2020 dermMentors™ Resident of Distinction Award™ at the Coastal Dermatology Symposium

The dermMentors™ Resident of Distinction Award™ recognizes top residents in dermatology. DermMentors.org and the dermMentors™ Resident of Distinction Award™ are sponsored by Beiersdorf Inc and administered by DermEd, Inc. The 2020 dermMentors™ Residents of Distinction™ presented new scientific research during the general sessions of the virtual 16th Annual Coastal Dermatology Symposium on October 16, 2020.

Overall Grand Prize
Topical Cantharidin Revisited: A Phase 2 Study Investigating a Commercially Viable Formulation of Cantharidin (VP-102) for the Treatment of Molluscum Contagiosum

Anthony K. Guzman, MD; Jessica L. Garelik, DO; Steven R. Cohen, MD, MPH, Department of Internal Medicine, Division of Dermatology, Albert Einstein College of Medicine, Bronx, New York 
Disclosures: None. 

Background 
Molluscum contagiosum (MC) is a common cutaneous infection caused by a DNA poxvirus, predominantly affecting children. There is a paucity of high-quality evidence on which to make clinical decisions in treating MC.¹ Cantharidin, a topical vesicant historically derived from a blister beetle, is a commonly used treatment for this condition. However, despite the prevalence of its use, cantharidin is not approved by the US Food and Drug Administration, is not standardized in formulation or treatment regimen, and is not always manufactured in accordance with good manufacturing practice (GMP), leading to a lack of commercial availability.^2,3

Objective 
To determine the efficacy and safety of VP-102, a novel, standardized, commercially viable cantharidin formulation produced under GMP for the treatment of MC.

Methods 
We conducted a 12-week, open-label pilot trial at a single outpatient dermatology clinic. Patients aged 2 to 17 years (N=30) with a clinical diagnosis of MC and fewer than 50 lesions were included. Patients were treated with a single-use vial containing a standardized 0.7% w/v cantharidin solution, produced under GMP (VP-102), applied with the wooden end of a cotton swab approximately every 21 days for up to 4 treatments or until complete lesion clearance. Patients were instructed to wash treatment off all lesions at either 6 hours (cohort 1: 14/30, 46.7%) or 24 hours (cohort 2: 16/30, 53.3%), or earlier if notable blistering occurred. Lesion counts and adverse events, including local skin reactions, were documented at each visit. Quality of life also was measured using the Children’s Dermatology Quality of Life Index at baseline and at the end of study (EOS). The primary end point was the percentage of patients achieving total clearance by EOS on day 84. 

Results 
The mean patient age was 5.8 years (range, 2–12 years). A total of 26 patients (86.7%) experienced at least 1 expected local skin reaction, such as blistering or erythema. No serious or unexpected treatment-related adverse events were encountered. A total of 25 patients pooled from both cohorts completed the study. Eleven patients (44.0%) achieved total lesion clearance by EOS. The mean (standard deviation) lesion count was significantly reduced from 23.0 (15.6) at baseline to 6.8 (11.7) at EOS (P<.0001). The mean (standard deviation) Children’s Dermatology Quality of Life Index score was markedly improved from 3.9 (5.6) at baseline to 0.38 (1.3) at EOS (P=.01).

Conclusions 
VP-102 was well tolerated with either a 6- or 24-hour exposure and was associated with a significantly reduced lesion count, improved quality of life, and complete clearance of MC lesions in nearly half of the patients.

References

1. van der Wouden JC, van der Sande R, Kruithof EJ, et al. Interventions for cutaneous molluscum contagiosum. Cochrane Database Syst Rev. 2017;5:CD004767.
2. Coloe J, Morrell DS. Cantharidin use among pediatric dermatologists in the treatment of molluscum contagiosum. Pediatr Dermatol. 2009;26:405-408.
3. Pompei DT, Rezzadeh KS, Viola KV, et al. Cantharidin therapy: practice patterns and attitudes of health care providers. J Am Acad Dermatol. 2013;68:1045-1046.

Up next: Autologous cell therapy for recessive dystrophic epidermolysis bullosa

Phase 1/2a Clinical Trial of Gene-Corrected Autologous Cell Therapy for Recessive Dystrophic Epidermolysis Bullosa

Shaundra Eichstadt, MD, Stanford University Department of Dermatology, Redwood City, California;  Tufts University Medical Center, Boston, Massachusetts 
Disclosures: None. 

Recessive dystrophic epidermolysis bullosa (RDEB) patients have mutations in the COL7A1 gene, thus lacking functional type VII collagen (C7) protein; they have marked skin fragility and blistering. This single-center phase 1/2a open-label study evaluated the long-term efficacy, safety, and patient-reported outcomes in RDEB patients treated with gene-corrected autologous cell therapy (ClinicalTrials.gov identifier NCT01263379). Autologous keratinocytes were isolated from participant skin biopsies. Epidermal sheets were prepared from cells transduced with a retrovirus carrying the full-length human COL7A1 gene. These gene-corrected autologous epidermal sheets measured 5×7 cm (35 cm²) and were transplanted onto 6 wound sites in each of 7 adult participants (N=42 sites) between 2013 and 2017. Participants were followed for 2 to 5 years. No participants experienced any serious related adverse events. Wound healing of 50% or more by Investigator Global Assessment was present in 95% (36/38) of treated wounds versus 0% (0/6) of untreated control wounds at 6 months (P<.0001). At year 1, 68% (26/38) of treated wounds had healing of 50% or more compared with 17% (1/6) of control wounds (P=.025). At year 2, 71% (27/38) of treated wounds had healing of 50% or more compared with 17% (1/6) of control wounds (P=.019). C7 expression persisted up to 2 years posttreatment in 2 participants. Treated wounds with 50% or more wound healing demonstrated improvement in patient-reported pain, itch, and wound durability. This study provides additional data to support the clinically meaningful benefit of treating chronic RDEB wounds with ex vivo, C7 gene-corrected autologous cell therapy. This approach was safe and promoted wound healing that was associated with improved patient-reported outcomes.

Up next: Skin toxicity in metastatic melanoma patients treated with ICIs

Nicholas Gulati, MD, PhD, NYU Grossman School of Medicine, New York, New York
Disclosures: None. 

Immune checkpoint inhibition (ICI) improves survival outcomes for patients with metastatic melanoma, but serious immune-related adverse events requiring intervention with immunosuppressive medications occur in a subset of patients. Skin toxicity (ST) has been reported to be associated with better response to ICI. However, understudied factors, such as ST severity and potential survivor bias, may influence the strength of these observed associations. To examine the potential confounding impact of such variables, we analyzed metastatic melanoma patients enrolled prospectively in a clinicopathological database with protocol-driven follow-up and treated with ICI. We tested the associations between developing ST, stratified as none (n=257), mild (n=86), and severe (n=44), and progression-free survival (PFS) and overall survival in univariable and multivariable analyses. We defined severe ST as a skin event that required treatment with systemic corticosteroids. To account for the possibility of longer survival leading to adverse events instead of the reverse, we treated ST as a time-dependent covariate in an adjusted model. Mild ST was significantly associated with improved PFS and overall survival (P=.001 and P=.018, respectively) in univariable analysis and with improved PFS in multivariable analysis (P=.020). However, these associations lost significance after adjusting for the time from treatment initiation to time of skin event (P>.05). Severe ST was not associated with improved outcomes. Our data reveal the influence of event severity and time to event as covariates in analyzing the relationship between ST and ICI outcomes. Further, we reinforce the importance of identifying baseline predictors of response and toxicity to ICI to optimize treatment selection and prophylactic care when indicated.

Up next: Risk of COVID-19 in patients receiving immunobiologic therapy

Nikolai Klebanov, MD, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts
Disclosures: None. 

Importance
Data on the risks of immunosuppressive biologics in the context of coronavirus disease 2019 (COVID-19) infection are limited, creating uncertainty for patients and providers whether to continue therapy during the pandemic.

Objective
To investigate whether patients treated with biologics were at an increased risk for COVID-19 infection as well as all-cause mortality once infected. 

Design
A multicenter retrospective study of 7361 patients prescribed biologics and 74,910 matched controls, cross-referenced with COVID-19 infection and all-cause mortality data through June 19, 2020, from the Massachusetts Department of Public Health.

Participants 
Patients with at least 1 prescription for an immunosuppressive biologic in the Mass General Brigham health care system between July 1, 2019, and February 29, 2020. Multivariate logistic regression was used on matched data to calculate the odds ratio (OR) for COVID-19 infection status between patients on biologics and controls, adjusting for age, gender, race, Charlson Comorbidity index (CCI) severity grade, median income, and local infection rate. An analysis adjusting for individual comorbidities was also performed. Multivariate Poisson regression was performed on COVID-19 positive patients to compare the risk for all-cause mortality, adjusting for gender, CCI severity grade, median income, and local COVID-19 rate.

Setting 
Retrospective matched cohort.

Exposure 
Biologic immunosuppressants.

Main Outcomes and Measures 
Odds of COVID-19 diagnosis and all-cause mortality following the diagnosis.

Results 
7,361 patients treated with biologics and 74,910 matched controls were included in the analysis (mean age, 50.6 years; 56.0% women, 84.5% white; mean age-adjusted CCI 2.8). There were 87 (1.2%) infections and 7 deaths (8.0%) in patients treated with biologics and 1063 (1.4%) infections and 71 deaths (6.7%) in the control group. Patients treated with immunosuppressive biologics were not at significantly increased risk of COVID-19 diagnosis (OR 0.88, 95% CI 0.71-1.09; P=.25) or subsequent mortality (OR 1.26, 95% CI 0.57-2.76; P=.57). 

A total of 7361 patients treated with biologics and 74,910 matched controls were included in the analysis (mean age, 50.6 years; 56.0% women and 84.5% white; mean age-adjusted CCI, 2.8). There were 87 (1.2%) infections and 7 deaths (8.0%) in patients treated with biologics, and 1063 (1.4%) infections and 71 deaths (6.7%) in the control group. Patients treated with immunosuppressive biologics were not at increased risk for COVID-19 diagnosis (OR, 0.88; 95% CI, 0.71-1.09; P=.25) or subsequent mortality (OR 1.26; 95% CI 0.57-2.76; P=.57). 

Conclusions and Relevance 
Given an absence of evidence that patients treated with biologics are more susceptible to COVID-19, patients should be encouraged to continue their therapy to prevent disease progression during this pandemic.

Up next: Compliance With Systemic Medications for AD and Psoriasis

Importance
The management of moderate to severe atopic dermatitis (AD) is being revolutionized by the development of novel systemic therapeutics. However, these new therapeutics are being implemented using the same treatment paradigms that are used for psoriasis treatment (ie, patients on systemic medications require indefinite therapy). While use of systemic therapeutics indefinitely is acceptable to many psoriasis patients because psoriasis severity is frequently stable over long periods of time, AD is hallmarked by seasonal flares followed by periods of relative quiescence, making indefinite therapy less attractive to patients with AD. 

Objective
This whole-population cohort study describes systemic medication adherence patterns in AD and psoriasis patients. These patterns are then compared to determine whether systemic medications requiring indefinite therapy are adhered to at similar rates in the AD and psoriasis populations. The aim of this comparison is to assess whether drugs requiring indefinite therapy meet the needs of AD patients requiring systemic treatment.

Design, Setting, and Participants 
This is a retrospective cohort study using the national Veterans Administration (VA) health database to identify all veterans with psoriasis and AD who are receiving care at any VA location. Veterans with psoriasis and AD were identified using International Classification of Diseases, Ninth Revision and Tenth Revision codes. Veterans were included in the study if they received nonsteroidal systemic immunosuppressive or immunomodulatory medications for their psoriasis or AD. 

Main Outcome(s) and Measure(s)
All medications filled at a VA pharmacy are time stamped. This unique data recording allows for real-world adherence to be evaluated by comparing actual medication fill dates to expected medication fill dates based on refill interval. Patients who fill a medication more than 7 days after the expected refill date are classified as nonadherent. We described systemic medication adherence rates and assessed for seasonal variation in adherence patterns for AD and psoriasis patients. Cofounding variables, including history of mental illness, substance use disorder, and patient income, were recorded and included in the analysis. 

Conclusions and Relevance 

This study's unique data source provides insight into the ways adherence patterns differ between individuals with AD and psoriasis, and insights into the ways mental illness, substance use, and poverty affect adherence to systemic therapeutics among dermatology patients with inflammatory skin conditions. 

The dermMentors™ Resident of Distinction Award™ recognizes top residents in dermatology. DermMentors.org and the dermMentors™ Resident of Distinction Award™ are sponsored by Beiersdorf Inc and administered by DermEd, Inc. The 2020 dermMentors™ Residents of Distinction™ presented new scientific research during the general sessions of the virtual 16th Annual Coastal Dermatology Symposium on October 16, 2020.

Overall Grand Prize
Topical Cantharidin Revisited: A Phase 2 Study Investigating a Commercially Viable Formulation of Cantharidin (VP-102) for the Treatment of Molluscum Contagiosum

Anthony K. Guzman, MD; Jessica L. Garelik, DO; Steven R. Cohen, MD, MPH, Department of Internal Medicine, Division of Dermatology, Albert Einstein College of Medicine, Bronx, New York 
Disclosures: None. 

Background 
Molluscum contagiosum (MC) is a common cutaneous infection caused by a DNA poxvirus, predominantly affecting children. There is a paucity of high-quality evidence on which to make clinical decisions in treating MC.¹ Cantharidin, a topical vesicant historically derived from a blister beetle, is a commonly used treatment for this condition. However, despite the prevalence of its use, cantharidin is not approved by the US Food and Drug Administration, is not standardized in formulation or treatment regimen, and is not always manufactured in accordance with good manufacturing practice (GMP), leading to a lack of commercial availability.^2,3

Objective 
To determine the efficacy and safety of VP-102, a novel, standardized, commercially viable cantharidin formulation produced under GMP for the treatment of MC.

Methods 
We conducted a 12-week, open-label pilot trial at a single outpatient dermatology clinic. Patients aged 2 to 17 years (N=30) with a clinical diagnosis of MC and fewer than 50 lesions were included. Patients were treated with a single-use vial containing a standardized 0.7% w/v cantharidin solution, produced under GMP (VP-102), applied with the wooden end of a cotton swab approximately every 21 days for up to 4 treatments or until complete lesion clearance. Patients were instructed to wash treatment off all lesions at either 6 hours (cohort 1: 14/30, 46.7%) or 24 hours (cohort 2: 16/30, 53.3%), or earlier if notable blistering occurred. Lesion counts and adverse events, including local skin reactions, were documented at each visit. Quality of life also was measured using the Children’s Dermatology Quality of Life Index at baseline and at the end of study (EOS). The primary end point was the percentage of patients achieving total clearance by EOS on day 84. 

Results 
The mean patient age was 5.8 years (range, 2–12 years). A total of 26 patients (86.7%) experienced at least 1 expected local skin reaction, such as blistering or erythema. No serious or unexpected treatment-related adverse events were encountered. A total of 25 patients pooled from both cohorts completed the study. Eleven patients (44.0%) achieved total lesion clearance by EOS. The mean (standard deviation) lesion count was significantly reduced from 23.0 (15.6) at baseline to 6.8 (11.7) at EOS (P<.0001). The mean (standard deviation) Children’s Dermatology Quality of Life Index score was markedly improved from 3.9 (5.6) at baseline to 0.38 (1.3) at EOS (P=.01).

Conclusions 
VP-102 was well tolerated with either a 6- or 24-hour exposure and was associated with a significantly reduced lesion count, improved quality of life, and complete clearance of MC lesions in nearly half of the patients.

References

1. van der Wouden JC, van der Sande R, Kruithof EJ, et al. Interventions for cutaneous molluscum contagiosum. Cochrane Database Syst Rev. 2017;5:CD004767.
2. Coloe J, Morrell DS. Cantharidin use among pediatric dermatologists in the treatment of molluscum contagiosum. Pediatr Dermatol. 2009;26:405-408.
3. Pompei DT, Rezzadeh KS, Viola KV, et al. Cantharidin therapy: practice patterns and attitudes of health care providers. J Am Acad Dermatol. 2013;68:1045-1046.

Up next: Autologous cell therapy for recessive dystrophic epidermolysis bullosa

Phase 1/2a Clinical Trial of Gene-Corrected Autologous Cell Therapy for Recessive Dystrophic Epidermolysis Bullosa

Shaundra Eichstadt, MD, Stanford University Department of Dermatology, Redwood City, California;  Tufts University Medical Center, Boston, Massachusetts 
Disclosures: None. 

Recessive dystrophic epidermolysis bullosa (RDEB) patients have mutations in the COL7A1 gene, thus lacking functional type VII collagen (C7) protein; they have marked skin fragility and blistering. This single-center phase 1/2a open-label study evaluated the long-term efficacy, safety, and patient-reported outcomes in RDEB patients treated with gene-corrected autologous cell therapy (ClinicalTrials.gov identifier NCT01263379). Autologous keratinocytes were isolated from participant skin biopsies. Epidermal sheets were prepared from cells transduced with a retrovirus carrying the full-length human COL7A1 gene. These gene-corrected autologous epidermal sheets measured 5×7 cm (35 cm²) and were transplanted onto 6 wound sites in each of 7 adult participants (N=42 sites) between 2013 and 2017. Participants were followed for 2 to 5 years. No participants experienced any serious related adverse events. Wound healing of 50% or more by Investigator Global Assessment was present in 95% (36/38) of treated wounds versus 0% (0/6) of untreated control wounds at 6 months (P<.0001). At year 1, 68% (26/38) of treated wounds had healing of 50% or more compared with 17% (1/6) of control wounds (P=.025). At year 2, 71% (27/38) of treated wounds had healing of 50% or more compared with 17% (1/6) of control wounds (P=.019). C7 expression persisted up to 2 years posttreatment in 2 participants. Treated wounds with 50% or more wound healing demonstrated improvement in patient-reported pain, itch, and wound durability. This study provides additional data to support the clinically meaningful benefit of treating chronic RDEB wounds with ex vivo, C7 gene-corrected autologous cell therapy. This approach was safe and promoted wound healing that was associated with improved patient-reported outcomes.

Up next: Skin toxicity in metastatic melanoma patients treated with ICIs

Nicholas Gulati, MD, PhD, NYU Grossman School of Medicine, New York, New York
Disclosures: None. 

Immune checkpoint inhibition (ICI) improves survival outcomes for patients with metastatic melanoma, but serious immune-related adverse events requiring intervention with immunosuppressive medications occur in a subset of patients. Skin toxicity (ST) has been reported to be associated with better response to ICI. However, understudied factors, such as ST severity and potential survivor bias, may influence the strength of these observed associations. To examine the potential confounding impact of such variables, we analyzed metastatic melanoma patients enrolled prospectively in a clinicopathological database with protocol-driven follow-up and treated with ICI. We tested the associations between developing ST, stratified as none (n=257), mild (n=86), and severe (n=44), and progression-free survival (PFS) and overall survival in univariable and multivariable analyses. We defined severe ST as a skin event that required treatment with systemic corticosteroids. To account for the possibility of longer survival leading to adverse events instead of the reverse, we treated ST as a time-dependent covariate in an adjusted model. Mild ST was significantly associated with improved PFS and overall survival (P=.001 and P=.018, respectively) in univariable analysis and with improved PFS in multivariable analysis (P=.020). However, these associations lost significance after adjusting for the time from treatment initiation to time of skin event (P>.05). Severe ST was not associated with improved outcomes. Our data reveal the influence of event severity and time to event as covariates in analyzing the relationship between ST and ICI outcomes. Further, we reinforce the importance of identifying baseline predictors of response and toxicity to ICI to optimize treatment selection and prophylactic care when indicated.

Up next: Risk of COVID-19 in patients receiving immunobiologic therapy

Nikolai Klebanov, MD, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts
Disclosures: None. 

Importance
Data on the risks of immunosuppressive biologics in the context of coronavirus disease 2019 (COVID-19) infection are limited, creating uncertainty for patients and providers whether to continue therapy during the pandemic.

Objective
To investigate whether patients treated with biologics were at an increased risk for COVID-19 infection as well as all-cause mortality once infected. 

Design
A multicenter retrospective study of 7361 patients prescribed biologics and 74,910 matched controls, cross-referenced with COVID-19 infection and all-cause mortality data through June 19, 2020, from the Massachusetts Department of Public Health.

Participants 
Patients with at least 1 prescription for an immunosuppressive biologic in the Mass General Brigham health care system between July 1, 2019, and February 29, 2020. Multivariate logistic regression was used on matched data to calculate the odds ratio (OR) for COVID-19 infection status between patients on biologics and controls, adjusting for age, gender, race, Charlson Comorbidity index (CCI) severity grade, median income, and local infection rate. An analysis adjusting for individual comorbidities was also performed. Multivariate Poisson regression was performed on COVID-19 positive patients to compare the risk for all-cause mortality, adjusting for gender, CCI severity grade, median income, and local COVID-19 rate.

Setting 
Retrospective matched cohort.

Exposure 
Biologic immunosuppressants.

Main Outcomes and Measures 
Odds of COVID-19 diagnosis and all-cause mortality following the diagnosis.

Results 
7,361 patients treated with biologics and 74,910 matched controls were included in the analysis (mean age, 50.6 years; 56.0% women, 84.5% white; mean age-adjusted CCI 2.8). There were 87 (1.2%) infections and 7 deaths (8.0%) in patients treated with biologics and 1063 (1.4%) infections and 71 deaths (6.7%) in the control group. Patients treated with immunosuppressive biologics were not at significantly increased risk of COVID-19 diagnosis (OR 0.88, 95% CI 0.71-1.09; P=.25) or subsequent mortality (OR 1.26, 95% CI 0.57-2.76; P=.57). 

A total of 7361 patients treated with biologics and 74,910 matched controls were included in the analysis (mean age, 50.6 years; 56.0% women and 84.5% white; mean age-adjusted CCI, 2.8). There were 87 (1.2%) infections and 7 deaths (8.0%) in patients treated with biologics, and 1063 (1.4%) infections and 71 deaths (6.7%) in the control group. Patients treated with immunosuppressive biologics were not at increased risk for COVID-19 diagnosis (OR, 0.88; 95% CI, 0.71-1.09; P=.25) or subsequent mortality (OR 1.26; 95% CI 0.57-2.76; P=.57). 

Conclusions and Relevance 
Given an absence of evidence that patients treated with biologics are more susceptible to COVID-19, patients should be encouraged to continue their therapy to prevent disease progression during this pandemic.

Up next: Compliance With Systemic Medications for AD and Psoriasis

Importance
The management of moderate to severe atopic dermatitis (AD) is being revolutionized by the development of novel systemic therapeutics. However, these new therapeutics are being implemented using the same treatment paradigms that are used for psoriasis treatment (ie, patients on systemic medications require indefinite therapy). While use of systemic therapeutics indefinitely is acceptable to many psoriasis patients because psoriasis severity is frequently stable over long periods of time, AD is hallmarked by seasonal flares followed by periods of relative quiescence, making indefinite therapy less attractive to patients with AD. 

Objective
This whole-population cohort study describes systemic medication adherence patterns in AD and psoriasis patients. These patterns are then compared to determine whether systemic medications requiring indefinite therapy are adhered to at similar rates in the AD and psoriasis populations. The aim of this comparison is to assess whether drugs requiring indefinite therapy meet the needs of AD patients requiring systemic treatment.

Design, Setting, and Participants 
This is a retrospective cohort study using the national Veterans Administration (VA) health database to identify all veterans with psoriasis and AD who are receiving care at any VA location. Veterans with psoriasis and AD were identified using International Classification of Diseases, Ninth Revision and Tenth Revision codes. Veterans were included in the study if they received nonsteroidal systemic immunosuppressive or immunomodulatory medications for their psoriasis or AD. 

Main Outcome(s) and Measure(s)
All medications filled at a VA pharmacy are time stamped. This unique data recording allows for real-world adherence to be evaluated by comparing actual medication fill dates to expected medication fill dates based on refill interval. Patients who fill a medication more than 7 days after the expected refill date are classified as nonadherent. We described systemic medication adherence rates and assessed for seasonal variation in adherence patterns for AD and psoriasis patients. Cofounding variables, including history of mental illness, substance use disorder, and patient income, were recorded and included in the analysis. 

Conclusions and Relevance 

This study's unique data source provides insight into the ways adherence patterns differ between individuals with AD and psoriasis, and insights into the ways mental illness, substance use, and poverty affect adherence to systemic therapeutics among dermatology patients with inflammatory skin conditions. 

The dermMentors™ Resident of Distinction Award™ recognizes top residents in dermatology. DermMentors.org and the dermMentors™ Resident of Distinction Award™ are sponsored by Beiersdorf Inc and administered by DermEd, Inc. The 2020 dermMentors™ Residents of Distinction™ presented new scientific research during the general sessions of the virtual 16th Annual Coastal Dermatology Symposium on October 16, 2020.

Overall Grand Prize
Topical Cantharidin Revisited: A Phase 2 Study Investigating a Commercially Viable Formulation of Cantharidin (VP-102) for the Treatment of Molluscum Contagiosum

Anthony K. Guzman, MD; Jessica L. Garelik, DO; Steven R. Cohen, MD, MPH, Department of Internal Medicine, Division of Dermatology, Albert Einstein College of Medicine, Bronx, New York 
Disclosures: None. 

Background 
Molluscum contagiosum (MC) is a common cutaneous infection caused by a DNA poxvirus, predominantly affecting children. There is a paucity of high-quality evidence on which to make clinical decisions in treating MC.¹ Cantharidin, a topical vesicant historically derived from a blister beetle, is a commonly used treatment for this condition. However, despite the prevalence of its use, cantharidin is not approved by the US Food and Drug Administration, is not standardized in formulation or treatment regimen, and is not always manufactured in accordance with good manufacturing practice (GMP), leading to a lack of commercial availability.^2,3

Objective 
To determine the efficacy and safety of VP-102, a novel, standardized, commercially viable cantharidin formulation produced under GMP for the treatment of MC.

Methods 
We conducted a 12-week, open-label pilot trial at a single outpatient dermatology clinic. Patients aged 2 to 17 years (N=30) with a clinical diagnosis of MC and fewer than 50 lesions were included. Patients were treated with a single-use vial containing a standardized 0.7% w/v cantharidin solution, produced under GMP (VP-102), applied with the wooden end of a cotton swab approximately every 21 days for up to 4 treatments or until complete lesion clearance. Patients were instructed to wash treatment off all lesions at either 6 hours (cohort 1: 14/30, 46.7%) or 24 hours (cohort 2: 16/30, 53.3%), or earlier if notable blistering occurred. Lesion counts and adverse events, including local skin reactions, were documented at each visit. Quality of life also was measured using the Children’s Dermatology Quality of Life Index at baseline and at the end of study (EOS). The primary end point was the percentage of patients achieving total clearance by EOS on day 84. 

Results 
The mean patient age was 5.8 years (range, 2–12 years). A total of 26 patients (86.7%) experienced at least 1 expected local skin reaction, such as blistering or erythema. No serious or unexpected treatment-related adverse events were encountered. A total of 25 patients pooled from both cohorts completed the study. Eleven patients (44.0%) achieved total lesion clearance by EOS. The mean (standard deviation) lesion count was significantly reduced from 23.0 (15.6) at baseline to 6.8 (11.7) at EOS (P<.0001). The mean (standard deviation) Children’s Dermatology Quality of Life Index score was markedly improved from 3.9 (5.6) at baseline to 0.38 (1.3) at EOS (P=.01).

Conclusions 
VP-102 was well tolerated with either a 6- or 24-hour exposure and was associated with a significantly reduced lesion count, improved quality of life, and complete clearance of MC lesions in nearly half of the patients.

References

1. van der Wouden JC, van der Sande R, Kruithof EJ, et al. Interventions for cutaneous molluscum contagiosum. Cochrane Database Syst Rev. 2017;5:CD004767.
2. Coloe J, Morrell DS. Cantharidin use among pediatric dermatologists in the treatment of molluscum contagiosum. Pediatr Dermatol. 2009;26:405-408.
3. Pompei DT, Rezzadeh KS, Viola KV, et al. Cantharidin therapy: practice patterns and attitudes of health care providers. J Am Acad Dermatol. 2013;68:1045-1046.

Up next: Autologous cell therapy for recessive dystrophic epidermolysis bullosa

Phase 1/2a Clinical Trial of Gene-Corrected Autologous Cell Therapy for Recessive Dystrophic Epidermolysis Bullosa

Shaundra Eichstadt, MD, Stanford University Department of Dermatology, Redwood City, California;  Tufts University Medical Center, Boston, Massachusetts 
Disclosures: None. 

Recessive dystrophic epidermolysis bullosa (RDEB) patients have mutations in the COL7A1 gene, thus lacking functional type VII collagen (C7) protein; they have marked skin fragility and blistering. This single-center phase 1/2a open-label study evaluated the long-term efficacy, safety, and patient-reported outcomes in RDEB patients treated with gene-corrected autologous cell therapy (ClinicalTrials.gov identifier NCT01263379). Autologous keratinocytes were isolated from participant skin biopsies. Epidermal sheets were prepared from cells transduced with a retrovirus carrying the full-length human COL7A1 gene. These gene-corrected autologous epidermal sheets measured 5×7 cm (35 cm²) and were transplanted onto 6 wound sites in each of 7 adult participants (N=42 sites) between 2013 and 2017. Participants were followed for 2 to 5 years. No participants experienced any serious related adverse events. Wound healing of 50% or more by Investigator Global Assessment was present in 95% (36/38) of treated wounds versus 0% (0/6) of untreated control wounds at 6 months (P<.0001). At year 1, 68% (26/38) of treated wounds had healing of 50% or more compared with 17% (1/6) of control wounds (P=.025). At year 2, 71% (27/38) of treated wounds had healing of 50% or more compared with 17% (1/6) of control wounds (P=.019). C7 expression persisted up to 2 years posttreatment in 2 participants. Treated wounds with 50% or more wound healing demonstrated improvement in patient-reported pain, itch, and wound durability. This study provides additional data to support the clinically meaningful benefit of treating chronic RDEB wounds with ex vivo, C7 gene-corrected autologous cell therapy. This approach was safe and promoted wound healing that was associated with improved patient-reported outcomes.

Up next: Skin toxicity in metastatic melanoma patients treated with ICIs

Nicholas Gulati, MD, PhD, NYU Grossman School of Medicine, New York, New York
Disclosures: None. 

Immune checkpoint inhibition (ICI) improves survival outcomes for patients with metastatic melanoma, but serious immune-related adverse events requiring intervention with immunosuppressive medications occur in a subset of patients. Skin toxicity (ST) has been reported to be associated with better response to ICI. However, understudied factors, such as ST severity and potential survivor bias, may influence the strength of these observed associations. To examine the potential confounding impact of such variables, we analyzed metastatic melanoma patients enrolled prospectively in a clinicopathological database with protocol-driven follow-up and treated with ICI. We tested the associations between developing ST, stratified as none (n=257), mild (n=86), and severe (n=44), and progression-free survival (PFS) and overall survival in univariable and multivariable analyses. We defined severe ST as a skin event that required treatment with systemic corticosteroids. To account for the possibility of longer survival leading to adverse events instead of the reverse, we treated ST as a time-dependent covariate in an adjusted model. Mild ST was significantly associated with improved PFS and overall survival (P=.001 and P=.018, respectively) in univariable analysis and with improved PFS in multivariable analysis (P=.020). However, these associations lost significance after adjusting for the time from treatment initiation to time of skin event (P>.05). Severe ST was not associated with improved outcomes. Our data reveal the influence of event severity and time to event as covariates in analyzing the relationship between ST and ICI outcomes. Further, we reinforce the importance of identifying baseline predictors of response and toxicity to ICI to optimize treatment selection and prophylactic care when indicated.

Up next: Risk of COVID-19 in patients receiving immunobiologic therapy

Nikolai Klebanov, MD, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts
Disclosures: None. 

Importance
Data on the risks of immunosuppressive biologics in the context of coronavirus disease 2019 (COVID-19) infection are limited, creating uncertainty for patients and providers whether to continue therapy during the pandemic.

Objective
To investigate whether patients treated with biologics were at an increased risk for COVID-19 infection as well as all-cause mortality once infected. 

Design
A multicenter retrospective study of 7361 patients prescribed biologics and 74,910 matched controls, cross-referenced with COVID-19 infection and all-cause mortality data through June 19, 2020, from the Massachusetts Department of Public Health.

Participants 
Patients with at least 1 prescription for an immunosuppressive biologic in the Mass General Brigham health care system between July 1, 2019, and February 29, 2020. Multivariate logistic regression was used on matched data to calculate the odds ratio (OR) for COVID-19 infection status between patients on biologics and controls, adjusting for age, gender, race, Charlson Comorbidity index (CCI) severity grade, median income, and local infection rate. An analysis adjusting for individual comorbidities was also performed. Multivariate Poisson regression was performed on COVID-19 positive patients to compare the risk for all-cause mortality, adjusting for gender, CCI severity grade, median income, and local COVID-19 rate.

Setting 
Retrospective matched cohort.

Exposure 
Biologic immunosuppressants.

Main Outcomes and Measures 
Odds of COVID-19 diagnosis and all-cause mortality following the diagnosis.

Results 
7,361 patients treated with biologics and 74,910 matched controls were included in the analysis (mean age, 50.6 years; 56.0% women, 84.5% white; mean age-adjusted CCI 2.8). There were 87 (1.2%) infections and 7 deaths (8.0%) in patients treated with biologics and 1063 (1.4%) infections and 71 deaths (6.7%) in the control group. Patients treated with immunosuppressive biologics were not at significantly increased risk of COVID-19 diagnosis (OR 0.88, 95% CI 0.71-1.09; P=.25) or subsequent mortality (OR 1.26, 95% CI 0.57-2.76; P=.57). 

A total of 7361 patients treated with biologics and 74,910 matched controls were included in the analysis (mean age, 50.6 years; 56.0% women and 84.5% white; mean age-adjusted CCI, 2.8). There were 87 (1.2%) infections and 7 deaths (8.0%) in patients treated with biologics, and 1063 (1.4%) infections and 71 deaths (6.7%) in the control group. Patients treated with immunosuppressive biologics were not at increased risk for COVID-19 diagnosis (OR, 0.88; 95% CI, 0.71-1.09; P=.25) or subsequent mortality (OR 1.26; 95% CI 0.57-2.76; P=.57). 

Conclusions and Relevance 
Given an absence of evidence that patients treated with biologics are more susceptible to COVID-19, patients should be encouraged to continue their therapy to prevent disease progression during this pandemic.

Up next: Compliance With Systemic Medications for AD and Psoriasis

Importance
The management of moderate to severe atopic dermatitis (AD) is being revolutionized by the development of novel systemic therapeutics. However, these new therapeutics are being implemented using the same treatment paradigms that are used for psoriasis treatment (ie, patients on systemic medications require indefinite therapy). While use of systemic therapeutics indefinitely is acceptable to many psoriasis patients because psoriasis severity is frequently stable over long periods of time, AD is hallmarked by seasonal flares followed by periods of relative quiescence, making indefinite therapy less attractive to patients with AD. 

Objective
This whole-population cohort study describes systemic medication adherence patterns in AD and psoriasis patients. These patterns are then compared to determine whether systemic medications requiring indefinite therapy are adhered to at similar rates in the AD and psoriasis populations. The aim of this comparison is to assess whether drugs requiring indefinite therapy meet the needs of AD patients requiring systemic treatment.

Design, Setting, and Participants 
This is a retrospective cohort study using the national Veterans Administration (VA) health database to identify all veterans with psoriasis and AD who are receiving care at any VA location. Veterans with psoriasis and AD were identified using International Classification of Diseases, Ninth Revision and Tenth Revision codes. Veterans were included in the study if they received nonsteroidal systemic immunosuppressive or immunomodulatory medications for their psoriasis or AD. 

Main Outcome(s) and Measure(s)
All medications filled at a VA pharmacy are time stamped. This unique data recording allows for real-world adherence to be evaluated by comparing actual medication fill dates to expected medication fill dates based on refill interval. Patients who fill a medication more than 7 days after the expected refill date are classified as nonadherent. We described systemic medication adherence rates and assessed for seasonal variation in adherence patterns for AD and psoriasis patients. Cofounding variables, including history of mental illness, substance use disorder, and patient income, were recorded and included in the analysis. 

Conclusions and Relevance 

This study's unique data source provides insight into the ways adherence patterns differ between individuals with AD and psoriasis, and insights into the ways mental illness, substance use, and poverty affect adherence to systemic therapeutics among dermatology patients with inflammatory skin conditions.