- Email: [email protected]
Human spermatogenesis is unaffected by 12 weeks of treatment with low-dose extended release minocycline
P606 Cardiovascular risk evaluation in psoriasis Carolina Covalski, MD, Universidade Federal de Santa Catarina, Floriano´polis, Santa Catarina, Brazil; Daniel Holthausen Nunes, MD, Universidade Federal de ´ polis, Santa Catarina, Brazil; Marina Besen Guerini, MD, Santa Catarina, Floriano Universidade Federal de Santa Catarina, Floriano´polis, Santa Catarina, Brazil; Naiana Bittencourt Sa, MD, Universidade Federal de Santa Catarina, Floriano´polis, Santa Catarina, Brazil Introduction: Psoriasis is a relatively common skin condition that involves chronic local and systemic inflammatory process. Currently, some studies seek to involve the chronic inflammatory disease with increased risk for atherosclerosis, cardiovascular events, and metabolic syndrome. Higher prevalences of diabetes, hypertension, and abnormal lipid profile have been associated with psoriasis, which may indicate that this disease can be a independent risk factor for cardiovascular events. Objective: To evaluate the prevalence of cardiovascular risk factors in patients with psoriasis, comparing them with a healthy control group without chronic inflammatory systemic diseases. Methods: The project was approved by the ethics committee. Participants were selected from a group of patients with psoriasis on treatment in the clinic of dermatology and a healthy control group, matched by sex and age. All participants were subjected to laboratory tests and interviews to complete the Protocol of Cardiovascular Risk in Psoriasis. The variables analyzed were: gender, age, body mass, height, calculation of body mass index (BMI) and waist circumference, personal history of diabetes, smoking, hypertension, recent treatment with corticosteroids, use of hypolipidemic and antihypertensive drugs, individual history of cardiovascular disease in first-degree relative, presence of first-degree relatives with psoriasis, analysis of total cholesterol (TC) and high-density lipoprotein (HDL), triglycerides, and uric acid. Were classified as bearer of dyslipidemia or not through the parameters: TC [200 mg/dL, triglycerides [150 mg/dL, HDL \40 mg/dL, and ratio TC/HDL [3.5. For uric acid, the cutoff was set at 7.0 mg/dL. For statistical analysis, P \.05 was considered significant. Results: There was a positive association between psoriasis and HDL \40 mg/dL (P ¼ .012), ratio TC/HDL-C [3.5 (P \0.001), triglycerides [150 mg/dL (P ¼ .0030), and dyslipidemia (P \.001). History of heart attack and stroke (P ¼ .021) and high uric acid (P ¼.010) showed significant association with psoriasis. Family history of psoriasis showed statistically proven relationship with the risk of developing this disease (P \.001). Conclusion: This sample shows that psoriasis is associated with higher prevalence of alterations in lipid profile, dyslipidemia, hyperuricemia, and history of cardiovascular disease. In addition, significant association with the presence of first-degree relatives with psoriasis was observed.
ACNE P700 Human spermatogenesis is unaffected by 12 weeks of treatment with lowdose extended release minocycline Larry Lipshultz, MD, Baylor College of Medicine, Houston, TX, United StatesUnited StatesUnited States; Ira Lawrence, MD, Medicis Pharmaceutical Corporation, Scottsdale, AZ, United States Background: Reports have suggested that minocycline adversely affects human spermatogenesis. Objective: The primary objective was to investigate the effects of an extended release (ER) minocycline on several parameters of spermatogenesis, including mean changes in sperm count. Secondary objectives included assessing the effects of ER minocycline on circulating follicle-stimulating hormone (FSH), serum testosterone levels, and the proportion of subjects with $ 50% reduction in sperm motility and with $ 20% reduction in normal sperm morphology. Methods: This randomized, double-blind, placebo-controlled study enrolled healthy men $ 18 years of age with clinically acceptable baseline sperm parameters, defined as a total sperm concentration of [20 3 106/mL, of which [50% were motile and [4.4% had normal morphology. The study drug was an ER minocycline (Medicis Pharmaceutical, Scottsdale, AZ). One tablet (1 mg/kg) was taken daily for 12 weeks. This treatment period corresponds to the approved ER minocycline product label and exceeds the human 75-day spermatogenesis cycle. After the baseline evaluation, blood and semen samples were collected after 12, 16, 20, and 24 weeks. Results: Study subjects were randomized to receive treatment with ER minocycline (N ¼ 92) or placebo (N ¼ 88); 146 subjects completed the study. At week 12, the mean change in sperm concentration was 9.8% in the minocycline group versus e1.3% in the placebo group (P ¼ not significant at all time points). At week 12, the number of minocycline- and placebo-treated subjects with a 50% reduction in sperm concentration was 11.1% and 11.0%, respectively; the number of subjects with a 50% reduction in motility was 0.0% and 1.4%, respectively, and the number of subjects with a 20% reduction in normal morphology was 20.8% and 32.9%, respectively (P ¼ not significant at all time points). At week 12, the mean FSH levels in minocycline- and placebo-treated subjects were 3.2 and 3.1 IU/L, respectively, and the mean testosterone levels were 465.1 and 476.9 ng/dL, respectively. At week 12, the mean change in FSH levels in minocycline- and placebo-treated subjects were e0.1 and 0.0 IU/L, respectively, and the mean change in testosterone levels were e2.4 and 5.3 ng/dL, respectively (P ¼ not significant at all time points). Conclusions: These results indicate that human spermatogenesis and circulating levels of FSH and testosterone are unaffected by the administration of low-dose ER minocycline for up to 12 weeks.
Commercial support: None identified. Commercial support: Medicis Pharmaceutical.
P701 P607 The molecular profile of psoriatic skin in responders to ustekinumab or etanercept after 12 weeks of treatment: Results from the ACCEPT trial James Krueger, MD, PhD, Rockefeller University, New York, NY, United States; Carrie Brodmerkel, PhD, Centocor Research and Development, Malvern, PA, United States; Katherine Li, PhD, Centocor Research and Development, Horsham, PA, United States; Mayte Suarez-Farinas, Rockefeller University, New York, NY, United States Aims: To assess the impact of p40 cytokine (IL-12/IL-23) or TNF-alfa blockade on resident and inflammatory cells and on the expression of gene circuits that may drive chronic immune activation and inflammation in the skin. Methods: In ACCEPT, a randomized, active-controlled study, the efficacy of etanercept and ustekinumab were compared in 903 patients with moderate to severe plaque psoriasis through week 12. Skin biopsies were performed in a subset of patients at baseline, weeks 1 and 12. Microarray analyses (Affymetrix U133 1 2 array) comparing nonlesional skin (n ¼ 85) to lesional skin (n ¼ 85) at baseline showed several thousand probe sets differentially expressed ([2-fold change FDR; P \ .05) in lesional skin. Results: Patients responding to each agent ( $ PASI 75, n ¼ 21 for etanercept, n ¼ 19 for ustekinumab) had significant changes in approximately 4000 transcripts compared to untreated lesions, indicating significant resolution of pathologic gene circuits. A set of 2922 transcripts, which included S100 genes, keratins 6/16, and innate defense products (cytokine-modulated genes in keratinocytes), were commonly regulated by ustekinumab or etanercept. The top 10 genes downregulated at week 12 by ustekinumab overlap with nine of the top 10 genes down regulated by etanercept at week 12; only two of the top 10 genes upregulated overlap (NTRK2, THRSP) in this comparison. The genes upregulated by ustekinumab include a number of keratin structural proteins indicating a unique effect of ustekinumab on keratinocytes. Conclusion: Elucidation of the common and unique effects of ustekinumab and etanercept define critical pathways involved in psoriasis pathogenesis and a successful therapeutic response. Broad genomic assessments provide an independent way to judge the extent to which disease pathology can be reversed by effective therapeutics. Commercial support: Centocor Research and Development, Inc.
MARCH 2010
Adapalene 0.1%/benzoyl peroxide 2.5% gel with doxycycline hyclate 100 mg tablets compared to vehicle gel with doxycycline hyclate 100 mg tablets in the treatment of severe acne vulgaris Linda Stein Gold, MD, Henry Ford Health Systems, Bloomfield Hills, MI, United States; Jean-Charles Dhuin, Medical and Marketing, Galderma, Sophia Antipolis, Sophia Antipolis, France; Jerry Tan, Windsor Clinical Research, Windsor, Ontario, Canada; Joseph Jorizzo, MD, Wake Forest University School of Medicine, Winston Salem, NC, United States A randomized, controlled, multicenter, double-blinded, parallel group study was conducted to evaluate the efficacy and safety of adapalene 0.1%/benzoyl peroxide 2.5% gel with doxycycline hyclate 100 mg tablets, QD compared to vehicle gel with doxycycline hyclate 100 mg tablets, QD in patients with severe acne vulgaris. Patients used Cetaphil daily facial moisturizer with SPF 15 during the study. A total of 459 patients, aged 12 to 35 years with a minimum of 20 inflammatory lesions and between 30 to120 noninflammatory lesions, were enrolled at 30 investigative sites in the United States and five investigative sites in Canada. Patients were instructed to apply the gel once daily in the evening and to take one tablet once daily in the morning for 12 weeks. Study visits occurred at baseline and weeks 2, 4, 8, and 12. A significant decrease in the median percent change from baseline in total lesion count was observed in the patients treated with adapalene 0.1%/benzoyl peroxide 2.5% gel with doxycycline compared to those treated with vehicle and doxycycline at all study visits (P\.001 for all time points; intent-to-treat population). At week 12, a 64% decrease in the median percent change from baseline in total lesion count was observed for the adapalene 0.1%/benzoyl peroxide 2.5% gel with doxycycline treatment group compared to a 41% decrease in the vehicle with doxycycline treatment group (P \.001). This significant decrease from baseline in total lesion count was seen as early as week 2 (e21% vs e13%; P \ .001) and continued throughout the study. Treatment with adapalene 0.1%/benzoyl peroxide 2.5% gel with doxycycline was also well tolerated and there were few cases (n ¼ 4, 1.7%) of treatment-related dermatologic adverse events reported. The results of this study demonstrated that adapalene 0.1%/benzoyl peroxide 2.5% gel with doxycycline hyclate 100 mg tablets regimen was significantly superior to vehicle gel with doxycycline hyclate 100 mg tablets in the treatment of severe acne vulgaris. Commercial support: Study and poster support provided by Galderma Laboratories, L.P.
J AM ACAD DERMATOL
AB13
ACNE P700 Human spermatogenesis is unaffected by 12 weeks of treatment with lowdose extended release minocycline Larry Lipshultz, MD, Baylor College of Medicine, Houston, TX, United StatesUnited StatesUnited States; Ira Lawrence, MD, Medicis Pharmaceutical Corporation, Scottsdale, AZ, United States Background: Reports have suggested that minocycline adversely affects human spermatogenesis. Objective: The primary objective was to investigate the effects of an extended release (ER) minocycline on several parameters of spermatogenesis, including mean changes in sperm count. Secondary objectives included assessing the effects of ER minocycline on circulating follicle-stimulating hormone (FSH), serum testosterone levels, and the proportion of subjects with $ 50% reduction in sperm motility and with $ 20% reduction in normal sperm morphology. Methods: This randomized, double-blind, placebo-controlled study enrolled healthy men $ 18 years of age with clinically acceptable baseline sperm parameters, defined as a total sperm concentration of [20 3 106/mL, of which [50% were motile and [4.4% had normal morphology. The study drug was an ER minocycline (Medicis Pharmaceutical, Scottsdale, AZ). One tablet (1 mg/kg) was taken daily for 12 weeks. This treatment period corresponds to the approved ER minocycline product label and exceeds the human 75-day spermatogenesis cycle. After the baseline evaluation, blood and semen samples were collected after 12, 16, 20, and 24 weeks. Results: Study subjects were randomized to receive treatment with ER minocycline (N ¼ 92) or placebo (N ¼ 88); 146 subjects completed the study. At week 12, the mean change in sperm concentration was 9.8% in the minocycline group versus e1.3% in the placebo group (P ¼ not significant at all time points). At week 12, the number of minocycline- and placebo-treated subjects with a 50% reduction in sperm concentration was 11.1% and 11.0%, respectively; the number of subjects with a 50% reduction in motility was 0.0% and 1.4%, respectively, and the number of subjects with a 20% reduction in normal morphology was 20.8% and 32.9%, respectively (P ¼ not significant at all time points). At week 12, the mean FSH levels in minocycline- and placebo-treated subjects were 3.2 and 3.1 IU/L, respectively, and the mean testosterone levels were 465.1 and 476.9 ng/dL, respectively. At week 12, the mean change in FSH levels in minocycline- and placebo-treated subjects were e0.1 and 0.0 IU/L, respectively, and the mean change in testosterone levels were e2.4 and 5.3 ng/dL, respectively (P ¼ not significant at all time points). Conclusions: These results indicate that human spermatogenesis and circulating levels of FSH and testosterone are unaffected by the administration of low-dose ER minocycline for up to 12 weeks.
Commercial support: None identified. Commercial support: Medicis Pharmaceutical.
P701 P607 The molecular profile of psoriatic skin in responders to ustekinumab or etanercept after 12 weeks of treatment: Results from the ACCEPT trial James Krueger, MD, PhD, Rockefeller University, New York, NY, United States; Carrie Brodmerkel, PhD, Centocor Research and Development, Malvern, PA, United States; Katherine Li, PhD, Centocor Research and Development, Horsham, PA, United States; Mayte Suarez-Farinas, Rockefeller University, New York, NY, United States Aims: To assess the impact of p40 cytokine (IL-12/IL-23) or TNF-alfa blockade on resident and inflammatory cells and on the expression of gene circuits that may drive chronic immune activation and inflammation in the skin. Methods: In ACCEPT, a randomized, active-controlled study, the efficacy of etanercept and ustekinumab were compared in 903 patients with moderate to severe plaque psoriasis through week 12. Skin biopsies were performed in a subset of patients at baseline, weeks 1 and 12. Microarray analyses (Affymetrix U133 1 2 array) comparing nonlesional skin (n ¼ 85) to lesional skin (n ¼ 85) at baseline showed several thousand probe sets differentially expressed ([2-fold change FDR; P \ .05) in lesional skin. Results: Patients responding to each agent ( $ PASI 75, n ¼ 21 for etanercept, n ¼ 19 for ustekinumab) had significant changes in approximately 4000 transcripts compared to untreated lesions, indicating significant resolution of pathologic gene circuits. A set of 2922 transcripts, which included S100 genes, keratins 6/16, and innate defense products (cytokine-modulated genes in keratinocytes), were commonly regulated by ustekinumab or etanercept. The top 10 genes downregulated at week 12 by ustekinumab overlap with nine of the top 10 genes down regulated by etanercept at week 12; only two of the top 10 genes upregulated overlap (NTRK2, THRSP) in this comparison. The genes upregulated by ustekinumab include a number of keratin structural proteins indicating a unique effect of ustekinumab on keratinocytes. Conclusion: Elucidation of the common and unique effects of ustekinumab and etanercept define critical pathways involved in psoriasis pathogenesis and a successful therapeutic response. Broad genomic assessments provide an independent way to judge the extent to which disease pathology can be reversed by effective therapeutics. Commercial support: Centocor Research and Development, Inc.
MARCH 2010
Adapalene 0.1%/benzoyl peroxide 2.5% gel with doxycycline hyclate 100 mg tablets compared to vehicle gel with doxycycline hyclate 100 mg tablets in the treatment of severe acne vulgaris Linda Stein Gold, MD, Henry Ford Health Systems, Bloomfield Hills, MI, United States; Jean-Charles Dhuin, Medical and Marketing, Galderma, Sophia Antipolis, Sophia Antipolis, France; Jerry Tan, Windsor Clinical Research, Windsor, Ontario, Canada; Joseph Jorizzo, MD, Wake Forest University School of Medicine, Winston Salem, NC, United States A randomized, controlled, multicenter, double-blinded, parallel group study was conducted to evaluate the efficacy and safety of adapalene 0.1%/benzoyl peroxide 2.5% gel with doxycycline hyclate 100 mg tablets, QD compared to vehicle gel with doxycycline hyclate 100 mg tablets, QD in patients with severe acne vulgaris. Patients used Cetaphil daily facial moisturizer with SPF 15 during the study. A total of 459 patients, aged 12 to 35 years with a minimum of 20 inflammatory lesions and between 30 to120 noninflammatory lesions, were enrolled at 30 investigative sites in the United States and five investigative sites in Canada. Patients were instructed to apply the gel once daily in the evening and to take one tablet once daily in the morning for 12 weeks. Study visits occurred at baseline and weeks 2, 4, 8, and 12. A significant decrease in the median percent change from baseline in total lesion count was observed in the patients treated with adapalene 0.1%/benzoyl peroxide 2.5% gel with doxycycline compared to those treated with vehicle and doxycycline at all study visits (P\.001 for all time points; intent-to-treat population). At week 12, a 64% decrease in the median percent change from baseline in total lesion count was observed for the adapalene 0.1%/benzoyl peroxide 2.5% gel with doxycycline treatment group compared to a 41% decrease in the vehicle with doxycycline treatment group (P \.001). This significant decrease from baseline in total lesion count was seen as early as week 2 (e21% vs e13%; P \ .001) and continued throughout the study. Treatment with adapalene 0.1%/benzoyl peroxide 2.5% gel with doxycycline was also well tolerated and there were few cases (n ¼ 4, 1.7%) of treatment-related dermatologic adverse events reported. The results of this study demonstrated that adapalene 0.1%/benzoyl peroxide 2.5% gel with doxycycline hyclate 100 mg tablets regimen was significantly superior to vehicle gel with doxycycline hyclate 100 mg tablets in the treatment of severe acne vulgaris. Commercial support: Study and poster support provided by Galderma Laboratories, L.P.
J AM ACAD DERMATOL
AB13