients from over 120 healthcare organizations, El Ayadi explained.
To perform the analyses, the research team queried the TriNetX database to find all patients diagnosed with AD via the International Classification of Diseases, Tenth Revision code L20. They then determined if patients had been treated with JAKi or not, and specifically, with upadacitinib or abrocitinib. Those who had not received any JAKi treatment were the control population.
For the first analysis, no age-specific filter was applied. The investigators identified 1674 people with AD who had been treated with the JAKis and around 1.2 million who had not. Propensity score matching, based on age at diagnosis, biologic sex, and CV comorbidities, was performed to give a total of 1674 patients who had and 1674 who had not been treated with these medications.
In the second analysis, only those aged 50 years or older were considered; 875 patients who had received JAKi treatment were identified and around 250,000 who had not. Propensity score matching based on the same variables gave two groups of 875 people who had or had not taken a JAKi.
Queried over the age cutoff used, El Ayadi noted, “We did an analysis looking at patients 65 and older. However, we came up with lower patient numbers. … We do have this data, and we did not see any significant risk.”
The study was independently supported. El Ayadi and Gilaberte Calzada reported no conflicts of interest in relation to the presented findings.
A version of this article first appeared on Medscape.com.
, suggested the results of a large, US-based, retrospective cohort study.
This holds true even in individuals aged 50 years or older, whose age puts them at increased cardiovascular (CV) risk, said Amina El Ayadi, PhD, of the University of Texas Medical Branch at Galveston. He presented the findings at the recent European Academy of Dermatology and Venereology (EADV) 2024 Congress.
Specifically, the analysis looked at treatment with the oral JAK1 inhibitors upadacitinib (Rinvoq) and abrocitinib (Cibinqo), both approved for treating AD in the United States, and found that the relative risk for MACE, such as acute myocardial infarction, cardiac arrest, stroke, or acute deep vein thrombosis, was ≤ 1.0 compared with those not treated with a JAKi.
Similarly, the relative risk for other CV safety endpoints, such as having an abnormal ECG or pericardial effusion, was also around 1.0. There was a slight increase in the relative risk for arrhythmias, peripheral edema, angina pectoris, or heart failure, but no value went > 1.6 and CIs spanned 1.0, indicating the results lack statistical significance.
Reassurance for Dermatologists?
“This suggests that oral administration of these drugs to the patient with atopic dermatitis does not increase the risk of major adverse cardiac events, and dermatologists, based on our data, can safely consider JAK inhibitors for treating moderate to severe dermatitis, even in patients with high risk for these diseases,” El Ayadi said during a late-breaking news session at the meeting.
Yolanda Gilaberte Calzada, MD, PhD, head of the Dermatology Department at Miguel Servet University Hospital in Zaragoza, Spain, who was one of the chairs for the session, said that this was “very good news for us.”
Gilaberte Calzada, president of the Spanish Academy of Dermatology and Venereology, asked if there were any data on the duration of treatment with the two JAKis included in the analysis. El Ayadi said that this was something that would be looked at in future data analyses.
Gilaberte Calzada also observed that because the CIs were wide, with more time, “we will have more defined data.”
Analyses Overview
For the two analyses — one in the overall population of patients with AD and the other in those aged 50 years or older — electronic medical record (EMR) data from the TriNetX Research Network were used. This is a global, federated health research network that contains EMRs for more than 275 million patients from over 120 healthcare organizations, El Ayadi explained.
To perform the analyses, the research team queried the TriNetX database to find all patients diagnosed with AD via the International Classification of Diseases, Tenth Revision code L20. They then determined if patients had been treated with JAKi or not, and specifically, with upadacitinib or abrocitinib. Those who had not received any JAKi treatment were the control population.
For the first analysis, no age-specific filter was applied. The investigators identified 1674 people with AD who had been treated with the JAKis and around 1.2 million who had not. Propensity score matching, based on age at diagnosis, biologic sex, and CV comorbidities, was performed to give a total of 1674 patients who had and 1674 who had not been treated with these medications.
In the second analysis, only those aged 50 years or older were considered; 875 patients who had received JAKi treatment were identified and around 250,000 who had not. Propensity score matching based on the same variables gave two groups of 875 people who had or had not taken a JAKi.
Queried over the age cutoff used, El Ayadi noted, “We did an analysis looking at patients 65 and older. However, we came up with lower patient numbers. … We do have this data, and we did not see any significant risk.”
The study was independently supported. El Ayadi and Gilaberte Calzada reported no conflicts of interest in relation to the presented findings.
A version of this article first appeared on Medscape.com.
, suggested the results of a large, US-based, retrospective cohort study.
This holds true even in individuals aged 50 years or older, whose age puts them at increased cardiovascular (CV) risk, said Amina El Ayadi, PhD, of the University of Texas Medical Branch at Galveston. He presented the findings at the recent European Academy of Dermatology and Venereology (EADV) 2024 Congress.
Specifically, the analysis looked at treatment with the oral JAK1 inhibitors upadacitinib (Rinvoq) and abrocitinib (Cibinqo), both approved for treating AD in the United States, and found that the relative risk for MACE, such as acute myocardial infarction, cardiac arrest, stroke, or acute deep vein thrombosis, was ≤ 1.0 compared with those not treated with a JAKi.
Similarly, the relative risk for other CV safety endpoints, such as having an abnormal ECG or pericardial effusion, was also around 1.0. There was a slight increase in the relative risk for arrhythmias, peripheral edema, angina pectoris, or heart failure, but no value went > 1.6 and CIs spanned 1.0, indicating the results lack statistical significance.
Reassurance for Dermatologists?
“This suggests that oral administration of these drugs to the patient with atopic dermatitis does not increase the risk of major adverse cardiac events, and dermatologists, based on our data, can safely consider JAK inhibitors for treating moderate to severe dermatitis, even in patients with high risk for these diseases,” El Ayadi said during a late-breaking news session at the meeting.
Yolanda Gilaberte Calzada, MD, PhD, head of the Dermatology Department at Miguel Servet University Hospital in Zaragoza, Spain, who was one of the chairs for the session, said that this was “very good news for us.”
Gilaberte Calzada, president of the Spanish Academy of Dermatology and Venereology, asked if there were any data on the duration of treatment with the two JAKis included in the analysis. El Ayadi said that this was something that would be looked at in future data analyses.
Gilaberte Calzada also observed that because the CIs were wide, with more time, “we will have more defined data.”
Analyses Overview
For the two analyses — one in the overall population of patients with AD and the other in those aged 50 years or older — electronic medical record (EMR) data from the TriNetX Research Network were used. This is a global, federated health research network that contains EMRs for more than 275 million patients from over 120 healthcare organizations, El Ayadi explained.
To perform the analyses, the research team queried the TriNetX database to find all patients diagnosed with AD via the International Classification of Diseases, Tenth Revision code L20. They then determined if patients had been treated with JAKi or not, and specifically, with upadacitinib or abrocitinib. Those who had not received any JAKi treatment were the control population.
For the first analysis, no age-specific filter was applied. The investigators identified 1674 people with AD who had been treated with the JAKis and around 1.2 million who had not. Propensity score matching, based on age at diagnosis, biologic sex, and CV comorbidities, was performed to give a total of 1674 patients who had and 1674 who had not been treated with these medications.
In the second analysis, only those aged 50 years or older were considered; 875 patients who had received JAKi treatment were identified and around 250,000 who had not. Propensity score matching based on the same variables gave two groups of 875 people who had or had not taken a JAKi.
Queried over the age cutoff used, El Ayadi noted, “We did an analysis looking at patients 65 and older. However, we came up with lower patient numbers. … We do have this data, and we did not see any significant risk.”
The study was independently supported. El Ayadi and Gilaberte Calzada reported no conflicts of interest in relation to the presented findings.
A version of this article first appeared on Medscape.com.
FROM EADV 2024
Topical JAK Inhibitor Effective for Hand Eczema, Two Studies Suggest
suggested the results of two separate studies presented during the late-breaking sessions at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.
In the 24-week, phase 3 DELTA FORCE trial, topical delgocitinib was compared head to head with oral alitretinoin for managing chronic hand eczema (CHE). Results showed that greater improvements from baseline to week 12 in Hand Eczema Severity Index (HECSI) scores could be achieved with delgocitinib cream than with alitretinoin capsules.
And in another analysis, which involved patients with the atopic subtype of CHE only, the application of topical delgocitinib was found to be as good as treatment with subcutaneous dupilumab (Dupixent) at improving both HECSI scores and the Investigator Global Assessment for CHE response (IGA-CHE).
Potentially a ‘Highly Impactful’ Therapy
“Chronic hand eczema is a common yet burdensome skin condition that poses a considerable challenge for dermatologists. Diversity in morphologic presentation and clinical etiology has been a key limitation for the development of a safe, targeted, one-size-fits-all therapeutic approach,” Raj Chovatiya, MD, PhD, clinical associate professor at Chicago Medical School, Rosalind Franklin University of Medicine and Science, and the founder and director of the Center for Medical Dermatology and Immunology Research in Chicago, Illinois, said in an interview.
“These data show that delgocitinib cream is poised to be a novel and highly impactful topical therapy for the treatment of CHE,” said Chovatiya.
DELTA FORCE showed that the efficacy and safety of delgocitinib cream was “superior to alitretinoin, the only approved oral option for CHE,” he said. And the other study, a comparative analysis, showed that delgocitinib’s efficacy was “comparable to the biologic dupilumab specifically for the treatment of atopic hand eczema,” said Chovatiya, one of the authors of that study. He was not an author of the DELTA FORCE study.
DELTA FORCE
While it remains an investigational drug in the United States, where it is under Food and Drug Administration review for CHE, delgocitinib cream (Anzupgo) was recently approved by the European Commission for use in adults with moderate to severe hand eczema who do not respond to or who are unable to use topical corticosteroids. Approval was based on data from two phase 3 studies , DELTA 1 and DELTA 2, which compared delgocitinib cream against a cream vehicle, as well as an open-label, long-term extension study, DELTA 3.
In the DELTA FORCE study, 513 adults with severe CHE (IGA-CHE score of 4) were recruited at 102 clinical centers in Europe and North America and randomly allocated to topical treatment with delgocitinib cream, 20 mg/g applied twice daily, or alitretinoin capsules, 30 mg once daily. Treatment with delgocitinib was for 16 weeks, and treatment with alitretinoin was for 12 weeks. The latter’s dose could be reduced to 10 mg in the event of intolerability, and both treatments could be reintroduced if necessary, with a final follow-up at 24 weeks.
Study investigator Ana Maria Giménez-Arnau, MD, PhD, of the Hospital del Mar Research Institute, Pompeu Fabra University, Barcelona, Spain, who presented the findings, noted that alitretinoin (Toctino) is an oral systemic retinoid approved in a few European countries, Canada, Israel, and South Korea for the treatment of severe CHE.
The mean age of the participants was 45 years, almost two thirds were women, and the majority (93%) were White; 90% of patients had been recruited in Europe. The median duration of CHE was 4 years.
At baseline, the median HECSI score was recorded as 79.5 in the delgocitinib arm and 80.0 in the alitretinoin arm. At 12 weeks, the least squares mean change in HECSI score from baseline was –67.6 in the delgocitinib arm and –51.5 in the alitretinoin arm, giving a significant difference of –16.1 between the two groups (P < .001).
Giménez-Arnau reported that delgocitinib also outperformed alitretinoin for all other endpoints assessed, including the following: ≥ 90% improvement in HECSI (HECSI-90), IGA-CHE treatment success (defined as a score of 0/1 indicating clear/almost clear skin), changes in Hand Eczema Symptom Diary (HESD) itch and HESD pain scores, area under the curve for HECSI-90, change in Dermatology Life Quality Index score — which were all assessed at 12 weeks — and change in HECSI from baseline to week 24.
There was “significant improvement in the reduction of the HECSI from the first week” of treatment, Giménez-Arnau said at the meeting. Notably, that the effect increased to 12 weeks and then was sustained. A similar pattern was seen for IGA-CHE treatment success and for HESD pain. This is important as “chronic hand eczema is really painful,” she said.
As for safety, 49.4% of patients in the delgocitinib arm vs 76.1% of patients in the alitretinoin arm experienced any type of adverse event (AE). Serious AEs occurred in 2% and 4.9% of patients in each group, respectively, with fewer AEs leading to trial drug discontinuation observed in the delgocitinib arm (1.2% vs 10.1%). The proportion of AEs “probably or possibly” related to the trial drug was 9.5% in the delgocitinib group vs 54.3% in the alitretinoin group.
Comparison With Dupilumab in Another Trial
Delgocitinib is no longer just an investigational medication, April W. Armstrong, MD, MPH, professor and chief of dermatology, University of California, Los Angeles, said during a separate late-breaking presentation at the EADV 2024 meeting. “I think it’s big news because now we have an important topical option for our patients with chronic hand eczema.”
Armstrong presented a matched-adjusted indirect comparison (MAIC) of delgocitinib vs dupilumab for the treatment of moderate to severe atopic hand eczema, which she described as “the next best thing” to a head-to-head trial.
MAICs are where patient level data from one or more clinical trials evaluating drug “A” are compared with aggregate data from one or more clinical trials evaluating drug “B.” In this case, individual patient data from the DELTA 1 and DELTA 2 trials of delgocitinib were compared with published aggregate data from the phase 3 LIBERTY-AD-HAFT trial of dupilumab.
A total of 201 patients with atopic hand eczema in the DELTA 1 and DELTA 2 trials were matched to 133 patients in the LIBERTY-AD-HAFT trial. Of these, 128 had been treated with delgocitinib cream, 73 with a cream vehicle, 67 with subcutaneous dupilumab, and 66 with a subcutaneous placebo.
“We’re trying to compare as much as possible apples to apples here in terms of the etiology of hand eczema,” Armstrong said. She noted that after matching and weighting based on age, sex, race, and baseline HECSI score, baseline characteristics in the two groups of patients were similar. The mean age was about 35.8 years in the two active treatment arms and 33.4 years in the two placebo arms, and mean baseline HESCI scores were about 79-80.
The endpoints compared were ≥ 75% improvement in HECSI; HECSI-90, HECSI percentage improvement, and IGA-CHE in the DELTA 1 and DELTA 2 trials; or a Hand and Foot IGA score of 0/1.
“The key message to take away from this is that there were no statistically significant differences between topical delgocitinib twice daily vs subcutaneous injection of dupilumab by week 16 in the treatment of patients with atopic hand dermatitis,” Armstrong reported. Odds ratios varied between 1.1 and 1.3 for the various endpoints.
Menno de Rie, MD, PhD, professor of dermatology and immunology at Amsterdam University Medical Center in the Netherlands, who cochaired the session, said that “I appreciate very much that you took the effort to compare these totally different compounds and showed us the methodology that you did. It’s really very impressive.”
Topical, Systemic, or Both?
Armstrong was questioned on how to manage someone with atopic hand dermatitis who developed lesions elsewhere on the body.
“I would take a really individualized approach to this patient,” she responded. If the eczema has been limited to the hands and has been there for a while, then perhaps delgocitinib would be her choice, but if they developed lesions elsewhere on the body, then a systemic treatment such as dupilumab may be preferable.
“The good thing is that this study shows that you can offer the patient either of those options and really engage the patient in a shared decision-making process.”
And with regards to whether the two might possibly be used together, Armstrong acknowledged insurance coverage restrictions could be a limiting factor in the United States, but elsewhere — and from a scientific point of view — this could make sense.
“If we have a patient, for example, who has moderate to severe atopic dermatitis involving the body, but also very severe hand eczema as well, one may possibly consider a combination of a systemic medication that’s helpful for the extensive area of involvement on the body ... and now you have a topical therapy, delgocitinib, where you can use it locally, have very deep efficacy locally, to kind of help augment that disease phenotype in that patient population.”
The studies were funded by Leo Pharma. Chovatiya, Giménez-Arnau, and Armstrong acknowledged ties to LEO Pharma, among other pharmaceutical companies.
A version of this article first appeared on Medscape.com.
suggested the results of two separate studies presented during the late-breaking sessions at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.
In the 24-week, phase 3 DELTA FORCE trial, topical delgocitinib was compared head to head with oral alitretinoin for managing chronic hand eczema (CHE). Results showed that greater improvements from baseline to week 12 in Hand Eczema Severity Index (HECSI) scores could be achieved with delgocitinib cream than with alitretinoin capsules.
And in another analysis, which involved patients with the atopic subtype of CHE only, the application of topical delgocitinib was found to be as good as treatment with subcutaneous dupilumab (Dupixent) at improving both HECSI scores and the Investigator Global Assessment for CHE response (IGA-CHE).
Potentially a ‘Highly Impactful’ Therapy
“Chronic hand eczema is a common yet burdensome skin condition that poses a considerable challenge for dermatologists. Diversity in morphologic presentation and clinical etiology has been a key limitation for the development of a safe, targeted, one-size-fits-all therapeutic approach,” Raj Chovatiya, MD, PhD, clinical associate professor at Chicago Medical School, Rosalind Franklin University of Medicine and Science, and the founder and director of the Center for Medical Dermatology and Immunology Research in Chicago, Illinois, said in an interview.
“These data show that delgocitinib cream is poised to be a novel and highly impactful topical therapy for the treatment of CHE,” said Chovatiya.
DELTA FORCE showed that the efficacy and safety of delgocitinib cream was “superior to alitretinoin, the only approved oral option for CHE,” he said. And the other study, a comparative analysis, showed that delgocitinib’s efficacy was “comparable to the biologic dupilumab specifically for the treatment of atopic hand eczema,” said Chovatiya, one of the authors of that study. He was not an author of the DELTA FORCE study.
DELTA FORCE
While it remains an investigational drug in the United States, where it is under Food and Drug Administration review for CHE, delgocitinib cream (Anzupgo) was recently approved by the European Commission for use in adults with moderate to severe hand eczema who do not respond to or who are unable to use topical corticosteroids. Approval was based on data from two phase 3 studies , DELTA 1 and DELTA 2, which compared delgocitinib cream against a cream vehicle, as well as an open-label, long-term extension study, DELTA 3.
In the DELTA FORCE study, 513 adults with severe CHE (IGA-CHE score of 4) were recruited at 102 clinical centers in Europe and North America and randomly allocated to topical treatment with delgocitinib cream, 20 mg/g applied twice daily, or alitretinoin capsules, 30 mg once daily. Treatment with delgocitinib was for 16 weeks, and treatment with alitretinoin was for 12 weeks. The latter’s dose could be reduced to 10 mg in the event of intolerability, and both treatments could be reintroduced if necessary, with a final follow-up at 24 weeks.
Study investigator Ana Maria Giménez-Arnau, MD, PhD, of the Hospital del Mar Research Institute, Pompeu Fabra University, Barcelona, Spain, who presented the findings, noted that alitretinoin (Toctino) is an oral systemic retinoid approved in a few European countries, Canada, Israel, and South Korea for the treatment of severe CHE.
The mean age of the participants was 45 years, almost two thirds were women, and the majority (93%) were White; 90% of patients had been recruited in Europe. The median duration of CHE was 4 years.
At baseline, the median HECSI score was recorded as 79.5 in the delgocitinib arm and 80.0 in the alitretinoin arm. At 12 weeks, the least squares mean change in HECSI score from baseline was –67.6 in the delgocitinib arm and –51.5 in the alitretinoin arm, giving a significant difference of –16.1 between the two groups (P < .001).
Giménez-Arnau reported that delgocitinib also outperformed alitretinoin for all other endpoints assessed, including the following: ≥ 90% improvement in HECSI (HECSI-90), IGA-CHE treatment success (defined as a score of 0/1 indicating clear/almost clear skin), changes in Hand Eczema Symptom Diary (HESD) itch and HESD pain scores, area under the curve for HECSI-90, change in Dermatology Life Quality Index score — which were all assessed at 12 weeks — and change in HECSI from baseline to week 24.
There was “significant improvement in the reduction of the HECSI from the first week” of treatment, Giménez-Arnau said at the meeting. Notably, that the effect increased to 12 weeks and then was sustained. A similar pattern was seen for IGA-CHE treatment success and for HESD pain. This is important as “chronic hand eczema is really painful,” she said.
As for safety, 49.4% of patients in the delgocitinib arm vs 76.1% of patients in the alitretinoin arm experienced any type of adverse event (AE). Serious AEs occurred in 2% and 4.9% of patients in each group, respectively, with fewer AEs leading to trial drug discontinuation observed in the delgocitinib arm (1.2% vs 10.1%). The proportion of AEs “probably or possibly” related to the trial drug was 9.5% in the delgocitinib group vs 54.3% in the alitretinoin group.
Comparison With Dupilumab in Another Trial
Delgocitinib is no longer just an investigational medication, April W. Armstrong, MD, MPH, professor and chief of dermatology, University of California, Los Angeles, said during a separate late-breaking presentation at the EADV 2024 meeting. “I think it’s big news because now we have an important topical option for our patients with chronic hand eczema.”
Armstrong presented a matched-adjusted indirect comparison (MAIC) of delgocitinib vs dupilumab for the treatment of moderate to severe atopic hand eczema, which she described as “the next best thing” to a head-to-head trial.
MAICs are where patient level data from one or more clinical trials evaluating drug “A” are compared with aggregate data from one or more clinical trials evaluating drug “B.” In this case, individual patient data from the DELTA 1 and DELTA 2 trials of delgocitinib were compared with published aggregate data from the phase 3 LIBERTY-AD-HAFT trial of dupilumab.
A total of 201 patients with atopic hand eczema in the DELTA 1 and DELTA 2 trials were matched to 133 patients in the LIBERTY-AD-HAFT trial. Of these, 128 had been treated with delgocitinib cream, 73 with a cream vehicle, 67 with subcutaneous dupilumab, and 66 with a subcutaneous placebo.
“We’re trying to compare as much as possible apples to apples here in terms of the etiology of hand eczema,” Armstrong said. She noted that after matching and weighting based on age, sex, race, and baseline HECSI score, baseline characteristics in the two groups of patients were similar. The mean age was about 35.8 years in the two active treatment arms and 33.4 years in the two placebo arms, and mean baseline HESCI scores were about 79-80.
The endpoints compared were ≥ 75% improvement in HECSI; HECSI-90, HECSI percentage improvement, and IGA-CHE in the DELTA 1 and DELTA 2 trials; or a Hand and Foot IGA score of 0/1.
“The key message to take away from this is that there were no statistically significant differences between topical delgocitinib twice daily vs subcutaneous injection of dupilumab by week 16 in the treatment of patients with atopic hand dermatitis,” Armstrong reported. Odds ratios varied between 1.1 and 1.3 for the various endpoints.
Menno de Rie, MD, PhD, professor of dermatology and immunology at Amsterdam University Medical Center in the Netherlands, who cochaired the session, said that “I appreciate very much that you took the effort to compare these totally different compounds and showed us the methodology that you did. It’s really very impressive.”
Topical, Systemic, or Both?
Armstrong was questioned on how to manage someone with atopic hand dermatitis who developed lesions elsewhere on the body.
“I would take a really individualized approach to this patient,” she responded. If the eczema has been limited to the hands and has been there for a while, then perhaps delgocitinib would be her choice, but if they developed lesions elsewhere on the body, then a systemic treatment such as dupilumab may be preferable.
“The good thing is that this study shows that you can offer the patient either of those options and really engage the patient in a shared decision-making process.”
And with regards to whether the two might possibly be used together, Armstrong acknowledged insurance coverage restrictions could be a limiting factor in the United States, but elsewhere — and from a scientific point of view — this could make sense.
“If we have a patient, for example, who has moderate to severe atopic dermatitis involving the body, but also very severe hand eczema as well, one may possibly consider a combination of a systemic medication that’s helpful for the extensive area of involvement on the body ... and now you have a topical therapy, delgocitinib, where you can use it locally, have very deep efficacy locally, to kind of help augment that disease phenotype in that patient population.”
The studies were funded by Leo Pharma. Chovatiya, Giménez-Arnau, and Armstrong acknowledged ties to LEO Pharma, among other pharmaceutical companies.
A version of this article first appeared on Medscape.com.
suggested the results of two separate studies presented during the late-breaking sessions at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.
In the 24-week, phase 3 DELTA FORCE trial, topical delgocitinib was compared head to head with oral alitretinoin for managing chronic hand eczema (CHE). Results showed that greater improvements from baseline to week 12 in Hand Eczema Severity Index (HECSI) scores could be achieved with delgocitinib cream than with alitretinoin capsules.
And in another analysis, which involved patients with the atopic subtype of CHE only, the application of topical delgocitinib was found to be as good as treatment with subcutaneous dupilumab (Dupixent) at improving both HECSI scores and the Investigator Global Assessment for CHE response (IGA-CHE).
Potentially a ‘Highly Impactful’ Therapy
“Chronic hand eczema is a common yet burdensome skin condition that poses a considerable challenge for dermatologists. Diversity in morphologic presentation and clinical etiology has been a key limitation for the development of a safe, targeted, one-size-fits-all therapeutic approach,” Raj Chovatiya, MD, PhD, clinical associate professor at Chicago Medical School, Rosalind Franklin University of Medicine and Science, and the founder and director of the Center for Medical Dermatology and Immunology Research in Chicago, Illinois, said in an interview.
“These data show that delgocitinib cream is poised to be a novel and highly impactful topical therapy for the treatment of CHE,” said Chovatiya.
DELTA FORCE showed that the efficacy and safety of delgocitinib cream was “superior to alitretinoin, the only approved oral option for CHE,” he said. And the other study, a comparative analysis, showed that delgocitinib’s efficacy was “comparable to the biologic dupilumab specifically for the treatment of atopic hand eczema,” said Chovatiya, one of the authors of that study. He was not an author of the DELTA FORCE study.
DELTA FORCE
While it remains an investigational drug in the United States, where it is under Food and Drug Administration review for CHE, delgocitinib cream (Anzupgo) was recently approved by the European Commission for use in adults with moderate to severe hand eczema who do not respond to or who are unable to use topical corticosteroids. Approval was based on data from two phase 3 studies , DELTA 1 and DELTA 2, which compared delgocitinib cream against a cream vehicle, as well as an open-label, long-term extension study, DELTA 3.
In the DELTA FORCE study, 513 adults with severe CHE (IGA-CHE score of 4) were recruited at 102 clinical centers in Europe and North America and randomly allocated to topical treatment with delgocitinib cream, 20 mg/g applied twice daily, or alitretinoin capsules, 30 mg once daily. Treatment with delgocitinib was for 16 weeks, and treatment with alitretinoin was for 12 weeks. The latter’s dose could be reduced to 10 mg in the event of intolerability, and both treatments could be reintroduced if necessary, with a final follow-up at 24 weeks.
Study investigator Ana Maria Giménez-Arnau, MD, PhD, of the Hospital del Mar Research Institute, Pompeu Fabra University, Barcelona, Spain, who presented the findings, noted that alitretinoin (Toctino) is an oral systemic retinoid approved in a few European countries, Canada, Israel, and South Korea for the treatment of severe CHE.
The mean age of the participants was 45 years, almost two thirds were women, and the majority (93%) were White; 90% of patients had been recruited in Europe. The median duration of CHE was 4 years.
At baseline, the median HECSI score was recorded as 79.5 in the delgocitinib arm and 80.0 in the alitretinoin arm. At 12 weeks, the least squares mean change in HECSI score from baseline was –67.6 in the delgocitinib arm and –51.5 in the alitretinoin arm, giving a significant difference of –16.1 between the two groups (P < .001).
Giménez-Arnau reported that delgocitinib also outperformed alitretinoin for all other endpoints assessed, including the following: ≥ 90% improvement in HECSI (HECSI-90), IGA-CHE treatment success (defined as a score of 0/1 indicating clear/almost clear skin), changes in Hand Eczema Symptom Diary (HESD) itch and HESD pain scores, area under the curve for HECSI-90, change in Dermatology Life Quality Index score — which were all assessed at 12 weeks — and change in HECSI from baseline to week 24.
There was “significant improvement in the reduction of the HECSI from the first week” of treatment, Giménez-Arnau said at the meeting. Notably, that the effect increased to 12 weeks and then was sustained. A similar pattern was seen for IGA-CHE treatment success and for HESD pain. This is important as “chronic hand eczema is really painful,” she said.
As for safety, 49.4% of patients in the delgocitinib arm vs 76.1% of patients in the alitretinoin arm experienced any type of adverse event (AE). Serious AEs occurred in 2% and 4.9% of patients in each group, respectively, with fewer AEs leading to trial drug discontinuation observed in the delgocitinib arm (1.2% vs 10.1%). The proportion of AEs “probably or possibly” related to the trial drug was 9.5% in the delgocitinib group vs 54.3% in the alitretinoin group.
Comparison With Dupilumab in Another Trial
Delgocitinib is no longer just an investigational medication, April W. Armstrong, MD, MPH, professor and chief of dermatology, University of California, Los Angeles, said during a separate late-breaking presentation at the EADV 2024 meeting. “I think it’s big news because now we have an important topical option for our patients with chronic hand eczema.”
Armstrong presented a matched-adjusted indirect comparison (MAIC) of delgocitinib vs dupilumab for the treatment of moderate to severe atopic hand eczema, which she described as “the next best thing” to a head-to-head trial.
MAICs are where patient level data from one or more clinical trials evaluating drug “A” are compared with aggregate data from one or more clinical trials evaluating drug “B.” In this case, individual patient data from the DELTA 1 and DELTA 2 trials of delgocitinib were compared with published aggregate data from the phase 3 LIBERTY-AD-HAFT trial of dupilumab.
A total of 201 patients with atopic hand eczema in the DELTA 1 and DELTA 2 trials were matched to 133 patients in the LIBERTY-AD-HAFT trial. Of these, 128 had been treated with delgocitinib cream, 73 with a cream vehicle, 67 with subcutaneous dupilumab, and 66 with a subcutaneous placebo.
“We’re trying to compare as much as possible apples to apples here in terms of the etiology of hand eczema,” Armstrong said. She noted that after matching and weighting based on age, sex, race, and baseline HECSI score, baseline characteristics in the two groups of patients were similar. The mean age was about 35.8 years in the two active treatment arms and 33.4 years in the two placebo arms, and mean baseline HESCI scores were about 79-80.
The endpoints compared were ≥ 75% improvement in HECSI; HECSI-90, HECSI percentage improvement, and IGA-CHE in the DELTA 1 and DELTA 2 trials; or a Hand and Foot IGA score of 0/1.
“The key message to take away from this is that there were no statistically significant differences between topical delgocitinib twice daily vs subcutaneous injection of dupilumab by week 16 in the treatment of patients with atopic hand dermatitis,” Armstrong reported. Odds ratios varied between 1.1 and 1.3 for the various endpoints.
Menno de Rie, MD, PhD, professor of dermatology and immunology at Amsterdam University Medical Center in the Netherlands, who cochaired the session, said that “I appreciate very much that you took the effort to compare these totally different compounds and showed us the methodology that you did. It’s really very impressive.”
Topical, Systemic, or Both?
Armstrong was questioned on how to manage someone with atopic hand dermatitis who developed lesions elsewhere on the body.
“I would take a really individualized approach to this patient,” she responded. If the eczema has been limited to the hands and has been there for a while, then perhaps delgocitinib would be her choice, but if they developed lesions elsewhere on the body, then a systemic treatment such as dupilumab may be preferable.
“The good thing is that this study shows that you can offer the patient either of those options and really engage the patient in a shared decision-making process.”
And with regards to whether the two might possibly be used together, Armstrong acknowledged insurance coverage restrictions could be a limiting factor in the United States, but elsewhere — and from a scientific point of view — this could make sense.
“If we have a patient, for example, who has moderate to severe atopic dermatitis involving the body, but also very severe hand eczema as well, one may possibly consider a combination of a systemic medication that’s helpful for the extensive area of involvement on the body ... and now you have a topical therapy, delgocitinib, where you can use it locally, have very deep efficacy locally, to kind of help augment that disease phenotype in that patient population.”
The studies were funded by Leo Pharma. Chovatiya, Giménez-Arnau, and Armstrong acknowledged ties to LEO Pharma, among other pharmaceutical companies.
A version of this article first appeared on Medscape.com.
FROM EADV 2024
Triple P
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.
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.
Triple P focuses on what Sanders calls the five key principles of positive parenting:
- 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 [email protected].
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.
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.
Triple P focuses on what Sanders calls the five key principles of positive parenting:
- 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 [email protected].
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.
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.
Triple P focuses on what Sanders calls the five key principles of positive parenting:
- 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 [email protected].
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.
Late-Onset Axial Spondyloarthritis: How Does It Differ From Early-Onset Disease?
TOPLINE:
METHODOLOGY:
- Researchers conducted a multicenter cross-sectional study including 2165 patients with a clinical diagnosis of axSpA who were identified from the Rheumatic Diseases Portuguese Register from June 2008 to December 2022.
- Patients with symptom onset at or after 45 years of age were referred as late-onset axSpA, whereas those with symptom onset before 45 years as early-onset axSpA.
- Overall, 273 had a diagnosis of late-onset axSpA (mean age at symptom onset, 51.4 years; 55% men) and 1892 had a diagnosis of early-onset axSpA (mean age at symptom onset, 28.9 years; 56% men).
- Independent associations between demographic, clinical, imaging, and treatment characteristics and late-onset axSpA were tested using multivariable logistic regression models.
TAKEAWAY:
- Patients with late-onset axSpA were less likely to be positive for HLA-B27 (51% vs 65%; P < .001) and to have a family history of SpA (8% vs 14%; P < .01), have inflammatory back pain (81% vs 88%; P < .01), and have acute anterior uveitis (13% vs 20%; P < .01) than those with early-onset axSpA.
- Patients with late-onset axSpA had a higher likelihood of having peripheral arthritis than those with early-onset axSpA (36% vs 28%; P < .05).
- The odds of having late-onset axSpA were lower in patients with HLA-B27 positivity (adjusted odds ratio [aOR], 0.6; 95% CI, 0.4-0.7), a family history of SpA (aOR, 0.6; 95% CI, 0.4-0.9), inflammatory back pain (aOR, 0.5; 95% CI, 0.4-0.8), and acute anterior uveitis (aOR, 0.6; 95% CI, 0.4-0.9).
- Conversely, patients with peripheral arthritis had a higher likelihood of developing late-onset axSpA (aOR, 1.5; 95% CI, 1.1-1.9).
IN PRACTICE:
“In this study, we found that [late-onset axSpA] may represent a distinct phenotype with a weaker association with HLA-B27,” the authors wrote. “Whether [late-onset axSpA] comprises a subset of axSpA with a (possibly) different genetic or epigenetic background or rather translates difficulties in recognizing a less typical disease presentation and a population without a genetic marker which can make the diagnostic process more challenging merits further investigation.”
SOURCE:
The study was led by Margarida Lucas Rocha, MD, Department of Rheumatology, ULSA, Faro, Portugal. It was published online in Joint Bone Spine.
LIMITATIONS:
No limitations were reported in the study.
DISCLOSURES:
No relevant funding information and conflicts of interest were disclosed by the authors.
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:
METHODOLOGY:
- Researchers conducted a multicenter cross-sectional study including 2165 patients with a clinical diagnosis of axSpA who were identified from the Rheumatic Diseases Portuguese Register from June 2008 to December 2022.
- Patients with symptom onset at or after 45 years of age were referred as late-onset axSpA, whereas those with symptom onset before 45 years as early-onset axSpA.
- Overall, 273 had a diagnosis of late-onset axSpA (mean age at symptom onset, 51.4 years; 55% men) and 1892 had a diagnosis of early-onset axSpA (mean age at symptom onset, 28.9 years; 56% men).
- Independent associations between demographic, clinical, imaging, and treatment characteristics and late-onset axSpA were tested using multivariable logistic regression models.
TAKEAWAY:
- Patients with late-onset axSpA were less likely to be positive for HLA-B27 (51% vs 65%; P < .001) and to have a family history of SpA (8% vs 14%; P < .01), have inflammatory back pain (81% vs 88%; P < .01), and have acute anterior uveitis (13% vs 20%; P < .01) than those with early-onset axSpA.
- Patients with late-onset axSpA had a higher likelihood of having peripheral arthritis than those with early-onset axSpA (36% vs 28%; P < .05).
- The odds of having late-onset axSpA were lower in patients with HLA-B27 positivity (adjusted odds ratio [aOR], 0.6; 95% CI, 0.4-0.7), a family history of SpA (aOR, 0.6; 95% CI, 0.4-0.9), inflammatory back pain (aOR, 0.5; 95% CI, 0.4-0.8), and acute anterior uveitis (aOR, 0.6; 95% CI, 0.4-0.9).
- Conversely, patients with peripheral arthritis had a higher likelihood of developing late-onset axSpA (aOR, 1.5; 95% CI, 1.1-1.9).
IN PRACTICE:
“In this study, we found that [late-onset axSpA] may represent a distinct phenotype with a weaker association with HLA-B27,” the authors wrote. “Whether [late-onset axSpA] comprises a subset of axSpA with a (possibly) different genetic or epigenetic background or rather translates difficulties in recognizing a less typical disease presentation and a population without a genetic marker which can make the diagnostic process more challenging merits further investigation.”
SOURCE:
The study was led by Margarida Lucas Rocha, MD, Department of Rheumatology, ULSA, Faro, Portugal. It was published online in Joint Bone Spine.
LIMITATIONS:
No limitations were reported in the study.
DISCLOSURES:
No relevant funding information and conflicts of interest were disclosed by the authors.
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:
METHODOLOGY:
- Researchers conducted a multicenter cross-sectional study including 2165 patients with a clinical diagnosis of axSpA who were identified from the Rheumatic Diseases Portuguese Register from June 2008 to December 2022.
- Patients with symptom onset at or after 45 years of age were referred as late-onset axSpA, whereas those with symptom onset before 45 years as early-onset axSpA.
- Overall, 273 had a diagnosis of late-onset axSpA (mean age at symptom onset, 51.4 years; 55% men) and 1892 had a diagnosis of early-onset axSpA (mean age at symptom onset, 28.9 years; 56% men).
- Independent associations between demographic, clinical, imaging, and treatment characteristics and late-onset axSpA were tested using multivariable logistic regression models.
TAKEAWAY:
- Patients with late-onset axSpA were less likely to be positive for HLA-B27 (51% vs 65%; P < .001) and to have a family history of SpA (8% vs 14%; P < .01), have inflammatory back pain (81% vs 88%; P < .01), and have acute anterior uveitis (13% vs 20%; P < .01) than those with early-onset axSpA.
- Patients with late-onset axSpA had a higher likelihood of having peripheral arthritis than those with early-onset axSpA (36% vs 28%; P < .05).
- The odds of having late-onset axSpA were lower in patients with HLA-B27 positivity (adjusted odds ratio [aOR], 0.6; 95% CI, 0.4-0.7), a family history of SpA (aOR, 0.6; 95% CI, 0.4-0.9), inflammatory back pain (aOR, 0.5; 95% CI, 0.4-0.8), and acute anterior uveitis (aOR, 0.6; 95% CI, 0.4-0.9).
- Conversely, patients with peripheral arthritis had a higher likelihood of developing late-onset axSpA (aOR, 1.5; 95% CI, 1.1-1.9).
IN PRACTICE:
“In this study, we found that [late-onset axSpA] may represent a distinct phenotype with a weaker association with HLA-B27,” the authors wrote. “Whether [late-onset axSpA] comprises a subset of axSpA with a (possibly) different genetic or epigenetic background or rather translates difficulties in recognizing a less typical disease presentation and a population without a genetic marker which can make the diagnostic process more challenging merits further investigation.”
SOURCE:
The study was led by Margarida Lucas Rocha, MD, Department of Rheumatology, ULSA, Faro, Portugal. It was published online in Joint Bone Spine.
LIMITATIONS:
No limitations were reported in the study.
DISCLOSURES:
No relevant funding information and conflicts of interest were disclosed by the authors.
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.
Solo Vs McDoctors Inc.
STAT News recently ran a series on UnitedHealthcare (UHC) and its growing physician empire. This includes the corporation pressuring its employed physicians to see more patients, work weekends, upcode visits, add in diagnoses that will increase reimbursement, yadda, yadda, yadda.
For legal disclaimer purposes, I’m not saying UHC did any of this, nor am I saying they didn’t. But the series on STAT is worth reading.
Reading the articles brings back memories of the last time I was an employed physician, 24 years ago. I didn’t have people telling me to upcode visits, but I do remember hearing terms such as “dollars per physician per square foot” bandied about concerning my performance. At least back then no one was going to yell at me about a 1-star online review from a disgruntled patient.
After a little over 2 years I’d had enough and went solo.
I have no desire at this point to go back to that. I certainly make a lot less money than my employed counterparts, but I also have time and a degree of peace, which are worth something.
I’m not paying for anyone else’s overhead. I don’t slack off, but at least I know what I’m working for, and where the money is going when I write out a check. I can work my schedule around having to take my dog to the vet, or pick a kid up at the airport, or whatever.
I can spend more time with the patients who need it. Isn’t that part of why I’m here?
Wearing Hawaiian shirts and shorts to the office everyday is also a plus (at least I think so).
It surprises me that more physicians aren’t willing to go into solo or small group practice. The big advantage is freedom, only needing to pay the overhead and your salary, and cover for others when needed.
The downside is financial. Like our hunting and gathering ancestors, you eat what you kill. If there’s a shortfall in cash flow, I’m the one who doesn’t get paid. It’s always good to have a line of credit available to fall back on in a pinch.
I can see why it’s daunting. Coming out of training you have loans to pay off. You may have a young family, and your first mortgage. You sure don’t want to take out another loan to start a private practice. The security of a guaranteed paycheck and no start-up costs is attractive. I was there, too, and I also took the first job I was offered back then.
There’s also the fear of suddenly working without a net for the first time in your career. It’s reassuring to get some added experience while being able to bounce a challenging case off another doctor. (I still do that, too, and always will.)
But no one tells me to upcode visits or add diagnostic codes just to get more money. Patients don’t call in panicked that they have an ICD-10 code for a condition no one told them they had.
At the end of the day I can tell the guy in the mirror that I’m doing my best.
Medicine has changed a lot over time ... but being a doctor hasn’t. The spark that led us all here is still there, somewhere, I hope. Go back and read Neighbor Rosicky by Willa Cather, and The Doctor Stories by William Carlos Williams.
In an age when technology is moving us forward, I think the practice of medicine should move backward, away from McDoctors Inc. A small, even solo, medical practice isn’t incompatible with the shiny toys of 2024 medicine. You can make good patient care happen with both.
I freely admit that it’s not for everyone.
But I wish more people would see it as a realistic option, and take the road less traveled.
Dr. Block has a solo neurology practice in Scottsdale, Arizona.
STAT News recently ran a series on UnitedHealthcare (UHC) and its growing physician empire. This includes the corporation pressuring its employed physicians to see more patients, work weekends, upcode visits, add in diagnoses that will increase reimbursement, yadda, yadda, yadda.
For legal disclaimer purposes, I’m not saying UHC did any of this, nor am I saying they didn’t. But the series on STAT is worth reading.
Reading the articles brings back memories of the last time I was an employed physician, 24 years ago. I didn’t have people telling me to upcode visits, but I do remember hearing terms such as “dollars per physician per square foot” bandied about concerning my performance. At least back then no one was going to yell at me about a 1-star online review from a disgruntled patient.
After a little over 2 years I’d had enough and went solo.
I have no desire at this point to go back to that. I certainly make a lot less money than my employed counterparts, but I also have time and a degree of peace, which are worth something.
I’m not paying for anyone else’s overhead. I don’t slack off, but at least I know what I’m working for, and where the money is going when I write out a check. I can work my schedule around having to take my dog to the vet, or pick a kid up at the airport, or whatever.
I can spend more time with the patients who need it. Isn’t that part of why I’m here?
Wearing Hawaiian shirts and shorts to the office everyday is also a plus (at least I think so).
It surprises me that more physicians aren’t willing to go into solo or small group practice. The big advantage is freedom, only needing to pay the overhead and your salary, and cover for others when needed.
The downside is financial. Like our hunting and gathering ancestors, you eat what you kill. If there’s a shortfall in cash flow, I’m the one who doesn’t get paid. It’s always good to have a line of credit available to fall back on in a pinch.
I can see why it’s daunting. Coming out of training you have loans to pay off. You may have a young family, and your first mortgage. You sure don’t want to take out another loan to start a private practice. The security of a guaranteed paycheck and no start-up costs is attractive. I was there, too, and I also took the first job I was offered back then.
There’s also the fear of suddenly working without a net for the first time in your career. It’s reassuring to get some added experience while being able to bounce a challenging case off another doctor. (I still do that, too, and always will.)
But no one tells me to upcode visits or add diagnostic codes just to get more money. Patients don’t call in panicked that they have an ICD-10 code for a condition no one told them they had.
At the end of the day I can tell the guy in the mirror that I’m doing my best.
Medicine has changed a lot over time ... but being a doctor hasn’t. The spark that led us all here is still there, somewhere, I hope. Go back and read Neighbor Rosicky by Willa Cather, and The Doctor Stories by William Carlos Williams.
In an age when technology is moving us forward, I think the practice of medicine should move backward, away from McDoctors Inc. A small, even solo, medical practice isn’t incompatible with the shiny toys of 2024 medicine. You can make good patient care happen with both.
I freely admit that it’s not for everyone.
But I wish more people would see it as a realistic option, and take the road less traveled.
Dr. Block has a solo neurology practice in Scottsdale, Arizona.
STAT News recently ran a series on UnitedHealthcare (UHC) and its growing physician empire. This includes the corporation pressuring its employed physicians to see more patients, work weekends, upcode visits, add in diagnoses that will increase reimbursement, yadda, yadda, yadda.
For legal disclaimer purposes, I’m not saying UHC did any of this, nor am I saying they didn’t. But the series on STAT is worth reading.
Reading the articles brings back memories of the last time I was an employed physician, 24 years ago. I didn’t have people telling me to upcode visits, but I do remember hearing terms such as “dollars per physician per square foot” bandied about concerning my performance. At least back then no one was going to yell at me about a 1-star online review from a disgruntled patient.
After a little over 2 years I’d had enough and went solo.
I have no desire at this point to go back to that. I certainly make a lot less money than my employed counterparts, but I also have time and a degree of peace, which are worth something.
I’m not paying for anyone else’s overhead. I don’t slack off, but at least I know what I’m working for, and where the money is going when I write out a check. I can work my schedule around having to take my dog to the vet, or pick a kid up at the airport, or whatever.
I can spend more time with the patients who need it. Isn’t that part of why I’m here?
Wearing Hawaiian shirts and shorts to the office everyday is also a plus (at least I think so).
It surprises me that more physicians aren’t willing to go into solo or small group practice. The big advantage is freedom, only needing to pay the overhead and your salary, and cover for others when needed.
The downside is financial. Like our hunting and gathering ancestors, you eat what you kill. If there’s a shortfall in cash flow, I’m the one who doesn’t get paid. It’s always good to have a line of credit available to fall back on in a pinch.
I can see why it’s daunting. Coming out of training you have loans to pay off. You may have a young family, and your first mortgage. You sure don’t want to take out another loan to start a private practice. The security of a guaranteed paycheck and no start-up costs is attractive. I was there, too, and I also took the first job I was offered back then.
There’s also the fear of suddenly working without a net for the first time in your career. It’s reassuring to get some added experience while being able to bounce a challenging case off another doctor. (I still do that, too, and always will.)
But no one tells me to upcode visits or add diagnostic codes just to get more money. Patients don’t call in panicked that they have an ICD-10 code for a condition no one told them they had.
At the end of the day I can tell the guy in the mirror that I’m doing my best.
Medicine has changed a lot over time ... but being a doctor hasn’t. The spark that led us all here is still there, somewhere, I hope. Go back and read Neighbor Rosicky by Willa Cather, and The Doctor Stories by William Carlos Williams.
In an age when technology is moving us forward, I think the practice of medicine should move backward, away from McDoctors Inc. A small, even solo, medical practice isn’t incompatible with the shiny toys of 2024 medicine. You can make good patient care happen with both.
I freely admit that it’s not for everyone.
But I wish more people would see it as a realistic option, and take the road less traveled.
Dr. Block has a solo neurology practice in Scottsdale, Arizona.
How is VA Doing? Report Card Grades Are In
The US Department of Veterans Affairs (VA) is earning high marks for the quality of care provided to veterans, according to multiple sources. For instance, systematic reviews published in 2023 found that VA health care is consistently as good as, or surpasses, non-VA health care. In the latest Centers for Medicare & Medicaid Services (CMS) annual Overall Hospital Quality Star Ratings, 67% of VA hospitals received either 4 or 5 stars, compared with only 41% of non-VA hospitals.
Veterans themselves are awarding high marks. According to the Medicare nationwide survey of patients, VA hospitals outperformed non-VA hospitals on all 10 core patient satisfaction metrics, including overall hospital rating, communication with doctors, communication about medications, and willingness to recommend the hospital. Furthermore, trust in VA outpatient care has reached an all-time record high of 92%, according to a survey of more than 440,000 veterans.
This year, in fact, the VA has broken a number of its own records. The VA cites other high points:
- More than 127.5 million health care appointments, a 6% increase over last year;
- Shorter wait times: new patients saw an 11% reduction in average wait times for VA primary care and a 7% reduction for mental health care compared to last year;
- $187 billion in benefits to 6.7 million veterans and survivors this year—an all-time record;
- 2,517,519 disability benefit claims processed, a 27% increase over 2023;
- No-cost emergency health care is provided to more than 50,000 veterans in acute suicidal crises; the Veterans Crisis Line supported 1,123,591 million calls, texts, and chats, up 12% from 2023;
- 47,925 veterans experiencing homelessness were housed in fiscal year 2024 and 96% remain housed long-term;
- 519,453 spouses and dependents received survivor benefits, a 4.5% increase from 2023;
- Services, resources, and assistance provided to a record 88,095 veteran family caregivers, an 18.6% increase over the 2023 record;
- A record 741,259 women veterans received compensation payments, 8.2% more than 2023;
- VA dental clinics provided > 6 million procedures to > 630,000 veterans; through community care, the VA delivered a record additional 3.4 million procedures to > 330,000 veterans.
Other actions this year include: expanding eligibility for VA healthcare to all toxin-exposed veterans years earlier than called for by the PACT Act; expanding access to care across the nation through VA Access Sprints, adding night and weekend clinics, and increasing the number of veterans scheduled into daily clinic schedules; removing copays for the first 3 outpatient mental health care and substance use disorder visits of each calendar year through 2027; expanding access to VA cancer care through establishing new cancer presumptive conditions, expanding access to genetic, lung, and colorectal cancer screening, and expanding the Close to Me cancer care program; expanding access to in vitro fertilization for eligible unmarried veterans and eligible veterans in same-sex marriages; expanding access to VA care and benefits for some former service members discharged under other than honorable conditions; and launching tele-emergency care for veterans nationwide.
The VA will continue to “aggressively reach out to and engage veterans to encourage them to come to VA for the care and benefits they have earned.”
“Veterans deserve the very best from VA and our nation, and we will never settle for anything less,” said VA Secretary Denis McDonough. “We’re honored that more veterans are getting their earned health care and benefits from VA than ever before, but make no mistake: there is still work to do. We will continue to work each and every day to earn the trust of those we serve — and ensure that all Veterans, their families, and their survivors get the care and benefits they so rightly deserve.”
The US Department of Veterans Affairs (VA) is earning high marks for the quality of care provided to veterans, according to multiple sources. For instance, systematic reviews published in 2023 found that VA health care is consistently as good as, or surpasses, non-VA health care. In the latest Centers for Medicare & Medicaid Services (CMS) annual Overall Hospital Quality Star Ratings, 67% of VA hospitals received either 4 or 5 stars, compared with only 41% of non-VA hospitals.
Veterans themselves are awarding high marks. According to the Medicare nationwide survey of patients, VA hospitals outperformed non-VA hospitals on all 10 core patient satisfaction metrics, including overall hospital rating, communication with doctors, communication about medications, and willingness to recommend the hospital. Furthermore, trust in VA outpatient care has reached an all-time record high of 92%, according to a survey of more than 440,000 veterans.
This year, in fact, the VA has broken a number of its own records. The VA cites other high points:
- More than 127.5 million health care appointments, a 6% increase over last year;
- Shorter wait times: new patients saw an 11% reduction in average wait times for VA primary care and a 7% reduction for mental health care compared to last year;
- $187 billion in benefits to 6.7 million veterans and survivors this year—an all-time record;
- 2,517,519 disability benefit claims processed, a 27% increase over 2023;
- No-cost emergency health care is provided to more than 50,000 veterans in acute suicidal crises; the Veterans Crisis Line supported 1,123,591 million calls, texts, and chats, up 12% from 2023;
- 47,925 veterans experiencing homelessness were housed in fiscal year 2024 and 96% remain housed long-term;
- 519,453 spouses and dependents received survivor benefits, a 4.5% increase from 2023;
- Services, resources, and assistance provided to a record 88,095 veteran family caregivers, an 18.6% increase over the 2023 record;
- A record 741,259 women veterans received compensation payments, 8.2% more than 2023;
- VA dental clinics provided > 6 million procedures to > 630,000 veterans; through community care, the VA delivered a record additional 3.4 million procedures to > 330,000 veterans.
Other actions this year include: expanding eligibility for VA healthcare to all toxin-exposed veterans years earlier than called for by the PACT Act; expanding access to care across the nation through VA Access Sprints, adding night and weekend clinics, and increasing the number of veterans scheduled into daily clinic schedules; removing copays for the first 3 outpatient mental health care and substance use disorder visits of each calendar year through 2027; expanding access to VA cancer care through establishing new cancer presumptive conditions, expanding access to genetic, lung, and colorectal cancer screening, and expanding the Close to Me cancer care program; expanding access to in vitro fertilization for eligible unmarried veterans and eligible veterans in same-sex marriages; expanding access to VA care and benefits for some former service members discharged under other than honorable conditions; and launching tele-emergency care for veterans nationwide.
The VA will continue to “aggressively reach out to and engage veterans to encourage them to come to VA for the care and benefits they have earned.”
“Veterans deserve the very best from VA and our nation, and we will never settle for anything less,” said VA Secretary Denis McDonough. “We’re honored that more veterans are getting their earned health care and benefits from VA than ever before, but make no mistake: there is still work to do. We will continue to work each and every day to earn the trust of those we serve — and ensure that all Veterans, their families, and their survivors get the care and benefits they so rightly deserve.”
The US Department of Veterans Affairs (VA) is earning high marks for the quality of care provided to veterans, according to multiple sources. For instance, systematic reviews published in 2023 found that VA health care is consistently as good as, or surpasses, non-VA health care. In the latest Centers for Medicare & Medicaid Services (CMS) annual Overall Hospital Quality Star Ratings, 67% of VA hospitals received either 4 or 5 stars, compared with only 41% of non-VA hospitals.
Veterans themselves are awarding high marks. According to the Medicare nationwide survey of patients, VA hospitals outperformed non-VA hospitals on all 10 core patient satisfaction metrics, including overall hospital rating, communication with doctors, communication about medications, and willingness to recommend the hospital. Furthermore, trust in VA outpatient care has reached an all-time record high of 92%, according to a survey of more than 440,000 veterans.
This year, in fact, the VA has broken a number of its own records. The VA cites other high points:
- More than 127.5 million health care appointments, a 6% increase over last year;
- Shorter wait times: new patients saw an 11% reduction in average wait times for VA primary care and a 7% reduction for mental health care compared to last year;
- $187 billion in benefits to 6.7 million veterans and survivors this year—an all-time record;
- 2,517,519 disability benefit claims processed, a 27% increase over 2023;
- No-cost emergency health care is provided to more than 50,000 veterans in acute suicidal crises; the Veterans Crisis Line supported 1,123,591 million calls, texts, and chats, up 12% from 2023;
- 47,925 veterans experiencing homelessness were housed in fiscal year 2024 and 96% remain housed long-term;
- 519,453 spouses and dependents received survivor benefits, a 4.5% increase from 2023;
- Services, resources, and assistance provided to a record 88,095 veteran family caregivers, an 18.6% increase over the 2023 record;
- A record 741,259 women veterans received compensation payments, 8.2% more than 2023;
- VA dental clinics provided > 6 million procedures to > 630,000 veterans; through community care, the VA delivered a record additional 3.4 million procedures to > 330,000 veterans.
Other actions this year include: expanding eligibility for VA healthcare to all toxin-exposed veterans years earlier than called for by the PACT Act; expanding access to care across the nation through VA Access Sprints, adding night and weekend clinics, and increasing the number of veterans scheduled into daily clinic schedules; removing copays for the first 3 outpatient mental health care and substance use disorder visits of each calendar year through 2027; expanding access to VA cancer care through establishing new cancer presumptive conditions, expanding access to genetic, lung, and colorectal cancer screening, and expanding the Close to Me cancer care program; expanding access to in vitro fertilization for eligible unmarried veterans and eligible veterans in same-sex marriages; expanding access to VA care and benefits for some former service members discharged under other than honorable conditions; and launching tele-emergency care for veterans nationwide.
The VA will continue to “aggressively reach out to and engage veterans to encourage them to come to VA for the care and benefits they have earned.”
“Veterans deserve the very best from VA and our nation, and we will never settle for anything less,” said VA Secretary Denis McDonough. “We’re honored that more veterans are getting their earned health care and benefits from VA than ever before, but make no mistake: there is still work to do. We will continue to work each and every day to earn the trust of those we serve — and ensure that all Veterans, their families, and their survivors get the care and benefits they so rightly deserve.”
Does Bezlotoxumab Boost FMT Efficacy in IBD Patients With Recurrent CDI?
PHILADELPHIA – , according to a randomized controlled trial.
“Given the high efficacy of FMT, the addition of bezlotoxumab may not provide a further reduction in CDI recurrence,” said study author Jessica R. Allegretti, MD, MPH, AGAF, with Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts.
Allegretti presented the findings during a plenary session at the annual meeting of the American College of Gastroenterology (ACG).
Common and Deadly
CDI is the most common cause of healthcare-associated infection in the United States, leading to roughly 4.8 billion in excess healthcare costs. There are an estimated 500,000 cases each year in the United States, with roughly 30,000 of those cases leading to death.
Patients with IBD have a prevalence of CDI that is 2.5- to 8-fold higher than in peers without IBD, and they also have 4.5-fold higher risk of recurrence. Sequelae of CDI in IBD include exacerbations of IBD, increased hospitalizations, escalation of IBD therapy, and colectomy.
FMT has been shown to be safe and effective in patients with IBD and rCDI.
Bezlotoxumab — a fully human monoclonal antibody that binds to C difficile toxin B — was approved by the US Food and Drug Administration (FDA) in 2016 to reduce the recurrence of CDI in patients aged 18 years and older.
However, there is only limited data on the value of combining these two strategies.
Allegretti and colleagues conducted a multicenter randomized controlled trial to evaluate the impact of FMT in combination with bezlotoxumab in patients with IBD and rCDI.
They enrolled 61 patients (mean age, 38 years, 54% men) with two or more episodes of CDI who received a single colonoscopic FMT. Twenty patients had Crohn’s disease, and 41 had ulcerative colitis.
Thirty patients were randomly allocated to receive a single bezlotoxumab infusion and 31 to receive a placebo infusion prior to FMT.
A total of five participants (8%) experienced a CDI recurrence with confirmed EIA+ stool –4 in the treatment group and 1 in the placebo group (13% vs 3%, P = .15).
Participants in the treatment group had higher odds of CDI recurrence, though this was not statistically significant (odds ratio [OR], 4.6; 95% CI, 0.5-43.9), Allegretti reported.
With regards to C difficile colonization, more patients in the treatment group were decolonized compared with placebo at week 1 (82% vs 68%, P = .22) and at week 12 (83% vs 72%, P = .34).
Steroid use at the time of FMT was associated with a significant increased risk of ongoing colonization of C difficile at week 12 post-FMT (OR, 4.90; 95% CI, 1.18-20.37; P = .03).
While there were no significant differences in IBD outcomes between groups, there were numerically higher rates of IBD improvement in the treatment group compared to the placebo group 56% vs 46%.
Only one patient had IBD worsen, and this patient was in the placebo group. There were no de novo IBD flares.
FMT alone and with bezlotoxumab were both safe and well tolerated. Two serious adverse events were reported; neither were deemed to be treatment-related.
“This is the first clinical trial to assess the clinical effect of FMT in combination with bezlotoxumab in patients with IBD and rCDI. The data suggest no clear efficacy benefit to this combination compared to FMT alone,” Allegretti told attendees.
“This finding is not surprising given the high rate of efficacy of FMT,” said Ashwin N. Ananthakrishnan, MD, MPH, AGAF, with Massachusetts General Hospital and Harvard Medical School, Boston, who was not involved in the study.
“It would have been interesting to compare bezlotoxumab vs FMT as primary treatment for recurrent CDI in this population,” Ananthakrishnan added.
This was an investigator-initiated study funded by Merck. Allegretti disclosed various relationships with Abbvie, Artugen, Bristol Myers Squibb, Ferring, Finch Therapeutics, Janssen, Merck, Pfizer, and Seres. Ananthakrishnan had no relevant disclosures.
A version of this article first appeared on Medscape.com.
PHILADELPHIA – , according to a randomized controlled trial.
“Given the high efficacy of FMT, the addition of bezlotoxumab may not provide a further reduction in CDI recurrence,” said study author Jessica R. Allegretti, MD, MPH, AGAF, with Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts.
Allegretti presented the findings during a plenary session at the annual meeting of the American College of Gastroenterology (ACG).
Common and Deadly
CDI is the most common cause of healthcare-associated infection in the United States, leading to roughly 4.8 billion in excess healthcare costs. There are an estimated 500,000 cases each year in the United States, with roughly 30,000 of those cases leading to death.
Patients with IBD have a prevalence of CDI that is 2.5- to 8-fold higher than in peers without IBD, and they also have 4.5-fold higher risk of recurrence. Sequelae of CDI in IBD include exacerbations of IBD, increased hospitalizations, escalation of IBD therapy, and colectomy.
FMT has been shown to be safe and effective in patients with IBD and rCDI.
Bezlotoxumab — a fully human monoclonal antibody that binds to C difficile toxin B — was approved by the US Food and Drug Administration (FDA) in 2016 to reduce the recurrence of CDI in patients aged 18 years and older.
However, there is only limited data on the value of combining these two strategies.
Allegretti and colleagues conducted a multicenter randomized controlled trial to evaluate the impact of FMT in combination with bezlotoxumab in patients with IBD and rCDI.
They enrolled 61 patients (mean age, 38 years, 54% men) with two or more episodes of CDI who received a single colonoscopic FMT. Twenty patients had Crohn’s disease, and 41 had ulcerative colitis.
Thirty patients were randomly allocated to receive a single bezlotoxumab infusion and 31 to receive a placebo infusion prior to FMT.
A total of five participants (8%) experienced a CDI recurrence with confirmed EIA+ stool –4 in the treatment group and 1 in the placebo group (13% vs 3%, P = .15).
Participants in the treatment group had higher odds of CDI recurrence, though this was not statistically significant (odds ratio [OR], 4.6; 95% CI, 0.5-43.9), Allegretti reported.
With regards to C difficile colonization, more patients in the treatment group were decolonized compared with placebo at week 1 (82% vs 68%, P = .22) and at week 12 (83% vs 72%, P = .34).
Steroid use at the time of FMT was associated with a significant increased risk of ongoing colonization of C difficile at week 12 post-FMT (OR, 4.90; 95% CI, 1.18-20.37; P = .03).
While there were no significant differences in IBD outcomes between groups, there were numerically higher rates of IBD improvement in the treatment group compared to the placebo group 56% vs 46%.
Only one patient had IBD worsen, and this patient was in the placebo group. There were no de novo IBD flares.
FMT alone and with bezlotoxumab were both safe and well tolerated. Two serious adverse events were reported; neither were deemed to be treatment-related.
“This is the first clinical trial to assess the clinical effect of FMT in combination with bezlotoxumab in patients with IBD and rCDI. The data suggest no clear efficacy benefit to this combination compared to FMT alone,” Allegretti told attendees.
“This finding is not surprising given the high rate of efficacy of FMT,” said Ashwin N. Ananthakrishnan, MD, MPH, AGAF, with Massachusetts General Hospital and Harvard Medical School, Boston, who was not involved in the study.
“It would have been interesting to compare bezlotoxumab vs FMT as primary treatment for recurrent CDI in this population,” Ananthakrishnan added.
This was an investigator-initiated study funded by Merck. Allegretti disclosed various relationships with Abbvie, Artugen, Bristol Myers Squibb, Ferring, Finch Therapeutics, Janssen, Merck, Pfizer, and Seres. Ananthakrishnan had no relevant disclosures.
A version of this article first appeared on Medscape.com.
PHILADELPHIA – , according to a randomized controlled trial.
“Given the high efficacy of FMT, the addition of bezlotoxumab may not provide a further reduction in CDI recurrence,” said study author Jessica R. Allegretti, MD, MPH, AGAF, with Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts.
Allegretti presented the findings during a plenary session at the annual meeting of the American College of Gastroenterology (ACG).
Common and Deadly
CDI is the most common cause of healthcare-associated infection in the United States, leading to roughly 4.8 billion in excess healthcare costs. There are an estimated 500,000 cases each year in the United States, with roughly 30,000 of those cases leading to death.
Patients with IBD have a prevalence of CDI that is 2.5- to 8-fold higher than in peers without IBD, and they also have 4.5-fold higher risk of recurrence. Sequelae of CDI in IBD include exacerbations of IBD, increased hospitalizations, escalation of IBD therapy, and colectomy.
FMT has been shown to be safe and effective in patients with IBD and rCDI.
Bezlotoxumab — a fully human monoclonal antibody that binds to C difficile toxin B — was approved by the US Food and Drug Administration (FDA) in 2016 to reduce the recurrence of CDI in patients aged 18 years and older.
However, there is only limited data on the value of combining these two strategies.
Allegretti and colleagues conducted a multicenter randomized controlled trial to evaluate the impact of FMT in combination with bezlotoxumab in patients with IBD and rCDI.
They enrolled 61 patients (mean age, 38 years, 54% men) with two or more episodes of CDI who received a single colonoscopic FMT. Twenty patients had Crohn’s disease, and 41 had ulcerative colitis.
Thirty patients were randomly allocated to receive a single bezlotoxumab infusion and 31 to receive a placebo infusion prior to FMT.
A total of five participants (8%) experienced a CDI recurrence with confirmed EIA+ stool –4 in the treatment group and 1 in the placebo group (13% vs 3%, P = .15).
Participants in the treatment group had higher odds of CDI recurrence, though this was not statistically significant (odds ratio [OR], 4.6; 95% CI, 0.5-43.9), Allegretti reported.
With regards to C difficile colonization, more patients in the treatment group were decolonized compared with placebo at week 1 (82% vs 68%, P = .22) and at week 12 (83% vs 72%, P = .34).
Steroid use at the time of FMT was associated with a significant increased risk of ongoing colonization of C difficile at week 12 post-FMT (OR, 4.90; 95% CI, 1.18-20.37; P = .03).
While there were no significant differences in IBD outcomes between groups, there were numerically higher rates of IBD improvement in the treatment group compared to the placebo group 56% vs 46%.
Only one patient had IBD worsen, and this patient was in the placebo group. There were no de novo IBD flares.
FMT alone and with bezlotoxumab were both safe and well tolerated. Two serious adverse events were reported; neither were deemed to be treatment-related.
“This is the first clinical trial to assess the clinical effect of FMT in combination with bezlotoxumab in patients with IBD and rCDI. The data suggest no clear efficacy benefit to this combination compared to FMT alone,” Allegretti told attendees.
“This finding is not surprising given the high rate of efficacy of FMT,” said Ashwin N. Ananthakrishnan, MD, MPH, AGAF, with Massachusetts General Hospital and Harvard Medical School, Boston, who was not involved in the study.
“It would have been interesting to compare bezlotoxumab vs FMT as primary treatment for recurrent CDI in this population,” Ananthakrishnan added.
This was an investigator-initiated study funded by Merck. Allegretti disclosed various relationships with Abbvie, Artugen, Bristol Myers Squibb, Ferring, Finch Therapeutics, Janssen, Merck, Pfizer, and Seres. Ananthakrishnan had no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM ACG 2024