- Email: [email protected]
Nga mice
P37
Acne
STEROID-SPARING EFFECT OF AN EMOLLIENT IN THE TREATMENT OF MILD TO MODERATE ATOPIC DERMATITIS IN CHILDREN Philippe Msika, Nathalie Piccardi, Jean Christophe Choulot, Bernard Chadoutaud, Laboratoires Expanscience, Epernon, France
P100
The application of emollients is widely recommended as a first-line therapy in atopic dermatitis. It is safe and it improves quality of life of the children and their parents. Additionally, it may allow application of a lesser amount of topical steroids during crisis and thus prevent skin atrophy. An emollient specifically formulated for atopic dermatitis has been studied. It contains 2% of a patented sunflower oleodistillate, obtained by molecular distillation and composed of 90% essential lipids (linoleic and oleic triglycerides), 5% phytosterols (beta-sitosterol), and 1% vitamin E. It has been shown to statistically increase the neosynthesis of cerebrosides, ceramides, and cholesterol when applied on human skin explant. This emollient also contains a multi-lamellar system composed by phytosphingosins E, cholesterol, and ceramides 3, 6, 1, mimicking lipids of the stratum corneum. A large multicenter study with 35 pediatricians including 175 atopic children was conducted for a 3-week period. The children were divided into 5 groups: A: desonide 0.05 %, 2 3 1 day; B: desonide 0.05%, 2 3 1 day + emollient 2 3 1 day; C: desonide 0.05%, 131 day; D: desonide 0.05%, 1 3 1 day + emollient 2 3 1 day; E: desonide 0.05%, 1 3 2 days + emollient 2 3 1 day. SCORAD score (SCORing Atopic Dermatitis) has been calculated at J0, J7, and J21; quality of life was evaluated at J0, J30. Preliminary results for 63 children show that the emollient improves effacy of steroids (B vs A) with a decrease of the SCORAD score of 86% vs 70% and improves quality of life (86% vs 64%). The emollient has a steroid-sparing effect: D vs A (steroids 1 3 1 day + emollients vs steroid 2 3 1 day alone) shows similar results: ÿ75% SCORAD score vs ÿ70%; E vs A (steroids one every other day + emollients vs steroid 2 3 1 day alone) idem with ÿ73% vs ÿ70%.
A META-ANALYSIS OF THE ANTI-INFLAMMATORY ACTIVITY OF TRETINOIN GEL Robert Day, PhD, Marge Nighland, BSc, Johnson & Johnson Consumer and Personal Products Worldwide, Skillman, NJ, United States The objective of this study was to analyze the integrated statistical analysis of the inflammatory lesion data from the two pivotal double-blind, placebo-controlled trials of tretinoin gel microsphere 0.04% to determine the efficacy of tretinoin gel microsphere 0.04% in the treatment of inflammatory lesions of acne vulgaris. A total of 451 patients were randomized to tretinoin gel microsphere 0.04% or vehicle. The statistical analysis included ITT/LOCF minus duplicate patients (19 patients) for the analyses combined across protocols. Results of combined studies of tretinoin gel microsphere 0.04% demonstrate the superiority of active drug over vehicle treatment in the reduction of inflammatory lesions. At 12 weeks (end of study) tretinoin gel 0.04% had statistically significant reductions (P \ .00125) of 43.3% compared with 22.2% for vehicle. Treatment superiority versus vehicle was consistently present at 2, 4, 6, 8, 10, and 12 weeks for percent reduction in inflammatory lesions. Treatment superiority emerges as early as week 2 with reductions of 14.8% for tretinoin gel microsphere 0.04% versus 0.5% for vehicle. This meta-analysis confirms that tretinoin gel microsphere 0.04% results in a rapid reduction in inflammatory lesions in acne vulgaris as early as 2 weeks after beginning treatment. Superior efficacy is maintained throughout the 12-week treatment period.
In conclusion, our 3-week comparative study on atopic children found that this emollient, containing a patented sunflower oleodistillate, can decrease the frequency of application of a topical steroid by a factor of 4.
Bibliography Management of acne—A report from a global alliance to improve outcomes in acne. J Am Acad Dermatol 2003:49:??.
P. Msika, N. Piccardi and J. C. Choulot are all employees of Laboratoires Expanscience. 100% supported by Laboratoires Expanscience
Dr. Day, Ms. Nighland, and Rachel Grossman are employees of Johnson & Johnson. Mark Van Buskirk received financial support from Johnson & Johnson for statistical services. 100% sponsored by Johnson & Johnson
P101 A MULTI-CENTER, INVESTIGATOR-BLIND CLINICAL TRIAL TO ASSESS THE SAFETY AND EFFICACY OF METRONIDAZOLE GEL 1% AS COMPARED TO METRONIDAZOLE GEL VEHICLE AND METRONIDAZOLE CREAM 1% IN THE TREATMENT OF ROSACEA Karl Beutner, MD, PhD, Barry Calvarese, MS, Dow Pharmaceuticals Sciences, Petaluma, CA, United States; Michael Graeber, MD, Galderma R&D Inc, Princeton, NJ, United States Objectives: To show the noninferiority of metronidazole gel 1% to metronidazole cream 1% in the treatment of rosacea, to show its superiority over its gel vehicle, and to evaluate safety and tolerability of the treatments.
P38 EFFECTS OF DA-9102 ON ATOPIC DERMATITIS IN NC/NgA MICE In-Ki Lee, MS, Miwon Son, PhD, Soon-Hoe Kim, PhD, Research Laboratories of Dong-A Pharmaceutical Co., Ltd., Yongin, Korea; Kyu-Han Kim, MD, PhD, Department of Dermatology, Seoul National University Hospital, Seoul, Korea Atopic dermatitis is a chronic, itchy, inflammatory skin disease that usually develops in early childhood. Although the origin of atopic dermatitis remains unclear, it has been shown that both Th1 and Th2 cytokines play pathogenic roles in the generation of atopic dermatitis. DA-9102 is an extract from Actinidia species containing an immune-modulating activity for allergy-related disease. We have examined whether DA-9102 suppresses the development of atopic dermatitis-like skin lesions in NC/Nga mice. NC/Nga mice were given daily DA-9102 starting at 6 weeks of age. Drugs were orally administered to the mice. The efficacy of DA-9102 in NC/Nga mice was judged by measurement of skin severity, scratching behavior, and plasma immunoglobulin levels (IgE, IgG1, and IgG2a). Dermatitis developed in control mice from 10 weeks of age continuously. However, oral administration of DA-9102 (100 mg/kg) suppressed the development of dermatitis. The skin severity score of the control group reached 5.3 6 2.0 at 13 weeks of age, whereas that of DA-9102 was 2.7 6 1.3. The plasma IgE level increased gradually with age, and treatment with DA-9102 reduced the plasma IgE level. The plasma IgE level was 3541.5 6 641.2 ng/mL for the control group but 1442.2 6 343.85 ng/mL for the DA9102-administered group after 7 weeks of administration (P \.05). Oral administration of DA-9102 also had an inhibitory effect on plasma IgG1 levels (control group, 2617.5 6 358.9 g/mL; DA-9102-administered group, 1034.9 6 100.9 g/mL; P \.01). However, the plasma IgG2a level was not affected. At the age of 13 weeks, we counted the amount of time scratching behaviors occurred during a 20minute period. The time of scratching decreased twofold after oral administration of DA-9102. These observations suggest that DA-9102 can be expected to be a useful drug for atopic dermatitis. Nothing to disclose.
P10
J AM ACAD DERMATOL
Methods: This was a multicenter, randomized, investigator-blind, active- and vehiclecontrolled, parallel comparison involving adult subjects of any race with rosacea. Subjects applied metronidazole gel 1%, metronidazole cream 1%, or metronidazole gel vehicle to the face once daily at bedtime for 10 weeks with evaluations at 2, 4, 7, and 10 weeks after baseline. Evaluations included inflammatory lesion count for forehead, chin, nose, right cheek, and left cheek at each visit and a blinded assessment of the signs and symptoms of rosacea (Investigator’s Global Severity Score; GSS). Primary efficacy analysis variables were percent reduction from baseline in inflammatory lesion counts at week 10 and percent of subjects rated as successes (clear or almost clear) in the dichotomized Investigator’s GSS at week 10. For the week 10 analysis in the ITT population, the median reduction in inflammatory lesion counts was 66.7% in the gel group, 58.3% in the cream group, and 46.2% in the gel vehicle group. Based on the primary analysis of week 10 LOCF data in the ITT population, metronidazole gel demonstrated superiority over its vehicle (P \.0001). The analysis of success rate showed that gel and cream had a comparable and higher percentage of subjects for whom treatment was successful (38.4% and 35.4%, respectively) compared with a success rate of 27.5% in the gel vehicle group. Success was noted in a greater percentage of gel-treated subjects than in the cream and gel vehicle groups beginning at week 4 and continuing through the end of the study. Based on the primary analysis of week 10 data in the ITT population, the gel demonstrated superiority over its vehicle (P = .006). Local adverse events occurred in 6.5% of subjects in the gel group, in 6.3% of the subjects in the cream group, and in 6.3% of the subjects in the gel vehicle group. Treatment-related adverse events occurred in 16 subjects (2.9%) in the gel group, in 22 subjects (4.0%) in the cream group, and in 8 subjects (4.2%) in the gel vehicle group. Conclusion: This clinical study demonstrated that metronidazole gel 1% had a higher efficacy rate than its cream formulation and its vehicle and was equally well tolerated. Dr. Beutner and Mr. Calvarese are employees of Dow Pharmaceutical Sciences. Dr. Graeber is an employee of Galderma R&D Inc. Supported by Galderma R&D Inc.
MARCH 2005
Acne
STEROID-SPARING EFFECT OF AN EMOLLIENT IN THE TREATMENT OF MILD TO MODERATE ATOPIC DERMATITIS IN CHILDREN Philippe Msika, Nathalie Piccardi, Jean Christophe Choulot, Bernard Chadoutaud, Laboratoires Expanscience, Epernon, France
P100
The application of emollients is widely recommended as a first-line therapy in atopic dermatitis. It is safe and it improves quality of life of the children and their parents. Additionally, it may allow application of a lesser amount of topical steroids during crisis and thus prevent skin atrophy. An emollient specifically formulated for atopic dermatitis has been studied. It contains 2% of a patented sunflower oleodistillate, obtained by molecular distillation and composed of 90% essential lipids (linoleic and oleic triglycerides), 5% phytosterols (beta-sitosterol), and 1% vitamin E. It has been shown to statistically increase the neosynthesis of cerebrosides, ceramides, and cholesterol when applied on human skin explant. This emollient also contains a multi-lamellar system composed by phytosphingosins E, cholesterol, and ceramides 3, 6, 1, mimicking lipids of the stratum corneum. A large multicenter study with 35 pediatricians including 175 atopic children was conducted for a 3-week period. The children were divided into 5 groups: A: desonide 0.05 %, 2 3 1 day; B: desonide 0.05%, 2 3 1 day + emollient 2 3 1 day; C: desonide 0.05%, 131 day; D: desonide 0.05%, 1 3 1 day + emollient 2 3 1 day; E: desonide 0.05%, 1 3 2 days + emollient 2 3 1 day. SCORAD score (SCORing Atopic Dermatitis) has been calculated at J0, J7, and J21; quality of life was evaluated at J0, J30. Preliminary results for 63 children show that the emollient improves effacy of steroids (B vs A) with a decrease of the SCORAD score of 86% vs 70% and improves quality of life (86% vs 64%). The emollient has a steroid-sparing effect: D vs A (steroids 1 3 1 day + emollients vs steroid 2 3 1 day alone) shows similar results: ÿ75% SCORAD score vs ÿ70%; E vs A (steroids one every other day + emollients vs steroid 2 3 1 day alone) idem with ÿ73% vs ÿ70%.
A META-ANALYSIS OF THE ANTI-INFLAMMATORY ACTIVITY OF TRETINOIN GEL Robert Day, PhD, Marge Nighland, BSc, Johnson & Johnson Consumer and Personal Products Worldwide, Skillman, NJ, United States The objective of this study was to analyze the integrated statistical analysis of the inflammatory lesion data from the two pivotal double-blind, placebo-controlled trials of tretinoin gel microsphere 0.04% to determine the efficacy of tretinoin gel microsphere 0.04% in the treatment of inflammatory lesions of acne vulgaris. A total of 451 patients were randomized to tretinoin gel microsphere 0.04% or vehicle. The statistical analysis included ITT/LOCF minus duplicate patients (19 patients) for the analyses combined across protocols. Results of combined studies of tretinoin gel microsphere 0.04% demonstrate the superiority of active drug over vehicle treatment in the reduction of inflammatory lesions. At 12 weeks (end of study) tretinoin gel 0.04% had statistically significant reductions (P \ .00125) of 43.3% compared with 22.2% for vehicle. Treatment superiority versus vehicle was consistently present at 2, 4, 6, 8, 10, and 12 weeks for percent reduction in inflammatory lesions. Treatment superiority emerges as early as week 2 with reductions of 14.8% for tretinoin gel microsphere 0.04% versus 0.5% for vehicle. This meta-analysis confirms that tretinoin gel microsphere 0.04% results in a rapid reduction in inflammatory lesions in acne vulgaris as early as 2 weeks after beginning treatment. Superior efficacy is maintained throughout the 12-week treatment period.
In conclusion, our 3-week comparative study on atopic children found that this emollient, containing a patented sunflower oleodistillate, can decrease the frequency of application of a topical steroid by a factor of 4.
Bibliography Management of acne—A report from a global alliance to improve outcomes in acne. J Am Acad Dermatol 2003:49:??.
P. Msika, N. Piccardi and J. C. Choulot are all employees of Laboratoires Expanscience. 100% supported by Laboratoires Expanscience
Dr. Day, Ms. Nighland, and Rachel Grossman are employees of Johnson & Johnson. Mark Van Buskirk received financial support from Johnson & Johnson for statistical services. 100% sponsored by Johnson & Johnson
P101 A MULTI-CENTER, INVESTIGATOR-BLIND CLINICAL TRIAL TO ASSESS THE SAFETY AND EFFICACY OF METRONIDAZOLE GEL 1% AS COMPARED TO METRONIDAZOLE GEL VEHICLE AND METRONIDAZOLE CREAM 1% IN THE TREATMENT OF ROSACEA Karl Beutner, MD, PhD, Barry Calvarese, MS, Dow Pharmaceuticals Sciences, Petaluma, CA, United States; Michael Graeber, MD, Galderma R&D Inc, Princeton, NJ, United States Objectives: To show the noninferiority of metronidazole gel 1% to metronidazole cream 1% in the treatment of rosacea, to show its superiority over its gel vehicle, and to evaluate safety and tolerability of the treatments.
P38 EFFECTS OF DA-9102 ON ATOPIC DERMATITIS IN NC/NgA MICE In-Ki Lee, MS, Miwon Son, PhD, Soon-Hoe Kim, PhD, Research Laboratories of Dong-A Pharmaceutical Co., Ltd., Yongin, Korea; Kyu-Han Kim, MD, PhD, Department of Dermatology, Seoul National University Hospital, Seoul, Korea Atopic dermatitis is a chronic, itchy, inflammatory skin disease that usually develops in early childhood. Although the origin of atopic dermatitis remains unclear, it has been shown that both Th1 and Th2 cytokines play pathogenic roles in the generation of atopic dermatitis. DA-9102 is an extract from Actinidia species containing an immune-modulating activity for allergy-related disease. We have examined whether DA-9102 suppresses the development of atopic dermatitis-like skin lesions in NC/Nga mice. NC/Nga mice were given daily DA-9102 starting at 6 weeks of age. Drugs were orally administered to the mice. The efficacy of DA-9102 in NC/Nga mice was judged by measurement of skin severity, scratching behavior, and plasma immunoglobulin levels (IgE, IgG1, and IgG2a). Dermatitis developed in control mice from 10 weeks of age continuously. However, oral administration of DA-9102 (100 mg/kg) suppressed the development of dermatitis. The skin severity score of the control group reached 5.3 6 2.0 at 13 weeks of age, whereas that of DA-9102 was 2.7 6 1.3. The plasma IgE level increased gradually with age, and treatment with DA-9102 reduced the plasma IgE level. The plasma IgE level was 3541.5 6 641.2 ng/mL for the control group but 1442.2 6 343.85 ng/mL for the DA9102-administered group after 7 weeks of administration (P \.05). Oral administration of DA-9102 also had an inhibitory effect on plasma IgG1 levels (control group, 2617.5 6 358.9 g/mL; DA-9102-administered group, 1034.9 6 100.9 g/mL; P \.01). However, the plasma IgG2a level was not affected. At the age of 13 weeks, we counted the amount of time scratching behaviors occurred during a 20minute period. The time of scratching decreased twofold after oral administration of DA-9102. These observations suggest that DA-9102 can be expected to be a useful drug for atopic dermatitis. Nothing to disclose.
P10
J AM ACAD DERMATOL
Methods: This was a multicenter, randomized, investigator-blind, active- and vehiclecontrolled, parallel comparison involving adult subjects of any race with rosacea. Subjects applied metronidazole gel 1%, metronidazole cream 1%, or metronidazole gel vehicle to the face once daily at bedtime for 10 weeks with evaluations at 2, 4, 7, and 10 weeks after baseline. Evaluations included inflammatory lesion count for forehead, chin, nose, right cheek, and left cheek at each visit and a blinded assessment of the signs and symptoms of rosacea (Investigator’s Global Severity Score; GSS). Primary efficacy analysis variables were percent reduction from baseline in inflammatory lesion counts at week 10 and percent of subjects rated as successes (clear or almost clear) in the dichotomized Investigator’s GSS at week 10. For the week 10 analysis in the ITT population, the median reduction in inflammatory lesion counts was 66.7% in the gel group, 58.3% in the cream group, and 46.2% in the gel vehicle group. Based on the primary analysis of week 10 LOCF data in the ITT population, metronidazole gel demonstrated superiority over its vehicle (P \.0001). The analysis of success rate showed that gel and cream had a comparable and higher percentage of subjects for whom treatment was successful (38.4% and 35.4%, respectively) compared with a success rate of 27.5% in the gel vehicle group. Success was noted in a greater percentage of gel-treated subjects than in the cream and gel vehicle groups beginning at week 4 and continuing through the end of the study. Based on the primary analysis of week 10 data in the ITT population, the gel demonstrated superiority over its vehicle (P = .006). Local adverse events occurred in 6.5% of subjects in the gel group, in 6.3% of the subjects in the cream group, and in 6.3% of the subjects in the gel vehicle group. Treatment-related adverse events occurred in 16 subjects (2.9%) in the gel group, in 22 subjects (4.0%) in the cream group, and in 8 subjects (4.2%) in the gel vehicle group. Conclusion: This clinical study demonstrated that metronidazole gel 1% had a higher efficacy rate than its cream formulation and its vehicle and was equally well tolerated. Dr. Beutner and Mr. Calvarese are employees of Dow Pharmaceutical Sciences. Dr. Graeber is an employee of Galderma R&D Inc. Supported by Galderma R&D Inc.
MARCH 2005