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Topical PDE-4 inhibitor for psoriasis effective in phase 2b trial
Once-daily – including challenging lesions in tough-to-treat intertriginous areas – in a phase 2b, randomized, double-blind, vehicle-controlled clinical trial, Mark G. Lebwohl, MD, reported at the virtual annual meeting of the American Academy of Dermatology.
The clinical improvement occurred rapidly. And topical roflumilast’s side effect profile was essentially the same as in vehicle-treated controls, which suggests a potential major advantage for the novel drug in future clinical practice. After all, topical treatment is the mainstay of psoriasis therapy, but the current topical agents – high-potency corticosteroids, vitamin D derivatives, and retinoids – have long-term tolerability, efficacy, or side effect issues, especially in treating sensitive skin areas, including the face and intertriginous areas.
“Roflumilast cream could really be a game changer,” predicted Dr. Lebwohl, professor and chair of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York.
Phosphodiesterase-4 (PDE-4) activity is elevated in psoriatic skin. Indeed, inhibition of PDE-4 via oral apremilast (Otezla) is an established strategy for improving psoriasis through down-regulation of inflammatory cytokines including tumor necrosis factor–alpha, interleukins-17 and -23, and interferon-gamma. Notably, however, roflumilast is orders of magnitude more potent than any other PDE-4 inhibitor. An oral version marketed as Daliresp has been available for treatment of chronic obstructive pulmonary disease for nearly a decade.
The 12-week, multicenter, phase 2b study included 331 patients with chronic plaque psoriasis who were randomized to once-daily 0.3% roflumilast cream, 0.15% roflumilast cream, or vehicle. Three-quarters of participants had a baseline Investigator Global Assessment (IGA) score of 3, indicative of moderate disease.
The primary endpoint was achievement of an IGA score of 0 or 1 (clear or almost clear) at week 6. The observed improvement was dose related, although both doses of roflumilast were significantly more effective than vehicle. However, peak improvement occurred at week 8, not week 6, with subsequent plateauing of response through week 12. A week 8 IGA of 0 or 1 plus at least a 2-grade improvement from baseline occurred in 32% of the high-dose roflumilast group, 25% of those on the 0.15% formulation, and 10% of controls.
“The effect in improvement was very rapid, with a statistically significant improvement compared to vehicle for both concentrations as early as week 2,” Dr. Lebwohl said.
A key secondary endpoint focused on treatment response in intertriginous areas, since “those are the areas where we really don’t want to use steroids because of major irritation problems,” the dermatologist explained. At week 12, treatment success as defined by an intertriginous IGA score of 0 or 1 plus at least a 2-point improvement from baseline was seen in 86% of the 0.3% roflumilast cream group, 50% on low-dose therapy, and 29% of controls.
About 65% of subjects on high-dose roflumilast cream reported at least a 4-point reduction in the Worst Itch–Numerical Rating Scale by week 8, as did 58% of those on the low-dose version and 42% of controls. Another secondary endpoint – patient-reported burden of disease as captured in a Psoriasis Symptoms Diary – showed a significant divergence between both doses of roflumilast and vehicle as early as week 2.
“Adverse events were negligible,” Dr. Lebwohl said. “In fact, there was only one discontinuation in the 0.3% arm, compared to none with 0.15% and two with vehicle.”
The phase 3 program is now recruiting participants.
The phase 2b study was funded by Arcutis Biotherapeutics. Dr. Lebwohl reported receiving research funding from and serving as a consultant to that company and numerous others.
Once-daily – including challenging lesions in tough-to-treat intertriginous areas – in a phase 2b, randomized, double-blind, vehicle-controlled clinical trial, Mark G. Lebwohl, MD, reported at the virtual annual meeting of the American Academy of Dermatology.
The clinical improvement occurred rapidly. And topical roflumilast’s side effect profile was essentially the same as in vehicle-treated controls, which suggests a potential major advantage for the novel drug in future clinical practice. After all, topical treatment is the mainstay of psoriasis therapy, but the current topical agents – high-potency corticosteroids, vitamin D derivatives, and retinoids – have long-term tolerability, efficacy, or side effect issues, especially in treating sensitive skin areas, including the face and intertriginous areas.
“Roflumilast cream could really be a game changer,” predicted Dr. Lebwohl, professor and chair of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York.
Phosphodiesterase-4 (PDE-4) activity is elevated in psoriatic skin. Indeed, inhibition of PDE-4 via oral apremilast (Otezla) is an established strategy for improving psoriasis through down-regulation of inflammatory cytokines including tumor necrosis factor–alpha, interleukins-17 and -23, and interferon-gamma. Notably, however, roflumilast is orders of magnitude more potent than any other PDE-4 inhibitor. An oral version marketed as Daliresp has been available for treatment of chronic obstructive pulmonary disease for nearly a decade.
The 12-week, multicenter, phase 2b study included 331 patients with chronic plaque psoriasis who were randomized to once-daily 0.3% roflumilast cream, 0.15% roflumilast cream, or vehicle. Three-quarters of participants had a baseline Investigator Global Assessment (IGA) score of 3, indicative of moderate disease.
The primary endpoint was achievement of an IGA score of 0 or 1 (clear or almost clear) at week 6. The observed improvement was dose related, although both doses of roflumilast were significantly more effective than vehicle. However, peak improvement occurred at week 8, not week 6, with subsequent plateauing of response through week 12. A week 8 IGA of 0 or 1 plus at least a 2-grade improvement from baseline occurred in 32% of the high-dose roflumilast group, 25% of those on the 0.15% formulation, and 10% of controls.
“The effect in improvement was very rapid, with a statistically significant improvement compared to vehicle for both concentrations as early as week 2,” Dr. Lebwohl said.
A key secondary endpoint focused on treatment response in intertriginous areas, since “those are the areas where we really don’t want to use steroids because of major irritation problems,” the dermatologist explained. At week 12, treatment success as defined by an intertriginous IGA score of 0 or 1 plus at least a 2-point improvement from baseline was seen in 86% of the 0.3% roflumilast cream group, 50% on low-dose therapy, and 29% of controls.
About 65% of subjects on high-dose roflumilast cream reported at least a 4-point reduction in the Worst Itch–Numerical Rating Scale by week 8, as did 58% of those on the low-dose version and 42% of controls. Another secondary endpoint – patient-reported burden of disease as captured in a Psoriasis Symptoms Diary – showed a significant divergence between both doses of roflumilast and vehicle as early as week 2.
“Adverse events were negligible,” Dr. Lebwohl said. “In fact, there was only one discontinuation in the 0.3% arm, compared to none with 0.15% and two with vehicle.”
The phase 3 program is now recruiting participants.
The phase 2b study was funded by Arcutis Biotherapeutics. Dr. Lebwohl reported receiving research funding from and serving as a consultant to that company and numerous others.
Once-daily – including challenging lesions in tough-to-treat intertriginous areas – in a phase 2b, randomized, double-blind, vehicle-controlled clinical trial, Mark G. Lebwohl, MD, reported at the virtual annual meeting of the American Academy of Dermatology.
The clinical improvement occurred rapidly. And topical roflumilast’s side effect profile was essentially the same as in vehicle-treated controls, which suggests a potential major advantage for the novel drug in future clinical practice. After all, topical treatment is the mainstay of psoriasis therapy, but the current topical agents – high-potency corticosteroids, vitamin D derivatives, and retinoids – have long-term tolerability, efficacy, or side effect issues, especially in treating sensitive skin areas, including the face and intertriginous areas.
“Roflumilast cream could really be a game changer,” predicted Dr. Lebwohl, professor and chair of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York.
Phosphodiesterase-4 (PDE-4) activity is elevated in psoriatic skin. Indeed, inhibition of PDE-4 via oral apremilast (Otezla) is an established strategy for improving psoriasis through down-regulation of inflammatory cytokines including tumor necrosis factor–alpha, interleukins-17 and -23, and interferon-gamma. Notably, however, roflumilast is orders of magnitude more potent than any other PDE-4 inhibitor. An oral version marketed as Daliresp has been available for treatment of chronic obstructive pulmonary disease for nearly a decade.
The 12-week, multicenter, phase 2b study included 331 patients with chronic plaque psoriasis who were randomized to once-daily 0.3% roflumilast cream, 0.15% roflumilast cream, or vehicle. Three-quarters of participants had a baseline Investigator Global Assessment (IGA) score of 3, indicative of moderate disease.
The primary endpoint was achievement of an IGA score of 0 or 1 (clear or almost clear) at week 6. The observed improvement was dose related, although both doses of roflumilast were significantly more effective than vehicle. However, peak improvement occurred at week 8, not week 6, with subsequent plateauing of response through week 12. A week 8 IGA of 0 or 1 plus at least a 2-grade improvement from baseline occurred in 32% of the high-dose roflumilast group, 25% of those on the 0.15% formulation, and 10% of controls.
“The effect in improvement was very rapid, with a statistically significant improvement compared to vehicle for both concentrations as early as week 2,” Dr. Lebwohl said.
A key secondary endpoint focused on treatment response in intertriginous areas, since “those are the areas where we really don’t want to use steroids because of major irritation problems,” the dermatologist explained. At week 12, treatment success as defined by an intertriginous IGA score of 0 or 1 plus at least a 2-point improvement from baseline was seen in 86% of the 0.3% roflumilast cream group, 50% on low-dose therapy, and 29% of controls.
About 65% of subjects on high-dose roflumilast cream reported at least a 4-point reduction in the Worst Itch–Numerical Rating Scale by week 8, as did 58% of those on the low-dose version and 42% of controls. Another secondary endpoint – patient-reported burden of disease as captured in a Psoriasis Symptoms Diary – showed a significant divergence between both doses of roflumilast and vehicle as early as week 2.
“Adverse events were negligible,” Dr. Lebwohl said. “In fact, there was only one discontinuation in the 0.3% arm, compared to none with 0.15% and two with vehicle.”
The phase 3 program is now recruiting participants.
The phase 2b study was funded by Arcutis Biotherapeutics. Dr. Lebwohl reported receiving research funding from and serving as a consultant to that company and numerous others.
FROM AAD 20
Oral difelikefalin quells severe chronic kidney disease–associated itch
, in a first-of-its-kind randomized clinical trial, Gil Yosipovitch, MD, said at the virtual annual meeting of the American Academy of Dermatology.
“Difelikefalin at 1.0 mg was associated with clinically meaningful improvements in pruritus. The improvement in itch was significant by week 2. And nearly 40% of patients achieved a complete response, which was more than two-and-one-half times more than with placebo,” noted Dr. Yosipovitch, professor of dermatology and director of the Miami Itch Center at the University of Miami.
Pruritus associated with chronic kidney disease (CKD) is a common, underrecognized, and distressing condition that causes markedly impaired quality of life. It occurs in patients across all stages of CKD, not just in those on hemodialysis, as is widely but mistakenly believed. And at present there is no approved drug in any country for treatment of CKD-associated itch.
Difelikefalin, a novel selective agonist of peripheral kappa opioid receptors, is designed to have very limited CNS penetration. The drug, which is renally excreted, doesn’t bind to mu or delta opioid receptors. Its antipruritic effect arises from activation of kappa opioid receptors on peripheral sensory neurons and immune cells, the dermatologist explained.
Dr. Yosipovitch presented the results of a phase 2, randomized, double-blind, placebo-controlled, 12-week trial in which 240 patients with severe chronic pruritus and stage 3-5 CKD were assigned to once-daily oral difelikefalin at 0.25 mg, 0.5 mg, or 1.0 mg, or placebo. More than 80% of participants were not on dialysis. Indeed, this was the first-ever clinical trial targeting itch in patients across such a broad spectrum of CKD stages.
The primary study endpoint was change from baseline to week 12 in the weekly mean score on the 24-hour Worst Itching Intensity Numerical Rating Scale. The average baseline score was 7, considered severe pruritus on the 0-10 scale. Patients randomized to difelikefalin at 1.0 mg/day had a mean 4.4-point decrease, a significantly greater improvement than the 3.3-point reduction in placebo-treated controls.
“More than a 4-point decrease is considered a very meaningful itch reduction,” Dr. Yosipovitch noted.
The mean reductions in itch score in patients on 0.25 mg and 0.5 mg/day of difelikefalin were 4.0 and 3.8 points, respectively, which fell short of statistical significance versus placebo.
A key prespecified secondary endpoint was the proportion of subjects with at least a 3-point improvement in itch score over 12 weeks. This was achieved in 72% of patients on the top dose of difelikefalin, compared with 58% of controls, a significant difference. A 4-point or larger decrease in itch score occurred in 65% of patients on 1.0 mg/day of the kappa opioid recent agonist, versus 50% of controls, also a significant difference.
A complete response, defined as an itch score of 0 or 1 at least 80% of the time, was significantly more common in all three active treatment groups than in controls, with rates of 33%, 31.6%, and 38.6% at difelikefalin 0.25, 0.5, and 1.0 mg, compared with 4.4% among those on placebo.
Falls occurred in 1.5% of patients on difelikefalin. “The therapy does seem to increase the risk of dizziness, falls, fatigue, and GI complaints,” according to the investigator.
Still, most of these adverse events were mild or moderate in severity. Only about 1% of participants discontinued treatment for such reasons.
Earlier this year, a positive phase 3 trial of an intravenous formulation of difelikefalin for pruritus was reported in CKD patients on hemodialysis (N Engl J Med. 2020 Jan 16;382[3]:222-32).
In an interview, Dr. Yosipovitch said that this new phase 2 oral dose-finding study wasn’t powered to detect differences in treatment efficacy between the dialysis and nondialysis groups. However, the proportion of patients with at least a 3-point improvement in itch at week 12 was similar in the two groups.
“The oral formulation would of course be more convenient and would be preferred for patients not undergoing hemodialysis,” he said. “I would expect that the IV formulation would be the preferred route of administration for a patient undergoing hemodialysis. An IV formulation would be very convenient for such patients because it’s administered at the dialysis clinic at the end of the hemodialysis session.”
The oral difelikefalin phase 3 program is scheduled to start later in 2020.
CKD-associated itch poses a therapeutic challenge because it has so many contributory factors. These include CKD-induced peripheral neuropathy, functional and structural neuropathic changes in the brain, cutaneous mast cell activation, an imbalance between mu opioid receptor overexpression and kappa opioid receptor downregulation, secondary parathyroidism, and systemic accumulation of aluminum, beta 2 microglobulin, and other dialysis-related substances, the dermatologist observed.
Dr. Yosipovitch reported receiving research grants from a half-dozen pharmaceutical companies. He also serves as a consultant to numerous companies, including Cara Therapeutics, which sponsored the phase 2 trial.
, in a first-of-its-kind randomized clinical trial, Gil Yosipovitch, MD, said at the virtual annual meeting of the American Academy of Dermatology.
“Difelikefalin at 1.0 mg was associated with clinically meaningful improvements in pruritus. The improvement in itch was significant by week 2. And nearly 40% of patients achieved a complete response, which was more than two-and-one-half times more than with placebo,” noted Dr. Yosipovitch, professor of dermatology and director of the Miami Itch Center at the University of Miami.
Pruritus associated with chronic kidney disease (CKD) is a common, underrecognized, and distressing condition that causes markedly impaired quality of life. It occurs in patients across all stages of CKD, not just in those on hemodialysis, as is widely but mistakenly believed. And at present there is no approved drug in any country for treatment of CKD-associated itch.
Difelikefalin, a novel selective agonist of peripheral kappa opioid receptors, is designed to have very limited CNS penetration. The drug, which is renally excreted, doesn’t bind to mu or delta opioid receptors. Its antipruritic effect arises from activation of kappa opioid receptors on peripheral sensory neurons and immune cells, the dermatologist explained.
Dr. Yosipovitch presented the results of a phase 2, randomized, double-blind, placebo-controlled, 12-week trial in which 240 patients with severe chronic pruritus and stage 3-5 CKD were assigned to once-daily oral difelikefalin at 0.25 mg, 0.5 mg, or 1.0 mg, or placebo. More than 80% of participants were not on dialysis. Indeed, this was the first-ever clinical trial targeting itch in patients across such a broad spectrum of CKD stages.
The primary study endpoint was change from baseline to week 12 in the weekly mean score on the 24-hour Worst Itching Intensity Numerical Rating Scale. The average baseline score was 7, considered severe pruritus on the 0-10 scale. Patients randomized to difelikefalin at 1.0 mg/day had a mean 4.4-point decrease, a significantly greater improvement than the 3.3-point reduction in placebo-treated controls.
“More than a 4-point decrease is considered a very meaningful itch reduction,” Dr. Yosipovitch noted.
The mean reductions in itch score in patients on 0.25 mg and 0.5 mg/day of difelikefalin were 4.0 and 3.8 points, respectively, which fell short of statistical significance versus placebo.
A key prespecified secondary endpoint was the proportion of subjects with at least a 3-point improvement in itch score over 12 weeks. This was achieved in 72% of patients on the top dose of difelikefalin, compared with 58% of controls, a significant difference. A 4-point or larger decrease in itch score occurred in 65% of patients on 1.0 mg/day of the kappa opioid recent agonist, versus 50% of controls, also a significant difference.
A complete response, defined as an itch score of 0 or 1 at least 80% of the time, was significantly more common in all three active treatment groups than in controls, with rates of 33%, 31.6%, and 38.6% at difelikefalin 0.25, 0.5, and 1.0 mg, compared with 4.4% among those on placebo.
Falls occurred in 1.5% of patients on difelikefalin. “The therapy does seem to increase the risk of dizziness, falls, fatigue, and GI complaints,” according to the investigator.
Still, most of these adverse events were mild or moderate in severity. Only about 1% of participants discontinued treatment for such reasons.
Earlier this year, a positive phase 3 trial of an intravenous formulation of difelikefalin for pruritus was reported in CKD patients on hemodialysis (N Engl J Med. 2020 Jan 16;382[3]:222-32).
In an interview, Dr. Yosipovitch said that this new phase 2 oral dose-finding study wasn’t powered to detect differences in treatment efficacy between the dialysis and nondialysis groups. However, the proportion of patients with at least a 3-point improvement in itch at week 12 was similar in the two groups.
“The oral formulation would of course be more convenient and would be preferred for patients not undergoing hemodialysis,” he said. “I would expect that the IV formulation would be the preferred route of administration for a patient undergoing hemodialysis. An IV formulation would be very convenient for such patients because it’s administered at the dialysis clinic at the end of the hemodialysis session.”
The oral difelikefalin phase 3 program is scheduled to start later in 2020.
CKD-associated itch poses a therapeutic challenge because it has so many contributory factors. These include CKD-induced peripheral neuropathy, functional and structural neuropathic changes in the brain, cutaneous mast cell activation, an imbalance between mu opioid receptor overexpression and kappa opioid receptor downregulation, secondary parathyroidism, and systemic accumulation of aluminum, beta 2 microglobulin, and other dialysis-related substances, the dermatologist observed.
Dr. Yosipovitch reported receiving research grants from a half-dozen pharmaceutical companies. He also serves as a consultant to numerous companies, including Cara Therapeutics, which sponsored the phase 2 trial.
, in a first-of-its-kind randomized clinical trial, Gil Yosipovitch, MD, said at the virtual annual meeting of the American Academy of Dermatology.
“Difelikefalin at 1.0 mg was associated with clinically meaningful improvements in pruritus. The improvement in itch was significant by week 2. And nearly 40% of patients achieved a complete response, which was more than two-and-one-half times more than with placebo,” noted Dr. Yosipovitch, professor of dermatology and director of the Miami Itch Center at the University of Miami.
Pruritus associated with chronic kidney disease (CKD) is a common, underrecognized, and distressing condition that causes markedly impaired quality of life. It occurs in patients across all stages of CKD, not just in those on hemodialysis, as is widely but mistakenly believed. And at present there is no approved drug in any country for treatment of CKD-associated itch.
Difelikefalin, a novel selective agonist of peripheral kappa opioid receptors, is designed to have very limited CNS penetration. The drug, which is renally excreted, doesn’t bind to mu or delta opioid receptors. Its antipruritic effect arises from activation of kappa opioid receptors on peripheral sensory neurons and immune cells, the dermatologist explained.
Dr. Yosipovitch presented the results of a phase 2, randomized, double-blind, placebo-controlled, 12-week trial in which 240 patients with severe chronic pruritus and stage 3-5 CKD were assigned to once-daily oral difelikefalin at 0.25 mg, 0.5 mg, or 1.0 mg, or placebo. More than 80% of participants were not on dialysis. Indeed, this was the first-ever clinical trial targeting itch in patients across such a broad spectrum of CKD stages.
The primary study endpoint was change from baseline to week 12 in the weekly mean score on the 24-hour Worst Itching Intensity Numerical Rating Scale. The average baseline score was 7, considered severe pruritus on the 0-10 scale. Patients randomized to difelikefalin at 1.0 mg/day had a mean 4.4-point decrease, a significantly greater improvement than the 3.3-point reduction in placebo-treated controls.
“More than a 4-point decrease is considered a very meaningful itch reduction,” Dr. Yosipovitch noted.
The mean reductions in itch score in patients on 0.25 mg and 0.5 mg/day of difelikefalin were 4.0 and 3.8 points, respectively, which fell short of statistical significance versus placebo.
A key prespecified secondary endpoint was the proportion of subjects with at least a 3-point improvement in itch score over 12 weeks. This was achieved in 72% of patients on the top dose of difelikefalin, compared with 58% of controls, a significant difference. A 4-point or larger decrease in itch score occurred in 65% of patients on 1.0 mg/day of the kappa opioid recent agonist, versus 50% of controls, also a significant difference.
A complete response, defined as an itch score of 0 or 1 at least 80% of the time, was significantly more common in all three active treatment groups than in controls, with rates of 33%, 31.6%, and 38.6% at difelikefalin 0.25, 0.5, and 1.0 mg, compared with 4.4% among those on placebo.
Falls occurred in 1.5% of patients on difelikefalin. “The therapy does seem to increase the risk of dizziness, falls, fatigue, and GI complaints,” according to the investigator.
Still, most of these adverse events were mild or moderate in severity. Only about 1% of participants discontinued treatment for such reasons.
Earlier this year, a positive phase 3 trial of an intravenous formulation of difelikefalin for pruritus was reported in CKD patients on hemodialysis (N Engl J Med. 2020 Jan 16;382[3]:222-32).
In an interview, Dr. Yosipovitch said that this new phase 2 oral dose-finding study wasn’t powered to detect differences in treatment efficacy between the dialysis and nondialysis groups. However, the proportion of patients with at least a 3-point improvement in itch at week 12 was similar in the two groups.
“The oral formulation would of course be more convenient and would be preferred for patients not undergoing hemodialysis,” he said. “I would expect that the IV formulation would be the preferred route of administration for a patient undergoing hemodialysis. An IV formulation would be very convenient for such patients because it’s administered at the dialysis clinic at the end of the hemodialysis session.”
The oral difelikefalin phase 3 program is scheduled to start later in 2020.
CKD-associated itch poses a therapeutic challenge because it has so many contributory factors. These include CKD-induced peripheral neuropathy, functional and structural neuropathic changes in the brain, cutaneous mast cell activation, an imbalance between mu opioid receptor overexpression and kappa opioid receptor downregulation, secondary parathyroidism, and systemic accumulation of aluminum, beta 2 microglobulin, and other dialysis-related substances, the dermatologist observed.
Dr. Yosipovitch reported receiving research grants from a half-dozen pharmaceutical companies. He also serves as a consultant to numerous companies, including Cara Therapeutics, which sponsored the phase 2 trial.
FROM AAD 2020
Skin patterns of COVID-19 vary widely
according to Christine Ko, MD.
“Things are very fluid,” Dr. Ko, professor of dermatology and pathology at Yale University, New Haven, Conn., said during the virtual annual meeting of the American Academy of Dermatology. “New studies are coming out daily. Due to the need for rapid dissemination, a lot of the studies are case reports, but there are some nice case series. Another caveat for the literature is that a lot of these cases were not necessarily confirmed with testing for SARS-CoV-2, but some were.”
Dr. Ko framed her remarks largely on a case collection survey of images and clinical data from 375 patients in Spain with suspected or confirmed COVID-19 that was published online April 29, 2020, in the British Journal of Dermatology (doi: 10.1111/bjd.19163). Cutaneous manifestations included early vesicular eruptions mainly on the trunk or limbs (9%), maculopapular (47%) to urticarial lesions (19%) mainly on the trunk, and acral areas of erythema sometimes with vesicles or erosion (perniosis-like) (19%) that seemed to be a later manifestation of COVID-19. Retiform purpura or necrosis (6%) was most concerning in terms of skin disease, with an associated with a mortality of 10%.
On histology, the early vesicular eruptions are typically marked by dyskeratotic keratinocytes, Dr. Ko said, while urticarial lesions are characterized by a mixed dermal infiltrate; maculopapular lesions were a broad category. “There are some case reports that show spongiotic dermatitis or parakeratosis with a lymphocytic infiltrate,” she said. “A caveat to keep in mind is that, although these patients may definitely have COVID-19 and be confirmed to have it by testing, hypersensitivity reactions may be due to the multiple medications they’re on.”
Patients can develop a spectrum of lesions that are suggestive of vascular damage or occlusion, Dr. Ko continued. Livedoid lesions may remain static and not eventuate into necrosis or purpura but will self-resolve. Purpuric lesions and acral gangrene have been described, and these lesions correspond to vascular occlusion on biopsy.
A later manifestation are the so-called “COVID toes” with a superficial and deep lymphocytic infiltrate, as published June 1, 2020, in JAAD Case Reports: (doi: 10.1016/j.jdcr.2020.04.011).
“There are patients in the literature that have slightly different pathology, with lymphocytic inflammation as well as occlusion of vessels,” Dr. Ko said. A paper published June 20, 2020, in the British Journal of Dermatology used immunohistochemical staining against the SARS-CoV-2 spike protein, and biopsies of “COVID toes” had positive staining of endothelial cells, supporting the notion that “COVID toes” are a direct manifestation of viral infection (doi: 10.1111/bjd.19327).
“There’s a lot that we still don’t know, and some patterns are going to be outliers,” Dr. Ko concluded. “[As for] determining which skin manifestations are directly from coronavirus infection within the skin, more study is needed and likely time will tell.” She reported having no financial disclosures relevant to her talk.
according to Christine Ko, MD.
“Things are very fluid,” Dr. Ko, professor of dermatology and pathology at Yale University, New Haven, Conn., said during the virtual annual meeting of the American Academy of Dermatology. “New studies are coming out daily. Due to the need for rapid dissemination, a lot of the studies are case reports, but there are some nice case series. Another caveat for the literature is that a lot of these cases were not necessarily confirmed with testing for SARS-CoV-2, but some were.”
Dr. Ko framed her remarks largely on a case collection survey of images and clinical data from 375 patients in Spain with suspected or confirmed COVID-19 that was published online April 29, 2020, in the British Journal of Dermatology (doi: 10.1111/bjd.19163). Cutaneous manifestations included early vesicular eruptions mainly on the trunk or limbs (9%), maculopapular (47%) to urticarial lesions (19%) mainly on the trunk, and acral areas of erythema sometimes with vesicles or erosion (perniosis-like) (19%) that seemed to be a later manifestation of COVID-19. Retiform purpura or necrosis (6%) was most concerning in terms of skin disease, with an associated with a mortality of 10%.
On histology, the early vesicular eruptions are typically marked by dyskeratotic keratinocytes, Dr. Ko said, while urticarial lesions are characterized by a mixed dermal infiltrate; maculopapular lesions were a broad category. “There are some case reports that show spongiotic dermatitis or parakeratosis with a lymphocytic infiltrate,” she said. “A caveat to keep in mind is that, although these patients may definitely have COVID-19 and be confirmed to have it by testing, hypersensitivity reactions may be due to the multiple medications they’re on.”
Patients can develop a spectrum of lesions that are suggestive of vascular damage or occlusion, Dr. Ko continued. Livedoid lesions may remain static and not eventuate into necrosis or purpura but will self-resolve. Purpuric lesions and acral gangrene have been described, and these lesions correspond to vascular occlusion on biopsy.
A later manifestation are the so-called “COVID toes” with a superficial and deep lymphocytic infiltrate, as published June 1, 2020, in JAAD Case Reports: (doi: 10.1016/j.jdcr.2020.04.011).
“There are patients in the literature that have slightly different pathology, with lymphocytic inflammation as well as occlusion of vessels,” Dr. Ko said. A paper published June 20, 2020, in the British Journal of Dermatology used immunohistochemical staining against the SARS-CoV-2 spike protein, and biopsies of “COVID toes” had positive staining of endothelial cells, supporting the notion that “COVID toes” are a direct manifestation of viral infection (doi: 10.1111/bjd.19327).
“There’s a lot that we still don’t know, and some patterns are going to be outliers,” Dr. Ko concluded. “[As for] determining which skin manifestations are directly from coronavirus infection within the skin, more study is needed and likely time will tell.” She reported having no financial disclosures relevant to her talk.
according to Christine Ko, MD.
“Things are very fluid,” Dr. Ko, professor of dermatology and pathology at Yale University, New Haven, Conn., said during the virtual annual meeting of the American Academy of Dermatology. “New studies are coming out daily. Due to the need for rapid dissemination, a lot of the studies are case reports, but there are some nice case series. Another caveat for the literature is that a lot of these cases were not necessarily confirmed with testing for SARS-CoV-2, but some were.”
Dr. Ko framed her remarks largely on a case collection survey of images and clinical data from 375 patients in Spain with suspected or confirmed COVID-19 that was published online April 29, 2020, in the British Journal of Dermatology (doi: 10.1111/bjd.19163). Cutaneous manifestations included early vesicular eruptions mainly on the trunk or limbs (9%), maculopapular (47%) to urticarial lesions (19%) mainly on the trunk, and acral areas of erythema sometimes with vesicles or erosion (perniosis-like) (19%) that seemed to be a later manifestation of COVID-19. Retiform purpura or necrosis (6%) was most concerning in terms of skin disease, with an associated with a mortality of 10%.
On histology, the early vesicular eruptions are typically marked by dyskeratotic keratinocytes, Dr. Ko said, while urticarial lesions are characterized by a mixed dermal infiltrate; maculopapular lesions were a broad category. “There are some case reports that show spongiotic dermatitis or parakeratosis with a lymphocytic infiltrate,” she said. “A caveat to keep in mind is that, although these patients may definitely have COVID-19 and be confirmed to have it by testing, hypersensitivity reactions may be due to the multiple medications they’re on.”
Patients can develop a spectrum of lesions that are suggestive of vascular damage or occlusion, Dr. Ko continued. Livedoid lesions may remain static and not eventuate into necrosis or purpura but will self-resolve. Purpuric lesions and acral gangrene have been described, and these lesions correspond to vascular occlusion on biopsy.
A later manifestation are the so-called “COVID toes” with a superficial and deep lymphocytic infiltrate, as published June 1, 2020, in JAAD Case Reports: (doi: 10.1016/j.jdcr.2020.04.011).
“There are patients in the literature that have slightly different pathology, with lymphocytic inflammation as well as occlusion of vessels,” Dr. Ko said. A paper published June 20, 2020, in the British Journal of Dermatology used immunohistochemical staining against the SARS-CoV-2 spike protein, and biopsies of “COVID toes” had positive staining of endothelial cells, supporting the notion that “COVID toes” are a direct manifestation of viral infection (doi: 10.1111/bjd.19327).
“There’s a lot that we still don’t know, and some patterns are going to be outliers,” Dr. Ko concluded. “[As for] determining which skin manifestations are directly from coronavirus infection within the skin, more study is needed and likely time will tell.” She reported having no financial disclosures relevant to her talk.
FROM AAD 20
Novel rapid acoustic pulse device shows promise for treating cellulite
After a single treatment, it provided a roughly 1.16 point reduction in the five-point Cellulite Severity Scale at 12 weeks, which corresponds to a roughly 32.5% reduction in cellulite.
“In cellulite, we know that the septa within the fat – those fibrous bands that pull down the skin and tether – lead to the traditional look of cellulite dimples and ridges,” lead study author Elizabeth Tanzi, MD, said during a late-breaking abstract session at the virtual annual meeting of the American Academy of Dermatology. A rapid acoustic pulse (RAP) device being developed by Soliton emits rapid acoustic pulses and shock waves at 50 Hz that are transmitted through the skin. The pulses “rupture and shear the fibrotic septa, which causes release of the septa and smoothing of the skin dimples,” explained Dr. Tanzi, director of Capital Laser & Skin Care in Chevy Chase, Md.
She added that the repetition rate of the RAP device makes it stand out from other technologies currently on the market for cellulite treatment. “The repetition rate and very short rise times provide microscopic mechanical destruction to the targeted cellular level structures and the vacuoles,” Dr. Tanzi said. “The high peak pressure and fast repetition rate exploit the viscoelastic nature of the tissue. It’s the rapid rate at which the energy is being delivered, as well as the very short times that energy is being delivered, that makes the technology an entirely different device-tissue interaction.”
The physical effects observed occur in the extracellular matrix and in the destruction of fibrous septa. “That’s the acoustic subcision,” she continued. “But also, there’s no cavitation and there are nonthermal physical effects. There is some investigational research going into what biologic effects those shock waves have on the rest of the tissue, looking into neocollagenesis, potential angiogenesis, potential lymphangiogenesis, as well as inflammation inhibition.”
In a prospective pivotal clinical trial conducted at four sites, Dr. Tanzi and her colleagues evaluated the safety and effectiveness of the RAP device in 62 female patients who were treated with a single, rapid acoustic pulse treatment comprised of 1-2 minutes on each identified dimple or large ridge of cellulite. This amounted to a 19- to 33-minute treatment session for each patient. No anesthesia was required, and photographs were taken on all sites with QuantifiCare medical imaging software.
“It’s completely noninvasive and it’s truly an incisionless treatment,” Dr. Tanzi said of the procedure. “The skin’s never punctured. There’s physician oversight, but it is highly delegatable, and there is no recovery time for the patient.”
Following treatment, adverse effects and tolerability were reported, and safety and efficacy were assessed at 12 weeks. Efficacy was determined by photographic assessment by three blinded independent physicians who used a validated, simplified version of the Cellulite Severity Scale (CSS), a 0-5 scale based on the number of cellulite depressions, as well as the average depth of those depressions.
The mean age of patients was 43 years, 92% were white, and their mean body mass index was 24.5 kg/m2. The average time of treatment was 28 minutes. Based on the CSS scores, the researchers found that 87% of the study subjects had some improvement of their cellulite after a single RAP treatment. “If you break the data down further, half of patients had at least a 30% reduction of their CSS, and almost one-quarter had a 50% improvement of their CSS,” Dr. Tanzi said. “Overall, we saw a reduction of a 1.16 level on that six-point scale, which translates roughly into 32.5% reduction of the look of their cellulite from the baseline score.”
In addition, 84% of the time, the blinded assessors were able to correctly identify pre- and posttreatment unlabeled photos that they were presented at the 3-month mark. Those same blinded assessors graded about 86% of the treated cellulite areas as appearing either improved, much improved, or very much improved on the Global Aesthetic Improvement Scale (GAIS).
“We found a very favorable side-effect profile, although 95% of patients had some redness to their skin,” Dr. Tanzi added. “They had some erythema and folliculitis, but it was transient and very mild. In addition, 98% of patients said that the procedure was tolerable.”
As for pain, on a 0-10 scale, with 10 being the worst, subjects rated their pain level at 2.4 during the treatment and 0.3 immediately afterward. On subject satisfaction surveys, 92% of the patient said that they “agree” or “strongly agree” that their cellulite appeared improved.
“Patients with moderate cellulite seem to respond [to this treatment], too,” Dr. Tanzi said. “I don’t think there’s a ceiling or a floor to which we have to pigeonhole patients into potentially treating with this device. I think the key is [targeting] cellulite and not necessarily skin laxity.”
She emphasized that much remains to be known about the RAP device for treating cellulite. “What happens if we do multiple treatments to the tissue?” she asked. “Also, we need to further investigate what’s happening in the tissue, because not only does it seem like we’re getting a cleaving of the fibrous septa, but what is happening to the fibroblasts? What’s really happening in the tissue on a molecular level when those rapid acoustic pulses are going through the skin? There’s a lot of unanswered questions, but this is exciting technology.”
According to a news release from Soliton, the company is further reviewing and analyzing these results for inclusion in a marketing application to the Food and Drug Administration.
Soliton sponsored the trial. Dr. Tanzi disclosed that she is either a consultant for or is a member of the scientific advisory board for Allergan/Coolsculpting, Beiersdorf, Cutera, Merz/Ulthera, Pulse Biosciences, Sciton, Soliton, Solta, and Syneron/Candela.
After a single treatment, it provided a roughly 1.16 point reduction in the five-point Cellulite Severity Scale at 12 weeks, which corresponds to a roughly 32.5% reduction in cellulite.
“In cellulite, we know that the septa within the fat – those fibrous bands that pull down the skin and tether – lead to the traditional look of cellulite dimples and ridges,” lead study author Elizabeth Tanzi, MD, said during a late-breaking abstract session at the virtual annual meeting of the American Academy of Dermatology. A rapid acoustic pulse (RAP) device being developed by Soliton emits rapid acoustic pulses and shock waves at 50 Hz that are transmitted through the skin. The pulses “rupture and shear the fibrotic septa, which causes release of the septa and smoothing of the skin dimples,” explained Dr. Tanzi, director of Capital Laser & Skin Care in Chevy Chase, Md.
She added that the repetition rate of the RAP device makes it stand out from other technologies currently on the market for cellulite treatment. “The repetition rate and very short rise times provide microscopic mechanical destruction to the targeted cellular level structures and the vacuoles,” Dr. Tanzi said. “The high peak pressure and fast repetition rate exploit the viscoelastic nature of the tissue. It’s the rapid rate at which the energy is being delivered, as well as the very short times that energy is being delivered, that makes the technology an entirely different device-tissue interaction.”
The physical effects observed occur in the extracellular matrix and in the destruction of fibrous septa. “That’s the acoustic subcision,” she continued. “But also, there’s no cavitation and there are nonthermal physical effects. There is some investigational research going into what biologic effects those shock waves have on the rest of the tissue, looking into neocollagenesis, potential angiogenesis, potential lymphangiogenesis, as well as inflammation inhibition.”
In a prospective pivotal clinical trial conducted at four sites, Dr. Tanzi and her colleagues evaluated the safety and effectiveness of the RAP device in 62 female patients who were treated with a single, rapid acoustic pulse treatment comprised of 1-2 minutes on each identified dimple or large ridge of cellulite. This amounted to a 19- to 33-minute treatment session for each patient. No anesthesia was required, and photographs were taken on all sites with QuantifiCare medical imaging software.
“It’s completely noninvasive and it’s truly an incisionless treatment,” Dr. Tanzi said of the procedure. “The skin’s never punctured. There’s physician oversight, but it is highly delegatable, and there is no recovery time for the patient.”
Following treatment, adverse effects and tolerability were reported, and safety and efficacy were assessed at 12 weeks. Efficacy was determined by photographic assessment by three blinded independent physicians who used a validated, simplified version of the Cellulite Severity Scale (CSS), a 0-5 scale based on the number of cellulite depressions, as well as the average depth of those depressions.
The mean age of patients was 43 years, 92% were white, and their mean body mass index was 24.5 kg/m2. The average time of treatment was 28 minutes. Based on the CSS scores, the researchers found that 87% of the study subjects had some improvement of their cellulite after a single RAP treatment. “If you break the data down further, half of patients had at least a 30% reduction of their CSS, and almost one-quarter had a 50% improvement of their CSS,” Dr. Tanzi said. “Overall, we saw a reduction of a 1.16 level on that six-point scale, which translates roughly into 32.5% reduction of the look of their cellulite from the baseline score.”
In addition, 84% of the time, the blinded assessors were able to correctly identify pre- and posttreatment unlabeled photos that they were presented at the 3-month mark. Those same blinded assessors graded about 86% of the treated cellulite areas as appearing either improved, much improved, or very much improved on the Global Aesthetic Improvement Scale (GAIS).
“We found a very favorable side-effect profile, although 95% of patients had some redness to their skin,” Dr. Tanzi added. “They had some erythema and folliculitis, but it was transient and very mild. In addition, 98% of patients said that the procedure was tolerable.”
As for pain, on a 0-10 scale, with 10 being the worst, subjects rated their pain level at 2.4 during the treatment and 0.3 immediately afterward. On subject satisfaction surveys, 92% of the patient said that they “agree” or “strongly agree” that their cellulite appeared improved.
“Patients with moderate cellulite seem to respond [to this treatment], too,” Dr. Tanzi said. “I don’t think there’s a ceiling or a floor to which we have to pigeonhole patients into potentially treating with this device. I think the key is [targeting] cellulite and not necessarily skin laxity.”
She emphasized that much remains to be known about the RAP device for treating cellulite. “What happens if we do multiple treatments to the tissue?” she asked. “Also, we need to further investigate what’s happening in the tissue, because not only does it seem like we’re getting a cleaving of the fibrous septa, but what is happening to the fibroblasts? What’s really happening in the tissue on a molecular level when those rapid acoustic pulses are going through the skin? There’s a lot of unanswered questions, but this is exciting technology.”
According to a news release from Soliton, the company is further reviewing and analyzing these results for inclusion in a marketing application to the Food and Drug Administration.
Soliton sponsored the trial. Dr. Tanzi disclosed that she is either a consultant for or is a member of the scientific advisory board for Allergan/Coolsculpting, Beiersdorf, Cutera, Merz/Ulthera, Pulse Biosciences, Sciton, Soliton, Solta, and Syneron/Candela.
After a single treatment, it provided a roughly 1.16 point reduction in the five-point Cellulite Severity Scale at 12 weeks, which corresponds to a roughly 32.5% reduction in cellulite.
“In cellulite, we know that the septa within the fat – those fibrous bands that pull down the skin and tether – lead to the traditional look of cellulite dimples and ridges,” lead study author Elizabeth Tanzi, MD, said during a late-breaking abstract session at the virtual annual meeting of the American Academy of Dermatology. A rapid acoustic pulse (RAP) device being developed by Soliton emits rapid acoustic pulses and shock waves at 50 Hz that are transmitted through the skin. The pulses “rupture and shear the fibrotic septa, which causes release of the septa and smoothing of the skin dimples,” explained Dr. Tanzi, director of Capital Laser & Skin Care in Chevy Chase, Md.
She added that the repetition rate of the RAP device makes it stand out from other technologies currently on the market for cellulite treatment. “The repetition rate and very short rise times provide microscopic mechanical destruction to the targeted cellular level structures and the vacuoles,” Dr. Tanzi said. “The high peak pressure and fast repetition rate exploit the viscoelastic nature of the tissue. It’s the rapid rate at which the energy is being delivered, as well as the very short times that energy is being delivered, that makes the technology an entirely different device-tissue interaction.”
The physical effects observed occur in the extracellular matrix and in the destruction of fibrous septa. “That’s the acoustic subcision,” she continued. “But also, there’s no cavitation and there are nonthermal physical effects. There is some investigational research going into what biologic effects those shock waves have on the rest of the tissue, looking into neocollagenesis, potential angiogenesis, potential lymphangiogenesis, as well as inflammation inhibition.”
In a prospective pivotal clinical trial conducted at four sites, Dr. Tanzi and her colleagues evaluated the safety and effectiveness of the RAP device in 62 female patients who were treated with a single, rapid acoustic pulse treatment comprised of 1-2 minutes on each identified dimple or large ridge of cellulite. This amounted to a 19- to 33-minute treatment session for each patient. No anesthesia was required, and photographs were taken on all sites with QuantifiCare medical imaging software.
“It’s completely noninvasive and it’s truly an incisionless treatment,” Dr. Tanzi said of the procedure. “The skin’s never punctured. There’s physician oversight, but it is highly delegatable, and there is no recovery time for the patient.”
Following treatment, adverse effects and tolerability were reported, and safety and efficacy were assessed at 12 weeks. Efficacy was determined by photographic assessment by three blinded independent physicians who used a validated, simplified version of the Cellulite Severity Scale (CSS), a 0-5 scale based on the number of cellulite depressions, as well as the average depth of those depressions.
The mean age of patients was 43 years, 92% were white, and their mean body mass index was 24.5 kg/m2. The average time of treatment was 28 minutes. Based on the CSS scores, the researchers found that 87% of the study subjects had some improvement of their cellulite after a single RAP treatment. “If you break the data down further, half of patients had at least a 30% reduction of their CSS, and almost one-quarter had a 50% improvement of their CSS,” Dr. Tanzi said. “Overall, we saw a reduction of a 1.16 level on that six-point scale, which translates roughly into 32.5% reduction of the look of their cellulite from the baseline score.”
In addition, 84% of the time, the blinded assessors were able to correctly identify pre- and posttreatment unlabeled photos that they were presented at the 3-month mark. Those same blinded assessors graded about 86% of the treated cellulite areas as appearing either improved, much improved, or very much improved on the Global Aesthetic Improvement Scale (GAIS).
“We found a very favorable side-effect profile, although 95% of patients had some redness to their skin,” Dr. Tanzi added. “They had some erythema and folliculitis, but it was transient and very mild. In addition, 98% of patients said that the procedure was tolerable.”
As for pain, on a 0-10 scale, with 10 being the worst, subjects rated their pain level at 2.4 during the treatment and 0.3 immediately afterward. On subject satisfaction surveys, 92% of the patient said that they “agree” or “strongly agree” that their cellulite appeared improved.
“Patients with moderate cellulite seem to respond [to this treatment], too,” Dr. Tanzi said. “I don’t think there’s a ceiling or a floor to which we have to pigeonhole patients into potentially treating with this device. I think the key is [targeting] cellulite and not necessarily skin laxity.”
She emphasized that much remains to be known about the RAP device for treating cellulite. “What happens if we do multiple treatments to the tissue?” she asked. “Also, we need to further investigate what’s happening in the tissue, because not only does it seem like we’re getting a cleaving of the fibrous septa, but what is happening to the fibroblasts? What’s really happening in the tissue on a molecular level when those rapid acoustic pulses are going through the skin? There’s a lot of unanswered questions, but this is exciting technology.”
According to a news release from Soliton, the company is further reviewing and analyzing these results for inclusion in a marketing application to the Food and Drug Administration.
Soliton sponsored the trial. Dr. Tanzi disclosed that she is either a consultant for or is a member of the scientific advisory board for Allergan/Coolsculpting, Beiersdorf, Cutera, Merz/Ulthera, Pulse Biosciences, Sciton, Soliton, Solta, and Syneron/Candela.
FROM AAD 20
First validated classification criteria for discoid lupus erythematosus unveiled
The first validated classification criteria for discoid lupus erythematosus has a sensitivity that ranges between 73.9% and 84.1% and a specificity that ranges between 75.9% and 92.9%.
“Discoid lupus erythematosus [DLE] is the most common type of chronic cutaneous lupus,” lead study author Scott A. Elman, MD, said during the virtual annual meeting of the American Academy of Dermatology. “It’s one of the most potentially disfiguring forms of cutaneous lupus erythematosus [CLE], which can lead to scarring, hair loss, and dyspigmentation if not treated early or promptly. It has a significant impact on patient quality of life and there are currently no classification criteria for DLE, which has led to problematic heterogeneity in observational and interventional research efforts. As there is increasing interest in drug development programs for CLE and DLE, there is a need to develop classification criteria.”
Dr. Elman, of the Harvard combined medicine-dermatology training program at Brigham and Women’s Hospital, Boston, pointed out that classification criteria are the standard definitions that are primarily intended to enroll uniform cohorts for research. “These emphasize high specificity, whereas diagnostic criteria reflect a more broad and variable set of features of a given disease, and therefore require a higher sensitivity,” he explained. “While classification criteria are not synonymous with diagnostic criteria, they typically mirror the list of criteria that are used for diagnosis.”
In 2017, Dr. Elman and colleagues generated an item list of 12 potential classification criteria using an international Delphi consensus process: 5 criteria represented disease morphology, 2 represented discoid lupus location, and 5 represented histopathology (J Am Acad Dermatol. 2017 Aug 1;77[2]:261-7). The purpose of the current study, which was presented as a late-breaking abstract, was to validate the proposed classification criteria in a multicenter, international trial. “The point is to be able to differentiate between discoid lupus and its disease mimickers, which could be confused in enrollment in clinical trials,” he said.
At nine participating sites, patients were identified at clinical visits as having either DLE or a DLE mimicker. After each visit, dermatologists determined if morphological features were present. One dermatopathologist at each site reviewed pathology, if available, to see if the histopathologic features were present. Diagnosis by clinical features and dermatopathology were tabulated and presented as counts and percentages. Clinical features among those with and without DLE were calculated and compared with chi-square or Fisher’s exact tests. The researchers used best subsets logistic regression analysis to identify candidate models.
A total of 215 patients were enrolled: 94 that were consistent with DLE and 121 that were consistent with a DLE mimicker. Most cases (83%) were from North America, 11% were from Asia, and 6% were from Europe. Only 86 cases (40%) had biopsies for dermatopathology review.
The following clinical features were found to be more commonly associated with DLE, compared with DLE mimickers: atrophic scarring (83% vs. 24%; P < .001), dyspigmentation (84% vs. 55%; P < .001), follicular hyperkeratosis/plugging (43% vs. 11%; P < .001), scarring alopecia (61% vs. 21%; P < .001), location in the conchal bowl (49% vs. 10%; P < .001), preference for the head and neck (87% vs. 49%; P < .001), and erythematous to violaceous in color (93% vs. 85%, a nonsignificant difference; P = .09).
When histopathological items were assessed, the following features were found to be more commonly associated with DLE, compared with DLE mimickers: interface/vacuolar dermatitis (83% vs. 53%; P = .004), perivascular and/or periappendageal lymphohistiocytic infiltrate (95% vs. 84%, a nonsignificant difference; P = .18), follicular keratin plugs (57% vs. 20%; P < .001), mucin deposition (73% vs. 39%; P = .002), and basement membrane thickening (57% vs. 14%; P < .001).
“There was good agreement between the diagnoses made by dermatologists and dermatopathologists, with a Cohen’s kappa statistic of 0.83,” Dr. Elman added. “Similarly, in many of the cases, the dermatopathologists and the dermatologists felt confident in their diagnosis.”
For the final model, the researchers excluded patients who had any missing data as well as those who had a diagnosis that was uncertain. This left 200 cases in the final model. Clinical variables associated with DLE were: atrophic scarring (odds ratio, 8.70; P < .001), location in the conchal bowl (OR, 6.80; P < .001), preference for head and neck (OR, 9.41; P < .001), dyspigmentation (OR, 3.23; P = .020), follicular hyperkeratosis/plugging (OR, 2.94; P = .054), and erythematous to violaceous in color (OR, 3.44; P = .056). The area under the curve for the model was 0.91.
According to Dr. Elman, the final model is a points-based model with 3 points assigned to atrophic scarring, 2 points assigned to location in the conchal bowl, 2 points assigned to preference for head and neck, 1 point assigned to dyspigmentation, 1 point assigned to follicular hyperkeratosis/plugging, and 1 point assigned to erythematous to violaceous in color. A score of 5 or greater yields a classification as DLE with 84.1% sensitivity and 75.9% specificity, while a score of 7 or greater yields a 73.9% sensitivity and 92.9% specificity.
Dr. Elman acknowledged certain limitations of the study, including the fact that information related to histopathology was not included in the final model. “This was a result of having only 40% of cases with relevant dermatopathology,” he said. “This limited our ability to meaningfully incorporate these items into a classification criteria set. However, with the data we’ve collected, efforts are under way to make a DLE-specific histopathology classification criteria.”
Another limitation is that the researchers relied on expert diagnosis as the preferred option. “Similarly, many of the cases came from large referral centers, and no demographic data were obtained, so this limits the generalizability of our study,” he said.
Dr. Elman reported having no financial disclosures.
The first validated classification criteria for discoid lupus erythematosus has a sensitivity that ranges between 73.9% and 84.1% and a specificity that ranges between 75.9% and 92.9%.
“Discoid lupus erythematosus [DLE] is the most common type of chronic cutaneous lupus,” lead study author Scott A. Elman, MD, said during the virtual annual meeting of the American Academy of Dermatology. “It’s one of the most potentially disfiguring forms of cutaneous lupus erythematosus [CLE], which can lead to scarring, hair loss, and dyspigmentation if not treated early or promptly. It has a significant impact on patient quality of life and there are currently no classification criteria for DLE, which has led to problematic heterogeneity in observational and interventional research efforts. As there is increasing interest in drug development programs for CLE and DLE, there is a need to develop classification criteria.”
Dr. Elman, of the Harvard combined medicine-dermatology training program at Brigham and Women’s Hospital, Boston, pointed out that classification criteria are the standard definitions that are primarily intended to enroll uniform cohorts for research. “These emphasize high specificity, whereas diagnostic criteria reflect a more broad and variable set of features of a given disease, and therefore require a higher sensitivity,” he explained. “While classification criteria are not synonymous with diagnostic criteria, they typically mirror the list of criteria that are used for diagnosis.”
In 2017, Dr. Elman and colleagues generated an item list of 12 potential classification criteria using an international Delphi consensus process: 5 criteria represented disease morphology, 2 represented discoid lupus location, and 5 represented histopathology (J Am Acad Dermatol. 2017 Aug 1;77[2]:261-7). The purpose of the current study, which was presented as a late-breaking abstract, was to validate the proposed classification criteria in a multicenter, international trial. “The point is to be able to differentiate between discoid lupus and its disease mimickers, which could be confused in enrollment in clinical trials,” he said.
At nine participating sites, patients were identified at clinical visits as having either DLE or a DLE mimicker. After each visit, dermatologists determined if morphological features were present. One dermatopathologist at each site reviewed pathology, if available, to see if the histopathologic features were present. Diagnosis by clinical features and dermatopathology were tabulated and presented as counts and percentages. Clinical features among those with and without DLE were calculated and compared with chi-square or Fisher’s exact tests. The researchers used best subsets logistic regression analysis to identify candidate models.
A total of 215 patients were enrolled: 94 that were consistent with DLE and 121 that were consistent with a DLE mimicker. Most cases (83%) were from North America, 11% were from Asia, and 6% were from Europe. Only 86 cases (40%) had biopsies for dermatopathology review.
The following clinical features were found to be more commonly associated with DLE, compared with DLE mimickers: atrophic scarring (83% vs. 24%; P < .001), dyspigmentation (84% vs. 55%; P < .001), follicular hyperkeratosis/plugging (43% vs. 11%; P < .001), scarring alopecia (61% vs. 21%; P < .001), location in the conchal bowl (49% vs. 10%; P < .001), preference for the head and neck (87% vs. 49%; P < .001), and erythematous to violaceous in color (93% vs. 85%, a nonsignificant difference; P = .09).
When histopathological items were assessed, the following features were found to be more commonly associated with DLE, compared with DLE mimickers: interface/vacuolar dermatitis (83% vs. 53%; P = .004), perivascular and/or periappendageal lymphohistiocytic infiltrate (95% vs. 84%, a nonsignificant difference; P = .18), follicular keratin plugs (57% vs. 20%; P < .001), mucin deposition (73% vs. 39%; P = .002), and basement membrane thickening (57% vs. 14%; P < .001).
“There was good agreement between the diagnoses made by dermatologists and dermatopathologists, with a Cohen’s kappa statistic of 0.83,” Dr. Elman added. “Similarly, in many of the cases, the dermatopathologists and the dermatologists felt confident in their diagnosis.”
For the final model, the researchers excluded patients who had any missing data as well as those who had a diagnosis that was uncertain. This left 200 cases in the final model. Clinical variables associated with DLE were: atrophic scarring (odds ratio, 8.70; P < .001), location in the conchal bowl (OR, 6.80; P < .001), preference for head and neck (OR, 9.41; P < .001), dyspigmentation (OR, 3.23; P = .020), follicular hyperkeratosis/plugging (OR, 2.94; P = .054), and erythematous to violaceous in color (OR, 3.44; P = .056). The area under the curve for the model was 0.91.
According to Dr. Elman, the final model is a points-based model with 3 points assigned to atrophic scarring, 2 points assigned to location in the conchal bowl, 2 points assigned to preference for head and neck, 1 point assigned to dyspigmentation, 1 point assigned to follicular hyperkeratosis/plugging, and 1 point assigned to erythematous to violaceous in color. A score of 5 or greater yields a classification as DLE with 84.1% sensitivity and 75.9% specificity, while a score of 7 or greater yields a 73.9% sensitivity and 92.9% specificity.
Dr. Elman acknowledged certain limitations of the study, including the fact that information related to histopathology was not included in the final model. “This was a result of having only 40% of cases with relevant dermatopathology,” he said. “This limited our ability to meaningfully incorporate these items into a classification criteria set. However, with the data we’ve collected, efforts are under way to make a DLE-specific histopathology classification criteria.”
Another limitation is that the researchers relied on expert diagnosis as the preferred option. “Similarly, many of the cases came from large referral centers, and no demographic data were obtained, so this limits the generalizability of our study,” he said.
Dr. Elman reported having no financial disclosures.
The first validated classification criteria for discoid lupus erythematosus has a sensitivity that ranges between 73.9% and 84.1% and a specificity that ranges between 75.9% and 92.9%.
“Discoid lupus erythematosus [DLE] is the most common type of chronic cutaneous lupus,” lead study author Scott A. Elman, MD, said during the virtual annual meeting of the American Academy of Dermatology. “It’s one of the most potentially disfiguring forms of cutaneous lupus erythematosus [CLE], which can lead to scarring, hair loss, and dyspigmentation if not treated early or promptly. It has a significant impact on patient quality of life and there are currently no classification criteria for DLE, which has led to problematic heterogeneity in observational and interventional research efforts. As there is increasing interest in drug development programs for CLE and DLE, there is a need to develop classification criteria.”
Dr. Elman, of the Harvard combined medicine-dermatology training program at Brigham and Women’s Hospital, Boston, pointed out that classification criteria are the standard definitions that are primarily intended to enroll uniform cohorts for research. “These emphasize high specificity, whereas diagnostic criteria reflect a more broad and variable set of features of a given disease, and therefore require a higher sensitivity,” he explained. “While classification criteria are not synonymous with diagnostic criteria, they typically mirror the list of criteria that are used for diagnosis.”
In 2017, Dr. Elman and colleagues generated an item list of 12 potential classification criteria using an international Delphi consensus process: 5 criteria represented disease morphology, 2 represented discoid lupus location, and 5 represented histopathology (J Am Acad Dermatol. 2017 Aug 1;77[2]:261-7). The purpose of the current study, which was presented as a late-breaking abstract, was to validate the proposed classification criteria in a multicenter, international trial. “The point is to be able to differentiate between discoid lupus and its disease mimickers, which could be confused in enrollment in clinical trials,” he said.
At nine participating sites, patients were identified at clinical visits as having either DLE or a DLE mimicker. After each visit, dermatologists determined if morphological features were present. One dermatopathologist at each site reviewed pathology, if available, to see if the histopathologic features were present. Diagnosis by clinical features and dermatopathology were tabulated and presented as counts and percentages. Clinical features among those with and without DLE were calculated and compared with chi-square or Fisher’s exact tests. The researchers used best subsets logistic regression analysis to identify candidate models.
A total of 215 patients were enrolled: 94 that were consistent with DLE and 121 that were consistent with a DLE mimicker. Most cases (83%) were from North America, 11% were from Asia, and 6% were from Europe. Only 86 cases (40%) had biopsies for dermatopathology review.
The following clinical features were found to be more commonly associated with DLE, compared with DLE mimickers: atrophic scarring (83% vs. 24%; P < .001), dyspigmentation (84% vs. 55%; P < .001), follicular hyperkeratosis/plugging (43% vs. 11%; P < .001), scarring alopecia (61% vs. 21%; P < .001), location in the conchal bowl (49% vs. 10%; P < .001), preference for the head and neck (87% vs. 49%; P < .001), and erythematous to violaceous in color (93% vs. 85%, a nonsignificant difference; P = .09).
When histopathological items were assessed, the following features were found to be more commonly associated with DLE, compared with DLE mimickers: interface/vacuolar dermatitis (83% vs. 53%; P = .004), perivascular and/or periappendageal lymphohistiocytic infiltrate (95% vs. 84%, a nonsignificant difference; P = .18), follicular keratin plugs (57% vs. 20%; P < .001), mucin deposition (73% vs. 39%; P = .002), and basement membrane thickening (57% vs. 14%; P < .001).
“There was good agreement between the diagnoses made by dermatologists and dermatopathologists, with a Cohen’s kappa statistic of 0.83,” Dr. Elman added. “Similarly, in many of the cases, the dermatopathologists and the dermatologists felt confident in their diagnosis.”
For the final model, the researchers excluded patients who had any missing data as well as those who had a diagnosis that was uncertain. This left 200 cases in the final model. Clinical variables associated with DLE were: atrophic scarring (odds ratio, 8.70; P < .001), location in the conchal bowl (OR, 6.80; P < .001), preference for head and neck (OR, 9.41; P < .001), dyspigmentation (OR, 3.23; P = .020), follicular hyperkeratosis/plugging (OR, 2.94; P = .054), and erythematous to violaceous in color (OR, 3.44; P = .056). The area under the curve for the model was 0.91.
According to Dr. Elman, the final model is a points-based model with 3 points assigned to atrophic scarring, 2 points assigned to location in the conchal bowl, 2 points assigned to preference for head and neck, 1 point assigned to dyspigmentation, 1 point assigned to follicular hyperkeratosis/plugging, and 1 point assigned to erythematous to violaceous in color. A score of 5 or greater yields a classification as DLE with 84.1% sensitivity and 75.9% specificity, while a score of 7 or greater yields a 73.9% sensitivity and 92.9% specificity.
Dr. Elman acknowledged certain limitations of the study, including the fact that information related to histopathology was not included in the final model. “This was a result of having only 40% of cases with relevant dermatopathology,” he said. “This limited our ability to meaningfully incorporate these items into a classification criteria set. However, with the data we’ve collected, efforts are under way to make a DLE-specific histopathology classification criteria.”
Another limitation is that the researchers relied on expert diagnosis as the preferred option. “Similarly, many of the cases came from large referral centers, and no demographic data were obtained, so this limits the generalizability of our study,” he said.
Dr. Elman reported having no financial disclosures.
FROM AAD 20
Microneedling plus 10% TCA peels bests CO2 laser alone for infraorbital dark circles
In a study of patients with mild to moderate infraorbital dark circles, treatment with carbon dioxide laser resurfacing did not produce a significant improvement in infraorbital hyperpigmentation. However, the combination of microneedling and 10% trichloroacetic acid peels did.
The finding comes from what is believed to be the first head-to-head comparison of the two procedures for infraorbital dark circles, which are a common cosmetic concern with increased age.
During a late-breaking abstract session at the virtual annual meeting of the American Academy of Dermatology, lead study author Banu Farabi, MD, said that dark circles seen in the periorbital area are defined as bilateral, round homogeneous pigmented macules whose etiology is thought to be multifactorial. Available treatments include bleaching creams, topical retinoids, chemical peels, lasers, autologous fat transplantation, injectable fillers, and blepharoplasty.
“Microneedling has been recently suggested as an effective and efficient method for reducing infraorbital dark circles,” Dr. Farabi said. “This technique is based on creating microchannels that can stimulate the production of subcutaneous collagen and elastin. It also enhances the revascularization and fibroblast activity, which increases the skin thickness and gives a shiny appearance to the skin. The fractional CO2 has also been introduced as an effective procedure to remove infraorbital dark circles. However, there are some potential complications with that therapy.”
For the current study, Dr. Farabi, of the department of dermatology at Ankara (Turkey) University, and Mohamad Goldust, MD, of University Hospital Basel (Switzerland), They used the handheld Automatic Microneedle Therapy System-Handhold from MCure. After creating microchannels, the investigators topically applied 10% trichloroacetic acid peels to each infraorbital area and waited for 5 minutes.
In the carbon dioxide laser group, a Lutronic CO2 laser was used with a pulse energy of 10 J/cm2, a 100-microsecond pulse rate, 30 W of power, and a pulse width of 4 mm. The treatment outcome was assessed with the patient’s satisfaction and the physician’s judgment, which were no response, partial response, and complete response. Patients in both study groups were followed up for blinded-investigator assessment of infraorbital hyperpigmentation, adverse events, and improvement, compared with baseline.
The mean age of patients was 40 years, with a range between 27 and 58 years. About one-third of patients in each group had Fitzpatrick skin types II, III, and IV, respectively. In the blinded investigator assessment, the laser-resurfacing procedure did not demonstrate a significant improvement in infraorbital hyperpigmentation at day 90 (P = .24). However, the combination of microneedling and 10% trichloroacetic acid peels significantly improved infraorbital hyperpigmentation by day 90, with improvement maintained through day 180 (P = .012 and .002, respectively).
Adverse events were mild and temporary in both groups. In the laser-resurfacing group, 7 of the patients (22.5%) developed transient infraorbital hyperpigmentation postoperatively that lasted 4 weeks. In the combination treatment group, 18 patients (58%) developed transient erythema that lasted for up to 1 week.
“We suggest using microneedling plus 10% [trichloroacetic acid] as a cost-effective and efficient method for reducing infraorbital dark circles,” Dr. Farabi concluded.
The researchers reported having no financial disclosures.
In a study of patients with mild to moderate infraorbital dark circles, treatment with carbon dioxide laser resurfacing did not produce a significant improvement in infraorbital hyperpigmentation. However, the combination of microneedling and 10% trichloroacetic acid peels did.
The finding comes from what is believed to be the first head-to-head comparison of the two procedures for infraorbital dark circles, which are a common cosmetic concern with increased age.
During a late-breaking abstract session at the virtual annual meeting of the American Academy of Dermatology, lead study author Banu Farabi, MD, said that dark circles seen in the periorbital area are defined as bilateral, round homogeneous pigmented macules whose etiology is thought to be multifactorial. Available treatments include bleaching creams, topical retinoids, chemical peels, lasers, autologous fat transplantation, injectable fillers, and blepharoplasty.
“Microneedling has been recently suggested as an effective and efficient method for reducing infraorbital dark circles,” Dr. Farabi said. “This technique is based on creating microchannels that can stimulate the production of subcutaneous collagen and elastin. It also enhances the revascularization and fibroblast activity, which increases the skin thickness and gives a shiny appearance to the skin. The fractional CO2 has also been introduced as an effective procedure to remove infraorbital dark circles. However, there are some potential complications with that therapy.”
For the current study, Dr. Farabi, of the department of dermatology at Ankara (Turkey) University, and Mohamad Goldust, MD, of University Hospital Basel (Switzerland), They used the handheld Automatic Microneedle Therapy System-Handhold from MCure. After creating microchannels, the investigators topically applied 10% trichloroacetic acid peels to each infraorbital area and waited for 5 minutes.
In the carbon dioxide laser group, a Lutronic CO2 laser was used with a pulse energy of 10 J/cm2, a 100-microsecond pulse rate, 30 W of power, and a pulse width of 4 mm. The treatment outcome was assessed with the patient’s satisfaction and the physician’s judgment, which were no response, partial response, and complete response. Patients in both study groups were followed up for blinded-investigator assessment of infraorbital hyperpigmentation, adverse events, and improvement, compared with baseline.
The mean age of patients was 40 years, with a range between 27 and 58 years. About one-third of patients in each group had Fitzpatrick skin types II, III, and IV, respectively. In the blinded investigator assessment, the laser-resurfacing procedure did not demonstrate a significant improvement in infraorbital hyperpigmentation at day 90 (P = .24). However, the combination of microneedling and 10% trichloroacetic acid peels significantly improved infraorbital hyperpigmentation by day 90, with improvement maintained through day 180 (P = .012 and .002, respectively).
Adverse events were mild and temporary in both groups. In the laser-resurfacing group, 7 of the patients (22.5%) developed transient infraorbital hyperpigmentation postoperatively that lasted 4 weeks. In the combination treatment group, 18 patients (58%) developed transient erythema that lasted for up to 1 week.
“We suggest using microneedling plus 10% [trichloroacetic acid] as a cost-effective and efficient method for reducing infraorbital dark circles,” Dr. Farabi concluded.
The researchers reported having no financial disclosures.
In a study of patients with mild to moderate infraorbital dark circles, treatment with carbon dioxide laser resurfacing did not produce a significant improvement in infraorbital hyperpigmentation. However, the combination of microneedling and 10% trichloroacetic acid peels did.
The finding comes from what is believed to be the first head-to-head comparison of the two procedures for infraorbital dark circles, which are a common cosmetic concern with increased age.
During a late-breaking abstract session at the virtual annual meeting of the American Academy of Dermatology, lead study author Banu Farabi, MD, said that dark circles seen in the periorbital area are defined as bilateral, round homogeneous pigmented macules whose etiology is thought to be multifactorial. Available treatments include bleaching creams, topical retinoids, chemical peels, lasers, autologous fat transplantation, injectable fillers, and blepharoplasty.
“Microneedling has been recently suggested as an effective and efficient method for reducing infraorbital dark circles,” Dr. Farabi said. “This technique is based on creating microchannels that can stimulate the production of subcutaneous collagen and elastin. It also enhances the revascularization and fibroblast activity, which increases the skin thickness and gives a shiny appearance to the skin. The fractional CO2 has also been introduced as an effective procedure to remove infraorbital dark circles. However, there are some potential complications with that therapy.”
For the current study, Dr. Farabi, of the department of dermatology at Ankara (Turkey) University, and Mohamad Goldust, MD, of University Hospital Basel (Switzerland), They used the handheld Automatic Microneedle Therapy System-Handhold from MCure. After creating microchannels, the investigators topically applied 10% trichloroacetic acid peels to each infraorbital area and waited for 5 minutes.
In the carbon dioxide laser group, a Lutronic CO2 laser was used with a pulse energy of 10 J/cm2, a 100-microsecond pulse rate, 30 W of power, and a pulse width of 4 mm. The treatment outcome was assessed with the patient’s satisfaction and the physician’s judgment, which were no response, partial response, and complete response. Patients in both study groups were followed up for blinded-investigator assessment of infraorbital hyperpigmentation, adverse events, and improvement, compared with baseline.
The mean age of patients was 40 years, with a range between 27 and 58 years. About one-third of patients in each group had Fitzpatrick skin types II, III, and IV, respectively. In the blinded investigator assessment, the laser-resurfacing procedure did not demonstrate a significant improvement in infraorbital hyperpigmentation at day 90 (P = .24). However, the combination of microneedling and 10% trichloroacetic acid peels significantly improved infraorbital hyperpigmentation by day 90, with improvement maintained through day 180 (P = .012 and .002, respectively).
Adverse events were mild and temporary in both groups. In the laser-resurfacing group, 7 of the patients (22.5%) developed transient infraorbital hyperpigmentation postoperatively that lasted 4 weeks. In the combination treatment group, 18 patients (58%) developed transient erythema that lasted for up to 1 week.
“We suggest using microneedling plus 10% [trichloroacetic acid] as a cost-effective and efficient method for reducing infraorbital dark circles,” Dr. Farabi concluded.
The researchers reported having no financial disclosures.
FROM AAD 20
Risankizumab compared with secukinumab in 52-week psoriasis trial
.
Risankizumab was better tolerated, with a significantly lower rate of treatment-emergent adverse events and a lower study dropout rate, Richard B. Warren, MBChB, PhD, reported at the virtual annual meeting of the American Academy of Dermatology.
In addition, the dosing schedule for risankizumab (Skyrizi) is more convenient, with maintenance dosing by subcutaneous injection once every 12 weeks, compared with monthly for secukinumab (Cosentyx), a biologic for psoriasis considered state-of-the-art not long ago, noted Dr. Warren, a dermatologist at the Salford (England) Royal NHS Foundation Trust and the Manchester NIHR Biomedical Research Center as well as professor of dermatology at the University of Manchester.
The phase 3 IMMERGE trial included 327 patients with moderate to severe psoriasis randomized to risankizumab or secukinumab for 52 weeks at their approved dosing. The trial, conducted mainly in the United States, Canada, and Europe, was open label, but evaluator blinded.
The coprimary endpoints were a 90% improvement from baseline in Psoriasis Area and Severity Index scores (PASI 90) at weeks 16 and 52. The week 52 PASI 90 response rates were 87% in the risankizumab group and 57% with secukinumab, for a highly significant absolute 30% difference. The week 16 result was a prespecified noninferiority analysis, and here again risankizumab met its mark, with a PASI 90 rate of 74%, statistically noninferior to the 66% rate with secukinumab, even though at that point patients had received only two doses of risankizumab, versus seven doses of secukinumab.
The PASI 100 response rate at 52 weeks, a key secondary endpoint, was 66% with risankizumab and 40% with secukinumab. Another secondary endpoint was achievement of a static Physician Global Assessment score of 0 or 1 – clear or almost clear – at week 52; the rates were 88% with risankizumab, 58% with secukinumab.
Ninety-two percent of participants randomized to risankizumab completed the full 52-week study, as did 82.8% of the secukinumab group. The nearly 10% absolute lower completion rate in the secukinumab group was driven by a higher rate of lack of efficacy – 4.3%, compared to 0.6% for risankizumab – and a greater incidence of adverse events. Indeed, treatment-emergent adverse events were fourfold more common in the secukinumab arm, with a rate of 4.9%, versus 1.2% with risankizumab, according to Dr. Warren.
He reported receiving research grants from and serving as a consultant to the study sponsor, AbbVie, as well as roughly a dozen other pharmaceutical companies.
.
Risankizumab was better tolerated, with a significantly lower rate of treatment-emergent adverse events and a lower study dropout rate, Richard B. Warren, MBChB, PhD, reported at the virtual annual meeting of the American Academy of Dermatology.
In addition, the dosing schedule for risankizumab (Skyrizi) is more convenient, with maintenance dosing by subcutaneous injection once every 12 weeks, compared with monthly for secukinumab (Cosentyx), a biologic for psoriasis considered state-of-the-art not long ago, noted Dr. Warren, a dermatologist at the Salford (England) Royal NHS Foundation Trust and the Manchester NIHR Biomedical Research Center as well as professor of dermatology at the University of Manchester.
The phase 3 IMMERGE trial included 327 patients with moderate to severe psoriasis randomized to risankizumab or secukinumab for 52 weeks at their approved dosing. The trial, conducted mainly in the United States, Canada, and Europe, was open label, but evaluator blinded.
The coprimary endpoints were a 90% improvement from baseline in Psoriasis Area and Severity Index scores (PASI 90) at weeks 16 and 52. The week 52 PASI 90 response rates were 87% in the risankizumab group and 57% with secukinumab, for a highly significant absolute 30% difference. The week 16 result was a prespecified noninferiority analysis, and here again risankizumab met its mark, with a PASI 90 rate of 74%, statistically noninferior to the 66% rate with secukinumab, even though at that point patients had received only two doses of risankizumab, versus seven doses of secukinumab.
The PASI 100 response rate at 52 weeks, a key secondary endpoint, was 66% with risankizumab and 40% with secukinumab. Another secondary endpoint was achievement of a static Physician Global Assessment score of 0 or 1 – clear or almost clear – at week 52; the rates were 88% with risankizumab, 58% with secukinumab.
Ninety-two percent of participants randomized to risankizumab completed the full 52-week study, as did 82.8% of the secukinumab group. The nearly 10% absolute lower completion rate in the secukinumab group was driven by a higher rate of lack of efficacy – 4.3%, compared to 0.6% for risankizumab – and a greater incidence of adverse events. Indeed, treatment-emergent adverse events were fourfold more common in the secukinumab arm, with a rate of 4.9%, versus 1.2% with risankizumab, according to Dr. Warren.
He reported receiving research grants from and serving as a consultant to the study sponsor, AbbVie, as well as roughly a dozen other pharmaceutical companies.
.
Risankizumab was better tolerated, with a significantly lower rate of treatment-emergent adverse events and a lower study dropout rate, Richard B. Warren, MBChB, PhD, reported at the virtual annual meeting of the American Academy of Dermatology.
In addition, the dosing schedule for risankizumab (Skyrizi) is more convenient, with maintenance dosing by subcutaneous injection once every 12 weeks, compared with monthly for secukinumab (Cosentyx), a biologic for psoriasis considered state-of-the-art not long ago, noted Dr. Warren, a dermatologist at the Salford (England) Royal NHS Foundation Trust and the Manchester NIHR Biomedical Research Center as well as professor of dermatology at the University of Manchester.
The phase 3 IMMERGE trial included 327 patients with moderate to severe psoriasis randomized to risankizumab or secukinumab for 52 weeks at their approved dosing. The trial, conducted mainly in the United States, Canada, and Europe, was open label, but evaluator blinded.
The coprimary endpoints were a 90% improvement from baseline in Psoriasis Area and Severity Index scores (PASI 90) at weeks 16 and 52. The week 52 PASI 90 response rates were 87% in the risankizumab group and 57% with secukinumab, for a highly significant absolute 30% difference. The week 16 result was a prespecified noninferiority analysis, and here again risankizumab met its mark, with a PASI 90 rate of 74%, statistically noninferior to the 66% rate with secukinumab, even though at that point patients had received only two doses of risankizumab, versus seven doses of secukinumab.
The PASI 100 response rate at 52 weeks, a key secondary endpoint, was 66% with risankizumab and 40% with secukinumab. Another secondary endpoint was achievement of a static Physician Global Assessment score of 0 or 1 – clear or almost clear – at week 52; the rates were 88% with risankizumab, 58% with secukinumab.
Ninety-two percent of participants randomized to risankizumab completed the full 52-week study, as did 82.8% of the secukinumab group. The nearly 10% absolute lower completion rate in the secukinumab group was driven by a higher rate of lack of efficacy – 4.3%, compared to 0.6% for risankizumab – and a greater incidence of adverse events. Indeed, treatment-emergent adverse events were fourfold more common in the secukinumab arm, with a rate of 4.9%, versus 1.2% with risankizumab, according to Dr. Warren.
He reported receiving research grants from and serving as a consultant to the study sponsor, AbbVie, as well as roughly a dozen other pharmaceutical companies.
FROM AAD 20
Trifarotene sails through 52-week acne trial
James Q. Del Rosso, MD, reported at the virtual annual meeting of the American Academy of Dermatology.
The study is noteworthy because, even though roughly half of patients with facial acne also have truncal acne, there is actually very little clinical trial data on the treatment of truncal acne other than this new long-term study and the two earlier pivotal phase 3, 12-week trials which led to the October 2019 approval of trifarotene 50 mcg/g cream (Aklief) as the first novel retinoid for acne to reach the market in 20 years, observed Dr. Del Rosso, research director at JDR Research in Las Vegas and a member of the dermatology faculty at Touro University in Henderson, Nev.
The 52-week study, known as SATISFY, began with 454 patients with moderate facial and truncal acne who treated themselves with trifarotene once daily. Among the 348 patients who completed the full year, 67% achieved a score of 0 or 1 – clear or almost clear – with at least a 2-grade improvement from baseline by Investigator’s Global Assessment on their facial acne, and 65% met the same measure of success on the trunk. Moreover, 58% of patients met that standard at both acne sites.
The IGA success rate rose throughout the study period without ever reaching a plateau. However, it should be noted that 23% of participants dropped out of the study over the course of the year.
Mean tolerability scores reflecting redness, scaling, stinging or burning, and skin dryness remained well below the threshold for mild severity, peaking at weeks 2-4 of the study. The most common treatment-related adverse events were mild to moderate itching and irritation, each occurring in less than 5% of subjects.
Trifarotene is a first-in-class retinoid that specifically targets the retinoic acid receptor gamma, the most common cutaneous retinoic acid receptor.
Dr. Del Rosso reported serving as an investigator and consultant for Galderma, which sponsored the study and markets trifarotene cream.
James Q. Del Rosso, MD, reported at the virtual annual meeting of the American Academy of Dermatology.
The study is noteworthy because, even though roughly half of patients with facial acne also have truncal acne, there is actually very little clinical trial data on the treatment of truncal acne other than this new long-term study and the two earlier pivotal phase 3, 12-week trials which led to the October 2019 approval of trifarotene 50 mcg/g cream (Aklief) as the first novel retinoid for acne to reach the market in 20 years, observed Dr. Del Rosso, research director at JDR Research in Las Vegas and a member of the dermatology faculty at Touro University in Henderson, Nev.
The 52-week study, known as SATISFY, began with 454 patients with moderate facial and truncal acne who treated themselves with trifarotene once daily. Among the 348 patients who completed the full year, 67% achieved a score of 0 or 1 – clear or almost clear – with at least a 2-grade improvement from baseline by Investigator’s Global Assessment on their facial acne, and 65% met the same measure of success on the trunk. Moreover, 58% of patients met that standard at both acne sites.
The IGA success rate rose throughout the study period without ever reaching a plateau. However, it should be noted that 23% of participants dropped out of the study over the course of the year.
Mean tolerability scores reflecting redness, scaling, stinging or burning, and skin dryness remained well below the threshold for mild severity, peaking at weeks 2-4 of the study. The most common treatment-related adverse events were mild to moderate itching and irritation, each occurring in less than 5% of subjects.
Trifarotene is a first-in-class retinoid that specifically targets the retinoic acid receptor gamma, the most common cutaneous retinoic acid receptor.
Dr. Del Rosso reported serving as an investigator and consultant for Galderma, which sponsored the study and markets trifarotene cream.
James Q. Del Rosso, MD, reported at the virtual annual meeting of the American Academy of Dermatology.
The study is noteworthy because, even though roughly half of patients with facial acne also have truncal acne, there is actually very little clinical trial data on the treatment of truncal acne other than this new long-term study and the two earlier pivotal phase 3, 12-week trials which led to the October 2019 approval of trifarotene 50 mcg/g cream (Aklief) as the first novel retinoid for acne to reach the market in 20 years, observed Dr. Del Rosso, research director at JDR Research in Las Vegas and a member of the dermatology faculty at Touro University in Henderson, Nev.
The 52-week study, known as SATISFY, began with 454 patients with moderate facial and truncal acne who treated themselves with trifarotene once daily. Among the 348 patients who completed the full year, 67% achieved a score of 0 or 1 – clear or almost clear – with at least a 2-grade improvement from baseline by Investigator’s Global Assessment on their facial acne, and 65% met the same measure of success on the trunk. Moreover, 58% of patients met that standard at both acne sites.
The IGA success rate rose throughout the study period without ever reaching a plateau. However, it should be noted that 23% of participants dropped out of the study over the course of the year.
Mean tolerability scores reflecting redness, scaling, stinging or burning, and skin dryness remained well below the threshold for mild severity, peaking at weeks 2-4 of the study. The most common treatment-related adverse events were mild to moderate itching and irritation, each occurring in less than 5% of subjects.
Trifarotene is a first-in-class retinoid that specifically targets the retinoic acid receptor gamma, the most common cutaneous retinoic acid receptor.
Dr. Del Rosso reported serving as an investigator and consultant for Galderma, which sponsored the study and markets trifarotene cream.
FROM AAD 2020
Study evaluates number of needed to refer, biopsy for diagnosing a melanoma
At the same time, the number needed to refer to diagnose non-melanoma skin cancer was 4 and the number needed to biopsy was 1.5.
The findings come from a retrospective review of 707 patients referred to a tertiary medical center dermatology practice for suspicious lesions, presented in a poster session at the virtual annual meeting of the American Academy of Dermatology
“Multiple studies in the dermatology literature have looked at the number needed to treat (NNT) as a quality metric for dermatology clinics, where a lower number is ‘better,’” the study’s first author, Nikolai Klebanov, MD, said in an interview following the virtual meeting. “Our particular study is unique in that we estimated both the number needed to refer and number needed to biopsy to closely examine the process of referrals for suspicious lesions from primary care settings to specialists. We also looked closely at the underlying patient-centered characteristics, which could be used by all clinicians to streamline the referral process by reducing the volume of low-risk referrals.”
Dr. Klebanov, of the department of dermatology at Massachusetts General Hospital, Boston, and his associates reviewed 707 unique patient visits to the department during July 2015–February 2016. They calculated the number needed to refer and biopsy for melanoma as the ratio of biopsy-proven melanoma diagnoses among benign and dysplastic nevi and seborrheic keratoses. For nonmelanoma skin cancer, they used the ratio of basal and squamous cell carcinoma among actinic keratoses and seborrheic keratoses.
Of the 707 patients, 54% were female, and males were slightly older than females (a mean of 58 vs. 54 years, respectively). The researchers found that lesions were more commonly benign among all age groups, while the frequency of premalignant and malignant lesions such as actinic keratoses, nonmelanoma skin cancer, and melanoma was highest for males and increased with age. Nevi were the most common benign diagnosis among patients 39 years of age and younger, while seborrheic keratoses were more common among patients aged 40 years and older.
The researchers found that the number needed to treat for melanoma was 31.5 and the number needed to biopsy was 7.5, which represents a 4.2-fold difference. Meanwhile, the number needed to refer for nonmelanoma skin cancer was 4, and the number needed to biopsy was 1.5, which represents a 2.7-fold difference. Despite variable rates of skin cancer between demographics, the biopsy rate ranged between 18% and 30%, for a mean of 23.4%.
“We found that most young patients referred for a ‘suspicious lesion’ on clinical prebiopsy assessment by the dermatologist were determined to actually have a benign nevus, and that older patients were most likely to have a seborrheic keratosis as the underlying lesion,” Dr. Klebanov said. “Among the minority of patients in each demographic group who were selected for biopsy, those lesions which were found to be benign were also largely nevi and keratoses. Even by being mindful of just the patient’s age, primary care providers can follow patients clinically with a tailored differential diagnosis in mind before referral, and dermatologists can reduce the number of biopsies they perform on patients who are being referred.”
He added that he and his colleagues were surprised that despite very low rates of skin cancer in young patients, and thus different pretest probabilities of cancer, biopsy rates across demographics were consistently around 20%. “We also found a disproportionate number of female patients younger than age 40 who were referred for suspicious lesions, while in the older age groups, the ratio of males to females was approximately equal.”
Dr. Klebanov acknowledged certain limitations of the study, including its single-center, retrospective design, and that information was not collected on patients’ family history of skin cancer, Fitzpatrick skin type, nor the clinical course of the lesion while it was followed by the primary care office. “The nuanced differences in these factors may certainly play a role in decisions for individual patients,” he said.
The study’s principal investigator was Hensin Tsao MD, PhD, clinical director of the MGH Melanoma & Pigmented Lesion Center The work was supported by the Alpha Omega Alpha Carolyn Kuckein Research Fellowship. The researchers reported having no financial disclosures.
SOURCE: Klebanov N et al. AAD 20. Abstract 15881.
At the same time, the number needed to refer to diagnose non-melanoma skin cancer was 4 and the number needed to biopsy was 1.5.
The findings come from a retrospective review of 707 patients referred to a tertiary medical center dermatology practice for suspicious lesions, presented in a poster session at the virtual annual meeting of the American Academy of Dermatology
“Multiple studies in the dermatology literature have looked at the number needed to treat (NNT) as a quality metric for dermatology clinics, where a lower number is ‘better,’” the study’s first author, Nikolai Klebanov, MD, said in an interview following the virtual meeting. “Our particular study is unique in that we estimated both the number needed to refer and number needed to biopsy to closely examine the process of referrals for suspicious lesions from primary care settings to specialists. We also looked closely at the underlying patient-centered characteristics, which could be used by all clinicians to streamline the referral process by reducing the volume of low-risk referrals.”
Dr. Klebanov, of the department of dermatology at Massachusetts General Hospital, Boston, and his associates reviewed 707 unique patient visits to the department during July 2015–February 2016. They calculated the number needed to refer and biopsy for melanoma as the ratio of biopsy-proven melanoma diagnoses among benign and dysplastic nevi and seborrheic keratoses. For nonmelanoma skin cancer, they used the ratio of basal and squamous cell carcinoma among actinic keratoses and seborrheic keratoses.
Of the 707 patients, 54% were female, and males were slightly older than females (a mean of 58 vs. 54 years, respectively). The researchers found that lesions were more commonly benign among all age groups, while the frequency of premalignant and malignant lesions such as actinic keratoses, nonmelanoma skin cancer, and melanoma was highest for males and increased with age. Nevi were the most common benign diagnosis among patients 39 years of age and younger, while seborrheic keratoses were more common among patients aged 40 years and older.
The researchers found that the number needed to treat for melanoma was 31.5 and the number needed to biopsy was 7.5, which represents a 4.2-fold difference. Meanwhile, the number needed to refer for nonmelanoma skin cancer was 4, and the number needed to biopsy was 1.5, which represents a 2.7-fold difference. Despite variable rates of skin cancer between demographics, the biopsy rate ranged between 18% and 30%, for a mean of 23.4%.
“We found that most young patients referred for a ‘suspicious lesion’ on clinical prebiopsy assessment by the dermatologist were determined to actually have a benign nevus, and that older patients were most likely to have a seborrheic keratosis as the underlying lesion,” Dr. Klebanov said. “Among the minority of patients in each demographic group who were selected for biopsy, those lesions which were found to be benign were also largely nevi and keratoses. Even by being mindful of just the patient’s age, primary care providers can follow patients clinically with a tailored differential diagnosis in mind before referral, and dermatologists can reduce the number of biopsies they perform on patients who are being referred.”
He added that he and his colleagues were surprised that despite very low rates of skin cancer in young patients, and thus different pretest probabilities of cancer, biopsy rates across demographics were consistently around 20%. “We also found a disproportionate number of female patients younger than age 40 who were referred for suspicious lesions, while in the older age groups, the ratio of males to females was approximately equal.”
Dr. Klebanov acknowledged certain limitations of the study, including its single-center, retrospective design, and that information was not collected on patients’ family history of skin cancer, Fitzpatrick skin type, nor the clinical course of the lesion while it was followed by the primary care office. “The nuanced differences in these factors may certainly play a role in decisions for individual patients,” he said.
The study’s principal investigator was Hensin Tsao MD, PhD, clinical director of the MGH Melanoma & Pigmented Lesion Center The work was supported by the Alpha Omega Alpha Carolyn Kuckein Research Fellowship. The researchers reported having no financial disclosures.
SOURCE: Klebanov N et al. AAD 20. Abstract 15881.
At the same time, the number needed to refer to diagnose non-melanoma skin cancer was 4 and the number needed to biopsy was 1.5.
The findings come from a retrospective review of 707 patients referred to a tertiary medical center dermatology practice for suspicious lesions, presented in a poster session at the virtual annual meeting of the American Academy of Dermatology
“Multiple studies in the dermatology literature have looked at the number needed to treat (NNT) as a quality metric for dermatology clinics, where a lower number is ‘better,’” the study’s first author, Nikolai Klebanov, MD, said in an interview following the virtual meeting. “Our particular study is unique in that we estimated both the number needed to refer and number needed to biopsy to closely examine the process of referrals for suspicious lesions from primary care settings to specialists. We also looked closely at the underlying patient-centered characteristics, which could be used by all clinicians to streamline the referral process by reducing the volume of low-risk referrals.”
Dr. Klebanov, of the department of dermatology at Massachusetts General Hospital, Boston, and his associates reviewed 707 unique patient visits to the department during July 2015–February 2016. They calculated the number needed to refer and biopsy for melanoma as the ratio of biopsy-proven melanoma diagnoses among benign and dysplastic nevi and seborrheic keratoses. For nonmelanoma skin cancer, they used the ratio of basal and squamous cell carcinoma among actinic keratoses and seborrheic keratoses.
Of the 707 patients, 54% were female, and males were slightly older than females (a mean of 58 vs. 54 years, respectively). The researchers found that lesions were more commonly benign among all age groups, while the frequency of premalignant and malignant lesions such as actinic keratoses, nonmelanoma skin cancer, and melanoma was highest for males and increased with age. Nevi were the most common benign diagnosis among patients 39 years of age and younger, while seborrheic keratoses were more common among patients aged 40 years and older.
The researchers found that the number needed to treat for melanoma was 31.5 and the number needed to biopsy was 7.5, which represents a 4.2-fold difference. Meanwhile, the number needed to refer for nonmelanoma skin cancer was 4, and the number needed to biopsy was 1.5, which represents a 2.7-fold difference. Despite variable rates of skin cancer between demographics, the biopsy rate ranged between 18% and 30%, for a mean of 23.4%.
“We found that most young patients referred for a ‘suspicious lesion’ on clinical prebiopsy assessment by the dermatologist were determined to actually have a benign nevus, and that older patients were most likely to have a seborrheic keratosis as the underlying lesion,” Dr. Klebanov said. “Among the minority of patients in each demographic group who were selected for biopsy, those lesions which were found to be benign were also largely nevi and keratoses. Even by being mindful of just the patient’s age, primary care providers can follow patients clinically with a tailored differential diagnosis in mind before referral, and dermatologists can reduce the number of biopsies they perform on patients who are being referred.”
He added that he and his colleagues were surprised that despite very low rates of skin cancer in young patients, and thus different pretest probabilities of cancer, biopsy rates across demographics were consistently around 20%. “We also found a disproportionate number of female patients younger than age 40 who were referred for suspicious lesions, while in the older age groups, the ratio of males to females was approximately equal.”
Dr. Klebanov acknowledged certain limitations of the study, including its single-center, retrospective design, and that information was not collected on patients’ family history of skin cancer, Fitzpatrick skin type, nor the clinical course of the lesion while it was followed by the primary care office. “The nuanced differences in these factors may certainly play a role in decisions for individual patients,” he said.
The study’s principal investigator was Hensin Tsao MD, PhD, clinical director of the MGH Melanoma & Pigmented Lesion Center The work was supported by the Alpha Omega Alpha Carolyn Kuckein Research Fellowship. The researchers reported having no financial disclosures.
SOURCE: Klebanov N et al. AAD 20. Abstract 15881.
FROM AAD 20
Pilot study shows apremilast effective for severe recurrent canker sores
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“Canker sores [aphthous ulcers] are very common, yet are often not well managed as the diagnosis is not always correctly made,” lead study author Alison J. Bruce, MB, ChB, said in an interview following the virtual annual meeting of the American Academy of Dermatology. “They’re often mistaken for herpes infection and therefore treated with antiviral therapy. Of the available therapies, several have common side effects or require lab monitoring or are not uniformly effective.”
In their poster abstract, Dr. Bruce, of the division of dermatology at the Mayo Clinic, Jacksonville, Fla., and colleagues noted that, while no principal etiology has been established for recurrent aphthous stomatitis (RAS), immune up-regulation plays a role in the pathogenesis of the condition. “Attacks of RAS may be precipitated by local trauma, stress, food intake, drugs, hormonal changes and vitamin and trace element deficiencies,” they wrote. “Local and systemic conditions and genetic, immunological and microbial factors all may play a role in the pathogenesis.”
Apremilast, a phosphodiesterase-4 inhibitor, down-regulates inflammatory response by modulating expression of tumor necrosis factor–alpha; interferon-gamma; and interleukin-2, IL-12, IL-17, and IL-23. It is approved by the Food and Drug Administration for treating plaque psoriasis and psoriatic arthritis, and in July 2019, was approved for treating ulcers associated with Behçet’s disease, in adults.*
For the pilot study, the researchers enrolled 15 patients with RAS to receive apremilast 30 mg twice daily for 15 weeks after 1 week titration. To be eligible for the trial, patients must have had monthly oral ulcers in preceding 6 months, at least two ulcers in previous 4 weeks prior to enrollment at baseline, at least three ulcers during flares, inadequate control with topical therapy, and no evidence of systemic disease. They excluded patients on immune-modulating therapy or systemic steroids, pregnant or breastfeeding women, those with a systemic infection, those with a history of recurrent bacterial, viral, fungal, or mycobacterial infection, those with a history of depression, as well as those with a known malignancy or vitamin deficiencies. Patients were assessed monthly, evaluating number of ulcers, visual analog pain scale, physician’s global assessment and Chronic Oral Mucosal Disease Questionnaire (COMDQ).
Dr. Bruce and colleagues found that, within 4 weeks of therapy, complete clearance of RAS lesions occurred in all patients except one in whom ulcers were reported to be less severe. That patient had considerable reduction in number, size, and duration of oral ulcers. Remission in all patients was sustained during 16 weeks of treatment. COMDQ responses improved considerably from baseline to week 8, and this was continued until week 16.
“Onset of response [to apremilast] was rapid,” Dr. Bruce said. “For many other therapies, patients are counseled that [they] may take several weeks to become effective. Response was also dramatic. Almost all patients had complete remission from their ulcers, compared with other therapies where oftentimes reduction or attenuation is achieved, as opposed to complete resolution. There was a suggestion that a lower dose [of apremilast] may still be effective. This adds to our ‘toolbox’ of therapeutic options.”
The most common adverse effects were nausea/vomiting and headache, but these were mild and tolerable and generally resolved by week 4.
The researchers acknowledged certain limitations of the study, including its small sample size. “The challenge will most likely be insurance coverage,” Dr. Bruce said. “This is unfortunate, as it would be ideal to offer a safe treatment without the need for monitoring.”
The investigator-initiated study was supported by Celgene. The researchers reported having no financial disclosures.
SOURCE: Bruce AJ et al. AAD 20, Abstract 17701.
*Correction 6/23/2020: An earlier version of this story misstated the approved indications for apremilast.
showed.
“Canker sores [aphthous ulcers] are very common, yet are often not well managed as the diagnosis is not always correctly made,” lead study author Alison J. Bruce, MB, ChB, said in an interview following the virtual annual meeting of the American Academy of Dermatology. “They’re often mistaken for herpes infection and therefore treated with antiviral therapy. Of the available therapies, several have common side effects or require lab monitoring or are not uniformly effective.”
In their poster abstract, Dr. Bruce, of the division of dermatology at the Mayo Clinic, Jacksonville, Fla., and colleagues noted that, while no principal etiology has been established for recurrent aphthous stomatitis (RAS), immune up-regulation plays a role in the pathogenesis of the condition. “Attacks of RAS may be precipitated by local trauma, stress, food intake, drugs, hormonal changes and vitamin and trace element deficiencies,” they wrote. “Local and systemic conditions and genetic, immunological and microbial factors all may play a role in the pathogenesis.”
Apremilast, a phosphodiesterase-4 inhibitor, down-regulates inflammatory response by modulating expression of tumor necrosis factor–alpha; interferon-gamma; and interleukin-2, IL-12, IL-17, and IL-23. It is approved by the Food and Drug Administration for treating plaque psoriasis and psoriatic arthritis, and in July 2019, was approved for treating ulcers associated with Behçet’s disease, in adults.*
For the pilot study, the researchers enrolled 15 patients with RAS to receive apremilast 30 mg twice daily for 15 weeks after 1 week titration. To be eligible for the trial, patients must have had monthly oral ulcers in preceding 6 months, at least two ulcers in previous 4 weeks prior to enrollment at baseline, at least three ulcers during flares, inadequate control with topical therapy, and no evidence of systemic disease. They excluded patients on immune-modulating therapy or systemic steroids, pregnant or breastfeeding women, those with a systemic infection, those with a history of recurrent bacterial, viral, fungal, or mycobacterial infection, those with a history of depression, as well as those with a known malignancy or vitamin deficiencies. Patients were assessed monthly, evaluating number of ulcers, visual analog pain scale, physician’s global assessment and Chronic Oral Mucosal Disease Questionnaire (COMDQ).
Dr. Bruce and colleagues found that, within 4 weeks of therapy, complete clearance of RAS lesions occurred in all patients except one in whom ulcers were reported to be less severe. That patient had considerable reduction in number, size, and duration of oral ulcers. Remission in all patients was sustained during 16 weeks of treatment. COMDQ responses improved considerably from baseline to week 8, and this was continued until week 16.
“Onset of response [to apremilast] was rapid,” Dr. Bruce said. “For many other therapies, patients are counseled that [they] may take several weeks to become effective. Response was also dramatic. Almost all patients had complete remission from their ulcers, compared with other therapies where oftentimes reduction or attenuation is achieved, as opposed to complete resolution. There was a suggestion that a lower dose [of apremilast] may still be effective. This adds to our ‘toolbox’ of therapeutic options.”
The most common adverse effects were nausea/vomiting and headache, but these were mild and tolerable and generally resolved by week 4.
The researchers acknowledged certain limitations of the study, including its small sample size. “The challenge will most likely be insurance coverage,” Dr. Bruce said. “This is unfortunate, as it would be ideal to offer a safe treatment without the need for monitoring.”
The investigator-initiated study was supported by Celgene. The researchers reported having no financial disclosures.
SOURCE: Bruce AJ et al. AAD 20, Abstract 17701.
*Correction 6/23/2020: An earlier version of this story misstated the approved indications for apremilast.
showed.
“Canker sores [aphthous ulcers] are very common, yet are often not well managed as the diagnosis is not always correctly made,” lead study author Alison J. Bruce, MB, ChB, said in an interview following the virtual annual meeting of the American Academy of Dermatology. “They’re often mistaken for herpes infection and therefore treated with antiviral therapy. Of the available therapies, several have common side effects or require lab monitoring or are not uniformly effective.”
In their poster abstract, Dr. Bruce, of the division of dermatology at the Mayo Clinic, Jacksonville, Fla., and colleagues noted that, while no principal etiology has been established for recurrent aphthous stomatitis (RAS), immune up-regulation plays a role in the pathogenesis of the condition. “Attacks of RAS may be precipitated by local trauma, stress, food intake, drugs, hormonal changes and vitamin and trace element deficiencies,” they wrote. “Local and systemic conditions and genetic, immunological and microbial factors all may play a role in the pathogenesis.”
Apremilast, a phosphodiesterase-4 inhibitor, down-regulates inflammatory response by modulating expression of tumor necrosis factor–alpha; interferon-gamma; and interleukin-2, IL-12, IL-17, and IL-23. It is approved by the Food and Drug Administration for treating plaque psoriasis and psoriatic arthritis, and in July 2019, was approved for treating ulcers associated with Behçet’s disease, in adults.*
For the pilot study, the researchers enrolled 15 patients with RAS to receive apremilast 30 mg twice daily for 15 weeks after 1 week titration. To be eligible for the trial, patients must have had monthly oral ulcers in preceding 6 months, at least two ulcers in previous 4 weeks prior to enrollment at baseline, at least three ulcers during flares, inadequate control with topical therapy, and no evidence of systemic disease. They excluded patients on immune-modulating therapy or systemic steroids, pregnant or breastfeeding women, those with a systemic infection, those with a history of recurrent bacterial, viral, fungal, or mycobacterial infection, those with a history of depression, as well as those with a known malignancy or vitamin deficiencies. Patients were assessed monthly, evaluating number of ulcers, visual analog pain scale, physician’s global assessment and Chronic Oral Mucosal Disease Questionnaire (COMDQ).
Dr. Bruce and colleagues found that, within 4 weeks of therapy, complete clearance of RAS lesions occurred in all patients except one in whom ulcers were reported to be less severe. That patient had considerable reduction in number, size, and duration of oral ulcers. Remission in all patients was sustained during 16 weeks of treatment. COMDQ responses improved considerably from baseline to week 8, and this was continued until week 16.
“Onset of response [to apremilast] was rapid,” Dr. Bruce said. “For many other therapies, patients are counseled that [they] may take several weeks to become effective. Response was also dramatic. Almost all patients had complete remission from their ulcers, compared with other therapies where oftentimes reduction or attenuation is achieved, as opposed to complete resolution. There was a suggestion that a lower dose [of apremilast] may still be effective. This adds to our ‘toolbox’ of therapeutic options.”
The most common adverse effects were nausea/vomiting and headache, but these were mild and tolerable and generally resolved by week 4.
The researchers acknowledged certain limitations of the study, including its small sample size. “The challenge will most likely be insurance coverage,” Dr. Bruce said. “This is unfortunate, as it would be ideal to offer a safe treatment without the need for monitoring.”
The investigator-initiated study was supported by Celgene. The researchers reported having no financial disclosures.
SOURCE: Bruce AJ et al. AAD 20, Abstract 17701.
*Correction 6/23/2020: An earlier version of this story misstated the approved indications for apremilast.
FROM AAD 20