Dermatology News

Abrocitinib, an investigational drug proven to be a safe and effective treatment for moderate to severe atopic dermatitis (AD) in adults 18 years and older, is also safe and effective in patients aged 12-17 years, according to a randomized trial of the oral, once-daily Janus kinase (JAK) 1 selective inhibitor, used in combination with medicated topical therapy.

The results, from the phase 3 JADE TEEN study, were presented during an oral abstract session at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, held virtually this year.

“We’re very excited about the introduction of oral JAKs into our armamentarium for atopic dermatitis,” lead author Lawrence Eichenfield, MD, professor of dermatology and pediatrics, University of California, San Diego, and chief of pediatric and adolescent dermatology, Rady Children’s Hospital, also in San Diego, said in an interview.

AD ranges in severity, and there is a great deal of moderate to severe AD that has a tremendous negative impact on the individual, Dr. Eichenfield said. “Traditionally we have treated it with intermittent topical corticosteroids, but this has left a significant percentage of patients without long-term disease control.”

JAK inhibitors are effective mediators of the inflammation response that occurs in moderate to severe AD. They inhibit the stimulation of the JAK pathway and allow anti-inflammatory effects and therefore have potential, especially in more severe disease, Dr. Eichenfield said.

In the current study, which is a spin-off of the original study that looked at abrocitinib in adults, he and his team randomly assigned 285 teens (mean age, 14.9 years; 50.9% male; 56.1% White) with moderate to severe AD to receive one of the following treatments for 12 weeks: abrocitinib 200 mg plus topical therapy (95); abrocitinib 100 mg plus topical therapy (95); or placebo, which consisted of topical therapy alone (95).

The primary endpoints were an Investigator’s Global Assessment response of clear or almost clear (scores of 0 and 1, respectively), with an improvement of at least 2 points, and an improvement in Eczema Area and Severity Index score of at least 75% at week 12.

Secondary endpoints included an improvement in Peak Pruritus Numerical Rating Scale (PP-NRS) response of at least 4 points at week 12.

The teens who received abrocitinib along with medicated topical therapy showed significant improvement in the severity of their AD at the end of the 12-week period, compared with those in the placebo group.

“The percentage of patients achieving essentially no itch, as captured in the fact that more than half of those on the higher dose of abrocitinib made it to no itch, is a new data point and is important to note,” Dr. Eichenfield said. “A lot of the other medicines don’t really get a significant percentage of the population to an itch score of 0 to 1. This drug brought about a rapid and profound itch relief.”

He added: “The results from JADE TEEN extend the drug’s utility in this younger population and show that abrocitinib performs the same with regard to efficacy and safety in the teenagers. Having atopic dermatitis that does not respond to treatment is especially hard for adolescents, but now we know that abrocitinib will be safe and effective and so we now have something to offer these kids.”

“Abrocitinib achieved a good response in this study that was statistically significant, compared to standard treatment,” Jonathan A. Bernstein, MD, professor of medicine at the University of Cincinnati, commented in an interview.

“JAK inhibitors are very promising, and this study adds to that promise. They play an important role in atopic dermatitis, so obviously, teenagers with AD represent an important population,” said Dr. Bernstein, who was not part of the study. “These results are very encouraging, and I think that we will probably see some of these JAK inhibitors approved by the FDA, if not this year, probably next.”

The study was sponsored by Pfizer. Dr. Eichenfield serves as an investigator, speaker, and consultant for Pfizer; and as an investigator, speaker, consultant, and/or is on a data safety monitoring board for AbbVie, Almirall, Amgen, Arcutis, Asana, Dermavant, Dermira, Forte, Galderma, Ichnos/Glenmark, Incyte, LEO, Lilly, L’Oreal, Novartis, Regeneron, Sanofi-Genzyme, and Verrica. Dr. Bernstein disclosed no relevant financial relationships.
 

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

Abrocitinib, an investigational drug proven to be a safe and effective treatment for moderate to severe atopic dermatitis (AD) in adults 18 years and older, is also safe and effective in patients aged 12-17 years, according to a randomized trial of the oral, once-daily Janus kinase (JAK) 1 selective inhibitor, used in combination with medicated topical therapy.

The results, from the phase 3 JADE TEEN study, were presented during an oral abstract session at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, held virtually this year.

“We’re very excited about the introduction of oral JAKs into our armamentarium for atopic dermatitis,” lead author Lawrence Eichenfield, MD, professor of dermatology and pediatrics, University of California, San Diego, and chief of pediatric and adolescent dermatology, Rady Children’s Hospital, also in San Diego, said in an interview.

AD ranges in severity, and there is a great deal of moderate to severe AD that has a tremendous negative impact on the individual, Dr. Eichenfield said. “Traditionally we have treated it with intermittent topical corticosteroids, but this has left a significant percentage of patients without long-term disease control.”

JAK inhibitors are effective mediators of the inflammation response that occurs in moderate to severe AD. They inhibit the stimulation of the JAK pathway and allow anti-inflammatory effects and therefore have potential, especially in more severe disease, Dr. Eichenfield said.

In the current study, which is a spin-off of the original study that looked at abrocitinib in adults, he and his team randomly assigned 285 teens (mean age, 14.9 years; 50.9% male; 56.1% White) with moderate to severe AD to receive one of the following treatments for 12 weeks: abrocitinib 200 mg plus topical therapy (95); abrocitinib 100 mg plus topical therapy (95); or placebo, which consisted of topical therapy alone (95).

The primary endpoints were an Investigator’s Global Assessment response of clear or almost clear (scores of 0 and 1, respectively), with an improvement of at least 2 points, and an improvement in Eczema Area and Severity Index score of at least 75% at week 12.

Secondary endpoints included an improvement in Peak Pruritus Numerical Rating Scale (PP-NRS) response of at least 4 points at week 12.

The teens who received abrocitinib along with medicated topical therapy showed significant improvement in the severity of their AD at the end of the 12-week period, compared with those in the placebo group.

“The percentage of patients achieving essentially no itch, as captured in the fact that more than half of those on the higher dose of abrocitinib made it to no itch, is a new data point and is important to note,” Dr. Eichenfield said. “A lot of the other medicines don’t really get a significant percentage of the population to an itch score of 0 to 1. This drug brought about a rapid and profound itch relief.”

He added: “The results from JADE TEEN extend the drug’s utility in this younger population and show that abrocitinib performs the same with regard to efficacy and safety in the teenagers. Having atopic dermatitis that does not respond to treatment is especially hard for adolescents, but now we know that abrocitinib will be safe and effective and so we now have something to offer these kids.”

“Abrocitinib achieved a good response in this study that was statistically significant, compared to standard treatment,” Jonathan A. Bernstein, MD, professor of medicine at the University of Cincinnati, commented in an interview.

“JAK inhibitors are very promising, and this study adds to that promise. They play an important role in atopic dermatitis, so obviously, teenagers with AD represent an important population,” said Dr. Bernstein, who was not part of the study. “These results are very encouraging, and I think that we will probably see some of these JAK inhibitors approved by the FDA, if not this year, probably next.”

The study was sponsored by Pfizer. Dr. Eichenfield serves as an investigator, speaker, and consultant for Pfizer; and as an investigator, speaker, consultant, and/or is on a data safety monitoring board for AbbVie, Almirall, Amgen, Arcutis, Asana, Dermavant, Dermira, Forte, Galderma, Ichnos/Glenmark, Incyte, LEO, Lilly, L’Oreal, Novartis, Regeneron, Sanofi-Genzyme, and Verrica. Dr. Bernstein disclosed no relevant financial relationships.
 

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

Abrocitinib, an investigational drug proven to be a safe and effective treatment for moderate to severe atopic dermatitis (AD) in adults 18 years and older, is also safe and effective in patients aged 12-17 years, according to a randomized trial of the oral, once-daily Janus kinase (JAK) 1 selective inhibitor, used in combination with medicated topical therapy.

The results, from the phase 3 JADE TEEN study, were presented during an oral abstract session at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, held virtually this year.

“We’re very excited about the introduction of oral JAKs into our armamentarium for atopic dermatitis,” lead author Lawrence Eichenfield, MD, professor of dermatology and pediatrics, University of California, San Diego, and chief of pediatric and adolescent dermatology, Rady Children’s Hospital, also in San Diego, said in an interview.

AD ranges in severity, and there is a great deal of moderate to severe AD that has a tremendous negative impact on the individual, Dr. Eichenfield said. “Traditionally we have treated it with intermittent topical corticosteroids, but this has left a significant percentage of patients without long-term disease control.”

JAK inhibitors are effective mediators of the inflammation response that occurs in moderate to severe AD. They inhibit the stimulation of the JAK pathway and allow anti-inflammatory effects and therefore have potential, especially in more severe disease, Dr. Eichenfield said.

In the current study, which is a spin-off of the original study that looked at abrocitinib in adults, he and his team randomly assigned 285 teens (mean age, 14.9 years; 50.9% male; 56.1% White) with moderate to severe AD to receive one of the following treatments for 12 weeks: abrocitinib 200 mg plus topical therapy (95); abrocitinib 100 mg plus topical therapy (95); or placebo, which consisted of topical therapy alone (95).

The primary endpoints were an Investigator’s Global Assessment response of clear or almost clear (scores of 0 and 1, respectively), with an improvement of at least 2 points, and an improvement in Eczema Area and Severity Index score of at least 75% at week 12.

Secondary endpoints included an improvement in Peak Pruritus Numerical Rating Scale (PP-NRS) response of at least 4 points at week 12.

The teens who received abrocitinib along with medicated topical therapy showed significant improvement in the severity of their AD at the end of the 12-week period, compared with those in the placebo group.

“The percentage of patients achieving essentially no itch, as captured in the fact that more than half of those on the higher dose of abrocitinib made it to no itch, is a new data point and is important to note,” Dr. Eichenfield said. “A lot of the other medicines don’t really get a significant percentage of the population to an itch score of 0 to 1. This drug brought about a rapid and profound itch relief.”

He added: “The results from JADE TEEN extend the drug’s utility in this younger population and show that abrocitinib performs the same with regard to efficacy and safety in the teenagers. Having atopic dermatitis that does not respond to treatment is especially hard for adolescents, but now we know that abrocitinib will be safe and effective and so we now have something to offer these kids.”

“Abrocitinib achieved a good response in this study that was statistically significant, compared to standard treatment,” Jonathan A. Bernstein, MD, professor of medicine at the University of Cincinnati, commented in an interview.

“JAK inhibitors are very promising, and this study adds to that promise. They play an important role in atopic dermatitis, so obviously, teenagers with AD represent an important population,” said Dr. Bernstein, who was not part of the study. “These results are very encouraging, and I think that we will probably see some of these JAK inhibitors approved by the FDA, if not this year, probably next.”

The study was sponsored by Pfizer. Dr. Eichenfield serves as an investigator, speaker, and consultant for Pfizer; and as an investigator, speaker, consultant, and/or is on a data safety monitoring board for AbbVie, Almirall, Amgen, Arcutis, Asana, Dermavant, Dermira, Forte, Galderma, Ichnos/Glenmark, Incyte, LEO, Lilly, L’Oreal, Novartis, Regeneron, Sanofi-Genzyme, and Verrica. Dr. Bernstein disclosed no relevant financial relationships.
 

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

Several surprising recent insights into the pathophysiology of psoriasis may eventually lead to superior treatment strategies for this common T-cell-mediated disease, Kenneth Brian Gordon, MD, said at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually.

Courtesy National Psoriasis Foundation

Among these unexpected developments was the startling finding that skin inflammation in mild psoriasis is at least as great as in severe disease; evidence that psoriasis may actually be an autoimmune disease rather than a nonspecific immune-mediated disease; and the newly appreciated importance of interleukin-19 (IL-19) in keratinocyte proliferation, according to Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.

Immunoregulatory deficits in mild vs. severe psoriasis

Conventional wisdom has held that mild psoriasis as defined by limited affected body surface area involves less skin inflammation than more extensive severe psoriasis, so less-potent topical therapies are appropriate. Not so, according to Dr. Gordon, who highlighted work by James G. Krueger, MD, PhD, head of the laboratory of investigative dermatology at Rockefeller University, New York, and coinvestigators. They demonstrated that overall skin inflammation expressed as the sum of T-cell activation and IL-19-mediated epidermal responses didn’t differ in lesions of mild as compared with severe psoriasis. Indeed, mild skin lesions featured a greater number of T-cells, stronger expression of proinflammatory cytokine IL-17A, and greater expression of the central psoriasis transcriptome. The big difference between skin lesions of mild versus severe psoriasis was that severe psoriasis was characterized by strikingly weaker expression of immunoregulatory genes, including programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4), than that of mild lesions.

The implication is that IL-17-targeted therapies may be of benefit in a much larger segment of the psoriatic population: namely, those with mild disease, who comprise the majority of psoriasis patients by a wide margin, according to the investigators.

Dr. Gordon concurs.

“The primary problem in psoriasis is not so much the inflammatory activity, but the ability to turn off the activity,” he explained. “That implies that if a patient wants to get clear or have significant improvement in disease, you can’t use a less effective medication just because they have less amount of disease. You’re going to need to treat it just as aggressively because the great majority of our medications block the proinflammatory pathways.”

The deficit in immunoregulatory action identified by Dr. Krueger and colleagues in patients with severe disease could provide a novel therapeutic target. If the deficient immunoregulation could be boosted, it might achieve disease control without need for continuous anti-inflammatory therapy.

 

Autoimmunity in psoriasis

“When I started work in psoriasis, we always thought there would be a common antigen for the immune process in the disease. We never found it. So for that reason, we sort of put it aside and called psoriasis a nonspecific immune-mediated disease,” Dr. Gordon recalled.

That view is being reexamined. “While we’re not completely certain, there is now some evidence that there might be autoimmunity in psoriasis,” he said.

He cited work by an international team of investigators who identified the cathelicidin antimicrobial peptide LL37 as being overexpressed in psoriatic skin, where it appears to serve as a T-cell autoantigen. LL37-specific CD4+ and CD8+ T-cells are skin homing: They can infiltrate lesional skin, where they produce interferon-gamma and proinflammatory Th17 cytokines. The investigators reported that levels of circulating LL37-specific T cells correlated with disease activity such that they were found in three-quarters of patients with moderate to severe plaque psoriasis.

“As LL37 is able to activate innate immune cells and break innate tolerance to self-nucleic acids, it represents an even more appealing target to treat psoriasis. Therapeutic targeting of LL37-specific T cells may provide new avenues to prevent or treat psoriasis without inducing indiscriminate immunosuppression,” the investigators concluded.

Similarly, German investigators have identified ADAMTS-like protein 5 (ADAMTSL5) as an autoantigen specific for melanocytes in psoriasis patients who possess the central psoriasis risk gene, known as HLA-C*06:02, which is present in two-thirds of patients with psoriasis. They proposed that their newly recognized autoimmune pathway may explain how HLA-C*06.02 predisposes to psoriasis.

Growing clinical relevance of IL-19

It’s now well-established that IL-17 is the pivotal force driving the changes in keratinocytes that define the visible expressions of psoriasis, including plaque scale and thickness, which are due to abnormal keratinocyte maturation and proliferation, respectively. Less well appreciated is the fact that IL-17-activated keratinocytes produce IL-19, which feeds back and further stimulates keratinocyte proliferation.

In light of mounting evidence that IL-19 plays an important role in the pathogenesis of psoriasis and that naked eye assessment of visible psoriasis may not reflect the true extent of inflammation, Brian J. Nickoloff, MD, PhD, and coworkers at Lilly Research Laboratories have developed a novel serum IL-19 immunoassay that appears to provide a much-needed objective biomarker of disease activity in psoriasis patients. They demonstrated that serum IL-19 levels correlated with Psoriasis Area and Severity Index scores, and that treatment with the anti-IL-17A biologic ixekizumab (Taltz) led to rapid reduction of IL-19 down to a normal level.

Moreover, following withdrawal of ixekizumab, IL-19 levels rose prior to clinical relapse, then dropped again in response to retreatment. The hope is that this assay will serve as an accurate tool for assessment of response to therapy.

Dr. Gordon reported receiving research funding and/or honoraria from more than a dozen pharmaceutical companies involved in psoriasis therapy.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

Several surprising recent insights into the pathophysiology of psoriasis may eventually lead to superior treatment strategies for this common T-cell-mediated disease, Kenneth Brian Gordon, MD, said at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually.

Courtesy National Psoriasis Foundation

Among these unexpected developments was the startling finding that skin inflammation in mild psoriasis is at least as great as in severe disease; evidence that psoriasis may actually be an autoimmune disease rather than a nonspecific immune-mediated disease; and the newly appreciated importance of interleukin-19 (IL-19) in keratinocyte proliferation, according to Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.

Immunoregulatory deficits in mild vs. severe psoriasis

Conventional wisdom has held that mild psoriasis as defined by limited affected body surface area involves less skin inflammation than more extensive severe psoriasis, so less-potent topical therapies are appropriate. Not so, according to Dr. Gordon, who highlighted work by James G. Krueger, MD, PhD, head of the laboratory of investigative dermatology at Rockefeller University, New York, and coinvestigators. They demonstrated that overall skin inflammation expressed as the sum of T-cell activation and IL-19-mediated epidermal responses didn’t differ in lesions of mild as compared with severe psoriasis. Indeed, mild skin lesions featured a greater number of T-cells, stronger expression of proinflammatory cytokine IL-17A, and greater expression of the central psoriasis transcriptome. The big difference between skin lesions of mild versus severe psoriasis was that severe psoriasis was characterized by strikingly weaker expression of immunoregulatory genes, including programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4), than that of mild lesions.

The implication is that IL-17-targeted therapies may be of benefit in a much larger segment of the psoriatic population: namely, those with mild disease, who comprise the majority of psoriasis patients by a wide margin, according to the investigators.

Dr. Gordon concurs.

“The primary problem in psoriasis is not so much the inflammatory activity, but the ability to turn off the activity,” he explained. “That implies that if a patient wants to get clear or have significant improvement in disease, you can’t use a less effective medication just because they have less amount of disease. You’re going to need to treat it just as aggressively because the great majority of our medications block the proinflammatory pathways.”

The deficit in immunoregulatory action identified by Dr. Krueger and colleagues in patients with severe disease could provide a novel therapeutic target. If the deficient immunoregulation could be boosted, it might achieve disease control without need for continuous anti-inflammatory therapy.

 

Autoimmunity in psoriasis

“When I started work in psoriasis, we always thought there would be a common antigen for the immune process in the disease. We never found it. So for that reason, we sort of put it aside and called psoriasis a nonspecific immune-mediated disease,” Dr. Gordon recalled.

That view is being reexamined. “While we’re not completely certain, there is now some evidence that there might be autoimmunity in psoriasis,” he said.

He cited work by an international team of investigators who identified the cathelicidin antimicrobial peptide LL37 as being overexpressed in psoriatic skin, where it appears to serve as a T-cell autoantigen. LL37-specific CD4+ and CD8+ T-cells are skin homing: They can infiltrate lesional skin, where they produce interferon-gamma and proinflammatory Th17 cytokines. The investigators reported that levels of circulating LL37-specific T cells correlated with disease activity such that they were found in three-quarters of patients with moderate to severe plaque psoriasis.

“As LL37 is able to activate innate immune cells and break innate tolerance to self-nucleic acids, it represents an even more appealing target to treat psoriasis. Therapeutic targeting of LL37-specific T cells may provide new avenues to prevent or treat psoriasis without inducing indiscriminate immunosuppression,” the investigators concluded.

Similarly, German investigators have identified ADAMTS-like protein 5 (ADAMTSL5) as an autoantigen specific for melanocytes in psoriasis patients who possess the central psoriasis risk gene, known as HLA-C*06:02, which is present in two-thirds of patients with psoriasis. They proposed that their newly recognized autoimmune pathway may explain how HLA-C*06.02 predisposes to psoriasis.

Growing clinical relevance of IL-19

It’s now well-established that IL-17 is the pivotal force driving the changes in keratinocytes that define the visible expressions of psoriasis, including plaque scale and thickness, which are due to abnormal keratinocyte maturation and proliferation, respectively. Less well appreciated is the fact that IL-17-activated keratinocytes produce IL-19, which feeds back and further stimulates keratinocyte proliferation.

In light of mounting evidence that IL-19 plays an important role in the pathogenesis of psoriasis and that naked eye assessment of visible psoriasis may not reflect the true extent of inflammation, Brian J. Nickoloff, MD, PhD, and coworkers at Lilly Research Laboratories have developed a novel serum IL-19 immunoassay that appears to provide a much-needed objective biomarker of disease activity in psoriasis patients. They demonstrated that serum IL-19 levels correlated with Psoriasis Area and Severity Index scores, and that treatment with the anti-IL-17A biologic ixekizumab (Taltz) led to rapid reduction of IL-19 down to a normal level.

Moreover, following withdrawal of ixekizumab, IL-19 levels rose prior to clinical relapse, then dropped again in response to retreatment. The hope is that this assay will serve as an accurate tool for assessment of response to therapy.

Dr. Gordon reported receiving research funding and/or honoraria from more than a dozen pharmaceutical companies involved in psoriasis therapy.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

Several surprising recent insights into the pathophysiology of psoriasis may eventually lead to superior treatment strategies for this common T-cell-mediated disease, Kenneth Brian Gordon, MD, said at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually.

Courtesy National Psoriasis Foundation

Among these unexpected developments was the startling finding that skin inflammation in mild psoriasis is at least as great as in severe disease; evidence that psoriasis may actually be an autoimmune disease rather than a nonspecific immune-mediated disease; and the newly appreciated importance of interleukin-19 (IL-19) in keratinocyte proliferation, according to Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.

Immunoregulatory deficits in mild vs. severe psoriasis

Conventional wisdom has held that mild psoriasis as defined by limited affected body surface area involves less skin inflammation than more extensive severe psoriasis, so less-potent topical therapies are appropriate. Not so, according to Dr. Gordon, who highlighted work by James G. Krueger, MD, PhD, head of the laboratory of investigative dermatology at Rockefeller University, New York, and coinvestigators. They demonstrated that overall skin inflammation expressed as the sum of T-cell activation and IL-19-mediated epidermal responses didn’t differ in lesions of mild as compared with severe psoriasis. Indeed, mild skin lesions featured a greater number of T-cells, stronger expression of proinflammatory cytokine IL-17A, and greater expression of the central psoriasis transcriptome. The big difference between skin lesions of mild versus severe psoriasis was that severe psoriasis was characterized by strikingly weaker expression of immunoregulatory genes, including programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4), than that of mild lesions.

The implication is that IL-17-targeted therapies may be of benefit in a much larger segment of the psoriatic population: namely, those with mild disease, who comprise the majority of psoriasis patients by a wide margin, according to the investigators.

Dr. Gordon concurs.

“The primary problem in psoriasis is not so much the inflammatory activity, but the ability to turn off the activity,” he explained. “That implies that if a patient wants to get clear or have significant improvement in disease, you can’t use a less effective medication just because they have less amount of disease. You’re going to need to treat it just as aggressively because the great majority of our medications block the proinflammatory pathways.”

The deficit in immunoregulatory action identified by Dr. Krueger and colleagues in patients with severe disease could provide a novel therapeutic target. If the deficient immunoregulation could be boosted, it might achieve disease control without need for continuous anti-inflammatory therapy.

 

Autoimmunity in psoriasis

“When I started work in psoriasis, we always thought there would be a common antigen for the immune process in the disease. We never found it. So for that reason, we sort of put it aside and called psoriasis a nonspecific immune-mediated disease,” Dr. Gordon recalled.

That view is being reexamined. “While we’re not completely certain, there is now some evidence that there might be autoimmunity in psoriasis,” he said.

He cited work by an international team of investigators who identified the cathelicidin antimicrobial peptide LL37 as being overexpressed in psoriatic skin, where it appears to serve as a T-cell autoantigen. LL37-specific CD4+ and CD8+ T-cells are skin homing: They can infiltrate lesional skin, where they produce interferon-gamma and proinflammatory Th17 cytokines. The investigators reported that levels of circulating LL37-specific T cells correlated with disease activity such that they were found in three-quarters of patients with moderate to severe plaque psoriasis.

“As LL37 is able to activate innate immune cells and break innate tolerance to self-nucleic acids, it represents an even more appealing target to treat psoriasis. Therapeutic targeting of LL37-specific T cells may provide new avenues to prevent or treat psoriasis without inducing indiscriminate immunosuppression,” the investigators concluded.

Similarly, German investigators have identified ADAMTS-like protein 5 (ADAMTSL5) as an autoantigen specific for melanocytes in psoriasis patients who possess the central psoriasis risk gene, known as HLA-C*06:02, which is present in two-thirds of patients with psoriasis. They proposed that their newly recognized autoimmune pathway may explain how HLA-C*06.02 predisposes to psoriasis.

Growing clinical relevance of IL-19

It’s now well-established that IL-17 is the pivotal force driving the changes in keratinocytes that define the visible expressions of psoriasis, including plaque scale and thickness, which are due to abnormal keratinocyte maturation and proliferation, respectively. Less well appreciated is the fact that IL-17-activated keratinocytes produce IL-19, which feeds back and further stimulates keratinocyte proliferation.

In light of mounting evidence that IL-19 plays an important role in the pathogenesis of psoriasis and that naked eye assessment of visible psoriasis may not reflect the true extent of inflammation, Brian J. Nickoloff, MD, PhD, and coworkers at Lilly Research Laboratories have developed a novel serum IL-19 immunoassay that appears to provide a much-needed objective biomarker of disease activity in psoriasis patients. They demonstrated that serum IL-19 levels correlated with Psoriasis Area and Severity Index scores, and that treatment with the anti-IL-17A biologic ixekizumab (Taltz) led to rapid reduction of IL-19 down to a normal level.

Moreover, following withdrawal of ixekizumab, IL-19 levels rose prior to clinical relapse, then dropped again in response to retreatment. The hope is that this assay will serve as an accurate tool for assessment of response to therapy.

Dr. Gordon reported receiving research funding and/or honoraria from more than a dozen pharmaceutical companies involved in psoriasis therapy.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

In his role as head of the division of pediatric behavioral health at National Jewish Health, Denver, Bruce G. Bender, PhD, helps children and adults navigate the adverse effects of severe atopic dermatitis (AD) on their quality of life.

“There have been many surveys of adults with AD who report impairment of their sleep, reduced activity level, increased work absence, financial burden, emotional distress, and social avoidance,” he said at the Revolutionizing Atopic Dermatitis virtual symposium. “Similarly, children with AD or their parents report emotional distress, reduced activity, and increased school absence, social avoidance, and sleep disturbance. Families report financial burdens, conflict, particularly among the adults, social avoidance, sleep disturbance in the parents, and reduction of well-being in the siblings.”

Getting adequate sleep is especially challenging for patients with AD, and loss of sleep can have serious daytime consequences. In an effort to objectively measure sleep change in this population, Dr. Bender and colleagues recruited 14 adults with AD and 14 healthy controls who wore an ActiGraph for 1 week and completed questionnaires about sleep, itch, and quality of life. Patients with AD were awake almost twice as many minutes each night as the healthy controls (a mean of 57.3 vs. 32.3 minutes, respectively; P = .0480). Consequently, their sleep efficiency was significantly reduced based on the Pittsburgh sleep quality index (a mean of 90.6 vs. 95; P = .0305).

In another study, Dr. Bender and colleagues enrolled 20 adults with AD who underwent 2 nights of polysomnography and actigraphy. The lab was set up to measure a scratching event, which was recorded when a burst of electromyographic activity of at least 3 seconds was accompanied by a visible scratching motion. “We learned that sleep efficiency as measured by both PSG and actigraphy correlated with total body surface area and scratching index,” he said. “As we might assume, the more skin involved, the more patients scratch, the less well they sleep.”
 

Behavioral, neurocognitive effects

In a separate study of AD, sleep, and behavior, the researchers studied 1,041 children with asthma who were enrolled in the Childhood Asthma Management Program at eight North American sites. They used baseline parent ratings on standardized sleep and behavior rating scales and found that increased awakenings were associated with increased school absence and daytime behavior problems. “So, not only do children with AD sleep less well, but this shows up to impair their functioning during the day,” said Dr. Bender, professor of psychiatry at the University of Colorado, Denver.

In a report from Australia, researchers set out to explore the association between sleep and neurocognitive function in 21 children with eczema and 20 healthy controls. Participants underwent cognitive testing and polysomnography. The authors found that the children with eczema demonstrated lower test scores. Reduced scores were correlated with parental reports of sleep problems but not polysomnography.

In a much larger study funded by the Agency for Healthcare Research and Quality, investigators analyzed data on 354,416 children and 34,613 adults from 19 U.S. population surveys including the National Health Interview Survey 1997-2013 and the National Survey of Children’s Health 2003/4 and 2007/8. They found that AD was associated with ADHD in children (adjusted odds ratio, 1.14) and adults (aOR, 1.61). Higher odds of ADHD were found in children who had significant sleep disturbance (aOR, 16.83) and other allergic disease and asthma (aOR, 1.61).

“All of these findings show that AD can impact quality of life, especially sleep, with the result of poorer daytime functioning,” Dr. Bender said. “But those studies don’t answer this question: Are patients with AD at increased risk for psychological disorders such as depression and anxiety?”
 

Impact on depression, anxiety

Two systematic reviews on the topic suggest that patients with AD are twice as likely to experience depression. One was published in 2018 and the other in 2019. The 2018 review reported a little more than a twofold increase (OR, 2.19), the 2019 review a little bit less (OR, 1.71).

“At the more severe end of the depression continuum, we sometimes see suicidal ideation and suicide attempts,” Dr. Bender said. “A number of studies have asked whether these are increased in patients with AD. Quite a few studies collectively show an increased incidence of suicidal ideation. The question of suicide attempts is reflected in fewer studies. And while the result is small, it is significant. There is a significant increase reported of suicide attempts in AD patients.”

The 2018 review also found an increased incidence of anxiety in AD patients: a little more than twofold in adults (OR, 2.19) and a little less than twofold in children (OR, 1.81).

“It’s a two-way relationship between AD and psychological factors,” Dr. Bender said. “We generally think about AD – the stress that it brings, the burden that it puts on children, adults, and families. But it can work the other way around,” he said, referring to patients who have psychological problems, experience a great deal of stress, have trouble being adherent to their treatment regimen, and find it difficult to resist scratching. “The behavioral/psychological characteristics of the patient also drive the AD. It is well established that acute and chronic stress can result in a worsening of skin conditions in AD patients.”

Behavioral health interventions that have been described in the literature include cognitive therapy, stress management, biofeedback, hypnotherapy, relaxation training, mindfulness, habit reversal, and patient education – some of which have been tested in randomized trials. “All of them report a decrease in scratching as a consequence of the behavioral intervention,” Dr. Bender said.

“Other studies have been reported that look at the impact of behavioral interventions on the severity of the skin condition. Most report an improvement in the skin condition from these behavioral interventions but it’s not a perfect literature.” Critiques of these studies include the fact that there is often not enough detail about the intervention or the framework for the intervention that would allow a clinician to test an intervention in another study or actually pull that intervention into clinical practice (Cochrane Database Syst Rev. 2014 Jan 7;2014[1]:CD004054), (Int Arch Allergy Immunol.2007;144[1]:1-9).

“Some of the studies lack rigorous designs, some have sampling bias, and some have inadequate outcome measurements,” he said. “We really need additional, high-quality studies to look at what is helpful for patients with AD.”

Dr. Bender reported having no financial disclosures.

[email protected]

In his role as head of the division of pediatric behavioral health at National Jewish Health, Denver, Bruce G. Bender, PhD, helps children and adults navigate the adverse effects of severe atopic dermatitis (AD) on their quality of life.

“There have been many surveys of adults with AD who report impairment of their sleep, reduced activity level, increased work absence, financial burden, emotional distress, and social avoidance,” he said at the Revolutionizing Atopic Dermatitis virtual symposium. “Similarly, children with AD or their parents report emotional distress, reduced activity, and increased school absence, social avoidance, and sleep disturbance. Families report financial burdens, conflict, particularly among the adults, social avoidance, sleep disturbance in the parents, and reduction of well-being in the siblings.”

Getting adequate sleep is especially challenging for patients with AD, and loss of sleep can have serious daytime consequences. In an effort to objectively measure sleep change in this population, Dr. Bender and colleagues recruited 14 adults with AD and 14 healthy controls who wore an ActiGraph for 1 week and completed questionnaires about sleep, itch, and quality of life. Patients with AD were awake almost twice as many minutes each night as the healthy controls (a mean of 57.3 vs. 32.3 minutes, respectively; P = .0480). Consequently, their sleep efficiency was significantly reduced based on the Pittsburgh sleep quality index (a mean of 90.6 vs. 95; P = .0305).

In another study, Dr. Bender and colleagues enrolled 20 adults with AD who underwent 2 nights of polysomnography and actigraphy. The lab was set up to measure a scratching event, which was recorded when a burst of electromyographic activity of at least 3 seconds was accompanied by a visible scratching motion. “We learned that sleep efficiency as measured by both PSG and actigraphy correlated with total body surface area and scratching index,” he said. “As we might assume, the more skin involved, the more patients scratch, the less well they sleep.”
 

Behavioral, neurocognitive effects

In a separate study of AD, sleep, and behavior, the researchers studied 1,041 children with asthma who were enrolled in the Childhood Asthma Management Program at eight North American sites. They used baseline parent ratings on standardized sleep and behavior rating scales and found that increased awakenings were associated with increased school absence and daytime behavior problems. “So, not only do children with AD sleep less well, but this shows up to impair their functioning during the day,” said Dr. Bender, professor of psychiatry at the University of Colorado, Denver.

In a report from Australia, researchers set out to explore the association between sleep and neurocognitive function in 21 children with eczema and 20 healthy controls. Participants underwent cognitive testing and polysomnography. The authors found that the children with eczema demonstrated lower test scores. Reduced scores were correlated with parental reports of sleep problems but not polysomnography.

In a much larger study funded by the Agency for Healthcare Research and Quality, investigators analyzed data on 354,416 children and 34,613 adults from 19 U.S. population surveys including the National Health Interview Survey 1997-2013 and the National Survey of Children’s Health 2003/4 and 2007/8. They found that AD was associated with ADHD in children (adjusted odds ratio, 1.14) and adults (aOR, 1.61). Higher odds of ADHD were found in children who had significant sleep disturbance (aOR, 16.83) and other allergic disease and asthma (aOR, 1.61).

“All of these findings show that AD can impact quality of life, especially sleep, with the result of poorer daytime functioning,” Dr. Bender said. “But those studies don’t answer this question: Are patients with AD at increased risk for psychological disorders such as depression and anxiety?”
 

Impact on depression, anxiety

Two systematic reviews on the topic suggest that patients with AD are twice as likely to experience depression. One was published in 2018 and the other in 2019. The 2018 review reported a little more than a twofold increase (OR, 2.19), the 2019 review a little bit less (OR, 1.71).

“At the more severe end of the depression continuum, we sometimes see suicidal ideation and suicide attempts,” Dr. Bender said. “A number of studies have asked whether these are increased in patients with AD. Quite a few studies collectively show an increased incidence of suicidal ideation. The question of suicide attempts is reflected in fewer studies. And while the result is small, it is significant. There is a significant increase reported of suicide attempts in AD patients.”

The 2018 review also found an increased incidence of anxiety in AD patients: a little more than twofold in adults (OR, 2.19) and a little less than twofold in children (OR, 1.81).

“It’s a two-way relationship between AD and psychological factors,” Dr. Bender said. “We generally think about AD – the stress that it brings, the burden that it puts on children, adults, and families. But it can work the other way around,” he said, referring to patients who have psychological problems, experience a great deal of stress, have trouble being adherent to their treatment regimen, and find it difficult to resist scratching. “The behavioral/psychological characteristics of the patient also drive the AD. It is well established that acute and chronic stress can result in a worsening of skin conditions in AD patients.”

Behavioral health interventions that have been described in the literature include cognitive therapy, stress management, biofeedback, hypnotherapy, relaxation training, mindfulness, habit reversal, and patient education – some of which have been tested in randomized trials. “All of them report a decrease in scratching as a consequence of the behavioral intervention,” Dr. Bender said.

“Other studies have been reported that look at the impact of behavioral interventions on the severity of the skin condition. Most report an improvement in the skin condition from these behavioral interventions but it’s not a perfect literature.” Critiques of these studies include the fact that there is often not enough detail about the intervention or the framework for the intervention that would allow a clinician to test an intervention in another study or actually pull that intervention into clinical practice (Cochrane Database Syst Rev. 2014 Jan 7;2014[1]:CD004054), (Int Arch Allergy Immunol.2007;144[1]:1-9).

“Some of the studies lack rigorous designs, some have sampling bias, and some have inadequate outcome measurements,” he said. “We really need additional, high-quality studies to look at what is helpful for patients with AD.”

Dr. Bender reported having no financial disclosures.

[email protected]

In his role as head of the division of pediatric behavioral health at National Jewish Health, Denver, Bruce G. Bender, PhD, helps children and adults navigate the adverse effects of severe atopic dermatitis (AD) on their quality of life.

“There have been many surveys of adults with AD who report impairment of their sleep, reduced activity level, increased work absence, financial burden, emotional distress, and social avoidance,” he said at the Revolutionizing Atopic Dermatitis virtual symposium. “Similarly, children with AD or their parents report emotional distress, reduced activity, and increased school absence, social avoidance, and sleep disturbance. Families report financial burdens, conflict, particularly among the adults, social avoidance, sleep disturbance in the parents, and reduction of well-being in the siblings.”

Getting adequate sleep is especially challenging for patients with AD, and loss of sleep can have serious daytime consequences. In an effort to objectively measure sleep change in this population, Dr. Bender and colleagues recruited 14 adults with AD and 14 healthy controls who wore an ActiGraph for 1 week and completed questionnaires about sleep, itch, and quality of life. Patients with AD were awake almost twice as many minutes each night as the healthy controls (a mean of 57.3 vs. 32.3 minutes, respectively; P = .0480). Consequently, their sleep efficiency was significantly reduced based on the Pittsburgh sleep quality index (a mean of 90.6 vs. 95; P = .0305).

In another study, Dr. Bender and colleagues enrolled 20 adults with AD who underwent 2 nights of polysomnography and actigraphy. The lab was set up to measure a scratching event, which was recorded when a burst of electromyographic activity of at least 3 seconds was accompanied by a visible scratching motion. “We learned that sleep efficiency as measured by both PSG and actigraphy correlated with total body surface area and scratching index,” he said. “As we might assume, the more skin involved, the more patients scratch, the less well they sleep.”
 

Behavioral, neurocognitive effects

In a separate study of AD, sleep, and behavior, the researchers studied 1,041 children with asthma who were enrolled in the Childhood Asthma Management Program at eight North American sites. They used baseline parent ratings on standardized sleep and behavior rating scales and found that increased awakenings were associated with increased school absence and daytime behavior problems. “So, not only do children with AD sleep less well, but this shows up to impair their functioning during the day,” said Dr. Bender, professor of psychiatry at the University of Colorado, Denver.

In a report from Australia, researchers set out to explore the association between sleep and neurocognitive function in 21 children with eczema and 20 healthy controls. Participants underwent cognitive testing and polysomnography. The authors found that the children with eczema demonstrated lower test scores. Reduced scores were correlated with parental reports of sleep problems but not polysomnography.

In a much larger study funded by the Agency for Healthcare Research and Quality, investigators analyzed data on 354,416 children and 34,613 adults from 19 U.S. population surveys including the National Health Interview Survey 1997-2013 and the National Survey of Children’s Health 2003/4 and 2007/8. They found that AD was associated with ADHD in children (adjusted odds ratio, 1.14) and adults (aOR, 1.61). Higher odds of ADHD were found in children who had significant sleep disturbance (aOR, 16.83) and other allergic disease and asthma (aOR, 1.61).

“All of these findings show that AD can impact quality of life, especially sleep, with the result of poorer daytime functioning,” Dr. Bender said. “But those studies don’t answer this question: Are patients with AD at increased risk for psychological disorders such as depression and anxiety?”
 

Impact on depression, anxiety

Two systematic reviews on the topic suggest that patients with AD are twice as likely to experience depression. One was published in 2018 and the other in 2019. The 2018 review reported a little more than a twofold increase (OR, 2.19), the 2019 review a little bit less (OR, 1.71).

“At the more severe end of the depression continuum, we sometimes see suicidal ideation and suicide attempts,” Dr. Bender said. “A number of studies have asked whether these are increased in patients with AD. Quite a few studies collectively show an increased incidence of suicidal ideation. The question of suicide attempts is reflected in fewer studies. And while the result is small, it is significant. There is a significant increase reported of suicide attempts in AD patients.”

The 2018 review also found an increased incidence of anxiety in AD patients: a little more than twofold in adults (OR, 2.19) and a little less than twofold in children (OR, 1.81).

“It’s a two-way relationship between AD and psychological factors,” Dr. Bender said. “We generally think about AD – the stress that it brings, the burden that it puts on children, adults, and families. But it can work the other way around,” he said, referring to patients who have psychological problems, experience a great deal of stress, have trouble being adherent to their treatment regimen, and find it difficult to resist scratching. “The behavioral/psychological characteristics of the patient also drive the AD. It is well established that acute and chronic stress can result in a worsening of skin conditions in AD patients.”

Behavioral health interventions that have been described in the literature include cognitive therapy, stress management, biofeedback, hypnotherapy, relaxation training, mindfulness, habit reversal, and patient education – some of which have been tested in randomized trials. “All of them report a decrease in scratching as a consequence of the behavioral intervention,” Dr. Bender said.

“Other studies have been reported that look at the impact of behavioral interventions on the severity of the skin condition. Most report an improvement in the skin condition from these behavioral interventions but it’s not a perfect literature.” Critiques of these studies include the fact that there is often not enough detail about the intervention or the framework for the intervention that would allow a clinician to test an intervention in another study or actually pull that intervention into clinical practice (Cochrane Database Syst Rev. 2014 Jan 7;2014[1]:CD004054), (Int Arch Allergy Immunol.2007;144[1]:1-9).

“Some of the studies lack rigorous designs, some have sampling bias, and some have inadequate outcome measurements,” he said. “We really need additional, high-quality studies to look at what is helpful for patients with AD.”

Dr. Bender reported having no financial disclosures.

[email protected]

A study of post–COVID-19 patients in the United Kingdom who developed severe lung inflammation after they left the hospital may provide greater clarity on which patients are most likely to have persistent lung dysfunction.

In addition to pinpointing those most at risk, the findings showed that conventional corticosteroid treatment is highly effective in improving lung function and reducing symptoms.

Researchers from Guy’s and St. Thomas’ National Health Foundation Trust in London reported that a small percentage of patients – 4.8%, or 35 of 837 patients in the study – had severe persistent interstitial lung disease (ILD), mostly organizing pneumonia, 4 weeks after discharge. Of these patients, 30 received steroid treatment, all of whom showed improvement in lung function.

Lead author Katherine Jane Myall, MRCP, and colleagues wrote that the most common radiologic finding in acute COVID-19 is bilateral ground-glass opacification, and findings of organizing pneumonia are common. However, no reports exist of the role of inflammatory infiltrates during recovery from COVID-19 or of the effectiveness of treatments for persistent ILD. “The long-term respiratory morbidity remains unclear,” Dr. Myall and colleagues wrote.

The study findings are significant because they quantify the degree of lung disease that patients have after COVID-19, said Sachin Gupta, MD, FCCP, a pulmonologist and critical care specialist at Alameda Health System in Oakland, Calif. He added that the disease course and presentation followed the pattern of organizing pneumonia in some patients, and traditional corticosteroid therapy seemed to resolve symptoms and improve lung function.

“This is a really important piece to get out there because it describes what a lot of us are worried about in patients with post-COVID lung disease and about what type of lung disease they have. It offers a potential treatment,” he said.

Dr. Myall and colleagues noted that even a “relatively small proportion” of patients with persistent, severe ILD – as reported in this study – pose “a significant disease burden.” They added: “Prompt therapy may avoid potentially permanent fibrosis and functional impairment.”

The single-center, prospective, observational study followed discharged patients with telephone calls 4 weeks after discharge to determine their status. At that point, 39% of the study cohort (n = 325) reported ongoing symptoms.

The patients had outpatient examinations at 6 weeks post discharge, at which time 42.9% (n = 138) had no signs or symptoms of persistent disease; 33.8% (n = 110) had symptoms but no radiologic findings and received referrals to other departments; and 24% (n = 77) were referred to the post-COVID lung disease multidisciplinary team. A total of 59 were diagnosed with persistent post-COVID interstitial change, 35 of whom had organizing pneumonia, hence the rationale for using steroids in this group, Dr. Myall and colleagues stated.

The 30 patients treated with corticosteroids received a maximum initial dose of 0.5 mg/kg prednisolone, which was rapidly weaned over 3 weeks. Some patients received lower doses depending on their comorbidities.

Treatment resulted in an average relative increase in transfer factor of 31.6% (P < .001) and forced vital capacity of 9.6% (P = .014), along with significant improvement in symptoms and x-ray signs.

The study identified some key characteristics of the patients who had persistent post–COVID-19 inflammatory ILD. They were mostly male (71.5%) and overweight with an average body mass index of 28.3, but only 26% were obese. Most had at least one comorbidity, with the most common being diabetes and asthma (22.9%). Their average hospital stay was 16.9 days, 82.9% required oxygen, 55% were in the ICU, and 46% needed invasive mechanical ventilation.

The patients most vulnerable to ILD and organizing pneumonia were the “sicker” of the whole cohort, Dr. Gupta said. “In one sense, it’s reassuring that this is not just happening in anyone; this is happening in patients who had the worst course and were hospitalized in the ICU for the most part.”

The study shows that identifying these patients early on and initiating steroid therapy could avoid persistent lung injury and scarring, Dr. Gupta said.

The London researchers noted that theirs wasn’t a radiologic study, so CT scans weren’t formally scored before and after treatment. They also acknowledged vagueness about imaging and clinical findings representing “nothing other than slow ongoing recovery.”

Patients with post–COVID-19 ILD will require ongoing follow-up to better understand the disease course, Dr. Myall and colleagues stated, although they predicted organizing pneumonia is unlikely to recur once it resolves.

Dr. Myall and coauthors had no relevant relationships to disclose. Dr. Gupta disclosed he is also an employee and shareholder at Genentech.

A study of post–COVID-19 patients in the United Kingdom who developed severe lung inflammation after they left the hospital may provide greater clarity on which patients are most likely to have persistent lung dysfunction.

In addition to pinpointing those most at risk, the findings showed that conventional corticosteroid treatment is highly effective in improving lung function and reducing symptoms.

Researchers from Guy’s and St. Thomas’ National Health Foundation Trust in London reported that a small percentage of patients – 4.8%, or 35 of 837 patients in the study – had severe persistent interstitial lung disease (ILD), mostly organizing pneumonia, 4 weeks after discharge. Of these patients, 30 received steroid treatment, all of whom showed improvement in lung function.

Lead author Katherine Jane Myall, MRCP, and colleagues wrote that the most common radiologic finding in acute COVID-19 is bilateral ground-glass opacification, and findings of organizing pneumonia are common. However, no reports exist of the role of inflammatory infiltrates during recovery from COVID-19 or of the effectiveness of treatments for persistent ILD. “The long-term respiratory morbidity remains unclear,” Dr. Myall and colleagues wrote.

The study findings are significant because they quantify the degree of lung disease that patients have after COVID-19, said Sachin Gupta, MD, FCCP, a pulmonologist and critical care specialist at Alameda Health System in Oakland, Calif. He added that the disease course and presentation followed the pattern of organizing pneumonia in some patients, and traditional corticosteroid therapy seemed to resolve symptoms and improve lung function.

“This is a really important piece to get out there because it describes what a lot of us are worried about in patients with post-COVID lung disease and about what type of lung disease they have. It offers a potential treatment,” he said.

Dr. Myall and colleagues noted that even a “relatively small proportion” of patients with persistent, severe ILD – as reported in this study – pose “a significant disease burden.” They added: “Prompt therapy may avoid potentially permanent fibrosis and functional impairment.”

The single-center, prospective, observational study followed discharged patients with telephone calls 4 weeks after discharge to determine their status. At that point, 39% of the study cohort (n = 325) reported ongoing symptoms.

The patients had outpatient examinations at 6 weeks post discharge, at which time 42.9% (n = 138) had no signs or symptoms of persistent disease; 33.8% (n = 110) had symptoms but no radiologic findings and received referrals to other departments; and 24% (n = 77) were referred to the post-COVID lung disease multidisciplinary team. A total of 59 were diagnosed with persistent post-COVID interstitial change, 35 of whom had organizing pneumonia, hence the rationale for using steroids in this group, Dr. Myall and colleagues stated.

The 30 patients treated with corticosteroids received a maximum initial dose of 0.5 mg/kg prednisolone, which was rapidly weaned over 3 weeks. Some patients received lower doses depending on their comorbidities.

Treatment resulted in an average relative increase in transfer factor of 31.6% (P < .001) and forced vital capacity of 9.6% (P = .014), along with significant improvement in symptoms and x-ray signs.

The study identified some key characteristics of the patients who had persistent post–COVID-19 inflammatory ILD. They were mostly male (71.5%) and overweight with an average body mass index of 28.3, but only 26% were obese. Most had at least one comorbidity, with the most common being diabetes and asthma (22.9%). Their average hospital stay was 16.9 days, 82.9% required oxygen, 55% were in the ICU, and 46% needed invasive mechanical ventilation.

The patients most vulnerable to ILD and organizing pneumonia were the “sicker” of the whole cohort, Dr. Gupta said. “In one sense, it’s reassuring that this is not just happening in anyone; this is happening in patients who had the worst course and were hospitalized in the ICU for the most part.”

The study shows that identifying these patients early on and initiating steroid therapy could avoid persistent lung injury and scarring, Dr. Gupta said.

The London researchers noted that theirs wasn’t a radiologic study, so CT scans weren’t formally scored before and after treatment. They also acknowledged vagueness about imaging and clinical findings representing “nothing other than slow ongoing recovery.”

Patients with post–COVID-19 ILD will require ongoing follow-up to better understand the disease course, Dr. Myall and colleagues stated, although they predicted organizing pneumonia is unlikely to recur once it resolves.

Dr. Myall and coauthors had no relevant relationships to disclose. Dr. Gupta disclosed he is also an employee and shareholder at Genentech.

A study of post–COVID-19 patients in the United Kingdom who developed severe lung inflammation after they left the hospital may provide greater clarity on which patients are most likely to have persistent lung dysfunction.

In addition to pinpointing those most at risk, the findings showed that conventional corticosteroid treatment is highly effective in improving lung function and reducing symptoms.

Researchers from Guy’s and St. Thomas’ National Health Foundation Trust in London reported that a small percentage of patients – 4.8%, or 35 of 837 patients in the study – had severe persistent interstitial lung disease (ILD), mostly organizing pneumonia, 4 weeks after discharge. Of these patients, 30 received steroid treatment, all of whom showed improvement in lung function.

Lead author Katherine Jane Myall, MRCP, and colleagues wrote that the most common radiologic finding in acute COVID-19 is bilateral ground-glass opacification, and findings of organizing pneumonia are common. However, no reports exist of the role of inflammatory infiltrates during recovery from COVID-19 or of the effectiveness of treatments for persistent ILD. “The long-term respiratory morbidity remains unclear,” Dr. Myall and colleagues wrote.

The study findings are significant because they quantify the degree of lung disease that patients have after COVID-19, said Sachin Gupta, MD, FCCP, a pulmonologist and critical care specialist at Alameda Health System in Oakland, Calif. He added that the disease course and presentation followed the pattern of organizing pneumonia in some patients, and traditional corticosteroid therapy seemed to resolve symptoms and improve lung function.

“This is a really important piece to get out there because it describes what a lot of us are worried about in patients with post-COVID lung disease and about what type of lung disease they have. It offers a potential treatment,” he said.

Dr. Myall and colleagues noted that even a “relatively small proportion” of patients with persistent, severe ILD – as reported in this study – pose “a significant disease burden.” They added: “Prompt therapy may avoid potentially permanent fibrosis and functional impairment.”

The single-center, prospective, observational study followed discharged patients with telephone calls 4 weeks after discharge to determine their status. At that point, 39% of the study cohort (n = 325) reported ongoing symptoms.

The patients had outpatient examinations at 6 weeks post discharge, at which time 42.9% (n = 138) had no signs or symptoms of persistent disease; 33.8% (n = 110) had symptoms but no radiologic findings and received referrals to other departments; and 24% (n = 77) were referred to the post-COVID lung disease multidisciplinary team. A total of 59 were diagnosed with persistent post-COVID interstitial change, 35 of whom had organizing pneumonia, hence the rationale for using steroids in this group, Dr. Myall and colleagues stated.

The 30 patients treated with corticosteroids received a maximum initial dose of 0.5 mg/kg prednisolone, which was rapidly weaned over 3 weeks. Some patients received lower doses depending on their comorbidities.

Treatment resulted in an average relative increase in transfer factor of 31.6% (P < .001) and forced vital capacity of 9.6% (P = .014), along with significant improvement in symptoms and x-ray signs.

The study identified some key characteristics of the patients who had persistent post–COVID-19 inflammatory ILD. They were mostly male (71.5%) and overweight with an average body mass index of 28.3, but only 26% were obese. Most had at least one comorbidity, with the most common being diabetes and asthma (22.9%). Their average hospital stay was 16.9 days, 82.9% required oxygen, 55% were in the ICU, and 46% needed invasive mechanical ventilation.

The patients most vulnerable to ILD and organizing pneumonia were the “sicker” of the whole cohort, Dr. Gupta said. “In one sense, it’s reassuring that this is not just happening in anyone; this is happening in patients who had the worst course and were hospitalized in the ICU for the most part.”

The study shows that identifying these patients early on and initiating steroid therapy could avoid persistent lung injury and scarring, Dr. Gupta said.

The London researchers noted that theirs wasn’t a radiologic study, so CT scans weren’t formally scored before and after treatment. They also acknowledged vagueness about imaging and clinical findings representing “nothing other than slow ongoing recovery.”

Patients with post–COVID-19 ILD will require ongoing follow-up to better understand the disease course, Dr. Myall and colleagues stated, although they predicted organizing pneumonia is unlikely to recur once it resolves.

Dr. Myall and coauthors had no relevant relationships to disclose. Dr. Gupta disclosed he is also an employee and shareholder at Genentech.

The American Society for Dermatologic Surgery Association and the department of dermatology at Northwestern University, Chicago, have launched the Cutaneous Procedures Adverse Events Reporting (CAPER) registry.

CAPER is a voluntary reporting system designed to collect reports of patients’ adverse events encountered during dermatologic surgery procedures, both cosmetic and those related to skin cancer. The goals of the CAPER registry are to provide safety monitoring, identify practice and/or education gaps associated with adverse events, and identify potential adverse event risk factors.

“CAPER is a registry overseen by a group of board-certified dermatologists, clinicians, and researchers with more than 20 years of experience in patient care and physician advocacy who are committed to improving safety outcomes,” according to an ASDSA press release. “The collaboration between Northwestern University and ASDSA will ensure that CAPER becomes the common place for dermatologic surgeons and their staff to report adverse events from devices, drugs or biologics.”

The launch of the database is important because it fills a gap in adverse event reporting, Murad Alam, MD, professor of dermatology and chief of cutaneous and aesthetic surgery in the department of dermatology at Northwestern University, said in an interview.

There has been no central registry specifically for reporting adverse events associated with dermatologic surgical procedures, including cosmetic and injectable treatments, he said. “While minimally invasive cosmetic and skin procedures have been proven to be exceedingly safe, this registry will provide an early warning system to identify any problems that do occur, so these can be addressed promptly. This registry will allow dermatologists, patients, and industry scientists to work together to further improve the safety of dermatologic procedures,” added Dr. Alam, the past ASDSA president, and current chair of the ASDSA’s Federal Affairs Work Group.

In addition, “recent reports of the possible interaction between some filler injections and certain COVID vaccines confirms the timeliness of redoubling our emphasis on safety. Dermatologists have always been at the forefront of maximizing the patient experience while minimizing risk; this registry is further evidence of that ongoing commitment,” he emphasized.

The CAPER database will gather information on a variety of dermatologic and cosmetic procedures, including those involving topicals and injectables (such as botulinum toxin, fillers, and chemical peels), devices (such as lasers and microneedling devices), cellular-based therapies (such as platelet-rich plasma and stem cell treatments), and surgical treatments (such as liposuction and hair transplantation), Dr. Alam said.

“Novel procedures, and those yet to be devised, as long as they relate to skin surgery or cosmetic improvement, will also be able to be reported. We encourage the reporting of all associated adverse events, even if it is not clear what caused the event. No dermatologic or cosmetic procedures will be excluded from reporting,” he added.

The purpose of the CAPER registry is “to help patients, physicians, and industry work collaboratively to ensure the highest levels of patient safety,” Dr. Alam continued. Data entered into the registry will be deidentified and will remain confidential, and as data on particular topics accumulate, the data “may be analyzed to better understand the patient experience and, secondly, to develop strategies to further improve safety,” he noted.

“One unique element of this registry is that it is focused on dermatologic and cosmetic procedures,” Dr. Alam added. “As a result, those managing and analyzing the data collected will be attuned to the particular concerns associated with such procedures and the patients receiving them.”

For more information and to report dermatologic surgery-related adverse events, go to caper.net.

The American Society for Dermatologic Surgery Association and the department of dermatology at Northwestern University, Chicago, have launched the Cutaneous Procedures Adverse Events Reporting (CAPER) registry.

CAPER is a voluntary reporting system designed to collect reports of patients’ adverse events encountered during dermatologic surgery procedures, both cosmetic and those related to skin cancer. The goals of the CAPER registry are to provide safety monitoring, identify practice and/or education gaps associated with adverse events, and identify potential adverse event risk factors.

“CAPER is a registry overseen by a group of board-certified dermatologists, clinicians, and researchers with more than 20 years of experience in patient care and physician advocacy who are committed to improving safety outcomes,” according to an ASDSA press release. “The collaboration between Northwestern University and ASDSA will ensure that CAPER becomes the common place for dermatologic surgeons and their staff to report adverse events from devices, drugs or biologics.”

The launch of the database is important because it fills a gap in adverse event reporting, Murad Alam, MD, professor of dermatology and chief of cutaneous and aesthetic surgery in the department of dermatology at Northwestern University, said in an interview.

There has been no central registry specifically for reporting adverse events associated with dermatologic surgical procedures, including cosmetic and injectable treatments, he said. “While minimally invasive cosmetic and skin procedures have been proven to be exceedingly safe, this registry will provide an early warning system to identify any problems that do occur, so these can be addressed promptly. This registry will allow dermatologists, patients, and industry scientists to work together to further improve the safety of dermatologic procedures,” added Dr. Alam, the past ASDSA president, and current chair of the ASDSA’s Federal Affairs Work Group.

In addition, “recent reports of the possible interaction between some filler injections and certain COVID vaccines confirms the timeliness of redoubling our emphasis on safety. Dermatologists have always been at the forefront of maximizing the patient experience while minimizing risk; this registry is further evidence of that ongoing commitment,” he emphasized.

The CAPER database will gather information on a variety of dermatologic and cosmetic procedures, including those involving topicals and injectables (such as botulinum toxin, fillers, and chemical peels), devices (such as lasers and microneedling devices), cellular-based therapies (such as platelet-rich plasma and stem cell treatments), and surgical treatments (such as liposuction and hair transplantation), Dr. Alam said.

“Novel procedures, and those yet to be devised, as long as they relate to skin surgery or cosmetic improvement, will also be able to be reported. We encourage the reporting of all associated adverse events, even if it is not clear what caused the event. No dermatologic or cosmetic procedures will be excluded from reporting,” he added.

The purpose of the CAPER registry is “to help patients, physicians, and industry work collaboratively to ensure the highest levels of patient safety,” Dr. Alam continued. Data entered into the registry will be deidentified and will remain confidential, and as data on particular topics accumulate, the data “may be analyzed to better understand the patient experience and, secondly, to develop strategies to further improve safety,” he noted.

“One unique element of this registry is that it is focused on dermatologic and cosmetic procedures,” Dr. Alam added. “As a result, those managing and analyzing the data collected will be attuned to the particular concerns associated with such procedures and the patients receiving them.”

For more information and to report dermatologic surgery-related adverse events, go to caper.net.

The American Society for Dermatologic Surgery Association and the department of dermatology at Northwestern University, Chicago, have launched the Cutaneous Procedures Adverse Events Reporting (CAPER) registry.

CAPER is a voluntary reporting system designed to collect reports of patients’ adverse events encountered during dermatologic surgery procedures, both cosmetic and those related to skin cancer. The goals of the CAPER registry are to provide safety monitoring, identify practice and/or education gaps associated with adverse events, and identify potential adverse event risk factors.

“CAPER is a registry overseen by a group of board-certified dermatologists, clinicians, and researchers with more than 20 years of experience in patient care and physician advocacy who are committed to improving safety outcomes,” according to an ASDSA press release. “The collaboration between Northwestern University and ASDSA will ensure that CAPER becomes the common place for dermatologic surgeons and their staff to report adverse events from devices, drugs or biologics.”

The launch of the database is important because it fills a gap in adverse event reporting, Murad Alam, MD, professor of dermatology and chief of cutaneous and aesthetic surgery in the department of dermatology at Northwestern University, said in an interview.

There has been no central registry specifically for reporting adverse events associated with dermatologic surgical procedures, including cosmetic and injectable treatments, he said. “While minimally invasive cosmetic and skin procedures have been proven to be exceedingly safe, this registry will provide an early warning system to identify any problems that do occur, so these can be addressed promptly. This registry will allow dermatologists, patients, and industry scientists to work together to further improve the safety of dermatologic procedures,” added Dr. Alam, the past ASDSA president, and current chair of the ASDSA’s Federal Affairs Work Group.

In addition, “recent reports of the possible interaction between some filler injections and certain COVID vaccines confirms the timeliness of redoubling our emphasis on safety. Dermatologists have always been at the forefront of maximizing the patient experience while minimizing risk; this registry is further evidence of that ongoing commitment,” he emphasized.

The CAPER database will gather information on a variety of dermatologic and cosmetic procedures, including those involving topicals and injectables (such as botulinum toxin, fillers, and chemical peels), devices (such as lasers and microneedling devices), cellular-based therapies (such as platelet-rich plasma and stem cell treatments), and surgical treatments (such as liposuction and hair transplantation), Dr. Alam said.

“Novel procedures, and those yet to be devised, as long as they relate to skin surgery or cosmetic improvement, will also be able to be reported. We encourage the reporting of all associated adverse events, even if it is not clear what caused the event. No dermatologic or cosmetic procedures will be excluded from reporting,” he added.

The purpose of the CAPER registry is “to help patients, physicians, and industry work collaboratively to ensure the highest levels of patient safety,” Dr. Alam continued. Data entered into the registry will be deidentified and will remain confidential, and as data on particular topics accumulate, the data “may be analyzed to better understand the patient experience and, secondly, to develop strategies to further improve safety,” he noted.

“One unique element of this registry is that it is focused on dermatologic and cosmetic procedures,” Dr. Alam added. “As a result, those managing and analyzing the data collected will be attuned to the particular concerns associated with such procedures and the patients receiving them.”

For more information and to report dermatologic surgery-related adverse events, go to caper.net.

One dose of the novel agent, REGN1908-1909 (Regeneron Pharmaceuticals) resulted in a rapid and durable reduction in cat-allergen-induced bronchoconstriction in cat-allergic subjects with mild asthma.

vladans/iStock/Getty Images Plus

The finding, from a phase 2 randomized placebo-controlled study, is good news for the millions of people who are plagued by cat allergies, the investigators say.

The study, which was sponsored by Regeneron, was presented in a late breaking oral abstract session at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, held virtually this year.

“REGN1908-1909 contains antibodies against Fel d 1, the major cat allergen, and here we show that it quickly and lastingly reduces acute bronchoconstriction in people with cat allergy,” lead author Frederic J. de Blay, MD, Strasbourg University Hospital, France, said in an interview.

Dr. de Blay admitted he is “quite excited” about the results.

“This study was performed in an environmental exposure chamber, and we clearly demonstrate that these antibodies decrease the asthmatic response to cat allergen within 8 days, and that these effects last 3 months. I never saw that in my life. I was a little bit skeptical at first, so to obtain such robust results after just 8 days, after just one injection, I was very surprised,” he said.

Dr. de Blay and his team screened potential participants to make sure they were cat allergic by exposing them to cat allergen for up to 2 hours while they were in the environmental exposure chamber. To be eligible for the study, participants had to show an early asthmatic response (EAR), defined as a reduction in forced expiratory volume in 1 second (FEV₁₎ of at least 20% from baseline.

The participants were then randomized to receive either single-dose REGN1908-1909, 600 mg, subcutaneously (n = 29 patients) or placebo (n = 27 patients) prior to cat-allergen exposure in the controlled environmental chamber.

Dr. de Blay developed the chamber used in the study: the ALYATEC environmental exposure chamber.

“The chamber is 60 meters square, or 150 cubic meters, and can accommodate 20 patients. We are able to nebulize cat allergen, mice allergen, or whatever we wish to study so we can standardize the exposure. We can control the particle size and the amount so we know the exact amount of allergen that the patient has been exposed to,” he explained.

To test the efficacy of REGN1908-1909 in reducing acute bronchoconstriction, or EAR, the researchers measured FEV₁ at baseline, and on days 8, 29, 57, and 85 in both groups. During each exposure, measurements were taken every 10 minutes for periods that lasted up to 4 hours.

They found that the probability of remaining in the chamber with no asthmatic response was substantially elevated in the group treated with REGN1908-1909.

Compared with placebo, REGN1908-1909 significantly increased the median time to EAR, from 51 minutes at baseline to more than 4 hours on day 8, (hazard ratio [HR], 0.36; P < .0083), day 29 (HR, 0.24; P < .0001), day 57 (HR, 0.45; P = .0222), and day 85 (HR, 0.27; P = .0003).

The FEV₁ area under the curve (AUC) was also better with REGN1908-1909 than with placebo at day 8 (15.2% vs. 1.6%; P < .001). And a single dose reduced skin-test reactivity to cat allergen at 1 week, which persisted for up to 4 months.

In addition, participants who received REGN1908-1909 were able to tolerate a threefold higher amount of the cat allergen than those who received placebo (P = .003).

“We initially gave 40 nanograms of cat allergen, and then 8 days later they were able to stay longer in the chamber and inhale more of the allergen, to almost triple the amount they had originally been given. That 40 nanograms is very close to real world exposure,” Dr. de Blay noted.

Regeneron plans to start a phase 3 trial soon, he reported.
 

Promising results

“The study is well designed and shows a reduction in drop of FEV₁ in response to cat allergen provocation and a decreased AUC in cat SPT response over 4 months,” Jonathan A. Bernstein, MD, professor of medicine at the University of Cincinnati, said in an interview.

“These are very promising results, which show that REGN1908-1909 can be a novel treatment for cat-induced asthma, which is often the only sensitization patients have. And they love their cats – one-third of the U.S. population has a cat and one-third has a dog, and 50% have both,” noted Dr. Bernstein, who was not involved with the study.

“This novel study used our scientific knowledge of the cat allergen itself to design a targeted antibody-based treatment that demonstrates significant benefit even after the first shot,” added Edwin H. Kim, MD, director of the UNC Food Allergy Initiative at the University of North Carolina at Chapel Hill.

“This strategy has the potential to revolutionize not only our treatment of common environmental allergies but also other allergic diseases with well-described triggers, such as food and drug allergy,” Dr. Kim, who was not part of the study, said in an interview.

Dr. de Blay reported a financial relationship with Regeneron Pharmaceuticals, which sponsored the study. Dr. Bernstein and Dr. Kim have disclosed no relevant financial relationships.

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

One dose of the novel agent, REGN1908-1909 (Regeneron Pharmaceuticals) resulted in a rapid and durable reduction in cat-allergen-induced bronchoconstriction in cat-allergic subjects with mild asthma.

vladans/iStock/Getty Images Plus

The finding, from a phase 2 randomized placebo-controlled study, is good news for the millions of people who are plagued by cat allergies, the investigators say.

The study, which was sponsored by Regeneron, was presented in a late breaking oral abstract session at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, held virtually this year.

“REGN1908-1909 contains antibodies against Fel d 1, the major cat allergen, and here we show that it quickly and lastingly reduces acute bronchoconstriction in people with cat allergy,” lead author Frederic J. de Blay, MD, Strasbourg University Hospital, France, said in an interview.

Dr. de Blay admitted he is “quite excited” about the results.

“This study was performed in an environmental exposure chamber, and we clearly demonstrate that these antibodies decrease the asthmatic response to cat allergen within 8 days, and that these effects last 3 months. I never saw that in my life. I was a little bit skeptical at first, so to obtain such robust results after just 8 days, after just one injection, I was very surprised,” he said.

Dr. de Blay and his team screened potential participants to make sure they were cat allergic by exposing them to cat allergen for up to 2 hours while they were in the environmental exposure chamber. To be eligible for the study, participants had to show an early asthmatic response (EAR), defined as a reduction in forced expiratory volume in 1 second (FEV₁₎ of at least 20% from baseline.

The participants were then randomized to receive either single-dose REGN1908-1909, 600 mg, subcutaneously (n = 29 patients) or placebo (n = 27 patients) prior to cat-allergen exposure in the controlled environmental chamber.

Dr. de Blay developed the chamber used in the study: the ALYATEC environmental exposure chamber.

“The chamber is 60 meters square, or 150 cubic meters, and can accommodate 20 patients. We are able to nebulize cat allergen, mice allergen, or whatever we wish to study so we can standardize the exposure. We can control the particle size and the amount so we know the exact amount of allergen that the patient has been exposed to,” he explained.

To test the efficacy of REGN1908-1909 in reducing acute bronchoconstriction, or EAR, the researchers measured FEV₁ at baseline, and on days 8, 29, 57, and 85 in both groups. During each exposure, measurements were taken every 10 minutes for periods that lasted up to 4 hours.

They found that the probability of remaining in the chamber with no asthmatic response was substantially elevated in the group treated with REGN1908-1909.

Compared with placebo, REGN1908-1909 significantly increased the median time to EAR, from 51 minutes at baseline to more than 4 hours on day 8, (hazard ratio [HR], 0.36; P < .0083), day 29 (HR, 0.24; P < .0001), day 57 (HR, 0.45; P = .0222), and day 85 (HR, 0.27; P = .0003).

The FEV₁ area under the curve (AUC) was also better with REGN1908-1909 than with placebo at day 8 (15.2% vs. 1.6%; P < .001). And a single dose reduced skin-test reactivity to cat allergen at 1 week, which persisted for up to 4 months.

In addition, participants who received REGN1908-1909 were able to tolerate a threefold higher amount of the cat allergen than those who received placebo (P = .003).

“We initially gave 40 nanograms of cat allergen, and then 8 days later they were able to stay longer in the chamber and inhale more of the allergen, to almost triple the amount they had originally been given. That 40 nanograms is very close to real world exposure,” Dr. de Blay noted.

Regeneron plans to start a phase 3 trial soon, he reported.
 

Promising results

“The study is well designed and shows a reduction in drop of FEV₁ in response to cat allergen provocation and a decreased AUC in cat SPT response over 4 months,” Jonathan A. Bernstein, MD, professor of medicine at the University of Cincinnati, said in an interview.

“These are very promising results, which show that REGN1908-1909 can be a novel treatment for cat-induced asthma, which is often the only sensitization patients have. And they love their cats – one-third of the U.S. population has a cat and one-third has a dog, and 50% have both,” noted Dr. Bernstein, who was not involved with the study.

“This novel study used our scientific knowledge of the cat allergen itself to design a targeted antibody-based treatment that demonstrates significant benefit even after the first shot,” added Edwin H. Kim, MD, director of the UNC Food Allergy Initiative at the University of North Carolina at Chapel Hill.

“This strategy has the potential to revolutionize not only our treatment of common environmental allergies but also other allergic diseases with well-described triggers, such as food and drug allergy,” Dr. Kim, who was not part of the study, said in an interview.

Dr. de Blay reported a financial relationship with Regeneron Pharmaceuticals, which sponsored the study. Dr. Bernstein and Dr. Kim have disclosed no relevant financial relationships.

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

One dose of the novel agent, REGN1908-1909 (Regeneron Pharmaceuticals) resulted in a rapid and durable reduction in cat-allergen-induced bronchoconstriction in cat-allergic subjects with mild asthma.

vladans/iStock/Getty Images Plus

The finding, from a phase 2 randomized placebo-controlled study, is good news for the millions of people who are plagued by cat allergies, the investigators say.

The study, which was sponsored by Regeneron, was presented in a late breaking oral abstract session at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, held virtually this year.

“REGN1908-1909 contains antibodies against Fel d 1, the major cat allergen, and here we show that it quickly and lastingly reduces acute bronchoconstriction in people with cat allergy,” lead author Frederic J. de Blay, MD, Strasbourg University Hospital, France, said in an interview.

Dr. de Blay admitted he is “quite excited” about the results.

“This study was performed in an environmental exposure chamber, and we clearly demonstrate that these antibodies decrease the asthmatic response to cat allergen within 8 days, and that these effects last 3 months. I never saw that in my life. I was a little bit skeptical at first, so to obtain such robust results after just 8 days, after just one injection, I was very surprised,” he said.

Dr. de Blay and his team screened potential participants to make sure they were cat allergic by exposing them to cat allergen for up to 2 hours while they were in the environmental exposure chamber. To be eligible for the study, participants had to show an early asthmatic response (EAR), defined as a reduction in forced expiratory volume in 1 second (FEV₁₎ of at least 20% from baseline.

The participants were then randomized to receive either single-dose REGN1908-1909, 600 mg, subcutaneously (n = 29 patients) or placebo (n = 27 patients) prior to cat-allergen exposure in the controlled environmental chamber.

Dr. de Blay developed the chamber used in the study: the ALYATEC environmental exposure chamber.

“The chamber is 60 meters square, or 150 cubic meters, and can accommodate 20 patients. We are able to nebulize cat allergen, mice allergen, or whatever we wish to study so we can standardize the exposure. We can control the particle size and the amount so we know the exact amount of allergen that the patient has been exposed to,” he explained.

To test the efficacy of REGN1908-1909 in reducing acute bronchoconstriction, or EAR, the researchers measured FEV₁ at baseline, and on days 8, 29, 57, and 85 in both groups. During each exposure, measurements were taken every 10 minutes for periods that lasted up to 4 hours.

They found that the probability of remaining in the chamber with no asthmatic response was substantially elevated in the group treated with REGN1908-1909.

Compared with placebo, REGN1908-1909 significantly increased the median time to EAR, from 51 minutes at baseline to more than 4 hours on day 8, (hazard ratio [HR], 0.36; P < .0083), day 29 (HR, 0.24; P < .0001), day 57 (HR, 0.45; P = .0222), and day 85 (HR, 0.27; P = .0003).

The FEV₁ area under the curve (AUC) was also better with REGN1908-1909 than with placebo at day 8 (15.2% vs. 1.6%; P < .001). And a single dose reduced skin-test reactivity to cat allergen at 1 week, which persisted for up to 4 months.

In addition, participants who received REGN1908-1909 were able to tolerate a threefold higher amount of the cat allergen than those who received placebo (P = .003).

“We initially gave 40 nanograms of cat allergen, and then 8 days later they were able to stay longer in the chamber and inhale more of the allergen, to almost triple the amount they had originally been given. That 40 nanograms is very close to real world exposure,” Dr. de Blay noted.

Regeneron plans to start a phase 3 trial soon, he reported.
 

Promising results

“The study is well designed and shows a reduction in drop of FEV₁ in response to cat allergen provocation and a decreased AUC in cat SPT response over 4 months,” Jonathan A. Bernstein, MD, professor of medicine at the University of Cincinnati, said in an interview.

“These are very promising results, which show that REGN1908-1909 can be a novel treatment for cat-induced asthma, which is often the only sensitization patients have. And they love their cats – one-third of the U.S. population has a cat and one-third has a dog, and 50% have both,” noted Dr. Bernstein, who was not involved with the study.

“This novel study used our scientific knowledge of the cat allergen itself to design a targeted antibody-based treatment that demonstrates significant benefit even after the first shot,” added Edwin H. Kim, MD, director of the UNC Food Allergy Initiative at the University of North Carolina at Chapel Hill.

“This strategy has the potential to revolutionize not only our treatment of common environmental allergies but also other allergic diseases with well-described triggers, such as food and drug allergy,” Dr. Kim, who was not part of the study, said in an interview.

Dr. de Blay reported a financial relationship with Regeneron Pharmaceuticals, which sponsored the study. Dr. Bernstein and Dr. Kim have disclosed no relevant financial relationships.

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

Patients with severe asthma and comorbid atopy, obesity, and depression/anxiety had fewer annual exacerbations after receiving mepolizumab, according to research from the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

“Mepolizumab has clearly been shown to improve severe asthma control in many clinical trials, but atopy, obesity, and depression/anxiety affect patients with asthma at an increased rate,” Thomas B. Casale, MD, former AAAAI president and professor of medicine and pediatrics at the University of South Florida in Tampa, said in a presentation at the meeting. “Yet, few studies have examined whether asthma therapy with these comorbidities works.”

Dr. Casale and colleagues performed a retrospective analysis of patients in the United States from the MarketScan Commercial and Medicare Supplemental Database between November 2014 and December 2018 who had atopy, obesity, or depression/anxiety in addition to asthma and were receiving mepolizumab. Atopy in the study was defined as allergic rhinitis, anaphylaxis, atopic dermatitis, conjunctivitis, eosinophilic esophagitis, and food allergies. Patients were at least age 12 years, had at least one diagnosis for asthma, at least one diagnosis code for atopic disease, obesity, or depression/anxiety at baseline, and at least two administrations of mepolizumab within 180 days.

The researchers examined the number of exacerbations, oral corticosteroid (OCS) claims, and OCS bursts per year at 12-month follow-up, compared with baseline. They identified exacerbations by examining patients who had an emergency department or outpatient claim related to their asthma, and a claim for systemic corticosteroids made in the 4 days prior to or 5 days after a visit, or if their inpatient hospital admission contained a primary asthma diagnosis. Dr. Casale and colleagues measured OCS bursts as a pharmacy claim of at least 20 mg of prednisone per day for between 3 and 28 days plus a claim for an emergency department visit related to asthma in the 7 days prior or 6 days after the claim.

At baseline, patients across all groups were mean age 50.5-52.4 years with a Charleson Comorbidity Index score between 1.1 and 1.4, a majority were women (59.0%-72.0%) and nearly all were commercially insured (88.0%-90.0%). Patients who used biologics at baseline and/or used a biologic that wasn’t mepolizumab during the follow-up period were excluded.

Medication claims in the groups included inhaled corticosteroids (ICS) (36.8%-48.6%), ICS/long-acting beta-agonist (LABA) (60.2%-63.0%), LABA/ long-acting muscarinic antagonist (LAMA) (1.2%-3.5%), ICS/LABA/LAMA (21.2%-25.1%), short-acting beta-agonist (SABA) (83.2%-87.7%), LAMA alone (33.5%-42.1%), or leukotriene receptor antagonist (LTRA).

In the non–mutually exclusive group of patients with atopy (468 patients), 28.0% had comorbid obesity and 26.0% had comorbid depression/anxiety. For patients with obesity categorized in a non–mutually exclusive subgroup (171 patients), 79.0% had comorbid atopy and 32.0% had comorbid depression/anxiety. Among patients with non–mutually exclusive depression/anxiety (173 patients), 70.0% had comorbid atopy, while 32.0% had comorbid obesity.

The results showed the mean number of overall exacerbations decreased by 48% at 12 months in the atopic group (2.3 vs. 1.2; P < .001), 52% in the group with obesity (2.5 vs. 1.2; P < .001), and 38% in the depression/anxiety group (2.4 vs. 1.5; P < .001). The mean number of exacerbations leading to hospitalizations decreased by 64% in the atopic group (0.11 vs. 0.04; P < .001), 65% in the group with obesity (0.20 vs. 0.07; P < .001), and 68% in the group with depression/anxiety (0.22 vs. 0.07; P < .001).

The researchers also found the mean number of OCS claims and OCS bursts also significantly decreased over the 12-month follow-up period. Mean OCS claims decreased by 33% for patients in the atopic group (5.5 vs. 3.7; P < .001), by 38% in the group with obesity (6.1 vs. 3.8; P < .001), and by 31% in the group with depression/anxiety (6.2 vs. 4.3; P < .001).

The mean number of OCS bursts also significantly decreased by 40% in the atopic group (2.0 vs. 2.1; P < .001), 48% in the group with obesity (2.3 vs. 1.2; P < .001), and by 37% in the group with depression/anxiety (1.9 vs. 1.2; P < .001). In total, 69% of patients with comorbid atopy, 70.8% of patients with comorbid obesity, and 68.2% of patients with comorbid depression/anxiety experienced a mean decrease in their OCS dose over 12 months.

“These data demonstrate that patients with asthma and atopy, obesity, or depression and anxiety have significantly fewer exacerbations and reduced OCS use in a real-world setting with treatment of mepolizumab,” Dr. Casale said. “Thus, holistic patient care for severe asthma is critical, and mepolizumab provides tangible clinical benefit despite the complexities of medical comorbidities.”

This study was funded by GlaxoSmithKline, and the company also funded graphic design support of the poster. Dr. Casale reports he has received research funds from GlaxoSmithKline. Four authors report being current or former GlaxoSmithKline employees; three authors report holding stock and/or shares of GlaxoSmithKline. Three authors are IBM Watson Health employees, a company GlaxoSmithKline has provided research funding.

Patients with severe asthma and comorbid atopy, obesity, and depression/anxiety had fewer annual exacerbations after receiving mepolizumab, according to research from the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

“Mepolizumab has clearly been shown to improve severe asthma control in many clinical trials, but atopy, obesity, and depression/anxiety affect patients with asthma at an increased rate,” Thomas B. Casale, MD, former AAAAI president and professor of medicine and pediatrics at the University of South Florida in Tampa, said in a presentation at the meeting. “Yet, few studies have examined whether asthma therapy with these comorbidities works.”

Dr. Casale and colleagues performed a retrospective analysis of patients in the United States from the MarketScan Commercial and Medicare Supplemental Database between November 2014 and December 2018 who had atopy, obesity, or depression/anxiety in addition to asthma and were receiving mepolizumab. Atopy in the study was defined as allergic rhinitis, anaphylaxis, atopic dermatitis, conjunctivitis, eosinophilic esophagitis, and food allergies. Patients were at least age 12 years, had at least one diagnosis for asthma, at least one diagnosis code for atopic disease, obesity, or depression/anxiety at baseline, and at least two administrations of mepolizumab within 180 days.

The researchers examined the number of exacerbations, oral corticosteroid (OCS) claims, and OCS bursts per year at 12-month follow-up, compared with baseline. They identified exacerbations by examining patients who had an emergency department or outpatient claim related to their asthma, and a claim for systemic corticosteroids made in the 4 days prior to or 5 days after a visit, or if their inpatient hospital admission contained a primary asthma diagnosis. Dr. Casale and colleagues measured OCS bursts as a pharmacy claim of at least 20 mg of prednisone per day for between 3 and 28 days plus a claim for an emergency department visit related to asthma in the 7 days prior or 6 days after the claim.

At baseline, patients across all groups were mean age 50.5-52.4 years with a Charleson Comorbidity Index score between 1.1 and 1.4, a majority were women (59.0%-72.0%) and nearly all were commercially insured (88.0%-90.0%). Patients who used biologics at baseline and/or used a biologic that wasn’t mepolizumab during the follow-up period were excluded.

Medication claims in the groups included inhaled corticosteroids (ICS) (36.8%-48.6%), ICS/long-acting beta-agonist (LABA) (60.2%-63.0%), LABA/ long-acting muscarinic antagonist (LAMA) (1.2%-3.5%), ICS/LABA/LAMA (21.2%-25.1%), short-acting beta-agonist (SABA) (83.2%-87.7%), LAMA alone (33.5%-42.1%), or leukotriene receptor antagonist (LTRA).

In the non–mutually exclusive group of patients with atopy (468 patients), 28.0% had comorbid obesity and 26.0% had comorbid depression/anxiety. For patients with obesity categorized in a non–mutually exclusive subgroup (171 patients), 79.0% had comorbid atopy and 32.0% had comorbid depression/anxiety. Among patients with non–mutually exclusive depression/anxiety (173 patients), 70.0% had comorbid atopy, while 32.0% had comorbid obesity.

The results showed the mean number of overall exacerbations decreased by 48% at 12 months in the atopic group (2.3 vs. 1.2; P < .001), 52% in the group with obesity (2.5 vs. 1.2; P < .001), and 38% in the depression/anxiety group (2.4 vs. 1.5; P < .001). The mean number of exacerbations leading to hospitalizations decreased by 64% in the atopic group (0.11 vs. 0.04; P < .001), 65% in the group with obesity (0.20 vs. 0.07; P < .001), and 68% in the group with depression/anxiety (0.22 vs. 0.07; P < .001).

The researchers also found the mean number of OCS claims and OCS bursts also significantly decreased over the 12-month follow-up period. Mean OCS claims decreased by 33% for patients in the atopic group (5.5 vs. 3.7; P < .001), by 38% in the group with obesity (6.1 vs. 3.8; P < .001), and by 31% in the group with depression/anxiety (6.2 vs. 4.3; P < .001).

The mean number of OCS bursts also significantly decreased by 40% in the atopic group (2.0 vs. 2.1; P < .001), 48% in the group with obesity (2.3 vs. 1.2; P < .001), and by 37% in the group with depression/anxiety (1.9 vs. 1.2; P < .001). In total, 69% of patients with comorbid atopy, 70.8% of patients with comorbid obesity, and 68.2% of patients with comorbid depression/anxiety experienced a mean decrease in their OCS dose over 12 months.

“These data demonstrate that patients with asthma and atopy, obesity, or depression and anxiety have significantly fewer exacerbations and reduced OCS use in a real-world setting with treatment of mepolizumab,” Dr. Casale said. “Thus, holistic patient care for severe asthma is critical, and mepolizumab provides tangible clinical benefit despite the complexities of medical comorbidities.”

This study was funded by GlaxoSmithKline, and the company also funded graphic design support of the poster. Dr. Casale reports he has received research funds from GlaxoSmithKline. Four authors report being current or former GlaxoSmithKline employees; three authors report holding stock and/or shares of GlaxoSmithKline. Three authors are IBM Watson Health employees, a company GlaxoSmithKline has provided research funding.

Patients with severe asthma and comorbid atopy, obesity, and depression/anxiety had fewer annual exacerbations after receiving mepolizumab, according to research from the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

“Mepolizumab has clearly been shown to improve severe asthma control in many clinical trials, but atopy, obesity, and depression/anxiety affect patients with asthma at an increased rate,” Thomas B. Casale, MD, former AAAAI president and professor of medicine and pediatrics at the University of South Florida in Tampa, said in a presentation at the meeting. “Yet, few studies have examined whether asthma therapy with these comorbidities works.”

Dr. Casale and colleagues performed a retrospective analysis of patients in the United States from the MarketScan Commercial and Medicare Supplemental Database between November 2014 and December 2018 who had atopy, obesity, or depression/anxiety in addition to asthma and were receiving mepolizumab. Atopy in the study was defined as allergic rhinitis, anaphylaxis, atopic dermatitis, conjunctivitis, eosinophilic esophagitis, and food allergies. Patients were at least age 12 years, had at least one diagnosis for asthma, at least one diagnosis code for atopic disease, obesity, or depression/anxiety at baseline, and at least two administrations of mepolizumab within 180 days.

The researchers examined the number of exacerbations, oral corticosteroid (OCS) claims, and OCS bursts per year at 12-month follow-up, compared with baseline. They identified exacerbations by examining patients who had an emergency department or outpatient claim related to their asthma, and a claim for systemic corticosteroids made in the 4 days prior to or 5 days after a visit, or if their inpatient hospital admission contained a primary asthma diagnosis. Dr. Casale and colleagues measured OCS bursts as a pharmacy claim of at least 20 mg of prednisone per day for between 3 and 28 days plus a claim for an emergency department visit related to asthma in the 7 days prior or 6 days after the claim.

At baseline, patients across all groups were mean age 50.5-52.4 years with a Charleson Comorbidity Index score between 1.1 and 1.4, a majority were women (59.0%-72.0%) and nearly all were commercially insured (88.0%-90.0%). Patients who used biologics at baseline and/or used a biologic that wasn’t mepolizumab during the follow-up period were excluded.

Medication claims in the groups included inhaled corticosteroids (ICS) (36.8%-48.6%), ICS/long-acting beta-agonist (LABA) (60.2%-63.0%), LABA/ long-acting muscarinic antagonist (LAMA) (1.2%-3.5%), ICS/LABA/LAMA (21.2%-25.1%), short-acting beta-agonist (SABA) (83.2%-87.7%), LAMA alone (33.5%-42.1%), or leukotriene receptor antagonist (LTRA).

In the non–mutually exclusive group of patients with atopy (468 patients), 28.0% had comorbid obesity and 26.0% had comorbid depression/anxiety. For patients with obesity categorized in a non–mutually exclusive subgroup (171 patients), 79.0% had comorbid atopy and 32.0% had comorbid depression/anxiety. Among patients with non–mutually exclusive depression/anxiety (173 patients), 70.0% had comorbid atopy, while 32.0% had comorbid obesity.

The results showed the mean number of overall exacerbations decreased by 48% at 12 months in the atopic group (2.3 vs. 1.2; P < .001), 52% in the group with obesity (2.5 vs. 1.2; P < .001), and 38% in the depression/anxiety group (2.4 vs. 1.5; P < .001). The mean number of exacerbations leading to hospitalizations decreased by 64% in the atopic group (0.11 vs. 0.04; P < .001), 65% in the group with obesity (0.20 vs. 0.07; P < .001), and 68% in the group with depression/anxiety (0.22 vs. 0.07; P < .001).

The researchers also found the mean number of OCS claims and OCS bursts also significantly decreased over the 12-month follow-up period. Mean OCS claims decreased by 33% for patients in the atopic group (5.5 vs. 3.7; P < .001), by 38% in the group with obesity (6.1 vs. 3.8; P < .001), and by 31% in the group with depression/anxiety (6.2 vs. 4.3; P < .001).

The mean number of OCS bursts also significantly decreased by 40% in the atopic group (2.0 vs. 2.1; P < .001), 48% in the group with obesity (2.3 vs. 1.2; P < .001), and by 37% in the group with depression/anxiety (1.9 vs. 1.2; P < .001). In total, 69% of patients with comorbid atopy, 70.8% of patients with comorbid obesity, and 68.2% of patients with comorbid depression/anxiety experienced a mean decrease in their OCS dose over 12 months.

“These data demonstrate that patients with asthma and atopy, obesity, or depression and anxiety have significantly fewer exacerbations and reduced OCS use in a real-world setting with treatment of mepolizumab,” Dr. Casale said. “Thus, holistic patient care for severe asthma is critical, and mepolizumab provides tangible clinical benefit despite the complexities of medical comorbidities.”

This study was funded by GlaxoSmithKline, and the company also funded graphic design support of the poster. Dr. Casale reports he has received research funds from GlaxoSmithKline. Four authors report being current or former GlaxoSmithKline employees; three authors report holding stock and/or shares of GlaxoSmithKline. Three authors are IBM Watson Health employees, a company GlaxoSmithKline has provided research funding.

What happened to Hasan Gokal, MD, should stick painfully in the craws of all physicians. It should serve as a call to action, because Dr. Gokal is sitting at home today without a job and under threat of further legal action while we continue about our day.

Dr. Gokal’s “crime” is that he vaccinated 10 strangers and acquaintances with soon-to-expire doses of the Moderna COVID-19 vaccine. He drove to the homes of some in the dark of night and injected others on his Sugar Land, Texas, lawn. He spent hours in a frantic search for willing recipients to beat the expiration clock. With minutes to spare, he gave the last dose to his at-risk wife, who has symptomatic pulmonary sarcoidosis, but whose age meant she did not fall into a vaccine priority tier.

According to the New York Times, Dr. Gokal’s wife was hesitant, afraid he might get into trouble. But why would she be hesitant? He wasn’t doing anything immoral. Perhaps she knew how far physicians have fallen and how bitterly they both could suffer.

In Barren County, Ky., where I live, a state of emergency was declared by our judge executive because of inclement weather. This directive allows our emergency management to “waive procedures and formalities otherwise required by the law.” It’s too bad that the same courtesy was not afforded to Dr. Gokal in Texas. It’s a shame that ice and snow didn’t drive his actions. Perhaps that would have protected him against the harsh criticism. Rather, it was his oath to patients and dedication to his fellow humans that motivated him, and for that, he was made to suffer.

Dr. Gokal was right to think that pouring the last 10 vaccine doses down the toilet would be an egregious act. But he was wrong in thinking his decision to find takers for the vaccine would be viewed as expedient. Instead, he was accused of graft and even nepotism. And there is the rub. That he was fired and charged with the theft of $137 worth of vaccines says everything about how physicians are treated in the year 2021. Dr. Gokal’s lawyer says the charge carried a maximum penalty of 1 year in prison and a fine of nearly $4,000.

Thank God a sage judge threw out the case and “rebuked” the office of District Attorney Kim Ogg. That hasn’t stopped her from threatening to bring the case to a grand jury. That threat invites anyone faced with the same scenario to flush the extra vaccine doses into the septic system. It encourages us to choose the toilet handle to avoid a mug shot.

And we can’t ignore the racial slant to this story. The Times reported that Dr. Gokal asked the officials, “Are you suggesting that there were too many Indian names in this group?”

“Exactly” was the answer. Let that sink in.

None of this would have happened 20 years ago. Back then, no one would have questioned the wisdom a physician gains from all our years of training and residency. In an age when anyone who conducts an office visit is now called “doctor,” respect for the letters “MD” has been leveled. We physicians have lost our autonomy and been cowed into submission.

But whatever his profession, Hasan Gokal was fired for being a good human. Today, the sun rose on 10 individuals who now enjoy better protection against a deadly pandemic. They include a bed-bound nonagenarian. A woman in her 80s with dementia. A mother with a child who uses a ventilator. All now have antibodies against SARS-CoV2 because of the tireless actions of Dr. Gokal.

Yet Dr. Gokal’s future is uncertain. Will we help him, or will we leave him to the wolves? In an email exchange with his lawyer’s office, I learned that Dr. Gokal has received offers of employment but is unable to entertain them because the actions by the Harris County District Attorney triggered an automatic review by the Texas Medical Board. A GoFundMe page was launched, but an appreciative Dr. Gokal stated publicly that he’d rather the money go to a needy charity.

 In the last paragraph of the Times article, Dr. Gokal asks, “How can I take it back?” referencing stories about “the Pakistani doctor in Houston who stole all those vaccines.”

Let’s help him take back his story. In helping him, perhaps we can take back a little control. We could start with letters of support that could be mailed to his lawyer, Paul Doyle, Esq., of Houston, or tweet, respectfully of course, to the district attorney @Kimoggforda.

We can also let the Harris County Public Health Department in Houston know what we think of their actions.

On Martin Luther King Day, Kim Ogg, the district attorney who charged Dr. Gokal, tweeted MLK’s famous quote: “Injustice anywhere is a threat to justice everywhere.”

Let that motivate us to action.

Melissa Walton-Shirley, MD, is a native Kentuckian who retired from full-time invasive cardiology. She enjoys locums work in Montana and is a champion of physician rights and patient safety. In addition to opinion writing, she enjoys spending time with her husband, daughters and parents, and sidelines as a backing vocalist for local rock bands. A version of this article first appeared on Medscape.com.

What happened to Hasan Gokal, MD, should stick painfully in the craws of all physicians. It should serve as a call to action, because Dr. Gokal is sitting at home today without a job and under threat of further legal action while we continue about our day.

Dr. Gokal’s “crime” is that he vaccinated 10 strangers and acquaintances with soon-to-expire doses of the Moderna COVID-19 vaccine. He drove to the homes of some in the dark of night and injected others on his Sugar Land, Texas, lawn. He spent hours in a frantic search for willing recipients to beat the expiration clock. With minutes to spare, he gave the last dose to his at-risk wife, who has symptomatic pulmonary sarcoidosis, but whose age meant she did not fall into a vaccine priority tier.

According to the New York Times, Dr. Gokal’s wife was hesitant, afraid he might get into trouble. But why would she be hesitant? He wasn’t doing anything immoral. Perhaps she knew how far physicians have fallen and how bitterly they both could suffer.

In Barren County, Ky., where I live, a state of emergency was declared by our judge executive because of inclement weather. This directive allows our emergency management to “waive procedures and formalities otherwise required by the law.” It’s too bad that the same courtesy was not afforded to Dr. Gokal in Texas. It’s a shame that ice and snow didn’t drive his actions. Perhaps that would have protected him against the harsh criticism. Rather, it was his oath to patients and dedication to his fellow humans that motivated him, and for that, he was made to suffer.

Dr. Gokal was right to think that pouring the last 10 vaccine doses down the toilet would be an egregious act. But he was wrong in thinking his decision to find takers for the vaccine would be viewed as expedient. Instead, he was accused of graft and even nepotism. And there is the rub. That he was fired and charged with the theft of $137 worth of vaccines says everything about how physicians are treated in the year 2021. Dr. Gokal’s lawyer says the charge carried a maximum penalty of 1 year in prison and a fine of nearly $4,000.

Thank God a sage judge threw out the case and “rebuked” the office of District Attorney Kim Ogg. That hasn’t stopped her from threatening to bring the case to a grand jury. That threat invites anyone faced with the same scenario to flush the extra vaccine doses into the septic system. It encourages us to choose the toilet handle to avoid a mug shot.

And we can’t ignore the racial slant to this story. The Times reported that Dr. Gokal asked the officials, “Are you suggesting that there were too many Indian names in this group?”

“Exactly” was the answer. Let that sink in.

None of this would have happened 20 years ago. Back then, no one would have questioned the wisdom a physician gains from all our years of training and residency. In an age when anyone who conducts an office visit is now called “doctor,” respect for the letters “MD” has been leveled. We physicians have lost our autonomy and been cowed into submission.

But whatever his profession, Hasan Gokal was fired for being a good human. Today, the sun rose on 10 individuals who now enjoy better protection against a deadly pandemic. They include a bed-bound nonagenarian. A woman in her 80s with dementia. A mother with a child who uses a ventilator. All now have antibodies against SARS-CoV2 because of the tireless actions of Dr. Gokal.

Yet Dr. Gokal’s future is uncertain. Will we help him, or will we leave him to the wolves? In an email exchange with his lawyer’s office, I learned that Dr. Gokal has received offers of employment but is unable to entertain them because the actions by the Harris County District Attorney triggered an automatic review by the Texas Medical Board. A GoFundMe page was launched, but an appreciative Dr. Gokal stated publicly that he’d rather the money go to a needy charity.

 In the last paragraph of the Times article, Dr. Gokal asks, “How can I take it back?” referencing stories about “the Pakistani doctor in Houston who stole all those vaccines.”

Let’s help him take back his story. In helping him, perhaps we can take back a little control. We could start with letters of support that could be mailed to his lawyer, Paul Doyle, Esq., of Houston, or tweet, respectfully of course, to the district attorney @Kimoggforda.

We can also let the Harris County Public Health Department in Houston know what we think of their actions.

On Martin Luther King Day, Kim Ogg, the district attorney who charged Dr. Gokal, tweeted MLK’s famous quote: “Injustice anywhere is a threat to justice everywhere.”

Let that motivate us to action.

Melissa Walton-Shirley, MD, is a native Kentuckian who retired from full-time invasive cardiology. She enjoys locums work in Montana and is a champion of physician rights and patient safety. In addition to opinion writing, she enjoys spending time with her husband, daughters and parents, and sidelines as a backing vocalist for local rock bands. A version of this article first appeared on Medscape.com.

What happened to Hasan Gokal, MD, should stick painfully in the craws of all physicians. It should serve as a call to action, because Dr. Gokal is sitting at home today without a job and under threat of further legal action while we continue about our day.

Dr. Gokal’s “crime” is that he vaccinated 10 strangers and acquaintances with soon-to-expire doses of the Moderna COVID-19 vaccine. He drove to the homes of some in the dark of night and injected others on his Sugar Land, Texas, lawn. He spent hours in a frantic search for willing recipients to beat the expiration clock. With minutes to spare, he gave the last dose to his at-risk wife, who has symptomatic pulmonary sarcoidosis, but whose age meant she did not fall into a vaccine priority tier.

According to the New York Times, Dr. Gokal’s wife was hesitant, afraid he might get into trouble. But why would she be hesitant? He wasn’t doing anything immoral. Perhaps she knew how far physicians have fallen and how bitterly they both could suffer.

In Barren County, Ky., where I live, a state of emergency was declared by our judge executive because of inclement weather. This directive allows our emergency management to “waive procedures and formalities otherwise required by the law.” It’s too bad that the same courtesy was not afforded to Dr. Gokal in Texas. It’s a shame that ice and snow didn’t drive his actions. Perhaps that would have protected him against the harsh criticism. Rather, it was his oath to patients and dedication to his fellow humans that motivated him, and for that, he was made to suffer.

Dr. Gokal was right to think that pouring the last 10 vaccine doses down the toilet would be an egregious act. But he was wrong in thinking his decision to find takers for the vaccine would be viewed as expedient. Instead, he was accused of graft and even nepotism. And there is the rub. That he was fired and charged with the theft of $137 worth of vaccines says everything about how physicians are treated in the year 2021. Dr. Gokal’s lawyer says the charge carried a maximum penalty of 1 year in prison and a fine of nearly $4,000.

Thank God a sage judge threw out the case and “rebuked” the office of District Attorney Kim Ogg. That hasn’t stopped her from threatening to bring the case to a grand jury. That threat invites anyone faced with the same scenario to flush the extra vaccine doses into the septic system. It encourages us to choose the toilet handle to avoid a mug shot.

And we can’t ignore the racial slant to this story. The Times reported that Dr. Gokal asked the officials, “Are you suggesting that there were too many Indian names in this group?”

“Exactly” was the answer. Let that sink in.

None of this would have happened 20 years ago. Back then, no one would have questioned the wisdom a physician gains from all our years of training and residency. In an age when anyone who conducts an office visit is now called “doctor,” respect for the letters “MD” has been leveled. We physicians have lost our autonomy and been cowed into submission.

But whatever his profession, Hasan Gokal was fired for being a good human. Today, the sun rose on 10 individuals who now enjoy better protection against a deadly pandemic. They include a bed-bound nonagenarian. A woman in her 80s with dementia. A mother with a child who uses a ventilator. All now have antibodies against SARS-CoV2 because of the tireless actions of Dr. Gokal.

Yet Dr. Gokal’s future is uncertain. Will we help him, or will we leave him to the wolves? In an email exchange with his lawyer’s office, I learned that Dr. Gokal has received offers of employment but is unable to entertain them because the actions by the Harris County District Attorney triggered an automatic review by the Texas Medical Board. A GoFundMe page was launched, but an appreciative Dr. Gokal stated publicly that he’d rather the money go to a needy charity.

 In the last paragraph of the Times article, Dr. Gokal asks, “How can I take it back?” referencing stories about “the Pakistani doctor in Houston who stole all those vaccines.”

Let’s help him take back his story. In helping him, perhaps we can take back a little control. We could start with letters of support that could be mailed to his lawyer, Paul Doyle, Esq., of Houston, or tweet, respectfully of course, to the district attorney @Kimoggforda.

We can also let the Harris County Public Health Department in Houston know what we think of their actions.

On Martin Luther King Day, Kim Ogg, the district attorney who charged Dr. Gokal, tweeted MLK’s famous quote: “Injustice anywhere is a threat to justice everywhere.”

Let that motivate us to action.

Melissa Walton-Shirley, MD, is a native Kentuckian who retired from full-time invasive cardiology. She enjoys locums work in Montana and is a champion of physician rights and patient safety. In addition to opinion writing, she enjoys spending time with her husband, daughters and parents, and sidelines as a backing vocalist for local rock bands. A version of this article first appeared on Medscape.com.

Hydroxychloroquine can be used safely and effectively with attention to dosing, risk factors, and screening, but communication among physicians, patients, and eye care specialists is key to optimizing outcomes and preventing complications, according to a joint statement from four medical societies.

The American College of Rheumatology, American Academy of Dermatology, Rheumatologic Dermatology Society, and the American Academy of Ophthalmology have produced a statement, published in Arthritis & Rheumatology, “to emphasize points of agreement that should be recognized by practitioners in all specialties,” lead author James T. Rosenbaum, MD, of Oregon Health & Science University, Portland, and colleagues wrote.

The statement was developed by a working group that included rheumatologists, ophthalmologists, and dermatologists with records of published studies on the use of hydroxychloroquine (HCQ) and its toxicity. The statement updated elements of the 2016 American Academy of Ophthalmology guidelines for monitoring patients for retinal toxicity when using HCQ.

“The need for collaborative management has triggered this joint statement, which applies only to managing the risk of HCQ retinopathy and does not include consideration of cardiac, muscle, dermatologic, or other toxicities,” the authors noted.

The authors emphasized that HCQ plays a valuable role in controlling many rheumatic diseases, and should not be abandoned out of fear of retinopathy. However, proper dosing, recognition of risk factors, and screening strategies are essential.
 

Dosing data

Data on HCQ dosing and retinopathy are limited, but the authors cited a study of 2,361 rheumatic disease patients with an average HCQ dosing regimen of 5.0 mg/kg per day or less in which the toxicity risk was less than 2% for up to 10 years of use. Although data show some increase in risk with duration of use, “for a patient with a normal screening exam in a given year, the risk of developing retinopathy in the ensuing year is low (e.g., less than 5%), even after 20 years of use,” the authors said.

Risk factor recognition

“High daily [HCQ] dosage relative to body weight and cumulative dose are the primary risk factors for retinopathy,” the authors noted. Reduced renal function is an additional risk factor, and patients with renal insufficiency should be monitored and may need lower doses.

In addition, patients with a phenotype of initial parafoveal toxicity may be at increased risk for advanced disease evidenced by damage to the foveal center. “The phenotype of initial parafoveal toxicity is not universal, and in many patients (East Asians particularly) the retinal changes may appear initially along the pericentral vascular arcades,” so these patients should be screened with additional tests beyond the central macula, they emphasized.

Screening strategies

Patients should receive a baseline retinal exam within a few months of starting HCQ to rule out underlying retinal disease, according to the statement. The goal of screening is “to detect early retinopathy before a bullseye becomes visible on ophthalmoscopy, since at that severe stage the damage tends to progress even after discontinuing the medication and may eventually threaten central vision,” the authors said.

Marc Bruxelle/Getty Images

In the absence of risk factors, patients can defer screening for 5 years, but should be screened annually from 5 years and forward, they said. Examples of underlying retinal disease include “significant macular degeneration, severe diabetic retinopathy, or hereditary disorders of retinal function, but these are judgments best made by the ophthalmologist since mild and stable abnormalities that do not interfere with interpretation of critical diagnostic tests may not be a contraindication” to use of HCQ.

The consensus opinion statement has limitations, notably the shortage of data on optimum HCQ dosage and the lack of prospective studies of toxicity, including the need for studies of the impact of blood levels on toxicity and studies of pharmacogenomics to stratify risk, the authors noted.

“It is important that the drug is not stopped prematurely, but also that it is not continued in the face of definitive evidence of retinal toxicity except in some situations with unusual medical need,” they said.

“Suggestive or uncertain findings should be discussed with the patient and prescribing physician to justify further examinations, but the drug need not be stopped until evidence for retinopathy is definitive, in particular for patients with active rheumatic or cutaneous disease,” and the overall risk of retinopathy remains low if the principles described in the statement are followed, they concluded.

First author Dr. Rosenbaum disclosed financial relationships with AbbVie, UCB, Gilead, Novartis, Horizon, Roche, Eyevensys, Santen, Corvus, Affibody, Kyverna, Pfizer, Horizon, and UpToDate. Another 5 of the study’s 11 authors also disclosed relationships with multiple companies.

Hydroxychloroquine can be used safely and effectively with attention to dosing, risk factors, and screening, but communication among physicians, patients, and eye care specialists is key to optimizing outcomes and preventing complications, according to a joint statement from four medical societies.

The American College of Rheumatology, American Academy of Dermatology, Rheumatologic Dermatology Society, and the American Academy of Ophthalmology have produced a statement, published in Arthritis & Rheumatology, “to emphasize points of agreement that should be recognized by practitioners in all specialties,” lead author James T. Rosenbaum, MD, of Oregon Health & Science University, Portland, and colleagues wrote.

The statement was developed by a working group that included rheumatologists, ophthalmologists, and dermatologists with records of published studies on the use of hydroxychloroquine (HCQ) and its toxicity. The statement updated elements of the 2016 American Academy of Ophthalmology guidelines for monitoring patients for retinal toxicity when using HCQ.

“The need for collaborative management has triggered this joint statement, which applies only to managing the risk of HCQ retinopathy and does not include consideration of cardiac, muscle, dermatologic, or other toxicities,” the authors noted.

The authors emphasized that HCQ plays a valuable role in controlling many rheumatic diseases, and should not be abandoned out of fear of retinopathy. However, proper dosing, recognition of risk factors, and screening strategies are essential.
 

Dosing data

Data on HCQ dosing and retinopathy are limited, but the authors cited a study of 2,361 rheumatic disease patients with an average HCQ dosing regimen of 5.0 mg/kg per day or less in which the toxicity risk was less than 2% for up to 10 years of use. Although data show some increase in risk with duration of use, “for a patient with a normal screening exam in a given year, the risk of developing retinopathy in the ensuing year is low (e.g., less than 5%), even after 20 years of use,” the authors said.

Risk factor recognition

“High daily [HCQ] dosage relative to body weight and cumulative dose are the primary risk factors for retinopathy,” the authors noted. Reduced renal function is an additional risk factor, and patients with renal insufficiency should be monitored and may need lower doses.

In addition, patients with a phenotype of initial parafoveal toxicity may be at increased risk for advanced disease evidenced by damage to the foveal center. “The phenotype of initial parafoveal toxicity is not universal, and in many patients (East Asians particularly) the retinal changes may appear initially along the pericentral vascular arcades,” so these patients should be screened with additional tests beyond the central macula, they emphasized.

Screening strategies

Patients should receive a baseline retinal exam within a few months of starting HCQ to rule out underlying retinal disease, according to the statement. The goal of screening is “to detect early retinopathy before a bullseye becomes visible on ophthalmoscopy, since at that severe stage the damage tends to progress even after discontinuing the medication and may eventually threaten central vision,” the authors said.

Marc Bruxelle/Getty Images

In the absence of risk factors, patients can defer screening for 5 years, but should be screened annually from 5 years and forward, they said. Examples of underlying retinal disease include “significant macular degeneration, severe diabetic retinopathy, or hereditary disorders of retinal function, but these are judgments best made by the ophthalmologist since mild and stable abnormalities that do not interfere with interpretation of critical diagnostic tests may not be a contraindication” to use of HCQ.

The consensus opinion statement has limitations, notably the shortage of data on optimum HCQ dosage and the lack of prospective studies of toxicity, including the need for studies of the impact of blood levels on toxicity and studies of pharmacogenomics to stratify risk, the authors noted.

“It is important that the drug is not stopped prematurely, but also that it is not continued in the face of definitive evidence of retinal toxicity except in some situations with unusual medical need,” they said.

“Suggestive or uncertain findings should be discussed with the patient and prescribing physician to justify further examinations, but the drug need not be stopped until evidence for retinopathy is definitive, in particular for patients with active rheumatic or cutaneous disease,” and the overall risk of retinopathy remains low if the principles described in the statement are followed, they concluded.

First author Dr. Rosenbaum disclosed financial relationships with AbbVie, UCB, Gilead, Novartis, Horizon, Roche, Eyevensys, Santen, Corvus, Affibody, Kyverna, Pfizer, Horizon, and UpToDate. Another 5 of the study’s 11 authors also disclosed relationships with multiple companies.

Hydroxychloroquine can be used safely and effectively with attention to dosing, risk factors, and screening, but communication among physicians, patients, and eye care specialists is key to optimizing outcomes and preventing complications, according to a joint statement from four medical societies.

The American College of Rheumatology, American Academy of Dermatology, Rheumatologic Dermatology Society, and the American Academy of Ophthalmology have produced a statement, published in Arthritis & Rheumatology, “to emphasize points of agreement that should be recognized by practitioners in all specialties,” lead author James T. Rosenbaum, MD, of Oregon Health & Science University, Portland, and colleagues wrote.

The statement was developed by a working group that included rheumatologists, ophthalmologists, and dermatologists with records of published studies on the use of hydroxychloroquine (HCQ) and its toxicity. The statement updated elements of the 2016 American Academy of Ophthalmology guidelines for monitoring patients for retinal toxicity when using HCQ.

“The need for collaborative management has triggered this joint statement, which applies only to managing the risk of HCQ retinopathy and does not include consideration of cardiac, muscle, dermatologic, or other toxicities,” the authors noted.

The authors emphasized that HCQ plays a valuable role in controlling many rheumatic diseases, and should not be abandoned out of fear of retinopathy. However, proper dosing, recognition of risk factors, and screening strategies are essential.
 

Dosing data

Data on HCQ dosing and retinopathy are limited, but the authors cited a study of 2,361 rheumatic disease patients with an average HCQ dosing regimen of 5.0 mg/kg per day or less in which the toxicity risk was less than 2% for up to 10 years of use. Although data show some increase in risk with duration of use, “for a patient with a normal screening exam in a given year, the risk of developing retinopathy in the ensuing year is low (e.g., less than 5%), even after 20 years of use,” the authors said.

Risk factor recognition

“High daily [HCQ] dosage relative to body weight and cumulative dose are the primary risk factors for retinopathy,” the authors noted. Reduced renal function is an additional risk factor, and patients with renal insufficiency should be monitored and may need lower doses.

In addition, patients with a phenotype of initial parafoveal toxicity may be at increased risk for advanced disease evidenced by damage to the foveal center. “The phenotype of initial parafoveal toxicity is not universal, and in many patients (East Asians particularly) the retinal changes may appear initially along the pericentral vascular arcades,” so these patients should be screened with additional tests beyond the central macula, they emphasized.

Screening strategies

Patients should receive a baseline retinal exam within a few months of starting HCQ to rule out underlying retinal disease, according to the statement. The goal of screening is “to detect early retinopathy before a bullseye becomes visible on ophthalmoscopy, since at that severe stage the damage tends to progress even after discontinuing the medication and may eventually threaten central vision,” the authors said.

Marc Bruxelle/Getty Images

In the absence of risk factors, patients can defer screening for 5 years, but should be screened annually from 5 years and forward, they said. Examples of underlying retinal disease include “significant macular degeneration, severe diabetic retinopathy, or hereditary disorders of retinal function, but these are judgments best made by the ophthalmologist since mild and stable abnormalities that do not interfere with interpretation of critical diagnostic tests may not be a contraindication” to use of HCQ.

The consensus opinion statement has limitations, notably the shortage of data on optimum HCQ dosage and the lack of prospective studies of toxicity, including the need for studies of the impact of blood levels on toxicity and studies of pharmacogenomics to stratify risk, the authors noted.

“It is important that the drug is not stopped prematurely, but also that it is not continued in the face of definitive evidence of retinal toxicity except in some situations with unusual medical need,” they said.

“Suggestive or uncertain findings should be discussed with the patient and prescribing physician to justify further examinations, but the drug need not be stopped until evidence for retinopathy is definitive, in particular for patients with active rheumatic or cutaneous disease,” and the overall risk of retinopathy remains low if the principles described in the statement are followed, they concluded.

First author Dr. Rosenbaum disclosed financial relationships with AbbVie, UCB, Gilead, Novartis, Horizon, Roche, Eyevensys, Santen, Corvus, Affibody, Kyverna, Pfizer, Horizon, and UpToDate. Another 5 of the study’s 11 authors also disclosed relationships with multiple companies.

Sublingual immunotherapy for the treatment of peanut allergy is safe and effective, even in children as young as age 1 year.

In a double-blind, placebo-controlled, food challenge (DBPCFC) of some 36 peanut-allergic children (mean age 2.2 years, range 1-4 years), those who were randomly assigned to receive peanut sublingual immunotherapy (PNSLIT) showed significant desensitization compared with those who received placebo.

In addition, there was a “strong potential” for sustained unresponsiveness at 3 months for the toddlers who received the active treatment.

The findings were presented in a late breaking oral abstract session at the 2021 American Academy of Allergy, Asthma & Immunology virtual annual meeting (Abstract L2).

“A year ago, the Food and Drug Administration approved the oral agent Palforzia (peanut allergen powder) for the treatment of peanut allergy in children 4 and older, and it is a great option, but I think what we have learned over time is that this approach is not for everybody,” Edwin H. Kim, MD, director of the UNC Food Allergy Initiative, University of North Carolina at Chapel Hill, said in an interview.

Palforzia is a powder that is mixed in food like yogurt or pudding which the child then eats daily, according to a rigorous schedule. But Palforzia treatment presents some difficulties.

“Palforzia requires getting the powder dose, mixing it with food, like pudding or apple sauce, then eating it, which can take up to 30 minutes depending on age and kids’ cooperation. It tastes and smells like peanut which can cause aversion. Kids have to refrain from exercise or strenuous activity for at least 30 minutes before and after dosing and have to be observed for up to 2 hours post dose for symptoms,” Dr. Kim said.

“It’s a great drug, but the treatment could be overly difficult for certain families to be able to do, and in some cases the side effects may be more than certain patients are able or willing to handle, so there is a real urgent need for alternative approaches,” Dr. Kim said. “SLIT is several drops under the tongue, held for 2 minutes, swallowed and done.”

In the current placebo-controlled study, he and his group tested the feasibility, efficacy, and safety of the sublingual approach to peanut allergy in children age 4 years and younger.

Both groups were similar with regard to gender, race, ethnicity, atopic history, peanut skin prick test, and qualifying DBPCFC, and all children were previously allergic with positive blood and skin tests, with a positive reaction during baseline food challenge, thus proving the allergy and establishing the baseline threshold.

“We have learned from some studies, for instance the DEVIL and LEAP studies, that strongly suggest that the immune systems in younger patients may be more amenable to change, and there may be some justification for early intervention,” he said.

“Based on both of those ideas, we wanted to take our sublingual approach, which we have shown to have a pretty good efficacy in older children, and bring it down to this younger group and see if it still could have the same efficacy and also maintain what seems to be a very good safety signal.”

The researchers randomly assigned the children to receive PNSLIT at a daily maintenance dose of 4 mg peanut protein (n = 19) or to receive placebo (n = 17) for 36 months.

“There was a 5- to 6-month buildup period where the SLIT dose was increased every 1-2 weeks up to the target dose of 4 mg, and then the final dose of 4 mg was continued through to the end of the study,” Dr. Kim noted.

Over a total of 20,593 potential dosing days, the children took 91.2% of SLIT doses and 93.5% of placebo doses.

At the end of the 3-year study period, the children were challenged by DBPCFC with up to 4,333 mg of peanut protein.

Sustained unresponsiveness was assessed by an identical DBPCFC after discontinuation of the immunotherapy for 3 months.

Cumulative tolerated dose increased from a median of 143 mg to 4,443 mg in the PNSLIT group, compared with a median of 43 mg to 143 mg in the placebo group (P < .0001).

Fourteen of the children receiving PNSLIT, and none of the children receiving placebo, passed the desensitization food challenge. Twelve of the children receiving PNSLIT and two of the children receiving placebo passed the sustained unresponsiveness challenge.

Children who underwent the immunotherapy saw a decrease in their peanut skin prick test from 10 mm to 3.25 mm, compared to an increase from 11.5 mm to 12 mm with placebo (P < .0001).

The most common side effect reported was itching or irritation in the mouth. Most side effects resolved on their own, although some patients used an antihistamine. Getting children as young as 1 to hold the dose under their tongue was a challenge in some instances, but it eventually worked out, Dr. Kim said.

“It took a lot of work from the parents as well as from our research coordinators in trying to train these young kids to, first of all, allow us to put the peanut medication in the mouth and then to try as best as possible to keep it in their mouth for up to 2 minutes, but the families involved in our study were very dedicated and so we were able to get through that,” he said.
 

Study merits larger numbers

“Among the 36 who completed the 3 years of therapy, the authors report significant rates of desensitization among treated children compared with those receiving placebo. Furthermore, this effect was persistent for at least 3 months after stopping therapy in a subgroup of the children,” said Leonard B. Bacharier, MD, director of the Center for Pediatric Asthma, Monroe Carell Jr. Children’s Hospital at Vanderbilt, Nashville, Tenn.

“Overall, these findings suggest the promise of peanut SLIT, which should be studied in larger numbers of preschool children,” Dr. Bacharier, who was not part of the study, said in an interview.

Jonathan A. Bernstein, MD, professor of medicine, University of Cincinnati, agreed.

“It’s a well-designed study, it’s small, but it’s promising,” Dr. Bernstein, who was not involved with the study, said in an interview.

“They did show that most of the patients who got the sublingual therapy were able to get to the target dose and develop tolerance, so I think it’s promising. We know that this stuff works. This is just more data from a well-controlled study in a younger population,” he said.

“We do OIT [oral immunotherapy] and sublingual but we don’t do it in such young children in our practice. The youngest is 3 years old, because they have to understand what is going on and cooperate. If they don’t cooperate it’s not possible.”

Dr. Kim reported financial relationships with DBV Technologies, Kenota Health, Ukko, Aimmune Therapeutics, ALK, AllerGenis, Belhaven Pharma, Duke Clinical Research Institute, Nutricia, NIH/NIAID, NIH/NCCIH, NIH/Immune Tolerance Network, FARE, and the Wallace Foundation. Dr. Bacharier and Dr. Bernstein have disclosed no relevant financial relationships.

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

Sublingual immunotherapy for the treatment of peanut allergy is safe and effective, even in children as young as age 1 year.

In a double-blind, placebo-controlled, food challenge (DBPCFC) of some 36 peanut-allergic children (mean age 2.2 years, range 1-4 years), those who were randomly assigned to receive peanut sublingual immunotherapy (PNSLIT) showed significant desensitization compared with those who received placebo.

In addition, there was a “strong potential” for sustained unresponsiveness at 3 months for the toddlers who received the active treatment.

The findings were presented in a late breaking oral abstract session at the 2021 American Academy of Allergy, Asthma & Immunology virtual annual meeting (Abstract L2).

“A year ago, the Food and Drug Administration approved the oral agent Palforzia (peanut allergen powder) for the treatment of peanut allergy in children 4 and older, and it is a great option, but I think what we have learned over time is that this approach is not for everybody,” Edwin H. Kim, MD, director of the UNC Food Allergy Initiative, University of North Carolina at Chapel Hill, said in an interview.

Palforzia is a powder that is mixed in food like yogurt or pudding which the child then eats daily, according to a rigorous schedule. But Palforzia treatment presents some difficulties.

“Palforzia requires getting the powder dose, mixing it with food, like pudding or apple sauce, then eating it, which can take up to 30 minutes depending on age and kids’ cooperation. It tastes and smells like peanut which can cause aversion. Kids have to refrain from exercise or strenuous activity for at least 30 minutes before and after dosing and have to be observed for up to 2 hours post dose for symptoms,” Dr. Kim said.

“It’s a great drug, but the treatment could be overly difficult for certain families to be able to do, and in some cases the side effects may be more than certain patients are able or willing to handle, so there is a real urgent need for alternative approaches,” Dr. Kim said. “SLIT is several drops under the tongue, held for 2 minutes, swallowed and done.”

In the current placebo-controlled study, he and his group tested the feasibility, efficacy, and safety of the sublingual approach to peanut allergy in children age 4 years and younger.

Both groups were similar with regard to gender, race, ethnicity, atopic history, peanut skin prick test, and qualifying DBPCFC, and all children were previously allergic with positive blood and skin tests, with a positive reaction during baseline food challenge, thus proving the allergy and establishing the baseline threshold.

“We have learned from some studies, for instance the DEVIL and LEAP studies, that strongly suggest that the immune systems in younger patients may be more amenable to change, and there may be some justification for early intervention,” he said.

“Based on both of those ideas, we wanted to take our sublingual approach, which we have shown to have a pretty good efficacy in older children, and bring it down to this younger group and see if it still could have the same efficacy and also maintain what seems to be a very good safety signal.”

The researchers randomly assigned the children to receive PNSLIT at a daily maintenance dose of 4 mg peanut protein (n = 19) or to receive placebo (n = 17) for 36 months.

“There was a 5- to 6-month buildup period where the SLIT dose was increased every 1-2 weeks up to the target dose of 4 mg, and then the final dose of 4 mg was continued through to the end of the study,” Dr. Kim noted.

Over a total of 20,593 potential dosing days, the children took 91.2% of SLIT doses and 93.5% of placebo doses.

At the end of the 3-year study period, the children were challenged by DBPCFC with up to 4,333 mg of peanut protein.

Sustained unresponsiveness was assessed by an identical DBPCFC after discontinuation of the immunotherapy for 3 months.

Cumulative tolerated dose increased from a median of 143 mg to 4,443 mg in the PNSLIT group, compared with a median of 43 mg to 143 mg in the placebo group (P < .0001).

Fourteen of the children receiving PNSLIT, and none of the children receiving placebo, passed the desensitization food challenge. Twelve of the children receiving PNSLIT and two of the children receiving placebo passed the sustained unresponsiveness challenge.

Children who underwent the immunotherapy saw a decrease in their peanut skin prick test from 10 mm to 3.25 mm, compared to an increase from 11.5 mm to 12 mm with placebo (P < .0001).

The most common side effect reported was itching or irritation in the mouth. Most side effects resolved on their own, although some patients used an antihistamine. Getting children as young as 1 to hold the dose under their tongue was a challenge in some instances, but it eventually worked out, Dr. Kim said.

“It took a lot of work from the parents as well as from our research coordinators in trying to train these young kids to, first of all, allow us to put the peanut medication in the mouth and then to try as best as possible to keep it in their mouth for up to 2 minutes, but the families involved in our study were very dedicated and so we were able to get through that,” he said.
 

Study merits larger numbers

“Among the 36 who completed the 3 years of therapy, the authors report significant rates of desensitization among treated children compared with those receiving placebo. Furthermore, this effect was persistent for at least 3 months after stopping therapy in a subgroup of the children,” said Leonard B. Bacharier, MD, director of the Center for Pediatric Asthma, Monroe Carell Jr. Children’s Hospital at Vanderbilt, Nashville, Tenn.

“Overall, these findings suggest the promise of peanut SLIT, which should be studied in larger numbers of preschool children,” Dr. Bacharier, who was not part of the study, said in an interview.

Jonathan A. Bernstein, MD, professor of medicine, University of Cincinnati, agreed.

“It’s a well-designed study, it’s small, but it’s promising,” Dr. Bernstein, who was not involved with the study, said in an interview.

“They did show that most of the patients who got the sublingual therapy were able to get to the target dose and develop tolerance, so I think it’s promising. We know that this stuff works. This is just more data from a well-controlled study in a younger population,” he said.

“We do OIT [oral immunotherapy] and sublingual but we don’t do it in such young children in our practice. The youngest is 3 years old, because they have to understand what is going on and cooperate. If they don’t cooperate it’s not possible.”

Dr. Kim reported financial relationships with DBV Technologies, Kenota Health, Ukko, Aimmune Therapeutics, ALK, AllerGenis, Belhaven Pharma, Duke Clinical Research Institute, Nutricia, NIH/NIAID, NIH/NCCIH, NIH/Immune Tolerance Network, FARE, and the Wallace Foundation. Dr. Bacharier and Dr. Bernstein have disclosed no relevant financial relationships.

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

Sublingual immunotherapy for the treatment of peanut allergy is safe and effective, even in children as young as age 1 year.

In a double-blind, placebo-controlled, food challenge (DBPCFC) of some 36 peanut-allergic children (mean age 2.2 years, range 1-4 years), those who were randomly assigned to receive peanut sublingual immunotherapy (PNSLIT) showed significant desensitization compared with those who received placebo.

In addition, there was a “strong potential” for sustained unresponsiveness at 3 months for the toddlers who received the active treatment.

The findings were presented in a late breaking oral abstract session at the 2021 American Academy of Allergy, Asthma & Immunology virtual annual meeting (Abstract L2).

“A year ago, the Food and Drug Administration approved the oral agent Palforzia (peanut allergen powder) for the treatment of peanut allergy in children 4 and older, and it is a great option, but I think what we have learned over time is that this approach is not for everybody,” Edwin H. Kim, MD, director of the UNC Food Allergy Initiative, University of North Carolina at Chapel Hill, said in an interview.

Palforzia is a powder that is mixed in food like yogurt or pudding which the child then eats daily, according to a rigorous schedule. But Palforzia treatment presents some difficulties.

“Palforzia requires getting the powder dose, mixing it with food, like pudding or apple sauce, then eating it, which can take up to 30 minutes depending on age and kids’ cooperation. It tastes and smells like peanut which can cause aversion. Kids have to refrain from exercise or strenuous activity for at least 30 minutes before and after dosing and have to be observed for up to 2 hours post dose for symptoms,” Dr. Kim said.

“It’s a great drug, but the treatment could be overly difficult for certain families to be able to do, and in some cases the side effects may be more than certain patients are able or willing to handle, so there is a real urgent need for alternative approaches,” Dr. Kim said. “SLIT is several drops under the tongue, held for 2 minutes, swallowed and done.”

In the current placebo-controlled study, he and his group tested the feasibility, efficacy, and safety of the sublingual approach to peanut allergy in children age 4 years and younger.

Both groups were similar with regard to gender, race, ethnicity, atopic history, peanut skin prick test, and qualifying DBPCFC, and all children were previously allergic with positive blood and skin tests, with a positive reaction during baseline food challenge, thus proving the allergy and establishing the baseline threshold.

“We have learned from some studies, for instance the DEVIL and LEAP studies, that strongly suggest that the immune systems in younger patients may be more amenable to change, and there may be some justification for early intervention,” he said.

“Based on both of those ideas, we wanted to take our sublingual approach, which we have shown to have a pretty good efficacy in older children, and bring it down to this younger group and see if it still could have the same efficacy and also maintain what seems to be a very good safety signal.”

The researchers randomly assigned the children to receive PNSLIT at a daily maintenance dose of 4 mg peanut protein (n = 19) or to receive placebo (n = 17) for 36 months.

“There was a 5- to 6-month buildup period where the SLIT dose was increased every 1-2 weeks up to the target dose of 4 mg, and then the final dose of 4 mg was continued through to the end of the study,” Dr. Kim noted.

Over a total of 20,593 potential dosing days, the children took 91.2% of SLIT doses and 93.5% of placebo doses.

At the end of the 3-year study period, the children were challenged by DBPCFC with up to 4,333 mg of peanut protein.

Sustained unresponsiveness was assessed by an identical DBPCFC after discontinuation of the immunotherapy for 3 months.

Cumulative tolerated dose increased from a median of 143 mg to 4,443 mg in the PNSLIT group, compared with a median of 43 mg to 143 mg in the placebo group (P < .0001).

Fourteen of the children receiving PNSLIT, and none of the children receiving placebo, passed the desensitization food challenge. Twelve of the children receiving PNSLIT and two of the children receiving placebo passed the sustained unresponsiveness challenge.

Children who underwent the immunotherapy saw a decrease in their peanut skin prick test from 10 mm to 3.25 mm, compared to an increase from 11.5 mm to 12 mm with placebo (P < .0001).

The most common side effect reported was itching or irritation in the mouth. Most side effects resolved on their own, although some patients used an antihistamine. Getting children as young as 1 to hold the dose under their tongue was a challenge in some instances, but it eventually worked out, Dr. Kim said.

“It took a lot of work from the parents as well as from our research coordinators in trying to train these young kids to, first of all, allow us to put the peanut medication in the mouth and then to try as best as possible to keep it in their mouth for up to 2 minutes, but the families involved in our study were very dedicated and so we were able to get through that,” he said.
 

Study merits larger numbers

“Among the 36 who completed the 3 years of therapy, the authors report significant rates of desensitization among treated children compared with those receiving placebo. Furthermore, this effect was persistent for at least 3 months after stopping therapy in a subgroup of the children,” said Leonard B. Bacharier, MD, director of the Center for Pediatric Asthma, Monroe Carell Jr. Children’s Hospital at Vanderbilt, Nashville, Tenn.

“Overall, these findings suggest the promise of peanut SLIT, which should be studied in larger numbers of preschool children,” Dr. Bacharier, who was not part of the study, said in an interview.

Jonathan A. Bernstein, MD, professor of medicine, University of Cincinnati, agreed.

“It’s a well-designed study, it’s small, but it’s promising,” Dr. Bernstein, who was not involved with the study, said in an interview.

“They did show that most of the patients who got the sublingual therapy were able to get to the target dose and develop tolerance, so I think it’s promising. We know that this stuff works. This is just more data from a well-controlled study in a younger population,” he said.

“We do OIT [oral immunotherapy] and sublingual but we don’t do it in such young children in our practice. The youngest is 3 years old, because they have to understand what is going on and cooperate. If they don’t cooperate it’s not possible.”

Dr. Kim reported financial relationships with DBV Technologies, Kenota Health, Ukko, Aimmune Therapeutics, ALK, AllerGenis, Belhaven Pharma, Duke Clinical Research Institute, Nutricia, NIH/NIAID, NIH/NCCIH, NIH/Immune Tolerance Network, FARE, and the Wallace Foundation. Dr. Bacharier and Dr. Bernstein have disclosed no relevant financial relationships.

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