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FDA warns of potentially lethal reaction to seizure meds
that can be life threatening if not detected and treated promptly, the Food and Drug Administration warns in an alert.
Known as drug reaction with eosinophilia and systemic symptoms (DRESS), it may start as a rash but can quickly progress and cause injury to internal organs, the need for hospitalization, and death, the FDA notes.
A search of the FDA Adverse Event Reporting System (FAERS) and the medical literature through March 2023 identified 32 serious cases of DRESS worldwide that were associated with levetiracetam.
Three cases occurred in the United States, and 29 occurred abroad. In all 32 cases, the patients were hospitalized and received medical treatment; in 2 cases, the patients died.
The median time to onset of DRESS in the levetiracetam cases was 24 days; times ranged from 7 to 170 days. The reported signs and symptoms included skin rash (n = 22), fever (n = 20), eosinophilia (n = 17), lymph node swelling (n = 9), and atypical lymphocytes (n = 4).
Twenty-two levetiracetam-associated cases of DRESS involved injury to one or more organs, including the liver, lungs, kidneys, and gallbladder.
In 25 of the 29 cases for which information on treatment discontinuation was available, DRESS symptoms resolved when levetiracetam was discontinued.
As for clobazam, a search of FAERS and the medical literature through July 2023 identified 10 serious cases of DRESS worldwide – 1 in the United States and 9 abroad. All 10 patients were hospitalized and received medical treatment. No deaths were reported.
The median time to onset of clobazam-associated DRESS was 21.5 days (range, 7-103 days). The reported signs and symptoms included skin rash (n = 10), fever (n = 8), eosinophilia (n = 7), facial swelling (n = 7), leukocytosis (n = 4), lymph node swelling (n = 4), and leukopenia/thrombocytopenia (n = 1).
In nine cases, there was injury to one or more organs, including the liver, kidneys, and gastrointestinal tract.
DRESS symptoms resolved in all 10 cases when treatment with clobazam was stopped. DRESS and other serious skin reactions reported with clobazam, a benzodiazepine, have not generally been associated with other benzodiazepines, the FDA notes.
Label updates
As a result of these cases, warnings about the risk of DRESS will be added to the prescribing information and patient medication guides for these medicines, the FDA announced.
“Health care professionals should be aware that prompt recognition and early treatment is important for improving DRESS outcomes and decreasing mortality,” the FDA said.
They noted that diagnosis is often difficult because early signs and symptoms, such as fever and swollen lymph nodes, may be present without evidence of a rash.
DRESS may develop 2-8 weeks after starting levetiracetam or clobazam. Symptoms and intensity can vary widely.
DRESS can also be confused with other serious skin reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis.
The FDA says patients should be advised of the signs and symptoms of DRESS and be told to stop taking the medicine and seek immediate medical attention if DRESS is suspected during treatment with levetiracetam or clobazam.
Adverse reactions with these medications should be reported to the FDA’s MedWatch program.
A version of this article appeared on Medscape.com.
that can be life threatening if not detected and treated promptly, the Food and Drug Administration warns in an alert.
Known as drug reaction with eosinophilia and systemic symptoms (DRESS), it may start as a rash but can quickly progress and cause injury to internal organs, the need for hospitalization, and death, the FDA notes.
A search of the FDA Adverse Event Reporting System (FAERS) and the medical literature through March 2023 identified 32 serious cases of DRESS worldwide that were associated with levetiracetam.
Three cases occurred in the United States, and 29 occurred abroad. In all 32 cases, the patients were hospitalized and received medical treatment; in 2 cases, the patients died.
The median time to onset of DRESS in the levetiracetam cases was 24 days; times ranged from 7 to 170 days. The reported signs and symptoms included skin rash (n = 22), fever (n = 20), eosinophilia (n = 17), lymph node swelling (n = 9), and atypical lymphocytes (n = 4).
Twenty-two levetiracetam-associated cases of DRESS involved injury to one or more organs, including the liver, lungs, kidneys, and gallbladder.
In 25 of the 29 cases for which information on treatment discontinuation was available, DRESS symptoms resolved when levetiracetam was discontinued.
As for clobazam, a search of FAERS and the medical literature through July 2023 identified 10 serious cases of DRESS worldwide – 1 in the United States and 9 abroad. All 10 patients were hospitalized and received medical treatment. No deaths were reported.
The median time to onset of clobazam-associated DRESS was 21.5 days (range, 7-103 days). The reported signs and symptoms included skin rash (n = 10), fever (n = 8), eosinophilia (n = 7), facial swelling (n = 7), leukocytosis (n = 4), lymph node swelling (n = 4), and leukopenia/thrombocytopenia (n = 1).
In nine cases, there was injury to one or more organs, including the liver, kidneys, and gastrointestinal tract.
DRESS symptoms resolved in all 10 cases when treatment with clobazam was stopped. DRESS and other serious skin reactions reported with clobazam, a benzodiazepine, have not generally been associated with other benzodiazepines, the FDA notes.
Label updates
As a result of these cases, warnings about the risk of DRESS will be added to the prescribing information and patient medication guides for these medicines, the FDA announced.
“Health care professionals should be aware that prompt recognition and early treatment is important for improving DRESS outcomes and decreasing mortality,” the FDA said.
They noted that diagnosis is often difficult because early signs and symptoms, such as fever and swollen lymph nodes, may be present without evidence of a rash.
DRESS may develop 2-8 weeks after starting levetiracetam or clobazam. Symptoms and intensity can vary widely.
DRESS can also be confused with other serious skin reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis.
The FDA says patients should be advised of the signs and symptoms of DRESS and be told to stop taking the medicine and seek immediate medical attention if DRESS is suspected during treatment with levetiracetam or clobazam.
Adverse reactions with these medications should be reported to the FDA’s MedWatch program.
A version of this article appeared on Medscape.com.
that can be life threatening if not detected and treated promptly, the Food and Drug Administration warns in an alert.
Known as drug reaction with eosinophilia and systemic symptoms (DRESS), it may start as a rash but can quickly progress and cause injury to internal organs, the need for hospitalization, and death, the FDA notes.
A search of the FDA Adverse Event Reporting System (FAERS) and the medical literature through March 2023 identified 32 serious cases of DRESS worldwide that were associated with levetiracetam.
Three cases occurred in the United States, and 29 occurred abroad. In all 32 cases, the patients were hospitalized and received medical treatment; in 2 cases, the patients died.
The median time to onset of DRESS in the levetiracetam cases was 24 days; times ranged from 7 to 170 days. The reported signs and symptoms included skin rash (n = 22), fever (n = 20), eosinophilia (n = 17), lymph node swelling (n = 9), and atypical lymphocytes (n = 4).
Twenty-two levetiracetam-associated cases of DRESS involved injury to one or more organs, including the liver, lungs, kidneys, and gallbladder.
In 25 of the 29 cases for which information on treatment discontinuation was available, DRESS symptoms resolved when levetiracetam was discontinued.
As for clobazam, a search of FAERS and the medical literature through July 2023 identified 10 serious cases of DRESS worldwide – 1 in the United States and 9 abroad. All 10 patients were hospitalized and received medical treatment. No deaths were reported.
The median time to onset of clobazam-associated DRESS was 21.5 days (range, 7-103 days). The reported signs and symptoms included skin rash (n = 10), fever (n = 8), eosinophilia (n = 7), facial swelling (n = 7), leukocytosis (n = 4), lymph node swelling (n = 4), and leukopenia/thrombocytopenia (n = 1).
In nine cases, there was injury to one or more organs, including the liver, kidneys, and gastrointestinal tract.
DRESS symptoms resolved in all 10 cases when treatment with clobazam was stopped. DRESS and other serious skin reactions reported with clobazam, a benzodiazepine, have not generally been associated with other benzodiazepines, the FDA notes.
Label updates
As a result of these cases, warnings about the risk of DRESS will be added to the prescribing information and patient medication guides for these medicines, the FDA announced.
“Health care professionals should be aware that prompt recognition and early treatment is important for improving DRESS outcomes and decreasing mortality,” the FDA said.
They noted that diagnosis is often difficult because early signs and symptoms, such as fever and swollen lymph nodes, may be present without evidence of a rash.
DRESS may develop 2-8 weeks after starting levetiracetam or clobazam. Symptoms and intensity can vary widely.
DRESS can also be confused with other serious skin reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis.
The FDA says patients should be advised of the signs and symptoms of DRESS and be told to stop taking the medicine and seek immediate medical attention if DRESS is suspected during treatment with levetiracetam or clobazam.
Adverse reactions with these medications should be reported to the FDA’s MedWatch program.
A version of this article appeared on Medscape.com.
New consensus guide on rare drug hypersensitivity reaction
TOPLINE:
).
METHODOLOGY:
Data on the evaluation, assessment, and treatment of the rare but potentially life-threatening drug hypersensitivity reaction are lacking.
To support clinicians in diagnosing and managing DRESS, a steering committee conducted a literature review to examine current research, identify evidence, and develop consensus statements. They invited experts from 21 countries across four continents to participate in a Delphi consensus process.
An international panel of 54 experts (including 45 dermatologists) initially assessed 100 statements related to baseline workup, severity of the condition, and treatment. Two more statements were added in the second round.
After revisions and the second round, the group reached consensus for 93 statements overall.
TAKEAWAY:
The statements generating the most disagreement involved diagnosis. The group ultimately supported the value of measuring the viral load of Epstein-Barr virus, cytomegalovirus, and human herpesvirus 6 in all patients with suspected DRESS. The group also agreed on screening for hepatitis A, B, and C in cases of liver involvement and screening for hepatitis B and C before starting systemic therapy.
The group agreed with previous severity criteria that differentiate between mild, moderate, and severe DRESS based on the extent of liver, kidney, and blood involvement and the damage of other organs.
Consensus on treatment was reached for all 12 relevant statements in the first Delphi round. Recommendations included the use of corticosteroids and immediate discontinuation of the drugs causing the reaction.
IN PRACTICE:
“This Delphi exercise aimed to provide a common ground of consensus,” the authors noted. However, “each of the addressed categories needs more in-depth follow-up studies to improve the clinical management of patients.”
SOURCE:
The DRESS Delphi consensus group conducted its exercise under the leadership of Marie-Charlotte Brüggen, MD, of the University Hospital of Zürich. The consensus was published online in the JAMA Dermatology.
LIMITATIONS:
Published evidence was limited because of the low prevalence of DRESS. The consensus statements should therefore be considered with caution and in the context of a clinician’s expertise and available resources. Research gaps also persist in how DRESS may vary with region and ethnicity. The severity thresholds need validation in a revised multicenter statement.
DISCLOSURES:
The consensus review received no outside funding. Dr. Brüggen disclosed relationships with the Swiss National Science Foundation, Christine Kühne – Center for Allergy Research and Education, FreeNovation, LEO Foundation, Olga Mayenfisch Foundation, University of Zürich, LEO Pharma, Pierre Fabre Eczema Foundation, Eli Lilly, AbbVie, GSK, and AstraZeneca. Coauthors disclosed relationships with multiple pharmaceutical companies, foundations, and medical publishing companies.
A version of this article appeared on Medscape.com.
TOPLINE:
).
METHODOLOGY:
Data on the evaluation, assessment, and treatment of the rare but potentially life-threatening drug hypersensitivity reaction are lacking.
To support clinicians in diagnosing and managing DRESS, a steering committee conducted a literature review to examine current research, identify evidence, and develop consensus statements. They invited experts from 21 countries across four continents to participate in a Delphi consensus process.
An international panel of 54 experts (including 45 dermatologists) initially assessed 100 statements related to baseline workup, severity of the condition, and treatment. Two more statements were added in the second round.
After revisions and the second round, the group reached consensus for 93 statements overall.
TAKEAWAY:
The statements generating the most disagreement involved diagnosis. The group ultimately supported the value of measuring the viral load of Epstein-Barr virus, cytomegalovirus, and human herpesvirus 6 in all patients with suspected DRESS. The group also agreed on screening for hepatitis A, B, and C in cases of liver involvement and screening for hepatitis B and C before starting systemic therapy.
The group agreed with previous severity criteria that differentiate between mild, moderate, and severe DRESS based on the extent of liver, kidney, and blood involvement and the damage of other organs.
Consensus on treatment was reached for all 12 relevant statements in the first Delphi round. Recommendations included the use of corticosteroids and immediate discontinuation of the drugs causing the reaction.
IN PRACTICE:
“This Delphi exercise aimed to provide a common ground of consensus,” the authors noted. However, “each of the addressed categories needs more in-depth follow-up studies to improve the clinical management of patients.”
SOURCE:
The DRESS Delphi consensus group conducted its exercise under the leadership of Marie-Charlotte Brüggen, MD, of the University Hospital of Zürich. The consensus was published online in the JAMA Dermatology.
LIMITATIONS:
Published evidence was limited because of the low prevalence of DRESS. The consensus statements should therefore be considered with caution and in the context of a clinician’s expertise and available resources. Research gaps also persist in how DRESS may vary with region and ethnicity. The severity thresholds need validation in a revised multicenter statement.
DISCLOSURES:
The consensus review received no outside funding. Dr. Brüggen disclosed relationships with the Swiss National Science Foundation, Christine Kühne – Center for Allergy Research and Education, FreeNovation, LEO Foundation, Olga Mayenfisch Foundation, University of Zürich, LEO Pharma, Pierre Fabre Eczema Foundation, Eli Lilly, AbbVie, GSK, and AstraZeneca. Coauthors disclosed relationships with multiple pharmaceutical companies, foundations, and medical publishing companies.
A version of this article appeared on Medscape.com.
TOPLINE:
).
METHODOLOGY:
Data on the evaluation, assessment, and treatment of the rare but potentially life-threatening drug hypersensitivity reaction are lacking.
To support clinicians in diagnosing and managing DRESS, a steering committee conducted a literature review to examine current research, identify evidence, and develop consensus statements. They invited experts from 21 countries across four continents to participate in a Delphi consensus process.
An international panel of 54 experts (including 45 dermatologists) initially assessed 100 statements related to baseline workup, severity of the condition, and treatment. Two more statements were added in the second round.
After revisions and the second round, the group reached consensus for 93 statements overall.
TAKEAWAY:
The statements generating the most disagreement involved diagnosis. The group ultimately supported the value of measuring the viral load of Epstein-Barr virus, cytomegalovirus, and human herpesvirus 6 in all patients with suspected DRESS. The group also agreed on screening for hepatitis A, B, and C in cases of liver involvement and screening for hepatitis B and C before starting systemic therapy.
The group agreed with previous severity criteria that differentiate between mild, moderate, and severe DRESS based on the extent of liver, kidney, and blood involvement and the damage of other organs.
Consensus on treatment was reached for all 12 relevant statements in the first Delphi round. Recommendations included the use of corticosteroids and immediate discontinuation of the drugs causing the reaction.
IN PRACTICE:
“This Delphi exercise aimed to provide a common ground of consensus,” the authors noted. However, “each of the addressed categories needs more in-depth follow-up studies to improve the clinical management of patients.”
SOURCE:
The DRESS Delphi consensus group conducted its exercise under the leadership of Marie-Charlotte Brüggen, MD, of the University Hospital of Zürich. The consensus was published online in the JAMA Dermatology.
LIMITATIONS:
Published evidence was limited because of the low prevalence of DRESS. The consensus statements should therefore be considered with caution and in the context of a clinician’s expertise and available resources. Research gaps also persist in how DRESS may vary with region and ethnicity. The severity thresholds need validation in a revised multicenter statement.
DISCLOSURES:
The consensus review received no outside funding. Dr. Brüggen disclosed relationships with the Swiss National Science Foundation, Christine Kühne – Center for Allergy Research and Education, FreeNovation, LEO Foundation, Olga Mayenfisch Foundation, University of Zürich, LEO Pharma, Pierre Fabre Eczema Foundation, Eli Lilly, AbbVie, GSK, and AstraZeneca. Coauthors disclosed relationships with multiple pharmaceutical companies, foundations, and medical publishing companies.
A version of this article appeared on Medscape.com.
Laser epilation may reduce pilonidal disease recurrences when added to standard care
according to the results of a randomized trial.
The study, recently published in JAMA Surgery, enrolled 302 patients ages 11-21 with pilonidal disease. Half of the participants were assigned to receive LE (laser hair removal) plus standard treatment (improved hygiene plus mechanical or chemical hair removal), and half were assigned to receive standard care alone.
At 1 year, 10.4% of the patients who had received LE plus standard treatment had experienced a recurrence of pilonidal disease, compared with 33.6% of patients in the standard treatment group (P < .001). Rates were based on the data available on 96 patients in the LE group and 134 patients in the standard care group.
“These results provide further evidence that laser epilation is safe, well-tolerated, and should be available as an initial treatment option or adjunct treatment modality for all eligible patients,” first author Peter C. Minneci, MD, chair of surgery at Nemours Children’s Health, Delaware Valley, Wilmington, Del, said in a press release reporting the results. “There have been few comparative studies that have investigated recurrence rates after LE versus other treatment modalities,” he and his coauthors wrote in the study, noting that the study “was the first, to our knowledge, to compare LE as an adjunct to standard care versus standard care alone and demonstrate a decrease in recurrence rates.”
Pilonidal disease, a common condition, results when cysts form between the buttocks and is most common in adolescents and young adults. It is thought to recur about 33% of the time, with most cases recurring within 1 year of treatment.
In practice, there are large variations in management strategies for pilonidal disease because evidence for an ideal treatment approach is lacking, Dr. Minneci and coauthors wrote. Although lifestyle modifications and nonepilation hair removal strategies have been linked to a reduced need for surgery, compliance with these strategies is low. Additionally, recurrence contributes to “a high degree of psychosocial stress in patients, who often miss school or sports and may avoid social activities,” Dr. Minneci said in the press release. Therefore, some practitioners have begun using LE – which uses selective thermolysis to remove the hair shaft, follicle, and bulb – as an adjunct to standard treatments in the hopes of avoiding surgery.
A few studies have shown LE is effective in reducing pilonidal disease recurrence, but these studies had small sample sizes, according to the authors.
Study methods
The randomized, nonblinded clinical trial was conducted between 2017 and 2022 at Nationwide Children’s Hospital, Columbus, and enrolled patients aged 11-21 years with a history of pilonidal disease, who did not have active disease.
Those in the control group (151 patients) had an in-person clinic visit where they received education and training about hair removal in the gluteal cleft, and were provided with supplies for hair removal (chemical epilation or shaving) for 6 months (standard of care). Those in the LE group (151 patients) received standard of care therapy, and also received one LE treatment every 4-6 weeks for a total of five treatments. They were encouraged to perform hair removal using chemical or mechanical depilation between visits.
At the 1-year follow-up, data were available in 96 patients in the LE group and 134 patients in the standard care group. At that time, the proportion of those who had a recurrence within 1 year was significantly lower in the LE group than in the standard care group (mean difference, –23.2%; 95% CI, –33.2% to –13.1%; P < .001).
In addition, over the course of a year, those in the LE-treated group had significantly higher Child Attitude Toward Illness scores, indicating that they felt more positively about their illness at 6 months than participants in the standard care group. There were no differences between the groups in terms of patient or caregiver disability days, patient- or caregiver-reported health-related quality of life, health care satisfaction, or perceived stigma. In the LE group, no burns were reported, and no inability to tolerate treatment because of pain.
The study had several limitations, including the potential for participation bias, and because of a loss to follow-up, primary and secondary outcomes were missing data points, which was higher in the LE group. Loss to follow-up in the LE arm increased after 6 months, when laser treatments ended, with many of those patients not completing surveys at 9 and 12 months. The hospital’s pilonidal clinic shut down for 3 months during the COVID-19 pandemic, and when the clinic reopened, 15 patients in the LE arm withdrew from the study.
|In the press release, Dr. Minneci said that confirmation of the effectiveness of LE could help justify insurance coverage for pilonidal disease, noting that LE is usually not covered with insurance, and a course of treatment could cost $800-$1,500.
Dr. Minneci and four of the other six coauthors reported receiving grants from Patient-Centered Outcomes Research Institute during the conduct of the study. One author reported receiving grants from the National Institute on Minority Health and Health Disparities outside the submitted work. The research was funded by a grant from the Patient-Centered Outcomes Research Institute.
according to the results of a randomized trial.
The study, recently published in JAMA Surgery, enrolled 302 patients ages 11-21 with pilonidal disease. Half of the participants were assigned to receive LE (laser hair removal) plus standard treatment (improved hygiene plus mechanical or chemical hair removal), and half were assigned to receive standard care alone.
At 1 year, 10.4% of the patients who had received LE plus standard treatment had experienced a recurrence of pilonidal disease, compared with 33.6% of patients in the standard treatment group (P < .001). Rates were based on the data available on 96 patients in the LE group and 134 patients in the standard care group.
“These results provide further evidence that laser epilation is safe, well-tolerated, and should be available as an initial treatment option or adjunct treatment modality for all eligible patients,” first author Peter C. Minneci, MD, chair of surgery at Nemours Children’s Health, Delaware Valley, Wilmington, Del, said in a press release reporting the results. “There have been few comparative studies that have investigated recurrence rates after LE versus other treatment modalities,” he and his coauthors wrote in the study, noting that the study “was the first, to our knowledge, to compare LE as an adjunct to standard care versus standard care alone and demonstrate a decrease in recurrence rates.”
Pilonidal disease, a common condition, results when cysts form between the buttocks and is most common in adolescents and young adults. It is thought to recur about 33% of the time, with most cases recurring within 1 year of treatment.
In practice, there are large variations in management strategies for pilonidal disease because evidence for an ideal treatment approach is lacking, Dr. Minneci and coauthors wrote. Although lifestyle modifications and nonepilation hair removal strategies have been linked to a reduced need for surgery, compliance with these strategies is low. Additionally, recurrence contributes to “a high degree of psychosocial stress in patients, who often miss school or sports and may avoid social activities,” Dr. Minneci said in the press release. Therefore, some practitioners have begun using LE – which uses selective thermolysis to remove the hair shaft, follicle, and bulb – as an adjunct to standard treatments in the hopes of avoiding surgery.
A few studies have shown LE is effective in reducing pilonidal disease recurrence, but these studies had small sample sizes, according to the authors.
Study methods
The randomized, nonblinded clinical trial was conducted between 2017 and 2022 at Nationwide Children’s Hospital, Columbus, and enrolled patients aged 11-21 years with a history of pilonidal disease, who did not have active disease.
Those in the control group (151 patients) had an in-person clinic visit where they received education and training about hair removal in the gluteal cleft, and were provided with supplies for hair removal (chemical epilation or shaving) for 6 months (standard of care). Those in the LE group (151 patients) received standard of care therapy, and also received one LE treatment every 4-6 weeks for a total of five treatments. They were encouraged to perform hair removal using chemical or mechanical depilation between visits.
At the 1-year follow-up, data were available in 96 patients in the LE group and 134 patients in the standard care group. At that time, the proportion of those who had a recurrence within 1 year was significantly lower in the LE group than in the standard care group (mean difference, –23.2%; 95% CI, –33.2% to –13.1%; P < .001).
In addition, over the course of a year, those in the LE-treated group had significantly higher Child Attitude Toward Illness scores, indicating that they felt more positively about their illness at 6 months than participants in the standard care group. There were no differences between the groups in terms of patient or caregiver disability days, patient- or caregiver-reported health-related quality of life, health care satisfaction, or perceived stigma. In the LE group, no burns were reported, and no inability to tolerate treatment because of pain.
The study had several limitations, including the potential for participation bias, and because of a loss to follow-up, primary and secondary outcomes were missing data points, which was higher in the LE group. Loss to follow-up in the LE arm increased after 6 months, when laser treatments ended, with many of those patients not completing surveys at 9 and 12 months. The hospital’s pilonidal clinic shut down for 3 months during the COVID-19 pandemic, and when the clinic reopened, 15 patients in the LE arm withdrew from the study.
|In the press release, Dr. Minneci said that confirmation of the effectiveness of LE could help justify insurance coverage for pilonidal disease, noting that LE is usually not covered with insurance, and a course of treatment could cost $800-$1,500.
Dr. Minneci and four of the other six coauthors reported receiving grants from Patient-Centered Outcomes Research Institute during the conduct of the study. One author reported receiving grants from the National Institute on Minority Health and Health Disparities outside the submitted work. The research was funded by a grant from the Patient-Centered Outcomes Research Institute.
according to the results of a randomized trial.
The study, recently published in JAMA Surgery, enrolled 302 patients ages 11-21 with pilonidal disease. Half of the participants were assigned to receive LE (laser hair removal) plus standard treatment (improved hygiene plus mechanical or chemical hair removal), and half were assigned to receive standard care alone.
At 1 year, 10.4% of the patients who had received LE plus standard treatment had experienced a recurrence of pilonidal disease, compared with 33.6% of patients in the standard treatment group (P < .001). Rates were based on the data available on 96 patients in the LE group and 134 patients in the standard care group.
“These results provide further evidence that laser epilation is safe, well-tolerated, and should be available as an initial treatment option or adjunct treatment modality for all eligible patients,” first author Peter C. Minneci, MD, chair of surgery at Nemours Children’s Health, Delaware Valley, Wilmington, Del, said in a press release reporting the results. “There have been few comparative studies that have investigated recurrence rates after LE versus other treatment modalities,” he and his coauthors wrote in the study, noting that the study “was the first, to our knowledge, to compare LE as an adjunct to standard care versus standard care alone and demonstrate a decrease in recurrence rates.”
Pilonidal disease, a common condition, results when cysts form between the buttocks and is most common in adolescents and young adults. It is thought to recur about 33% of the time, with most cases recurring within 1 year of treatment.
In practice, there are large variations in management strategies for pilonidal disease because evidence for an ideal treatment approach is lacking, Dr. Minneci and coauthors wrote. Although lifestyle modifications and nonepilation hair removal strategies have been linked to a reduced need for surgery, compliance with these strategies is low. Additionally, recurrence contributes to “a high degree of psychosocial stress in patients, who often miss school or sports and may avoid social activities,” Dr. Minneci said in the press release. Therefore, some practitioners have begun using LE – which uses selective thermolysis to remove the hair shaft, follicle, and bulb – as an adjunct to standard treatments in the hopes of avoiding surgery.
A few studies have shown LE is effective in reducing pilonidal disease recurrence, but these studies had small sample sizes, according to the authors.
Study methods
The randomized, nonblinded clinical trial was conducted between 2017 and 2022 at Nationwide Children’s Hospital, Columbus, and enrolled patients aged 11-21 years with a history of pilonidal disease, who did not have active disease.
Those in the control group (151 patients) had an in-person clinic visit where they received education and training about hair removal in the gluteal cleft, and were provided with supplies for hair removal (chemical epilation or shaving) for 6 months (standard of care). Those in the LE group (151 patients) received standard of care therapy, and also received one LE treatment every 4-6 weeks for a total of five treatments. They were encouraged to perform hair removal using chemical or mechanical depilation between visits.
At the 1-year follow-up, data were available in 96 patients in the LE group and 134 patients in the standard care group. At that time, the proportion of those who had a recurrence within 1 year was significantly lower in the LE group than in the standard care group (mean difference, –23.2%; 95% CI, –33.2% to –13.1%; P < .001).
In addition, over the course of a year, those in the LE-treated group had significantly higher Child Attitude Toward Illness scores, indicating that they felt more positively about their illness at 6 months than participants in the standard care group. There were no differences between the groups in terms of patient or caregiver disability days, patient- or caregiver-reported health-related quality of life, health care satisfaction, or perceived stigma. In the LE group, no burns were reported, and no inability to tolerate treatment because of pain.
The study had several limitations, including the potential for participation bias, and because of a loss to follow-up, primary and secondary outcomes were missing data points, which was higher in the LE group. Loss to follow-up in the LE arm increased after 6 months, when laser treatments ended, with many of those patients not completing surveys at 9 and 12 months. The hospital’s pilonidal clinic shut down for 3 months during the COVID-19 pandemic, and when the clinic reopened, 15 patients in the LE arm withdrew from the study.
|In the press release, Dr. Minneci said that confirmation of the effectiveness of LE could help justify insurance coverage for pilonidal disease, noting that LE is usually not covered with insurance, and a course of treatment could cost $800-$1,500.
Dr. Minneci and four of the other six coauthors reported receiving grants from Patient-Centered Outcomes Research Institute during the conduct of the study. One author reported receiving grants from the National Institute on Minority Health and Health Disparities outside the submitted work. The research was funded by a grant from the Patient-Centered Outcomes Research Institute.
FROM JAMA SURGERY
Nail psoriasis in Black patients often overlooked
NEW YORK – From clinical trials to textbooks, , even when the skin disease has already been diagnosed, according to Shari R. Lipner, MD.
In a recently published review of 45 randomized controlled trials of therapies for nail psoriasis, almost all included information about the gender of the patients enrolled, but only about 35% reported race and/or ethnicity, Dr. Lipner, associate professor of dermatology, Weill Cornell Medical College, New York, said at the Skin of Color Update 2023. The proportion climbed to 59% in trials that included at least one study site in the United States, although representation of non-White patients in studies conducted in the United States was not proportional to the population (13.4% vs. 39.9%), said Dr. Lipner, senior author of the review .
Black patients largely unrepresented in photos
When an Internet search was conducted for images of nail psoriasis, the proportion of images fell as the number of the Fitzpatrick scale increased. Fitzpatrick skin types 1 or 2 represented 70% of the images, skin types 3 to 4 represented about 27%, leaving just 3% represented by darker skin types, Dr. Lipner said.
“Unfortunately, things are not much better if you look at the dermatology and nail-specific textbooks. In fact, the percentages we see are almost identical,” said Dr. Lipner, noting that her review of images suggested that only about 3% of images in textbooks are of Fitzpatrick skin types 5 or 6, an obstacle for clinicians learning to recognize nail involvement in skin of color patients with psoriasis.
“We have written a couple of papers on this topic, including a call to action” in a letter to the editor in the Journal of the American Academy of Dermatology, Dr. Lipner noted. “To ensure access to safe and effective treatments for all patient populations,” she and her coauthor wrote, “we advocate the prioritized enrollment of racial and ethnic minority groups in psoriasis, PsA [psoriatic arthritis], and NP [nail psoriasis] clinical trials.”
Data from the 2009-2010 U.S. National Health and Nutrition Examination Survey (NHANES) confirms that psoriasis is less common in Blacks (1.9%) and Hispanics (1.6%) than Whites (3.6%). But these lower numbers still translate into substantial numbers nationally. Of those with psoriasis, the lifetime incidence of nail involvement has been variously estimated between 80% and 90%, Dr. Lipner said.
In about 10% of patients with psoriasis, nail involvement is isolated, occurring in the absence of skin lesions, a proportion that appears to be similar in Blacks and Whites according to Dr. Lipner.
Patient characteristics similar by race
In a study conducted at her own center, many of the characteristics of psoriasis were similar when those with a Fitzpatrick skin type 4 or higher were compared to those of 3 or lower. This included male-female distribution, smoking history, and presence of accompanying psoriatic arthritis. There was one discrepancy between lighter and darker skin.
“The big difference was that it took almost 3 years longer [on average] for darker skin to be diagnosed, and there was worse severity of disease,” Dr. Lipner said.
Like cutaneous manifestations of psoriasis, there are differences in appearance in the nail, many of which are simply produced by how skin color alters the appearance, such as the brownish hue of erythema in darker versus lighter skin. Dr. Lipner also noted that many of the features, such as keratosis, can be more severe in patients with darker skin types, but this is likely because of the delay in diagnosis.
The problem with overlooking nail psoriasis in patients of any skin color is the significant and independent adverse impact imposed by nail disease on quality of life, she added. She recounted the case of a 22-year-old Black patient whose nail psoriasis was overlooked even as she was being treated for her skin lesions.
“The diagnosis of nail psoriasis was missed for 3 years,” said Dr. Lipner, noting that the nail involvement was not trivial. “She had trouble doing her daily activities of life, but also, she was very embarrassed by her nails, not surprisingly.”
The problem of underrepresentation of Blacks in photos depicting nail diseases is not going unnoticed.
“Recently, there has been a concerted effort on the part of authors and editors to include more images of skin of color patients in published articles and textbooks,” said Jane S. Bellet, MD, professor of dermatology, Duke University, Durham, N.C.
An expert in nail disorders, particularly in children, Dr. Bellet said in an interview that this trend “must continue and increase in volume.” She said that the need for more images of nail disease in skin of color is not restricted to textbooks but includes “other learning materials, such as online atlases.”
Dr. Lipner and Dr. Bellet reported no potential conflicts of interest relative to this topic.
NEW YORK – From clinical trials to textbooks, , even when the skin disease has already been diagnosed, according to Shari R. Lipner, MD.
In a recently published review of 45 randomized controlled trials of therapies for nail psoriasis, almost all included information about the gender of the patients enrolled, but only about 35% reported race and/or ethnicity, Dr. Lipner, associate professor of dermatology, Weill Cornell Medical College, New York, said at the Skin of Color Update 2023. The proportion climbed to 59% in trials that included at least one study site in the United States, although representation of non-White patients in studies conducted in the United States was not proportional to the population (13.4% vs. 39.9%), said Dr. Lipner, senior author of the review .
Black patients largely unrepresented in photos
When an Internet search was conducted for images of nail psoriasis, the proportion of images fell as the number of the Fitzpatrick scale increased. Fitzpatrick skin types 1 or 2 represented 70% of the images, skin types 3 to 4 represented about 27%, leaving just 3% represented by darker skin types, Dr. Lipner said.
“Unfortunately, things are not much better if you look at the dermatology and nail-specific textbooks. In fact, the percentages we see are almost identical,” said Dr. Lipner, noting that her review of images suggested that only about 3% of images in textbooks are of Fitzpatrick skin types 5 or 6, an obstacle for clinicians learning to recognize nail involvement in skin of color patients with psoriasis.
“We have written a couple of papers on this topic, including a call to action” in a letter to the editor in the Journal of the American Academy of Dermatology, Dr. Lipner noted. “To ensure access to safe and effective treatments for all patient populations,” she and her coauthor wrote, “we advocate the prioritized enrollment of racial and ethnic minority groups in psoriasis, PsA [psoriatic arthritis], and NP [nail psoriasis] clinical trials.”
Data from the 2009-2010 U.S. National Health and Nutrition Examination Survey (NHANES) confirms that psoriasis is less common in Blacks (1.9%) and Hispanics (1.6%) than Whites (3.6%). But these lower numbers still translate into substantial numbers nationally. Of those with psoriasis, the lifetime incidence of nail involvement has been variously estimated between 80% and 90%, Dr. Lipner said.
In about 10% of patients with psoriasis, nail involvement is isolated, occurring in the absence of skin lesions, a proportion that appears to be similar in Blacks and Whites according to Dr. Lipner.
Patient characteristics similar by race
In a study conducted at her own center, many of the characteristics of psoriasis were similar when those with a Fitzpatrick skin type 4 or higher were compared to those of 3 or lower. This included male-female distribution, smoking history, and presence of accompanying psoriatic arthritis. There was one discrepancy between lighter and darker skin.
“The big difference was that it took almost 3 years longer [on average] for darker skin to be diagnosed, and there was worse severity of disease,” Dr. Lipner said.
Like cutaneous manifestations of psoriasis, there are differences in appearance in the nail, many of which are simply produced by how skin color alters the appearance, such as the brownish hue of erythema in darker versus lighter skin. Dr. Lipner also noted that many of the features, such as keratosis, can be more severe in patients with darker skin types, but this is likely because of the delay in diagnosis.
The problem with overlooking nail psoriasis in patients of any skin color is the significant and independent adverse impact imposed by nail disease on quality of life, she added. She recounted the case of a 22-year-old Black patient whose nail psoriasis was overlooked even as she was being treated for her skin lesions.
“The diagnosis of nail psoriasis was missed for 3 years,” said Dr. Lipner, noting that the nail involvement was not trivial. “She had trouble doing her daily activities of life, but also, she was very embarrassed by her nails, not surprisingly.”
The problem of underrepresentation of Blacks in photos depicting nail diseases is not going unnoticed.
“Recently, there has been a concerted effort on the part of authors and editors to include more images of skin of color patients in published articles and textbooks,” said Jane S. Bellet, MD, professor of dermatology, Duke University, Durham, N.C.
An expert in nail disorders, particularly in children, Dr. Bellet said in an interview that this trend “must continue and increase in volume.” She said that the need for more images of nail disease in skin of color is not restricted to textbooks but includes “other learning materials, such as online atlases.”
Dr. Lipner and Dr. Bellet reported no potential conflicts of interest relative to this topic.
NEW YORK – From clinical trials to textbooks, , even when the skin disease has already been diagnosed, according to Shari R. Lipner, MD.
In a recently published review of 45 randomized controlled trials of therapies for nail psoriasis, almost all included information about the gender of the patients enrolled, but only about 35% reported race and/or ethnicity, Dr. Lipner, associate professor of dermatology, Weill Cornell Medical College, New York, said at the Skin of Color Update 2023. The proportion climbed to 59% in trials that included at least one study site in the United States, although representation of non-White patients in studies conducted in the United States was not proportional to the population (13.4% vs. 39.9%), said Dr. Lipner, senior author of the review .
Black patients largely unrepresented in photos
When an Internet search was conducted for images of nail psoriasis, the proportion of images fell as the number of the Fitzpatrick scale increased. Fitzpatrick skin types 1 or 2 represented 70% of the images, skin types 3 to 4 represented about 27%, leaving just 3% represented by darker skin types, Dr. Lipner said.
“Unfortunately, things are not much better if you look at the dermatology and nail-specific textbooks. In fact, the percentages we see are almost identical,” said Dr. Lipner, noting that her review of images suggested that only about 3% of images in textbooks are of Fitzpatrick skin types 5 or 6, an obstacle for clinicians learning to recognize nail involvement in skin of color patients with psoriasis.
“We have written a couple of papers on this topic, including a call to action” in a letter to the editor in the Journal of the American Academy of Dermatology, Dr. Lipner noted. “To ensure access to safe and effective treatments for all patient populations,” she and her coauthor wrote, “we advocate the prioritized enrollment of racial and ethnic minority groups in psoriasis, PsA [psoriatic arthritis], and NP [nail psoriasis] clinical trials.”
Data from the 2009-2010 U.S. National Health and Nutrition Examination Survey (NHANES) confirms that psoriasis is less common in Blacks (1.9%) and Hispanics (1.6%) than Whites (3.6%). But these lower numbers still translate into substantial numbers nationally. Of those with psoriasis, the lifetime incidence of nail involvement has been variously estimated between 80% and 90%, Dr. Lipner said.
In about 10% of patients with psoriasis, nail involvement is isolated, occurring in the absence of skin lesions, a proportion that appears to be similar in Blacks and Whites according to Dr. Lipner.
Patient characteristics similar by race
In a study conducted at her own center, many of the characteristics of psoriasis were similar when those with a Fitzpatrick skin type 4 or higher were compared to those of 3 or lower. This included male-female distribution, smoking history, and presence of accompanying psoriatic arthritis. There was one discrepancy between lighter and darker skin.
“The big difference was that it took almost 3 years longer [on average] for darker skin to be diagnosed, and there was worse severity of disease,” Dr. Lipner said.
Like cutaneous manifestations of psoriasis, there are differences in appearance in the nail, many of which are simply produced by how skin color alters the appearance, such as the brownish hue of erythema in darker versus lighter skin. Dr. Lipner also noted that many of the features, such as keratosis, can be more severe in patients with darker skin types, but this is likely because of the delay in diagnosis.
The problem with overlooking nail psoriasis in patients of any skin color is the significant and independent adverse impact imposed by nail disease on quality of life, she added. She recounted the case of a 22-year-old Black patient whose nail psoriasis was overlooked even as she was being treated for her skin lesions.
“The diagnosis of nail psoriasis was missed for 3 years,” said Dr. Lipner, noting that the nail involvement was not trivial. “She had trouble doing her daily activities of life, but also, she was very embarrassed by her nails, not surprisingly.”
The problem of underrepresentation of Blacks in photos depicting nail diseases is not going unnoticed.
“Recently, there has been a concerted effort on the part of authors and editors to include more images of skin of color patients in published articles and textbooks,” said Jane S. Bellet, MD, professor of dermatology, Duke University, Durham, N.C.
An expert in nail disorders, particularly in children, Dr. Bellet said in an interview that this trend “must continue and increase in volume.” She said that the need for more images of nail disease in skin of color is not restricted to textbooks but includes “other learning materials, such as online atlases.”
Dr. Lipner and Dr. Bellet reported no potential conflicts of interest relative to this topic.
AT SOC 2023
At 52 weeks, complete hair regrowth rates still climbing on deuruxolitinib
BERLIN – at the annual congress of the European Academy of Dermatology and Venereology.
With response curves still climbing at follow-up to date, the results are “truly, truly remarkable,” said Brett King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn.
Deuruxolitinib is a JAK inhibitor that has specificity for the 1 and 2 subtypes. At 24 weeks in the phase 3 THRIVE-AA1 and THRIVE-AA2 trials, presented at the American Academy of Dermatology annual meeting earlier this year, about 40% of those on the 12-mg twice-daily dose and 32% of those on the 8-mg twice-daily dose achieved a Severity of Alopecia Tool (SALT) score of ≤ 20%, signifying 80% or greater hair regrowth at 24 weeks. The placebo response was 0%.
By 52 weeks, the proportion had climbed to 62% among those on continuous deuruxolitinib whether maintained on the 8-mg or 12-mg twice daily doses. Among patients on placebo, 58.4% reached this endpoint after being switched at 24 weeks to the 12-mg twice daily dose. Of the patients on placebo switched to 8 mg twice daily, the 52-week response was 45.2%, according to Dr. King.
There were 741 patients available at 52 weeks for this on-going analysis. The mean SALT scores at entry exceeded 80%, meaning complete or near complete hair loss. The substantial proportion of patients who met the primary endpoint of SALT ≤ 20 at the end of the blinded period was encouraging, but Dr. King said that the 52-week results are important, not only showing the response was sustained, but that greater regrowth occurs over time.
“Alopecia takes time to treat,” said Dr. King, summarizing the lesson from these data. Moreover, he added that the long-term data are likely to under represent the absolute benefit even if no further growth is achieved with even longer follow-up. One reason is that missing long-term data were accounted for with a last-observation-carried-forward approach.
In other words, “this is the floor when considering response at 52 weeks,” Dr. King said. “In the real world, where adjunctive measures such as intralesional Kenalog [triamcinolone acetonide] or topical treatments are added, we are likely to do even better,” he added.
Adverse events remained low
Treatment-emergent adverse events remained low with “nothing particularly surprising,” Dr. King said. The rate of serious adverse events over 52 weeks was less than 2% on either dose of deuruxolitinib. The proportion of patients who discontinued treatment because of an adverse event was 0.7% in the 8-mg twice-daily arm and 1.1% in the 12-mg twice-daily arm.
Most approved oral JAK inhibitors carry a boxed warning based on a trial conducted with the relatively nonspecific tofacitinib. The trial enrolled older patients with rheumatoid arthritis at risk for thrombotic events, raising questions about its relevance to selective JAK inhibitors employed for other indications. There was only one thrombosis observed in the 52-week alopecia areata follow-up in a patient on deuruxolitinib. Dr. King noted that this patient, who was obese and was on the higher of the two doses, had multiple comorbidities, including systemic lupus erythematosus.
There were no major adverse cardiac events reported in long-term follow-up or cases of tuberculosis. The rate of opportunistic infections was 0.1% in the 8-mg twice-daily arm and 0.2% in the 12-mg twice-daily arm. Serious infections were observed in 0.6% and 0.4% of these two arms, respectively. There were four malignancies (0.5%) in each of the two study arms.
Of the side effects likely to be related to deuruxolitinib, acne was observed in about 10% of patients on either dose. The mechanism is unclear, but Dr. King reported this has been commonly observed with other JAK inhibitors.
Asked his opinion about the optimal starting dose of deuruxolitinib, Dr. King said, “in my mind, the efficacy of 8 mg is so impressive that I would not struggle at all in starting there,” noting that the higher dose could be considered with a slow or inadequate response.
Two JAK inhibitors are already approved
If approved for alopecia areata, deuruxolitinib will be the third JAK inhibitor available for this indication, following the recent approvals of baricitinib and ritlecitinib.
Calling JAK inhibitors “a major advance in the treatment of alopecia areata, particularly for those patients with severe, refractory disease,” Lynne Goldberg, MD, professor of dermatology at Boston University, and director of the hair clinic, Boston Medical Center, said that the proportion of patients with SALT scores ≤ 20 at 52-weeks is “huge.”
She is generally comfortable with the safety of the JAK inhibitors for alopecia areata.
“I believe that, in general, these medications are well tolerated in the alopecia areata population, particularly in otherwise healthy, young patients,” she said, indicating the benefit-to-risk ratio is particularly acceptable when disease is severe.
“This disease has tremendous emotional and functional implications, and many patients with severe or recurrent disease are willing to chance the side effects to live with a full head of hair,” she said. She added that well-informed patients can “make their own, individual assessment.”
Dr. King has financial relationships with approximately 20 pharmaceutical companies, including Concert Pharmaceuticals, which makes deuruxolitinib and provided funding for this study. Dr. Goldberg reports no financial conflicts relevant to this topic.
BERLIN – at the annual congress of the European Academy of Dermatology and Venereology.
With response curves still climbing at follow-up to date, the results are “truly, truly remarkable,” said Brett King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn.
Deuruxolitinib is a JAK inhibitor that has specificity for the 1 and 2 subtypes. At 24 weeks in the phase 3 THRIVE-AA1 and THRIVE-AA2 trials, presented at the American Academy of Dermatology annual meeting earlier this year, about 40% of those on the 12-mg twice-daily dose and 32% of those on the 8-mg twice-daily dose achieved a Severity of Alopecia Tool (SALT) score of ≤ 20%, signifying 80% or greater hair regrowth at 24 weeks. The placebo response was 0%.
By 52 weeks, the proportion had climbed to 62% among those on continuous deuruxolitinib whether maintained on the 8-mg or 12-mg twice daily doses. Among patients on placebo, 58.4% reached this endpoint after being switched at 24 weeks to the 12-mg twice daily dose. Of the patients on placebo switched to 8 mg twice daily, the 52-week response was 45.2%, according to Dr. King.
There were 741 patients available at 52 weeks for this on-going analysis. The mean SALT scores at entry exceeded 80%, meaning complete or near complete hair loss. The substantial proportion of patients who met the primary endpoint of SALT ≤ 20 at the end of the blinded period was encouraging, but Dr. King said that the 52-week results are important, not only showing the response was sustained, but that greater regrowth occurs over time.
“Alopecia takes time to treat,” said Dr. King, summarizing the lesson from these data. Moreover, he added that the long-term data are likely to under represent the absolute benefit even if no further growth is achieved with even longer follow-up. One reason is that missing long-term data were accounted for with a last-observation-carried-forward approach.
In other words, “this is the floor when considering response at 52 weeks,” Dr. King said. “In the real world, where adjunctive measures such as intralesional Kenalog [triamcinolone acetonide] or topical treatments are added, we are likely to do even better,” he added.
Adverse events remained low
Treatment-emergent adverse events remained low with “nothing particularly surprising,” Dr. King said. The rate of serious adverse events over 52 weeks was less than 2% on either dose of deuruxolitinib. The proportion of patients who discontinued treatment because of an adverse event was 0.7% in the 8-mg twice-daily arm and 1.1% in the 12-mg twice-daily arm.
Most approved oral JAK inhibitors carry a boxed warning based on a trial conducted with the relatively nonspecific tofacitinib. The trial enrolled older patients with rheumatoid arthritis at risk for thrombotic events, raising questions about its relevance to selective JAK inhibitors employed for other indications. There was only one thrombosis observed in the 52-week alopecia areata follow-up in a patient on deuruxolitinib. Dr. King noted that this patient, who was obese and was on the higher of the two doses, had multiple comorbidities, including systemic lupus erythematosus.
There were no major adverse cardiac events reported in long-term follow-up or cases of tuberculosis. The rate of opportunistic infections was 0.1% in the 8-mg twice-daily arm and 0.2% in the 12-mg twice-daily arm. Serious infections were observed in 0.6% and 0.4% of these two arms, respectively. There were four malignancies (0.5%) in each of the two study arms.
Of the side effects likely to be related to deuruxolitinib, acne was observed in about 10% of patients on either dose. The mechanism is unclear, but Dr. King reported this has been commonly observed with other JAK inhibitors.
Asked his opinion about the optimal starting dose of deuruxolitinib, Dr. King said, “in my mind, the efficacy of 8 mg is so impressive that I would not struggle at all in starting there,” noting that the higher dose could be considered with a slow or inadequate response.
Two JAK inhibitors are already approved
If approved for alopecia areata, deuruxolitinib will be the third JAK inhibitor available for this indication, following the recent approvals of baricitinib and ritlecitinib.
Calling JAK inhibitors “a major advance in the treatment of alopecia areata, particularly for those patients with severe, refractory disease,” Lynne Goldberg, MD, professor of dermatology at Boston University, and director of the hair clinic, Boston Medical Center, said that the proportion of patients with SALT scores ≤ 20 at 52-weeks is “huge.”
She is generally comfortable with the safety of the JAK inhibitors for alopecia areata.
“I believe that, in general, these medications are well tolerated in the alopecia areata population, particularly in otherwise healthy, young patients,” she said, indicating the benefit-to-risk ratio is particularly acceptable when disease is severe.
“This disease has tremendous emotional and functional implications, and many patients with severe or recurrent disease are willing to chance the side effects to live with a full head of hair,” she said. She added that well-informed patients can “make their own, individual assessment.”
Dr. King has financial relationships with approximately 20 pharmaceutical companies, including Concert Pharmaceuticals, which makes deuruxolitinib and provided funding for this study. Dr. Goldberg reports no financial conflicts relevant to this topic.
BERLIN – at the annual congress of the European Academy of Dermatology and Venereology.
With response curves still climbing at follow-up to date, the results are “truly, truly remarkable,” said Brett King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn.
Deuruxolitinib is a JAK inhibitor that has specificity for the 1 and 2 subtypes. At 24 weeks in the phase 3 THRIVE-AA1 and THRIVE-AA2 trials, presented at the American Academy of Dermatology annual meeting earlier this year, about 40% of those on the 12-mg twice-daily dose and 32% of those on the 8-mg twice-daily dose achieved a Severity of Alopecia Tool (SALT) score of ≤ 20%, signifying 80% or greater hair regrowth at 24 weeks. The placebo response was 0%.
By 52 weeks, the proportion had climbed to 62% among those on continuous deuruxolitinib whether maintained on the 8-mg or 12-mg twice daily doses. Among patients on placebo, 58.4% reached this endpoint after being switched at 24 weeks to the 12-mg twice daily dose. Of the patients on placebo switched to 8 mg twice daily, the 52-week response was 45.2%, according to Dr. King.
There were 741 patients available at 52 weeks for this on-going analysis. The mean SALT scores at entry exceeded 80%, meaning complete or near complete hair loss. The substantial proportion of patients who met the primary endpoint of SALT ≤ 20 at the end of the blinded period was encouraging, but Dr. King said that the 52-week results are important, not only showing the response was sustained, but that greater regrowth occurs over time.
“Alopecia takes time to treat,” said Dr. King, summarizing the lesson from these data. Moreover, he added that the long-term data are likely to under represent the absolute benefit even if no further growth is achieved with even longer follow-up. One reason is that missing long-term data were accounted for with a last-observation-carried-forward approach.
In other words, “this is the floor when considering response at 52 weeks,” Dr. King said. “In the real world, where adjunctive measures such as intralesional Kenalog [triamcinolone acetonide] or topical treatments are added, we are likely to do even better,” he added.
Adverse events remained low
Treatment-emergent adverse events remained low with “nothing particularly surprising,” Dr. King said. The rate of serious adverse events over 52 weeks was less than 2% on either dose of deuruxolitinib. The proportion of patients who discontinued treatment because of an adverse event was 0.7% in the 8-mg twice-daily arm and 1.1% in the 12-mg twice-daily arm.
Most approved oral JAK inhibitors carry a boxed warning based on a trial conducted with the relatively nonspecific tofacitinib. The trial enrolled older patients with rheumatoid arthritis at risk for thrombotic events, raising questions about its relevance to selective JAK inhibitors employed for other indications. There was only one thrombosis observed in the 52-week alopecia areata follow-up in a patient on deuruxolitinib. Dr. King noted that this patient, who was obese and was on the higher of the two doses, had multiple comorbidities, including systemic lupus erythematosus.
There were no major adverse cardiac events reported in long-term follow-up or cases of tuberculosis. The rate of opportunistic infections was 0.1% in the 8-mg twice-daily arm and 0.2% in the 12-mg twice-daily arm. Serious infections were observed in 0.6% and 0.4% of these two arms, respectively. There were four malignancies (0.5%) in each of the two study arms.
Of the side effects likely to be related to deuruxolitinib, acne was observed in about 10% of patients on either dose. The mechanism is unclear, but Dr. King reported this has been commonly observed with other JAK inhibitors.
Asked his opinion about the optimal starting dose of deuruxolitinib, Dr. King said, “in my mind, the efficacy of 8 mg is so impressive that I would not struggle at all in starting there,” noting that the higher dose could be considered with a slow or inadequate response.
Two JAK inhibitors are already approved
If approved for alopecia areata, deuruxolitinib will be the third JAK inhibitor available for this indication, following the recent approvals of baricitinib and ritlecitinib.
Calling JAK inhibitors “a major advance in the treatment of alopecia areata, particularly for those patients with severe, refractory disease,” Lynne Goldberg, MD, professor of dermatology at Boston University, and director of the hair clinic, Boston Medical Center, said that the proportion of patients with SALT scores ≤ 20 at 52-weeks is “huge.”
She is generally comfortable with the safety of the JAK inhibitors for alopecia areata.
“I believe that, in general, these medications are well tolerated in the alopecia areata population, particularly in otherwise healthy, young patients,” she said, indicating the benefit-to-risk ratio is particularly acceptable when disease is severe.
“This disease has tremendous emotional and functional implications, and many patients with severe or recurrent disease are willing to chance the side effects to live with a full head of hair,” she said. She added that well-informed patients can “make their own, individual assessment.”
Dr. King has financial relationships with approximately 20 pharmaceutical companies, including Concert Pharmaceuticals, which makes deuruxolitinib and provided funding for this study. Dr. Goldberg reports no financial conflicts relevant to this topic.
At THE EADV CONGRESS
Tapinarof effective for AD in patients as young as 2 years
BERLIN – of age, according to results of two pivotal trials presented at the at the annual congress of the European Academy of Dermatology and Venereology.
If approved for AD, one advantage of tapinarof cream relative to topical corticosteroids is potential use “without restrictions on duration, extent, or site of application,” reported Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research, George Washington University, Washington.
Tapinarof cream, 1%, an aryl hydrocarbon receptor agonist, was approved in 2022 for treating plaque psoriasis in adults.
In the two phase 3 trials, ADORING 1 and ADORING 2, which were presented together at the meeting, the primary endpoint was Validated Investigator Global Assessment (vIGA) for AD of 0 (clear) or 1 (almost clear) at 8 weeks. For this endpoint and all secondary endpoints, the relative advantage of the active cream over the vehicle alone was about the same in both studies.
For example, the vIGA clear or almost clear response was met by 45.4% and 46.4% of those in the experimental arm of ADORING 1 and 2, respectively, but only 13.9% and 18.0% in the control arms (P < .0001 for both).
For the secondary endpoint of Eczema Area and Severity Index (EASI75), signifying 75% clearance of skin lesions, the response rates were 55.8% and 59.1% in the two trials, but only 22.9% and 24.1% in the respective control arms (P < .0001 for both).
The two identically designed trials randomized patients with moderate to severe AD in a 2:1 ratio to tapinarof cream or vehicle alone. There were 407 patients ages 2-81 years in ADORING I and 406 in ADORING 2. Patients were instructed to apply the active cream or vehicle once per day.
The safety data for tapinarof in these studies was generally consistent with the experience with this agent in plaque psoriasis. According to Dr. Silverberg, there was a modest increase in reports of headache early in this study, but these were transient. Follicular events were also more common on tapinarof than on its vehicle, but Dr. Silverberg said that the rate of discontinuations for adverse events, although low in both arms, was numerically lower in the active treatment arm in both trials.
“There were reports of contact dermatitis in the psoriasis studies, but we have not seen this in the AD trials,” Dr. Silverberg said.
Itch control evaluated
In a separate presentation of ADORING 1 and 2 results, Eric Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland, provided detailed information about itch control, which was evaluated with the Peak Pruritus–Numerical Rating Scale (PP-NRS).
“The PP-NRS considers a person’s worst itch over the past 24 hours based on an 11-point scale,” explained Dr. Simpson, who said that patients scored itch daily with comparisons made at weeks 1, 2, 4, and 8.
Over time, pruritus scores fell in both groups, but reductions were far steeper among those in the active treatment arms.
“In ADORING 1, there were greater reductions in itch as early as day 1,” Dr. Simpson reported. Although the differences in itch were not detected until day 2 in ADORING 2, the differences were already significant and clinically meaningful in both studies by the end of the first week.
By week 8, the mean reductions in PP-NRS scores were 2.6 and 2.4 in the vehicle arms of ADORING 1 and 2, respectively. In the treatment arm, the reduction was 4.1 points in both arms (P < .0001 for both studies).
Forty-eight–week follow-up planned
More than 90% of patients in both studies have rolled over into the open-label extension ADORING 3 trial, with a planned follow-up of 48 weeks, according to Dr. Silverberg, who said that those in the placebo arm have been crossed over to tapinarof.
The response and the safety appear to be similar in adults and children, although Dr. Silverberg said that further analyses of outcomes by age are planned. He noted that there is also an ongoing study of tapinarof in children with plaque psoriasis.
In AD in particular, Dr. Silverberg said there is “an unmet need” for a topical nonsteroidal anti-inflammatory. While topical corticosteroids are a mainstay of AD therapy in children as well as adults, he noted the limitations of these drugs, including that they can only be applied for limited periods.
Tapinarof binds to the aryl hydrocarbon receptor (AhR), which regulates immune function in the skin and is expressed in many skin cell types. By inhibiting AhR, tapinarof blocks cytokine activation and has an antioxidant effect.
Adelaide A. Hebert, MD, professor and director of pediatric dermatology, McGovern Medical School at UTHealth, Houston, has participated in clinical studies of tapinarof for AD, and said she has been impressed with its efficacy and tolerability in children as well as adults. In the case of children, parents, as well as patients, “valued the rapid onset of disease control, the once-daily application regimen, and the itch control,” she said in an interview after the meeting.
If approved, Dr. Hebert said, “this novel steroid-free medication has the potential to change the management arena for pediatric and adult patients with moderate to severe atopic dermatitis.”
The recent introduction of new systemic therapies for AD, such as JAK inhibitors, has increased options for AD control, but “we still need effective and safe topical therapies, especially in children and young adults,” said Sonja Ständer, MD, head of the Interdisciplinary Center for Chronic Pruritus, University of Münster (Germany). Author of a comprehensive review article on AD in the New England Journal of Medicine 2 years ago, Dr. Ständer said results from the phase 3 topical tapinarof trials, as well as the phase 3 topical ruxolitinib trials, which were also presented as late breakers at the 2023 EADV meeting, provide “hope that an alternative to topical steroids will soon be available.”
Based on their safety and rapid control of itch in children with AD, “these will complement our current portfolio of topical therapies very well and have the potential to replace topical steroids early in therapy or to replace them altogether,” she told this news organization.
Dermavant Sciences, manufacturer of tapinarof, anticipates filing for Food and Drug Administration approval for AD in the first quarter of 2024, according to a company statement.
Dr. Silverberg and Dr. Simpson reported financial relationships with multiple pharmaceutical companies, including Dermavant, which provided funding for the ADORING trials. Dr. Hebert has financial relationship with more than 15 pharmaceutical companies, including Dermavent and other companies that have or are developing therapies for AD. Dr. Ständer reported financial relationships with Beiersdorf, Eli Lilly, Galderma, Kiniksa, Pfizer, and Sanofi.
BERLIN – of age, according to results of two pivotal trials presented at the at the annual congress of the European Academy of Dermatology and Venereology.
If approved for AD, one advantage of tapinarof cream relative to topical corticosteroids is potential use “without restrictions on duration, extent, or site of application,” reported Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research, George Washington University, Washington.
Tapinarof cream, 1%, an aryl hydrocarbon receptor agonist, was approved in 2022 for treating plaque psoriasis in adults.
In the two phase 3 trials, ADORING 1 and ADORING 2, which were presented together at the meeting, the primary endpoint was Validated Investigator Global Assessment (vIGA) for AD of 0 (clear) or 1 (almost clear) at 8 weeks. For this endpoint and all secondary endpoints, the relative advantage of the active cream over the vehicle alone was about the same in both studies.
For example, the vIGA clear or almost clear response was met by 45.4% and 46.4% of those in the experimental arm of ADORING 1 and 2, respectively, but only 13.9% and 18.0% in the control arms (P < .0001 for both).
For the secondary endpoint of Eczema Area and Severity Index (EASI75), signifying 75% clearance of skin lesions, the response rates were 55.8% and 59.1% in the two trials, but only 22.9% and 24.1% in the respective control arms (P < .0001 for both).
The two identically designed trials randomized patients with moderate to severe AD in a 2:1 ratio to tapinarof cream or vehicle alone. There were 407 patients ages 2-81 years in ADORING I and 406 in ADORING 2. Patients were instructed to apply the active cream or vehicle once per day.
The safety data for tapinarof in these studies was generally consistent with the experience with this agent in plaque psoriasis. According to Dr. Silverberg, there was a modest increase in reports of headache early in this study, but these were transient. Follicular events were also more common on tapinarof than on its vehicle, but Dr. Silverberg said that the rate of discontinuations for adverse events, although low in both arms, was numerically lower in the active treatment arm in both trials.
“There were reports of contact dermatitis in the psoriasis studies, but we have not seen this in the AD trials,” Dr. Silverberg said.
Itch control evaluated
In a separate presentation of ADORING 1 and 2 results, Eric Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland, provided detailed information about itch control, which was evaluated with the Peak Pruritus–Numerical Rating Scale (PP-NRS).
“The PP-NRS considers a person’s worst itch over the past 24 hours based on an 11-point scale,” explained Dr. Simpson, who said that patients scored itch daily with comparisons made at weeks 1, 2, 4, and 8.
Over time, pruritus scores fell in both groups, but reductions were far steeper among those in the active treatment arms.
“In ADORING 1, there were greater reductions in itch as early as day 1,” Dr. Simpson reported. Although the differences in itch were not detected until day 2 in ADORING 2, the differences were already significant and clinically meaningful in both studies by the end of the first week.
By week 8, the mean reductions in PP-NRS scores were 2.6 and 2.4 in the vehicle arms of ADORING 1 and 2, respectively. In the treatment arm, the reduction was 4.1 points in both arms (P < .0001 for both studies).
Forty-eight–week follow-up planned
More than 90% of patients in both studies have rolled over into the open-label extension ADORING 3 trial, with a planned follow-up of 48 weeks, according to Dr. Silverberg, who said that those in the placebo arm have been crossed over to tapinarof.
The response and the safety appear to be similar in adults and children, although Dr. Silverberg said that further analyses of outcomes by age are planned. He noted that there is also an ongoing study of tapinarof in children with plaque psoriasis.
In AD in particular, Dr. Silverberg said there is “an unmet need” for a topical nonsteroidal anti-inflammatory. While topical corticosteroids are a mainstay of AD therapy in children as well as adults, he noted the limitations of these drugs, including that they can only be applied for limited periods.
Tapinarof binds to the aryl hydrocarbon receptor (AhR), which regulates immune function in the skin and is expressed in many skin cell types. By inhibiting AhR, tapinarof blocks cytokine activation and has an antioxidant effect.
Adelaide A. Hebert, MD, professor and director of pediatric dermatology, McGovern Medical School at UTHealth, Houston, has participated in clinical studies of tapinarof for AD, and said she has been impressed with its efficacy and tolerability in children as well as adults. In the case of children, parents, as well as patients, “valued the rapid onset of disease control, the once-daily application regimen, and the itch control,” she said in an interview after the meeting.
If approved, Dr. Hebert said, “this novel steroid-free medication has the potential to change the management arena for pediatric and adult patients with moderate to severe atopic dermatitis.”
The recent introduction of new systemic therapies for AD, such as JAK inhibitors, has increased options for AD control, but “we still need effective and safe topical therapies, especially in children and young adults,” said Sonja Ständer, MD, head of the Interdisciplinary Center for Chronic Pruritus, University of Münster (Germany). Author of a comprehensive review article on AD in the New England Journal of Medicine 2 years ago, Dr. Ständer said results from the phase 3 topical tapinarof trials, as well as the phase 3 topical ruxolitinib trials, which were also presented as late breakers at the 2023 EADV meeting, provide “hope that an alternative to topical steroids will soon be available.”
Based on their safety and rapid control of itch in children with AD, “these will complement our current portfolio of topical therapies very well and have the potential to replace topical steroids early in therapy or to replace them altogether,” she told this news organization.
Dermavant Sciences, manufacturer of tapinarof, anticipates filing for Food and Drug Administration approval for AD in the first quarter of 2024, according to a company statement.
Dr. Silverberg and Dr. Simpson reported financial relationships with multiple pharmaceutical companies, including Dermavant, which provided funding for the ADORING trials. Dr. Hebert has financial relationship with more than 15 pharmaceutical companies, including Dermavent and other companies that have or are developing therapies for AD. Dr. Ständer reported financial relationships with Beiersdorf, Eli Lilly, Galderma, Kiniksa, Pfizer, and Sanofi.
BERLIN – of age, according to results of two pivotal trials presented at the at the annual congress of the European Academy of Dermatology and Venereology.
If approved for AD, one advantage of tapinarof cream relative to topical corticosteroids is potential use “without restrictions on duration, extent, or site of application,” reported Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research, George Washington University, Washington.
Tapinarof cream, 1%, an aryl hydrocarbon receptor agonist, was approved in 2022 for treating plaque psoriasis in adults.
In the two phase 3 trials, ADORING 1 and ADORING 2, which were presented together at the meeting, the primary endpoint was Validated Investigator Global Assessment (vIGA) for AD of 0 (clear) or 1 (almost clear) at 8 weeks. For this endpoint and all secondary endpoints, the relative advantage of the active cream over the vehicle alone was about the same in both studies.
For example, the vIGA clear or almost clear response was met by 45.4% and 46.4% of those in the experimental arm of ADORING 1 and 2, respectively, but only 13.9% and 18.0% in the control arms (P < .0001 for both).
For the secondary endpoint of Eczema Area and Severity Index (EASI75), signifying 75% clearance of skin lesions, the response rates were 55.8% and 59.1% in the two trials, but only 22.9% and 24.1% in the respective control arms (P < .0001 for both).
The two identically designed trials randomized patients with moderate to severe AD in a 2:1 ratio to tapinarof cream or vehicle alone. There were 407 patients ages 2-81 years in ADORING I and 406 in ADORING 2. Patients were instructed to apply the active cream or vehicle once per day.
The safety data for tapinarof in these studies was generally consistent with the experience with this agent in plaque psoriasis. According to Dr. Silverberg, there was a modest increase in reports of headache early in this study, but these were transient. Follicular events were also more common on tapinarof than on its vehicle, but Dr. Silverberg said that the rate of discontinuations for adverse events, although low in both arms, was numerically lower in the active treatment arm in both trials.
“There were reports of contact dermatitis in the psoriasis studies, but we have not seen this in the AD trials,” Dr. Silverberg said.
Itch control evaluated
In a separate presentation of ADORING 1 and 2 results, Eric Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland, provided detailed information about itch control, which was evaluated with the Peak Pruritus–Numerical Rating Scale (PP-NRS).
“The PP-NRS considers a person’s worst itch over the past 24 hours based on an 11-point scale,” explained Dr. Simpson, who said that patients scored itch daily with comparisons made at weeks 1, 2, 4, and 8.
Over time, pruritus scores fell in both groups, but reductions were far steeper among those in the active treatment arms.
“In ADORING 1, there were greater reductions in itch as early as day 1,” Dr. Simpson reported. Although the differences in itch were not detected until day 2 in ADORING 2, the differences were already significant and clinically meaningful in both studies by the end of the first week.
By week 8, the mean reductions in PP-NRS scores were 2.6 and 2.4 in the vehicle arms of ADORING 1 and 2, respectively. In the treatment arm, the reduction was 4.1 points in both arms (P < .0001 for both studies).
Forty-eight–week follow-up planned
More than 90% of patients in both studies have rolled over into the open-label extension ADORING 3 trial, with a planned follow-up of 48 weeks, according to Dr. Silverberg, who said that those in the placebo arm have been crossed over to tapinarof.
The response and the safety appear to be similar in adults and children, although Dr. Silverberg said that further analyses of outcomes by age are planned. He noted that there is also an ongoing study of tapinarof in children with plaque psoriasis.
In AD in particular, Dr. Silverberg said there is “an unmet need” for a topical nonsteroidal anti-inflammatory. While topical corticosteroids are a mainstay of AD therapy in children as well as adults, he noted the limitations of these drugs, including that they can only be applied for limited periods.
Tapinarof binds to the aryl hydrocarbon receptor (AhR), which regulates immune function in the skin and is expressed in many skin cell types. By inhibiting AhR, tapinarof blocks cytokine activation and has an antioxidant effect.
Adelaide A. Hebert, MD, professor and director of pediatric dermatology, McGovern Medical School at UTHealth, Houston, has participated in clinical studies of tapinarof for AD, and said she has been impressed with its efficacy and tolerability in children as well as adults. In the case of children, parents, as well as patients, “valued the rapid onset of disease control, the once-daily application regimen, and the itch control,” she said in an interview after the meeting.
If approved, Dr. Hebert said, “this novel steroid-free medication has the potential to change the management arena for pediatric and adult patients with moderate to severe atopic dermatitis.”
The recent introduction of new systemic therapies for AD, such as JAK inhibitors, has increased options for AD control, but “we still need effective and safe topical therapies, especially in children and young adults,” said Sonja Ständer, MD, head of the Interdisciplinary Center for Chronic Pruritus, University of Münster (Germany). Author of a comprehensive review article on AD in the New England Journal of Medicine 2 years ago, Dr. Ständer said results from the phase 3 topical tapinarof trials, as well as the phase 3 topical ruxolitinib trials, which were also presented as late breakers at the 2023 EADV meeting, provide “hope that an alternative to topical steroids will soon be available.”
Based on their safety and rapid control of itch in children with AD, “these will complement our current portfolio of topical therapies very well and have the potential to replace topical steroids early in therapy or to replace them altogether,” she told this news organization.
Dermavant Sciences, manufacturer of tapinarof, anticipates filing for Food and Drug Administration approval for AD in the first quarter of 2024, according to a company statement.
Dr. Silverberg and Dr. Simpson reported financial relationships with multiple pharmaceutical companies, including Dermavant, which provided funding for the ADORING trials. Dr. Hebert has financial relationship with more than 15 pharmaceutical companies, including Dermavent and other companies that have or are developing therapies for AD. Dr. Ständer reported financial relationships with Beiersdorf, Eli Lilly, Galderma, Kiniksa, Pfizer, and Sanofi.
AT THE EADV CONGRESS
Hidradenitis suppurativa: Two anti-IL17A/F therapies yield positive results
BERLIN – In separate trials conducted in patients with hidradenitis suppurativa (HS), two biologics that inhibit the activity of interleukin-17A (IL-17A) and IL-17F were associated with highly encouraging rates of control.
One of the trials evaluated a nanobody inhibitor, sonelokimab, a molecule with a substantially smaller size than traditional monoclonal antibodies (40 kilodaltons vs. 150 kilodaltons). After 24 weeks of treatment, the most effective of the two study doses almost doubled the proportion of patients with complete resolution of draining tunnels (41.1% vs. 23.8%; P < .05) relative to placebo.
“I think the size of sonelokimab is important,” Brian Kirby, MD, a consultant dermatologist at St. Vincent’s Hospital, Dublin, said at the annual congress of the European Academy of Dermatology and Venereology. “We think the smaller size results in better penetration of inflamed tissue,” he added, noting that penetration of abscesses, fistulae, and tunnels has been recognized in the past as a potential weakness of the larger monoclonal antibodies.
The other set of anti-17-A/F set of data were generated by a pooled 48-week maintenance from the BE HEARD I and II trials with bimekizumab. The 16-week data from these two trials were presented at the annual meeting of the American Academy of Dermatology earlier this year.
IL-17A/F trials
Both the
In the sonelokimab trial, called MIRA, 234 adults with HS were randomized in a 2:2:2:1 ratio to one of the two experimental arms, placebo, or a reference arm with the tumor necrosis factor (TNF) inhibitor adalimumab. Nearly 64% had Hurley stage II HS.
The primary endpoint was a 75% or greater reduction in total abscesses and nodules with no increase in draining tunnel count (HiSCR75) from baseline. Dr. Kirby said that this is more rigorous than the HiSCR50 endpoint more commonly used in HS clinical trials. Treatments were administered every 2 weeks for the first 8 weeks of a planned follow-up of 24 weeks and then every 4 weeks thereafter.
At 16 weeks, according to the data Dr. Kirby presented, both doses of sonelokimab were more active than placebo, but Dr. Kirby reported that the lower dose performed better for most objective endpoints.
For example, the HiSCR75 was reached by 43.3% of those randomized to the 120-mg dose (P < .001 vs. placebo), 34.8% of those randomized to the 240-mg dose (P <.01), and 14.7% of those randomized to placebo.
For HiSCR50, response rates were 65.7%, 53.0%, and 27.9%, for the 120-mg, 240-mg, and placebo arms, respectively. Again, both the lower dose (P < .001) and the higher dose (P < .01) were significantly superior to placebo.
On the International Hidradenitis Suppurativa Severity Score System (IHS4), which counts nodules and abscesses, score reductions were 19.3, 14.5, and 7.9 for the lower dose, higher dose, and placebo, respectively, with a greater statistical advantage for the lower relative to the higher dose over placebo (P <.001 vs. P <.01).
However, patient-focused outcomes were not necessarily greater for the lower dose. For the patient-completed measure, the Numerical Rating Scale 50% reduction in skin pain (NRS50), the proportion of patients responding at 12 weeks was numerically greater for the 240-mg dose (41.3%) than with the 120-mg dose (32.0%), although both reached the same statistical advantage (P < .001) over the 4.3% who reached this level of response on placebo.
For the Dermatology Life Quality Index (DLQI) and the Patient Global Impression of Severity (PGI-S), improvements from baseline were similar for the lower and higher dose, although there was a modest numerical and statistical advantage for the higher dose over placebo (P < .001 vs. P <.01).
The HiSCR50 (57.6%) and HiSCR75 (36.4%) responses were both lower for those randomized to the TNF inhibitor adalimumab relative to sonelokimab, but the smaller number of patients in this arm prohibited a statistical comparison.
Although oral candidiasis was more common among patients receiving either dose of sonelokimab than placebo, these were of mild to moderate severity. Dr. Kirby said that there were no unexpected safety issues, and sonelokimab was generally well tolerated.
The results are encouraging, but Dr. Kirby acknowledged that data are now needed to confirm that resolution of tunnels and fistulae is greater with a nanobody inhibitor of IL-17A/F than other targeted therapies. Even if this is validated, he said studies are needed to prove that the small relative molecule size is the reason behind the benefits.
Forty-eight–week bimekizumab data
From the pooled BE HEARD I and BE HEARD II maintenance data, the major message is that the robust responses observed at 16 weeks versus placebo were maintained at 48 weeks. More than 75% of patients retained a HiSCR50 response and more than 55% achieved a HiSCR75 response at the 48-week follow-up. The durable response was also reflected in other measures, according to Christos C. Zouboulis, MD, PhD, director of the department of dermatology, Brandenburg Medical School, Neuruppin, Germany.
“Improvements in disease severity were seen over time,” Dr. Zouboulis reported. “The majority of patients with severe HS at baseline shifted to mild to moderate disease according to the IHS4 classification.”
To the degree that both sonelokimab and bimekizumab target IL-17A/F, these data are mutually reinforcing. Dr. Kirby said that there is a sizable body of data implicating IL-17A/F in driving HS, and the activity of inhibitors in support the clinical value of IL-17A/F suppression.
On Oct. 18, shortly after the EADV meeting concluded, the Food and Drug Administration approved bimekizumab for treating moderate to severe plaque psoriasis, the first approved indication in the United States. In the European Union, it was approved for psoriasis in 2021, and for psoriatic arthritis and ankylosing spondylitis in June 2023.
Dr. Kirby has financial relationships with more than 10 pharmaceutical companies, including MoonLake, which is developing sonelokimab and sponsored the MIRA trial. Dr. Christos, president of the European HS Foundation, has financial relationships with multiple pharmaceutical companies, including UCB, which makes bimekizumab and provided funding for the BE HEARD I and II trials.
BERLIN – In separate trials conducted in patients with hidradenitis suppurativa (HS), two biologics that inhibit the activity of interleukin-17A (IL-17A) and IL-17F were associated with highly encouraging rates of control.
One of the trials evaluated a nanobody inhibitor, sonelokimab, a molecule with a substantially smaller size than traditional monoclonal antibodies (40 kilodaltons vs. 150 kilodaltons). After 24 weeks of treatment, the most effective of the two study doses almost doubled the proportion of patients with complete resolution of draining tunnels (41.1% vs. 23.8%; P < .05) relative to placebo.
“I think the size of sonelokimab is important,” Brian Kirby, MD, a consultant dermatologist at St. Vincent’s Hospital, Dublin, said at the annual congress of the European Academy of Dermatology and Venereology. “We think the smaller size results in better penetration of inflamed tissue,” he added, noting that penetration of abscesses, fistulae, and tunnels has been recognized in the past as a potential weakness of the larger monoclonal antibodies.
The other set of anti-17-A/F set of data were generated by a pooled 48-week maintenance from the BE HEARD I and II trials with bimekizumab. The 16-week data from these two trials were presented at the annual meeting of the American Academy of Dermatology earlier this year.
IL-17A/F trials
Both the
In the sonelokimab trial, called MIRA, 234 adults with HS were randomized in a 2:2:2:1 ratio to one of the two experimental arms, placebo, or a reference arm with the tumor necrosis factor (TNF) inhibitor adalimumab. Nearly 64% had Hurley stage II HS.
The primary endpoint was a 75% or greater reduction in total abscesses and nodules with no increase in draining tunnel count (HiSCR75) from baseline. Dr. Kirby said that this is more rigorous than the HiSCR50 endpoint more commonly used in HS clinical trials. Treatments were administered every 2 weeks for the first 8 weeks of a planned follow-up of 24 weeks and then every 4 weeks thereafter.
At 16 weeks, according to the data Dr. Kirby presented, both doses of sonelokimab were more active than placebo, but Dr. Kirby reported that the lower dose performed better for most objective endpoints.
For example, the HiSCR75 was reached by 43.3% of those randomized to the 120-mg dose (P < .001 vs. placebo), 34.8% of those randomized to the 240-mg dose (P <.01), and 14.7% of those randomized to placebo.
For HiSCR50, response rates were 65.7%, 53.0%, and 27.9%, for the 120-mg, 240-mg, and placebo arms, respectively. Again, both the lower dose (P < .001) and the higher dose (P < .01) were significantly superior to placebo.
On the International Hidradenitis Suppurativa Severity Score System (IHS4), which counts nodules and abscesses, score reductions were 19.3, 14.5, and 7.9 for the lower dose, higher dose, and placebo, respectively, with a greater statistical advantage for the lower relative to the higher dose over placebo (P <.001 vs. P <.01).
However, patient-focused outcomes were not necessarily greater for the lower dose. For the patient-completed measure, the Numerical Rating Scale 50% reduction in skin pain (NRS50), the proportion of patients responding at 12 weeks was numerically greater for the 240-mg dose (41.3%) than with the 120-mg dose (32.0%), although both reached the same statistical advantage (P < .001) over the 4.3% who reached this level of response on placebo.
For the Dermatology Life Quality Index (DLQI) and the Patient Global Impression of Severity (PGI-S), improvements from baseline were similar for the lower and higher dose, although there was a modest numerical and statistical advantage for the higher dose over placebo (P < .001 vs. P <.01).
The HiSCR50 (57.6%) and HiSCR75 (36.4%) responses were both lower for those randomized to the TNF inhibitor adalimumab relative to sonelokimab, but the smaller number of patients in this arm prohibited a statistical comparison.
Although oral candidiasis was more common among patients receiving either dose of sonelokimab than placebo, these were of mild to moderate severity. Dr. Kirby said that there were no unexpected safety issues, and sonelokimab was generally well tolerated.
The results are encouraging, but Dr. Kirby acknowledged that data are now needed to confirm that resolution of tunnels and fistulae is greater with a nanobody inhibitor of IL-17A/F than other targeted therapies. Even if this is validated, he said studies are needed to prove that the small relative molecule size is the reason behind the benefits.
Forty-eight–week bimekizumab data
From the pooled BE HEARD I and BE HEARD II maintenance data, the major message is that the robust responses observed at 16 weeks versus placebo were maintained at 48 weeks. More than 75% of patients retained a HiSCR50 response and more than 55% achieved a HiSCR75 response at the 48-week follow-up. The durable response was also reflected in other measures, according to Christos C. Zouboulis, MD, PhD, director of the department of dermatology, Brandenburg Medical School, Neuruppin, Germany.
“Improvements in disease severity were seen over time,” Dr. Zouboulis reported. “The majority of patients with severe HS at baseline shifted to mild to moderate disease according to the IHS4 classification.”
To the degree that both sonelokimab and bimekizumab target IL-17A/F, these data are mutually reinforcing. Dr. Kirby said that there is a sizable body of data implicating IL-17A/F in driving HS, and the activity of inhibitors in support the clinical value of IL-17A/F suppression.
On Oct. 18, shortly after the EADV meeting concluded, the Food and Drug Administration approved bimekizumab for treating moderate to severe plaque psoriasis, the first approved indication in the United States. In the European Union, it was approved for psoriasis in 2021, and for psoriatic arthritis and ankylosing spondylitis in June 2023.
Dr. Kirby has financial relationships with more than 10 pharmaceutical companies, including MoonLake, which is developing sonelokimab and sponsored the MIRA trial. Dr. Christos, president of the European HS Foundation, has financial relationships with multiple pharmaceutical companies, including UCB, which makes bimekizumab and provided funding for the BE HEARD I and II trials.
BERLIN – In separate trials conducted in patients with hidradenitis suppurativa (HS), two biologics that inhibit the activity of interleukin-17A (IL-17A) and IL-17F were associated with highly encouraging rates of control.
One of the trials evaluated a nanobody inhibitor, sonelokimab, a molecule with a substantially smaller size than traditional monoclonal antibodies (40 kilodaltons vs. 150 kilodaltons). After 24 weeks of treatment, the most effective of the two study doses almost doubled the proportion of patients with complete resolution of draining tunnels (41.1% vs. 23.8%; P < .05) relative to placebo.
“I think the size of sonelokimab is important,” Brian Kirby, MD, a consultant dermatologist at St. Vincent’s Hospital, Dublin, said at the annual congress of the European Academy of Dermatology and Venereology. “We think the smaller size results in better penetration of inflamed tissue,” he added, noting that penetration of abscesses, fistulae, and tunnels has been recognized in the past as a potential weakness of the larger monoclonal antibodies.
The other set of anti-17-A/F set of data were generated by a pooled 48-week maintenance from the BE HEARD I and II trials with bimekizumab. The 16-week data from these two trials were presented at the annual meeting of the American Academy of Dermatology earlier this year.
IL-17A/F trials
Both the
In the sonelokimab trial, called MIRA, 234 adults with HS were randomized in a 2:2:2:1 ratio to one of the two experimental arms, placebo, or a reference arm with the tumor necrosis factor (TNF) inhibitor adalimumab. Nearly 64% had Hurley stage II HS.
The primary endpoint was a 75% or greater reduction in total abscesses and nodules with no increase in draining tunnel count (HiSCR75) from baseline. Dr. Kirby said that this is more rigorous than the HiSCR50 endpoint more commonly used in HS clinical trials. Treatments were administered every 2 weeks for the first 8 weeks of a planned follow-up of 24 weeks and then every 4 weeks thereafter.
At 16 weeks, according to the data Dr. Kirby presented, both doses of sonelokimab were more active than placebo, but Dr. Kirby reported that the lower dose performed better for most objective endpoints.
For example, the HiSCR75 was reached by 43.3% of those randomized to the 120-mg dose (P < .001 vs. placebo), 34.8% of those randomized to the 240-mg dose (P <.01), and 14.7% of those randomized to placebo.
For HiSCR50, response rates were 65.7%, 53.0%, and 27.9%, for the 120-mg, 240-mg, and placebo arms, respectively. Again, both the lower dose (P < .001) and the higher dose (P < .01) were significantly superior to placebo.
On the International Hidradenitis Suppurativa Severity Score System (IHS4), which counts nodules and abscesses, score reductions were 19.3, 14.5, and 7.9 for the lower dose, higher dose, and placebo, respectively, with a greater statistical advantage for the lower relative to the higher dose over placebo (P <.001 vs. P <.01).
However, patient-focused outcomes were not necessarily greater for the lower dose. For the patient-completed measure, the Numerical Rating Scale 50% reduction in skin pain (NRS50), the proportion of patients responding at 12 weeks was numerically greater for the 240-mg dose (41.3%) than with the 120-mg dose (32.0%), although both reached the same statistical advantage (P < .001) over the 4.3% who reached this level of response on placebo.
For the Dermatology Life Quality Index (DLQI) and the Patient Global Impression of Severity (PGI-S), improvements from baseline were similar for the lower and higher dose, although there was a modest numerical and statistical advantage for the higher dose over placebo (P < .001 vs. P <.01).
The HiSCR50 (57.6%) and HiSCR75 (36.4%) responses were both lower for those randomized to the TNF inhibitor adalimumab relative to sonelokimab, but the smaller number of patients in this arm prohibited a statistical comparison.
Although oral candidiasis was more common among patients receiving either dose of sonelokimab than placebo, these were of mild to moderate severity. Dr. Kirby said that there were no unexpected safety issues, and sonelokimab was generally well tolerated.
The results are encouraging, but Dr. Kirby acknowledged that data are now needed to confirm that resolution of tunnels and fistulae is greater with a nanobody inhibitor of IL-17A/F than other targeted therapies. Even if this is validated, he said studies are needed to prove that the small relative molecule size is the reason behind the benefits.
Forty-eight–week bimekizumab data
From the pooled BE HEARD I and BE HEARD II maintenance data, the major message is that the robust responses observed at 16 weeks versus placebo were maintained at 48 weeks. More than 75% of patients retained a HiSCR50 response and more than 55% achieved a HiSCR75 response at the 48-week follow-up. The durable response was also reflected in other measures, according to Christos C. Zouboulis, MD, PhD, director of the department of dermatology, Brandenburg Medical School, Neuruppin, Germany.
“Improvements in disease severity were seen over time,” Dr. Zouboulis reported. “The majority of patients with severe HS at baseline shifted to mild to moderate disease according to the IHS4 classification.”
To the degree that both sonelokimab and bimekizumab target IL-17A/F, these data are mutually reinforcing. Dr. Kirby said that there is a sizable body of data implicating IL-17A/F in driving HS, and the activity of inhibitors in support the clinical value of IL-17A/F suppression.
On Oct. 18, shortly after the EADV meeting concluded, the Food and Drug Administration approved bimekizumab for treating moderate to severe plaque psoriasis, the first approved indication in the United States. In the European Union, it was approved for psoriasis in 2021, and for psoriatic arthritis and ankylosing spondylitis in June 2023.
Dr. Kirby has financial relationships with more than 10 pharmaceutical companies, including MoonLake, which is developing sonelokimab and sponsored the MIRA trial. Dr. Christos, president of the European HS Foundation, has financial relationships with multiple pharmaceutical companies, including UCB, which makes bimekizumab and provided funding for the BE HEARD I and II trials.
AT THE EADV CONGRESS
Parent concerns a factor when treating eczema in children with darker skin types
NEW YORK –
Skin diseases pose a greater risk of both hyper- and hypopigmentation in patients with darker skin types, but the fear and concern that this raises for permanent disfigurement is not limited to Blacks, Dr. Heath, assistant professor of pediatric dermatology at Temple University, Philadelphia, said at the Skin of Color Update 2023.
“Culturally, pigmentation changes can be huge. For people of Indian descent, for example, pigmentary changes like light spots on the skin might be an obstacle to marriage, so it can really be life changing,” she added.
In patients with darker skin tones presenting with an inflammatory skin disease, such as AD or psoriasis, Dr. Heath advised asking specifically about change in skin tone even if it is not readily apparent. In pediatric patients, it is also appropriate to include parents in this conversation.
Consider the parent’s perspective
“When you are taking care of a child or adolescent, the patient is likely to be concerned about changes in pigmentation, but it is important to remember that the adult in the room might have had their own journey with brown skin and has dealt with the burden of pigment changes,” Dr. Heath said.
For the parent, the pigmentation changes, rather than the inflammation, might be the governing issue and the reason that he or she brought the child to the clinician. Dr. Heath suggested that it is important for caregivers to explicitly recognize their concern, explain that addressing the pigmentary changes is part of the treatment plan, and to create realistic expectations about how long pigmentary changes will take to resolve.
As an example, Dr. Heath recounted a difficult case of a Black infant with disseminated hyperpigmentation and features that did not preclude pathology other than AD. Dr. Heath created a multifaceted treatment plan to address the inflammation in distinct areas of the body that included low-strength topical steroids for the face, stronger steroids for the body, and advice on scalp and skin care.
“I thought this was a great treatment plan out of the gate – I was covering all of the things on my differential list – I thought that the mom would be thinking, this doctor is amazing,” Dr. Heath said.
Pigmentary changes are a priority
However, that was not what the patient’s mother was thinking. Having failed to explicitly recognize her concern about the pigmentation changes and how the treatment would address this issue, the mother was disappointed.
“She had one question: Will my baby ever be one color? That was her main concern,” said Dr. Heath, indicating that other clinicians seeing inflammatory diseases in children with darker skin types can learn from her experience.
“Really, you have to acknowledge that the condition you are treating is causing the pigmentation change, and we do see that and that we have a treatment plan in place,” she said.
Because of differences in how inflammatory skin diseases present in darker skin types, there is plenty of room for a delayed diagnosis for clinicians who do not see many of these patients, according to Dr. Heath. Follicular eczema, which is common in skin of color, often presents with pruritus but differences in the appearance of the underlying disease can threaten a delay in diagnosis.
In cases of follicular eczema with itch in darker skin, the bumps look and feel like goose bumps, which “means that the eczema is really active and inflamed,” Dr. Heath said. When the skin becomes smooth and the itch dissipates, “you know that they are under great control.”
Psoriasis is often missed in children with darker skin types based on the misperception that it is rare. Although it is true that it is less common in Blacks than Whites, it is not rare, according to Dr. Heath. In inspecting the telltale erythematous plaque–like lesions, clinicians might start to consider alternative diagnoses when they do not detect the same erythematous appearance, but the reddish tone is often concealed in darker skin.
She said that predominant involvement in the head and neck and diaper area is often more common in children of color and that nail or scalp involvement, when present, is often a clue that psoriasis is the diagnosis.
Again, because many clinicians do not think immediately of psoriasis in darker skin children with lesions in the scalp, Dr. Heath advised this is another reason to include psoriasis in the differential diagnosis.
“If you have a child that has failed multiple courses of treatment for tinea capitis and they have well-demarcated plaques, it’s time to really start to think about pediatric psoriasis,” she said.
Restoring skin tone can be the priority
Asked to comment on Dr. Heath’s advice about the importance of acknowledging pigmentary changes associated with inflammatory skin diseases in patients of color, Jenna Lester, MD, the founding director of the Skin of Color Clinic at the University of California, San Francisco, called it an “often unspoken concern of patients.”
“Pigmentary changes that occur secondary to an inflammatory condition should be addressed and treated alongside the inciting condition,” she agreed.
Even if changes in skin color or skin tone are not a specific complaint of the patients, Dr. Lester also urged clinicians to raise the topic. If change in skin pigmentation is part of the clinical picture, this should be targeted in the treatment plan.
“In acne, for example, often times I find that patients are as worried about postinflammatory hyperpigmentation as they are about their acne,” she said, reiterating the advice provided by Dr. Heath.
Dr. Heath has financial relationships with Arcutis, Janssen, Johnson & Johnson, Lilly, and Regeneron. Dr. Lester reported no potential conflicts of interest.
NEW YORK –
Skin diseases pose a greater risk of both hyper- and hypopigmentation in patients with darker skin types, but the fear and concern that this raises for permanent disfigurement is not limited to Blacks, Dr. Heath, assistant professor of pediatric dermatology at Temple University, Philadelphia, said at the Skin of Color Update 2023.
“Culturally, pigmentation changes can be huge. For people of Indian descent, for example, pigmentary changes like light spots on the skin might be an obstacle to marriage, so it can really be life changing,” she added.
In patients with darker skin tones presenting with an inflammatory skin disease, such as AD or psoriasis, Dr. Heath advised asking specifically about change in skin tone even if it is not readily apparent. In pediatric patients, it is also appropriate to include parents in this conversation.
Consider the parent’s perspective
“When you are taking care of a child or adolescent, the patient is likely to be concerned about changes in pigmentation, but it is important to remember that the adult in the room might have had their own journey with brown skin and has dealt with the burden of pigment changes,” Dr. Heath said.
For the parent, the pigmentation changes, rather than the inflammation, might be the governing issue and the reason that he or she brought the child to the clinician. Dr. Heath suggested that it is important for caregivers to explicitly recognize their concern, explain that addressing the pigmentary changes is part of the treatment plan, and to create realistic expectations about how long pigmentary changes will take to resolve.
As an example, Dr. Heath recounted a difficult case of a Black infant with disseminated hyperpigmentation and features that did not preclude pathology other than AD. Dr. Heath created a multifaceted treatment plan to address the inflammation in distinct areas of the body that included low-strength topical steroids for the face, stronger steroids for the body, and advice on scalp and skin care.
“I thought this was a great treatment plan out of the gate – I was covering all of the things on my differential list – I thought that the mom would be thinking, this doctor is amazing,” Dr. Heath said.
Pigmentary changes are a priority
However, that was not what the patient’s mother was thinking. Having failed to explicitly recognize her concern about the pigmentation changes and how the treatment would address this issue, the mother was disappointed.
“She had one question: Will my baby ever be one color? That was her main concern,” said Dr. Heath, indicating that other clinicians seeing inflammatory diseases in children with darker skin types can learn from her experience.
“Really, you have to acknowledge that the condition you are treating is causing the pigmentation change, and we do see that and that we have a treatment plan in place,” she said.
Because of differences in how inflammatory skin diseases present in darker skin types, there is plenty of room for a delayed diagnosis for clinicians who do not see many of these patients, according to Dr. Heath. Follicular eczema, which is common in skin of color, often presents with pruritus but differences in the appearance of the underlying disease can threaten a delay in diagnosis.
In cases of follicular eczema with itch in darker skin, the bumps look and feel like goose bumps, which “means that the eczema is really active and inflamed,” Dr. Heath said. When the skin becomes smooth and the itch dissipates, “you know that they are under great control.”
Psoriasis is often missed in children with darker skin types based on the misperception that it is rare. Although it is true that it is less common in Blacks than Whites, it is not rare, according to Dr. Heath. In inspecting the telltale erythematous plaque–like lesions, clinicians might start to consider alternative diagnoses when they do not detect the same erythematous appearance, but the reddish tone is often concealed in darker skin.
She said that predominant involvement in the head and neck and diaper area is often more common in children of color and that nail or scalp involvement, when present, is often a clue that psoriasis is the diagnosis.
Again, because many clinicians do not think immediately of psoriasis in darker skin children with lesions in the scalp, Dr. Heath advised this is another reason to include psoriasis in the differential diagnosis.
“If you have a child that has failed multiple courses of treatment for tinea capitis and they have well-demarcated plaques, it’s time to really start to think about pediatric psoriasis,” she said.
Restoring skin tone can be the priority
Asked to comment on Dr. Heath’s advice about the importance of acknowledging pigmentary changes associated with inflammatory skin diseases in patients of color, Jenna Lester, MD, the founding director of the Skin of Color Clinic at the University of California, San Francisco, called it an “often unspoken concern of patients.”
“Pigmentary changes that occur secondary to an inflammatory condition should be addressed and treated alongside the inciting condition,” she agreed.
Even if changes in skin color or skin tone are not a specific complaint of the patients, Dr. Lester also urged clinicians to raise the topic. If change in skin pigmentation is part of the clinical picture, this should be targeted in the treatment plan.
“In acne, for example, often times I find that patients are as worried about postinflammatory hyperpigmentation as they are about their acne,” she said, reiterating the advice provided by Dr. Heath.
Dr. Heath has financial relationships with Arcutis, Janssen, Johnson & Johnson, Lilly, and Regeneron. Dr. Lester reported no potential conflicts of interest.
NEW YORK –
Skin diseases pose a greater risk of both hyper- and hypopigmentation in patients with darker skin types, but the fear and concern that this raises for permanent disfigurement is not limited to Blacks, Dr. Heath, assistant professor of pediatric dermatology at Temple University, Philadelphia, said at the Skin of Color Update 2023.
“Culturally, pigmentation changes can be huge. For people of Indian descent, for example, pigmentary changes like light spots on the skin might be an obstacle to marriage, so it can really be life changing,” she added.
In patients with darker skin tones presenting with an inflammatory skin disease, such as AD or psoriasis, Dr. Heath advised asking specifically about change in skin tone even if it is not readily apparent. In pediatric patients, it is also appropriate to include parents in this conversation.
Consider the parent’s perspective
“When you are taking care of a child or adolescent, the patient is likely to be concerned about changes in pigmentation, but it is important to remember that the adult in the room might have had their own journey with brown skin and has dealt with the burden of pigment changes,” Dr. Heath said.
For the parent, the pigmentation changes, rather than the inflammation, might be the governing issue and the reason that he or she brought the child to the clinician. Dr. Heath suggested that it is important for caregivers to explicitly recognize their concern, explain that addressing the pigmentary changes is part of the treatment plan, and to create realistic expectations about how long pigmentary changes will take to resolve.
As an example, Dr. Heath recounted a difficult case of a Black infant with disseminated hyperpigmentation and features that did not preclude pathology other than AD. Dr. Heath created a multifaceted treatment plan to address the inflammation in distinct areas of the body that included low-strength topical steroids for the face, stronger steroids for the body, and advice on scalp and skin care.
“I thought this was a great treatment plan out of the gate – I was covering all of the things on my differential list – I thought that the mom would be thinking, this doctor is amazing,” Dr. Heath said.
Pigmentary changes are a priority
However, that was not what the patient’s mother was thinking. Having failed to explicitly recognize her concern about the pigmentation changes and how the treatment would address this issue, the mother was disappointed.
“She had one question: Will my baby ever be one color? That was her main concern,” said Dr. Heath, indicating that other clinicians seeing inflammatory diseases in children with darker skin types can learn from her experience.
“Really, you have to acknowledge that the condition you are treating is causing the pigmentation change, and we do see that and that we have a treatment plan in place,” she said.
Because of differences in how inflammatory skin diseases present in darker skin types, there is plenty of room for a delayed diagnosis for clinicians who do not see many of these patients, according to Dr. Heath. Follicular eczema, which is common in skin of color, often presents with pruritus but differences in the appearance of the underlying disease can threaten a delay in diagnosis.
In cases of follicular eczema with itch in darker skin, the bumps look and feel like goose bumps, which “means that the eczema is really active and inflamed,” Dr. Heath said. When the skin becomes smooth and the itch dissipates, “you know that they are under great control.”
Psoriasis is often missed in children with darker skin types based on the misperception that it is rare. Although it is true that it is less common in Blacks than Whites, it is not rare, according to Dr. Heath. In inspecting the telltale erythematous plaque–like lesions, clinicians might start to consider alternative diagnoses when they do not detect the same erythematous appearance, but the reddish tone is often concealed in darker skin.
She said that predominant involvement in the head and neck and diaper area is often more common in children of color and that nail or scalp involvement, when present, is often a clue that psoriasis is the diagnosis.
Again, because many clinicians do not think immediately of psoriasis in darker skin children with lesions in the scalp, Dr. Heath advised this is another reason to include psoriasis in the differential diagnosis.
“If you have a child that has failed multiple courses of treatment for tinea capitis and they have well-demarcated plaques, it’s time to really start to think about pediatric psoriasis,” she said.
Restoring skin tone can be the priority
Asked to comment on Dr. Heath’s advice about the importance of acknowledging pigmentary changes associated with inflammatory skin diseases in patients of color, Jenna Lester, MD, the founding director of the Skin of Color Clinic at the University of California, San Francisco, called it an “often unspoken concern of patients.”
“Pigmentary changes that occur secondary to an inflammatory condition should be addressed and treated alongside the inciting condition,” she agreed.
Even if changes in skin color or skin tone are not a specific complaint of the patients, Dr. Lester also urged clinicians to raise the topic. If change in skin pigmentation is part of the clinical picture, this should be targeted in the treatment plan.
“In acne, for example, often times I find that patients are as worried about postinflammatory hyperpigmentation as they are about their acne,” she said, reiterating the advice provided by Dr. Heath.
Dr. Heath has financial relationships with Arcutis, Janssen, Johnson & Johnson, Lilly, and Regeneron. Dr. Lester reported no potential conflicts of interest.
AT SOC 2023
Bilateral facial swelling
The patient was given a diagnosis of sialadenosis (also known as sialosis), a noninflammatory, non-neoplastic enlargement of the parotid glands. It can often manifest as fatty degeneration of the parotid glands, which may be associated with underlying conditions such as hypertriglyceridemia, diabetes, and metabolic syndrome.1-3
Ultrasonography and a subsequent computed tomography with contrast demonstrated fatty hypertrophy of the parotid glands without any concerning parotid mass or enlarged cervical lymph nodes. No abnormalities of the ductal system (eg, stricture or obstruction with stone) were noted, so sialography and sialendoscopy were not indicated.
Evaluation for inflammatory, autoimmune, and granulomatous diseases was negative, including negative anti-Ro/SSA and anti-La/SSB antibodies and negative HIV screen. However, our patient had an elevated serum triglyceride level of 589 mg/dL (reference range, < 150 mg/dL), while serum total cholesterol was within the reference range (< 200 mg/dL). (Interestingly, his triglycerides were normal a year earlier.) The patient’s A1c level was normal.
The differential diagnosis for this patient included Sjögren syndrome, abscess, viral infection (eg, mumps, HIV sialopathy), Kimura disease, sarcoidosis, masseter hypertrophy, and tumors of the parotid gland (eg, Warthin tumor and pleomorphic adenoma). Drug-induced sialadenitis was another possibility, as several drugs may be associated with salivary gland enlargement.4 However, no association was found for our patient.
Primary management is focused on treating the underlying disorder. The application of heat, massage, and sialagogues (eg, pilocarpine 5 mg orally tid) can be used to stimulate salivation, which may help reduce the swelling. Bilateral parotid gland swelling in patients with increased triglyceride levels often resolves after treatment of hypertriglyceridemia.3,5 Less common modalities include botulinum neurotoxin injection, tympanic neurectomy, and parotidectomy.6
The treatment plan for this patient included aggressive dietary modification and increasing his current dosage of atorvastatin from 20 mg to 80 mg at bedtime. Increasing the dosage of statin was preferred over adding another agent (such as fibrates) to decrease the risk of myopathy. Fine-needle aspiration biopsy may be considered if the swelling does not resolve after correction of lipid abnormalities, which can take between 6 months and 3 years.3
Photo courtesy of Faryal Tahir, MD. Text courtesy of Faryal Tahir, MD, Assistant Professor, and Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University, Homer Stryker, MD School of Medicine, Kalamazoo.
1. Garcia DS, Bussoloti Filho I. Fat deposition of parotid glands. Braz J Otorhinolaryngol. 2013;79:173-176
2. Hida A, Akahoshi M, Takagi Y, et al. Lipid infiltration in the parotid glands: a clinical manifestation of metabolic syndrome. Exp Clin Endocrinol Diabetes. 2012;120:110-115. doi: 10.1055/s-0031-1291315
3. Sheikh JS, Sharma M, Kunath A, et al. Reversible parotid enlargement and pseudo-Sjögren's syndrome secondary to hypertriglyceridemia. J Rheumatol. 1996;23:1288-1291
4. Vinayak V, Annigeri RG, Patel HA, et al. Adverse effects of drugs on saliva and salivary glands. J Orofac Sci. 2013;5:15-20. doi: 10.4103/0975-8844.113684
5. Kaltreider HB, Talal N. Bilateral parotid gland enlargement and hyperlipoproteinemia. JAMA. 1969;210:2067-2070. doi:10.1001/jama.1969.03160370051010
6. Davis AB, Hoffman HT. Management options for sialadenosis. Otolaryngol Clin North Am. 2021;54:605-611. doi: 10.1016/j.otc.2021.02.005
The patient was given a diagnosis of sialadenosis (also known as sialosis), a noninflammatory, non-neoplastic enlargement of the parotid glands. It can often manifest as fatty degeneration of the parotid glands, which may be associated with underlying conditions such as hypertriglyceridemia, diabetes, and metabolic syndrome.1-3
Ultrasonography and a subsequent computed tomography with contrast demonstrated fatty hypertrophy of the parotid glands without any concerning parotid mass or enlarged cervical lymph nodes. No abnormalities of the ductal system (eg, stricture or obstruction with stone) were noted, so sialography and sialendoscopy were not indicated.
Evaluation for inflammatory, autoimmune, and granulomatous diseases was negative, including negative anti-Ro/SSA and anti-La/SSB antibodies and negative HIV screen. However, our patient had an elevated serum triglyceride level of 589 mg/dL (reference range, < 150 mg/dL), while serum total cholesterol was within the reference range (< 200 mg/dL). (Interestingly, his triglycerides were normal a year earlier.) The patient’s A1c level was normal.
The differential diagnosis for this patient included Sjögren syndrome, abscess, viral infection (eg, mumps, HIV sialopathy), Kimura disease, sarcoidosis, masseter hypertrophy, and tumors of the parotid gland (eg, Warthin tumor and pleomorphic adenoma). Drug-induced sialadenitis was another possibility, as several drugs may be associated with salivary gland enlargement.4 However, no association was found for our patient.
Primary management is focused on treating the underlying disorder. The application of heat, massage, and sialagogues (eg, pilocarpine 5 mg orally tid) can be used to stimulate salivation, which may help reduce the swelling. Bilateral parotid gland swelling in patients with increased triglyceride levels often resolves after treatment of hypertriglyceridemia.3,5 Less common modalities include botulinum neurotoxin injection, tympanic neurectomy, and parotidectomy.6
The treatment plan for this patient included aggressive dietary modification and increasing his current dosage of atorvastatin from 20 mg to 80 mg at bedtime. Increasing the dosage of statin was preferred over adding another agent (such as fibrates) to decrease the risk of myopathy. Fine-needle aspiration biopsy may be considered if the swelling does not resolve after correction of lipid abnormalities, which can take between 6 months and 3 years.3
Photo courtesy of Faryal Tahir, MD. Text courtesy of Faryal Tahir, MD, Assistant Professor, and Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University, Homer Stryker, MD School of Medicine, Kalamazoo.
The patient was given a diagnosis of sialadenosis (also known as sialosis), a noninflammatory, non-neoplastic enlargement of the parotid glands. It can often manifest as fatty degeneration of the parotid glands, which may be associated with underlying conditions such as hypertriglyceridemia, diabetes, and metabolic syndrome.1-3
Ultrasonography and a subsequent computed tomography with contrast demonstrated fatty hypertrophy of the parotid glands without any concerning parotid mass or enlarged cervical lymph nodes. No abnormalities of the ductal system (eg, stricture or obstruction with stone) were noted, so sialography and sialendoscopy were not indicated.
Evaluation for inflammatory, autoimmune, and granulomatous diseases was negative, including negative anti-Ro/SSA and anti-La/SSB antibodies and negative HIV screen. However, our patient had an elevated serum triglyceride level of 589 mg/dL (reference range, < 150 mg/dL), while serum total cholesterol was within the reference range (< 200 mg/dL). (Interestingly, his triglycerides were normal a year earlier.) The patient’s A1c level was normal.
The differential diagnosis for this patient included Sjögren syndrome, abscess, viral infection (eg, mumps, HIV sialopathy), Kimura disease, sarcoidosis, masseter hypertrophy, and tumors of the parotid gland (eg, Warthin tumor and pleomorphic adenoma). Drug-induced sialadenitis was another possibility, as several drugs may be associated with salivary gland enlargement.4 However, no association was found for our patient.
Primary management is focused on treating the underlying disorder. The application of heat, massage, and sialagogues (eg, pilocarpine 5 mg orally tid) can be used to stimulate salivation, which may help reduce the swelling. Bilateral parotid gland swelling in patients with increased triglyceride levels often resolves after treatment of hypertriglyceridemia.3,5 Less common modalities include botulinum neurotoxin injection, tympanic neurectomy, and parotidectomy.6
The treatment plan for this patient included aggressive dietary modification and increasing his current dosage of atorvastatin from 20 mg to 80 mg at bedtime. Increasing the dosage of statin was preferred over adding another agent (such as fibrates) to decrease the risk of myopathy. Fine-needle aspiration biopsy may be considered if the swelling does not resolve after correction of lipid abnormalities, which can take between 6 months and 3 years.3
Photo courtesy of Faryal Tahir, MD. Text courtesy of Faryal Tahir, MD, Assistant Professor, and Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University, Homer Stryker, MD School of Medicine, Kalamazoo.
1. Garcia DS, Bussoloti Filho I. Fat deposition of parotid glands. Braz J Otorhinolaryngol. 2013;79:173-176
2. Hida A, Akahoshi M, Takagi Y, et al. Lipid infiltration in the parotid glands: a clinical manifestation of metabolic syndrome. Exp Clin Endocrinol Diabetes. 2012;120:110-115. doi: 10.1055/s-0031-1291315
3. Sheikh JS, Sharma M, Kunath A, et al. Reversible parotid enlargement and pseudo-Sjögren's syndrome secondary to hypertriglyceridemia. J Rheumatol. 1996;23:1288-1291
4. Vinayak V, Annigeri RG, Patel HA, et al. Adverse effects of drugs on saliva and salivary glands. J Orofac Sci. 2013;5:15-20. doi: 10.4103/0975-8844.113684
5. Kaltreider HB, Talal N. Bilateral parotid gland enlargement and hyperlipoproteinemia. JAMA. 1969;210:2067-2070. doi:10.1001/jama.1969.03160370051010
6. Davis AB, Hoffman HT. Management options for sialadenosis. Otolaryngol Clin North Am. 2021;54:605-611. doi: 10.1016/j.otc.2021.02.005
1. Garcia DS, Bussoloti Filho I. Fat deposition of parotid glands. Braz J Otorhinolaryngol. 2013;79:173-176
2. Hida A, Akahoshi M, Takagi Y, et al. Lipid infiltration in the parotid glands: a clinical manifestation of metabolic syndrome. Exp Clin Endocrinol Diabetes. 2012;120:110-115. doi: 10.1055/s-0031-1291315
3. Sheikh JS, Sharma M, Kunath A, et al. Reversible parotid enlargement and pseudo-Sjögren's syndrome secondary to hypertriglyceridemia. J Rheumatol. 1996;23:1288-1291
4. Vinayak V, Annigeri RG, Patel HA, et al. Adverse effects of drugs on saliva and salivary glands. J Orofac Sci. 2013;5:15-20. doi: 10.4103/0975-8844.113684
5. Kaltreider HB, Talal N. Bilateral parotid gland enlargement and hyperlipoproteinemia. JAMA. 1969;210:2067-2070. doi:10.1001/jama.1969.03160370051010
6. Davis AB, Hoffman HT. Management options for sialadenosis. Otolaryngol Clin North Am. 2021;54:605-611. doi: 10.1016/j.otc.2021.02.005
Lebrikizumab gets European nod for treating moderate-to-severe atopic dermatitis
The , according to a press release from the manufacturer.
Lebrikizumab, which selectively targets interleukin-13 and inhibits its signaling pathway, will first be available in Germany, with a rollout in other European countries expected through 2024, according to Almirall, the manufacturer.
The European approval of lebrikizumab (Ebglyss) was based on data from a trio of pivotal phase 3 studies including ADvocate1 and ADvocate2, which evaluated lebrikizumab as monotherapy, and ADhere, which evaluated lebrikizumab in combination with topical corticosteroids. All three trials included adult and adolescent patients aged 12 years and older with moderate-to-severe AD.
In the two ADvocate studies, published in the New England Journal of Medicine, participants were randomized to a 250-mg injection of lebrikizumab or placebo every 2 weeks. The primary outcome was a score of clear or almost clear skin based on the Investigator’s Global Assessment with at least a 2-point reduction from baseline to 16 weeks.
Compared with placebo, lebrikizumab showed significant clinical efficacy in both studies. In study 1, 43.1% of 283 patients treated with lebrikizumab versus 12.7% of 141 patients on placebo met the primary endpoint (P < .001), as did 33.2% of the 281 patients on lebrikizumab and 10.8% of 146 patients on placebo in study 2 (P < .001). In addition, 58.8% and 52.1% of patients on lebrikizumab in studies 1 and 2, respectively, met the secondary endpoint of a 75% reduction in the Eczema Area and Severity Index score (EASI-75), versus 16.2% and 18.1% of patients on placebo in study 1 and 2, respectively (P < .001 for both).
In the ADhere study, published in JAMA Dermatology, 41.2% of patients receiving a lebrikizumab/corticosteroid combination and 22.1% of those randomized to a placebo/corticosteroid combination met the primary endpoint of IGA scores of 0 or 1 at 16 weeks, and nearly 70% patients treated with a combination of lebrikizumab and topical corticosteroids achieved EASI-75, compared with 42% of those on the combination.
Nearly 80% of patients who responded at 16 weeks and continued treatment with lebrikizumab as monotherapy or combination therapy showed sustained results up to 52 weeks with maintenance monthly dosing, according to the Almirall press release.
Most adverse events across the studies were mild or moderate and were not associated with treatment discontinuation. The most common adverse reactions were conjunctivitis, injection site reactions, allergic conjunctivitis, and dry eye.
Further research has shown showed clinical efficacy and safety in patients who used lebrikizumab for up to 2 years, either as monotherapy or in combination with topical corticosteroids, according to the manufacturer.
Lebrikizumab remains under review in the United States after the Food and Drug Administration issued a complete response letter in October regarding findings made during an inspection of a third-party contract manufacturer that included the “monoclonal antibody drug substance” for lebrikizumab, although no concerns about clinical data or safety were raised, Eli Lilly announced in October. Eli Lilly has the rights to develop lebrikizumab in the United States and the rest of the world excluding Europe.
The , according to a press release from the manufacturer.
Lebrikizumab, which selectively targets interleukin-13 and inhibits its signaling pathway, will first be available in Germany, with a rollout in other European countries expected through 2024, according to Almirall, the manufacturer.
The European approval of lebrikizumab (Ebglyss) was based on data from a trio of pivotal phase 3 studies including ADvocate1 and ADvocate2, which evaluated lebrikizumab as monotherapy, and ADhere, which evaluated lebrikizumab in combination with topical corticosteroids. All three trials included adult and adolescent patients aged 12 years and older with moderate-to-severe AD.
In the two ADvocate studies, published in the New England Journal of Medicine, participants were randomized to a 250-mg injection of lebrikizumab or placebo every 2 weeks. The primary outcome was a score of clear or almost clear skin based on the Investigator’s Global Assessment with at least a 2-point reduction from baseline to 16 weeks.
Compared with placebo, lebrikizumab showed significant clinical efficacy in both studies. In study 1, 43.1% of 283 patients treated with lebrikizumab versus 12.7% of 141 patients on placebo met the primary endpoint (P < .001), as did 33.2% of the 281 patients on lebrikizumab and 10.8% of 146 patients on placebo in study 2 (P < .001). In addition, 58.8% and 52.1% of patients on lebrikizumab in studies 1 and 2, respectively, met the secondary endpoint of a 75% reduction in the Eczema Area and Severity Index score (EASI-75), versus 16.2% and 18.1% of patients on placebo in study 1 and 2, respectively (P < .001 for both).
In the ADhere study, published in JAMA Dermatology, 41.2% of patients receiving a lebrikizumab/corticosteroid combination and 22.1% of those randomized to a placebo/corticosteroid combination met the primary endpoint of IGA scores of 0 or 1 at 16 weeks, and nearly 70% patients treated with a combination of lebrikizumab and topical corticosteroids achieved EASI-75, compared with 42% of those on the combination.
Nearly 80% of patients who responded at 16 weeks and continued treatment with lebrikizumab as monotherapy or combination therapy showed sustained results up to 52 weeks with maintenance monthly dosing, according to the Almirall press release.
Most adverse events across the studies were mild or moderate and were not associated with treatment discontinuation. The most common adverse reactions were conjunctivitis, injection site reactions, allergic conjunctivitis, and dry eye.
Further research has shown showed clinical efficacy and safety in patients who used lebrikizumab for up to 2 years, either as monotherapy or in combination with topical corticosteroids, according to the manufacturer.
Lebrikizumab remains under review in the United States after the Food and Drug Administration issued a complete response letter in October regarding findings made during an inspection of a third-party contract manufacturer that included the “monoclonal antibody drug substance” for lebrikizumab, although no concerns about clinical data or safety were raised, Eli Lilly announced in October. Eli Lilly has the rights to develop lebrikizumab in the United States and the rest of the world excluding Europe.
The , according to a press release from the manufacturer.
Lebrikizumab, which selectively targets interleukin-13 and inhibits its signaling pathway, will first be available in Germany, with a rollout in other European countries expected through 2024, according to Almirall, the manufacturer.
The European approval of lebrikizumab (Ebglyss) was based on data from a trio of pivotal phase 3 studies including ADvocate1 and ADvocate2, which evaluated lebrikizumab as monotherapy, and ADhere, which evaluated lebrikizumab in combination with topical corticosteroids. All three trials included adult and adolescent patients aged 12 years and older with moderate-to-severe AD.
In the two ADvocate studies, published in the New England Journal of Medicine, participants were randomized to a 250-mg injection of lebrikizumab or placebo every 2 weeks. The primary outcome was a score of clear or almost clear skin based on the Investigator’s Global Assessment with at least a 2-point reduction from baseline to 16 weeks.
Compared with placebo, lebrikizumab showed significant clinical efficacy in both studies. In study 1, 43.1% of 283 patients treated with lebrikizumab versus 12.7% of 141 patients on placebo met the primary endpoint (P < .001), as did 33.2% of the 281 patients on lebrikizumab and 10.8% of 146 patients on placebo in study 2 (P < .001). In addition, 58.8% and 52.1% of patients on lebrikizumab in studies 1 and 2, respectively, met the secondary endpoint of a 75% reduction in the Eczema Area and Severity Index score (EASI-75), versus 16.2% and 18.1% of patients on placebo in study 1 and 2, respectively (P < .001 for both).
In the ADhere study, published in JAMA Dermatology, 41.2% of patients receiving a lebrikizumab/corticosteroid combination and 22.1% of those randomized to a placebo/corticosteroid combination met the primary endpoint of IGA scores of 0 or 1 at 16 weeks, and nearly 70% patients treated with a combination of lebrikizumab and topical corticosteroids achieved EASI-75, compared with 42% of those on the combination.
Nearly 80% of patients who responded at 16 weeks and continued treatment with lebrikizumab as monotherapy or combination therapy showed sustained results up to 52 weeks with maintenance monthly dosing, according to the Almirall press release.
Most adverse events across the studies were mild or moderate and were not associated with treatment discontinuation. The most common adverse reactions were conjunctivitis, injection site reactions, allergic conjunctivitis, and dry eye.
Further research has shown showed clinical efficacy and safety in patients who used lebrikizumab for up to 2 years, either as monotherapy or in combination with topical corticosteroids, according to the manufacturer.
Lebrikizumab remains under review in the United States after the Food and Drug Administration issued a complete response letter in October regarding findings made during an inspection of a third-party contract manufacturer that included the “monoclonal antibody drug substance” for lebrikizumab, although no concerns about clinical data or safety were raised, Eli Lilly announced in October. Eli Lilly has the rights to develop lebrikizumab in the United States and the rest of the world excluding Europe.