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Oral sarecycline promising for papulopustular rosacea
Linda Stein Gold, MD, said at Innovations in Dermatology: Virtual Spring Conference 2021.
The oral broad-spectrum second-generation tetracyclines doxycycline and minocycline have long been considered first-line therapy for papulopustular rosacea that isn’t cleared using topical agents. But the widespread use of these oral tetracyclines has encouraged the development of antimicrobial resistance. In contrast, sarecycline (Seysara) is a third-generation, narrow-spectrum tetracycline designed to minimize antibiotic resistance. The Food and Drug Administration approved the drug for treatment of moderate to severe acne vulgaris in 2018.
At the meeting, Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit, highlighted a recent pilot study of oral sarecycline for papulopustular rosacea carried out by James Q. Del Rosso, DO, of Las Vegas and coinvestigators. Although she wasn’t involved in the study, she is a veteran clinical trialist with vast experience leading studies of new therapies for rosacea, acne, and other major dermatologic disorders.
The 12-week, prospective, investigator-blinded study included 97 adults with moderate to severe papulopustular rosacea; 72 were randomized to weight-based dosing of once-daily sarecycline, while the 25 controls took a daily oral vitamin.
One coprimary endpoint was achievement of an Investigator Global Assessment score of 0 or 1, meaning clear or almost clear skin, at week 12. The rates were 75% in the sarecycline group and 16% in controls. The other coprimary endpoint was the percent reduction from baseline to week 12 in inflammatory lesion count. Here again, there was a statistically significant difference in favor of the third-generation tetracycline derivative, which achieved an 80% reduction, compared with 50% in the control group.
Of note, the difference was already significant at the first evaluation at week 4, with a 58% reduction in inflammatory lesions in the sarecycline group versus 31% decrease in controls, Dr. Stein Gold observed at the conference, sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.
Also at week 12, 96% of patients on sarecycline reported having no or only trace symptoms of facial burning, 63% had no or only trace facial erythema, and 94% had no or trace facial itch, compared with 76%, 12%, and 76% of controls, respectively. The sarecycline group was also significantly more likely to report no or trace skin dryness and oiliness.
The side-effect profile was favorable and the same as encountered with the use of sarecycline for acne: no major photosensitivity issues, no serious adverse events, and only 2 of the original 75 patients in the active-treatment arm discontinued sarecycline for treatment-emergent headache or gastroenteritis considered “probably” related to the study drug. The investigators deemed further studies of sarecycline for rosacea to be warranted as a potential expanded indication.
Aiming for clear skin rather than ‘almost clear’
Dr. Stein Gold shared her mantra for rosacea therapy: “Always aim for clear skin.”
She cited a study led by Guy Webster, MD, professor of dermatology, Thomas Jefferson University, Philadelphia, in which he and his coinvestigators looked at the durability of treatment response in a pooled analysis of 1,366 rosacea patients in four clinical trials. If patients improved to “almost clear” after treatment, their median time to relapse was 3 months; if they reached “clear,” it was more than 8 months. Also, more clear patients rated their outcomes as excellent and reported that their skin disease no longer had any effect on their quality of life.
“That’s more than a 5-month difference,” Dr. Stein Gold noted. “It shows the importance of really striving to get that skin completely clear.”
The sarecycline study was funded by Almirall, which markets the antibiotic. Dr. Stein Gold, who has no financial relationship with Almirall, has received research funding from and/or served as a consultant to roughly a dozen other pharmaceutical companies. MedscapeLIVE! and this news organization are owned by the same parent company.
Linda Stein Gold, MD, said at Innovations in Dermatology: Virtual Spring Conference 2021.
The oral broad-spectrum second-generation tetracyclines doxycycline and minocycline have long been considered first-line therapy for papulopustular rosacea that isn’t cleared using topical agents. But the widespread use of these oral tetracyclines has encouraged the development of antimicrobial resistance. In contrast, sarecycline (Seysara) is a third-generation, narrow-spectrum tetracycline designed to minimize antibiotic resistance. The Food and Drug Administration approved the drug for treatment of moderate to severe acne vulgaris in 2018.
At the meeting, Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit, highlighted a recent pilot study of oral sarecycline for papulopustular rosacea carried out by James Q. Del Rosso, DO, of Las Vegas and coinvestigators. Although she wasn’t involved in the study, she is a veteran clinical trialist with vast experience leading studies of new therapies for rosacea, acne, and other major dermatologic disorders.
The 12-week, prospective, investigator-blinded study included 97 adults with moderate to severe papulopustular rosacea; 72 were randomized to weight-based dosing of once-daily sarecycline, while the 25 controls took a daily oral vitamin.
One coprimary endpoint was achievement of an Investigator Global Assessment score of 0 or 1, meaning clear or almost clear skin, at week 12. The rates were 75% in the sarecycline group and 16% in controls. The other coprimary endpoint was the percent reduction from baseline to week 12 in inflammatory lesion count. Here again, there was a statistically significant difference in favor of the third-generation tetracycline derivative, which achieved an 80% reduction, compared with 50% in the control group.
Of note, the difference was already significant at the first evaluation at week 4, with a 58% reduction in inflammatory lesions in the sarecycline group versus 31% decrease in controls, Dr. Stein Gold observed at the conference, sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.
Also at week 12, 96% of patients on sarecycline reported having no or only trace symptoms of facial burning, 63% had no or only trace facial erythema, and 94% had no or trace facial itch, compared with 76%, 12%, and 76% of controls, respectively. The sarecycline group was also significantly more likely to report no or trace skin dryness and oiliness.
The side-effect profile was favorable and the same as encountered with the use of sarecycline for acne: no major photosensitivity issues, no serious adverse events, and only 2 of the original 75 patients in the active-treatment arm discontinued sarecycline for treatment-emergent headache or gastroenteritis considered “probably” related to the study drug. The investigators deemed further studies of sarecycline for rosacea to be warranted as a potential expanded indication.
Aiming for clear skin rather than ‘almost clear’
Dr. Stein Gold shared her mantra for rosacea therapy: “Always aim for clear skin.”
She cited a study led by Guy Webster, MD, professor of dermatology, Thomas Jefferson University, Philadelphia, in which he and his coinvestigators looked at the durability of treatment response in a pooled analysis of 1,366 rosacea patients in four clinical trials. If patients improved to “almost clear” after treatment, their median time to relapse was 3 months; if they reached “clear,” it was more than 8 months. Also, more clear patients rated their outcomes as excellent and reported that their skin disease no longer had any effect on their quality of life.
“That’s more than a 5-month difference,” Dr. Stein Gold noted. “It shows the importance of really striving to get that skin completely clear.”
The sarecycline study was funded by Almirall, which markets the antibiotic. Dr. Stein Gold, who has no financial relationship with Almirall, has received research funding from and/or served as a consultant to roughly a dozen other pharmaceutical companies. MedscapeLIVE! and this news organization are owned by the same parent company.
Linda Stein Gold, MD, said at Innovations in Dermatology: Virtual Spring Conference 2021.
The oral broad-spectrum second-generation tetracyclines doxycycline and minocycline have long been considered first-line therapy for papulopustular rosacea that isn’t cleared using topical agents. But the widespread use of these oral tetracyclines has encouraged the development of antimicrobial resistance. In contrast, sarecycline (Seysara) is a third-generation, narrow-spectrum tetracycline designed to minimize antibiotic resistance. The Food and Drug Administration approved the drug for treatment of moderate to severe acne vulgaris in 2018.
At the meeting, Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit, highlighted a recent pilot study of oral sarecycline for papulopustular rosacea carried out by James Q. Del Rosso, DO, of Las Vegas and coinvestigators. Although she wasn’t involved in the study, she is a veteran clinical trialist with vast experience leading studies of new therapies for rosacea, acne, and other major dermatologic disorders.
The 12-week, prospective, investigator-blinded study included 97 adults with moderate to severe papulopustular rosacea; 72 were randomized to weight-based dosing of once-daily sarecycline, while the 25 controls took a daily oral vitamin.
One coprimary endpoint was achievement of an Investigator Global Assessment score of 0 or 1, meaning clear or almost clear skin, at week 12. The rates were 75% in the sarecycline group and 16% in controls. The other coprimary endpoint was the percent reduction from baseline to week 12 in inflammatory lesion count. Here again, there was a statistically significant difference in favor of the third-generation tetracycline derivative, which achieved an 80% reduction, compared with 50% in the control group.
Of note, the difference was already significant at the first evaluation at week 4, with a 58% reduction in inflammatory lesions in the sarecycline group versus 31% decrease in controls, Dr. Stein Gold observed at the conference, sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.
Also at week 12, 96% of patients on sarecycline reported having no or only trace symptoms of facial burning, 63% had no or only trace facial erythema, and 94% had no or trace facial itch, compared with 76%, 12%, and 76% of controls, respectively. The sarecycline group was also significantly more likely to report no or trace skin dryness and oiliness.
The side-effect profile was favorable and the same as encountered with the use of sarecycline for acne: no major photosensitivity issues, no serious adverse events, and only 2 of the original 75 patients in the active-treatment arm discontinued sarecycline for treatment-emergent headache or gastroenteritis considered “probably” related to the study drug. The investigators deemed further studies of sarecycline for rosacea to be warranted as a potential expanded indication.
Aiming for clear skin rather than ‘almost clear’
Dr. Stein Gold shared her mantra for rosacea therapy: “Always aim for clear skin.”
She cited a study led by Guy Webster, MD, professor of dermatology, Thomas Jefferson University, Philadelphia, in which he and his coinvestigators looked at the durability of treatment response in a pooled analysis of 1,366 rosacea patients in four clinical trials. If patients improved to “almost clear” after treatment, their median time to relapse was 3 months; if they reached “clear,” it was more than 8 months. Also, more clear patients rated their outcomes as excellent and reported that their skin disease no longer had any effect on their quality of life.
“That’s more than a 5-month difference,” Dr. Stein Gold noted. “It shows the importance of really striving to get that skin completely clear.”
The sarecycline study was funded by Almirall, which markets the antibiotic. Dr. Stein Gold, who has no financial relationship with Almirall, has received research funding from and/or served as a consultant to roughly a dozen other pharmaceutical companies. MedscapeLIVE! and this news organization are owned by the same parent company.
FROM INNOVATIONS IN DERMATOLOGY
Vasodilatory medications found protective against rosacea
.
“Our initial hypothesis was that perhaps antihypertensive agents might be associated with worsening rosacea,” one of the study authors, Jennifer G. Powers, MD, associate professor of dermatology at the University of Iowa, Iowa City, said in an interview. “What we found was exactly the opposite – that in fact their presence in a medical chart correlated with lower rates of rosacea diagnoses, as defined by ICD 9/10 codes.”
According to the researchers, who published their findings in the Journal of the American Academy of Dermatology, cases of acute vasodilator-induced rosacea have been reported, but no long-term association has been established. “In fact, many widely used antihypertensive medications modulate peripheral vascular tone,” they wrote. “Therefore, chronic use in patients with hypertension may reduce damage to peripheral vessels, and thus decrease risk of rosacea.”
To determine the correlates between vasodilator use and risk of rosacea, Dr. Powers and colleagues identified 680 hypertensive patients being treated with vasodilators or a thiazide diuretic in whom rosacea developed within 5 years of initiating therapy between June 1, 2006, and April 31, 2019. Vasodilator therapies included angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), beta-blockers, and calcium channel blockers (CCBs). Patients on thiazide diuretics served as the control group. The researchers stratified the patients by age, gender, race, diabetes, chronic kidney disease, and coronary artery disease and calculated relative risk estimates comparing vasodilators with thiazides between strata.
Of the 680 patients, all but 40 were White; 127 were on thiazides, and the remaining 553 were on vasodilators. Overall, the researchers observed that use of vasodilators had a protective effect on the development of rosacea within 5 years, compared with thiazides (relative risk [RR], 0.56; P less than .0001). Specifically, the relative risk was 0.50 for ACE-inhibitors (P less than .0001); 0.69 for ARBs (P = .041); 0.55 for beta-blockers (P less than .0001); and 0.39 for CCBs (P less than .0001).
Dr. Powers and colleagues also observed significant inverse correlations in ACE-inhibitors, beta-blockers, and CCBs among White women aged 50 and older, but no significance was observed in non-White subgroups. The cohorts of patients with chronic kidney disease and coronary artery disease were too small for analysis.
“We were very surprised to find that many of the agents we think of as vasodilators might actually be beneficial for rosacea,” Dr. Powers said. “We would like to see these results reproduced in larger population studies. There are also potential questions about the mechanism at play. However, should these findings hold true, [it’s] all the more reason for our rosacea patients with hypertension to be managed well. They need not fear that those medications are worsening disease. Also, there might be new therapeutic options based on this data.”
The study received funding support from the National Center for Advancing Translational Sciences. The researchers reported having no financial disclosures.
One of Dr. Powers’ coauthors is her husband, Edward M. Powers, MD, a cardiology fellow at the University of Iowa. “We sometimes bounce ideas off one another and will talk about how systemic effects on the vasculature may impact skin disease,” she said, noting that they also published a report on statins and atopic dermatitis.
.
“Our initial hypothesis was that perhaps antihypertensive agents might be associated with worsening rosacea,” one of the study authors, Jennifer G. Powers, MD, associate professor of dermatology at the University of Iowa, Iowa City, said in an interview. “What we found was exactly the opposite – that in fact their presence in a medical chart correlated with lower rates of rosacea diagnoses, as defined by ICD 9/10 codes.”
According to the researchers, who published their findings in the Journal of the American Academy of Dermatology, cases of acute vasodilator-induced rosacea have been reported, but no long-term association has been established. “In fact, many widely used antihypertensive medications modulate peripheral vascular tone,” they wrote. “Therefore, chronic use in patients with hypertension may reduce damage to peripheral vessels, and thus decrease risk of rosacea.”
To determine the correlates between vasodilator use and risk of rosacea, Dr. Powers and colleagues identified 680 hypertensive patients being treated with vasodilators or a thiazide diuretic in whom rosacea developed within 5 years of initiating therapy between June 1, 2006, and April 31, 2019. Vasodilator therapies included angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), beta-blockers, and calcium channel blockers (CCBs). Patients on thiazide diuretics served as the control group. The researchers stratified the patients by age, gender, race, diabetes, chronic kidney disease, and coronary artery disease and calculated relative risk estimates comparing vasodilators with thiazides between strata.
Of the 680 patients, all but 40 were White; 127 were on thiazides, and the remaining 553 were on vasodilators. Overall, the researchers observed that use of vasodilators had a protective effect on the development of rosacea within 5 years, compared with thiazides (relative risk [RR], 0.56; P less than .0001). Specifically, the relative risk was 0.50 for ACE-inhibitors (P less than .0001); 0.69 for ARBs (P = .041); 0.55 for beta-blockers (P less than .0001); and 0.39 for CCBs (P less than .0001).
Dr. Powers and colleagues also observed significant inverse correlations in ACE-inhibitors, beta-blockers, and CCBs among White women aged 50 and older, but no significance was observed in non-White subgroups. The cohorts of patients with chronic kidney disease and coronary artery disease were too small for analysis.
“We were very surprised to find that many of the agents we think of as vasodilators might actually be beneficial for rosacea,” Dr. Powers said. “We would like to see these results reproduced in larger population studies. There are also potential questions about the mechanism at play. However, should these findings hold true, [it’s] all the more reason for our rosacea patients with hypertension to be managed well. They need not fear that those medications are worsening disease. Also, there might be new therapeutic options based on this data.”
The study received funding support from the National Center for Advancing Translational Sciences. The researchers reported having no financial disclosures.
One of Dr. Powers’ coauthors is her husband, Edward M. Powers, MD, a cardiology fellow at the University of Iowa. “We sometimes bounce ideas off one another and will talk about how systemic effects on the vasculature may impact skin disease,” she said, noting that they also published a report on statins and atopic dermatitis.
.
“Our initial hypothesis was that perhaps antihypertensive agents might be associated with worsening rosacea,” one of the study authors, Jennifer G. Powers, MD, associate professor of dermatology at the University of Iowa, Iowa City, said in an interview. “What we found was exactly the opposite – that in fact their presence in a medical chart correlated with lower rates of rosacea diagnoses, as defined by ICD 9/10 codes.”
According to the researchers, who published their findings in the Journal of the American Academy of Dermatology, cases of acute vasodilator-induced rosacea have been reported, but no long-term association has been established. “In fact, many widely used antihypertensive medications modulate peripheral vascular tone,” they wrote. “Therefore, chronic use in patients with hypertension may reduce damage to peripheral vessels, and thus decrease risk of rosacea.”
To determine the correlates between vasodilator use and risk of rosacea, Dr. Powers and colleagues identified 680 hypertensive patients being treated with vasodilators or a thiazide diuretic in whom rosacea developed within 5 years of initiating therapy between June 1, 2006, and April 31, 2019. Vasodilator therapies included angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), beta-blockers, and calcium channel blockers (CCBs). Patients on thiazide diuretics served as the control group. The researchers stratified the patients by age, gender, race, diabetes, chronic kidney disease, and coronary artery disease and calculated relative risk estimates comparing vasodilators with thiazides between strata.
Of the 680 patients, all but 40 were White; 127 were on thiazides, and the remaining 553 were on vasodilators. Overall, the researchers observed that use of vasodilators had a protective effect on the development of rosacea within 5 years, compared with thiazides (relative risk [RR], 0.56; P less than .0001). Specifically, the relative risk was 0.50 for ACE-inhibitors (P less than .0001); 0.69 for ARBs (P = .041); 0.55 for beta-blockers (P less than .0001); and 0.39 for CCBs (P less than .0001).
Dr. Powers and colleagues also observed significant inverse correlations in ACE-inhibitors, beta-blockers, and CCBs among White women aged 50 and older, but no significance was observed in non-White subgroups. The cohorts of patients with chronic kidney disease and coronary artery disease were too small for analysis.
“We were very surprised to find that many of the agents we think of as vasodilators might actually be beneficial for rosacea,” Dr. Powers said. “We would like to see these results reproduced in larger population studies. There are also potential questions about the mechanism at play. However, should these findings hold true, [it’s] all the more reason for our rosacea patients with hypertension to be managed well. They need not fear that those medications are worsening disease. Also, there might be new therapeutic options based on this data.”
The study received funding support from the National Center for Advancing Translational Sciences. The researchers reported having no financial disclosures.
One of Dr. Powers’ coauthors is her husband, Edward M. Powers, MD, a cardiology fellow at the University of Iowa. “We sometimes bounce ideas off one another and will talk about how systemic effects on the vasculature may impact skin disease,” she said, noting that they also published a report on statins and atopic dermatitis.
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
Energy-based devices: Expert shares treatment tips for rosacea, scars
, according to a 2020 international consensus publication that Jeremy B. Green, MD, reviewed during a virtual course on laser and aesthetic skin therapy.
During his presentation, he also reviewed laser treatment of scars. “Erythema is an indicator of scar activity,” said Dr. Green, a dermatologist in Coral Gables, Fla. “So, with flat, red scars, vascular devices are the first choice. If you’re going to treat with multiple lasers in a single session, use the vascular laser first, followed by a resurfacing laser if needed. If you treat with a resurfacing laser first, you’ll cause erythema and edema and you’ll obscure that blood vessel target.”
The manuscript, which was created by a panel of 26 dermatologists and plastic and reconstructive surgeons from 13 different countries, also calls for using scar treatment settings that are lower than those used for port wine stains, with mild purpura as the clinical endpoint to strive for.
Vascular lasers are also the expert panel’s first choice when a scar is painful or pruritic, while the second choice is an ablative fractional laser with intralesional triamcinolone and/or 5-fluorouracil (5-FU). “If the scar is hypertrophic, I will combine a vascular laser, then a nonablative or an ablative fractional laser, then intralesional triamcinolone mixed with 5-FU,” said Dr. Green, who was not involved in drafting the recommendations.
As for the first treatment of choice, 80% of the experts chose a pulsed dye laser, while others chose the KTP laser, intense pulsed light (IPL) and the neodymium yttrium aluminum garnet (Nd:YAG) laser. With regard to settings, when using a PDL and a 10-mm spot size, 41% of experts recommend a fluence of 5-6 J/cm2, 27% recommend a fluence of 4-5 J/cm2, and 27% recommend a fluence of 6-7 J/cm2. Pertaining to pulse duration, 50% favor 1.5 milliseconds, 18% use 3 milliseconds, and 18% use .45 milliseconds.
As for timing post surgery, 70% report treating less than 1 week after surgery and 90% report treating within 1 month post surgery. “I prefer to treat about 1 week after sutures are removed so the skin is re-epithelialized,” Dr. Green said. “The bottom line is, with postsurgical, posttraumatic scars, once the skin is healed, the sooner you get at it, the better.”
Rosacea
He also discussed the microvascular effects of PDL in combination with oxymetazoline 1% cream, an alpha1A adrenoceptor agonist, which is approved by the Food and Drug Administration for treatment of persistent facial erythema associated with rosacea. “This has been a hot topic lately,” Dr. Green said. “When the studies were done for FDA approval, there was an observation that vasodilation occurs 5 minutes after application of oxymetazoline, so the venule diameter increases. Sixty minutes after application, vasoconstriction happens, which is the desired clinical effect for patients with facial erythema.”
In a mouse study, researchers led by Bernard Choi, PhD, and Kristin M. Kelly, MD, of the Beckman Laser Institute and Medical Clinic, University of California, Irvine, found that the combination protocol of oxymetazoline application, followed 5 minutes later by PDL, induced persistent vascular shutdown 7 days after irradiation. Vascular shutdown occurred in 67% of vessels treated with oxymetazoline plus PDL at day 7 vs. 17% in those treated with saline plus PDL.
“This is fascinating,” Dr. Green said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “There is no publication I’m aware of in humans that has explored this timing, but I have used oxymetazoline in my clinic in patients with stubborn erythema and treated them with the vascular laser 5 minutes later.”
In a separate open-label study of 46 patients with moderate to severe facial erythema associated with rosacea, researchers found that oxymetazoline 1% as adjunctive therapy with energy-based therapy was safe and well tolerated, and reduced facial erythema in patients with moderate to severe persistent facial erythema associated with rosacea. Energy sources used were the PDL, KTP, or IPL.
In a study presented during the 2020 American Society for Laser Medicine & Surgery meeting, researchers led by Pooja Sodha, MD, of George Washington University, Washington, conducted a pilot trial of PDL plus oxymetazoline 1% cream for erythematotelangiectatic rosacea. Between baseline and 6 months’ follow-up the Clinician’s Erythema Assessment score fell from 4 to 2.
“Of note, I would also throw the kitchen sink at these patients medically, meaning I love topical ivermectin 1% cream,” Dr. Green said. “In some cases I’ll even use oral ivermectin and an oral tetracycline class antibiotic.”
He reported having received research funding and/or consulting fees from numerous device and pharmaceutical companies.
, according to a 2020 international consensus publication that Jeremy B. Green, MD, reviewed during a virtual course on laser and aesthetic skin therapy.
During his presentation, he also reviewed laser treatment of scars. “Erythema is an indicator of scar activity,” said Dr. Green, a dermatologist in Coral Gables, Fla. “So, with flat, red scars, vascular devices are the first choice. If you’re going to treat with multiple lasers in a single session, use the vascular laser first, followed by a resurfacing laser if needed. If you treat with a resurfacing laser first, you’ll cause erythema and edema and you’ll obscure that blood vessel target.”
The manuscript, which was created by a panel of 26 dermatologists and plastic and reconstructive surgeons from 13 different countries, also calls for using scar treatment settings that are lower than those used for port wine stains, with mild purpura as the clinical endpoint to strive for.
Vascular lasers are also the expert panel’s first choice when a scar is painful or pruritic, while the second choice is an ablative fractional laser with intralesional triamcinolone and/or 5-fluorouracil (5-FU). “If the scar is hypertrophic, I will combine a vascular laser, then a nonablative or an ablative fractional laser, then intralesional triamcinolone mixed with 5-FU,” said Dr. Green, who was not involved in drafting the recommendations.
As for the first treatment of choice, 80% of the experts chose a pulsed dye laser, while others chose the KTP laser, intense pulsed light (IPL) and the neodymium yttrium aluminum garnet (Nd:YAG) laser. With regard to settings, when using a PDL and a 10-mm spot size, 41% of experts recommend a fluence of 5-6 J/cm2, 27% recommend a fluence of 4-5 J/cm2, and 27% recommend a fluence of 6-7 J/cm2. Pertaining to pulse duration, 50% favor 1.5 milliseconds, 18% use 3 milliseconds, and 18% use .45 milliseconds.
As for timing post surgery, 70% report treating less than 1 week after surgery and 90% report treating within 1 month post surgery. “I prefer to treat about 1 week after sutures are removed so the skin is re-epithelialized,” Dr. Green said. “The bottom line is, with postsurgical, posttraumatic scars, once the skin is healed, the sooner you get at it, the better.”
Rosacea
He also discussed the microvascular effects of PDL in combination with oxymetazoline 1% cream, an alpha1A adrenoceptor agonist, which is approved by the Food and Drug Administration for treatment of persistent facial erythema associated with rosacea. “This has been a hot topic lately,” Dr. Green said. “When the studies were done for FDA approval, there was an observation that vasodilation occurs 5 minutes after application of oxymetazoline, so the venule diameter increases. Sixty minutes after application, vasoconstriction happens, which is the desired clinical effect for patients with facial erythema.”
In a mouse study, researchers led by Bernard Choi, PhD, and Kristin M. Kelly, MD, of the Beckman Laser Institute and Medical Clinic, University of California, Irvine, found that the combination protocol of oxymetazoline application, followed 5 minutes later by PDL, induced persistent vascular shutdown 7 days after irradiation. Vascular shutdown occurred in 67% of vessels treated with oxymetazoline plus PDL at day 7 vs. 17% in those treated with saline plus PDL.
“This is fascinating,” Dr. Green said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “There is no publication I’m aware of in humans that has explored this timing, but I have used oxymetazoline in my clinic in patients with stubborn erythema and treated them with the vascular laser 5 minutes later.”
In a separate open-label study of 46 patients with moderate to severe facial erythema associated with rosacea, researchers found that oxymetazoline 1% as adjunctive therapy with energy-based therapy was safe and well tolerated, and reduced facial erythema in patients with moderate to severe persistent facial erythema associated with rosacea. Energy sources used were the PDL, KTP, or IPL.
In a study presented during the 2020 American Society for Laser Medicine & Surgery meeting, researchers led by Pooja Sodha, MD, of George Washington University, Washington, conducted a pilot trial of PDL plus oxymetazoline 1% cream for erythematotelangiectatic rosacea. Between baseline and 6 months’ follow-up the Clinician’s Erythema Assessment score fell from 4 to 2.
“Of note, I would also throw the kitchen sink at these patients medically, meaning I love topical ivermectin 1% cream,” Dr. Green said. “In some cases I’ll even use oral ivermectin and an oral tetracycline class antibiotic.”
He reported having received research funding and/or consulting fees from numerous device and pharmaceutical companies.
, according to a 2020 international consensus publication that Jeremy B. Green, MD, reviewed during a virtual course on laser and aesthetic skin therapy.
During his presentation, he also reviewed laser treatment of scars. “Erythema is an indicator of scar activity,” said Dr. Green, a dermatologist in Coral Gables, Fla. “So, with flat, red scars, vascular devices are the first choice. If you’re going to treat with multiple lasers in a single session, use the vascular laser first, followed by a resurfacing laser if needed. If you treat with a resurfacing laser first, you’ll cause erythema and edema and you’ll obscure that blood vessel target.”
The manuscript, which was created by a panel of 26 dermatologists and plastic and reconstructive surgeons from 13 different countries, also calls for using scar treatment settings that are lower than those used for port wine stains, with mild purpura as the clinical endpoint to strive for.
Vascular lasers are also the expert panel’s first choice when a scar is painful or pruritic, while the second choice is an ablative fractional laser with intralesional triamcinolone and/or 5-fluorouracil (5-FU). “If the scar is hypertrophic, I will combine a vascular laser, then a nonablative or an ablative fractional laser, then intralesional triamcinolone mixed with 5-FU,” said Dr. Green, who was not involved in drafting the recommendations.
As for the first treatment of choice, 80% of the experts chose a pulsed dye laser, while others chose the KTP laser, intense pulsed light (IPL) and the neodymium yttrium aluminum garnet (Nd:YAG) laser. With regard to settings, when using a PDL and a 10-mm spot size, 41% of experts recommend a fluence of 5-6 J/cm2, 27% recommend a fluence of 4-5 J/cm2, and 27% recommend a fluence of 6-7 J/cm2. Pertaining to pulse duration, 50% favor 1.5 milliseconds, 18% use 3 milliseconds, and 18% use .45 milliseconds.
As for timing post surgery, 70% report treating less than 1 week after surgery and 90% report treating within 1 month post surgery. “I prefer to treat about 1 week after sutures are removed so the skin is re-epithelialized,” Dr. Green said. “The bottom line is, with postsurgical, posttraumatic scars, once the skin is healed, the sooner you get at it, the better.”
Rosacea
He also discussed the microvascular effects of PDL in combination with oxymetazoline 1% cream, an alpha1A adrenoceptor agonist, which is approved by the Food and Drug Administration for treatment of persistent facial erythema associated with rosacea. “This has been a hot topic lately,” Dr. Green said. “When the studies were done for FDA approval, there was an observation that vasodilation occurs 5 minutes after application of oxymetazoline, so the venule diameter increases. Sixty minutes after application, vasoconstriction happens, which is the desired clinical effect for patients with facial erythema.”
In a mouse study, researchers led by Bernard Choi, PhD, and Kristin M. Kelly, MD, of the Beckman Laser Institute and Medical Clinic, University of California, Irvine, found that the combination protocol of oxymetazoline application, followed 5 minutes later by PDL, induced persistent vascular shutdown 7 days after irradiation. Vascular shutdown occurred in 67% of vessels treated with oxymetazoline plus PDL at day 7 vs. 17% in those treated with saline plus PDL.
“This is fascinating,” Dr. Green said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “There is no publication I’m aware of in humans that has explored this timing, but I have used oxymetazoline in my clinic in patients with stubborn erythema and treated them with the vascular laser 5 minutes later.”
In a separate open-label study of 46 patients with moderate to severe facial erythema associated with rosacea, researchers found that oxymetazoline 1% as adjunctive therapy with energy-based therapy was safe and well tolerated, and reduced facial erythema in patients with moderate to severe persistent facial erythema associated with rosacea. Energy sources used were the PDL, KTP, or IPL.
In a study presented during the 2020 American Society for Laser Medicine & Surgery meeting, researchers led by Pooja Sodha, MD, of George Washington University, Washington, conducted a pilot trial of PDL plus oxymetazoline 1% cream for erythematotelangiectatic rosacea. Between baseline and 6 months’ follow-up the Clinician’s Erythema Assessment score fell from 4 to 2.
“Of note, I would also throw the kitchen sink at these patients medically, meaning I love topical ivermectin 1% cream,” Dr. Green said. “In some cases I’ll even use oral ivermectin and an oral tetracycline class antibiotic.”
He reported having received research funding and/or consulting fees from numerous device and pharmaceutical companies.
EXPERT ANALYSIS FROM A LASER & AESTHETIC SKIN THERAPY COURSE
Face masks can aggravate rosacea
The “maskne” phenomenon – that is, new onset or exacerbation of preexisting acne due to prolonged wearing of protective face masks – has become commonplace during the COVID-19 pandemic. Less well appreciated is that rosacea often markedly worsens, too, Giovanni Damiani, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
“This is particularly interesting because two inflammatory dermatoses with different pathogenesis are both mechanically and microbiologically triggered by mask use,” observed Dr. Damiani, a dermatologist at the University of Milan.
He presented . These patients – 23 with papulopustular and 13 with erythematotelangiectatic rosacea – were wearing face masks for at least 6 hours per day during quarantine. Most were using what Dr. Damiani termed “community masks,” meaning they weren’t approved by the European regulatory agency as personal protective equipment.
Every yardstick Dr. Damiani and coinvestigators employed to characterize the patients’ rosacea demonstrated that the dermatosis was significantly worse during the prolonged mask-wearing period. For example, the average prequarantine score on the Global Flushing Severity Scale was 2.56, jumping to 3.97 after a month of masked quarantine. The flushing score climbed from 1.83 to 2.78 in the subgroup with papulopustular rosacea, and from 3.85 to 6.08 in patients with erythematotelangiectatic rosacea. Scores on the Clinician’s Erythema Assessment rose from 1.09 to 1.7 in the papulopustular rosacea patients, and from 2.46 to 3.54 in those with erythematotelangiectatic rosacea.
Scores on the Dermatology Life Quality Index climbed from 7.35 prequarantine to 10.65 in the subgroup with papulopustular rosacea and from 5.15 to 8.69 in patients with erythematotelangiectatic rosacea. Investigator Global Assessment and Patient’s Self-Assessment scores also deteriorated significantly after a month in masked quarantine.
Clinically, the mask-aggravated rosacea, or “maskacea,” was mainly localized to the dorsal lower third of the nose as well as the cheeks. The ocular and perioral areas and the chin were least affected.
Dr. Damiani advised his colleagues to intensify therapy promptly when patients report any worsening of their preexisting rosacea in connection with use of face masks. He has found this condition is often relatively treatment resistant so long as affected patients continue to wear face masks as an essential tool in preventing transmission of COVID-19.
The dermatologist noted that not all face masks are equal offenders when it comes to aggravating common facial dermatoses. During the spring 2020 pandemic quarantine in Milan, 11.6% of 318 mask wearers, none health care professionals, presented to Dr. Damiani and coinvestigators for treatment of facial dermatoses. The facial dermatosis rate was 5.4% among 168 users of masks bearing the European Union CE mark signifying the devices met relevant safety and performance standards, compared with 18.7% in 150 users of community masks with no CE mark. The rate of irritant contact dermatitis was zero with the CE mark masks and 4.7% with the community masks.
During quarantine, however, these patients wore their protective face masks for only a limited time, since for the most part they were restricted to home. In contrast, during the first week after the quarantine was lifted in early May and the daily hours of mask use increased, facial dermatoses were diagnosed in 8.7% of 23 users of CE-approved masks, compared with 45% of 71 wearers of community masks. Dr. Damiani and colleagues diagnosed irritant contact dermatitis in 16% of the community mask wearers post quarantine, but in not a single user of a mask bearing the CE mark.
The National Rosacea Society has issued patient guidance on avoiding rosacea flare-ups during the Covid-19 pandemic.
Dr. Damiani reported having no financial conflicts regarding his study.
The “maskne” phenomenon – that is, new onset or exacerbation of preexisting acne due to prolonged wearing of protective face masks – has become commonplace during the COVID-19 pandemic. Less well appreciated is that rosacea often markedly worsens, too, Giovanni Damiani, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
“This is particularly interesting because two inflammatory dermatoses with different pathogenesis are both mechanically and microbiologically triggered by mask use,” observed Dr. Damiani, a dermatologist at the University of Milan.
He presented . These patients – 23 with papulopustular and 13 with erythematotelangiectatic rosacea – were wearing face masks for at least 6 hours per day during quarantine. Most were using what Dr. Damiani termed “community masks,” meaning they weren’t approved by the European regulatory agency as personal protective equipment.
Every yardstick Dr. Damiani and coinvestigators employed to characterize the patients’ rosacea demonstrated that the dermatosis was significantly worse during the prolonged mask-wearing period. For example, the average prequarantine score on the Global Flushing Severity Scale was 2.56, jumping to 3.97 after a month of masked quarantine. The flushing score climbed from 1.83 to 2.78 in the subgroup with papulopustular rosacea, and from 3.85 to 6.08 in patients with erythematotelangiectatic rosacea. Scores on the Clinician’s Erythema Assessment rose from 1.09 to 1.7 in the papulopustular rosacea patients, and from 2.46 to 3.54 in those with erythematotelangiectatic rosacea.
Scores on the Dermatology Life Quality Index climbed from 7.35 prequarantine to 10.65 in the subgroup with papulopustular rosacea and from 5.15 to 8.69 in patients with erythematotelangiectatic rosacea. Investigator Global Assessment and Patient’s Self-Assessment scores also deteriorated significantly after a month in masked quarantine.
Clinically, the mask-aggravated rosacea, or “maskacea,” was mainly localized to the dorsal lower third of the nose as well as the cheeks. The ocular and perioral areas and the chin were least affected.
Dr. Damiani advised his colleagues to intensify therapy promptly when patients report any worsening of their preexisting rosacea in connection with use of face masks. He has found this condition is often relatively treatment resistant so long as affected patients continue to wear face masks as an essential tool in preventing transmission of COVID-19.
The dermatologist noted that not all face masks are equal offenders when it comes to aggravating common facial dermatoses. During the spring 2020 pandemic quarantine in Milan, 11.6% of 318 mask wearers, none health care professionals, presented to Dr. Damiani and coinvestigators for treatment of facial dermatoses. The facial dermatosis rate was 5.4% among 168 users of masks bearing the European Union CE mark signifying the devices met relevant safety and performance standards, compared with 18.7% in 150 users of community masks with no CE mark. The rate of irritant contact dermatitis was zero with the CE mark masks and 4.7% with the community masks.
During quarantine, however, these patients wore their protective face masks for only a limited time, since for the most part they were restricted to home. In contrast, during the first week after the quarantine was lifted in early May and the daily hours of mask use increased, facial dermatoses were diagnosed in 8.7% of 23 users of CE-approved masks, compared with 45% of 71 wearers of community masks. Dr. Damiani and colleagues diagnosed irritant contact dermatitis in 16% of the community mask wearers post quarantine, but in not a single user of a mask bearing the CE mark.
The National Rosacea Society has issued patient guidance on avoiding rosacea flare-ups during the Covid-19 pandemic.
Dr. Damiani reported having no financial conflicts regarding his study.
The “maskne” phenomenon – that is, new onset or exacerbation of preexisting acne due to prolonged wearing of protective face masks – has become commonplace during the COVID-19 pandemic. Less well appreciated is that rosacea often markedly worsens, too, Giovanni Damiani, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
“This is particularly interesting because two inflammatory dermatoses with different pathogenesis are both mechanically and microbiologically triggered by mask use,” observed Dr. Damiani, a dermatologist at the University of Milan.
He presented . These patients – 23 with papulopustular and 13 with erythematotelangiectatic rosacea – were wearing face masks for at least 6 hours per day during quarantine. Most were using what Dr. Damiani termed “community masks,” meaning they weren’t approved by the European regulatory agency as personal protective equipment.
Every yardstick Dr. Damiani and coinvestigators employed to characterize the patients’ rosacea demonstrated that the dermatosis was significantly worse during the prolonged mask-wearing period. For example, the average prequarantine score on the Global Flushing Severity Scale was 2.56, jumping to 3.97 after a month of masked quarantine. The flushing score climbed from 1.83 to 2.78 in the subgroup with papulopustular rosacea, and from 3.85 to 6.08 in patients with erythematotelangiectatic rosacea. Scores on the Clinician’s Erythema Assessment rose from 1.09 to 1.7 in the papulopustular rosacea patients, and from 2.46 to 3.54 in those with erythematotelangiectatic rosacea.
Scores on the Dermatology Life Quality Index climbed from 7.35 prequarantine to 10.65 in the subgroup with papulopustular rosacea and from 5.15 to 8.69 in patients with erythematotelangiectatic rosacea. Investigator Global Assessment and Patient’s Self-Assessment scores also deteriorated significantly after a month in masked quarantine.
Clinically, the mask-aggravated rosacea, or “maskacea,” was mainly localized to the dorsal lower third of the nose as well as the cheeks. The ocular and perioral areas and the chin were least affected.
Dr. Damiani advised his colleagues to intensify therapy promptly when patients report any worsening of their preexisting rosacea in connection with use of face masks. He has found this condition is often relatively treatment resistant so long as affected patients continue to wear face masks as an essential tool in preventing transmission of COVID-19.
The dermatologist noted that not all face masks are equal offenders when it comes to aggravating common facial dermatoses. During the spring 2020 pandemic quarantine in Milan, 11.6% of 318 mask wearers, none health care professionals, presented to Dr. Damiani and coinvestigators for treatment of facial dermatoses. The facial dermatosis rate was 5.4% among 168 users of masks bearing the European Union CE mark signifying the devices met relevant safety and performance standards, compared with 18.7% in 150 users of community masks with no CE mark. The rate of irritant contact dermatitis was zero with the CE mark masks and 4.7% with the community masks.
During quarantine, however, these patients wore their protective face masks for only a limited time, since for the most part they were restricted to home. In contrast, during the first week after the quarantine was lifted in early May and the daily hours of mask use increased, facial dermatoses were diagnosed in 8.7% of 23 users of CE-approved masks, compared with 45% of 71 wearers of community masks. Dr. Damiani and colleagues diagnosed irritant contact dermatitis in 16% of the community mask wearers post quarantine, but in not a single user of a mask bearing the CE mark.
The National Rosacea Society has issued patient guidance on avoiding rosacea flare-ups during the Covid-19 pandemic.
Dr. Damiani reported having no financial conflicts regarding his study.
FROM THE EADV CONGRESS
Study results support screening rosacea patients for cardiometabolic disease
according to the results of a meta-analysis of more than 50,000 patients.
To date, “mounting comorbidities of rosacea have been identified, suggesting that rosacea is not simply a skin disease but has links to multiple systemic illnesses,” wrote Qi Chen, MD, of Central South University, Changsha, China, and colleagues. The association with rosacea and cardiometabolic disease has been controversial, they added.
In a study published in the Journal of the American Academy of Dermatology, they identified 13 studies including 50,442 rosacea patients and 1,525,864 controls. Approximately 71% of the rosacea patients were women.
Overall, patients with rosacea showed a statistically significant association for hypertension (risk ratio, 1.20; 95% confidence interval, 1.08-1.34; P = .001) and dyslipidemia (RR, 1.32; 95% CI, 1.10-1.58; P = .002). Specifically, rosacea patients averaged higher standard mean differences of systolic and diastolic blood pressure, total cholesterol, HDL cholesterol and LDL cholesterol, and triglycerides, compared with controls.
Rosacea was not significantly associated with an increased risk for ischemic heart disease, stroke, or diabetes, although the rosacea patients showed significantly increased risk of higher fasting blood glucose, compared with controls.
Findings don’t show causality
The study findings were limited by several factors, including the observational nature of some of the studies and the inability to perform subgroup analyses based on subtype and disease severity, the researchers noted. In addition, most of the rosacea patients were outpatients. “Further investigations are warranted to identify the relationship between rosacea and [cardiometabolic disease] in general populations to further validate the significance of our findings.”
However, the results support the value of screening for cardiometabolic disease in rosacea patients to facilitate diagnosis and treatment of disease at an early stage, they concluded.
“Rosacea has been linked statistically to many comorbidities including depression, anxiety, hypertension, and diabetes mellitus,” Julie Harper, MD, of the Dermatology and Skin Care Center of Birmingham (Alabama), said in an interview.
“This study looked more specifically at cardiometabolic disease and found a statistically significant correlation between rosacea and hypertension, higher total cholesterol, higher triglycerides and higher fasting blood glucose,” she said. However, “while there is an association present in this meta-analysis, we cannot assume a cause-and-effect relationship.”
Although the analysis does not prove causality, the key message for clinicians is that cardiometabolic disease is quite common in rosacea patients, and risk factors should be identified and treated early, said Dr. Harper. “Our patients with and without rosacea will benefit from age-appropriate screening, physical examination, and laboratory evaluation with a primary care physician. For rosacea patients in particular, we can advise them that early research suggests that individuals with rosacea might have an increased risk of hypertension and/or high cholesterol and triglycerides. It never hurts to make an appointment with primary care and to be checked.”
“We need more confirmatory studies that minimize the influence of confounding,” Dr. Harper added. Rosacea also has also been linked to obesity, which is another risk factor for cardiometabolic disease.
The study was supported by multiple grants from the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose. Dr. Harper had no relevant financial conflicts to disclose.
SOURCE: Chen Q et al. J Am Acad Dermatol. 2020 Nov;83(5):1331-40.
according to the results of a meta-analysis of more than 50,000 patients.
To date, “mounting comorbidities of rosacea have been identified, suggesting that rosacea is not simply a skin disease but has links to multiple systemic illnesses,” wrote Qi Chen, MD, of Central South University, Changsha, China, and colleagues. The association with rosacea and cardiometabolic disease has been controversial, they added.
In a study published in the Journal of the American Academy of Dermatology, they identified 13 studies including 50,442 rosacea patients and 1,525,864 controls. Approximately 71% of the rosacea patients were women.
Overall, patients with rosacea showed a statistically significant association for hypertension (risk ratio, 1.20; 95% confidence interval, 1.08-1.34; P = .001) and dyslipidemia (RR, 1.32; 95% CI, 1.10-1.58; P = .002). Specifically, rosacea patients averaged higher standard mean differences of systolic and diastolic blood pressure, total cholesterol, HDL cholesterol and LDL cholesterol, and triglycerides, compared with controls.
Rosacea was not significantly associated with an increased risk for ischemic heart disease, stroke, or diabetes, although the rosacea patients showed significantly increased risk of higher fasting blood glucose, compared with controls.
Findings don’t show causality
The study findings were limited by several factors, including the observational nature of some of the studies and the inability to perform subgroup analyses based on subtype and disease severity, the researchers noted. In addition, most of the rosacea patients were outpatients. “Further investigations are warranted to identify the relationship between rosacea and [cardiometabolic disease] in general populations to further validate the significance of our findings.”
However, the results support the value of screening for cardiometabolic disease in rosacea patients to facilitate diagnosis and treatment of disease at an early stage, they concluded.
“Rosacea has been linked statistically to many comorbidities including depression, anxiety, hypertension, and diabetes mellitus,” Julie Harper, MD, of the Dermatology and Skin Care Center of Birmingham (Alabama), said in an interview.
“This study looked more specifically at cardiometabolic disease and found a statistically significant correlation between rosacea and hypertension, higher total cholesterol, higher triglycerides and higher fasting blood glucose,” she said. However, “while there is an association present in this meta-analysis, we cannot assume a cause-and-effect relationship.”
Although the analysis does not prove causality, the key message for clinicians is that cardiometabolic disease is quite common in rosacea patients, and risk factors should be identified and treated early, said Dr. Harper. “Our patients with and without rosacea will benefit from age-appropriate screening, physical examination, and laboratory evaluation with a primary care physician. For rosacea patients in particular, we can advise them that early research suggests that individuals with rosacea might have an increased risk of hypertension and/or high cholesterol and triglycerides. It never hurts to make an appointment with primary care and to be checked.”
“We need more confirmatory studies that minimize the influence of confounding,” Dr. Harper added. Rosacea also has also been linked to obesity, which is another risk factor for cardiometabolic disease.
The study was supported by multiple grants from the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose. Dr. Harper had no relevant financial conflicts to disclose.
SOURCE: Chen Q et al. J Am Acad Dermatol. 2020 Nov;83(5):1331-40.
according to the results of a meta-analysis of more than 50,000 patients.
To date, “mounting comorbidities of rosacea have been identified, suggesting that rosacea is not simply a skin disease but has links to multiple systemic illnesses,” wrote Qi Chen, MD, of Central South University, Changsha, China, and colleagues. The association with rosacea and cardiometabolic disease has been controversial, they added.
In a study published in the Journal of the American Academy of Dermatology, they identified 13 studies including 50,442 rosacea patients and 1,525,864 controls. Approximately 71% of the rosacea patients were women.
Overall, patients with rosacea showed a statistically significant association for hypertension (risk ratio, 1.20; 95% confidence interval, 1.08-1.34; P = .001) and dyslipidemia (RR, 1.32; 95% CI, 1.10-1.58; P = .002). Specifically, rosacea patients averaged higher standard mean differences of systolic and diastolic blood pressure, total cholesterol, HDL cholesterol and LDL cholesterol, and triglycerides, compared with controls.
Rosacea was not significantly associated with an increased risk for ischemic heart disease, stroke, or diabetes, although the rosacea patients showed significantly increased risk of higher fasting blood glucose, compared with controls.
Findings don’t show causality
The study findings were limited by several factors, including the observational nature of some of the studies and the inability to perform subgroup analyses based on subtype and disease severity, the researchers noted. In addition, most of the rosacea patients were outpatients. “Further investigations are warranted to identify the relationship between rosacea and [cardiometabolic disease] in general populations to further validate the significance of our findings.”
However, the results support the value of screening for cardiometabolic disease in rosacea patients to facilitate diagnosis and treatment of disease at an early stage, they concluded.
“Rosacea has been linked statistically to many comorbidities including depression, anxiety, hypertension, and diabetes mellitus,” Julie Harper, MD, of the Dermatology and Skin Care Center of Birmingham (Alabama), said in an interview.
“This study looked more specifically at cardiometabolic disease and found a statistically significant correlation between rosacea and hypertension, higher total cholesterol, higher triglycerides and higher fasting blood glucose,” she said. However, “while there is an association present in this meta-analysis, we cannot assume a cause-and-effect relationship.”
Although the analysis does not prove causality, the key message for clinicians is that cardiometabolic disease is quite common in rosacea patients, and risk factors should be identified and treated early, said Dr. Harper. “Our patients with and without rosacea will benefit from age-appropriate screening, physical examination, and laboratory evaluation with a primary care physician. For rosacea patients in particular, we can advise them that early research suggests that individuals with rosacea might have an increased risk of hypertension and/or high cholesterol and triglycerides. It never hurts to make an appointment with primary care and to be checked.”
“We need more confirmatory studies that minimize the influence of confounding,” Dr. Harper added. Rosacea also has also been linked to obesity, which is another risk factor for cardiometabolic disease.
The study was supported by multiple grants from the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose. Dr. Harper had no relevant financial conflicts to disclose.
SOURCE: Chen Q et al. J Am Acad Dermatol. 2020 Nov;83(5):1331-40.
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
Moving from subtypes to phenotypes is simplifying management of rosacea
When a new phenotype approach to the diagnosis of rosacea was proposed 2 years ago, this simpler and more accurate method was accompanied by several corollary advantages, including a more rational approach to treatment and better methods of measuring treatment efficacy, according to an expert speaking at the annual Coastal Dermatology Symposium, held virtually.
“By looking at rosacea in a more simple way – but a more accurate way – we are able to track what happens [to key features] over time,” explained Jerry Tan, MD, of the University of Western Ontario, London.
With the previous method of subtyping, many rosacea patients failed to fit neatly into any of the four categories, producing confusion and diverting attention from troublesome symptoms.
“Rosacea patients often present with a range of features that span multiple subtypes or progress between them,” Dr. Tan explained. The risk is not just a delay in diagnosis but a failure to focus on symptoms patients find most bothersome.
The previous diagnostic criteria for rosacea, published in 2002, identified primary and secondary symptoms within its four subtypes. The new diagnostic criteria, endorsed by the National Rosacea Society and published in 2018, rely on phenotypes defined by diagnostic, major, and minor symptoms. Rather than the four previous subtypes, which were erythematotelangiectatic, papulopustular, phymatous, and ocular, the phenotypes facilitate diagnosis in patients with mixed features.
By replacing “the old thought process of subtyping” with a newer focus on phenotypes, the updated criteria were “aimed toward accuracy, simplicity and practicality,” Dr. Tan said.
Moreover, without squeezing patients into subgroups where they do not neatly fit, the new criteria draw attention to the specific symptoms that bring patients to the clinician.
The phenotype approach to treatment strategies was reflected in a systematic review of treatments based on phenotypes that was published in 2019, not long after the new classification system became available. In this review, coauthored by Dr. Tan, the GRADE certainty-of-evidence approach was employed to identify effective therapies, matching specific symptoms with specific therapies such as low-dose isotretinoin for papules or omega-3 fatty acids for dry eyes.
Based on a patient-centric approach that emphasizes control of key symptoms, Dr. Tan also described a method of documenting the severity of major and minor symptoms at each visit. With this method, called a rosacea patient tracker, patients and physicians can determine whether therapies are effective against the signs and symptoms of disease that they find most burdensome, according to Dr. Tan, who was the first author of an article he cited as a reference to this phenotype-based methodology.
Overall, the phenotype approach to rosacea “rationalizes treatment,” he said.
Specifically, the heterogeneity of symptoms in rosacea is mirrored in the heterogeneity of underlying pathophysiology. According to Dr. Tan, the upregulation of cytokines for inflammation, of angiogenic pathways for vascular symptoms, and of matrix metalloproteinases for tissue remodeling are all implicated in rosacea but drive different types of symptoms. While appropriate skin care and efforts to identify and minimize symptom triggers is appropriate for all patients, phenotypes provide a guide to the most appropriate therapies.
He said he hopes that the focus on phenotypes will draw attention to differences in these pathophysiological mechanisms. According to Dr. Tan, evaluating rosacea from the perspective of phenotypes has represented an important paradigm shift that extends beyond diagnosis.
“The move to the phenotype approach is hopefully simpler, more accurate, and more relevant,” Dr. Tan said.
This same approach has been advocated by others, including Esther J. van Zurren, MD, professor of dermatology at Leiden University Medical Centre in the Netherlands, the lead author of the 2018 systematic review article discussed by Dr. Tan. In this review article on the phenotype approach, specific strategies were recommended for specific symptoms on the basis of grading by an international group of experts that included Dr. Tan, a coauthor.
“These strategies should be directed toward achieving improvements in general well-being by targeting those aspects most bothersome to the patient,” the article advises. Like Dr. Tan, she considers this phenotype-based approach to diagnosis and treatment to be a meaningful clinical advance over the guidelines published in 2002.
“Management strategies for people with rosacea should include phenotype-based treatments,” she agreed, adding that specific choices should be made on the basis of these phenotypes “instead of the previous subtype classification.”
The meeting was jointly presented by the University of Louisville and Global Academy for Medical Education. This publication and Global Academy for Medical Education are owned by the same parent company.
When a new phenotype approach to the diagnosis of rosacea was proposed 2 years ago, this simpler and more accurate method was accompanied by several corollary advantages, including a more rational approach to treatment and better methods of measuring treatment efficacy, according to an expert speaking at the annual Coastal Dermatology Symposium, held virtually.
“By looking at rosacea in a more simple way – but a more accurate way – we are able to track what happens [to key features] over time,” explained Jerry Tan, MD, of the University of Western Ontario, London.
With the previous method of subtyping, many rosacea patients failed to fit neatly into any of the four categories, producing confusion and diverting attention from troublesome symptoms.
“Rosacea patients often present with a range of features that span multiple subtypes or progress between them,” Dr. Tan explained. The risk is not just a delay in diagnosis but a failure to focus on symptoms patients find most bothersome.
The previous diagnostic criteria for rosacea, published in 2002, identified primary and secondary symptoms within its four subtypes. The new diagnostic criteria, endorsed by the National Rosacea Society and published in 2018, rely on phenotypes defined by diagnostic, major, and minor symptoms. Rather than the four previous subtypes, which were erythematotelangiectatic, papulopustular, phymatous, and ocular, the phenotypes facilitate diagnosis in patients with mixed features.
By replacing “the old thought process of subtyping” with a newer focus on phenotypes, the updated criteria were “aimed toward accuracy, simplicity and practicality,” Dr. Tan said.
Moreover, without squeezing patients into subgroups where they do not neatly fit, the new criteria draw attention to the specific symptoms that bring patients to the clinician.
The phenotype approach to treatment strategies was reflected in a systematic review of treatments based on phenotypes that was published in 2019, not long after the new classification system became available. In this review, coauthored by Dr. Tan, the GRADE certainty-of-evidence approach was employed to identify effective therapies, matching specific symptoms with specific therapies such as low-dose isotretinoin for papules or omega-3 fatty acids for dry eyes.
Based on a patient-centric approach that emphasizes control of key symptoms, Dr. Tan also described a method of documenting the severity of major and minor symptoms at each visit. With this method, called a rosacea patient tracker, patients and physicians can determine whether therapies are effective against the signs and symptoms of disease that they find most burdensome, according to Dr. Tan, who was the first author of an article he cited as a reference to this phenotype-based methodology.
Overall, the phenotype approach to rosacea “rationalizes treatment,” he said.
Specifically, the heterogeneity of symptoms in rosacea is mirrored in the heterogeneity of underlying pathophysiology. According to Dr. Tan, the upregulation of cytokines for inflammation, of angiogenic pathways for vascular symptoms, and of matrix metalloproteinases for tissue remodeling are all implicated in rosacea but drive different types of symptoms. While appropriate skin care and efforts to identify and minimize symptom triggers is appropriate for all patients, phenotypes provide a guide to the most appropriate therapies.
He said he hopes that the focus on phenotypes will draw attention to differences in these pathophysiological mechanisms. According to Dr. Tan, evaluating rosacea from the perspective of phenotypes has represented an important paradigm shift that extends beyond diagnosis.
“The move to the phenotype approach is hopefully simpler, more accurate, and more relevant,” Dr. Tan said.
This same approach has been advocated by others, including Esther J. van Zurren, MD, professor of dermatology at Leiden University Medical Centre in the Netherlands, the lead author of the 2018 systematic review article discussed by Dr. Tan. In this review article on the phenotype approach, specific strategies were recommended for specific symptoms on the basis of grading by an international group of experts that included Dr. Tan, a coauthor.
“These strategies should be directed toward achieving improvements in general well-being by targeting those aspects most bothersome to the patient,” the article advises. Like Dr. Tan, she considers this phenotype-based approach to diagnosis and treatment to be a meaningful clinical advance over the guidelines published in 2002.
“Management strategies for people with rosacea should include phenotype-based treatments,” she agreed, adding that specific choices should be made on the basis of these phenotypes “instead of the previous subtype classification.”
The meeting was jointly presented by the University of Louisville and Global Academy for Medical Education. This publication and Global Academy for Medical Education are owned by the same parent company.
When a new phenotype approach to the diagnosis of rosacea was proposed 2 years ago, this simpler and more accurate method was accompanied by several corollary advantages, including a more rational approach to treatment and better methods of measuring treatment efficacy, according to an expert speaking at the annual Coastal Dermatology Symposium, held virtually.
“By looking at rosacea in a more simple way – but a more accurate way – we are able to track what happens [to key features] over time,” explained Jerry Tan, MD, of the University of Western Ontario, London.
With the previous method of subtyping, many rosacea patients failed to fit neatly into any of the four categories, producing confusion and diverting attention from troublesome symptoms.
“Rosacea patients often present with a range of features that span multiple subtypes or progress between them,” Dr. Tan explained. The risk is not just a delay in diagnosis but a failure to focus on symptoms patients find most bothersome.
The previous diagnostic criteria for rosacea, published in 2002, identified primary and secondary symptoms within its four subtypes. The new diagnostic criteria, endorsed by the National Rosacea Society and published in 2018, rely on phenotypes defined by diagnostic, major, and minor symptoms. Rather than the four previous subtypes, which were erythematotelangiectatic, papulopustular, phymatous, and ocular, the phenotypes facilitate diagnosis in patients with mixed features.
By replacing “the old thought process of subtyping” with a newer focus on phenotypes, the updated criteria were “aimed toward accuracy, simplicity and practicality,” Dr. Tan said.
Moreover, without squeezing patients into subgroups where they do not neatly fit, the new criteria draw attention to the specific symptoms that bring patients to the clinician.
The phenotype approach to treatment strategies was reflected in a systematic review of treatments based on phenotypes that was published in 2019, not long after the new classification system became available. In this review, coauthored by Dr. Tan, the GRADE certainty-of-evidence approach was employed to identify effective therapies, matching specific symptoms with specific therapies such as low-dose isotretinoin for papules or omega-3 fatty acids for dry eyes.
Based on a patient-centric approach that emphasizes control of key symptoms, Dr. Tan also described a method of documenting the severity of major and minor symptoms at each visit. With this method, called a rosacea patient tracker, patients and physicians can determine whether therapies are effective against the signs and symptoms of disease that they find most burdensome, according to Dr. Tan, who was the first author of an article he cited as a reference to this phenotype-based methodology.
Overall, the phenotype approach to rosacea “rationalizes treatment,” he said.
Specifically, the heterogeneity of symptoms in rosacea is mirrored in the heterogeneity of underlying pathophysiology. According to Dr. Tan, the upregulation of cytokines for inflammation, of angiogenic pathways for vascular symptoms, and of matrix metalloproteinases for tissue remodeling are all implicated in rosacea but drive different types of symptoms. While appropriate skin care and efforts to identify and minimize symptom triggers is appropriate for all patients, phenotypes provide a guide to the most appropriate therapies.
He said he hopes that the focus on phenotypes will draw attention to differences in these pathophysiological mechanisms. According to Dr. Tan, evaluating rosacea from the perspective of phenotypes has represented an important paradigm shift that extends beyond diagnosis.
“The move to the phenotype approach is hopefully simpler, more accurate, and more relevant,” Dr. Tan said.
This same approach has been advocated by others, including Esther J. van Zurren, MD, professor of dermatology at Leiden University Medical Centre in the Netherlands, the lead author of the 2018 systematic review article discussed by Dr. Tan. In this review article on the phenotype approach, specific strategies were recommended for specific symptoms on the basis of grading by an international group of experts that included Dr. Tan, a coauthor.
“These strategies should be directed toward achieving improvements in general well-being by targeting those aspects most bothersome to the patient,” the article advises. Like Dr. Tan, she considers this phenotype-based approach to diagnosis and treatment to be a meaningful clinical advance over the guidelines published in 2002.
“Management strategies for people with rosacea should include phenotype-based treatments,” she agreed, adding that specific choices should be made on the basis of these phenotypes “instead of the previous subtype classification.”
The meeting was jointly presented by the University of Louisville and Global Academy for Medical Education. This publication and Global Academy for Medical Education are owned by the same parent company.
FROM COASTAL DERM
Role of lasers and light sources in medicine continue to expand
suggests R. Rox Anderson, MD.
“I’ve been doing this in my practice for a number of years and it’s quite gratifying,” Dr. Anderson, a dermatologist who directs the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston, said during a virtual course on laser and aesthetic skin therapy. “You treat the periorbital skin, mostly under the eye, just as if you were treating telangiectasia rosacea. The meibomian glands under the upper eyelid that cause this disease are sebaceous glands, and most of the people with dry eye have rosacea.”
In a retrospective noncomparative, interventional case series, 78 patients with severe dry eye syndrome were treated with intense pulsed-light therapy and gland expression at a single outpatient clinic over 30 months. Physician-judged improvement in dry eye tear breakup time was found for 87% of patients with an average of seven treatment visits and four maintenance visits, while 93% of patients reported posttreatment satisfaction with the degree of dry eye syndrome symptoms. More information about the approach were published in Investigative Ophthalmology & Visual Science and Current Opinion in Ophthalmology.
“What’s gratifying here is that most patients will get about 2 months of relief after a single treatment,” Dr. Anderson said. “They are very happy – some of the happiest patients in my practice. Many ophthalmologists don’t have the technology, so I think you can do this depending on your local referral system.”
Light-based approaches are also making promising inroads in cancer treatment. A recent study led by Martin Purschke, PhD, at the Wellman Center evaluated the use of a novel radio-phototherapy approach for killing cancer cells. The center of solid tissue tumors that are treated with radiotherapy is hypoxic, Dr. Anderson explained, “and oxygen is typically located around the perimeter of the tumor. After a radiation therapy treatment, you kill only the outer portion of it, and then the remaining cells grow back, and you end up with the same tumor. This is why you have to do radiation therapy over and over again. In contrast, if you add scintillating nanoparticles, which are particles with a very high C number atoms in them that pick up the x-ray photon and then emit many UV photons from one x-ray photon, they are very efficient at converting x-ray energy to UV energy.” The x-ray, he added, “generates UV light, and the UV light kills the tumor. We’re hoping that we can make a dent in radiotherapy this way.”
Dr. Anderson predicted that fiber lasers, which are highly advanced for industrial applications, will play an increasing role in dermatology and in other areas of medicine. “There are not a new kid on the block anymore but fiber lasers are relatively new to medicine,” he said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “We are seeing incredible capabilities with fiber lasers: essentially any wavelength, any power, any pulse duration you want. The lasers are efficient, small, rugged, and their lifetime exceeds your lifetime. They are likely to displace many of our old lasers in dermatology. I don’t know when, but I know it will happen.”
He reported having received research funding and/or consulting fees from numerous device and pharmaceutical companies.
suggests R. Rox Anderson, MD.
“I’ve been doing this in my practice for a number of years and it’s quite gratifying,” Dr. Anderson, a dermatologist who directs the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston, said during a virtual course on laser and aesthetic skin therapy. “You treat the periorbital skin, mostly under the eye, just as if you were treating telangiectasia rosacea. The meibomian glands under the upper eyelid that cause this disease are sebaceous glands, and most of the people with dry eye have rosacea.”
In a retrospective noncomparative, interventional case series, 78 patients with severe dry eye syndrome were treated with intense pulsed-light therapy and gland expression at a single outpatient clinic over 30 months. Physician-judged improvement in dry eye tear breakup time was found for 87% of patients with an average of seven treatment visits and four maintenance visits, while 93% of patients reported posttreatment satisfaction with the degree of dry eye syndrome symptoms. More information about the approach were published in Investigative Ophthalmology & Visual Science and Current Opinion in Ophthalmology.
“What’s gratifying here is that most patients will get about 2 months of relief after a single treatment,” Dr. Anderson said. “They are very happy – some of the happiest patients in my practice. Many ophthalmologists don’t have the technology, so I think you can do this depending on your local referral system.”
Light-based approaches are also making promising inroads in cancer treatment. A recent study led by Martin Purschke, PhD, at the Wellman Center evaluated the use of a novel radio-phototherapy approach for killing cancer cells. The center of solid tissue tumors that are treated with radiotherapy is hypoxic, Dr. Anderson explained, “and oxygen is typically located around the perimeter of the tumor. After a radiation therapy treatment, you kill only the outer portion of it, and then the remaining cells grow back, and you end up with the same tumor. This is why you have to do radiation therapy over and over again. In contrast, if you add scintillating nanoparticles, which are particles with a very high C number atoms in them that pick up the x-ray photon and then emit many UV photons from one x-ray photon, they are very efficient at converting x-ray energy to UV energy.” The x-ray, he added, “generates UV light, and the UV light kills the tumor. We’re hoping that we can make a dent in radiotherapy this way.”
Dr. Anderson predicted that fiber lasers, which are highly advanced for industrial applications, will play an increasing role in dermatology and in other areas of medicine. “There are not a new kid on the block anymore but fiber lasers are relatively new to medicine,” he said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “We are seeing incredible capabilities with fiber lasers: essentially any wavelength, any power, any pulse duration you want. The lasers are efficient, small, rugged, and their lifetime exceeds your lifetime. They are likely to displace many of our old lasers in dermatology. I don’t know when, but I know it will happen.”
He reported having received research funding and/or consulting fees from numerous device and pharmaceutical companies.
suggests R. Rox Anderson, MD.
“I’ve been doing this in my practice for a number of years and it’s quite gratifying,” Dr. Anderson, a dermatologist who directs the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston, said during a virtual course on laser and aesthetic skin therapy. “You treat the periorbital skin, mostly under the eye, just as if you were treating telangiectasia rosacea. The meibomian glands under the upper eyelid that cause this disease are sebaceous glands, and most of the people with dry eye have rosacea.”
In a retrospective noncomparative, interventional case series, 78 patients with severe dry eye syndrome were treated with intense pulsed-light therapy and gland expression at a single outpatient clinic over 30 months. Physician-judged improvement in dry eye tear breakup time was found for 87% of patients with an average of seven treatment visits and four maintenance visits, while 93% of patients reported posttreatment satisfaction with the degree of dry eye syndrome symptoms. More information about the approach were published in Investigative Ophthalmology & Visual Science and Current Opinion in Ophthalmology.
“What’s gratifying here is that most patients will get about 2 months of relief after a single treatment,” Dr. Anderson said. “They are very happy – some of the happiest patients in my practice. Many ophthalmologists don’t have the technology, so I think you can do this depending on your local referral system.”
Light-based approaches are also making promising inroads in cancer treatment. A recent study led by Martin Purschke, PhD, at the Wellman Center evaluated the use of a novel radio-phototherapy approach for killing cancer cells. The center of solid tissue tumors that are treated with radiotherapy is hypoxic, Dr. Anderson explained, “and oxygen is typically located around the perimeter of the tumor. After a radiation therapy treatment, you kill only the outer portion of it, and then the remaining cells grow back, and you end up with the same tumor. This is why you have to do radiation therapy over and over again. In contrast, if you add scintillating nanoparticles, which are particles with a very high C number atoms in them that pick up the x-ray photon and then emit many UV photons from one x-ray photon, they are very efficient at converting x-ray energy to UV energy.” The x-ray, he added, “generates UV light, and the UV light kills the tumor. We’re hoping that we can make a dent in radiotherapy this way.”
Dr. Anderson predicted that fiber lasers, which are highly advanced for industrial applications, will play an increasing role in dermatology and in other areas of medicine. “There are not a new kid on the block anymore but fiber lasers are relatively new to medicine,” he said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “We are seeing incredible capabilities with fiber lasers: essentially any wavelength, any power, any pulse duration you want. The lasers are efficient, small, rugged, and their lifetime exceeds your lifetime. They are likely to displace many of our old lasers in dermatology. I don’t know when, but I know it will happen.”
He reported having received research funding and/or consulting fees from numerous device and pharmaceutical companies.
FROM A LASER & AESTHETIC SKIN THERAPY COURSE
Treatment pipeline holds promise for rosacea
, according to Linda Stein Gold, MD, director of clinical research, in the department of dermatology, Henry Ford Hospital in Detroit.
In addition, topical minocycline has recently been approved by the Food and Drug Administration for the treatment of rosacea in a 1.5% foam formulation. “The reason it has taken so long to have a minocycline product is that it is challenging to deliver it topically,” she said in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually. Studies of higher concentrations were not significantly better for rosacea, so development of the 1.5% foam was pursued, although a 4% foam is approved for the treatment of acne.
Dr. Stein Gold shared results from a pair of 12-week randomized trials in which significantly more patients treated with topical minocycline foam showed treatment success, compared with those on vehicle, based on Investigator’s Global Assessment (IGA) scores of clear or almost clear and a decrease of at least two grades from baseline: 52.1% versus 43.0% in one study and 49.1% versus 39.0% in the second, statistically significant differences. The product also was well tolerated, with most patients reporting no side effects or mild side effects.
Research on how to maximize effectiveness of available treatments such as ivermectin is ongoing, but several new treatments in the pipeline continue to show promising results, she noted.
An up-and-coming rosacea treatment is an old product used in a new way: Benzoyl peroxide in a microencapsulated form. “Benzoyl peroxide is encased in silica molecules that allow very slow release of the benzoyl peroxide into the skin and that leads to decreased irritation,” Dr. Stein Gold explained. The deposit of active ingredient on the skin appears to stay below the level of irritation.
Dr. Stein Gold and colleagues conducted two randomized, vehicle-controlled trials in which 733 adults with moderate to severe rosacea were treated with either the encapsulated benzoyl peroxide cream formulation or a vehicle applied once daily for 12 weeks.
At 12 weeks, IGA success increased over the course of the studies, and reached 43.5% in one and 50.1% in the other, compared with 16.1% and 25.9%, respectively, for the vehicle groups in those studies (P < .001 for both). Overall, she described this as “a nice improvement for a drug that we had not considered to be part of our treatment armamentarium for our rosacea patients.”
Dr. Stein Gold also shared data from a phase 2 study of low-dose oral minocycline in adults with papulopustular rosacea. A group of 200 patients used the drug or a placebo once daily for 16 weeks. The study examined 20-mg and 40-mg extended-release formulations, and found a significant improvement with the 40-mg dose over the 20-mg dose and over placebo, in terms of those who reached an IGA of 0 or 1, with a 2 grade improvement. While this is a phase 2 study, it may lead to oral minocycline as another treatment option, she said.
“It is an exciting time for the treatment of rosacea, with a variety of options and an active pipeline, so we can aim for clear skin for our patients,” she commented.
Dr. Stein Gold disclosed serving as an investigator and consultant for Galderma, Vyne, Sun, Sol Gel, and Almirall; she is a consultant and speaker for Ortho.
MedscapeLive and this news organization are owned by the same parent company.
, according to Linda Stein Gold, MD, director of clinical research, in the department of dermatology, Henry Ford Hospital in Detroit.
In addition, topical minocycline has recently been approved by the Food and Drug Administration for the treatment of rosacea in a 1.5% foam formulation. “The reason it has taken so long to have a minocycline product is that it is challenging to deliver it topically,” she said in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually. Studies of higher concentrations were not significantly better for rosacea, so development of the 1.5% foam was pursued, although a 4% foam is approved for the treatment of acne.
Dr. Stein Gold shared results from a pair of 12-week randomized trials in which significantly more patients treated with topical minocycline foam showed treatment success, compared with those on vehicle, based on Investigator’s Global Assessment (IGA) scores of clear or almost clear and a decrease of at least two grades from baseline: 52.1% versus 43.0% in one study and 49.1% versus 39.0% in the second, statistically significant differences. The product also was well tolerated, with most patients reporting no side effects or mild side effects.
Research on how to maximize effectiveness of available treatments such as ivermectin is ongoing, but several new treatments in the pipeline continue to show promising results, she noted.
An up-and-coming rosacea treatment is an old product used in a new way: Benzoyl peroxide in a microencapsulated form. “Benzoyl peroxide is encased in silica molecules that allow very slow release of the benzoyl peroxide into the skin and that leads to decreased irritation,” Dr. Stein Gold explained. The deposit of active ingredient on the skin appears to stay below the level of irritation.
Dr. Stein Gold and colleagues conducted two randomized, vehicle-controlled trials in which 733 adults with moderate to severe rosacea were treated with either the encapsulated benzoyl peroxide cream formulation or a vehicle applied once daily for 12 weeks.
At 12 weeks, IGA success increased over the course of the studies, and reached 43.5% in one and 50.1% in the other, compared with 16.1% and 25.9%, respectively, for the vehicle groups in those studies (P < .001 for both). Overall, she described this as “a nice improvement for a drug that we had not considered to be part of our treatment armamentarium for our rosacea patients.”
Dr. Stein Gold also shared data from a phase 2 study of low-dose oral minocycline in adults with papulopustular rosacea. A group of 200 patients used the drug or a placebo once daily for 16 weeks. The study examined 20-mg and 40-mg extended-release formulations, and found a significant improvement with the 40-mg dose over the 20-mg dose and over placebo, in terms of those who reached an IGA of 0 or 1, with a 2 grade improvement. While this is a phase 2 study, it may lead to oral minocycline as another treatment option, she said.
“It is an exciting time for the treatment of rosacea, with a variety of options and an active pipeline, so we can aim for clear skin for our patients,” she commented.
Dr. Stein Gold disclosed serving as an investigator and consultant for Galderma, Vyne, Sun, Sol Gel, and Almirall; she is a consultant and speaker for Ortho.
MedscapeLive and this news organization are owned by the same parent company.
, according to Linda Stein Gold, MD, director of clinical research, in the department of dermatology, Henry Ford Hospital in Detroit.
In addition, topical minocycline has recently been approved by the Food and Drug Administration for the treatment of rosacea in a 1.5% foam formulation. “The reason it has taken so long to have a minocycline product is that it is challenging to deliver it topically,” she said in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually. Studies of higher concentrations were not significantly better for rosacea, so development of the 1.5% foam was pursued, although a 4% foam is approved for the treatment of acne.
Dr. Stein Gold shared results from a pair of 12-week randomized trials in which significantly more patients treated with topical minocycline foam showed treatment success, compared with those on vehicle, based on Investigator’s Global Assessment (IGA) scores of clear or almost clear and a decrease of at least two grades from baseline: 52.1% versus 43.0% in one study and 49.1% versus 39.0% in the second, statistically significant differences. The product also was well tolerated, with most patients reporting no side effects or mild side effects.
Research on how to maximize effectiveness of available treatments such as ivermectin is ongoing, but several new treatments in the pipeline continue to show promising results, she noted.
An up-and-coming rosacea treatment is an old product used in a new way: Benzoyl peroxide in a microencapsulated form. “Benzoyl peroxide is encased in silica molecules that allow very slow release of the benzoyl peroxide into the skin and that leads to decreased irritation,” Dr. Stein Gold explained. The deposit of active ingredient on the skin appears to stay below the level of irritation.
Dr. Stein Gold and colleagues conducted two randomized, vehicle-controlled trials in which 733 adults with moderate to severe rosacea were treated with either the encapsulated benzoyl peroxide cream formulation or a vehicle applied once daily for 12 weeks.
At 12 weeks, IGA success increased over the course of the studies, and reached 43.5% in one and 50.1% in the other, compared with 16.1% and 25.9%, respectively, for the vehicle groups in those studies (P < .001 for both). Overall, she described this as “a nice improvement for a drug that we had not considered to be part of our treatment armamentarium for our rosacea patients.”
Dr. Stein Gold also shared data from a phase 2 study of low-dose oral minocycline in adults with papulopustular rosacea. A group of 200 patients used the drug or a placebo once daily for 16 weeks. The study examined 20-mg and 40-mg extended-release formulations, and found a significant improvement with the 40-mg dose over the 20-mg dose and over placebo, in terms of those who reached an IGA of 0 or 1, with a 2 grade improvement. While this is a phase 2 study, it may lead to oral minocycline as another treatment option, she said.
“It is an exciting time for the treatment of rosacea, with a variety of options and an active pipeline, so we can aim for clear skin for our patients,” she commented.
Dr. Stein Gold disclosed serving as an investigator and consultant for Galderma, Vyne, Sun, Sol Gel, and Almirall; she is a consultant and speaker for Ortho.
MedscapeLive and this news organization are owned by the same parent company.
FROM THE MEDSCAPELIVE LAS VEGAS DERMATOLOGY SEMINAR
Dermatologists and the history of skin care and beauty devices: Part 4
In this series on the role dermatologists have played in the history of skin care, I have covered dermatologists who developed cosmeceutical ingredients, dermatologists who consulted for the skin care industry, and those who developed a novel and successful skin care line. In this column, part 4 of the series, I will continue to discuss .
Dermatologists and Stiefel Laboratories
The Stiefel Medicinal Soap Company, founded in 1847, later became Stiefel Laboratories and was sold to GlaxoSmithKline in 2009. Stiefel Laboratories made many contributions over the years to the field of dermatology as chronicled in the excellent book, “Skin Saga” written by Charles Stiefel and published in 2018. The company was first known for soaps and groundbreaking products, such as “Freckle Soap” that sped epidermal turnover, resulting in a more even toned complexion.
Many dermatologists were involved in developing products and providing advice to the company. Herman Sharlit, MD, in New York, had the idea for a moisturizing soap (Oilatum), a detergent soap (Acne Aid detergent soap), and a coal tar soap (Polytar). Eugene Farber, MD, who was professor and chairman of the department of dermatology at Stanford (Calif.) University, consulted for Stiefel Laboratories and helped them identify and develop many products over the years.1 Stiefel Labs came out with the first facial scrub called Brasivol, an abrasive cream with aluminum oxide particles – the predecessor to modern day microdermabrasion. This facial scrub was conceived by dermatologist Rose Saperstein, MD, Los Angeles, who published a report2 on this in 1960 and also received a patent for it in 1963.3 Brasivol became the company’s first million dollar product.1
Stiefel Laboratories worked with many dermatologists to help them develop their ideas. They included Cleveland White, MD, who patented a highly absorbent foot and body powder known as Zeasorb powder. William Pace, MD, was a Canadian dermatologist who patented an acne treatment containing benzoyl peroxide and sulfur that Stiefel Labs marketed as Sulfoxyl Lotion. Dr. Pace is lovingly referred to as “the father of benzoyl peroxide” because his idea led Stiefel Labs to develop more benzoyl peroxide products. Benzoyl peroxide remains the most popular OTC ingredient to treat acne.
Comedone extractors
Many dermatologists have developed ways to extract comedones. There are publications on using paper clips,4,5safety pins,6 and medicine droppers,7 but some dermatologists have developed special comedone extractors, which include the following: Jay Schamberg, MD, developed a comedone extractor with a loop at each end. He disapproved of cutting a comedone, so did not include a needle or scalpel in his extractor.8
- Leonard Savitt, MD,9 attached a scalpel to one end of the Schamberg extractor.
- Alan Shalita, MD, developed a comedone extractor with a large, keyhole-shaped extracting orifice that made the tool easier to clean.10
The Saalfield comedone extractor combines a fixed pointed blade at one end and a small spoon-shaped expressor foot at the other end. (However, I have not been able to determine if Saalfield was a dermatologist.)
Dermatologist who developed methods for lesion excisions
Robert Segal, MD, a dermatologist at the University of Arizona, Tucson, invented the Dermablade. Although this is technically not a beauty device, I am including it because it has made the removal of unsightly moles and lesions much easier. He holds six patents on this device.
Dermatologists developed dermabrasion and microneedling
Ernst Kromayer, MD,11 a dermatologist in Germany, first described microneedling in 1905 when he mounted dental burrs on motor-driven flexible cord equipment to treat scars. Abner Kurtin, MD, a New York dermatologist, learned about Dr. Kromayer’s technique and modified it using stainless wireless brushes. Dr. Kurtin is known as the “father of dermabrasion.” His work was noted by Nobel Laureate Alexis Carrel, MD, who moved to New York City and began using the technique. Dr. Carrel’s protege, New York dermatologist, Norman Orentreich, MD, began using hypodermic needles instead of wire brushes. Microneedling has gained much popularity over the last decade and has been combined with platelet rich plasma injections.
Dermatologist-developed injection to shrink fat
Adam Rotunda, MD, was a dermatology resident at the University of California, Los Angeles, when he and his professor Michael Kolodney, MD, PhD, had the idea to develop deoxycholate as an injectable to reduce fat deposits. They filed a patent in 2004, conducted clinical trials, and it worked! In 2009, the patent for deoxycholic acid (ATX-10), marketed as Kybella, was granted. The rights to the drug were purchased by Aestherx, which later became Kythera Biopharmaceuticals. Kybella received Food and Drug Administration approval in 2015, and 6 months later, Kythera was acquired by Allergan.
Development of FDA-approved drugs to improve skin appearance
In 2004, dermatologists Stuart Shanler, MD, and Andrew Ondo, MD, filed a patent for the use of topical oxymetazoline for the treatment of the erythema of rosacea. They published their observations in 2007, noting that oxymetazoline improved facial flushing and erythema.11 Dr. Shanler then teamed up with dermatologist Neal Walker, MD, to form a start-up pharmaceutical company, Vicept Therapeutics, and took this compound through phase 2 clinical trials, while Dr. Shanler filed additional patents on oxymetazoline compositions and their uses. Once they successfully demonstrated the efficacy of topical oxymetazoline for rosacea, Allergan acquired the rights of the drug, successfully completed the phase 3 clinical trials, and Rhofade was approved by the FDA in 2017. It is the only topical drug invented and developed by a dermatologist to receive FDA approval since tretinoin (Renova) was developed by Albert Kligman, MD, and approved by the FDA for the improvement in appearance of fine wrinkling, mottled hyperpigmentation and roughness associated with photodamage in 1992.
The development of lasers
The last dermatologist I will discuss in this history series is R. Rox Anderson, MD, professor of dermatology at Harvard University, and director of the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston. It is impossible to list all his contributions in such a limited space. It would take a book. Building on efforts pioneered by Leon Goldman, MD, Dr. Anderson and his associates pioneered the use of lasers in dermatology and invented the idea of photothermolysis when they filed a patent on using light to remove hair in 1995.Dieter Manstein, MD, PhD,Dr. Anderson and others filed many patents that led to devices such as hair removal lasers, resurfacing lasers, and Fraxel lasers. They also made discoveries related to using cold to shrink fat. One of their inventions is known as CoolSculpting. They were so influential in the development of cosmetic dermatology that it is hard to imagine the field without their contributions.
This concludes my four-part series on the history of dermatologists’ role in the development of the skin care industry. I hope I have not forgotten anyone; if I did, I apologize. I have asked for ideas on Dermchat, Facebook and LinkedIn. Feel free to reach out if I missed one of your contributions. I will be giving lectures on this topic in the future and would be happy to include anyone I missed.
As the year 2020 ends, I want to say, Happy 50th Anniversary Dermatology News! I hope you enjoyed this historical series in honor of this anniversary.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. Stiefel, CW. (n.d.). Skin Saga: How a Tiny Family Soap Business Evolved Over Six Generations Into the #1 Dermatology Company in the World. United States: Smart Business Network.
2. Saperstein, RB. Arch Dermatol. 1960 Apr;81:601.
3. Saperstein, RB, and Stiefel, WK (1963). U.S. Patent No. 3,092,111. Washington, DC: U.S. Patent and Trademark Office.
4. George DE et al. J Am Acad Dermatol. 2006 Feb;54(2):326.
5. Cvancara JL, Meffert JJ. J Am Acad Dermatol. 1999 Mar;40(3):477-8.
6. Mukhtar M., Sharma R. Int J Dermatol. 2004 Dec;43(12):967-8.
7. Shellow, H. JAMA. 1951;147(18):1777.
8. Wright CS. Arch Dermatol. 1961;84(3):515.
9. Savitt LE. Arch Dermatol. 1961 Apr;83:660-1.
10. Shalita AR, Harris H. Arch Dermatol. 1972 May;105(5):759-60.
11. Shanler SD, Ondo AL. Arch Dermatol. 2007 Nov;143(11):1369-71.
In this series on the role dermatologists have played in the history of skin care, I have covered dermatologists who developed cosmeceutical ingredients, dermatologists who consulted for the skin care industry, and those who developed a novel and successful skin care line. In this column, part 4 of the series, I will continue to discuss .
Dermatologists and Stiefel Laboratories
The Stiefel Medicinal Soap Company, founded in 1847, later became Stiefel Laboratories and was sold to GlaxoSmithKline in 2009. Stiefel Laboratories made many contributions over the years to the field of dermatology as chronicled in the excellent book, “Skin Saga” written by Charles Stiefel and published in 2018. The company was first known for soaps and groundbreaking products, such as “Freckle Soap” that sped epidermal turnover, resulting in a more even toned complexion.
Many dermatologists were involved in developing products and providing advice to the company. Herman Sharlit, MD, in New York, had the idea for a moisturizing soap (Oilatum), a detergent soap (Acne Aid detergent soap), and a coal tar soap (Polytar). Eugene Farber, MD, who was professor and chairman of the department of dermatology at Stanford (Calif.) University, consulted for Stiefel Laboratories and helped them identify and develop many products over the years.1 Stiefel Labs came out with the first facial scrub called Brasivol, an abrasive cream with aluminum oxide particles – the predecessor to modern day microdermabrasion. This facial scrub was conceived by dermatologist Rose Saperstein, MD, Los Angeles, who published a report2 on this in 1960 and also received a patent for it in 1963.3 Brasivol became the company’s first million dollar product.1
Stiefel Laboratories worked with many dermatologists to help them develop their ideas. They included Cleveland White, MD, who patented a highly absorbent foot and body powder known as Zeasorb powder. William Pace, MD, was a Canadian dermatologist who patented an acne treatment containing benzoyl peroxide and sulfur that Stiefel Labs marketed as Sulfoxyl Lotion. Dr. Pace is lovingly referred to as “the father of benzoyl peroxide” because his idea led Stiefel Labs to develop more benzoyl peroxide products. Benzoyl peroxide remains the most popular OTC ingredient to treat acne.
Comedone extractors
Many dermatologists have developed ways to extract comedones. There are publications on using paper clips,4,5safety pins,6 and medicine droppers,7 but some dermatologists have developed special comedone extractors, which include the following: Jay Schamberg, MD, developed a comedone extractor with a loop at each end. He disapproved of cutting a comedone, so did not include a needle or scalpel in his extractor.8
- Leonard Savitt, MD,9 attached a scalpel to one end of the Schamberg extractor.
- Alan Shalita, MD, developed a comedone extractor with a large, keyhole-shaped extracting orifice that made the tool easier to clean.10
The Saalfield comedone extractor combines a fixed pointed blade at one end and a small spoon-shaped expressor foot at the other end. (However, I have not been able to determine if Saalfield was a dermatologist.)
Dermatologist who developed methods for lesion excisions
Robert Segal, MD, a dermatologist at the University of Arizona, Tucson, invented the Dermablade. Although this is technically not a beauty device, I am including it because it has made the removal of unsightly moles and lesions much easier. He holds six patents on this device.
Dermatologists developed dermabrasion and microneedling
Ernst Kromayer, MD,11 a dermatologist in Germany, first described microneedling in 1905 when he mounted dental burrs on motor-driven flexible cord equipment to treat scars. Abner Kurtin, MD, a New York dermatologist, learned about Dr. Kromayer’s technique and modified it using stainless wireless brushes. Dr. Kurtin is known as the “father of dermabrasion.” His work was noted by Nobel Laureate Alexis Carrel, MD, who moved to New York City and began using the technique. Dr. Carrel’s protege, New York dermatologist, Norman Orentreich, MD, began using hypodermic needles instead of wire brushes. Microneedling has gained much popularity over the last decade and has been combined with platelet rich plasma injections.
Dermatologist-developed injection to shrink fat
Adam Rotunda, MD, was a dermatology resident at the University of California, Los Angeles, when he and his professor Michael Kolodney, MD, PhD, had the idea to develop deoxycholate as an injectable to reduce fat deposits. They filed a patent in 2004, conducted clinical trials, and it worked! In 2009, the patent for deoxycholic acid (ATX-10), marketed as Kybella, was granted. The rights to the drug were purchased by Aestherx, which later became Kythera Biopharmaceuticals. Kybella received Food and Drug Administration approval in 2015, and 6 months later, Kythera was acquired by Allergan.
Development of FDA-approved drugs to improve skin appearance
In 2004, dermatologists Stuart Shanler, MD, and Andrew Ondo, MD, filed a patent for the use of topical oxymetazoline for the treatment of the erythema of rosacea. They published their observations in 2007, noting that oxymetazoline improved facial flushing and erythema.11 Dr. Shanler then teamed up with dermatologist Neal Walker, MD, to form a start-up pharmaceutical company, Vicept Therapeutics, and took this compound through phase 2 clinical trials, while Dr. Shanler filed additional patents on oxymetazoline compositions and their uses. Once they successfully demonstrated the efficacy of topical oxymetazoline for rosacea, Allergan acquired the rights of the drug, successfully completed the phase 3 clinical trials, and Rhofade was approved by the FDA in 2017. It is the only topical drug invented and developed by a dermatologist to receive FDA approval since tretinoin (Renova) was developed by Albert Kligman, MD, and approved by the FDA for the improvement in appearance of fine wrinkling, mottled hyperpigmentation and roughness associated with photodamage in 1992.
The development of lasers
The last dermatologist I will discuss in this history series is R. Rox Anderson, MD, professor of dermatology at Harvard University, and director of the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston. It is impossible to list all his contributions in such a limited space. It would take a book. Building on efforts pioneered by Leon Goldman, MD, Dr. Anderson and his associates pioneered the use of lasers in dermatology and invented the idea of photothermolysis when they filed a patent on using light to remove hair in 1995.Dieter Manstein, MD, PhD,Dr. Anderson and others filed many patents that led to devices such as hair removal lasers, resurfacing lasers, and Fraxel lasers. They also made discoveries related to using cold to shrink fat. One of their inventions is known as CoolSculpting. They were so influential in the development of cosmetic dermatology that it is hard to imagine the field without their contributions.
This concludes my four-part series on the history of dermatologists’ role in the development of the skin care industry. I hope I have not forgotten anyone; if I did, I apologize. I have asked for ideas on Dermchat, Facebook and LinkedIn. Feel free to reach out if I missed one of your contributions. I will be giving lectures on this topic in the future and would be happy to include anyone I missed.
As the year 2020 ends, I want to say, Happy 50th Anniversary Dermatology News! I hope you enjoyed this historical series in honor of this anniversary.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. Stiefel, CW. (n.d.). Skin Saga: How a Tiny Family Soap Business Evolved Over Six Generations Into the #1 Dermatology Company in the World. United States: Smart Business Network.
2. Saperstein, RB. Arch Dermatol. 1960 Apr;81:601.
3. Saperstein, RB, and Stiefel, WK (1963). U.S. Patent No. 3,092,111. Washington, DC: U.S. Patent and Trademark Office.
4. George DE et al. J Am Acad Dermatol. 2006 Feb;54(2):326.
5. Cvancara JL, Meffert JJ. J Am Acad Dermatol. 1999 Mar;40(3):477-8.
6. Mukhtar M., Sharma R. Int J Dermatol. 2004 Dec;43(12):967-8.
7. Shellow, H. JAMA. 1951;147(18):1777.
8. Wright CS. Arch Dermatol. 1961;84(3):515.
9. Savitt LE. Arch Dermatol. 1961 Apr;83:660-1.
10. Shalita AR, Harris H. Arch Dermatol. 1972 May;105(5):759-60.
11. Shanler SD, Ondo AL. Arch Dermatol. 2007 Nov;143(11):1369-71.
In this series on the role dermatologists have played in the history of skin care, I have covered dermatologists who developed cosmeceutical ingredients, dermatologists who consulted for the skin care industry, and those who developed a novel and successful skin care line. In this column, part 4 of the series, I will continue to discuss .
Dermatologists and Stiefel Laboratories
The Stiefel Medicinal Soap Company, founded in 1847, later became Stiefel Laboratories and was sold to GlaxoSmithKline in 2009. Stiefel Laboratories made many contributions over the years to the field of dermatology as chronicled in the excellent book, “Skin Saga” written by Charles Stiefel and published in 2018. The company was first known for soaps and groundbreaking products, such as “Freckle Soap” that sped epidermal turnover, resulting in a more even toned complexion.
Many dermatologists were involved in developing products and providing advice to the company. Herman Sharlit, MD, in New York, had the idea for a moisturizing soap (Oilatum), a detergent soap (Acne Aid detergent soap), and a coal tar soap (Polytar). Eugene Farber, MD, who was professor and chairman of the department of dermatology at Stanford (Calif.) University, consulted for Stiefel Laboratories and helped them identify and develop many products over the years.1 Stiefel Labs came out with the first facial scrub called Brasivol, an abrasive cream with aluminum oxide particles – the predecessor to modern day microdermabrasion. This facial scrub was conceived by dermatologist Rose Saperstein, MD, Los Angeles, who published a report2 on this in 1960 and also received a patent for it in 1963.3 Brasivol became the company’s first million dollar product.1
Stiefel Laboratories worked with many dermatologists to help them develop their ideas. They included Cleveland White, MD, who patented a highly absorbent foot and body powder known as Zeasorb powder. William Pace, MD, was a Canadian dermatologist who patented an acne treatment containing benzoyl peroxide and sulfur that Stiefel Labs marketed as Sulfoxyl Lotion. Dr. Pace is lovingly referred to as “the father of benzoyl peroxide” because his idea led Stiefel Labs to develop more benzoyl peroxide products. Benzoyl peroxide remains the most popular OTC ingredient to treat acne.
Comedone extractors
Many dermatologists have developed ways to extract comedones. There are publications on using paper clips,4,5safety pins,6 and medicine droppers,7 but some dermatologists have developed special comedone extractors, which include the following: Jay Schamberg, MD, developed a comedone extractor with a loop at each end. He disapproved of cutting a comedone, so did not include a needle or scalpel in his extractor.8
- Leonard Savitt, MD,9 attached a scalpel to one end of the Schamberg extractor.
- Alan Shalita, MD, developed a comedone extractor with a large, keyhole-shaped extracting orifice that made the tool easier to clean.10
The Saalfield comedone extractor combines a fixed pointed blade at one end and a small spoon-shaped expressor foot at the other end. (However, I have not been able to determine if Saalfield was a dermatologist.)
Dermatologist who developed methods for lesion excisions
Robert Segal, MD, a dermatologist at the University of Arizona, Tucson, invented the Dermablade. Although this is technically not a beauty device, I am including it because it has made the removal of unsightly moles and lesions much easier. He holds six patents on this device.
Dermatologists developed dermabrasion and microneedling
Ernst Kromayer, MD,11 a dermatologist in Germany, first described microneedling in 1905 when he mounted dental burrs on motor-driven flexible cord equipment to treat scars. Abner Kurtin, MD, a New York dermatologist, learned about Dr. Kromayer’s technique and modified it using stainless wireless brushes. Dr. Kurtin is known as the “father of dermabrasion.” His work was noted by Nobel Laureate Alexis Carrel, MD, who moved to New York City and began using the technique. Dr. Carrel’s protege, New York dermatologist, Norman Orentreich, MD, began using hypodermic needles instead of wire brushes. Microneedling has gained much popularity over the last decade and has been combined with platelet rich plasma injections.
Dermatologist-developed injection to shrink fat
Adam Rotunda, MD, was a dermatology resident at the University of California, Los Angeles, when he and his professor Michael Kolodney, MD, PhD, had the idea to develop deoxycholate as an injectable to reduce fat deposits. They filed a patent in 2004, conducted clinical trials, and it worked! In 2009, the patent for deoxycholic acid (ATX-10), marketed as Kybella, was granted. The rights to the drug were purchased by Aestherx, which later became Kythera Biopharmaceuticals. Kybella received Food and Drug Administration approval in 2015, and 6 months later, Kythera was acquired by Allergan.
Development of FDA-approved drugs to improve skin appearance
In 2004, dermatologists Stuart Shanler, MD, and Andrew Ondo, MD, filed a patent for the use of topical oxymetazoline for the treatment of the erythema of rosacea. They published their observations in 2007, noting that oxymetazoline improved facial flushing and erythema.11 Dr. Shanler then teamed up with dermatologist Neal Walker, MD, to form a start-up pharmaceutical company, Vicept Therapeutics, and took this compound through phase 2 clinical trials, while Dr. Shanler filed additional patents on oxymetazoline compositions and their uses. Once they successfully demonstrated the efficacy of topical oxymetazoline for rosacea, Allergan acquired the rights of the drug, successfully completed the phase 3 clinical trials, and Rhofade was approved by the FDA in 2017. It is the only topical drug invented and developed by a dermatologist to receive FDA approval since tretinoin (Renova) was developed by Albert Kligman, MD, and approved by the FDA for the improvement in appearance of fine wrinkling, mottled hyperpigmentation and roughness associated with photodamage in 1992.
The development of lasers
The last dermatologist I will discuss in this history series is R. Rox Anderson, MD, professor of dermatology at Harvard University, and director of the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston. It is impossible to list all his contributions in such a limited space. It would take a book. Building on efforts pioneered by Leon Goldman, MD, Dr. Anderson and his associates pioneered the use of lasers in dermatology and invented the idea of photothermolysis when they filed a patent on using light to remove hair in 1995.Dieter Manstein, MD, PhD,Dr. Anderson and others filed many patents that led to devices such as hair removal lasers, resurfacing lasers, and Fraxel lasers. They also made discoveries related to using cold to shrink fat. One of their inventions is known as CoolSculpting. They were so influential in the development of cosmetic dermatology that it is hard to imagine the field without their contributions.
This concludes my four-part series on the history of dermatologists’ role in the development of the skin care industry. I hope I have not forgotten anyone; if I did, I apologize. I have asked for ideas on Dermchat, Facebook and LinkedIn. Feel free to reach out if I missed one of your contributions. I will be giving lectures on this topic in the future and would be happy to include anyone I missed.
As the year 2020 ends, I want to say, Happy 50th Anniversary Dermatology News! I hope you enjoyed this historical series in honor of this anniversary.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. Stiefel, CW. (n.d.). Skin Saga: How a Tiny Family Soap Business Evolved Over Six Generations Into the #1 Dermatology Company in the World. United States: Smart Business Network.
2. Saperstein, RB. Arch Dermatol. 1960 Apr;81:601.
3. Saperstein, RB, and Stiefel, WK (1963). U.S. Patent No. 3,092,111. Washington, DC: U.S. Patent and Trademark Office.
4. George DE et al. J Am Acad Dermatol. 2006 Feb;54(2):326.
5. Cvancara JL, Meffert JJ. J Am Acad Dermatol. 1999 Mar;40(3):477-8.
6. Mukhtar M., Sharma R. Int J Dermatol. 2004 Dec;43(12):967-8.
7. Shellow, H. JAMA. 1951;147(18):1777.
8. Wright CS. Arch Dermatol. 1961;84(3):515.
9. Savitt LE. Arch Dermatol. 1961 Apr;83:660-1.
10. Shalita AR, Harris H. Arch Dermatol. 1972 May;105(5):759-60.
11. Shanler SD, Ondo AL. Arch Dermatol. 2007 Nov;143(11):1369-71.
Active Comparator Trial Designs Used to Promote Development of Innovative New Medications
Spending on medications is expected to grow from $344 billion in 2018 to $420 billion in 2023, largely driven by the introduction of new branded drugs.1 These costs place substantial financial burden on patients, with nearly 30% of patients not taking their prescriptions as directed because of costs. Although many new medications have transformed how we care for patients, others may not offer meaningful benefit over existing less-costly alternatives that are supported by declining effect sizes of conventional placebo-controlled trials.2 Most medications are approved based on placebo-controlled trial data that does not include an arm comparing the new drug to standard of care, leaving clinicians and patients unable to make meaningful comparisons when deciding on the most appropriate or cost-effective treatment. We consider ways in which clinicians, patients, payers, and regulators could compel more meaningful trials from industry.
Although we often look to the US Food and Drug Administration (FDA) to ensure rigorous and appropriate testing of new medications, the primary mission of the FDA is to ensure efficacy and safety. As a result, pharmaceutical companies seeking approval in the United States have little incentive to go beyond providing the minimal level of evidence required: placebo-controlled randomized trials. Although these trials provide important data on whether a treatment works and its associated risks, they do not provide data on comparative effectiveness. When relevant inexpensive medications are already on the market for the same indication, these placebo-controlled trials provide inadequate evidence to guide clinical decision-making. This issue is particularly relevant in dermatology given how easily topical medications can be combined or reformulated to pursue additional market exclusivity. The addition of an active comparator arm represents an important opportunity to improve the value of these studies.
In the pivotal trials of clindamycin phosphate 1.2%–benzoyl peroxide 2.5% gel for the treatment of acne, the experimental group was not only compared to vehicle but also the active comparator arms of clindamycin alone and benzoyl peroxide alone. The mean percentage change in total lesions was 47.9% with clindamycin phosphate 1.2%–benzoyl peroxide 2.5% gel, 41.6% with the active comparator arm of benzoyl peroxide alone, 40.4% with the active comparator arm of clindamycin alone, and 26.2% for vehicle.3 With these data in mind, clinicians and patients can decide whether the additional benefit of this new product over benzoyl peroxide alone is worth the increased cost.
In contrast, the trials of dapsone gel 7.5% for the treatment of acne did not include an active comparator. The mean percentage change in total lesions was 48.9% for dapsone gel and 43.2% for vehicle.4 Given these data, it is possible that dapsone gel may be no more effective, or possibly less effective, than alternatives such as benzoyl peroxide or other topical antibiotics. Nevertheless, dapsone annual sales were more than $200 million in 2016,5 suggesting that effectively marketed new products can achieve high sales even without convincing evidence of their value compared to standard of care. Although dapsone may be a useful treatment, we cannot effectively make patient-centered clinical decisions given the lack of an active comparator trial design.
This issue is not limited to acne. Phase 3 trials of halobetasol propionate foam 0.05% for psoriasis and crisaborole for atopic dermatitis also did not include an active comparator arm.6,7 Given that topical steroids—and calcineurin inhibitors for atopic dermatitis—are mainstays of treatment for each condition, it is difficult to determine whether these new treatments offer meaningful advantages over existing options and how to incorporate them into our management strategies.
Unfortunately, expensive new medications that are adopted without convincing evidence of their benefit above standard of care can put patients at risk for financial toxicity, either directly through higher out-of-pocket costs or indirectly through higher premiums. Given the impact of rising medication costs on clinicians, patients, and payers, we propose several approaches these stakeholders could adopt to encourage the use of active comparator trial designs.
Clinicians and patients can encourage these trials by remaining skeptical of new treatments that were only compared to vehicle or placebo. Because new medications often are more expensive, clinicians and patients could avoid using these treatments without evidence of either increased efficacy or improved safety and tolerability. In addition, health care institutions should consider reducing pharmaceutical representatives’ access to clinicians to encourage treatment decisions based on the published literature and comparative effectiveness data rather than marketing.
Payers, such as Medicare, also could play a role by requiring active comparator trials for coverage of new medications, particularly when there are already other effective treatments available or other medications in the same class. Payers also could give preferred coverage tier or step therapy status to medications that demonstrate value over existing options.
Although regulatory approaches to increase use of active comparator designs may be more politically challenging to introduce, these options would be more administratively robust. The FDA or a novel regulatory body could require that new treatments demonstrate value in addition to safety and efficacy. This approach would be similar to the role of The National Institute for Health and Care Excellence in the United Kingdom or the recommendations of the European Medicines Agency. Such a group also could provide independent adjudication to ensure appropriate selection of a relevant active comparator. Another approach would be to give extended market exclusivity to medications that are approved based on trials including an additional active comparator arm, an approach used by the European Medicines Agency.
Any approach that encourages increased use of active comparator trials is not without potential downsides. It will be important to avoid unintended consequences of reduced research for rare diseases with smaller markets that may not be able to support the increased cost of these trials. As a result, it would be reasonable to forgo active comparator designs for mediations indicated for rare and orphan diseases or for medications with novel mechanisms of action.
Another argument against including an active comparator arm is that it may stifle innovation by driving up the cost of conducting trials; however, if a product is so marginally innovative that it cannot demonstrate superior safety or efficacy to an existing product, such a new treatment may not be worth the increased cost. In addition, patients provide a notable contribution by participating in these trials, and it is important to ensure that their efforts result in the highest-quality data possible. Furthermore, given the adverse physical and psychosocial impact of a wide variety of dermatologic diseases, the inclusion of an active comparator arm reduces the likelihood that patients will receive placebo, which will make these trials more ethical when effective treatments are available.8 By raising the bar, we can encourage pharmaceutical companies to pursue novel approaches that are more likely to have a revolutionary impact rather than minor modifications or formulations that offer little to no benefit at substantially increased cost.
Although some recent clinical trials in dermatology have included active comparators, many new medications continue to be introduced without any evidence of how they compare to existing standards of care. Until clinicians, patients, payers, and regulators demand that pharmaceutical companies conduct the necessary trials to not only demonstrate whether a treatment is effective and safe but also how it provides value, there will be continued introduction of marginal innovations rather than revolutionary treatments that improve patients’ lives. The next time a new medication is approved, as clinicians, patients, and payers, we must ask ourselves, is this treatment worth it?
- Aitken M, Kleinrock M. Medicine Use and Spending in the U.S.: A Review of 2018 and Outlook to 2023. IQVIA Institute for Human Data Science. https://www.iqvia.com/insights/the-iqvia-institute/reports/medicine-use-and-spending-in-the-us-a-review-of-2018-and-outlook-to-2023. Published May 9, 2019. Accessed August 15, 2020.
- Olfson M, Marcus SC. Decline in placebo-controlled trial results suggests new directions for comparative effectiveness research. Health Aff Proj Hope. 2019;32:1116-1125.
- Thiboutot D, Zaenglein A, Weiss J, et al. An aqueous gel fixed combination of clindamycin phosphate 1.2% and benzoyl peroxide 2.5% for the once-daily treatment of moderate to severe acne vulgaris: assessment of efficacy and safety in 2813 patients. J Am Acad Dermatol. 2008;59:792-800.
- Eichenfield LF, Lain T, Frankel EH, et al. Efficacy and safety of once-daily dapsone gel, 7.5% for treatment of adolescents and adults with acne vulgaris: second of two identically designed, large, multicenter, randomized, vehicle-controlled trials. J Drugs Dermatol. 2016;15:962-969.
- Allergan. 2017 Form 10-K. https://www.abbvie.com/content/dam/abbvie-dotcom/uploads/PDFs/allergan/allergan-annual-report-form-10K-123117.pdf. Accessed August 19, 2020.
- Paller AS, Tom WL, Lebwohl MG, et al. Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults. J Am Acad Dermatol. 2016;75:494-503.e6.
- Bhatia N, Stein Gold L, Kircik LH, et al. Two multicenter, randomized, double-blind, parallel group comparison studies of a novel foam formulation of halobetasol propionate, 0.05% vs its vehicle in adult subjects with plaque psoriasis. J Drugs Dermatol. 2019;18:790-796.
- Temple R, Ellenberg SS. Placebo-controlled trials and active-control trials in the evaluation of new treatments. part 1: ethical and scientific issues. Ann Intern Med. 2000;133:455-463.
Spending on medications is expected to grow from $344 billion in 2018 to $420 billion in 2023, largely driven by the introduction of new branded drugs.1 These costs place substantial financial burden on patients, with nearly 30% of patients not taking their prescriptions as directed because of costs. Although many new medications have transformed how we care for patients, others may not offer meaningful benefit over existing less-costly alternatives that are supported by declining effect sizes of conventional placebo-controlled trials.2 Most medications are approved based on placebo-controlled trial data that does not include an arm comparing the new drug to standard of care, leaving clinicians and patients unable to make meaningful comparisons when deciding on the most appropriate or cost-effective treatment. We consider ways in which clinicians, patients, payers, and regulators could compel more meaningful trials from industry.
Although we often look to the US Food and Drug Administration (FDA) to ensure rigorous and appropriate testing of new medications, the primary mission of the FDA is to ensure efficacy and safety. As a result, pharmaceutical companies seeking approval in the United States have little incentive to go beyond providing the minimal level of evidence required: placebo-controlled randomized trials. Although these trials provide important data on whether a treatment works and its associated risks, they do not provide data on comparative effectiveness. When relevant inexpensive medications are already on the market for the same indication, these placebo-controlled trials provide inadequate evidence to guide clinical decision-making. This issue is particularly relevant in dermatology given how easily topical medications can be combined or reformulated to pursue additional market exclusivity. The addition of an active comparator arm represents an important opportunity to improve the value of these studies.
In the pivotal trials of clindamycin phosphate 1.2%–benzoyl peroxide 2.5% gel for the treatment of acne, the experimental group was not only compared to vehicle but also the active comparator arms of clindamycin alone and benzoyl peroxide alone. The mean percentage change in total lesions was 47.9% with clindamycin phosphate 1.2%–benzoyl peroxide 2.5% gel, 41.6% with the active comparator arm of benzoyl peroxide alone, 40.4% with the active comparator arm of clindamycin alone, and 26.2% for vehicle.3 With these data in mind, clinicians and patients can decide whether the additional benefit of this new product over benzoyl peroxide alone is worth the increased cost.
In contrast, the trials of dapsone gel 7.5% for the treatment of acne did not include an active comparator. The mean percentage change in total lesions was 48.9% for dapsone gel and 43.2% for vehicle.4 Given these data, it is possible that dapsone gel may be no more effective, or possibly less effective, than alternatives such as benzoyl peroxide or other topical antibiotics. Nevertheless, dapsone annual sales were more than $200 million in 2016,5 suggesting that effectively marketed new products can achieve high sales even without convincing evidence of their value compared to standard of care. Although dapsone may be a useful treatment, we cannot effectively make patient-centered clinical decisions given the lack of an active comparator trial design.
This issue is not limited to acne. Phase 3 trials of halobetasol propionate foam 0.05% for psoriasis and crisaborole for atopic dermatitis also did not include an active comparator arm.6,7 Given that topical steroids—and calcineurin inhibitors for atopic dermatitis—are mainstays of treatment for each condition, it is difficult to determine whether these new treatments offer meaningful advantages over existing options and how to incorporate them into our management strategies.
Unfortunately, expensive new medications that are adopted without convincing evidence of their benefit above standard of care can put patients at risk for financial toxicity, either directly through higher out-of-pocket costs or indirectly through higher premiums. Given the impact of rising medication costs on clinicians, patients, and payers, we propose several approaches these stakeholders could adopt to encourage the use of active comparator trial designs.
Clinicians and patients can encourage these trials by remaining skeptical of new treatments that were only compared to vehicle or placebo. Because new medications often are more expensive, clinicians and patients could avoid using these treatments without evidence of either increased efficacy or improved safety and tolerability. In addition, health care institutions should consider reducing pharmaceutical representatives’ access to clinicians to encourage treatment decisions based on the published literature and comparative effectiveness data rather than marketing.
Payers, such as Medicare, also could play a role by requiring active comparator trials for coverage of new medications, particularly when there are already other effective treatments available or other medications in the same class. Payers also could give preferred coverage tier or step therapy status to medications that demonstrate value over existing options.
Although regulatory approaches to increase use of active comparator designs may be more politically challenging to introduce, these options would be more administratively robust. The FDA or a novel regulatory body could require that new treatments demonstrate value in addition to safety and efficacy. This approach would be similar to the role of The National Institute for Health and Care Excellence in the United Kingdom or the recommendations of the European Medicines Agency. Such a group also could provide independent adjudication to ensure appropriate selection of a relevant active comparator. Another approach would be to give extended market exclusivity to medications that are approved based on trials including an additional active comparator arm, an approach used by the European Medicines Agency.
Any approach that encourages increased use of active comparator trials is not without potential downsides. It will be important to avoid unintended consequences of reduced research for rare diseases with smaller markets that may not be able to support the increased cost of these trials. As a result, it would be reasonable to forgo active comparator designs for mediations indicated for rare and orphan diseases or for medications with novel mechanisms of action.
Another argument against including an active comparator arm is that it may stifle innovation by driving up the cost of conducting trials; however, if a product is so marginally innovative that it cannot demonstrate superior safety or efficacy to an existing product, such a new treatment may not be worth the increased cost. In addition, patients provide a notable contribution by participating in these trials, and it is important to ensure that their efforts result in the highest-quality data possible. Furthermore, given the adverse physical and psychosocial impact of a wide variety of dermatologic diseases, the inclusion of an active comparator arm reduces the likelihood that patients will receive placebo, which will make these trials more ethical when effective treatments are available.8 By raising the bar, we can encourage pharmaceutical companies to pursue novel approaches that are more likely to have a revolutionary impact rather than minor modifications or formulations that offer little to no benefit at substantially increased cost.
Although some recent clinical trials in dermatology have included active comparators, many new medications continue to be introduced without any evidence of how they compare to existing standards of care. Until clinicians, patients, payers, and regulators demand that pharmaceutical companies conduct the necessary trials to not only demonstrate whether a treatment is effective and safe but also how it provides value, there will be continued introduction of marginal innovations rather than revolutionary treatments that improve patients’ lives. The next time a new medication is approved, as clinicians, patients, and payers, we must ask ourselves, is this treatment worth it?
Spending on medications is expected to grow from $344 billion in 2018 to $420 billion in 2023, largely driven by the introduction of new branded drugs.1 These costs place substantial financial burden on patients, with nearly 30% of patients not taking their prescriptions as directed because of costs. Although many new medications have transformed how we care for patients, others may not offer meaningful benefit over existing less-costly alternatives that are supported by declining effect sizes of conventional placebo-controlled trials.2 Most medications are approved based on placebo-controlled trial data that does not include an arm comparing the new drug to standard of care, leaving clinicians and patients unable to make meaningful comparisons when deciding on the most appropriate or cost-effective treatment. We consider ways in which clinicians, patients, payers, and regulators could compel more meaningful trials from industry.
Although we often look to the US Food and Drug Administration (FDA) to ensure rigorous and appropriate testing of new medications, the primary mission of the FDA is to ensure efficacy and safety. As a result, pharmaceutical companies seeking approval in the United States have little incentive to go beyond providing the minimal level of evidence required: placebo-controlled randomized trials. Although these trials provide important data on whether a treatment works and its associated risks, they do not provide data on comparative effectiveness. When relevant inexpensive medications are already on the market for the same indication, these placebo-controlled trials provide inadequate evidence to guide clinical decision-making. This issue is particularly relevant in dermatology given how easily topical medications can be combined or reformulated to pursue additional market exclusivity. The addition of an active comparator arm represents an important opportunity to improve the value of these studies.
In the pivotal trials of clindamycin phosphate 1.2%–benzoyl peroxide 2.5% gel for the treatment of acne, the experimental group was not only compared to vehicle but also the active comparator arms of clindamycin alone and benzoyl peroxide alone. The mean percentage change in total lesions was 47.9% with clindamycin phosphate 1.2%–benzoyl peroxide 2.5% gel, 41.6% with the active comparator arm of benzoyl peroxide alone, 40.4% with the active comparator arm of clindamycin alone, and 26.2% for vehicle.3 With these data in mind, clinicians and patients can decide whether the additional benefit of this new product over benzoyl peroxide alone is worth the increased cost.
In contrast, the trials of dapsone gel 7.5% for the treatment of acne did not include an active comparator. The mean percentage change in total lesions was 48.9% for dapsone gel and 43.2% for vehicle.4 Given these data, it is possible that dapsone gel may be no more effective, or possibly less effective, than alternatives such as benzoyl peroxide or other topical antibiotics. Nevertheless, dapsone annual sales were more than $200 million in 2016,5 suggesting that effectively marketed new products can achieve high sales even without convincing evidence of their value compared to standard of care. Although dapsone may be a useful treatment, we cannot effectively make patient-centered clinical decisions given the lack of an active comparator trial design.
This issue is not limited to acne. Phase 3 trials of halobetasol propionate foam 0.05% for psoriasis and crisaborole for atopic dermatitis also did not include an active comparator arm.6,7 Given that topical steroids—and calcineurin inhibitors for atopic dermatitis—are mainstays of treatment for each condition, it is difficult to determine whether these new treatments offer meaningful advantages over existing options and how to incorporate them into our management strategies.
Unfortunately, expensive new medications that are adopted without convincing evidence of their benefit above standard of care can put patients at risk for financial toxicity, either directly through higher out-of-pocket costs or indirectly through higher premiums. Given the impact of rising medication costs on clinicians, patients, and payers, we propose several approaches these stakeholders could adopt to encourage the use of active comparator trial designs.
Clinicians and patients can encourage these trials by remaining skeptical of new treatments that were only compared to vehicle or placebo. Because new medications often are more expensive, clinicians and patients could avoid using these treatments without evidence of either increased efficacy or improved safety and tolerability. In addition, health care institutions should consider reducing pharmaceutical representatives’ access to clinicians to encourage treatment decisions based on the published literature and comparative effectiveness data rather than marketing.
Payers, such as Medicare, also could play a role by requiring active comparator trials for coverage of new medications, particularly when there are already other effective treatments available or other medications in the same class. Payers also could give preferred coverage tier or step therapy status to medications that demonstrate value over existing options.
Although regulatory approaches to increase use of active comparator designs may be more politically challenging to introduce, these options would be more administratively robust. The FDA or a novel regulatory body could require that new treatments demonstrate value in addition to safety and efficacy. This approach would be similar to the role of The National Institute for Health and Care Excellence in the United Kingdom or the recommendations of the European Medicines Agency. Such a group also could provide independent adjudication to ensure appropriate selection of a relevant active comparator. Another approach would be to give extended market exclusivity to medications that are approved based on trials including an additional active comparator arm, an approach used by the European Medicines Agency.
Any approach that encourages increased use of active comparator trials is not without potential downsides. It will be important to avoid unintended consequences of reduced research for rare diseases with smaller markets that may not be able to support the increased cost of these trials. As a result, it would be reasonable to forgo active comparator designs for mediations indicated for rare and orphan diseases or for medications with novel mechanisms of action.
Another argument against including an active comparator arm is that it may stifle innovation by driving up the cost of conducting trials; however, if a product is so marginally innovative that it cannot demonstrate superior safety or efficacy to an existing product, such a new treatment may not be worth the increased cost. In addition, patients provide a notable contribution by participating in these trials, and it is important to ensure that their efforts result in the highest-quality data possible. Furthermore, given the adverse physical and psychosocial impact of a wide variety of dermatologic diseases, the inclusion of an active comparator arm reduces the likelihood that patients will receive placebo, which will make these trials more ethical when effective treatments are available.8 By raising the bar, we can encourage pharmaceutical companies to pursue novel approaches that are more likely to have a revolutionary impact rather than minor modifications or formulations that offer little to no benefit at substantially increased cost.
Although some recent clinical trials in dermatology have included active comparators, many new medications continue to be introduced without any evidence of how they compare to existing standards of care. Until clinicians, patients, payers, and regulators demand that pharmaceutical companies conduct the necessary trials to not only demonstrate whether a treatment is effective and safe but also how it provides value, there will be continued introduction of marginal innovations rather than revolutionary treatments that improve patients’ lives. The next time a new medication is approved, as clinicians, patients, and payers, we must ask ourselves, is this treatment worth it?
- Aitken M, Kleinrock M. Medicine Use and Spending in the U.S.: A Review of 2018 and Outlook to 2023. IQVIA Institute for Human Data Science. https://www.iqvia.com/insights/the-iqvia-institute/reports/medicine-use-and-spending-in-the-us-a-review-of-2018-and-outlook-to-2023. Published May 9, 2019. Accessed August 15, 2020.
- Olfson M, Marcus SC. Decline in placebo-controlled trial results suggests new directions for comparative effectiveness research. Health Aff Proj Hope. 2019;32:1116-1125.
- Thiboutot D, Zaenglein A, Weiss J, et al. An aqueous gel fixed combination of clindamycin phosphate 1.2% and benzoyl peroxide 2.5% for the once-daily treatment of moderate to severe acne vulgaris: assessment of efficacy and safety in 2813 patients. J Am Acad Dermatol. 2008;59:792-800.
- Eichenfield LF, Lain T, Frankel EH, et al. Efficacy and safety of once-daily dapsone gel, 7.5% for treatment of adolescents and adults with acne vulgaris: second of two identically designed, large, multicenter, randomized, vehicle-controlled trials. J Drugs Dermatol. 2016;15:962-969.
- Allergan. 2017 Form 10-K. https://www.abbvie.com/content/dam/abbvie-dotcom/uploads/PDFs/allergan/allergan-annual-report-form-10K-123117.pdf. Accessed August 19, 2020.
- Paller AS, Tom WL, Lebwohl MG, et al. Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults. J Am Acad Dermatol. 2016;75:494-503.e6.
- Bhatia N, Stein Gold L, Kircik LH, et al. Two multicenter, randomized, double-blind, parallel group comparison studies of a novel foam formulation of halobetasol propionate, 0.05% vs its vehicle in adult subjects with plaque psoriasis. J Drugs Dermatol. 2019;18:790-796.
- Temple R, Ellenberg SS. Placebo-controlled trials and active-control trials in the evaluation of new treatments. part 1: ethical and scientific issues. Ann Intern Med. 2000;133:455-463.
- Aitken M, Kleinrock M. Medicine Use and Spending in the U.S.: A Review of 2018 and Outlook to 2023. IQVIA Institute for Human Data Science. https://www.iqvia.com/insights/the-iqvia-institute/reports/medicine-use-and-spending-in-the-us-a-review-of-2018-and-outlook-to-2023. Published May 9, 2019. Accessed August 15, 2020.
- Olfson M, Marcus SC. Decline in placebo-controlled trial results suggests new directions for comparative effectiveness research. Health Aff Proj Hope. 2019;32:1116-1125.
- Thiboutot D, Zaenglein A, Weiss J, et al. An aqueous gel fixed combination of clindamycin phosphate 1.2% and benzoyl peroxide 2.5% for the once-daily treatment of moderate to severe acne vulgaris: assessment of efficacy and safety in 2813 patients. J Am Acad Dermatol. 2008;59:792-800.
- Eichenfield LF, Lain T, Frankel EH, et al. Efficacy and safety of once-daily dapsone gel, 7.5% for treatment of adolescents and adults with acne vulgaris: second of two identically designed, large, multicenter, randomized, vehicle-controlled trials. J Drugs Dermatol. 2016;15:962-969.
- Allergan. 2017 Form 10-K. https://www.abbvie.com/content/dam/abbvie-dotcom/uploads/PDFs/allergan/allergan-annual-report-form-10K-123117.pdf. Accessed August 19, 2020.
- Paller AS, Tom WL, Lebwohl MG, et al. Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults. J Am Acad Dermatol. 2016;75:494-503.e6.
- Bhatia N, Stein Gold L, Kircik LH, et al. Two multicenter, randomized, double-blind, parallel group comparison studies of a novel foam formulation of halobetasol propionate, 0.05% vs its vehicle in adult subjects with plaque psoriasis. J Drugs Dermatol. 2019;18:790-796.
- Temple R, Ellenberg SS. Placebo-controlled trials and active-control trials in the evaluation of new treatments. part 1: ethical and scientific issues. Ann Intern Med. 2000;133:455-463.
Practice Points
- When evaluating a new treatment, it is important to consider not only whether it is effective but also whether it provides additional value compared to existing treatment options.
- Encouraging active comparator trials will provide clinicians and patients with important data to guide decision-making regarding the most appropriate treatment options.