- Email: [email protected]
UV exposure in outdoor workers and the risk of developing nonmelanoma skin cancers (NMSC)
4377
Utilization of 440-nm blue light to target Propionibacterium acnes for treating acne vulgaris Jeff Boyd, Rutgers University; Sharrron Crane, Rutgers University; Kelly Dunn, Johnson & Johnson Consumer Inc.; Ali Fassih, Johnson & Johnson Consumer Inc.; Wen-Hwa Li, Johnson & Johnson Consumer Inc.; Davide Miksa, Johnson & Johnson Consumer Inc.; Juan Villegas, Rutgers University; Michael D. Southall, Johnson & Johnson Consumer Inc. Background: Acne vulgaris is a common skin condition affecting many sufferers including teens and adults. Light therapy has been used by dermatologists for decades as an effective treatment for acne and now at-home blue light therapy devices using light emitting diodes (LED) are available for acne patients as an additional treatment option. Blue light treatments used clinically have utilized blue light wavelengths between 405-420 nm targeting chromophores including the porphyrin cororphyrin III which are present in Propionibacterium acnes. Recent studies suggest the visible light in these wavelengths may induce subclinical inflammation and subsequently activate photo-damage pathways. We therefore investigated the hypothesis that LEDs emitting 440 nm blue light to deliver photons to P acnes results in photobiochemical reactions and subsequent antibacterial activity for P acnes without inducing sub-clinical inflammation. Methodology: Two in vitro models have been developed using LED photomodulation to monitor cellular death of bacterial strains including P acnes. Conclusion: Exposure of P acnes to 440 nm light resulted in bacterial cell death. This antibacterial activity was dependent on both time of exposure and light intensity. Preliminary data suggests that porphyrin production has a role in the 440 nm light mediated antibacterial activity. The production of chromophores by human commensal bacteria is thought to be unique, and therefore, treatment with 440 nm light was expected to selectively target organisms producing these compounds such as P. acnes. Exposure to the Gram-positive bacteria Staphylococcus epidermidis and Bacillus subtilis, as well as the Gram-negative bacterium Salmonella enterica to 440nm light at LED intensities that kill P acnes had no effect of cell viability of non-P acnes bacteria suggesting that 440nm treatment is somewhat selective for P acnes. The work presented demonstrates the antimicrobial activity of 440 nm blue light against P acnes—a causative agent of acne vulgaris. Collectively, the findings presented suggest that low-level light therapy using 440 nm blue light may provide an effective and safe treatment for acne vulgaris.
5810 UV exposure in outdoor workers and the risk of developing nonmelanoma skin cancers (NMSC) Ionela Manole, Colentina Clinical Hospital Outdoor workers (eg, construction workers, agriculture workers) are exposed to more sunlight and therefore to more carcinogenic ultraviolet radiation than other workers. It is estimated that outdoor workers are exposed to an ultraviolet radiation (UVR) dose 2-3 times higher than indoor workers and there is a growing body of research linking UV radiation exposure in outdoor workers to NMSC (ie, basal cell carcinoma, squamous cell carcinoma, actinic keratoses). This segment of population is crucial for the society and it is important to keep those adults healthy or to identify and treat as soon as possible all diseases that can remove them from work. It was performed a prospective, observational, analytical study of six outdoor workers (construction workers, agriculture workers), over a period of three summer months (July-September). The subjects recorded in diaries information like date, location, profession, start time and end time of the program, breaks during the day and weather conditions. Their UVR doses were measured by personal UVR dosimeters (X-2012-10 Personal UV Irradiance Dosimeter) worn on the arm. Sun-exposed areas were the face, ears, neck, forearms and hands, the remaining areas being covered by clothing. The subjects were examined before and after the measurements to detect any changes of the skin. Subject’ average daily UVR exposure on outdoor activities ranged from 1.79 SED (farm car driver) to 19 SED (agriculture worker). The maximum dose of exposure was between the hours 10: 00-16: 00. The measured values are very high as compared with the average exposure of general population of 130 SED / year. On clinical examination performed at the end of the agricultural season, no skin changes have been detected; the subjects did not shown any clinical signs of melanoma or NMSC. Our results emphasize the importance of changing the behavior of outdoor workers and the use of protective measures to reduce their personal annual UVR exposure doses, and possibly their risk of skin cancer. Future research activities should focus on the precise definition of at-risk groups among outdoor workers through increased data gathering, including UV-dosimetry, and evaluation. Commercial support: None identified.
Commercial support: Study sponsored by Johnson & Johnson Consumer Inc.
5063
5431 Utilization of a new IT platform promoted globally through social media to apply continuous quality improvement assessments to deliver patient-centered care in those with autoimmune diseases Katelyn Updyke, BS, University of Central Florida College of Medicine; Brittany Urso, BS, University of Central Florida College of Medicine; Jennifer Nergard, BS, University of Central Florida College of medicine; Renee Domozych, BS, University of Central Florida College of Medicine; Ian Brooks, PhD, University of Illinois:; James Solomon, MD, Ameriderm Research Autoimmune diseases are conditions in which the patient has developed autoantibodies containing self-antigen that cause disease through tissue inflammation and multiorgan damage. Patients often experience exacerbations in their symptoms without known cause. This unpredictability in disease state often negatively impacts patients’ quality of life. New continuous quality improvement assessment survey platform will be developed and utilized to reach out to patients affected by autoimmune diseases across the globe. This new platform will allow participants to log in and out of the survey enabling them to address 20-50 pages of questions at baseline as well as to edit this delving into the minutia of the activities of daily living as well as lifestyle, diet, and exposures. These exposures can be helpful or harmful to this patient population. Patients will be asked to update survey responses monthly to capture changes in lifestyle and health as data points over time. Statistical analysis array using complex adaptive systems methodology will be performed on deidentified patient surveys in order to determine if patterns exist in subgroups of autoimmune disease affected patients who experience fluctuations in their disease state over time. Feedback will be given to patients who are then able to adapt accordingly while they participate in the study. Interpretations of this data will then be used to identify which exogenous exposures influence symptoms of these various disease processes in specific subgroups of patients. This information will then be used to make improvements in treatment plans for autoimmune diseases, and will ultimately result in enhancing the value of patient care. Commercial support: None identified.
AB278
J AM ACAD DERMATOL
Validation of the peak pruritus numerical rating scale: Results from clinical studies of dupilumab in adult patients with moderate-to-severe atopic dermatitis Gil Yosipovitch, MD, Miami School of Medicine; Matthew Reaney, Sanofi; Vera Mastey, B Pharm, Regeneron Pharmaceuticals, Inc.; Laurent Eckert, PhD, Sanofi; Lauren Nelson, PhD, RTI Health Solutions; Marci Clark, PharmD, RTI Health Solutions; Marius Ardeleanu, MD, Regeneron Pharmaceuticals, Inc; Allen Radin, MD, Regeneron Pharmaceuticals, Inc.; Abhijit Gadkari, PhD, Regeneron Pharmaceuticals, Inc Objective: To conduct content validation and psychometric assessment of the Peak Pruritus Numerical Rating Scale (PP-NRS) for measuring itch in patients with moderate-to-severe atopic dermatitis (AD). Methods: The PP-NRS is a single, self-completed item to assess the intensity of peak (worst) pruritus during the past 24 hours: ‘‘On a scale of 0 to 10, with 0 being ‘no itch’ and 10 being ‘worst itch imaginable’, how would you rate your itch at the worst moment during the previous 24 hours?’’ Content validation included interviews with US adults with AD self-reporting moderate-to-severe itch (n ¼ 14). Psychometric properties were assessed in a phase 2b (P2b) study (N ¼ 379; NCT01859988) and confirmed using pooled data from two phase 3 (P3) studies (N ¼ 1,379; NCT02277743, NCT02277769) in moderate-to-severe adult AD patients. Participants completed the PP-NRS once daily through end of treatment (Week 16). The analysis includes patients receiving $1 subcutaneous dose of dupilumab/placebo with $1 post-baseline PP-NRS assessment. Patient- and clinician-reported outcome measures (PROs and ClinROs) were used to examine cross-sectional (construct and known-groups validity) and longitudinal (test-retest and sensitivity to change) measurement properties. Results: Interview participants interpreted the PP-NRS consistently, and found it relevant, clear, comprehensive, and easy to select a response aligned with their personal rating of peak pruritus in the past 24 hours. In the P2b study, large positive baseline correlations were observed between PP-NRS and measures of similar constructs (Average Pruritus NRS [r ¼ 1.00], SCORAD itch VAS [r ¼ 0.77], Dermatology Life Quality Index (DLQI) itch item [r ¼ 0.67], P \.01 for all), and weak-to-moderate correlations with measures of different constructs (EASI [r ¼ 0.09] and Investigator’s Global Assessment (IGA) [r ¼ 0.17, P \ .01]). Similar relationships were observed in the P3 studies. The PP-NRS differed predictably and significantly across known groups (P \.0001) in P2b and P3. Intraclass correlation coefficients of the test-retest analysis were $0.95 in P2b and P3. Moderate-to-strong correlations of change were observed on the PP-NRS with PROs (P2b/P3 SCORAD itch VAS r ¼ 0.77/0.73; DLQI itch item r ¼ 0.66/0.64; PCS r ¼ 0.71/0.72) and ClinROs (EASI, r ¼ 0.50/0.46; IGA, r ¼ 0.50/0.46) (P \.01 for all). Conclusions: Peak Pruritus NRS is a well-defined, reliable, sensitive, and valid scale to assess itch intensity in adult patients with moderate-to-severe AD. Commercial support: Research sponsored by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc. ClinicalTrials.gov Identifiers: NCT01859988, NCT02277743, and NCT02277769. Editorial assistance provided by Sven Holm, PhD, of Excerpta Medica, funded by Sanofi Genzyme and Regeneron.
JUNE 2017
Utilization of 440-nm blue light to target Propionibacterium acnes for treating acne vulgaris Jeff Boyd, Rutgers University; Sharrron Crane, Rutgers University; Kelly Dunn, Johnson & Johnson Consumer Inc.; Ali Fassih, Johnson & Johnson Consumer Inc.; Wen-Hwa Li, Johnson & Johnson Consumer Inc.; Davide Miksa, Johnson & Johnson Consumer Inc.; Juan Villegas, Rutgers University; Michael D. Southall, Johnson & Johnson Consumer Inc. Background: Acne vulgaris is a common skin condition affecting many sufferers including teens and adults. Light therapy has been used by dermatologists for decades as an effective treatment for acne and now at-home blue light therapy devices using light emitting diodes (LED) are available for acne patients as an additional treatment option. Blue light treatments used clinically have utilized blue light wavelengths between 405-420 nm targeting chromophores including the porphyrin cororphyrin III which are present in Propionibacterium acnes. Recent studies suggest the visible light in these wavelengths may induce subclinical inflammation and subsequently activate photo-damage pathways. We therefore investigated the hypothesis that LEDs emitting 440 nm blue light to deliver photons to P acnes results in photobiochemical reactions and subsequent antibacterial activity for P acnes without inducing sub-clinical inflammation. Methodology: Two in vitro models have been developed using LED photomodulation to monitor cellular death of bacterial strains including P acnes. Conclusion: Exposure of P acnes to 440 nm light resulted in bacterial cell death. This antibacterial activity was dependent on both time of exposure and light intensity. Preliminary data suggests that porphyrin production has a role in the 440 nm light mediated antibacterial activity. The production of chromophores by human commensal bacteria is thought to be unique, and therefore, treatment with 440 nm light was expected to selectively target organisms producing these compounds such as P. acnes. Exposure to the Gram-positive bacteria Staphylococcus epidermidis and Bacillus subtilis, as well as the Gram-negative bacterium Salmonella enterica to 440nm light at LED intensities that kill P acnes had no effect of cell viability of non-P acnes bacteria suggesting that 440nm treatment is somewhat selective for P acnes. The work presented demonstrates the antimicrobial activity of 440 nm blue light against P acnes—a causative agent of acne vulgaris. Collectively, the findings presented suggest that low-level light therapy using 440 nm blue light may provide an effective and safe treatment for acne vulgaris.
5810 UV exposure in outdoor workers and the risk of developing nonmelanoma skin cancers (NMSC) Ionela Manole, Colentina Clinical Hospital Outdoor workers (eg, construction workers, agriculture workers) are exposed to more sunlight and therefore to more carcinogenic ultraviolet radiation than other workers. It is estimated that outdoor workers are exposed to an ultraviolet radiation (UVR) dose 2-3 times higher than indoor workers and there is a growing body of research linking UV radiation exposure in outdoor workers to NMSC (ie, basal cell carcinoma, squamous cell carcinoma, actinic keratoses). This segment of population is crucial for the society and it is important to keep those adults healthy or to identify and treat as soon as possible all diseases that can remove them from work. It was performed a prospective, observational, analytical study of six outdoor workers (construction workers, agriculture workers), over a period of three summer months (July-September). The subjects recorded in diaries information like date, location, profession, start time and end time of the program, breaks during the day and weather conditions. Their UVR doses were measured by personal UVR dosimeters (X-2012-10 Personal UV Irradiance Dosimeter) worn on the arm. Sun-exposed areas were the face, ears, neck, forearms and hands, the remaining areas being covered by clothing. The subjects were examined before and after the measurements to detect any changes of the skin. Subject’ average daily UVR exposure on outdoor activities ranged from 1.79 SED (farm car driver) to 19 SED (agriculture worker). The maximum dose of exposure was between the hours 10: 00-16: 00. The measured values are very high as compared with the average exposure of general population of 130 SED / year. On clinical examination performed at the end of the agricultural season, no skin changes have been detected; the subjects did not shown any clinical signs of melanoma or NMSC. Our results emphasize the importance of changing the behavior of outdoor workers and the use of protective measures to reduce their personal annual UVR exposure doses, and possibly their risk of skin cancer. Future research activities should focus on the precise definition of at-risk groups among outdoor workers through increased data gathering, including UV-dosimetry, and evaluation. Commercial support: None identified.
Commercial support: Study sponsored by Johnson & Johnson Consumer Inc.
5063
5431 Utilization of a new IT platform promoted globally through social media to apply continuous quality improvement assessments to deliver patient-centered care in those with autoimmune diseases Katelyn Updyke, BS, University of Central Florida College of Medicine; Brittany Urso, BS, University of Central Florida College of Medicine; Jennifer Nergard, BS, University of Central Florida College of medicine; Renee Domozych, BS, University of Central Florida College of Medicine; Ian Brooks, PhD, University of Illinois:; James Solomon, MD, Ameriderm Research Autoimmune diseases are conditions in which the patient has developed autoantibodies containing self-antigen that cause disease through tissue inflammation and multiorgan damage. Patients often experience exacerbations in their symptoms without known cause. This unpredictability in disease state often negatively impacts patients’ quality of life. New continuous quality improvement assessment survey platform will be developed and utilized to reach out to patients affected by autoimmune diseases across the globe. This new platform will allow participants to log in and out of the survey enabling them to address 20-50 pages of questions at baseline as well as to edit this delving into the minutia of the activities of daily living as well as lifestyle, diet, and exposures. These exposures can be helpful or harmful to this patient population. Patients will be asked to update survey responses monthly to capture changes in lifestyle and health as data points over time. Statistical analysis array using complex adaptive systems methodology will be performed on deidentified patient surveys in order to determine if patterns exist in subgroups of autoimmune disease affected patients who experience fluctuations in their disease state over time. Feedback will be given to patients who are then able to adapt accordingly while they participate in the study. Interpretations of this data will then be used to identify which exogenous exposures influence symptoms of these various disease processes in specific subgroups of patients. This information will then be used to make improvements in treatment plans for autoimmune diseases, and will ultimately result in enhancing the value of patient care. Commercial support: None identified.
AB278
J AM ACAD DERMATOL
Validation of the peak pruritus numerical rating scale: Results from clinical studies of dupilumab in adult patients with moderate-to-severe atopic dermatitis Gil Yosipovitch, MD, Miami School of Medicine; Matthew Reaney, Sanofi; Vera Mastey, B Pharm, Regeneron Pharmaceuticals, Inc.; Laurent Eckert, PhD, Sanofi; Lauren Nelson, PhD, RTI Health Solutions; Marci Clark, PharmD, RTI Health Solutions; Marius Ardeleanu, MD, Regeneron Pharmaceuticals, Inc; Allen Radin, MD, Regeneron Pharmaceuticals, Inc.; Abhijit Gadkari, PhD, Regeneron Pharmaceuticals, Inc Objective: To conduct content validation and psychometric assessment of the Peak Pruritus Numerical Rating Scale (PP-NRS) for measuring itch in patients with moderate-to-severe atopic dermatitis (AD). Methods: The PP-NRS is a single, self-completed item to assess the intensity of peak (worst) pruritus during the past 24 hours: ‘‘On a scale of 0 to 10, with 0 being ‘no itch’ and 10 being ‘worst itch imaginable’, how would you rate your itch at the worst moment during the previous 24 hours?’’ Content validation included interviews with US adults with AD self-reporting moderate-to-severe itch (n ¼ 14). Psychometric properties were assessed in a phase 2b (P2b) study (N ¼ 379; NCT01859988) and confirmed using pooled data from two phase 3 (P3) studies (N ¼ 1,379; NCT02277743, NCT02277769) in moderate-to-severe adult AD patients. Participants completed the PP-NRS once daily through end of treatment (Week 16). The analysis includes patients receiving $1 subcutaneous dose of dupilumab/placebo with $1 post-baseline PP-NRS assessment. Patient- and clinician-reported outcome measures (PROs and ClinROs) were used to examine cross-sectional (construct and known-groups validity) and longitudinal (test-retest and sensitivity to change) measurement properties. Results: Interview participants interpreted the PP-NRS consistently, and found it relevant, clear, comprehensive, and easy to select a response aligned with their personal rating of peak pruritus in the past 24 hours. In the P2b study, large positive baseline correlations were observed between PP-NRS and measures of similar constructs (Average Pruritus NRS [r ¼ 1.00], SCORAD itch VAS [r ¼ 0.77], Dermatology Life Quality Index (DLQI) itch item [r ¼ 0.67], P \.01 for all), and weak-to-moderate correlations with measures of different constructs (EASI [r ¼ 0.09] and Investigator’s Global Assessment (IGA) [r ¼ 0.17, P \ .01]). Similar relationships were observed in the P3 studies. The PP-NRS differed predictably and significantly across known groups (P \.0001) in P2b and P3. Intraclass correlation coefficients of the test-retest analysis were $0.95 in P2b and P3. Moderate-to-strong correlations of change were observed on the PP-NRS with PROs (P2b/P3 SCORAD itch VAS r ¼ 0.77/0.73; DLQI itch item r ¼ 0.66/0.64; PCS r ¼ 0.71/0.72) and ClinROs (EASI, r ¼ 0.50/0.46; IGA, r ¼ 0.50/0.46) (P \.01 for all). Conclusions: Peak Pruritus NRS is a well-defined, reliable, sensitive, and valid scale to assess itch intensity in adult patients with moderate-to-severe AD. Commercial support: Research sponsored by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc. ClinicalTrials.gov Identifiers: NCT01859988, NCT02277743, and NCT02277769. Editorial assistance provided by Sven Holm, PhD, of Excerpta Medica, funded by Sanofi Genzyme and Regeneron.
JUNE 2017