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Doug Brunk is a San Diego-based award-winning reporter who began covering health care in 1991. Before joining the company, he wrote for the health sciences division of Columbia University and was an associate editor at Contemporary Long Term Care magazine when it won a Jesse H. Neal Award. His work has been syndicated by the Los Angeles Times and he is the author of two books related to the University of Kentucky Wildcats men's basketball program. Doug has a master’s degree in magazine journalism from the S.I. Newhouse School of Public Communications at Syracuse University. Follow him on Twitter @dougbrunk.
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
Inside Mercy’s mission to care for non-COVID patients in Los Angeles
When the hospital ship USNS Mercy departed San Diego’s Naval Station North Island on March 23, 2020, to support the Department of Defense efforts in Los Angeles during the coronavirus outbreak, Commander Erin Blevins remembers the crew’s excitement was palpable.
“We normally do partnerships abroad and respond to tsunamis and earthquakes,” said Cdr. Blevins, MD, a pediatric hematologist-oncologist who served as director of medical services for the mission. “This was a slight change in situation, but still disaster relief in the form of a pandemic. We switched our mindset to putting together the best experts for an infectious disease pandemic versus an earthquake disaster relief.”
A new mission
The 1,000-bed Mercy ship – a converted San Clemente–class oil tanker that was delivered in 1986 – spent nearly 50 days pier side in Los Angeles as a referral hospital for non–COVID-19 patients, so that clinicians at Los Angeles area hospitals could care for an anticipated surge of COVID-19 patients. “We went into it with expectations of, ‘We’ll treat as many patients as you need us to take,” Cdr. Blevins recalled. “I don’t even think Los Angeles [health officials] knew exactly where they were going to peak and what the need was going to be.”
Between March 29 and May 15, about 1,071 medical personnel aboard the Mercy cared for 77 patients with an average age of 53 years who were referred from 11 Los Angeles area hospitals. The physicians, nurses, and other medical support personnel were drawn from military treatment facilities across the country. “We had additional people join us as we scoped the mission to be more medically heavy and surgically light,” said Captain John Rotruck, MD, an anesthesiologist who is commanding officer of Mercy’s medical treatment facility. “We did adjust to make sure that we had the right staffing mix to meet the parameters that we were assigned. That was the crux of the change: a change in flavors of staffing to ensure that we focused on ICU and ward medical care as opposed to very heavy surgical care in support of a combat operation.”
About 10% of the team consisted of reservists who volunteered for the mission. “There’s no way you could have walked around the ship and known who was active duty and who was reservist,” said Capt. Rotruck, who was formerly chief of staff at Walter Reed National Military Medical Center, Bethesda, Md. “They worked together so well, and I think that marriage of active duty who are used to working in a military medical treatment facility – in our case, a Navy medical treatment facility – together with our reservist physician colleagues who work in civilian facilities around the country, was beneficial. It was a synergistic relationship. I think both sides walked away learning quite a bit from each other.”
Start with screening
All crew members underwent a temperature check and completed a health screening questionnaire: once before departing their home of record and again before boarding Mercy. Based on those results, crew members and medical staff were screened for COVID-19 and tested as needed in order to minimize the risk of an outbreak aboard the ship.
Fewer than 1% of crew members developed COVID-19 or tested positive for the virus during the mission, according to Capt. Rotruck. Affected individuals were isolated and quarantined. “All staff have recovered and are doing well,” he said.
Mercy personnel worked with local health officials to ensure that all patients transferred to the ship tested negative for COVID-19. Physicians aboard the Mercy then worked directly with the patients’ civilian physician to ensure a safe and thorough turnover process before the patients were transferred.
From basic medical to trauma care
Care aboard the ship, which consists of open-bay medical wards, ranged from basic medical and surgical care to critical care and trauma. The most common procedures were cholecystectomies and orthopedic procedures, and the average length of stay was 4-5 days, according to Cdr. Blevins. Over the course of the mission, the medical professionals conducted 36 surgeries, 77 x-ray exams, 26 CT scans, and administered hundreds of ancillary studies ranging from routine labs to high-end x-rays and blood transfusion support.
“Within our ICU, we did have some end-of-life patients who ended up dying on our ship in comfort care,” Cdr. Blevins said. “Fortunately, we had a wonderful ICU team who had a great deal of experience with end-of-life care and were able to take care of these patients very comfortably and ensure good communication with family and loved ones during that time. In most instances we tried to make sure that people got to FaceTime or video chat with their loved one before they passed away.”
The Mercy, which includes 12 operating rooms, four x-ray units, and one CAT-scan unit, was not equipped to deliver pediatric or obstetrical care. Other unavailable services included psychiatry, oncology, cardiac and thoracic surgery, nuclear medicine, MRI, mammography, electrophysiology, cardiac catheterization, negative-pressure isolation, speech therapy, and occupational therapy.
Not your typical hospital experience
But for patients who did receive medical care aboard the Mercy – which made three 150-day deployments in recent years for the military-led humanitarian response known as Pacific Partnership in 2015, 2016, and 2018 – it was an experience that they are unlikely to forget.
“Every time a patient left the ship, our team on the ground surveyed them to see how their experience was and see what we could do to improve,” Cdr. Blevins said. “Across the board, they were all very appreciative of the medical care. We had a couple of veterans on board. They got [USNS Mercy] hats on their way out and seemed to very much enjoy a slightly different experience than they would get at a regular hospital.”
Capt. Rotruck added that the enthusiasm crew members had for supporting fellow Americans “really energized our team and really saturated that caring aspect of the people who interacted directly with patients,” he said. “It wasn’t just the physicians and nurses, but it was the staff delivering the food and coming to take blood samples and every other interaction that the patients had with our team. I think they really felt that enthusiasm for being there and supporting our neighbors in LA [Los Angeles].”
Crew life aboard the Mercy
Just as with any hospital on shore, personnel aboard the Mercy practiced preventive hygiene measures recommended by the Centers for Disease Control and Prevention to help prevent the spread of COVID-19, such as wearing cloth face masks, spacing out tables in the dining hall, closing indoor gyms, and devising creative ways to stay physically fit. Popular options included jogging around the perimeter of the ship and practicing yoga and calisthenics on the deck, “making sure you were physically distanced appropriately, and when you were done, putting your mask back on,” Cdr. Blevins said. Others supplemented their workouts with a pull-up bar on the deck. “In addition, we have a series of ramps that run on the starboard side of the ship that we can use for patient movement with litters on wheels or patient beds,” Capt. Rotruck said. “The uphill portion of those ramps represents a good workout opportunity as well.”
Downtime in an era of physical distancing also afforded crew members the opportunity to call or FaceTime with loved ones, watch streamed TV shows and movies, and work on their own professional development. Some continued with coursework for online degree programs offered by colleges and universities they were enrolled in, while some enlisted personnel used the time to complete the Navy Enlisted Warfare Qualification Programs Instruction, which issues the basic overarching requirements for the qualification and designation of all enlisted warfare programs.
“As you can imagine, people spend a lot of time learning how the ship works and how it integrates into larger naval forces and so forth,” Capt. Rotruck said. “Not just our ship but also other ships: their weapons systems and defense mechanisms and navigation systems. We had people spending a significant amount of time working on that. We had people complete their Enlisted Surface Warfare qualification while we were on the mission.”
End of the mission
Mercy returned to its home base in San Diego on May 15, but about 60 medical personnel stayed behind in Los Angeles to support Federal Emergency Management Agency (FEMA), state, and local health care professionals. Some worked at a site where clinicians provided care for COVID-19–positive patients who had been transferred from area skilled nursing facilities.
In addition, a team consisting of one nurse and five corpsmen “would go out to individual skilled nursing facilities and mainly conduct assessments and training, such as training in donning proper PPE [personal protective equipment] and determining what needs they had,” Capt. Rotruck said. “They met those needs if possible or [communicated with California officials] and let them know what the requirements were and what the needs were in that facility.” The assignment for those who stayed behind ended on May 31.
On the opposite coast, Mercy’s sister ship, USNS Comfort, arrived in New York Harbor from Norfolk, Va., on March 30 and spent 3½ weeks assisting area hospitals in the COVID-19 pandemic fight. A few days into the mission, Comfort’s internal spaces were reconfigured to create separate COVID-negative and COVID-positive sections. Medical teams aboard the ship cared for a total of 182 patients during the assignment.
Looking back on Mercy’s mission, Cdr. Blevins marveled at the sense of teamwork that unfolded. “We have quarterly training exercises with a core set of personnel, [and] we train getting ready for activation in 5 days,” she said. “All of that training kicks in and it comes to fruition in a mission like this. It was terrific to see a group of very disparate subject matter experts from all over the country come together with one purpose: which was to serve our own country during the pandemic.”
Capt. Rotruck pointed out that the experience enabled enlisted and nonenlisted physicians to maintain their skill sets during a time when military and civilian hospitals had stopped doing elective procedures and routine appointments. “The fact that those people were able to come on board the ship and continue to conduct their medical practice and maintain their skills and competencies in an environment that they weren’t quite used to is great,” he said. “Otherwise, some of those medical personnel would have been sitting idle, wherever they were from. This is the power of Navy medicine on behalf of our country.”
When the hospital ship USNS Mercy departed San Diego’s Naval Station North Island on March 23, 2020, to support the Department of Defense efforts in Los Angeles during the coronavirus outbreak, Commander Erin Blevins remembers the crew’s excitement was palpable.
“We normally do partnerships abroad and respond to tsunamis and earthquakes,” said Cdr. Blevins, MD, a pediatric hematologist-oncologist who served as director of medical services for the mission. “This was a slight change in situation, but still disaster relief in the form of a pandemic. We switched our mindset to putting together the best experts for an infectious disease pandemic versus an earthquake disaster relief.”
A new mission
The 1,000-bed Mercy ship – a converted San Clemente–class oil tanker that was delivered in 1986 – spent nearly 50 days pier side in Los Angeles as a referral hospital for non–COVID-19 patients, so that clinicians at Los Angeles area hospitals could care for an anticipated surge of COVID-19 patients. “We went into it with expectations of, ‘We’ll treat as many patients as you need us to take,” Cdr. Blevins recalled. “I don’t even think Los Angeles [health officials] knew exactly where they were going to peak and what the need was going to be.”
Between March 29 and May 15, about 1,071 medical personnel aboard the Mercy cared for 77 patients with an average age of 53 years who were referred from 11 Los Angeles area hospitals. The physicians, nurses, and other medical support personnel were drawn from military treatment facilities across the country. “We had additional people join us as we scoped the mission to be more medically heavy and surgically light,” said Captain John Rotruck, MD, an anesthesiologist who is commanding officer of Mercy’s medical treatment facility. “We did adjust to make sure that we had the right staffing mix to meet the parameters that we were assigned. That was the crux of the change: a change in flavors of staffing to ensure that we focused on ICU and ward medical care as opposed to very heavy surgical care in support of a combat operation.”
About 10% of the team consisted of reservists who volunteered for the mission. “There’s no way you could have walked around the ship and known who was active duty and who was reservist,” said Capt. Rotruck, who was formerly chief of staff at Walter Reed National Military Medical Center, Bethesda, Md. “They worked together so well, and I think that marriage of active duty who are used to working in a military medical treatment facility – in our case, a Navy medical treatment facility – together with our reservist physician colleagues who work in civilian facilities around the country, was beneficial. It was a synergistic relationship. I think both sides walked away learning quite a bit from each other.”
Start with screening
All crew members underwent a temperature check and completed a health screening questionnaire: once before departing their home of record and again before boarding Mercy. Based on those results, crew members and medical staff were screened for COVID-19 and tested as needed in order to minimize the risk of an outbreak aboard the ship.
Fewer than 1% of crew members developed COVID-19 or tested positive for the virus during the mission, according to Capt. Rotruck. Affected individuals were isolated and quarantined. “All staff have recovered and are doing well,” he said.
Mercy personnel worked with local health officials to ensure that all patients transferred to the ship tested negative for COVID-19. Physicians aboard the Mercy then worked directly with the patients’ civilian physician to ensure a safe and thorough turnover process before the patients were transferred.
From basic medical to trauma care
Care aboard the ship, which consists of open-bay medical wards, ranged from basic medical and surgical care to critical care and trauma. The most common procedures were cholecystectomies and orthopedic procedures, and the average length of stay was 4-5 days, according to Cdr. Blevins. Over the course of the mission, the medical professionals conducted 36 surgeries, 77 x-ray exams, 26 CT scans, and administered hundreds of ancillary studies ranging from routine labs to high-end x-rays and blood transfusion support.
“Within our ICU, we did have some end-of-life patients who ended up dying on our ship in comfort care,” Cdr. Blevins said. “Fortunately, we had a wonderful ICU team who had a great deal of experience with end-of-life care and were able to take care of these patients very comfortably and ensure good communication with family and loved ones during that time. In most instances we tried to make sure that people got to FaceTime or video chat with their loved one before they passed away.”
The Mercy, which includes 12 operating rooms, four x-ray units, and one CAT-scan unit, was not equipped to deliver pediatric or obstetrical care. Other unavailable services included psychiatry, oncology, cardiac and thoracic surgery, nuclear medicine, MRI, mammography, electrophysiology, cardiac catheterization, negative-pressure isolation, speech therapy, and occupational therapy.
Not your typical hospital experience
But for patients who did receive medical care aboard the Mercy – which made three 150-day deployments in recent years for the military-led humanitarian response known as Pacific Partnership in 2015, 2016, and 2018 – it was an experience that they are unlikely to forget.
“Every time a patient left the ship, our team on the ground surveyed them to see how their experience was and see what we could do to improve,” Cdr. Blevins said. “Across the board, they were all very appreciative of the medical care. We had a couple of veterans on board. They got [USNS Mercy] hats on their way out and seemed to very much enjoy a slightly different experience than they would get at a regular hospital.”
Capt. Rotruck added that the enthusiasm crew members had for supporting fellow Americans “really energized our team and really saturated that caring aspect of the people who interacted directly with patients,” he said. “It wasn’t just the physicians and nurses, but it was the staff delivering the food and coming to take blood samples and every other interaction that the patients had with our team. I think they really felt that enthusiasm for being there and supporting our neighbors in LA [Los Angeles].”
Crew life aboard the Mercy
Just as with any hospital on shore, personnel aboard the Mercy practiced preventive hygiene measures recommended by the Centers for Disease Control and Prevention to help prevent the spread of COVID-19, such as wearing cloth face masks, spacing out tables in the dining hall, closing indoor gyms, and devising creative ways to stay physically fit. Popular options included jogging around the perimeter of the ship and practicing yoga and calisthenics on the deck, “making sure you were physically distanced appropriately, and when you were done, putting your mask back on,” Cdr. Blevins said. Others supplemented their workouts with a pull-up bar on the deck. “In addition, we have a series of ramps that run on the starboard side of the ship that we can use for patient movement with litters on wheels or patient beds,” Capt. Rotruck said. “The uphill portion of those ramps represents a good workout opportunity as well.”
Downtime in an era of physical distancing also afforded crew members the opportunity to call or FaceTime with loved ones, watch streamed TV shows and movies, and work on their own professional development. Some continued with coursework for online degree programs offered by colleges and universities they were enrolled in, while some enlisted personnel used the time to complete the Navy Enlisted Warfare Qualification Programs Instruction, which issues the basic overarching requirements for the qualification and designation of all enlisted warfare programs.
“As you can imagine, people spend a lot of time learning how the ship works and how it integrates into larger naval forces and so forth,” Capt. Rotruck said. “Not just our ship but also other ships: their weapons systems and defense mechanisms and navigation systems. We had people spending a significant amount of time working on that. We had people complete their Enlisted Surface Warfare qualification while we were on the mission.”
End of the mission
Mercy returned to its home base in San Diego on May 15, but about 60 medical personnel stayed behind in Los Angeles to support Federal Emergency Management Agency (FEMA), state, and local health care professionals. Some worked at a site where clinicians provided care for COVID-19–positive patients who had been transferred from area skilled nursing facilities.
In addition, a team consisting of one nurse and five corpsmen “would go out to individual skilled nursing facilities and mainly conduct assessments and training, such as training in donning proper PPE [personal protective equipment] and determining what needs they had,” Capt. Rotruck said. “They met those needs if possible or [communicated with California officials] and let them know what the requirements were and what the needs were in that facility.” The assignment for those who stayed behind ended on May 31.
On the opposite coast, Mercy’s sister ship, USNS Comfort, arrived in New York Harbor from Norfolk, Va., on March 30 and spent 3½ weeks assisting area hospitals in the COVID-19 pandemic fight. A few days into the mission, Comfort’s internal spaces were reconfigured to create separate COVID-negative and COVID-positive sections. Medical teams aboard the ship cared for a total of 182 patients during the assignment.
Looking back on Mercy’s mission, Cdr. Blevins marveled at the sense of teamwork that unfolded. “We have quarterly training exercises with a core set of personnel, [and] we train getting ready for activation in 5 days,” she said. “All of that training kicks in and it comes to fruition in a mission like this. It was terrific to see a group of very disparate subject matter experts from all over the country come together with one purpose: which was to serve our own country during the pandemic.”
Capt. Rotruck pointed out that the experience enabled enlisted and nonenlisted physicians to maintain their skill sets during a time when military and civilian hospitals had stopped doing elective procedures and routine appointments. “The fact that those people were able to come on board the ship and continue to conduct their medical practice and maintain their skills and competencies in an environment that they weren’t quite used to is great,” he said. “Otherwise, some of those medical personnel would have been sitting idle, wherever they were from. This is the power of Navy medicine on behalf of our country.”
When the hospital ship USNS Mercy departed San Diego’s Naval Station North Island on March 23, 2020, to support the Department of Defense efforts in Los Angeles during the coronavirus outbreak, Commander Erin Blevins remembers the crew’s excitement was palpable.
“We normally do partnerships abroad and respond to tsunamis and earthquakes,” said Cdr. Blevins, MD, a pediatric hematologist-oncologist who served as director of medical services for the mission. “This was a slight change in situation, but still disaster relief in the form of a pandemic. We switched our mindset to putting together the best experts for an infectious disease pandemic versus an earthquake disaster relief.”
A new mission
The 1,000-bed Mercy ship – a converted San Clemente–class oil tanker that was delivered in 1986 – spent nearly 50 days pier side in Los Angeles as a referral hospital for non–COVID-19 patients, so that clinicians at Los Angeles area hospitals could care for an anticipated surge of COVID-19 patients. “We went into it with expectations of, ‘We’ll treat as many patients as you need us to take,” Cdr. Blevins recalled. “I don’t even think Los Angeles [health officials] knew exactly where they were going to peak and what the need was going to be.”
Between March 29 and May 15, about 1,071 medical personnel aboard the Mercy cared for 77 patients with an average age of 53 years who were referred from 11 Los Angeles area hospitals. The physicians, nurses, and other medical support personnel were drawn from military treatment facilities across the country. “We had additional people join us as we scoped the mission to be more medically heavy and surgically light,” said Captain John Rotruck, MD, an anesthesiologist who is commanding officer of Mercy’s medical treatment facility. “We did adjust to make sure that we had the right staffing mix to meet the parameters that we were assigned. That was the crux of the change: a change in flavors of staffing to ensure that we focused on ICU and ward medical care as opposed to very heavy surgical care in support of a combat operation.”
About 10% of the team consisted of reservists who volunteered for the mission. “There’s no way you could have walked around the ship and known who was active duty and who was reservist,” said Capt. Rotruck, who was formerly chief of staff at Walter Reed National Military Medical Center, Bethesda, Md. “They worked together so well, and I think that marriage of active duty who are used to working in a military medical treatment facility – in our case, a Navy medical treatment facility – together with our reservist physician colleagues who work in civilian facilities around the country, was beneficial. It was a synergistic relationship. I think both sides walked away learning quite a bit from each other.”
Start with screening
All crew members underwent a temperature check and completed a health screening questionnaire: once before departing their home of record and again before boarding Mercy. Based on those results, crew members and medical staff were screened for COVID-19 and tested as needed in order to minimize the risk of an outbreak aboard the ship.
Fewer than 1% of crew members developed COVID-19 or tested positive for the virus during the mission, according to Capt. Rotruck. Affected individuals were isolated and quarantined. “All staff have recovered and are doing well,” he said.
Mercy personnel worked with local health officials to ensure that all patients transferred to the ship tested negative for COVID-19. Physicians aboard the Mercy then worked directly with the patients’ civilian physician to ensure a safe and thorough turnover process before the patients were transferred.
From basic medical to trauma care
Care aboard the ship, which consists of open-bay medical wards, ranged from basic medical and surgical care to critical care and trauma. The most common procedures were cholecystectomies and orthopedic procedures, and the average length of stay was 4-5 days, according to Cdr. Blevins. Over the course of the mission, the medical professionals conducted 36 surgeries, 77 x-ray exams, 26 CT scans, and administered hundreds of ancillary studies ranging from routine labs to high-end x-rays and blood transfusion support.
“Within our ICU, we did have some end-of-life patients who ended up dying on our ship in comfort care,” Cdr. Blevins said. “Fortunately, we had a wonderful ICU team who had a great deal of experience with end-of-life care and were able to take care of these patients very comfortably and ensure good communication with family and loved ones during that time. In most instances we tried to make sure that people got to FaceTime or video chat with their loved one before they passed away.”
The Mercy, which includes 12 operating rooms, four x-ray units, and one CAT-scan unit, was not equipped to deliver pediatric or obstetrical care. Other unavailable services included psychiatry, oncology, cardiac and thoracic surgery, nuclear medicine, MRI, mammography, electrophysiology, cardiac catheterization, negative-pressure isolation, speech therapy, and occupational therapy.
Not your typical hospital experience
But for patients who did receive medical care aboard the Mercy – which made three 150-day deployments in recent years for the military-led humanitarian response known as Pacific Partnership in 2015, 2016, and 2018 – it was an experience that they are unlikely to forget.
“Every time a patient left the ship, our team on the ground surveyed them to see how their experience was and see what we could do to improve,” Cdr. Blevins said. “Across the board, they were all very appreciative of the medical care. We had a couple of veterans on board. They got [USNS Mercy] hats on their way out and seemed to very much enjoy a slightly different experience than they would get at a regular hospital.”
Capt. Rotruck added that the enthusiasm crew members had for supporting fellow Americans “really energized our team and really saturated that caring aspect of the people who interacted directly with patients,” he said. “It wasn’t just the physicians and nurses, but it was the staff delivering the food and coming to take blood samples and every other interaction that the patients had with our team. I think they really felt that enthusiasm for being there and supporting our neighbors in LA [Los Angeles].”
Crew life aboard the Mercy
Just as with any hospital on shore, personnel aboard the Mercy practiced preventive hygiene measures recommended by the Centers for Disease Control and Prevention to help prevent the spread of COVID-19, such as wearing cloth face masks, spacing out tables in the dining hall, closing indoor gyms, and devising creative ways to stay physically fit. Popular options included jogging around the perimeter of the ship and practicing yoga and calisthenics on the deck, “making sure you were physically distanced appropriately, and when you were done, putting your mask back on,” Cdr. Blevins said. Others supplemented their workouts with a pull-up bar on the deck. “In addition, we have a series of ramps that run on the starboard side of the ship that we can use for patient movement with litters on wheels or patient beds,” Capt. Rotruck said. “The uphill portion of those ramps represents a good workout opportunity as well.”
Downtime in an era of physical distancing also afforded crew members the opportunity to call or FaceTime with loved ones, watch streamed TV shows and movies, and work on their own professional development. Some continued with coursework for online degree programs offered by colleges and universities they were enrolled in, while some enlisted personnel used the time to complete the Navy Enlisted Warfare Qualification Programs Instruction, which issues the basic overarching requirements for the qualification and designation of all enlisted warfare programs.
“As you can imagine, people spend a lot of time learning how the ship works and how it integrates into larger naval forces and so forth,” Capt. Rotruck said. “Not just our ship but also other ships: their weapons systems and defense mechanisms and navigation systems. We had people spending a significant amount of time working on that. We had people complete their Enlisted Surface Warfare qualification while we were on the mission.”
End of the mission
Mercy returned to its home base in San Diego on May 15, but about 60 medical personnel stayed behind in Los Angeles to support Federal Emergency Management Agency (FEMA), state, and local health care professionals. Some worked at a site where clinicians provided care for COVID-19–positive patients who had been transferred from area skilled nursing facilities.
In addition, a team consisting of one nurse and five corpsmen “would go out to individual skilled nursing facilities and mainly conduct assessments and training, such as training in donning proper PPE [personal protective equipment] and determining what needs they had,” Capt. Rotruck said. “They met those needs if possible or [communicated with California officials] and let them know what the requirements were and what the needs were in that facility.” The assignment for those who stayed behind ended on May 31.
On the opposite coast, Mercy’s sister ship, USNS Comfort, arrived in New York Harbor from Norfolk, Va., on March 30 and spent 3½ weeks assisting area hospitals in the COVID-19 pandemic fight. A few days into the mission, Comfort’s internal spaces were reconfigured to create separate COVID-negative and COVID-positive sections. Medical teams aboard the ship cared for a total of 182 patients during the assignment.
Looking back on Mercy’s mission, Cdr. Blevins marveled at the sense of teamwork that unfolded. “We have quarterly training exercises with a core set of personnel, [and] we train getting ready for activation in 5 days,” she said. “All of that training kicks in and it comes to fruition in a mission like this. It was terrific to see a group of very disparate subject matter experts from all over the country come together with one purpose: which was to serve our own country during the pandemic.”
Capt. Rotruck pointed out that the experience enabled enlisted and nonenlisted physicians to maintain their skill sets during a time when military and civilian hospitals had stopped doing elective procedures and routine appointments. “The fact that those people were able to come on board the ship and continue to conduct their medical practice and maintain their skills and competencies in an environment that they weren’t quite used to is great,” he said. “Otherwise, some of those medical personnel would have been sitting idle, wherever they were from. This is the power of Navy medicine on behalf of our country.”
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
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.
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
For urban-based African Americans, proximity to a dermatologist varies by ZIP code
Urban ZIP codes with higher percentages of African American people tend to have fewer dermatologists. In these areas, dermatologists are not able meet the populations’ needs, based on the suggested ratio of patients per dermatologist.
The findings come from an analysis which used U.S. Census data to compare dermatologists’ distribution in urban ZIP codes with high and low representation of African Americans.
“It has been demonstrated that there is a non-uniform geographic distribution of dermatologists, in which they tend to practice in urban settings,” the study’s first author, Nathan Vengalil, MD, said in an interview following the virtual annual meeting of the American Academy of Dermatology. “Furthermore, it is also an unfortunate reality that African Americans suffer from inferior access to care compared to whites across health care. The same is true within dermatology; for example, African Americans face higher morbidity and mortality from melanoma, compared to their white counterparts.”
For the current study, Dr. Vengalil, a recent graduate of the University of Michigan, Ann Arbor, and associates in the university’s department of dermatology drew from 2010 U.S. Census data to identify ZIP codes with populations of 25,000 people and greater, because these should have at least one dermatologist to care for a community of that size (JAMA Dermatology 2017;153[5]:472-3).
Next, they ordered these ZIP codes from low to high concentrations of African American people. Those that fell in the 15th percentile or fewer were categorized as “low” (a total of 370 ZIP codes), while those that fell in the 85th percentile or higher were categorized as “high” (a total of 443 ZIP codes). Following this, the Definitive Healthcare provider database was used to identify the number of dermatologists practicing within each ZIP code and to calculate the average number of people per dermatologist in the “low” and “high” categories.
The researchers found that ZIP codes with high percentage of African American people have an average of 1.02 dermatologists (1 per 39,367 people), which is below the recommended limit of 1 per 25,000 people. Meanwhile, ZIP codes with a low percentage of African American people averaged 2.84 dermatologists (1 per 14,000 people), which is above the adequate limit. “ZIP codes with a low percentage of African Americans had, on average, almost three times more dermatologists than ZIP codes with a high percentage of American Americans,” Dr. Vengalil said. “This means that predominantly African American urban communities may face consequences of low provider availability including longer waits times, decreased diagnosis of skin cancer, and worse health care outcomes.”
He acknowledged certain limitations of the study, including the fact that it focused only on the distribution of dermatologists to assess communities’ access to dermatologic care. “It would be interesting to measure how much mid-level providers such as nurse practitioners and physician assistants are able to compensate for the low number of dermatologists in urban ZIP codes with high numbers of African Americans,” Dr. Vengalil said.
The study’s findings suggest that the distribution of dermatologists is not uniform even within the urban environment, especially when comparing areas with different representations of African American persons. “This reveals that lack of provider proximity may contribute to barriers that urban African Americans face in accessing dermatologic care,” he concluded. “Looking toward the future, it will be important to incentivize the development of practice locations in urban African American communities to combat the health disparities of our most underserved patients.”
The study’s other authors were Mio Nakamura, MD, MS, and Yolanda Helfrich, MD. The researchers reported having no financial disclosures.
SOURCE: Vengalil N et al. AAD 20, abstract 16772.
Urban ZIP codes with higher percentages of African American people tend to have fewer dermatologists. In these areas, dermatologists are not able meet the populations’ needs, based on the suggested ratio of patients per dermatologist.
The findings come from an analysis which used U.S. Census data to compare dermatologists’ distribution in urban ZIP codes with high and low representation of African Americans.
“It has been demonstrated that there is a non-uniform geographic distribution of dermatologists, in which they tend to practice in urban settings,” the study’s first author, Nathan Vengalil, MD, said in an interview following the virtual annual meeting of the American Academy of Dermatology. “Furthermore, it is also an unfortunate reality that African Americans suffer from inferior access to care compared to whites across health care. The same is true within dermatology; for example, African Americans face higher morbidity and mortality from melanoma, compared to their white counterparts.”
For the current study, Dr. Vengalil, a recent graduate of the University of Michigan, Ann Arbor, and associates in the university’s department of dermatology drew from 2010 U.S. Census data to identify ZIP codes with populations of 25,000 people and greater, because these should have at least one dermatologist to care for a community of that size (JAMA Dermatology 2017;153[5]:472-3).
Next, they ordered these ZIP codes from low to high concentrations of African American people. Those that fell in the 15th percentile or fewer were categorized as “low” (a total of 370 ZIP codes), while those that fell in the 85th percentile or higher were categorized as “high” (a total of 443 ZIP codes). Following this, the Definitive Healthcare provider database was used to identify the number of dermatologists practicing within each ZIP code and to calculate the average number of people per dermatologist in the “low” and “high” categories.
The researchers found that ZIP codes with high percentage of African American people have an average of 1.02 dermatologists (1 per 39,367 people), which is below the recommended limit of 1 per 25,000 people. Meanwhile, ZIP codes with a low percentage of African American people averaged 2.84 dermatologists (1 per 14,000 people), which is above the adequate limit. “ZIP codes with a low percentage of African Americans had, on average, almost three times more dermatologists than ZIP codes with a high percentage of American Americans,” Dr. Vengalil said. “This means that predominantly African American urban communities may face consequences of low provider availability including longer waits times, decreased diagnosis of skin cancer, and worse health care outcomes.”
He acknowledged certain limitations of the study, including the fact that it focused only on the distribution of dermatologists to assess communities’ access to dermatologic care. “It would be interesting to measure how much mid-level providers such as nurse practitioners and physician assistants are able to compensate for the low number of dermatologists in urban ZIP codes with high numbers of African Americans,” Dr. Vengalil said.
The study’s findings suggest that the distribution of dermatologists is not uniform even within the urban environment, especially when comparing areas with different representations of African American persons. “This reveals that lack of provider proximity may contribute to barriers that urban African Americans face in accessing dermatologic care,” he concluded. “Looking toward the future, it will be important to incentivize the development of practice locations in urban African American communities to combat the health disparities of our most underserved patients.”
The study’s other authors were Mio Nakamura, MD, MS, and Yolanda Helfrich, MD. The researchers reported having no financial disclosures.
SOURCE: Vengalil N et al. AAD 20, abstract 16772.
Urban ZIP codes with higher percentages of African American people tend to have fewer dermatologists. In these areas, dermatologists are not able meet the populations’ needs, based on the suggested ratio of patients per dermatologist.
The findings come from an analysis which used U.S. Census data to compare dermatologists’ distribution in urban ZIP codes with high and low representation of African Americans.
“It has been demonstrated that there is a non-uniform geographic distribution of dermatologists, in which they tend to practice in urban settings,” the study’s first author, Nathan Vengalil, MD, said in an interview following the virtual annual meeting of the American Academy of Dermatology. “Furthermore, it is also an unfortunate reality that African Americans suffer from inferior access to care compared to whites across health care. The same is true within dermatology; for example, African Americans face higher morbidity and mortality from melanoma, compared to their white counterparts.”
For the current study, Dr. Vengalil, a recent graduate of the University of Michigan, Ann Arbor, and associates in the university’s department of dermatology drew from 2010 U.S. Census data to identify ZIP codes with populations of 25,000 people and greater, because these should have at least one dermatologist to care for a community of that size (JAMA Dermatology 2017;153[5]:472-3).
Next, they ordered these ZIP codes from low to high concentrations of African American people. Those that fell in the 15th percentile or fewer were categorized as “low” (a total of 370 ZIP codes), while those that fell in the 85th percentile or higher were categorized as “high” (a total of 443 ZIP codes). Following this, the Definitive Healthcare provider database was used to identify the number of dermatologists practicing within each ZIP code and to calculate the average number of people per dermatologist in the “low” and “high” categories.
The researchers found that ZIP codes with high percentage of African American people have an average of 1.02 dermatologists (1 per 39,367 people), which is below the recommended limit of 1 per 25,000 people. Meanwhile, ZIP codes with a low percentage of African American people averaged 2.84 dermatologists (1 per 14,000 people), which is above the adequate limit. “ZIP codes with a low percentage of African Americans had, on average, almost three times more dermatologists than ZIP codes with a high percentage of American Americans,” Dr. Vengalil said. “This means that predominantly African American urban communities may face consequences of low provider availability including longer waits times, decreased diagnosis of skin cancer, and worse health care outcomes.”
He acknowledged certain limitations of the study, including the fact that it focused only on the distribution of dermatologists to assess communities’ access to dermatologic care. “It would be interesting to measure how much mid-level providers such as nurse practitioners and physician assistants are able to compensate for the low number of dermatologists in urban ZIP codes with high numbers of African Americans,” Dr. Vengalil said.
The study’s findings suggest that the distribution of dermatologists is not uniform even within the urban environment, especially when comparing areas with different representations of African American persons. “This reveals that lack of provider proximity may contribute to barriers that urban African Americans face in accessing dermatologic care,” he concluded. “Looking toward the future, it will be important to incentivize the development of practice locations in urban African American communities to combat the health disparities of our most underserved patients.”
The study’s other authors were Mio Nakamura, MD, MS, and Yolanda Helfrich, MD. The researchers reported having no financial disclosures.
SOURCE: Vengalil N et al. AAD 20, abstract 16772.
FROM AAD 20
Study compares pulse vs. continuous therapy for dermatophyte toenail onychomycosis
There appear to be results from a systematic review and network meta-analysis showed.
“Previous meta-analyses of pulse and continuous therapies have generated ambiguous results,” study authors led by Aditya K. Gupta, MD, PhD, wrote in a poster abstract presented at the virtual annual meeting of the American Academy of Dermatology. “There are few head-to-head clinical studies and no meta-analyses comparing regimens of terbinafine to regimens of itraconazole.”
In what is believed to be the first study of its kind, Dr. Gupta, professor of dermatology at the University of Toronto, and colleagues used network meta-analysis to compare pulse and continuous systemic therapies for toenail onychomycosis. They used PubMed to search for randomized, controlled trials of oral antifungal treatments for the condition in patients aged 18 years and older that included data on mycologic cure, complete cure, adverse events, and dropout rates. Treatment effects were based on intention-to-treat cure rates, and the researchers excluded studies of ketoconazole and griseofulvin since they are no longer indicated for the condition.
For their network meta-analysis, Dr. Gupta and colleagues evaluated 22 studies from 20 publications that included 4,205 randomized patients. Data on complete cure were excluded because of a lack of studies. When the researchers compared all treatments to placebo, the likelihood of mycologic cure did not differ significantly between continuous and pulse regimens for terbinafine and itraconazole. Compared with placebo, the most successful treatments were continuous terbinafine 250 mg daily for 24 weeks (risk ratio of achieving mycologic cure, 11.0) and continuous terbinafine 250 mg daily for 16 weeks (RR, 8.90). The researchers also observed no significant differences in the likelihood of adverse events between any continuous and pulse regimens of terbinafine, itraconazole, and fluconazole.
“Although continuous terbinafine 250 mg for 24 weeks was significantly more likely to produce mycologic cure than continuous itraconazole 200 mg for 12 weeks and weekly fluconazole (150-450 mg), it is not significantly different from the other included treatments,” Dr. Gupta and colleagues wrote in the abstract. “Considering the fungal life cycle, pulse therapy should theoretically be as effective as, or more effective than, continuous therapies: the sudden high concentration of an antifungal drug eliminates hyphae, sparing already-present spores. During the ‘off’ portion, these spores may germinate and be eliminated during the next pulse. Continuous therapy spares the spores, allowing them to germinate once treatment ends.”
They went on to note that, in clinical practice, “neither continuous nor pulse therapy is necessarily better. It is possible that the drug concentration in the nail is maintained during the ‘off’ period of pulse therapy. In both therapies, it may be that residual spores that have not been eliminated by the end of therapy are left to germinate, possibly contributing to the recalcitrant nature of onychomycosis.”
The study was awarded fourth place in the AAD’s 2020 poster awards. Dr. Gupta disclosed that he is a clinical trials investigator for Moberg Pharma and Bausch Health Canada and a speaker for Bausch Health Canada.
SOURCE: Gupta A et al. AAD 20, Abstract 16014.
There appear to be results from a systematic review and network meta-analysis showed.
“Previous meta-analyses of pulse and continuous therapies have generated ambiguous results,” study authors led by Aditya K. Gupta, MD, PhD, wrote in a poster abstract presented at the virtual annual meeting of the American Academy of Dermatology. “There are few head-to-head clinical studies and no meta-analyses comparing regimens of terbinafine to regimens of itraconazole.”
In what is believed to be the first study of its kind, Dr. Gupta, professor of dermatology at the University of Toronto, and colleagues used network meta-analysis to compare pulse and continuous systemic therapies for toenail onychomycosis. They used PubMed to search for randomized, controlled trials of oral antifungal treatments for the condition in patients aged 18 years and older that included data on mycologic cure, complete cure, adverse events, and dropout rates. Treatment effects were based on intention-to-treat cure rates, and the researchers excluded studies of ketoconazole and griseofulvin since they are no longer indicated for the condition.
For their network meta-analysis, Dr. Gupta and colleagues evaluated 22 studies from 20 publications that included 4,205 randomized patients. Data on complete cure were excluded because of a lack of studies. When the researchers compared all treatments to placebo, the likelihood of mycologic cure did not differ significantly between continuous and pulse regimens for terbinafine and itraconazole. Compared with placebo, the most successful treatments were continuous terbinafine 250 mg daily for 24 weeks (risk ratio of achieving mycologic cure, 11.0) and continuous terbinafine 250 mg daily for 16 weeks (RR, 8.90). The researchers also observed no significant differences in the likelihood of adverse events between any continuous and pulse regimens of terbinafine, itraconazole, and fluconazole.
“Although continuous terbinafine 250 mg for 24 weeks was significantly more likely to produce mycologic cure than continuous itraconazole 200 mg for 12 weeks and weekly fluconazole (150-450 mg), it is not significantly different from the other included treatments,” Dr. Gupta and colleagues wrote in the abstract. “Considering the fungal life cycle, pulse therapy should theoretically be as effective as, or more effective than, continuous therapies: the sudden high concentration of an antifungal drug eliminates hyphae, sparing already-present spores. During the ‘off’ portion, these spores may germinate and be eliminated during the next pulse. Continuous therapy spares the spores, allowing them to germinate once treatment ends.”
They went on to note that, in clinical practice, “neither continuous nor pulse therapy is necessarily better. It is possible that the drug concentration in the nail is maintained during the ‘off’ period of pulse therapy. In both therapies, it may be that residual spores that have not been eliminated by the end of therapy are left to germinate, possibly contributing to the recalcitrant nature of onychomycosis.”
The study was awarded fourth place in the AAD’s 2020 poster awards. Dr. Gupta disclosed that he is a clinical trials investigator for Moberg Pharma and Bausch Health Canada and a speaker for Bausch Health Canada.
SOURCE: Gupta A et al. AAD 20, Abstract 16014.
There appear to be results from a systematic review and network meta-analysis showed.
“Previous meta-analyses of pulse and continuous therapies have generated ambiguous results,” study authors led by Aditya K. Gupta, MD, PhD, wrote in a poster abstract presented at the virtual annual meeting of the American Academy of Dermatology. “There are few head-to-head clinical studies and no meta-analyses comparing regimens of terbinafine to regimens of itraconazole.”
In what is believed to be the first study of its kind, Dr. Gupta, professor of dermatology at the University of Toronto, and colleagues used network meta-analysis to compare pulse and continuous systemic therapies for toenail onychomycosis. They used PubMed to search for randomized, controlled trials of oral antifungal treatments for the condition in patients aged 18 years and older that included data on mycologic cure, complete cure, adverse events, and dropout rates. Treatment effects were based on intention-to-treat cure rates, and the researchers excluded studies of ketoconazole and griseofulvin since they are no longer indicated for the condition.
For their network meta-analysis, Dr. Gupta and colleagues evaluated 22 studies from 20 publications that included 4,205 randomized patients. Data on complete cure were excluded because of a lack of studies. When the researchers compared all treatments to placebo, the likelihood of mycologic cure did not differ significantly between continuous and pulse regimens for terbinafine and itraconazole. Compared with placebo, the most successful treatments were continuous terbinafine 250 mg daily for 24 weeks (risk ratio of achieving mycologic cure, 11.0) and continuous terbinafine 250 mg daily for 16 weeks (RR, 8.90). The researchers also observed no significant differences in the likelihood of adverse events between any continuous and pulse regimens of terbinafine, itraconazole, and fluconazole.
“Although continuous terbinafine 250 mg for 24 weeks was significantly more likely to produce mycologic cure than continuous itraconazole 200 mg for 12 weeks and weekly fluconazole (150-450 mg), it is not significantly different from the other included treatments,” Dr. Gupta and colleagues wrote in the abstract. “Considering the fungal life cycle, pulse therapy should theoretically be as effective as, or more effective than, continuous therapies: the sudden high concentration of an antifungal drug eliminates hyphae, sparing already-present spores. During the ‘off’ portion, these spores may germinate and be eliminated during the next pulse. Continuous therapy spares the spores, allowing them to germinate once treatment ends.”
They went on to note that, in clinical practice, “neither continuous nor pulse therapy is necessarily better. It is possible that the drug concentration in the nail is maintained during the ‘off’ period of pulse therapy. In both therapies, it may be that residual spores that have not been eliminated by the end of therapy are left to germinate, possibly contributing to the recalcitrant nature of onychomycosis.”
The study was awarded fourth place in the AAD’s 2020 poster awards. Dr. Gupta disclosed that he is a clinical trials investigator for Moberg Pharma and Bausch Health Canada and a speaker for Bausch Health Canada.
SOURCE: Gupta A et al. AAD 20, Abstract 16014.
FROM AAD 20
Study spotlights the skin microbiome’s evolving nature
, while the skin microbiome of the mothers of the children whose microbiome was analyzed remained relatively constant over the same time period.
The findings come from what is believed to be the longest longitudinal study specific to the skin microbiome of infants and mothers.
“Even at 10 years, the skin microbiome does not look like an adult skin microbiome, based on composition of the ecosystem,” lead author Kimberly A. Capone, PhD, said in an interview during the virtual annual meeting of the American Academy of Dermatology. “The diversity of the microbiome in children’s skin is distinct to that of an adult’s skin. We all have the same bacteria present, but in children it is distributed differently because the bacteria set themselves up based on the nutrients and topography that they find on the skin. Since infant skin is unique to infants, so too is their microbiome when we compare it to adults. It’s been fascinating to observe these children grow and mature, and follow the skin microbiome along this same period.”
During five time points over a period of 10 years, Dr. Capone and her colleagues at the Skillman, N.J.–based Johnson & Johnson Consumer Experience Center, a research and development site, used 16s rRNA gene sequencing to evaluate the skin microbiome on the forearms and foreheads of 30 mothers and their 31 children. The study participants had Fitzpatrick skin types I-IV and the mean age of mothers was 37 years. “We used 16s rRNA gene sequencing for microbiome analysis at the beginning, as that was what was available 10 years ago,” said Dr. Capone, head of the microbiome platform for Johnson & Johnson Consumer Health. “Since then, we continue to use 16s for continuity, but also collected additional swabs for deeper analysis later.”
She and her colleagues often draw samples from the forearm in baby skin clinical studies, “as the arm is a good site to collect relevant data on the body overall,” she explained. “We chose the forearm and forehead specifically here so we can make same body site comparisons to adult sample data which we took from the mothers on the same areas of their body.” Time point 1 was 3 months to 1 year, time point 2 was 2-3 years, time point 3 was 5-6 years, time point 4 was 7-8 years, and time point 5 was 9-10 years.
The researchers found that the skin of infants during the first few weeks of life was similar at age 3 and 4 years. “From that second time point on, we see significant increases in richness and diversity, richness being presence or absence of various bacterial species, and diversity being the relative abundance of those species,” Dr. Capone said. “What you’re basically seeing is that there are new organisms, i.e., richness, coming into the microbiome. We start to detect new ones. Over time, the ecosystem is expanding. It’s evolving because it’s not yet set up.” The evolving skin microbiome on children was dominated by Streptococcus and Staphylococcus. In addition, children had higher levels of Streptococcus, Moraxella, Granulicatella, Gemella and Veillonella, compared with their adult mothers. Adult skin was colonized predominantly by Propionibacterium/Cutibacterium and Staphylococcus.
“The skin microbiome also increased in diversity over time on the forearm, but not face, of the mothers,” Dr. Capone said. “Previous studies have shown how stable the adult skin microbiome is, so it’s intriguing to see the changes that we saw on the mothers in this study.”
The increase in skin microbiome diversity observed in the children is likely due to a variety of factors, she continued, including inherent growth and development, dietary changes, as well as exposure to various environments and other people. “The fact remains that diversity is increasing over time, as the ecosystem evolves,” she said. “Eventually, the skin microbiome will become ‘adultlike’ in puberty, when lipid production increases. This drives increases in Cutibacterium acnes, particularly on the face.”
She acknowledged certain limitations of the study, including its relatively small size and the fact that some of the original subjects did not return for microbiome analysis at later time points. “We need larger cohort studies, additional deeper sequence data, metabolomics and transcriptomics to better understand the function of the skin microbiome over these various ages,” she said.
The study was sponsored by Johnson & Johnson Consumer. Dr. Capone and her two coauthors are employees of the company.
, while the skin microbiome of the mothers of the children whose microbiome was analyzed remained relatively constant over the same time period.
The findings come from what is believed to be the longest longitudinal study specific to the skin microbiome of infants and mothers.
“Even at 10 years, the skin microbiome does not look like an adult skin microbiome, based on composition of the ecosystem,” lead author Kimberly A. Capone, PhD, said in an interview during the virtual annual meeting of the American Academy of Dermatology. “The diversity of the microbiome in children’s skin is distinct to that of an adult’s skin. We all have the same bacteria present, but in children it is distributed differently because the bacteria set themselves up based on the nutrients and topography that they find on the skin. Since infant skin is unique to infants, so too is their microbiome when we compare it to adults. It’s been fascinating to observe these children grow and mature, and follow the skin microbiome along this same period.”
During five time points over a period of 10 years, Dr. Capone and her colleagues at the Skillman, N.J.–based Johnson & Johnson Consumer Experience Center, a research and development site, used 16s rRNA gene sequencing to evaluate the skin microbiome on the forearms and foreheads of 30 mothers and their 31 children. The study participants had Fitzpatrick skin types I-IV and the mean age of mothers was 37 years. “We used 16s rRNA gene sequencing for microbiome analysis at the beginning, as that was what was available 10 years ago,” said Dr. Capone, head of the microbiome platform for Johnson & Johnson Consumer Health. “Since then, we continue to use 16s for continuity, but also collected additional swabs for deeper analysis later.”
She and her colleagues often draw samples from the forearm in baby skin clinical studies, “as the arm is a good site to collect relevant data on the body overall,” she explained. “We chose the forearm and forehead specifically here so we can make same body site comparisons to adult sample data which we took from the mothers on the same areas of their body.” Time point 1 was 3 months to 1 year, time point 2 was 2-3 years, time point 3 was 5-6 years, time point 4 was 7-8 years, and time point 5 was 9-10 years.
The researchers found that the skin of infants during the first few weeks of life was similar at age 3 and 4 years. “From that second time point on, we see significant increases in richness and diversity, richness being presence or absence of various bacterial species, and diversity being the relative abundance of those species,” Dr. Capone said. “What you’re basically seeing is that there are new organisms, i.e., richness, coming into the microbiome. We start to detect new ones. Over time, the ecosystem is expanding. It’s evolving because it’s not yet set up.” The evolving skin microbiome on children was dominated by Streptococcus and Staphylococcus. In addition, children had higher levels of Streptococcus, Moraxella, Granulicatella, Gemella and Veillonella, compared with their adult mothers. Adult skin was colonized predominantly by Propionibacterium/Cutibacterium and Staphylococcus.
“The skin microbiome also increased in diversity over time on the forearm, but not face, of the mothers,” Dr. Capone said. “Previous studies have shown how stable the adult skin microbiome is, so it’s intriguing to see the changes that we saw on the mothers in this study.”
The increase in skin microbiome diversity observed in the children is likely due to a variety of factors, she continued, including inherent growth and development, dietary changes, as well as exposure to various environments and other people. “The fact remains that diversity is increasing over time, as the ecosystem evolves,” she said. “Eventually, the skin microbiome will become ‘adultlike’ in puberty, when lipid production increases. This drives increases in Cutibacterium acnes, particularly on the face.”
She acknowledged certain limitations of the study, including its relatively small size and the fact that some of the original subjects did not return for microbiome analysis at later time points. “We need larger cohort studies, additional deeper sequence data, metabolomics and transcriptomics to better understand the function of the skin microbiome over these various ages,” she said.
The study was sponsored by Johnson & Johnson Consumer. Dr. Capone and her two coauthors are employees of the company.
, while the skin microbiome of the mothers of the children whose microbiome was analyzed remained relatively constant over the same time period.
The findings come from what is believed to be the longest longitudinal study specific to the skin microbiome of infants and mothers.
“Even at 10 years, the skin microbiome does not look like an adult skin microbiome, based on composition of the ecosystem,” lead author Kimberly A. Capone, PhD, said in an interview during the virtual annual meeting of the American Academy of Dermatology. “The diversity of the microbiome in children’s skin is distinct to that of an adult’s skin. We all have the same bacteria present, but in children it is distributed differently because the bacteria set themselves up based on the nutrients and topography that they find on the skin. Since infant skin is unique to infants, so too is their microbiome when we compare it to adults. It’s been fascinating to observe these children grow and mature, and follow the skin microbiome along this same period.”
During five time points over a period of 10 years, Dr. Capone and her colleagues at the Skillman, N.J.–based Johnson & Johnson Consumer Experience Center, a research and development site, used 16s rRNA gene sequencing to evaluate the skin microbiome on the forearms and foreheads of 30 mothers and their 31 children. The study participants had Fitzpatrick skin types I-IV and the mean age of mothers was 37 years. “We used 16s rRNA gene sequencing for microbiome analysis at the beginning, as that was what was available 10 years ago,” said Dr. Capone, head of the microbiome platform for Johnson & Johnson Consumer Health. “Since then, we continue to use 16s for continuity, but also collected additional swabs for deeper analysis later.”
She and her colleagues often draw samples from the forearm in baby skin clinical studies, “as the arm is a good site to collect relevant data on the body overall,” she explained. “We chose the forearm and forehead specifically here so we can make same body site comparisons to adult sample data which we took from the mothers on the same areas of their body.” Time point 1 was 3 months to 1 year, time point 2 was 2-3 years, time point 3 was 5-6 years, time point 4 was 7-8 years, and time point 5 was 9-10 years.
The researchers found that the skin of infants during the first few weeks of life was similar at age 3 and 4 years. “From that second time point on, we see significant increases in richness and diversity, richness being presence or absence of various bacterial species, and diversity being the relative abundance of those species,” Dr. Capone said. “What you’re basically seeing is that there are new organisms, i.e., richness, coming into the microbiome. We start to detect new ones. Over time, the ecosystem is expanding. It’s evolving because it’s not yet set up.” The evolving skin microbiome on children was dominated by Streptococcus and Staphylococcus. In addition, children had higher levels of Streptococcus, Moraxella, Granulicatella, Gemella and Veillonella, compared with their adult mothers. Adult skin was colonized predominantly by Propionibacterium/Cutibacterium and Staphylococcus.
“The skin microbiome also increased in diversity over time on the forearm, but not face, of the mothers,” Dr. Capone said. “Previous studies have shown how stable the adult skin microbiome is, so it’s intriguing to see the changes that we saw on the mothers in this study.”
The increase in skin microbiome diversity observed in the children is likely due to a variety of factors, she continued, including inherent growth and development, dietary changes, as well as exposure to various environments and other people. “The fact remains that diversity is increasing over time, as the ecosystem evolves,” she said. “Eventually, the skin microbiome will become ‘adultlike’ in puberty, when lipid production increases. This drives increases in Cutibacterium acnes, particularly on the face.”
She acknowledged certain limitations of the study, including its relatively small size and the fact that some of the original subjects did not return for microbiome analysis at later time points. “We need larger cohort studies, additional deeper sequence data, metabolomics and transcriptomics to better understand the function of the skin microbiome over these various ages,” she said.
The study was sponsored by Johnson & Johnson Consumer. Dr. Capone and her two coauthors are employees of the company.
FROM AAD 20
Key clinical point: The skin’s microbial diversity changes with increasing age in children while remaining stable in adult mothers.
Major finding: The skin microbiome in children becomes more diverse between the ages of 3-4 to age 10.
Study details: A longitudinal analysis of 30 mothers and their 31 children.
Disclosures: The study was sponsored by Johnson & Johnson Consumer. Dr. Capone and her two coauthors are employees of the company.
Source: Capone K et al. AAD 20, Abstract F053.
Results from two phase 3 trials of bimekizumab unveiled
Results from two late-breaking
“The rapid and lasting skin clearance observed in the majority of patients in both clinical studies demonstrate bimekizumab’s strong potential to deliver across three key areas: speed, depth and durability,” Kristian Reich, MD, said in an interview during the virtual annual meeting of the American Academy of Dermatology.
Bimekizumab selectively inhibits IL-17A and IL-17F, two key cytokines that drive inflammation and tissue damage across multiple diseases. In BE VIVID, Dr. Reich, of the Center for Translational Research in Inflammatory Skin Diseases at the University Medical Center Hamburg-Eppendorf (Germany), and colleagues randomized 567 patients with moderate to severe psoriasis to bimekizumab 320 mg every 4 weeks (Q4W), ustekinumab (45/90 mg weight-based dosing at baseline and week 4, then every 12 weeks), or placebo (Q4W through week 16 then bimekizumab 320 mg Q4W). Coprimary endpoints were a Psoriasis Area and Severity Index (PASI) of at least 90 and an Investigator Global Assessment (IGA) response of 0 or 1. Secondary/other outcomes included PASI 100 at week 16; PASI 90, IGA 0/1, and PASI 100 at week 52; and safety. (Ustekinumab is an IL-12 and IL-23 antagonist.)
The mean age of patients was 46 years and 72% were male. The researchers found that the proportion of patients who achieved PASI 90 and an IGA of 0/1 was higher in the bimekizumab arm at week 16 (85.0% and 84.1%, respectively), compared with those in the ustekinumab arm (49.7% and 53.4%) and those on placebo (4.8% and 4.8%; P < .001 for all associations). In addition, 58.6% of patients in the bimekizumab arm achieved PASI 100, compared with 20.9% of those in the ustekinumab arm and none of those on placebo.
At week 52, patients in the bimekizumab arm achieved PASI 90, IGA 0/1, and PASI 100 response rates of 81.6%, 77.9%, and 64.2%, respectively, compared with 55.8%, 60.7%, and 38.0% of those in the ustekinumab arm. Over 52 weeks, incidence of serious treatment-emergent adverse events was 6.1% with bimekizumab arm, compared with 7.4% in the ustekinumab arm. Four deaths occurred (two in the bimekizumab arm, and one each in the ustekinumab and placebo arms), all considered unrelated to treatment. The most common reported adverse events in the bimekizumab arm through week 52 were nasopharyngitis (21.8%), oral candidiasis (15.2%), and upper respiratory tract infections (9.1%).
“The rapid and lasting skin clearance observed in the majority of patients treated with bimekizumab provide support for inhibiting IL-17F, in addition to IL-17A, to inhibit the IL-17 pathway,” Dr. Reich said. “This can make a meaningful difference for people living with psoriasis.” He added that the results of the head-to-head study of bimekizumab with secukinumab (an IL-17A antagonist) are expected later this year. “It will be very interesting to see if the marked differences in treatment effect seen in the BE VIVID study remain when comparing to an IL-17.”
In BE READY, a pivotal phase 3, randomized, withdrawal study, investigators led by Kenneth Gordon, MD, randomized 435 patients with moderate to severe psoriasis 4:1 to receive 320 mg Q4W or placebo, and followed them for 16 weeks. In a second part of the study, patients who had achieved at least a PASI 90 response at week 16 were rerandomized to receive continuous bimekizumab at two different dosing regimens: 320 mg Q4W or 320 mg every 8 weeks (Q8W), or to be withdrawn from treatment (placebo Q4W), and followed through week 56. Relapse was defined as a PASI score of less than 75 from week 20.
The mean age of patients was 44 years and 72% were male. At week 16, the proportion of patients who achieved a PASI 90 and an IGA of 0/1 was greatest in the bimekizumab arm (90.8% and 92.6%, respectively), compared with those on placebo. In addition, 68.2% of patients in the bimekizumab arm achieved PASI 100 at week 16, compared with only 1.2% of those on placebo (P < .001 for all associations). In the second part of the study, the researchers found that 86.8% of patients who received continuous bimekizumab 320 mg Q4W maintained PASI 90 at week 56, compared with 91% who were switched to bimekizumab 320 mg Q8W, and 16.2% of patients who were withdrawn from the trial.
“The speed of response and the number of patients who achieved clearance are extremely high, especially in a phase 3 trial,” Dr. Gordon, professor and Thomas R. Russell Family Chair of Dermatology at the Medical College of Wisconsin, Milwaukee, said in an interview. “However, the most surprising aspect may be the impressive maintenance of response in patients, even those who were treated with every-8-week dosing in the maintenance phase. While it is possible that there are some patients who may benefit from more frequent dosing in the long term, the possibility of every-8-week dosing would be a tremendous benefit for patients.”
As in the BE VIVID trial, the most frequently reported adverse events with bimekizumab between week 16 and week 56 in BE READY were nasopharyngitis (10.4% in the Q4W arm vs. 23% in the Q8W arm), oral candidiasis (11.3% Q4W vs. 9% Q8W), and upper respiratory tract infections (11.3% Q4W vs. 8% Q8W). The incidence of serious treatment-emergent adverse events with bimekizumab was 4.7% in the Q4W arm and 3% in the Q8W arm versus 3.8% in the placebo arm at week 56.
“The results from BE READY demonstrate that bimekizumab has the potential to deliver rapid and lasting skin improvement for psoriasis patients,” Dr. Gordon said. “The findings also support the hypothesis that inhibiting IL-17F, in addition to IL-17A, may be more effective in suppressing inflammation in suppressing inflammation in psoriasis than IL-17A inhibition alone.”
Both studies were funded by UCB Pharma. Dr. Reich disclosed that he has served as adviser and/or paid speaker for and/or participated in clinical trials sponsored by companies that include UCB. Dr. Gordon disclosed that he has received honoraria and/or research support from companies that include UCB..
Results from two late-breaking
“The rapid and lasting skin clearance observed in the majority of patients in both clinical studies demonstrate bimekizumab’s strong potential to deliver across three key areas: speed, depth and durability,” Kristian Reich, MD, said in an interview during the virtual annual meeting of the American Academy of Dermatology.
Bimekizumab selectively inhibits IL-17A and IL-17F, two key cytokines that drive inflammation and tissue damage across multiple diseases. In BE VIVID, Dr. Reich, of the Center for Translational Research in Inflammatory Skin Diseases at the University Medical Center Hamburg-Eppendorf (Germany), and colleagues randomized 567 patients with moderate to severe psoriasis to bimekizumab 320 mg every 4 weeks (Q4W), ustekinumab (45/90 mg weight-based dosing at baseline and week 4, then every 12 weeks), or placebo (Q4W through week 16 then bimekizumab 320 mg Q4W). Coprimary endpoints were a Psoriasis Area and Severity Index (PASI) of at least 90 and an Investigator Global Assessment (IGA) response of 0 or 1. Secondary/other outcomes included PASI 100 at week 16; PASI 90, IGA 0/1, and PASI 100 at week 52; and safety. (Ustekinumab is an IL-12 and IL-23 antagonist.)
The mean age of patients was 46 years and 72% were male. The researchers found that the proportion of patients who achieved PASI 90 and an IGA of 0/1 was higher in the bimekizumab arm at week 16 (85.0% and 84.1%, respectively), compared with those in the ustekinumab arm (49.7% and 53.4%) and those on placebo (4.8% and 4.8%; P < .001 for all associations). In addition, 58.6% of patients in the bimekizumab arm achieved PASI 100, compared with 20.9% of those in the ustekinumab arm and none of those on placebo.
At week 52, patients in the bimekizumab arm achieved PASI 90, IGA 0/1, and PASI 100 response rates of 81.6%, 77.9%, and 64.2%, respectively, compared with 55.8%, 60.7%, and 38.0% of those in the ustekinumab arm. Over 52 weeks, incidence of serious treatment-emergent adverse events was 6.1% with bimekizumab arm, compared with 7.4% in the ustekinumab arm. Four deaths occurred (two in the bimekizumab arm, and one each in the ustekinumab and placebo arms), all considered unrelated to treatment. The most common reported adverse events in the bimekizumab arm through week 52 were nasopharyngitis (21.8%), oral candidiasis (15.2%), and upper respiratory tract infections (9.1%).
“The rapid and lasting skin clearance observed in the majority of patients treated with bimekizumab provide support for inhibiting IL-17F, in addition to IL-17A, to inhibit the IL-17 pathway,” Dr. Reich said. “This can make a meaningful difference for people living with psoriasis.” He added that the results of the head-to-head study of bimekizumab with secukinumab (an IL-17A antagonist) are expected later this year. “It will be very interesting to see if the marked differences in treatment effect seen in the BE VIVID study remain when comparing to an IL-17.”
In BE READY, a pivotal phase 3, randomized, withdrawal study, investigators led by Kenneth Gordon, MD, randomized 435 patients with moderate to severe psoriasis 4:1 to receive 320 mg Q4W or placebo, and followed them for 16 weeks. In a second part of the study, patients who had achieved at least a PASI 90 response at week 16 were rerandomized to receive continuous bimekizumab at two different dosing regimens: 320 mg Q4W or 320 mg every 8 weeks (Q8W), or to be withdrawn from treatment (placebo Q4W), and followed through week 56. Relapse was defined as a PASI score of less than 75 from week 20.
The mean age of patients was 44 years and 72% were male. At week 16, the proportion of patients who achieved a PASI 90 and an IGA of 0/1 was greatest in the bimekizumab arm (90.8% and 92.6%, respectively), compared with those on placebo. In addition, 68.2% of patients in the bimekizumab arm achieved PASI 100 at week 16, compared with only 1.2% of those on placebo (P < .001 for all associations). In the second part of the study, the researchers found that 86.8% of patients who received continuous bimekizumab 320 mg Q4W maintained PASI 90 at week 56, compared with 91% who were switched to bimekizumab 320 mg Q8W, and 16.2% of patients who were withdrawn from the trial.
“The speed of response and the number of patients who achieved clearance are extremely high, especially in a phase 3 trial,” Dr. Gordon, professor and Thomas R. Russell Family Chair of Dermatology at the Medical College of Wisconsin, Milwaukee, said in an interview. “However, the most surprising aspect may be the impressive maintenance of response in patients, even those who were treated with every-8-week dosing in the maintenance phase. While it is possible that there are some patients who may benefit from more frequent dosing in the long term, the possibility of every-8-week dosing would be a tremendous benefit for patients.”
As in the BE VIVID trial, the most frequently reported adverse events with bimekizumab between week 16 and week 56 in BE READY were nasopharyngitis (10.4% in the Q4W arm vs. 23% in the Q8W arm), oral candidiasis (11.3% Q4W vs. 9% Q8W), and upper respiratory tract infections (11.3% Q4W vs. 8% Q8W). The incidence of serious treatment-emergent adverse events with bimekizumab was 4.7% in the Q4W arm and 3% in the Q8W arm versus 3.8% in the placebo arm at week 56.
“The results from BE READY demonstrate that bimekizumab has the potential to deliver rapid and lasting skin improvement for psoriasis patients,” Dr. Gordon said. “The findings also support the hypothesis that inhibiting IL-17F, in addition to IL-17A, may be more effective in suppressing inflammation in suppressing inflammation in psoriasis than IL-17A inhibition alone.”
Both studies were funded by UCB Pharma. Dr. Reich disclosed that he has served as adviser and/or paid speaker for and/or participated in clinical trials sponsored by companies that include UCB. Dr. Gordon disclosed that he has received honoraria and/or research support from companies that include UCB..
Results from two late-breaking
“The rapid and lasting skin clearance observed in the majority of patients in both clinical studies demonstrate bimekizumab’s strong potential to deliver across three key areas: speed, depth and durability,” Kristian Reich, MD, said in an interview during the virtual annual meeting of the American Academy of Dermatology.
Bimekizumab selectively inhibits IL-17A and IL-17F, two key cytokines that drive inflammation and tissue damage across multiple diseases. In BE VIVID, Dr. Reich, of the Center for Translational Research in Inflammatory Skin Diseases at the University Medical Center Hamburg-Eppendorf (Germany), and colleagues randomized 567 patients with moderate to severe psoriasis to bimekizumab 320 mg every 4 weeks (Q4W), ustekinumab (45/90 mg weight-based dosing at baseline and week 4, then every 12 weeks), or placebo (Q4W through week 16 then bimekizumab 320 mg Q4W). Coprimary endpoints were a Psoriasis Area and Severity Index (PASI) of at least 90 and an Investigator Global Assessment (IGA) response of 0 or 1. Secondary/other outcomes included PASI 100 at week 16; PASI 90, IGA 0/1, and PASI 100 at week 52; and safety. (Ustekinumab is an IL-12 and IL-23 antagonist.)
The mean age of patients was 46 years and 72% were male. The researchers found that the proportion of patients who achieved PASI 90 and an IGA of 0/1 was higher in the bimekizumab arm at week 16 (85.0% and 84.1%, respectively), compared with those in the ustekinumab arm (49.7% and 53.4%) and those on placebo (4.8% and 4.8%; P < .001 for all associations). In addition, 58.6% of patients in the bimekizumab arm achieved PASI 100, compared with 20.9% of those in the ustekinumab arm and none of those on placebo.
At week 52, patients in the bimekizumab arm achieved PASI 90, IGA 0/1, and PASI 100 response rates of 81.6%, 77.9%, and 64.2%, respectively, compared with 55.8%, 60.7%, and 38.0% of those in the ustekinumab arm. Over 52 weeks, incidence of serious treatment-emergent adverse events was 6.1% with bimekizumab arm, compared with 7.4% in the ustekinumab arm. Four deaths occurred (two in the bimekizumab arm, and one each in the ustekinumab and placebo arms), all considered unrelated to treatment. The most common reported adverse events in the bimekizumab arm through week 52 were nasopharyngitis (21.8%), oral candidiasis (15.2%), and upper respiratory tract infections (9.1%).
“The rapid and lasting skin clearance observed in the majority of patients treated with bimekizumab provide support for inhibiting IL-17F, in addition to IL-17A, to inhibit the IL-17 pathway,” Dr. Reich said. “This can make a meaningful difference for people living with psoriasis.” He added that the results of the head-to-head study of bimekizumab with secukinumab (an IL-17A antagonist) are expected later this year. “It will be very interesting to see if the marked differences in treatment effect seen in the BE VIVID study remain when comparing to an IL-17.”
In BE READY, a pivotal phase 3, randomized, withdrawal study, investigators led by Kenneth Gordon, MD, randomized 435 patients with moderate to severe psoriasis 4:1 to receive 320 mg Q4W or placebo, and followed them for 16 weeks. In a second part of the study, patients who had achieved at least a PASI 90 response at week 16 were rerandomized to receive continuous bimekizumab at two different dosing regimens: 320 mg Q4W or 320 mg every 8 weeks (Q8W), or to be withdrawn from treatment (placebo Q4W), and followed through week 56. Relapse was defined as a PASI score of less than 75 from week 20.
The mean age of patients was 44 years and 72% were male. At week 16, the proportion of patients who achieved a PASI 90 and an IGA of 0/1 was greatest in the bimekizumab arm (90.8% and 92.6%, respectively), compared with those on placebo. In addition, 68.2% of patients in the bimekizumab arm achieved PASI 100 at week 16, compared with only 1.2% of those on placebo (P < .001 for all associations). In the second part of the study, the researchers found that 86.8% of patients who received continuous bimekizumab 320 mg Q4W maintained PASI 90 at week 56, compared with 91% who were switched to bimekizumab 320 mg Q8W, and 16.2% of patients who were withdrawn from the trial.
“The speed of response and the number of patients who achieved clearance are extremely high, especially in a phase 3 trial,” Dr. Gordon, professor and Thomas R. Russell Family Chair of Dermatology at the Medical College of Wisconsin, Milwaukee, said in an interview. “However, the most surprising aspect may be the impressive maintenance of response in patients, even those who were treated with every-8-week dosing in the maintenance phase. While it is possible that there are some patients who may benefit from more frequent dosing in the long term, the possibility of every-8-week dosing would be a tremendous benefit for patients.”
As in the BE VIVID trial, the most frequently reported adverse events with bimekizumab between week 16 and week 56 in BE READY were nasopharyngitis (10.4% in the Q4W arm vs. 23% in the Q8W arm), oral candidiasis (11.3% Q4W vs. 9% Q8W), and upper respiratory tract infections (11.3% Q4W vs. 8% Q8W). The incidence of serious treatment-emergent adverse events with bimekizumab was 4.7% in the Q4W arm and 3% in the Q8W arm versus 3.8% in the placebo arm at week 56.
“The results from BE READY demonstrate that bimekizumab has the potential to deliver rapid and lasting skin improvement for psoriasis patients,” Dr. Gordon said. “The findings also support the hypothesis that inhibiting IL-17F, in addition to IL-17A, may be more effective in suppressing inflammation in suppressing inflammation in psoriasis than IL-17A inhibition alone.”
Both studies were funded by UCB Pharma. Dr. Reich disclosed that he has served as adviser and/or paid speaker for and/or participated in clinical trials sponsored by companies that include UCB. Dr. Gordon disclosed that he has received honoraria and/or research support from companies that include UCB..
FROM AAD 2020