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Emerging treatments for molluscum contagiosum and acne show promise
, but that could soon change, according to Leon H. Kircik, MD.
“The treatment of molluscum is still an unmet need,” Dr. Kircik, clinical professor of dermatology at the Icahn School of Medicine at Mount Sinai, New York, said at the Orlando Dermatology Aesthetic and Clinical Conference. However, a proprietary drug-device combination of cantharidin 0.7% administered through a single-use precision applicator, which has been tested in phase 3 studies, is currently under FDA review. The manufacturer, Verrica Pharmaceuticals resubmitted a new drug application for the product, VP-102, in December 2020.
“VP-102 features a visualization agent so the injector can see which lesions have been treated, as well as a bittering agent to mitigate oral ingestion by children. Complete clearance at 12 weeks ranged from 46% to 54% of patients, while lesion count reduction compared with baseline ranged from 69% to 82%.”
Acne
In August, 2020, clascoterone 1% cream was approved for the treatment of acne in patients 12 years and older, a development that Dr. Kircik said “can be a game changer in acne treatment.” Clascoterone cream 1% exhibits strong, selective anti-androgen activity by targeting androgen receptors in the skin, not systemically. “It limits or blocks transcription of androgen responsive genes, but it also has an anti-inflammatory effect and an anti-sebum effect,” he explained.
According to results from two phase 3 trials of the product, a response of clear or almost clear on the IGA scale at week 12 was achieved in 18.4% of those on treatment vs. 9% of those on vehicle in one study (P less than .001) and 20.3% vs. 6.5%, respectively, in the second study (P less than .001). Clascoterone is also being evaluated for treating androgenetic alopecia.
In Dr. Kircik’s clinical experience, retinoids can be helpful for patients with moderate to severe acne. “We always use them for anticomedogenic effects, but we also know that they have anti-inflammatory effects,” he said. “They actually inhibit toll-like receptor activity. They also inhibit the AP-1 pathway by causing a reduction in inflammatory signaling associated with collagen degradation and scarring.”
The most recent retinoid to be approved for the topical treatment of acne was 0.005% trifarotene cream, in 2019, for patients aged 9 years and older. “But when we got the results, it was not that exciting,” a difference of about 3.6 (mean) inflammatory lesion reduction between the active and the vehicle arm, said Dr. Kircik, medical director of Physicians Skin Care in Louisville, Ky. “According to the package insert, treatment side effects included mild to moderate erythema in 59% of patients, scaling in 65%, dryness in 69%, and stinging/burning in 56%, which makes it difficult to use in our clinical practice.”
The drug was also tested for treating truncal acne. However, one comparative study showed that tazarotene 0.045% lotion spread an average of 36.7 square centimeters farther than the trifarotene cream, which makes the tazarotene lotion easier to use on the chest and back, he said.
Dr. Kircik also discussed 4% minocycline, a hydrophobic, topical foam formulation of minocycline that was approved by the FDA in 2019 for the treatment of moderate to severe acne, for patients aged 9 and older. In a 12-week study that involved 1,488 patients (mean age was about 20 years), investigators observed a 56% reduction in inflammatory lesion count among those treated with minocycline 4%, compared with 43% in the vehicle group.
Dr. Kircik, one of the authors of the study, noted that the hydrophobic composition of minocycline 4% allows for stable and efficient delivery of an inherently unstable active pharmaceutical ingredient such as minocycline. “It’s free of primary irritants such as surfactants and short chain alcohols, which makes it much more tolerable,” he said. “The unique physical foam characteristics facilitate ease of application and absorption at target sites.”
Dr. Kircik reported that he serves as a consultant and/or adviser to numerous pharmaceutical companies, including Galderma, the manufacturer of trifarotene cream.
dbrunk@mdedge.com
, but that could soon change, according to Leon H. Kircik, MD.
“The treatment of molluscum is still an unmet need,” Dr. Kircik, clinical professor of dermatology at the Icahn School of Medicine at Mount Sinai, New York, said at the Orlando Dermatology Aesthetic and Clinical Conference. However, a proprietary drug-device combination of cantharidin 0.7% administered through a single-use precision applicator, which has been tested in phase 3 studies, is currently under FDA review. The manufacturer, Verrica Pharmaceuticals resubmitted a new drug application for the product, VP-102, in December 2020.
“VP-102 features a visualization agent so the injector can see which lesions have been treated, as well as a bittering agent to mitigate oral ingestion by children. Complete clearance at 12 weeks ranged from 46% to 54% of patients, while lesion count reduction compared with baseline ranged from 69% to 82%.”
Acne
In August, 2020, clascoterone 1% cream was approved for the treatment of acne in patients 12 years and older, a development that Dr. Kircik said “can be a game changer in acne treatment.” Clascoterone cream 1% exhibits strong, selective anti-androgen activity by targeting androgen receptors in the skin, not systemically. “It limits or blocks transcription of androgen responsive genes, but it also has an anti-inflammatory effect and an anti-sebum effect,” he explained.
According to results from two phase 3 trials of the product, a response of clear or almost clear on the IGA scale at week 12 was achieved in 18.4% of those on treatment vs. 9% of those on vehicle in one study (P less than .001) and 20.3% vs. 6.5%, respectively, in the second study (P less than .001). Clascoterone is also being evaluated for treating androgenetic alopecia.
In Dr. Kircik’s clinical experience, retinoids can be helpful for patients with moderate to severe acne. “We always use them for anticomedogenic effects, but we also know that they have anti-inflammatory effects,” he said. “They actually inhibit toll-like receptor activity. They also inhibit the AP-1 pathway by causing a reduction in inflammatory signaling associated with collagen degradation and scarring.”
The most recent retinoid to be approved for the topical treatment of acne was 0.005% trifarotene cream, in 2019, for patients aged 9 years and older. “But when we got the results, it was not that exciting,” a difference of about 3.6 (mean) inflammatory lesion reduction between the active and the vehicle arm, said Dr. Kircik, medical director of Physicians Skin Care in Louisville, Ky. “According to the package insert, treatment side effects included mild to moderate erythema in 59% of patients, scaling in 65%, dryness in 69%, and stinging/burning in 56%, which makes it difficult to use in our clinical practice.”
The drug was also tested for treating truncal acne. However, one comparative study showed that tazarotene 0.045% lotion spread an average of 36.7 square centimeters farther than the trifarotene cream, which makes the tazarotene lotion easier to use on the chest and back, he said.
Dr. Kircik also discussed 4% minocycline, a hydrophobic, topical foam formulation of minocycline that was approved by the FDA in 2019 for the treatment of moderate to severe acne, for patients aged 9 and older. In a 12-week study that involved 1,488 patients (mean age was about 20 years), investigators observed a 56% reduction in inflammatory lesion count among those treated with minocycline 4%, compared with 43% in the vehicle group.
Dr. Kircik, one of the authors of the study, noted that the hydrophobic composition of minocycline 4% allows for stable and efficient delivery of an inherently unstable active pharmaceutical ingredient such as minocycline. “It’s free of primary irritants such as surfactants and short chain alcohols, which makes it much more tolerable,” he said. “The unique physical foam characteristics facilitate ease of application and absorption at target sites.”
Dr. Kircik reported that he serves as a consultant and/or adviser to numerous pharmaceutical companies, including Galderma, the manufacturer of trifarotene cream.
dbrunk@mdedge.com
, but that could soon change, according to Leon H. Kircik, MD.
“The treatment of molluscum is still an unmet need,” Dr. Kircik, clinical professor of dermatology at the Icahn School of Medicine at Mount Sinai, New York, said at the Orlando Dermatology Aesthetic and Clinical Conference. However, a proprietary drug-device combination of cantharidin 0.7% administered through a single-use precision applicator, which has been tested in phase 3 studies, is currently under FDA review. The manufacturer, Verrica Pharmaceuticals resubmitted a new drug application for the product, VP-102, in December 2020.
“VP-102 features a visualization agent so the injector can see which lesions have been treated, as well as a bittering agent to mitigate oral ingestion by children. Complete clearance at 12 weeks ranged from 46% to 54% of patients, while lesion count reduction compared with baseline ranged from 69% to 82%.”
Acne
In August, 2020, clascoterone 1% cream was approved for the treatment of acne in patients 12 years and older, a development that Dr. Kircik said “can be a game changer in acne treatment.” Clascoterone cream 1% exhibits strong, selective anti-androgen activity by targeting androgen receptors in the skin, not systemically. “It limits or blocks transcription of androgen responsive genes, but it also has an anti-inflammatory effect and an anti-sebum effect,” he explained.
According to results from two phase 3 trials of the product, a response of clear or almost clear on the IGA scale at week 12 was achieved in 18.4% of those on treatment vs. 9% of those on vehicle in one study (P less than .001) and 20.3% vs. 6.5%, respectively, in the second study (P less than .001). Clascoterone is also being evaluated for treating androgenetic alopecia.
In Dr. Kircik’s clinical experience, retinoids can be helpful for patients with moderate to severe acne. “We always use them for anticomedogenic effects, but we also know that they have anti-inflammatory effects,” he said. “They actually inhibit toll-like receptor activity. They also inhibit the AP-1 pathway by causing a reduction in inflammatory signaling associated with collagen degradation and scarring.”
The most recent retinoid to be approved for the topical treatment of acne was 0.005% trifarotene cream, in 2019, for patients aged 9 years and older. “But when we got the results, it was not that exciting,” a difference of about 3.6 (mean) inflammatory lesion reduction between the active and the vehicle arm, said Dr. Kircik, medical director of Physicians Skin Care in Louisville, Ky. “According to the package insert, treatment side effects included mild to moderate erythema in 59% of patients, scaling in 65%, dryness in 69%, and stinging/burning in 56%, which makes it difficult to use in our clinical practice.”
The drug was also tested for treating truncal acne. However, one comparative study showed that tazarotene 0.045% lotion spread an average of 36.7 square centimeters farther than the trifarotene cream, which makes the tazarotene lotion easier to use on the chest and back, he said.
Dr. Kircik also discussed 4% minocycline, a hydrophobic, topical foam formulation of minocycline that was approved by the FDA in 2019 for the treatment of moderate to severe acne, for patients aged 9 and older. In a 12-week study that involved 1,488 patients (mean age was about 20 years), investigators observed a 56% reduction in inflammatory lesion count among those treated with minocycline 4%, compared with 43% in the vehicle group.
Dr. Kircik, one of the authors of the study, noted that the hydrophobic composition of minocycline 4% allows for stable and efficient delivery of an inherently unstable active pharmaceutical ingredient such as minocycline. “It’s free of primary irritants such as surfactants and short chain alcohols, which makes it much more tolerable,” he said. “The unique physical foam characteristics facilitate ease of application and absorption at target sites.”
Dr. Kircik reported that he serves as a consultant and/or adviser to numerous pharmaceutical companies, including Galderma, the manufacturer of trifarotene cream.
dbrunk@mdedge.com
FROM ODAC 2021
Cellulitis treatment recommendations
He noticed discomfort today and saw that his left lower leg had redness and was warm. He does not recall scratches or injury to his leg. He has not had fever or chills. He has no other symptoms. His diabetes has been well controlled with diet and metformin.
On exam, his blood pressure is 120/70, pulse is 80, temperature is 37 degrees Celsius.
In the left lower extremity, the patient had 1+ edema at the ankle, with a 14-cm x 20-cm warm, erythematous area just above the ankle and extending proximally.
His labs found an HCT of 44 and a WBC of 12,000. What do you recommend?
A) Vascular duplex exam
B) 1st generation cephalosporin
C) 1st generation cephalosporin + TMP/Sulfa
D) Oral clindamycin
E) IV vancomycin
This patient has cellulitis and should receive a beta lactam antibiotic, which will have the best coverage and lowest minimal inhibitory concentration for the likely organism, beta hemolytic streptococci. Clindamycin would likely work, but it has greater side effects. This patient does not need coverage for methicillin-resistant staphylococcus aureus (MRSA). I know many of you, if not most, know this, but I want to go through relevant data and formal recommendations, because of a recent call I received from a patient.
My patient had a full body rash after receiving cephalexin + TMP/sulfa [trimethoprim-sulfamethoxazole] treatment for cellulitis. In recent years the addition of TMP/sulfa to strep treatment to also cover MRSA has become popular, especially in emergency department and urgent care settings.
Moran and colleagues studied cephalexin + TMP/sulfa vs. cephalexin and placebo in patients with uncomplicated cellulitis.1 The outcome measured was clinical cure, and there was no difference between groups; clinical cure occurred in 182 (83.5%) of 218 participants in the cephalexin plus TMP/sulfa group vs. 165 (85.5%) of 193 in the cephalexin group (difference, −2.0%; 95% confidence interval, −9.7% to 5.7%; P = .50).
Jeng and colleagues studied patients admitted for a cellulitis, and evaluated the patients’ response to beta-lactam antibiotics.2 Patients had acute and convalescent serologies for beta hemolytic strep. Almost all evaluable patients with positive strep studies (97%) responded to beta-lactams, and 21 of 23 (91%) with negative studies responded to beta-lactams (overall response rate 95%). This study was done during a time of high MRSA prevalence.
The most recent Infectious Diseases Society of America guidelines for skin and soft tissue infections, recommend oral penicillin, cephalexin, dicloxacillin, or clindamycin for mild cellulitis, and IV equivalent if patients have moderate cellulitis.3 If abscesses are present, then drainage is recommended and MRSA coverage. Kamath and colleagues reported on how closely guidelines for skin and soft tissue infections were followed.4 In patients with mild cellulitis, only 36% received guideline-suggested antibiotics. The most common antibiotic prescribed that was outside the guidelines was trimethoprim-sulfamethoxazole.
Myth: Cellulitis treatment should include MRSA coverage.
My advice: Stick with beta-lactam antibiotics, unless an abscess is present. There is no need to add MRSA coverage for initial treatment of mild to moderate cellulitis.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.
References
1. Moran GJ et al. Effect of cephalexin plus trimethoprim-sulfamethoxazole vs. cephalexin alone on clinical cure of uncomplicated cellulitis: A randomized clinical trial. JAMA 2017 May 23;317(20):2088-96.
2. Jeng Arthur et al. The role of beta-hemolytic streptococci in causing diffuse, nonculturable cellulitis. Medicine. 2010;July;89(4):217-26.
3. Stevens DL et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014;59(2):e10-e52.
4. Kamath RS et al. Guidelines vs. actual management of skin and soft tissue infections in the emergency department. Open Forum Infect Dis. 2018 Jan 12;5(1):ofx188.
He noticed discomfort today and saw that his left lower leg had redness and was warm. He does not recall scratches or injury to his leg. He has not had fever or chills. He has no other symptoms. His diabetes has been well controlled with diet and metformin.
On exam, his blood pressure is 120/70, pulse is 80, temperature is 37 degrees Celsius.
In the left lower extremity, the patient had 1+ edema at the ankle, with a 14-cm x 20-cm warm, erythematous area just above the ankle and extending proximally.
His labs found an HCT of 44 and a WBC of 12,000. What do you recommend?
A) Vascular duplex exam
B) 1st generation cephalosporin
C) 1st generation cephalosporin + TMP/Sulfa
D) Oral clindamycin
E) IV vancomycin
This patient has cellulitis and should receive a beta lactam antibiotic, which will have the best coverage and lowest minimal inhibitory concentration for the likely organism, beta hemolytic streptococci. Clindamycin would likely work, but it has greater side effects. This patient does not need coverage for methicillin-resistant staphylococcus aureus (MRSA). I know many of you, if not most, know this, but I want to go through relevant data and formal recommendations, because of a recent call I received from a patient.
My patient had a full body rash after receiving cephalexin + TMP/sulfa [trimethoprim-sulfamethoxazole] treatment for cellulitis. In recent years the addition of TMP/sulfa to strep treatment to also cover MRSA has become popular, especially in emergency department and urgent care settings.
Moran and colleagues studied cephalexin + TMP/sulfa vs. cephalexin and placebo in patients with uncomplicated cellulitis.1 The outcome measured was clinical cure, and there was no difference between groups; clinical cure occurred in 182 (83.5%) of 218 participants in the cephalexin plus TMP/sulfa group vs. 165 (85.5%) of 193 in the cephalexin group (difference, −2.0%; 95% confidence interval, −9.7% to 5.7%; P = .50).
Jeng and colleagues studied patients admitted for a cellulitis, and evaluated the patients’ response to beta-lactam antibiotics.2 Patients had acute and convalescent serologies for beta hemolytic strep. Almost all evaluable patients with positive strep studies (97%) responded to beta-lactams, and 21 of 23 (91%) with negative studies responded to beta-lactams (overall response rate 95%). This study was done during a time of high MRSA prevalence.
The most recent Infectious Diseases Society of America guidelines for skin and soft tissue infections, recommend oral penicillin, cephalexin, dicloxacillin, or clindamycin for mild cellulitis, and IV equivalent if patients have moderate cellulitis.3 If abscesses are present, then drainage is recommended and MRSA coverage. Kamath and colleagues reported on how closely guidelines for skin and soft tissue infections were followed.4 In patients with mild cellulitis, only 36% received guideline-suggested antibiotics. The most common antibiotic prescribed that was outside the guidelines was trimethoprim-sulfamethoxazole.
Myth: Cellulitis treatment should include MRSA coverage.
My advice: Stick with beta-lactam antibiotics, unless an abscess is present. There is no need to add MRSA coverage for initial treatment of mild to moderate cellulitis.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.
References
1. Moran GJ et al. Effect of cephalexin plus trimethoprim-sulfamethoxazole vs. cephalexin alone on clinical cure of uncomplicated cellulitis: A randomized clinical trial. JAMA 2017 May 23;317(20):2088-96.
2. Jeng Arthur et al. The role of beta-hemolytic streptococci in causing diffuse, nonculturable cellulitis. Medicine. 2010;July;89(4):217-26.
3. Stevens DL et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014;59(2):e10-e52.
4. Kamath RS et al. Guidelines vs. actual management of skin and soft tissue infections in the emergency department. Open Forum Infect Dis. 2018 Jan 12;5(1):ofx188.
He noticed discomfort today and saw that his left lower leg had redness and was warm. He does not recall scratches or injury to his leg. He has not had fever or chills. He has no other symptoms. His diabetes has been well controlled with diet and metformin.
On exam, his blood pressure is 120/70, pulse is 80, temperature is 37 degrees Celsius.
In the left lower extremity, the patient had 1+ edema at the ankle, with a 14-cm x 20-cm warm, erythematous area just above the ankle and extending proximally.
His labs found an HCT of 44 and a WBC of 12,000. What do you recommend?
A) Vascular duplex exam
B) 1st generation cephalosporin
C) 1st generation cephalosporin + TMP/Sulfa
D) Oral clindamycin
E) IV vancomycin
This patient has cellulitis and should receive a beta lactam antibiotic, which will have the best coverage and lowest minimal inhibitory concentration for the likely organism, beta hemolytic streptococci. Clindamycin would likely work, but it has greater side effects. This patient does not need coverage for methicillin-resistant staphylococcus aureus (MRSA). I know many of you, if not most, know this, but I want to go through relevant data and formal recommendations, because of a recent call I received from a patient.
My patient had a full body rash after receiving cephalexin + TMP/sulfa [trimethoprim-sulfamethoxazole] treatment for cellulitis. In recent years the addition of TMP/sulfa to strep treatment to also cover MRSA has become popular, especially in emergency department and urgent care settings.
Moran and colleagues studied cephalexin + TMP/sulfa vs. cephalexin and placebo in patients with uncomplicated cellulitis.1 The outcome measured was clinical cure, and there was no difference between groups; clinical cure occurred in 182 (83.5%) of 218 participants in the cephalexin plus TMP/sulfa group vs. 165 (85.5%) of 193 in the cephalexin group (difference, −2.0%; 95% confidence interval, −9.7% to 5.7%; P = .50).
Jeng and colleagues studied patients admitted for a cellulitis, and evaluated the patients’ response to beta-lactam antibiotics.2 Patients had acute and convalescent serologies for beta hemolytic strep. Almost all evaluable patients with positive strep studies (97%) responded to beta-lactams, and 21 of 23 (91%) with negative studies responded to beta-lactams (overall response rate 95%). This study was done during a time of high MRSA prevalence.
The most recent Infectious Diseases Society of America guidelines for skin and soft tissue infections, recommend oral penicillin, cephalexin, dicloxacillin, or clindamycin for mild cellulitis, and IV equivalent if patients have moderate cellulitis.3 If abscesses are present, then drainage is recommended and MRSA coverage. Kamath and colleagues reported on how closely guidelines for skin and soft tissue infections were followed.4 In patients with mild cellulitis, only 36% received guideline-suggested antibiotics. The most common antibiotic prescribed that was outside the guidelines was trimethoprim-sulfamethoxazole.
Myth: Cellulitis treatment should include MRSA coverage.
My advice: Stick with beta-lactam antibiotics, unless an abscess is present. There is no need to add MRSA coverage for initial treatment of mild to moderate cellulitis.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.
References
1. Moran GJ et al. Effect of cephalexin plus trimethoprim-sulfamethoxazole vs. cephalexin alone on clinical cure of uncomplicated cellulitis: A randomized clinical trial. JAMA 2017 May 23;317(20):2088-96.
2. Jeng Arthur et al. The role of beta-hemolytic streptococci in causing diffuse, nonculturable cellulitis. Medicine. 2010;July;89(4):217-26.
3. Stevens DL et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014;59(2):e10-e52.
4. Kamath RS et al. Guidelines vs. actual management of skin and soft tissue infections in the emergency department. Open Forum Infect Dis. 2018 Jan 12;5(1):ofx188.
Pandemic puts patients with psoriatic disease off seeking medical help
More than half of respondents to a recent survey looking at how the COVID-19 pandemic has affected people with psoriasis or psoriatic arthritis (PsA) said that they had avoided seeking medical care in person with a doctor or at a hospital.
Moreover, around a quarter had their appointment with a rheumatologist canceled, rescheduled, or conducted virtually. Another 1 in 10 had their treatment plan disrupted, and 6% had to change or stop treatment entirely.
The mental health impact of living with these conditions during the pandemic was also notable, said Rachael Manion, the executive director of the Canadian Association of Psoriasis Patients (CAPP), which conducted the survey in collaboration with the Canadian Psoriasis Network (CPN) and Unmasking Psoriasis.
“It’s important to know that there have been a lot of different impacts of the pandemic on people living with psoriatic arthritis and psoriasis. Mental health in particular has had a really big hit as a result,” she said at the Canadian Arthritis Research Conference: Research with Impact.
“About half of the people who responded to our survey noted that their mental health was ‘worse’ or ‘much worse’ during the pandemic,” she said at the meeting, which was sponsored by the Arthritis Society, the Canadian Rheumatology Association, and Canada’s Institute of Musculoskeletal Health and Arthritis. Anxiety and feelings of isolation were reported by a respective 57% and 58% of respondents, and 40% reported depression.
“We can compare that to our earlier information around depression,” Ms. Manion said, which showed that, prior to the pandemic, 24% of people with psoriasis and 23% of those with PsA had said they experienced depression.
“What I found alarming looking at these results was that about a third of people were experiencing despair. Now that’s a really big, scary, overwhelming emotion that has a lot of burden on your mental health,” Ms. Manion said.
Despite the substantial effects on mental health, only 29% of respondents said they had been able to access mental health services during the pandemic.
To look at the impact of the COVID-19 pandemic on the psoriasis and PsA community in Canada, three patient advocacy groups – CAPP, CPN, and Unmasking Psoriasis – codeveloped a survey to look at the disease experience before and after the start of the COVID-19 pandemic. The survey was performed once, with 830 respondents providing information on their lives with psoriasis or PsA in the months before the start of the pandemic and at the time they were surveyed in September and October 2020.
Most of the survey respondents lived in Ontario, Quebec, British Columbia, or Alberta, although other provinces or territories were represented. Almost all respondents (96%) had psoriasis, and 60% also had PsA.
Pre-COVID, nearly half (49%) of patients said that they had not been seen by a rheumatologist, and 39% had not seen a dermatologist for treatment. Asked why, 56% and 27%, respectively, had not been referred, 9% and 15% said they had no specialist located nearby, and 7% and 10% stated that the wait list was too long.
“This tells us that there’s a lot more work that can be done and a lot more education of general practitioners and family medicine professionals about the benefits and the value of specialized care for psoriatic arthritis,” Ms. Manion suggested.
Before the pandemic, joint pain was occurring in 88% of patients, stiffness in 71%, and joint swelling in 67%. Disease flares or sudden periods of worsening occurred on a daily basis for 17%, and around one in five (21%) experienced multiple flares every month.
Prepandemic data also highlighted the negative impact that living with psoriasis or PsA has on people’s ability to sleep, interactions and intimacy with others, and on their school or work lives.
During the pandemic, around a quarter (26%) of respondents said they had worse or much worse access to employment, as well as its benefits such as a stable income (24%). A minority of respondent also described worse access to prescription medication (15%) and over-the-counter medication (13%).
“There are all kinds of things going on for patients in our community: changes to their work, changes to their drug coverage, their ability to sleep and sleep well, their mental health, and their ability to access care and treatments as part of their disease management,” Ms. Manion said.
Her final message to health care professionals was: “I just want to encourage you to continue to check in with your patients about what their experiences have been during the pandemic, and to really consider those impacts as you’re working with them to manage their disease.”
The survey received funding support from AbbVie, Bausch Health, Boehringer Ingelheim, Janssen, LEO Pharma, and Novartis.
More than half of respondents to a recent survey looking at how the COVID-19 pandemic has affected people with psoriasis or psoriatic arthritis (PsA) said that they had avoided seeking medical care in person with a doctor or at a hospital.
Moreover, around a quarter had their appointment with a rheumatologist canceled, rescheduled, or conducted virtually. Another 1 in 10 had their treatment plan disrupted, and 6% had to change or stop treatment entirely.
The mental health impact of living with these conditions during the pandemic was also notable, said Rachael Manion, the executive director of the Canadian Association of Psoriasis Patients (CAPP), which conducted the survey in collaboration with the Canadian Psoriasis Network (CPN) and Unmasking Psoriasis.
“It’s important to know that there have been a lot of different impacts of the pandemic on people living with psoriatic arthritis and psoriasis. Mental health in particular has had a really big hit as a result,” she said at the Canadian Arthritis Research Conference: Research with Impact.
“About half of the people who responded to our survey noted that their mental health was ‘worse’ or ‘much worse’ during the pandemic,” she said at the meeting, which was sponsored by the Arthritis Society, the Canadian Rheumatology Association, and Canada’s Institute of Musculoskeletal Health and Arthritis. Anxiety and feelings of isolation were reported by a respective 57% and 58% of respondents, and 40% reported depression.
“We can compare that to our earlier information around depression,” Ms. Manion said, which showed that, prior to the pandemic, 24% of people with psoriasis and 23% of those with PsA had said they experienced depression.
“What I found alarming looking at these results was that about a third of people were experiencing despair. Now that’s a really big, scary, overwhelming emotion that has a lot of burden on your mental health,” Ms. Manion said.
Despite the substantial effects on mental health, only 29% of respondents said they had been able to access mental health services during the pandemic.
To look at the impact of the COVID-19 pandemic on the psoriasis and PsA community in Canada, three patient advocacy groups – CAPP, CPN, and Unmasking Psoriasis – codeveloped a survey to look at the disease experience before and after the start of the COVID-19 pandemic. The survey was performed once, with 830 respondents providing information on their lives with psoriasis or PsA in the months before the start of the pandemic and at the time they were surveyed in September and October 2020.
Most of the survey respondents lived in Ontario, Quebec, British Columbia, or Alberta, although other provinces or territories were represented. Almost all respondents (96%) had psoriasis, and 60% also had PsA.
Pre-COVID, nearly half (49%) of patients said that they had not been seen by a rheumatologist, and 39% had not seen a dermatologist for treatment. Asked why, 56% and 27%, respectively, had not been referred, 9% and 15% said they had no specialist located nearby, and 7% and 10% stated that the wait list was too long.
“This tells us that there’s a lot more work that can be done and a lot more education of general practitioners and family medicine professionals about the benefits and the value of specialized care for psoriatic arthritis,” Ms. Manion suggested.
Before the pandemic, joint pain was occurring in 88% of patients, stiffness in 71%, and joint swelling in 67%. Disease flares or sudden periods of worsening occurred on a daily basis for 17%, and around one in five (21%) experienced multiple flares every month.
Prepandemic data also highlighted the negative impact that living with psoriasis or PsA has on people’s ability to sleep, interactions and intimacy with others, and on their school or work lives.
During the pandemic, around a quarter (26%) of respondents said they had worse or much worse access to employment, as well as its benefits such as a stable income (24%). A minority of respondent also described worse access to prescription medication (15%) and over-the-counter medication (13%).
“There are all kinds of things going on for patients in our community: changes to their work, changes to their drug coverage, their ability to sleep and sleep well, their mental health, and their ability to access care and treatments as part of their disease management,” Ms. Manion said.
Her final message to health care professionals was: “I just want to encourage you to continue to check in with your patients about what their experiences have been during the pandemic, and to really consider those impacts as you’re working with them to manage their disease.”
The survey received funding support from AbbVie, Bausch Health, Boehringer Ingelheim, Janssen, LEO Pharma, and Novartis.
More than half of respondents to a recent survey looking at how the COVID-19 pandemic has affected people with psoriasis or psoriatic arthritis (PsA) said that they had avoided seeking medical care in person with a doctor or at a hospital.
Moreover, around a quarter had their appointment with a rheumatologist canceled, rescheduled, or conducted virtually. Another 1 in 10 had their treatment plan disrupted, and 6% had to change or stop treatment entirely.
The mental health impact of living with these conditions during the pandemic was also notable, said Rachael Manion, the executive director of the Canadian Association of Psoriasis Patients (CAPP), which conducted the survey in collaboration with the Canadian Psoriasis Network (CPN) and Unmasking Psoriasis.
“It’s important to know that there have been a lot of different impacts of the pandemic on people living with psoriatic arthritis and psoriasis. Mental health in particular has had a really big hit as a result,” she said at the Canadian Arthritis Research Conference: Research with Impact.
“About half of the people who responded to our survey noted that their mental health was ‘worse’ or ‘much worse’ during the pandemic,” she said at the meeting, which was sponsored by the Arthritis Society, the Canadian Rheumatology Association, and Canada’s Institute of Musculoskeletal Health and Arthritis. Anxiety and feelings of isolation were reported by a respective 57% and 58% of respondents, and 40% reported depression.
“We can compare that to our earlier information around depression,” Ms. Manion said, which showed that, prior to the pandemic, 24% of people with psoriasis and 23% of those with PsA had said they experienced depression.
“What I found alarming looking at these results was that about a third of people were experiencing despair. Now that’s a really big, scary, overwhelming emotion that has a lot of burden on your mental health,” Ms. Manion said.
Despite the substantial effects on mental health, only 29% of respondents said they had been able to access mental health services during the pandemic.
To look at the impact of the COVID-19 pandemic on the psoriasis and PsA community in Canada, three patient advocacy groups – CAPP, CPN, and Unmasking Psoriasis – codeveloped a survey to look at the disease experience before and after the start of the COVID-19 pandemic. The survey was performed once, with 830 respondents providing information on their lives with psoriasis or PsA in the months before the start of the pandemic and at the time they were surveyed in September and October 2020.
Most of the survey respondents lived in Ontario, Quebec, British Columbia, or Alberta, although other provinces or territories were represented. Almost all respondents (96%) had psoriasis, and 60% also had PsA.
Pre-COVID, nearly half (49%) of patients said that they had not been seen by a rheumatologist, and 39% had not seen a dermatologist for treatment. Asked why, 56% and 27%, respectively, had not been referred, 9% and 15% said they had no specialist located nearby, and 7% and 10% stated that the wait list was too long.
“This tells us that there’s a lot more work that can be done and a lot more education of general practitioners and family medicine professionals about the benefits and the value of specialized care for psoriatic arthritis,” Ms. Manion suggested.
Before the pandemic, joint pain was occurring in 88% of patients, stiffness in 71%, and joint swelling in 67%. Disease flares or sudden periods of worsening occurred on a daily basis for 17%, and around one in five (21%) experienced multiple flares every month.
Prepandemic data also highlighted the negative impact that living with psoriasis or PsA has on people’s ability to sleep, interactions and intimacy with others, and on their school or work lives.
During the pandemic, around a quarter (26%) of respondents said they had worse or much worse access to employment, as well as its benefits such as a stable income (24%). A minority of respondent also described worse access to prescription medication (15%) and over-the-counter medication (13%).
“There are all kinds of things going on for patients in our community: changes to their work, changes to their drug coverage, their ability to sleep and sleep well, their mental health, and their ability to access care and treatments as part of their disease management,” Ms. Manion said.
Her final message to health care professionals was: “I just want to encourage you to continue to check in with your patients about what their experiences have been during the pandemic, and to really consider those impacts as you’re working with them to manage their disease.”
The survey received funding support from AbbVie, Bausch Health, Boehringer Ingelheim, Janssen, LEO Pharma, and Novartis.
FROM CARC 2021
Less pain, same gain with tirbanibulin for actinic keratosis
“with transient local reactions,” according to the results of two identically designed trials.
However, the results, assessed at day 57 and out to 1 year of follow-up, were associated with recurrence of lesions at 1 year, noted lead author Andrew Blauvelt, MD, president of the Oregon Medical Research Center, Portland, and colleagues.
“The incidence of recurrence with conventional treatment has ranged from 20% to 96%,” they noted. “Among patients who had complete clearance at day 57 in the current trials, the estimated incidence of recurrence of previously cleared lesions was 47% at 1 year.” At 1 year, they added, “the estimated incidence of any lesions (new or recurrent) within the application area was 73%” and the estimate of sustained complete clearance was 27%.
A total of 700 adults completed the two multicenter, double-blind, parallel-group, vehicle-controlled trials, conducted concurrently between September 2017 and April 2019 at 62 U.S. sites. The results were published in the New England Journal of Medicine.
To be eligible, patients, mostly White men, had to have four to eight clinically typical, visible, and discrete AK lesions on the face or scalp within a contiguous area measuring 25 cm2. They were randomly assigned to treatment with either tirbanibulin 1% ointment or vehicle ointment (containing monoglycerides, diglycerides, and propylene glycol), which they applied once daily to the entire contiguous area for 5 days.
Pooled data across the two trials showed that the primary outcome, complete clearance of all lesions at day 57, occurred in 49% of the tirbanibulin groups versus 9% of the vehicle groups, and partial clearance (the secondary outcome) occurred in 72% versus 18% respectively. For both outcomes, and in both trials, all results were statistically significant.
Of the 174 patients who received tirbanibulin and had complete clearance, 124 had one or more lesions develop within the application area during follow-up, the authors reported. Of these, 58% had recurrences, while 42% had new lesions.
While individual AK lesions are typically treated with cryosurgery, the study authors noted that treatment of multiple lesions involves topical agents, such as fluorouracil, diclofenac, imiquimod, or ingenol mebutate, and photodynamic therapy, some of which have to be administered over periods of weeks or months and “may be associated with local reactions of pain, irritation, erosions, ulcerations, and irreversible skin changes of pigmentation and scarring,” which may reduce adherence.
In contrast, the current studies showed the most common local reactions to tirbanibulin were erythema in 91% of patients and flaking or scaling in 82%, with transient adverse events including application-site pain in 10% and pruritus in 9%.
“Unlike with most topical treatments for actinic keratosis ... severe local reactions, including vesiculation or pustulation and erosion or ulceration, were infrequent with tirbanibulin ointment,” the authors noted. “This could be due to the relatively short, 5-day course of once-daily treatment.”
They concluded that “larger and longer trials are necessary to determine the effects and risks” of treatment with tirbanibulin for treating AK.
Tirbanibulin, a synthetic inhibitor of tubulin polymerization and Src kinase signaling, was approved by the Food and Drug Administration in December 2020, for the topical treatment of AK of the face or scalp.
Asked to comment on the findings, Neal Bhatia, MD, a dermatologist and researcher at Therapeutics Dermatology, San Diego, who was not involved with the study, said that “a treatment with a 5-day course and excellent tolerability will make dermatologists rethink the old practice of ‘freeze and go.’ ”
In an interview, he added, “tirbanibulin comes to the U.S. market for treating AKs at a great time, as ingenol mebutate has been withdrawn and the others are not widely supported. The mechanism of promoting apoptosis and inducing cell cycle arrest directly correlates to the local skin reaction profile of less crusting, vesiculation, and overall signs of skin necrosis as compared to [5-fluorouracil] and ingenol mebutate, which work via that pathway. As a result, there is a direct impact on the hyperproliferation of atypical keratinocytes that will treat visible and subclinical disease.”
“The ointment vehicle is also novel as previous therapies have been in either creams or gels,” he said.
The two trials were funded by tirbanibulin manufacturer Athenex. Dr. Blauvelt reported receiving consulting fees from Athenex and other pharmaceutical companies, including Almirall, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant Sciences. Other author disclosures included serving as a consultant to Athenex and other companies. Several authors are Athenex employees. Dr. Bhatia disclosed that he is an adviser and consultant for Almirall and has been an investigator for multiple other AK treatments.
“with transient local reactions,” according to the results of two identically designed trials.
However, the results, assessed at day 57 and out to 1 year of follow-up, were associated with recurrence of lesions at 1 year, noted lead author Andrew Blauvelt, MD, president of the Oregon Medical Research Center, Portland, and colleagues.
“The incidence of recurrence with conventional treatment has ranged from 20% to 96%,” they noted. “Among patients who had complete clearance at day 57 in the current trials, the estimated incidence of recurrence of previously cleared lesions was 47% at 1 year.” At 1 year, they added, “the estimated incidence of any lesions (new or recurrent) within the application area was 73%” and the estimate of sustained complete clearance was 27%.
A total of 700 adults completed the two multicenter, double-blind, parallel-group, vehicle-controlled trials, conducted concurrently between September 2017 and April 2019 at 62 U.S. sites. The results were published in the New England Journal of Medicine.
To be eligible, patients, mostly White men, had to have four to eight clinically typical, visible, and discrete AK lesions on the face or scalp within a contiguous area measuring 25 cm2. They were randomly assigned to treatment with either tirbanibulin 1% ointment or vehicle ointment (containing monoglycerides, diglycerides, and propylene glycol), which they applied once daily to the entire contiguous area for 5 days.
Pooled data across the two trials showed that the primary outcome, complete clearance of all lesions at day 57, occurred in 49% of the tirbanibulin groups versus 9% of the vehicle groups, and partial clearance (the secondary outcome) occurred in 72% versus 18% respectively. For both outcomes, and in both trials, all results were statistically significant.
Of the 174 patients who received tirbanibulin and had complete clearance, 124 had one or more lesions develop within the application area during follow-up, the authors reported. Of these, 58% had recurrences, while 42% had new lesions.
While individual AK lesions are typically treated with cryosurgery, the study authors noted that treatment of multiple lesions involves topical agents, such as fluorouracil, diclofenac, imiquimod, or ingenol mebutate, and photodynamic therapy, some of which have to be administered over periods of weeks or months and “may be associated with local reactions of pain, irritation, erosions, ulcerations, and irreversible skin changes of pigmentation and scarring,” which may reduce adherence.
In contrast, the current studies showed the most common local reactions to tirbanibulin were erythema in 91% of patients and flaking or scaling in 82%, with transient adverse events including application-site pain in 10% and pruritus in 9%.
“Unlike with most topical treatments for actinic keratosis ... severe local reactions, including vesiculation or pustulation and erosion or ulceration, were infrequent with tirbanibulin ointment,” the authors noted. “This could be due to the relatively short, 5-day course of once-daily treatment.”
They concluded that “larger and longer trials are necessary to determine the effects and risks” of treatment with tirbanibulin for treating AK.
Tirbanibulin, a synthetic inhibitor of tubulin polymerization and Src kinase signaling, was approved by the Food and Drug Administration in December 2020, for the topical treatment of AK of the face or scalp.
Asked to comment on the findings, Neal Bhatia, MD, a dermatologist and researcher at Therapeutics Dermatology, San Diego, who was not involved with the study, said that “a treatment with a 5-day course and excellent tolerability will make dermatologists rethink the old practice of ‘freeze and go.’ ”
In an interview, he added, “tirbanibulin comes to the U.S. market for treating AKs at a great time, as ingenol mebutate has been withdrawn and the others are not widely supported. The mechanism of promoting apoptosis and inducing cell cycle arrest directly correlates to the local skin reaction profile of less crusting, vesiculation, and overall signs of skin necrosis as compared to [5-fluorouracil] and ingenol mebutate, which work via that pathway. As a result, there is a direct impact on the hyperproliferation of atypical keratinocytes that will treat visible and subclinical disease.”
“The ointment vehicle is also novel as previous therapies have been in either creams or gels,” he said.
The two trials were funded by tirbanibulin manufacturer Athenex. Dr. Blauvelt reported receiving consulting fees from Athenex and other pharmaceutical companies, including Almirall, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant Sciences. Other author disclosures included serving as a consultant to Athenex and other companies. Several authors are Athenex employees. Dr. Bhatia disclosed that he is an adviser and consultant for Almirall and has been an investigator for multiple other AK treatments.
“with transient local reactions,” according to the results of two identically designed trials.
However, the results, assessed at day 57 and out to 1 year of follow-up, were associated with recurrence of lesions at 1 year, noted lead author Andrew Blauvelt, MD, president of the Oregon Medical Research Center, Portland, and colleagues.
“The incidence of recurrence with conventional treatment has ranged from 20% to 96%,” they noted. “Among patients who had complete clearance at day 57 in the current trials, the estimated incidence of recurrence of previously cleared lesions was 47% at 1 year.” At 1 year, they added, “the estimated incidence of any lesions (new or recurrent) within the application area was 73%” and the estimate of sustained complete clearance was 27%.
A total of 700 adults completed the two multicenter, double-blind, parallel-group, vehicle-controlled trials, conducted concurrently between September 2017 and April 2019 at 62 U.S. sites. The results were published in the New England Journal of Medicine.
To be eligible, patients, mostly White men, had to have four to eight clinically typical, visible, and discrete AK lesions on the face or scalp within a contiguous area measuring 25 cm2. They were randomly assigned to treatment with either tirbanibulin 1% ointment or vehicle ointment (containing monoglycerides, diglycerides, and propylene glycol), which they applied once daily to the entire contiguous area for 5 days.
Pooled data across the two trials showed that the primary outcome, complete clearance of all lesions at day 57, occurred in 49% of the tirbanibulin groups versus 9% of the vehicle groups, and partial clearance (the secondary outcome) occurred in 72% versus 18% respectively. For both outcomes, and in both trials, all results were statistically significant.
Of the 174 patients who received tirbanibulin and had complete clearance, 124 had one or more lesions develop within the application area during follow-up, the authors reported. Of these, 58% had recurrences, while 42% had new lesions.
While individual AK lesions are typically treated with cryosurgery, the study authors noted that treatment of multiple lesions involves topical agents, such as fluorouracil, diclofenac, imiquimod, or ingenol mebutate, and photodynamic therapy, some of which have to be administered over periods of weeks or months and “may be associated with local reactions of pain, irritation, erosions, ulcerations, and irreversible skin changes of pigmentation and scarring,” which may reduce adherence.
In contrast, the current studies showed the most common local reactions to tirbanibulin were erythema in 91% of patients and flaking or scaling in 82%, with transient adverse events including application-site pain in 10% and pruritus in 9%.
“Unlike with most topical treatments for actinic keratosis ... severe local reactions, including vesiculation or pustulation and erosion or ulceration, were infrequent with tirbanibulin ointment,” the authors noted. “This could be due to the relatively short, 5-day course of once-daily treatment.”
They concluded that “larger and longer trials are necessary to determine the effects and risks” of treatment with tirbanibulin for treating AK.
Tirbanibulin, a synthetic inhibitor of tubulin polymerization and Src kinase signaling, was approved by the Food and Drug Administration in December 2020, for the topical treatment of AK of the face or scalp.
Asked to comment on the findings, Neal Bhatia, MD, a dermatologist and researcher at Therapeutics Dermatology, San Diego, who was not involved with the study, said that “a treatment with a 5-day course and excellent tolerability will make dermatologists rethink the old practice of ‘freeze and go.’ ”
In an interview, he added, “tirbanibulin comes to the U.S. market for treating AKs at a great time, as ingenol mebutate has been withdrawn and the others are not widely supported. The mechanism of promoting apoptosis and inducing cell cycle arrest directly correlates to the local skin reaction profile of less crusting, vesiculation, and overall signs of skin necrosis as compared to [5-fluorouracil] and ingenol mebutate, which work via that pathway. As a result, there is a direct impact on the hyperproliferation of atypical keratinocytes that will treat visible and subclinical disease.”
“The ointment vehicle is also novel as previous therapies have been in either creams or gels,” he said.
The two trials were funded by tirbanibulin manufacturer Athenex. Dr. Blauvelt reported receiving consulting fees from Athenex and other pharmaceutical companies, including Almirall, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant Sciences. Other author disclosures included serving as a consultant to Athenex and other companies. Several authors are Athenex employees. Dr. Bhatia disclosed that he is an adviser and consultant for Almirall and has been an investigator for multiple other AK treatments.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
ASDSA warns of rogue insulin pen use for DIY fillers
.
In the safety warning, issued on Feb. 18, the ASDSA reported that ASDSA members, all board-certified dermatologists, have seen evidence online of young people using so-called “hyaluron pens” to inject hyaluronic acid filler in the epidermal and upper dermal skin.
The pens being used and promoted in social media for do-it-yourself filler injections are medical devices originally developed for insulin injections. “The use of air pressure technology causes these pens to deliver the hyaluronic acid to insert nanoscale molecules of the filler through the skin,” according to the ASDSA statement. Marketing materials state that the pens can be used to create volume and shape in the lips, and to improve the appearance of nasolabial lines, marionette lines, brow lines known as “elevens,” and forehead wrinkles. Claims that the hyaluronic acid only reaches the papillary layer of the dermis, and is therefore safe, do not alleviate the risk of injury in inexperienced hands, the ASDSA statement points out.
“We are concerned about California children falling prey to products that are not appropriate and safe for them to use,” Elan Newland, MD, member of the ASDSA and the California Society for Dermatology and Dermatological Surgery (CalDerm), said in the statement. “The power of social media is very strong, especially for impressionable teenagers. CalDerm supports alerting consumers and regulators of the dangers of these pens,” he said.
“TikTok is proving to be an extremely powerful platform to communicate, entertain, and even educate, which is why many physicians are getting involved and finding success there. Unfortunately, just like the World Wide Web, there is misinformation there and even dangerous lies,” Sandra Lee, MD, who practices in Upland, Calif. (and is also known as “Dr. Pimple Popper”), said in the statement.
“It’s very concerning to see young people posting a How To on injecting their own lips with hyaluronic acid serum using an ‘airgun’ pen, which acts much like a BB gun to push with force the product under the skin,” she added. “So many things can go wrong.”
The ASDSA has contacted the Food and Drug Administration to report these safety concerns. “In addition, the ASDSA is alerting state medical and estheticians’ boards regarding these patient safety concerns and alerting consumers directly about the risks through social media and other education materials,” according to the statement.
.
In the safety warning, issued on Feb. 18, the ASDSA reported that ASDSA members, all board-certified dermatologists, have seen evidence online of young people using so-called “hyaluron pens” to inject hyaluronic acid filler in the epidermal and upper dermal skin.
The pens being used and promoted in social media for do-it-yourself filler injections are medical devices originally developed for insulin injections. “The use of air pressure technology causes these pens to deliver the hyaluronic acid to insert nanoscale molecules of the filler through the skin,” according to the ASDSA statement. Marketing materials state that the pens can be used to create volume and shape in the lips, and to improve the appearance of nasolabial lines, marionette lines, brow lines known as “elevens,” and forehead wrinkles. Claims that the hyaluronic acid only reaches the papillary layer of the dermis, and is therefore safe, do not alleviate the risk of injury in inexperienced hands, the ASDSA statement points out.
“We are concerned about California children falling prey to products that are not appropriate and safe for them to use,” Elan Newland, MD, member of the ASDSA and the California Society for Dermatology and Dermatological Surgery (CalDerm), said in the statement. “The power of social media is very strong, especially for impressionable teenagers. CalDerm supports alerting consumers and regulators of the dangers of these pens,” he said.
“TikTok is proving to be an extremely powerful platform to communicate, entertain, and even educate, which is why many physicians are getting involved and finding success there. Unfortunately, just like the World Wide Web, there is misinformation there and even dangerous lies,” Sandra Lee, MD, who practices in Upland, Calif. (and is also known as “Dr. Pimple Popper”), said in the statement.
“It’s very concerning to see young people posting a How To on injecting their own lips with hyaluronic acid serum using an ‘airgun’ pen, which acts much like a BB gun to push with force the product under the skin,” she added. “So many things can go wrong.”
The ASDSA has contacted the Food and Drug Administration to report these safety concerns. “In addition, the ASDSA is alerting state medical and estheticians’ boards regarding these patient safety concerns and alerting consumers directly about the risks through social media and other education materials,” according to the statement.
.
In the safety warning, issued on Feb. 18, the ASDSA reported that ASDSA members, all board-certified dermatologists, have seen evidence online of young people using so-called “hyaluron pens” to inject hyaluronic acid filler in the epidermal and upper dermal skin.
The pens being used and promoted in social media for do-it-yourself filler injections are medical devices originally developed for insulin injections. “The use of air pressure technology causes these pens to deliver the hyaluronic acid to insert nanoscale molecules of the filler through the skin,” according to the ASDSA statement. Marketing materials state that the pens can be used to create volume and shape in the lips, and to improve the appearance of nasolabial lines, marionette lines, brow lines known as “elevens,” and forehead wrinkles. Claims that the hyaluronic acid only reaches the papillary layer of the dermis, and is therefore safe, do not alleviate the risk of injury in inexperienced hands, the ASDSA statement points out.
“We are concerned about California children falling prey to products that are not appropriate and safe for them to use,” Elan Newland, MD, member of the ASDSA and the California Society for Dermatology and Dermatological Surgery (CalDerm), said in the statement. “The power of social media is very strong, especially for impressionable teenagers. CalDerm supports alerting consumers and regulators of the dangers of these pens,” he said.
“TikTok is proving to be an extremely powerful platform to communicate, entertain, and even educate, which is why many physicians are getting involved and finding success there. Unfortunately, just like the World Wide Web, there is misinformation there and even dangerous lies,” Sandra Lee, MD, who practices in Upland, Calif. (and is also known as “Dr. Pimple Popper”), said in the statement.
“It’s very concerning to see young people posting a How To on injecting their own lips with hyaluronic acid serum using an ‘airgun’ pen, which acts much like a BB gun to push with force the product under the skin,” she added. “So many things can go wrong.”
The ASDSA has contacted the Food and Drug Administration to report these safety concerns. “In addition, the ASDSA is alerting state medical and estheticians’ boards regarding these patient safety concerns and alerting consumers directly about the risks through social media and other education materials,” according to the statement.
Make the Diagnosis - March 2021
Because of the lack of improvement with topical corticosteroids, a skin biopsy was performed from a lesion on the lower back which showed an epidermis with compact hyperkeratosis and a thickened granular layer. Within the dermis, there was a lichenoid infiltrate of lymphocytes with a prominent interface change and rare dyskeratotic keratinocytes consistent with lichen planus.
Lichen planus is an inflammatory condition of the skin seen mainly in the adult population and is rare in children. This condition affects 0.5%-1% of the population, with maybe a higher prevalence in woman with no racial predilection in the adult or pediatric population. Most patients diagnosed are described to be over 40 years of age, but in children, the mean age for presentation is reported between the ages of 7 and 11.8 years.1 Interestingly, most of the published larger studies of lichen planus in children originate from India. In a U.K. study, about 80% of the cases reported were from children of Indian descent, as is our patient; so it is possible that lichen planus may be more prevalent in India.1 In a study based in the United States, cases were more prevalent in African American children.2
The exact cause of this condition is not known but studies have suggested that activated T cells, particularly CD8+, attack and cause apoptosis of the basal keratinocytes.3 There appears to be an up-regulation of Th1 cytokines such as interferon‐gamma, tumor necrosis factor–alpha, interleukin‐1 alpha, IL‐6, and IL‐8, as well as other apoptosis-related molecules.3
Lichen planus has been associated with other systemic conditions especially liver disease (chronic active hepatitis C and primary biliary cirrhosis). Children and adults may also have coexistence of other autoimmune diseases such as autoimmune polyendocrinopathy, myasthenia gravis, autoimmune thyroid disease, vitiligo, and thymoma. Some reports have also found a higher prevalence of atopic dermatitis in children with lichen planus.4
The lesions are typically described as the four “Ps” for pruritic, polygonal, purpuric flat-topped papules, and plaques. The papules of lichen planus have characteristically dry fine white streaks known as Wickham’s striae. The lesions can occur anywhere on the body, but they tend to occur more commonly on the flexures of the forearms, the wrists, ankles, shins, knees, and the torso. The face is rarely affected. In some patients oral, scalp (lichen planopilaris), nails, and rarely conjunctival, genital, and esophageal involvement can occur.2
In histopathology, the lesions are characterized by a wedge-shaped hypergranulosis, marked hyperkeratosis, and irregular sawtooth-like acanthosis of rete ridges on the epidermis. The dermal-epidermal junction typically shows an interstitial dermatitis. Civatte bodies may also be seen. On direct immunofluorescence, IgM-staining of the cytoid bodies in the dermal papilla or peribasilar areas are suggestive of lichen planus.1
The differential diagnosis of lichen planus includes severe lichenified atopic dermatitis, drug-induced lichen planus, graft-versus-host disease, psoriasis, pityriasis rosea, subacute cutaneous lupus, discoid lupus, secondary syphilis, and lichen simplex chronicus. Interestingly, our patient presented with lesions that were not pruritic and more generalized. Compared with eczema, were flexures are commonly affected, our patient’s lesions were localized to the ankles, wrists, extensor knees, and elbows, and no pruritus was reported. Lichenification of skin lesions occurs as a response to chronic scratching as it occurs in atopic dermatitis and lichen simplex chronicus, was considered in our patient, but the lack of pruritus and the more acute presentation made it unlikely.
Lichen planus is considered a self-limiting disease, so treatment is focused on the control of pruritus and to accelerate resolution. The first-line therapy for classic cutaneous lichen planus is the use of potent or superpotent topical corticosteroids for localized disease on the body and extremities and mild to mid-potency for intertriginous areas and the face. Clinical response should be assessed after 2-3 weeks of treatment. For patients with more generalized or recalcitrant disease like our patient, other treatment modalities like phototherapy (narrow-band UVB), a 4- to 6-week course of oral glucocorticoids, or acitretin may be considered. Our patient recently started narrow-band UVB. Other medications that have been reported beneficial for more severe cases include methotrexate, cyclosporine, griseofulvin, hydroxychloroquine, metronidazole, dapsone, and mycophenolate. Recent studies in the adult population have shown apremilast, a phosphodiesterase inhibitor, to be a promising medication for patients with cutaneous lichen planus, though this medication has not been approved yet for use in the pediatric population.5
Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.
References
1. Payette MJ et al. Clin Dermatol. 2015 Nov-Dec;33(6):631-43.
2. Walton KE et al. Pediatr Dermatol. 2010;27:34-8.
3. Lehman JS et al. Int J Dermatol. 2009 Jul;48(7):682-94.
4. Laughter D et al. J Am Acad Dermatol. 2000;43:649-55.
5. Paul J et al. J Am Acad Dermatol. 2013 Feb;68(2):255-61.
Because of the lack of improvement with topical corticosteroids, a skin biopsy was performed from a lesion on the lower back which showed an epidermis with compact hyperkeratosis and a thickened granular layer. Within the dermis, there was a lichenoid infiltrate of lymphocytes with a prominent interface change and rare dyskeratotic keratinocytes consistent with lichen planus.
Lichen planus is an inflammatory condition of the skin seen mainly in the adult population and is rare in children. This condition affects 0.5%-1% of the population, with maybe a higher prevalence in woman with no racial predilection in the adult or pediatric population. Most patients diagnosed are described to be over 40 years of age, but in children, the mean age for presentation is reported between the ages of 7 and 11.8 years.1 Interestingly, most of the published larger studies of lichen planus in children originate from India. In a U.K. study, about 80% of the cases reported were from children of Indian descent, as is our patient; so it is possible that lichen planus may be more prevalent in India.1 In a study based in the United States, cases were more prevalent in African American children.2
The exact cause of this condition is not known but studies have suggested that activated T cells, particularly CD8+, attack and cause apoptosis of the basal keratinocytes.3 There appears to be an up-regulation of Th1 cytokines such as interferon‐gamma, tumor necrosis factor–alpha, interleukin‐1 alpha, IL‐6, and IL‐8, as well as other apoptosis-related molecules.3
Lichen planus has been associated with other systemic conditions especially liver disease (chronic active hepatitis C and primary biliary cirrhosis). Children and adults may also have coexistence of other autoimmune diseases such as autoimmune polyendocrinopathy, myasthenia gravis, autoimmune thyroid disease, vitiligo, and thymoma. Some reports have also found a higher prevalence of atopic dermatitis in children with lichen planus.4
The lesions are typically described as the four “Ps” for pruritic, polygonal, purpuric flat-topped papules, and plaques. The papules of lichen planus have characteristically dry fine white streaks known as Wickham’s striae. The lesions can occur anywhere on the body, but they tend to occur more commonly on the flexures of the forearms, the wrists, ankles, shins, knees, and the torso. The face is rarely affected. In some patients oral, scalp (lichen planopilaris), nails, and rarely conjunctival, genital, and esophageal involvement can occur.2
In histopathology, the lesions are characterized by a wedge-shaped hypergranulosis, marked hyperkeratosis, and irregular sawtooth-like acanthosis of rete ridges on the epidermis. The dermal-epidermal junction typically shows an interstitial dermatitis. Civatte bodies may also be seen. On direct immunofluorescence, IgM-staining of the cytoid bodies in the dermal papilla or peribasilar areas are suggestive of lichen planus.1
The differential diagnosis of lichen planus includes severe lichenified atopic dermatitis, drug-induced lichen planus, graft-versus-host disease, psoriasis, pityriasis rosea, subacute cutaneous lupus, discoid lupus, secondary syphilis, and lichen simplex chronicus. Interestingly, our patient presented with lesions that were not pruritic and more generalized. Compared with eczema, were flexures are commonly affected, our patient’s lesions were localized to the ankles, wrists, extensor knees, and elbows, and no pruritus was reported. Lichenification of skin lesions occurs as a response to chronic scratching as it occurs in atopic dermatitis and lichen simplex chronicus, was considered in our patient, but the lack of pruritus and the more acute presentation made it unlikely.
Lichen planus is considered a self-limiting disease, so treatment is focused on the control of pruritus and to accelerate resolution. The first-line therapy for classic cutaneous lichen planus is the use of potent or superpotent topical corticosteroids for localized disease on the body and extremities and mild to mid-potency for intertriginous areas and the face. Clinical response should be assessed after 2-3 weeks of treatment. For patients with more generalized or recalcitrant disease like our patient, other treatment modalities like phototherapy (narrow-band UVB), a 4- to 6-week course of oral glucocorticoids, or acitretin may be considered. Our patient recently started narrow-band UVB. Other medications that have been reported beneficial for more severe cases include methotrexate, cyclosporine, griseofulvin, hydroxychloroquine, metronidazole, dapsone, and mycophenolate. Recent studies in the adult population have shown apremilast, a phosphodiesterase inhibitor, to be a promising medication for patients with cutaneous lichen planus, though this medication has not been approved yet for use in the pediatric population.5
Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.
References
1. Payette MJ et al. Clin Dermatol. 2015 Nov-Dec;33(6):631-43.
2. Walton KE et al. Pediatr Dermatol. 2010;27:34-8.
3. Lehman JS et al. Int J Dermatol. 2009 Jul;48(7):682-94.
4. Laughter D et al. J Am Acad Dermatol. 2000;43:649-55.
5. Paul J et al. J Am Acad Dermatol. 2013 Feb;68(2):255-61.
Because of the lack of improvement with topical corticosteroids, a skin biopsy was performed from a lesion on the lower back which showed an epidermis with compact hyperkeratosis and a thickened granular layer. Within the dermis, there was a lichenoid infiltrate of lymphocytes with a prominent interface change and rare dyskeratotic keratinocytes consistent with lichen planus.
Lichen planus is an inflammatory condition of the skin seen mainly in the adult population and is rare in children. This condition affects 0.5%-1% of the population, with maybe a higher prevalence in woman with no racial predilection in the adult or pediatric population. Most patients diagnosed are described to be over 40 years of age, but in children, the mean age for presentation is reported between the ages of 7 and 11.8 years.1 Interestingly, most of the published larger studies of lichen planus in children originate from India. In a U.K. study, about 80% of the cases reported were from children of Indian descent, as is our patient; so it is possible that lichen planus may be more prevalent in India.1 In a study based in the United States, cases were more prevalent in African American children.2
The exact cause of this condition is not known but studies have suggested that activated T cells, particularly CD8+, attack and cause apoptosis of the basal keratinocytes.3 There appears to be an up-regulation of Th1 cytokines such as interferon‐gamma, tumor necrosis factor–alpha, interleukin‐1 alpha, IL‐6, and IL‐8, as well as other apoptosis-related molecules.3
Lichen planus has been associated with other systemic conditions especially liver disease (chronic active hepatitis C and primary biliary cirrhosis). Children and adults may also have coexistence of other autoimmune diseases such as autoimmune polyendocrinopathy, myasthenia gravis, autoimmune thyroid disease, vitiligo, and thymoma. Some reports have also found a higher prevalence of atopic dermatitis in children with lichen planus.4
The lesions are typically described as the four “Ps” for pruritic, polygonal, purpuric flat-topped papules, and plaques. The papules of lichen planus have characteristically dry fine white streaks known as Wickham’s striae. The lesions can occur anywhere on the body, but they tend to occur more commonly on the flexures of the forearms, the wrists, ankles, shins, knees, and the torso. The face is rarely affected. In some patients oral, scalp (lichen planopilaris), nails, and rarely conjunctival, genital, and esophageal involvement can occur.2
In histopathology, the lesions are characterized by a wedge-shaped hypergranulosis, marked hyperkeratosis, and irregular sawtooth-like acanthosis of rete ridges on the epidermis. The dermal-epidermal junction typically shows an interstitial dermatitis. Civatte bodies may also be seen. On direct immunofluorescence, IgM-staining of the cytoid bodies in the dermal papilla or peribasilar areas are suggestive of lichen planus.1
The differential diagnosis of lichen planus includes severe lichenified atopic dermatitis, drug-induced lichen planus, graft-versus-host disease, psoriasis, pityriasis rosea, subacute cutaneous lupus, discoid lupus, secondary syphilis, and lichen simplex chronicus. Interestingly, our patient presented with lesions that were not pruritic and more generalized. Compared with eczema, were flexures are commonly affected, our patient’s lesions were localized to the ankles, wrists, extensor knees, and elbows, and no pruritus was reported. Lichenification of skin lesions occurs as a response to chronic scratching as it occurs in atopic dermatitis and lichen simplex chronicus, was considered in our patient, but the lack of pruritus and the more acute presentation made it unlikely.
Lichen planus is considered a self-limiting disease, so treatment is focused on the control of pruritus and to accelerate resolution. The first-line therapy for classic cutaneous lichen planus is the use of potent or superpotent topical corticosteroids for localized disease on the body and extremities and mild to mid-potency for intertriginous areas and the face. Clinical response should be assessed after 2-3 weeks of treatment. For patients with more generalized or recalcitrant disease like our patient, other treatment modalities like phototherapy (narrow-band UVB), a 4- to 6-week course of oral glucocorticoids, or acitretin may be considered. Our patient recently started narrow-band UVB. Other medications that have been reported beneficial for more severe cases include methotrexate, cyclosporine, griseofulvin, hydroxychloroquine, metronidazole, dapsone, and mycophenolate. Recent studies in the adult population have shown apremilast, a phosphodiesterase inhibitor, to be a promising medication for patients with cutaneous lichen planus, though this medication has not been approved yet for use in the pediatric population.5
Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.
References
1. Payette MJ et al. Clin Dermatol. 2015 Nov-Dec;33(6):631-43.
2. Walton KE et al. Pediatr Dermatol. 2010;27:34-8.
3. Lehman JS et al. Int J Dermatol. 2009 Jul;48(7):682-94.
4. Laughter D et al. J Am Acad Dermatol. 2000;43:649-55.
5. Paul J et al. J Am Acad Dermatol. 2013 Feb;68(2):255-61.
There was no prior personal or family history of atopic dermatitis or psoriasis. He has no other medical conditions and is not taking any medications.
He denied any joint pain, sun sensitivity, mouth sores, or other symptoms. After the initial consultation he was treated with fluocinonide 0.05% ointment for 2 weeks with slight improvement on the lesions.
On physical exam he presented with hyperpigmented and violaceous lichenified papules and plaques on the extremities and the torso. (photos 1 and 2). He also had hyperpigmented violaceous macules on the eyelids and around the mouth (photos 1 and 2).
Cluster of hyperpigmented spots
A large hyperpigmented patch with overlying darker macules and papules is characteristic of a speckled lentiginous nevus (SLN), also called a nevus spilus.
SLN is a cafe-au-lait˗like nevus that initially appears with a hyperpigmented background, usually at or around birth. Later, a speckled or polka-dot pattern of dark macules and papules appears over time. SLN is believed to be a form of congenital melanocytic nevus. There are believed to be 2 subtypes of SLN: nevus spilus maculosus and nevus spilus papulosus.
The maculosus subtype is characterized by flat and evenly distributed macules, that look like polka-dots. Histopathology reveals elongated interpapillary ridges containing increased numbers of melanocytes that form nests at the dermo-epidermal junction.
The papulosus subtype (which this patient had) is differentiated by superimposed speckles and papules whose size and distribution vary; this subype looks similar to a starry sky. Histopathology of the papulosus subtype shows melanocytic nevi of either the dermal or compound type—hence the papular appearance.
Given that SLN is a congenital melanocytic nevus, there is a small risk of transformation to malignant melanoma. The papulosus subtype is believed to have a more dynamic course with more lesions appearing over time. The maculosus subtype is considered to have a slightly higher risk of transformation into malignant melanoma compared to the papulosus subtype.
It is important to recognize that SLN is a distinct clinical entity, rather than a large irregular nevus. Mistaking it for a large suspicious nevus would require multiple biopsies of the most suspicious areas or excision of the entire lesion. Treatment for SLN includes serial surveillance with biopsy or excision of any suspicious areas that arise. In this case, the patient did not have any areas warranting biopsy, so the plan was to have him followed with annual clinical surveillance.
Photo and text courtesy of Erik Unruh, MD, MPH, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.
Happl, R. Speckled lentiginous naevus: which of the two disorders do you mean? Clin Exp Dermatol. 2009;34:133-135. doi: 10.1111/j.1365-2230.2008.02966.x.
A large hyperpigmented patch with overlying darker macules and papules is characteristic of a speckled lentiginous nevus (SLN), also called a nevus spilus.
SLN is a cafe-au-lait˗like nevus that initially appears with a hyperpigmented background, usually at or around birth. Later, a speckled or polka-dot pattern of dark macules and papules appears over time. SLN is believed to be a form of congenital melanocytic nevus. There are believed to be 2 subtypes of SLN: nevus spilus maculosus and nevus spilus papulosus.
The maculosus subtype is characterized by flat and evenly distributed macules, that look like polka-dots. Histopathology reveals elongated interpapillary ridges containing increased numbers of melanocytes that form nests at the dermo-epidermal junction.
The papulosus subtype (which this patient had) is differentiated by superimposed speckles and papules whose size and distribution vary; this subype looks similar to a starry sky. Histopathology of the papulosus subtype shows melanocytic nevi of either the dermal or compound type—hence the papular appearance.
Given that SLN is a congenital melanocytic nevus, there is a small risk of transformation to malignant melanoma. The papulosus subtype is believed to have a more dynamic course with more lesions appearing over time. The maculosus subtype is considered to have a slightly higher risk of transformation into malignant melanoma compared to the papulosus subtype.
It is important to recognize that SLN is a distinct clinical entity, rather than a large irregular nevus. Mistaking it for a large suspicious nevus would require multiple biopsies of the most suspicious areas or excision of the entire lesion. Treatment for SLN includes serial surveillance with biopsy or excision of any suspicious areas that arise. In this case, the patient did not have any areas warranting biopsy, so the plan was to have him followed with annual clinical surveillance.
Photo and text courtesy of Erik Unruh, MD, MPH, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.
A large hyperpigmented patch with overlying darker macules and papules is characteristic of a speckled lentiginous nevus (SLN), also called a nevus spilus.
SLN is a cafe-au-lait˗like nevus that initially appears with a hyperpigmented background, usually at or around birth. Later, a speckled or polka-dot pattern of dark macules and papules appears over time. SLN is believed to be a form of congenital melanocytic nevus. There are believed to be 2 subtypes of SLN: nevus spilus maculosus and nevus spilus papulosus.
The maculosus subtype is characterized by flat and evenly distributed macules, that look like polka-dots. Histopathology reveals elongated interpapillary ridges containing increased numbers of melanocytes that form nests at the dermo-epidermal junction.
The papulosus subtype (which this patient had) is differentiated by superimposed speckles and papules whose size and distribution vary; this subype looks similar to a starry sky. Histopathology of the papulosus subtype shows melanocytic nevi of either the dermal or compound type—hence the papular appearance.
Given that SLN is a congenital melanocytic nevus, there is a small risk of transformation to malignant melanoma. The papulosus subtype is believed to have a more dynamic course with more lesions appearing over time. The maculosus subtype is considered to have a slightly higher risk of transformation into malignant melanoma compared to the papulosus subtype.
It is important to recognize that SLN is a distinct clinical entity, rather than a large irregular nevus. Mistaking it for a large suspicious nevus would require multiple biopsies of the most suspicious areas or excision of the entire lesion. Treatment for SLN includes serial surveillance with biopsy or excision of any suspicious areas that arise. In this case, the patient did not have any areas warranting biopsy, so the plan was to have him followed with annual clinical surveillance.
Photo and text courtesy of Erik Unruh, MD, MPH, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.
Happl, R. Speckled lentiginous naevus: which of the two disorders do you mean? Clin Exp Dermatol. 2009;34:133-135. doi: 10.1111/j.1365-2230.2008.02966.x.
Happl, R. Speckled lentiginous naevus: which of the two disorders do you mean? Clin Exp Dermatol. 2009;34:133-135. doi: 10.1111/j.1365-2230.2008.02966.x.
Consider home subcutaneous immune globulin for refractory dermatomyositis
Home-based subcutaneous immune globulin therapy is a promising alternative to intravenous immune globulin therapy for patients with refractory dermatomyositis or polymyositis, Anna Postolova, MD, MPH, declared at the 2021 Rheumatology Winter Clinical Symposium.
“This is really exciting. I think in the years to come we may see a change to having our patients be able to do immune globulin therapy at home,” said Dr. Postolova, a rheumatologist and allergist/immunologist at Stanford (Calif.) Health Care.
“The technology is there. I think our patients might feel more comfortable getting immune globulin at home,” she said. “I would love to switch more patients from IVIg to SCIg [subcutaneous immune globulin] in my practice.”
A few caveats: SCIg remains off label for treatment of dermatomyositis (DM) or polymyositis (PM). Its approved indication is as replacement therapy in patients with primary or secondary immunodeficiency diseases. IVIg is approved for this indication, but is also approved for DM/PM refractory to high-dose corticosteroids and immunosuppressants. Yet SCIg is clearly effective for these autoimmune inflammatory diseases, albeit to date the supporting evidence comes chiefly from observational studies and anecdotal experience.
“I don’t know if insurers will cover it, but they should because it’s obviously a lot cheaper to do it at home,” she noted.
SCIg advantages
SCIg offers compelling advantages over IVIg in addition to its substantially lower cost. These include far fewer systemic side effects, shorter infusion time, greater bioavailability, and better quality of life. Patients self-administer SCIg at home, avoiding the inconvenience of IVIg therapy, which entails travel time for once-monthly hospitalization or long hours spent in an infusion center, she explained.
French investigators recently documented a previously unappreciated further advantage of home-based SCIg. They convened a focus group of patients with DM or PM experienced with both IVIg and home SCIg and determined that participants uniformly preferred home SCIg. The patients cited a new and welcome feeling of autonomy and control.
“All patients with experience of IVIg and SCIg expressed a clear preference for SCIg, which was described to be easy, less disruptive for daily life, well tolerated, and less time-consuming. Preference was mainly related to a restoration of autonomy. Home-based self-administration reinforced the feeling of independence,” according to the investigators.
Available products
Six preparations of SCIg are commercially available. Most are in 10% concentration, as are all IVIg products. However, a 20% formulation of SCIg known as Hizentra allows for a smaller infusion volume and quicker completion of a treatment session. And one SCIg product, HyQvia, uses recombinant human hyaluronidase-facilitated 10% immune globulin, allowing home infusion of large volumes of sustained-release immune globulin on a once-monthly basis.
The relatively recent introduction of home SCIg for treatment of autoimmune inflammatory diseases, including DM, PM, and chronic inflammatory demyelinating polyneuropathy, has been pioneered mainly by European investigators. The treatment is often given by programmable mechanical pump once weekly. Italian investigators have reported efficacy in DM using 0.2 g/kg per week, which is about half the monthly total dose of IVIg employed. The infusion rate is 10-40 mL/hour, with a volume of around 35 mL per injection site.
Alternatively, SCIg can be delivered by rapid push infusions of smaller volumes with a syringe two or three times per week; that’s the regimen that was used at 2 g/kg over the course of a month by patients in the French focus group study, who didn’t mind the more frequent dosing.
“As they have had severe long-lasting symptoms, SCIg was perceived as a curative rather than a preventive therapy,” according to the French investigators.
More than 40% of patients experience adverse reactions to IVIg. These often involve headaches, nausea, back or abdominal pain, arthralgias, and/or difficulty breathing. Thromboembolic events and acute renal failure occur occasionally. For this reason, many physicians give a prophylactic dose of corticosteroids an hour before a patient’s first dose of IVIg. These systemic side effects are so rare with SCIg that Dr. Postolova has never pretreated with steroids, even though the main reason she resorts to the home therapy is a patient’s track record of poor tolerance of IVIg. The lower abdomen and thigh are the most commonly used subcutaneous infusion sites. Mild local infusion site reactions are fairly common.
Formulating IVIg and SCIg is a complex process that entails plasma procurement and pooling, fractionation, and purification. It takes 10,000-60,000 plasma donations to make one lot of IVIg. Donations are accepted only from repeated donors. Samples are held for 6 months and tested for infectious agents. However, efforts are underway to develop bioengineered recombinant immune globulin products that don’t require donated plasma. These products are being designed to capture and enhance the most important mechanisms of benefit of plasma-derived immunoglobulins using Fc fragments that target key receptors, rather than relying on full-length immune globulin. The goal is enhanced efficacy at much lower doses than with IVIg or SCIg.
Dr. Postolova reported having no financial conflicts regarding her presentation.
Home-based subcutaneous immune globulin therapy is a promising alternative to intravenous immune globulin therapy for patients with refractory dermatomyositis or polymyositis, Anna Postolova, MD, MPH, declared at the 2021 Rheumatology Winter Clinical Symposium.
“This is really exciting. I think in the years to come we may see a change to having our patients be able to do immune globulin therapy at home,” said Dr. Postolova, a rheumatologist and allergist/immunologist at Stanford (Calif.) Health Care.
“The technology is there. I think our patients might feel more comfortable getting immune globulin at home,” she said. “I would love to switch more patients from IVIg to SCIg [subcutaneous immune globulin] in my practice.”
A few caveats: SCIg remains off label for treatment of dermatomyositis (DM) or polymyositis (PM). Its approved indication is as replacement therapy in patients with primary or secondary immunodeficiency diseases. IVIg is approved for this indication, but is also approved for DM/PM refractory to high-dose corticosteroids and immunosuppressants. Yet SCIg is clearly effective for these autoimmune inflammatory diseases, albeit to date the supporting evidence comes chiefly from observational studies and anecdotal experience.
“I don’t know if insurers will cover it, but they should because it’s obviously a lot cheaper to do it at home,” she noted.
SCIg advantages
SCIg offers compelling advantages over IVIg in addition to its substantially lower cost. These include far fewer systemic side effects, shorter infusion time, greater bioavailability, and better quality of life. Patients self-administer SCIg at home, avoiding the inconvenience of IVIg therapy, which entails travel time for once-monthly hospitalization or long hours spent in an infusion center, she explained.
French investigators recently documented a previously unappreciated further advantage of home-based SCIg. They convened a focus group of patients with DM or PM experienced with both IVIg and home SCIg and determined that participants uniformly preferred home SCIg. The patients cited a new and welcome feeling of autonomy and control.
“All patients with experience of IVIg and SCIg expressed a clear preference for SCIg, which was described to be easy, less disruptive for daily life, well tolerated, and less time-consuming. Preference was mainly related to a restoration of autonomy. Home-based self-administration reinforced the feeling of independence,” according to the investigators.
Available products
Six preparations of SCIg are commercially available. Most are in 10% concentration, as are all IVIg products. However, a 20% formulation of SCIg known as Hizentra allows for a smaller infusion volume and quicker completion of a treatment session. And one SCIg product, HyQvia, uses recombinant human hyaluronidase-facilitated 10% immune globulin, allowing home infusion of large volumes of sustained-release immune globulin on a once-monthly basis.
The relatively recent introduction of home SCIg for treatment of autoimmune inflammatory diseases, including DM, PM, and chronic inflammatory demyelinating polyneuropathy, has been pioneered mainly by European investigators. The treatment is often given by programmable mechanical pump once weekly. Italian investigators have reported efficacy in DM using 0.2 g/kg per week, which is about half the monthly total dose of IVIg employed. The infusion rate is 10-40 mL/hour, with a volume of around 35 mL per injection site.
Alternatively, SCIg can be delivered by rapid push infusions of smaller volumes with a syringe two or three times per week; that’s the regimen that was used at 2 g/kg over the course of a month by patients in the French focus group study, who didn’t mind the more frequent dosing.
“As they have had severe long-lasting symptoms, SCIg was perceived as a curative rather than a preventive therapy,” according to the French investigators.
More than 40% of patients experience adverse reactions to IVIg. These often involve headaches, nausea, back or abdominal pain, arthralgias, and/or difficulty breathing. Thromboembolic events and acute renal failure occur occasionally. For this reason, many physicians give a prophylactic dose of corticosteroids an hour before a patient’s first dose of IVIg. These systemic side effects are so rare with SCIg that Dr. Postolova has never pretreated with steroids, even though the main reason she resorts to the home therapy is a patient’s track record of poor tolerance of IVIg. The lower abdomen and thigh are the most commonly used subcutaneous infusion sites. Mild local infusion site reactions are fairly common.
Formulating IVIg and SCIg is a complex process that entails plasma procurement and pooling, fractionation, and purification. It takes 10,000-60,000 plasma donations to make one lot of IVIg. Donations are accepted only from repeated donors. Samples are held for 6 months and tested for infectious agents. However, efforts are underway to develop bioengineered recombinant immune globulin products that don’t require donated plasma. These products are being designed to capture and enhance the most important mechanisms of benefit of plasma-derived immunoglobulins using Fc fragments that target key receptors, rather than relying on full-length immune globulin. The goal is enhanced efficacy at much lower doses than with IVIg or SCIg.
Dr. Postolova reported having no financial conflicts regarding her presentation.
Home-based subcutaneous immune globulin therapy is a promising alternative to intravenous immune globulin therapy for patients with refractory dermatomyositis or polymyositis, Anna Postolova, MD, MPH, declared at the 2021 Rheumatology Winter Clinical Symposium.
“This is really exciting. I think in the years to come we may see a change to having our patients be able to do immune globulin therapy at home,” said Dr. Postolova, a rheumatologist and allergist/immunologist at Stanford (Calif.) Health Care.
“The technology is there. I think our patients might feel more comfortable getting immune globulin at home,” she said. “I would love to switch more patients from IVIg to SCIg [subcutaneous immune globulin] in my practice.”
A few caveats: SCIg remains off label for treatment of dermatomyositis (DM) or polymyositis (PM). Its approved indication is as replacement therapy in patients with primary or secondary immunodeficiency diseases. IVIg is approved for this indication, but is also approved for DM/PM refractory to high-dose corticosteroids and immunosuppressants. Yet SCIg is clearly effective for these autoimmune inflammatory diseases, albeit to date the supporting evidence comes chiefly from observational studies and anecdotal experience.
“I don’t know if insurers will cover it, but they should because it’s obviously a lot cheaper to do it at home,” she noted.
SCIg advantages
SCIg offers compelling advantages over IVIg in addition to its substantially lower cost. These include far fewer systemic side effects, shorter infusion time, greater bioavailability, and better quality of life. Patients self-administer SCIg at home, avoiding the inconvenience of IVIg therapy, which entails travel time for once-monthly hospitalization or long hours spent in an infusion center, she explained.
French investigators recently documented a previously unappreciated further advantage of home-based SCIg. They convened a focus group of patients with DM or PM experienced with both IVIg and home SCIg and determined that participants uniformly preferred home SCIg. The patients cited a new and welcome feeling of autonomy and control.
“All patients with experience of IVIg and SCIg expressed a clear preference for SCIg, which was described to be easy, less disruptive for daily life, well tolerated, and less time-consuming. Preference was mainly related to a restoration of autonomy. Home-based self-administration reinforced the feeling of independence,” according to the investigators.
Available products
Six preparations of SCIg are commercially available. Most are in 10% concentration, as are all IVIg products. However, a 20% formulation of SCIg known as Hizentra allows for a smaller infusion volume and quicker completion of a treatment session. And one SCIg product, HyQvia, uses recombinant human hyaluronidase-facilitated 10% immune globulin, allowing home infusion of large volumes of sustained-release immune globulin on a once-monthly basis.
The relatively recent introduction of home SCIg for treatment of autoimmune inflammatory diseases, including DM, PM, and chronic inflammatory demyelinating polyneuropathy, has been pioneered mainly by European investigators. The treatment is often given by programmable mechanical pump once weekly. Italian investigators have reported efficacy in DM using 0.2 g/kg per week, which is about half the monthly total dose of IVIg employed. The infusion rate is 10-40 mL/hour, with a volume of around 35 mL per injection site.
Alternatively, SCIg can be delivered by rapid push infusions of smaller volumes with a syringe two or three times per week; that’s the regimen that was used at 2 g/kg over the course of a month by patients in the French focus group study, who didn’t mind the more frequent dosing.
“As they have had severe long-lasting symptoms, SCIg was perceived as a curative rather than a preventive therapy,” according to the French investigators.
More than 40% of patients experience adverse reactions to IVIg. These often involve headaches, nausea, back or abdominal pain, arthralgias, and/or difficulty breathing. Thromboembolic events and acute renal failure occur occasionally. For this reason, many physicians give a prophylactic dose of corticosteroids an hour before a patient’s first dose of IVIg. These systemic side effects are so rare with SCIg that Dr. Postolova has never pretreated with steroids, even though the main reason she resorts to the home therapy is a patient’s track record of poor tolerance of IVIg. The lower abdomen and thigh are the most commonly used subcutaneous infusion sites. Mild local infusion site reactions are fairly common.
Formulating IVIg and SCIg is a complex process that entails plasma procurement and pooling, fractionation, and purification. It takes 10,000-60,000 plasma donations to make one lot of IVIg. Donations are accepted only from repeated donors. Samples are held for 6 months and tested for infectious agents. However, efforts are underway to develop bioengineered recombinant immune globulin products that don’t require donated plasma. These products are being designed to capture and enhance the most important mechanisms of benefit of plasma-derived immunoglobulins using Fc fragments that target key receptors, rather than relying on full-length immune globulin. The goal is enhanced efficacy at much lower doses than with IVIg or SCIg.
Dr. Postolova reported having no financial conflicts regarding her presentation.
FROM RWCS 2021
Checkpoint inhibitors’ ‘big picture’ safety shown with preexisting autoimmune diseases
Patients with advanced melanoma and preexisting autoimmune diseases (AIDs) who were treated with immune checkpoint inhibitors (ICIs) responded well and did not suffer more grade 3 or higher immune-related adverse events than patients without an AID, a new study finds, although some concerns were raised regarding patients with inflammatory bowel disease (IBD).
“To our knowledge, this is the first study to bridge this knowledge gap by presenting ‘real-world’ data on the safety and efficacy of ICI on a national scale,” wrote Monique K. van der Kooij, MD, of Leiden (the Netherlands) University Medical Center and coauthors. The study was published online in Annals of Internal Medicine.
To investigate ICI use and response among this specific subset of melanoma patients, the researchers launched a nationwide cohort study set in the Netherlands. Data were gathered via the Dutch Melanoma Treatment Registry (DMTR), in which 4,367 patients with advanced melanoma were enrolled between July 2013 and July 2018.
Within that cohort, 415 (9.5%) had preexisting AIDs. Nearly 55% had rheumatologic AIDs (n = 227) – which included RA, systemic lupus erythematosus, scleroderma, sarcoidosis, and vasculitis – with the next most frequent being endocrine AID (n = 143) and IBD (n = 55). Patients with AID were older than patients without (67 vs. 63 years) and were more likely to be female (53% vs. 41%).
The ICIs used in the study included anti-CTLA4 (ipilimumab), anti–programmed death 1 (PD-1) (nivolumab or pembrolizumab), or a combination of nivolumab and ipilimumab. Of the patients with AID, 55% (n = 228) were treated with ICI, compared with 58% of patients without AID. A total of 87 AID patients were treated with anti-CTLA4, 187 received anti-PD-1, and 34 received the combination. The combination was not readily available in the Netherlands until 2017, the authors stated, acknowledging that it may be wise to revisit its effects in the coming years.
Incidence of immune-related adverse events
The incidence of immune-related adverse events (irAEs) grade 3 and above for patients with and without AID who were given anti-CTLA4 was 30%. The incidence rate of irAEs was also similar for patients with (17%; 95% confidence interval, 12%-23%) and without (13%; 95% CI, 12%-15%) AID on anti-PD-1. Patients with AIDs who took anti-PD-1 therapy discontinued it more often because of toxicity than did the patients without AIDs.
The combination group had irAE incidence rates of 44% (95% CI, 27%-62%) for patients with AID, compared with 48% (95% CI, 43%-53%) for patients without AIDs. Overall, no patients with AIDs on ICIs died of toxicity, compared with three deaths among patients without AID on anti-CTLA4, five deaths among patients on anti-PD-1, and one patient on the combination.
Patients with IBD had a notably higher risk of anti-PD-1–induced colitis (19%; 95% CI, 7%-37%), compared with patients with other AIDs (3%; 95% CI, 0%-6%) and patients without AIDs (2%; 95% CI, 2%-3%). IBD patients were also more likely than all other groups on ICIs to stop treatment because of toxicity, leading the researchers to note that “close monitoring in patients with IBD is advised.”
Overall survival after diagnosis was similar in patients with AIDs (median, 13 months; 95% CI, 10-16 months) and without (median, 14 months; 95% CI, 13-15 months), as was the objective response rate to anti-CTLA4 treatment (10% vs. 16%), anti-PD-1 treatment (40% vs. 44%), and combination therapy (39% vs. 43%).
Study largely bypasses the effects of checkpoint inhibitors on RA patients
“For detail, you can’t look to this study,” Anne R. Bass, MD, of the division of rheumatology at the Hospital for Special Surgery in New York, said in an interview. “But for a big-picture look at ‘how safe are checkpoint inhibitors,’ I think it’s an important one.”
Dr. Bass noted that the investigators lumped certain elements together and bypassed others, including their focus on grade 3 or higher adverse events. That was a decision the authors themselves recognized as a potential limitation of their research.
“Understandably, they were worried about life-threatening adverse events, and that’s fine,” she said. But for patients with arthritis who flare, their events are usually grade 2 or even grade 1 and therefore not captured or analyzed in the study. “This does not really address the risk of flare in an RA patient.”
She also questioned their grouping of AIDs, with a bevy of rheumatic diseases categorized as one cluster and the “other” group being particularly broad in its inclusion of “all AIDs not listed” – though only eight patients were placed into that group.
That said, the researchers relied on an oncology database, not one aimed at AID or adverse events. “The numbers are so much bigger than any other study in this area that’s been done,” she said. “It’s both a strength and a weakness of this kind of database.”
Indeed, the authors considered their use of nationwide, population-based data from the DMTR a benefit, calling it “a strength of our approach.”
The DMTR was funded by a grant from the Netherlands Organization for Health Research and Development and sponsored by Bristol-Myers Squibb, Novartis, Roche Nederland, Merck Sharp & Dohme, and Pierre Fabre via the Dutch Institute for Clinical Auditing.
Patients with advanced melanoma and preexisting autoimmune diseases (AIDs) who were treated with immune checkpoint inhibitors (ICIs) responded well and did not suffer more grade 3 or higher immune-related adverse events than patients without an AID, a new study finds, although some concerns were raised regarding patients with inflammatory bowel disease (IBD).
“To our knowledge, this is the first study to bridge this knowledge gap by presenting ‘real-world’ data on the safety and efficacy of ICI on a national scale,” wrote Monique K. van der Kooij, MD, of Leiden (the Netherlands) University Medical Center and coauthors. The study was published online in Annals of Internal Medicine.
To investigate ICI use and response among this specific subset of melanoma patients, the researchers launched a nationwide cohort study set in the Netherlands. Data were gathered via the Dutch Melanoma Treatment Registry (DMTR), in which 4,367 patients with advanced melanoma were enrolled between July 2013 and July 2018.
Within that cohort, 415 (9.5%) had preexisting AIDs. Nearly 55% had rheumatologic AIDs (n = 227) – which included RA, systemic lupus erythematosus, scleroderma, sarcoidosis, and vasculitis – with the next most frequent being endocrine AID (n = 143) and IBD (n = 55). Patients with AID were older than patients without (67 vs. 63 years) and were more likely to be female (53% vs. 41%).
The ICIs used in the study included anti-CTLA4 (ipilimumab), anti–programmed death 1 (PD-1) (nivolumab or pembrolizumab), or a combination of nivolumab and ipilimumab. Of the patients with AID, 55% (n = 228) were treated with ICI, compared with 58% of patients without AID. A total of 87 AID patients were treated with anti-CTLA4, 187 received anti-PD-1, and 34 received the combination. The combination was not readily available in the Netherlands until 2017, the authors stated, acknowledging that it may be wise to revisit its effects in the coming years.
Incidence of immune-related adverse events
The incidence of immune-related adverse events (irAEs) grade 3 and above for patients with and without AID who were given anti-CTLA4 was 30%. The incidence rate of irAEs was also similar for patients with (17%; 95% confidence interval, 12%-23%) and without (13%; 95% CI, 12%-15%) AID on anti-PD-1. Patients with AIDs who took anti-PD-1 therapy discontinued it more often because of toxicity than did the patients without AIDs.
The combination group had irAE incidence rates of 44% (95% CI, 27%-62%) for patients with AID, compared with 48% (95% CI, 43%-53%) for patients without AIDs. Overall, no patients with AIDs on ICIs died of toxicity, compared with three deaths among patients without AID on anti-CTLA4, five deaths among patients on anti-PD-1, and one patient on the combination.
Patients with IBD had a notably higher risk of anti-PD-1–induced colitis (19%; 95% CI, 7%-37%), compared with patients with other AIDs (3%; 95% CI, 0%-6%) and patients without AIDs (2%; 95% CI, 2%-3%). IBD patients were also more likely than all other groups on ICIs to stop treatment because of toxicity, leading the researchers to note that “close monitoring in patients with IBD is advised.”
Overall survival after diagnosis was similar in patients with AIDs (median, 13 months; 95% CI, 10-16 months) and without (median, 14 months; 95% CI, 13-15 months), as was the objective response rate to anti-CTLA4 treatment (10% vs. 16%), anti-PD-1 treatment (40% vs. 44%), and combination therapy (39% vs. 43%).
Study largely bypasses the effects of checkpoint inhibitors on RA patients
“For detail, you can’t look to this study,” Anne R. Bass, MD, of the division of rheumatology at the Hospital for Special Surgery in New York, said in an interview. “But for a big-picture look at ‘how safe are checkpoint inhibitors,’ I think it’s an important one.”
Dr. Bass noted that the investigators lumped certain elements together and bypassed others, including their focus on grade 3 or higher adverse events. That was a decision the authors themselves recognized as a potential limitation of their research.
“Understandably, they were worried about life-threatening adverse events, and that’s fine,” she said. But for patients with arthritis who flare, their events are usually grade 2 or even grade 1 and therefore not captured or analyzed in the study. “This does not really address the risk of flare in an RA patient.”
She also questioned their grouping of AIDs, with a bevy of rheumatic diseases categorized as one cluster and the “other” group being particularly broad in its inclusion of “all AIDs not listed” – though only eight patients were placed into that group.
That said, the researchers relied on an oncology database, not one aimed at AID or adverse events. “The numbers are so much bigger than any other study in this area that’s been done,” she said. “It’s both a strength and a weakness of this kind of database.”
Indeed, the authors considered their use of nationwide, population-based data from the DMTR a benefit, calling it “a strength of our approach.”
The DMTR was funded by a grant from the Netherlands Organization for Health Research and Development and sponsored by Bristol-Myers Squibb, Novartis, Roche Nederland, Merck Sharp & Dohme, and Pierre Fabre via the Dutch Institute for Clinical Auditing.
Patients with advanced melanoma and preexisting autoimmune diseases (AIDs) who were treated with immune checkpoint inhibitors (ICIs) responded well and did not suffer more grade 3 or higher immune-related adverse events than patients without an AID, a new study finds, although some concerns were raised regarding patients with inflammatory bowel disease (IBD).
“To our knowledge, this is the first study to bridge this knowledge gap by presenting ‘real-world’ data on the safety and efficacy of ICI on a national scale,” wrote Monique K. van der Kooij, MD, of Leiden (the Netherlands) University Medical Center and coauthors. The study was published online in Annals of Internal Medicine.
To investigate ICI use and response among this specific subset of melanoma patients, the researchers launched a nationwide cohort study set in the Netherlands. Data were gathered via the Dutch Melanoma Treatment Registry (DMTR), in which 4,367 patients with advanced melanoma were enrolled between July 2013 and July 2018.
Within that cohort, 415 (9.5%) had preexisting AIDs. Nearly 55% had rheumatologic AIDs (n = 227) – which included RA, systemic lupus erythematosus, scleroderma, sarcoidosis, and vasculitis – with the next most frequent being endocrine AID (n = 143) and IBD (n = 55). Patients with AID were older than patients without (67 vs. 63 years) and were more likely to be female (53% vs. 41%).
The ICIs used in the study included anti-CTLA4 (ipilimumab), anti–programmed death 1 (PD-1) (nivolumab or pembrolizumab), or a combination of nivolumab and ipilimumab. Of the patients with AID, 55% (n = 228) were treated with ICI, compared with 58% of patients without AID. A total of 87 AID patients were treated with anti-CTLA4, 187 received anti-PD-1, and 34 received the combination. The combination was not readily available in the Netherlands until 2017, the authors stated, acknowledging that it may be wise to revisit its effects in the coming years.
Incidence of immune-related adverse events
The incidence of immune-related adverse events (irAEs) grade 3 and above for patients with and without AID who were given anti-CTLA4 was 30%. The incidence rate of irAEs was also similar for patients with (17%; 95% confidence interval, 12%-23%) and without (13%; 95% CI, 12%-15%) AID on anti-PD-1. Patients with AIDs who took anti-PD-1 therapy discontinued it more often because of toxicity than did the patients without AIDs.
The combination group had irAE incidence rates of 44% (95% CI, 27%-62%) for patients with AID, compared with 48% (95% CI, 43%-53%) for patients without AIDs. Overall, no patients with AIDs on ICIs died of toxicity, compared with three deaths among patients without AID on anti-CTLA4, five deaths among patients on anti-PD-1, and one patient on the combination.
Patients with IBD had a notably higher risk of anti-PD-1–induced colitis (19%; 95% CI, 7%-37%), compared with patients with other AIDs (3%; 95% CI, 0%-6%) and patients without AIDs (2%; 95% CI, 2%-3%). IBD patients were also more likely than all other groups on ICIs to stop treatment because of toxicity, leading the researchers to note that “close monitoring in patients with IBD is advised.”
Overall survival after diagnosis was similar in patients with AIDs (median, 13 months; 95% CI, 10-16 months) and without (median, 14 months; 95% CI, 13-15 months), as was the objective response rate to anti-CTLA4 treatment (10% vs. 16%), anti-PD-1 treatment (40% vs. 44%), and combination therapy (39% vs. 43%).
Study largely bypasses the effects of checkpoint inhibitors on RA patients
“For detail, you can’t look to this study,” Anne R. Bass, MD, of the division of rheumatology at the Hospital for Special Surgery in New York, said in an interview. “But for a big-picture look at ‘how safe are checkpoint inhibitors,’ I think it’s an important one.”
Dr. Bass noted that the investigators lumped certain elements together and bypassed others, including their focus on grade 3 or higher adverse events. That was a decision the authors themselves recognized as a potential limitation of their research.
“Understandably, they were worried about life-threatening adverse events, and that’s fine,” she said. But for patients with arthritis who flare, their events are usually grade 2 or even grade 1 and therefore not captured or analyzed in the study. “This does not really address the risk of flare in an RA patient.”
She also questioned their grouping of AIDs, with a bevy of rheumatic diseases categorized as one cluster and the “other” group being particularly broad in its inclusion of “all AIDs not listed” – though only eight patients were placed into that group.
That said, the researchers relied on an oncology database, not one aimed at AID or adverse events. “The numbers are so much bigger than any other study in this area that’s been done,” she said. “It’s both a strength and a weakness of this kind of database.”
Indeed, the authors considered their use of nationwide, population-based data from the DMTR a benefit, calling it “a strength of our approach.”
The DMTR was funded by a grant from the Netherlands Organization for Health Research and Development and sponsored by Bristol-Myers Squibb, Novartis, Roche Nederland, Merck Sharp & Dohme, and Pierre Fabre via the Dutch Institute for Clinical Auditing.
FROM ANNALS OF INTERNAL MEDICINE
Cumulative exposure to high-potency topical steroid doses drives osteoporosis fractures
In support of previously published case reports, in a dose-response relationship.
In a stepwise manner, the hazard ratios for major osteoporotic fracture (MOF) were found to start climbing incrementally for those with a cumulative topical steroid dose equivalent of more than 500 g of mometasone furoate when compared with exposure of 200-499 g, according to the team of investigators from the University of Copenhagen.
“Use of these drugs is very common, and we found an estimated population-attributable risk of as much as 4.3%,” the investigators reported in the study, published in JAMA Dermatology.
The retrospective cohort study drew data from the Danish National Patient Registry, which covers 99% of the country’s population. It was linked to the Danish National Prescription Registry, which captures data on pharmacy-dispensed medications. Data collected from the beginning of 2003 to the end of 2017 were evaluated.
Exposures to potent or very potent topical corticosteroids were converted into a single standard with potency equivalent to 1 mg/g of mometasone furoate. Four strata of exposure were compared to a reference exposure of 200-499 g. These were 500-999 g, 1,000-1,999 g, 2,000-9,999 g, and 10,000 g or greater.
For the first strata, the small increased risk for MOF did not reach significance (HR, 1.01; 95% confidence interval, 0.99-1.03), but each of the others did. These climbed from a 5% greater risk (HR 1.05 95% CI 1.02-1.08) for a cumulative exposure of 1,000 to 1,999 g, to a 10% greater risk (HR, 1.10; 95% CI, 1.07-1.13) for a cumulative exposure of 2,000-9,999 g, and finally to a 27% greater risk (HR, 1.27; 95% CI, 1.19-1.35) for a cumulative exposure of 10,000 g or higher.
The study included more than 700,000 individuals exposed to topical mometasone at a potency equivalent of 200 g or more over the study period. The reference group (200-499 g) was the largest (317,907 individuals). The first strata (500-999 g) included 186,359 patients; the second (1,000-1,999 g), 111,203 patients; the third (2,000-9,999 g), 94,334 patients; and the fifth (10,000 g or more), 13,448 patients.
“A 3% increase in the relative risk of osteoporosis and MOF was observed per doubling of the TCS dose,” according to the investigators.
Patients exposed to doses of high-potency topical steroids that put them at risk of MOF is limited but substantial, according to the senior author, Alexander Egeberg, MD, PhD, of the department of dermatology and allergy at Herlev and Gentofte Hospital, Copenhagen.
“It is true that the risk is modest for the average user of topical steroids,” Dr. Egeberg said in an interview. However, despite the fact that topical steroids are intended for short-term use, “2% of all our users had been exposed to the equivalent of 10,000 g of mometasone, which mean 100 tubes of 100 g.”
If the other two strata at significantly increased risk of MOF (greater than 1,000 g) are included, an additional 28% of all users are facing the potential for clinically significant osteoporosis, according to the Danish data.
The adverse effect of steroids on bone metabolism has been established previously, and several studies have linked systemic corticosteroid exposure, including inhaled corticosteroids, with increased risk of osteoporotic fracture. For example, one study showed that patients with chronic obstructive pulmonary disease on daily inhaled doses of the equivalent of fluticasone at or above 1,000 mcg for more than 4 years had about a 10% increased risk of MOF relative to those not exposed.
The data associate topical steroids with increased risk of osteoporotic fracture, but Dr. Egeberg said osteoporosis is not the only reason to use topical steroids prudently.
“It is important to keep in mind that osteoporosis and fractures are at the extreme end of the side-effect profile and that other side effects, such as striae formation, skin thinning, and dysregulated diabetes, can occur with much lower quantities of topical steroids,” Dr. Egeberg said
For avoiding this risk, “there are no specific cutoffs” recommended for topical steroids in current guidelines, but dermatologists should be aware that many of the indications for topical steroids, such as psoriasis and atopic dermatitis, involve skin with an impaired barrier function, exposing patients to an increased likelihood of absorption, according to Dr. Egeberg.
“A general rule of thumb that we use is that, if a patient with persistent disease activity requires a new prescription of the equivalent of 100 g mometasone every 1-2 months, it might be worth considering if there is a suitable alternative,” Dr. Egeberg said.
In an accompanying editorial, Rebecca D. Jackson, MD, of the division of endocrinology, diabetes, and metabolism in the department of internal medicine at Ohio State University, Columbus, agreed that no guidelines specific to avoiding the risks of topical corticosteroids are currently available, but she advised clinicians to be considering these risks nonetheless. In general, she suggested that topical steroids, like oral steroids, should be used at “the lowest dose for the shortest duration necessary to manage the underlying medical condition.”
The correlation between topical corticosteroids and increased risk of osteoporotic fracture, although not established previously in a large study, is not surprising, according to Victoria Werth, MD, chief of dermatology at the Philadelphia Veterans Affairs Hospital and professor of dermatology at the University of Pennsylvania, also in Philadelphia.
“Systemic absorption of potent topical steroids has previously been demonstrated with a rapid decrease in serum cortisol levels,” Dr. Werth said in an interview. She indicated that concern about the risk of osteoporosis imposed by use of potent steroids over large body surface areas is appropriate.
To minimize this risk, “it is reasonable to use the lowest dose of steroid possible and to try to substitute other medications when possible,” she said.
Dr. Egeberg reported financial relationships with Abbvie, Almirall, Bristol-Myers Squibb, Dermavant Sciences, Galderma, Janssen Pharmaceuticals, Eli Lilly, Novartis, Pfizer, Samsung, Bioepis, and UCB. Five authors had disclosures related to some of those pharmaceutical companies and/or others. Dr. Jackson had no disclosures.
In support of previously published case reports, in a dose-response relationship.
In a stepwise manner, the hazard ratios for major osteoporotic fracture (MOF) were found to start climbing incrementally for those with a cumulative topical steroid dose equivalent of more than 500 g of mometasone furoate when compared with exposure of 200-499 g, according to the team of investigators from the University of Copenhagen.
“Use of these drugs is very common, and we found an estimated population-attributable risk of as much as 4.3%,” the investigators reported in the study, published in JAMA Dermatology.
The retrospective cohort study drew data from the Danish National Patient Registry, which covers 99% of the country’s population. It was linked to the Danish National Prescription Registry, which captures data on pharmacy-dispensed medications. Data collected from the beginning of 2003 to the end of 2017 were evaluated.
Exposures to potent or very potent topical corticosteroids were converted into a single standard with potency equivalent to 1 mg/g of mometasone furoate. Four strata of exposure were compared to a reference exposure of 200-499 g. These were 500-999 g, 1,000-1,999 g, 2,000-9,999 g, and 10,000 g or greater.
For the first strata, the small increased risk for MOF did not reach significance (HR, 1.01; 95% confidence interval, 0.99-1.03), but each of the others did. These climbed from a 5% greater risk (HR 1.05 95% CI 1.02-1.08) for a cumulative exposure of 1,000 to 1,999 g, to a 10% greater risk (HR, 1.10; 95% CI, 1.07-1.13) for a cumulative exposure of 2,000-9,999 g, and finally to a 27% greater risk (HR, 1.27; 95% CI, 1.19-1.35) for a cumulative exposure of 10,000 g or higher.
The study included more than 700,000 individuals exposed to topical mometasone at a potency equivalent of 200 g or more over the study period. The reference group (200-499 g) was the largest (317,907 individuals). The first strata (500-999 g) included 186,359 patients; the second (1,000-1,999 g), 111,203 patients; the third (2,000-9,999 g), 94,334 patients; and the fifth (10,000 g or more), 13,448 patients.
“A 3% increase in the relative risk of osteoporosis and MOF was observed per doubling of the TCS dose,” according to the investigators.
Patients exposed to doses of high-potency topical steroids that put them at risk of MOF is limited but substantial, according to the senior author, Alexander Egeberg, MD, PhD, of the department of dermatology and allergy at Herlev and Gentofte Hospital, Copenhagen.
“It is true that the risk is modest for the average user of topical steroids,” Dr. Egeberg said in an interview. However, despite the fact that topical steroids are intended for short-term use, “2% of all our users had been exposed to the equivalent of 10,000 g of mometasone, which mean 100 tubes of 100 g.”
If the other two strata at significantly increased risk of MOF (greater than 1,000 g) are included, an additional 28% of all users are facing the potential for clinically significant osteoporosis, according to the Danish data.
The adverse effect of steroids on bone metabolism has been established previously, and several studies have linked systemic corticosteroid exposure, including inhaled corticosteroids, with increased risk of osteoporotic fracture. For example, one study showed that patients with chronic obstructive pulmonary disease on daily inhaled doses of the equivalent of fluticasone at or above 1,000 mcg for more than 4 years had about a 10% increased risk of MOF relative to those not exposed.
The data associate topical steroids with increased risk of osteoporotic fracture, but Dr. Egeberg said osteoporosis is not the only reason to use topical steroids prudently.
“It is important to keep in mind that osteoporosis and fractures are at the extreme end of the side-effect profile and that other side effects, such as striae formation, skin thinning, and dysregulated diabetes, can occur with much lower quantities of topical steroids,” Dr. Egeberg said
For avoiding this risk, “there are no specific cutoffs” recommended for topical steroids in current guidelines, but dermatologists should be aware that many of the indications for topical steroids, such as psoriasis and atopic dermatitis, involve skin with an impaired barrier function, exposing patients to an increased likelihood of absorption, according to Dr. Egeberg.
“A general rule of thumb that we use is that, if a patient with persistent disease activity requires a new prescription of the equivalent of 100 g mometasone every 1-2 months, it might be worth considering if there is a suitable alternative,” Dr. Egeberg said.
In an accompanying editorial, Rebecca D. Jackson, MD, of the division of endocrinology, diabetes, and metabolism in the department of internal medicine at Ohio State University, Columbus, agreed that no guidelines specific to avoiding the risks of topical corticosteroids are currently available, but she advised clinicians to be considering these risks nonetheless. In general, she suggested that topical steroids, like oral steroids, should be used at “the lowest dose for the shortest duration necessary to manage the underlying medical condition.”
The correlation between topical corticosteroids and increased risk of osteoporotic fracture, although not established previously in a large study, is not surprising, according to Victoria Werth, MD, chief of dermatology at the Philadelphia Veterans Affairs Hospital and professor of dermatology at the University of Pennsylvania, also in Philadelphia.
“Systemic absorption of potent topical steroids has previously been demonstrated with a rapid decrease in serum cortisol levels,” Dr. Werth said in an interview. She indicated that concern about the risk of osteoporosis imposed by use of potent steroids over large body surface areas is appropriate.
To minimize this risk, “it is reasonable to use the lowest dose of steroid possible and to try to substitute other medications when possible,” she said.
Dr. Egeberg reported financial relationships with Abbvie, Almirall, Bristol-Myers Squibb, Dermavant Sciences, Galderma, Janssen Pharmaceuticals, Eli Lilly, Novartis, Pfizer, Samsung, Bioepis, and UCB. Five authors had disclosures related to some of those pharmaceutical companies and/or others. Dr. Jackson had no disclosures.
In support of previously published case reports, in a dose-response relationship.
In a stepwise manner, the hazard ratios for major osteoporotic fracture (MOF) were found to start climbing incrementally for those with a cumulative topical steroid dose equivalent of more than 500 g of mometasone furoate when compared with exposure of 200-499 g, according to the team of investigators from the University of Copenhagen.
“Use of these drugs is very common, and we found an estimated population-attributable risk of as much as 4.3%,” the investigators reported in the study, published in JAMA Dermatology.
The retrospective cohort study drew data from the Danish National Patient Registry, which covers 99% of the country’s population. It was linked to the Danish National Prescription Registry, which captures data on pharmacy-dispensed medications. Data collected from the beginning of 2003 to the end of 2017 were evaluated.
Exposures to potent or very potent topical corticosteroids were converted into a single standard with potency equivalent to 1 mg/g of mometasone furoate. Four strata of exposure were compared to a reference exposure of 200-499 g. These were 500-999 g, 1,000-1,999 g, 2,000-9,999 g, and 10,000 g or greater.
For the first strata, the small increased risk for MOF did not reach significance (HR, 1.01; 95% confidence interval, 0.99-1.03), but each of the others did. These climbed from a 5% greater risk (HR 1.05 95% CI 1.02-1.08) for a cumulative exposure of 1,000 to 1,999 g, to a 10% greater risk (HR, 1.10; 95% CI, 1.07-1.13) for a cumulative exposure of 2,000-9,999 g, and finally to a 27% greater risk (HR, 1.27; 95% CI, 1.19-1.35) for a cumulative exposure of 10,000 g or higher.
The study included more than 700,000 individuals exposed to topical mometasone at a potency equivalent of 200 g or more over the study period. The reference group (200-499 g) was the largest (317,907 individuals). The first strata (500-999 g) included 186,359 patients; the second (1,000-1,999 g), 111,203 patients; the third (2,000-9,999 g), 94,334 patients; and the fifth (10,000 g or more), 13,448 patients.
“A 3% increase in the relative risk of osteoporosis and MOF was observed per doubling of the TCS dose,” according to the investigators.
Patients exposed to doses of high-potency topical steroids that put them at risk of MOF is limited but substantial, according to the senior author, Alexander Egeberg, MD, PhD, of the department of dermatology and allergy at Herlev and Gentofte Hospital, Copenhagen.
“It is true that the risk is modest for the average user of topical steroids,” Dr. Egeberg said in an interview. However, despite the fact that topical steroids are intended for short-term use, “2% of all our users had been exposed to the equivalent of 10,000 g of mometasone, which mean 100 tubes of 100 g.”
If the other two strata at significantly increased risk of MOF (greater than 1,000 g) are included, an additional 28% of all users are facing the potential for clinically significant osteoporosis, according to the Danish data.
The adverse effect of steroids on bone metabolism has been established previously, and several studies have linked systemic corticosteroid exposure, including inhaled corticosteroids, with increased risk of osteoporotic fracture. For example, one study showed that patients with chronic obstructive pulmonary disease on daily inhaled doses of the equivalent of fluticasone at or above 1,000 mcg for more than 4 years had about a 10% increased risk of MOF relative to those not exposed.
The data associate topical steroids with increased risk of osteoporotic fracture, but Dr. Egeberg said osteoporosis is not the only reason to use topical steroids prudently.
“It is important to keep in mind that osteoporosis and fractures are at the extreme end of the side-effect profile and that other side effects, such as striae formation, skin thinning, and dysregulated diabetes, can occur with much lower quantities of topical steroids,” Dr. Egeberg said
For avoiding this risk, “there are no specific cutoffs” recommended for topical steroids in current guidelines, but dermatologists should be aware that many of the indications for topical steroids, such as psoriasis and atopic dermatitis, involve skin with an impaired barrier function, exposing patients to an increased likelihood of absorption, according to Dr. Egeberg.
“A general rule of thumb that we use is that, if a patient with persistent disease activity requires a new prescription of the equivalent of 100 g mometasone every 1-2 months, it might be worth considering if there is a suitable alternative,” Dr. Egeberg said.
In an accompanying editorial, Rebecca D. Jackson, MD, of the division of endocrinology, diabetes, and metabolism in the department of internal medicine at Ohio State University, Columbus, agreed that no guidelines specific to avoiding the risks of topical corticosteroids are currently available, but she advised clinicians to be considering these risks nonetheless. In general, she suggested that topical steroids, like oral steroids, should be used at “the lowest dose for the shortest duration necessary to manage the underlying medical condition.”
The correlation between topical corticosteroids and increased risk of osteoporotic fracture, although not established previously in a large study, is not surprising, according to Victoria Werth, MD, chief of dermatology at the Philadelphia Veterans Affairs Hospital and professor of dermatology at the University of Pennsylvania, also in Philadelphia.
“Systemic absorption of potent topical steroids has previously been demonstrated with a rapid decrease in serum cortisol levels,” Dr. Werth said in an interview. She indicated that concern about the risk of osteoporosis imposed by use of potent steroids over large body surface areas is appropriate.
To minimize this risk, “it is reasonable to use the lowest dose of steroid possible and to try to substitute other medications when possible,” she said.
Dr. Egeberg reported financial relationships with Abbvie, Almirall, Bristol-Myers Squibb, Dermavant Sciences, Galderma, Janssen Pharmaceuticals, Eli Lilly, Novartis, Pfizer, Samsung, Bioepis, and UCB. Five authors had disclosures related to some of those pharmaceutical companies and/or others. Dr. Jackson had no disclosures.
FROM JAMA DERMATOLOGY