- Email: [email protected]
P334 Genital warts: Global patient perspective
S230
Posters
appointment. Anonymous questionnaires were sent to these patients and their referring physicians. 34% of patients and 88% of physicians replied. Mean patient age was 53; range 26-74. 69% of patients were married; 17% single; 6% separated and 6% divorced. 47% claimed problems, long distance, work commitments or travel abroad; 27% had spontaneous resolution of erectile dysfunction. Deteriorating health was a factor in 21% and 6% had a relationship termination. 25% claimed embarrassment and 31% anxiety. Partners objected to attendance in 6%. Patient deaths accounted for 5%. Only 6% received other treatment. Further appointments were requested by 52%. 80% of physicians had been informed of non-attendance. Physician referrals were made after one consultation in 53% of patients; after 2 in 31%; after 3 in 8% and after 4 or more in 5%. 23% of non-attenders subsequently saw their physician regarding erectile dysfunction and 8% were referred elsewhere. 0 P331 Liquorodiagnosis of early neurosyphilis A.Y. Beskrovnaya, K.A. Yuldashev. Research Institute of Dermatology
and Venereology,
Tashkent,
Uzbekistan
Increase in blood-brain barrier (BBB) permeability in 29% of patients with primary, 46% - with secondary fresh, 59% with recurrent syphilis accompanied by FTA positivity in spinal fluid (SF) has been registered. By FfA positivity 2 types of SF immuno-pathologies have been revealed: absence of A-, M-, G- treponematous antibodies was remarkable for the 1. type, absence of solely G-antibodies - for the 2. type. An early neurosyphilis has been determined in 60% of patients with the 1. type of SF immunopathology. It is discussed a matter of diagnosis of early neurosyphilis and necessity to correct specific treatment in patients with syphilis of the 1. type of SF immunopathology. ElP332 Optimal genital herpes management has
been curtailed by the lack of availability of HSV II serology tests
S. Bentley. Molecules to Market, Centre,
BlackstaflRoad,
Belfast
Unit BTll
5 Kennedy 9DT, UK
Enterprise
Despite the availability of effective therapeutics for treating genital herpes for over 10 years, the majority (> 70%) of those infected with HSV II remain untreated. A diagnosis based on clinical symptoms or antigen testing alone does not capture at risk groups within STD patients and pregnancy management. A marriage of serological screening of at risk groups with public awareness campaigns may begin to significantly impact the spread of genital herpes. The POCKIT HSV II test is the world’s first specific rapid serology test to aid the detection of genital herpes amongst the asymptomatic populations. It is an immunoassay designed to aid with the detection of HSV II amongst pregnant women and in STD clinics. Extensive clinical testing has shown the POCKIT test to have sensitivity and specificity greater than 95% with a result within 6 minutes. References
[1] Lange&erg et al. 1989: Ann. Intern. Med. 40,882-887.
- STD/HIV
[2] Pober et al. 1988: 15, 1031-S. 131 Wald et al. NEJM, 1995: Sept. 21, 770-775. [4] Barton et al. 1996: Int. J. of STD & AIDS, 7,229.232. [5] Arvin and Prober 1994: Infect. Agents and Disease, 375382.
ElP333 A safety assessment of topical imiquimod M.L. Owens, K.I. Tygum, T.A. Senta, J.A. Myers, T.L. Fox, M.H. Smith. 3M Pharmaceuticals, St. Paul, MN, USA Imiquimod (IQ) is a new immune response enhancer which stimulates the production of interferon-alpha and other cytokines. Topically applied IQ 5% cream has proven effective as a patient-applied treatment for genitabperianal warts. The safety of the market formulation of IQ 5% cream was assessed in a series of three clinical trials. The first trial was conducted in 40 healthy subjects and assessed irritation using a 21-day cumulative irritation protocol. Hill Top chambers’” containing IQ 5% cream, vehicle cream and Vaseline Intensive Care Lotion’” (VICL) were applied daily to the same test sites for 21 consecutive days to the back. Test sites were graded daily on a 7-point scale. The second trial assessed the sensitization potential using a modified Draize sensitization protocol; 139 healthy subjects were enrolled. During the 3-week induction phase, Hill Top chambers containing IQ 5% cream and vehicle cream were applied three-times-per-week to the same test sites on the upper arm. After a 14-day rest period, each subject was challenged with both materials and test sites were graded for sensitization. The third trial was conducted in 6 healthy subjects and assessed the percutaneous penetration from a single 8-hour application of radiolabelled IQ 5% cream. Blood, urine and feces were collected an analyzed for total radio-activity. In the first trial, IQ 5% and vehicle creams were shown to be significantly less irritating than the control VICL based on pairwise analysis of the test site scores. In the second trial, IQ 5% and vehicle creams were identical in sensitization potential; both have demonstrated minimal sensitization potential. The extent of percutaneous penetration in the third trial was < 0.9% of the single IQ dose. No radioactivity was detectable in serum over the 48-hour collection period. As demonstrated in these three trials, IQ, formulated as a 5% cream for topical application, is minimally absorbed and has a minimal irritation and sensitization potential. As a patient-applied treatment with low systemic absorption and minimal irritation potential, IQ 5% cream provides advantages over existing therapies for the treatment of external genital/perianal warts. 0 P334 Genital warts: Global patient perspective D. Brussee’, S. Labram 2 . ‘3M Pharmaceuticals, St. Paul, MN, USA, 2Taylor
Nelson
Healthcare,
London,
UK
Although genital warts are one of the most common sexuallytransmitted diseases, patients’ perceptions about this disease have not been widely studied. Our objective of this research was to better understand patient perceptions concerning genital warts, treatment, and the impact infection has on lifestyle. We interviewed 166 patients who had been treated for genital warts within the previous 6 months in five countries in North America (Canada, US) and Europe (France, Germany, UK) during 1993-1994. In each country 30 to 36 patients were
Posters
interviewed, with efforts made to divide equally by gender and age. Questionnaires were administered individually in the local language to patients in person. Although two-thirds of patients consulted a physician at first discovery of genital warts, among the remaining one-third, the greatest percentage (40%) did not do so because they thought the warts would go away. Patients reported that infection with genital warts was a concern - 85% of men and 91% of women indicated that they were at least slightly concerned. A greater level of concern was expressed among those in Canada, US and the UK with more patients “quite” or “very” concerned (Canada 70%, US 72%, UK 64%) than patients in France (36%) and Germany (42%) The most frequently cited concerns of both men and women were transmission (37%), recurrence (36%), pain (28%), emotional/sexual concerns (26%) and treatment efficacy (24%). When asked if genital warts had changed their lifestyle, approximatley two-thirds of patients reported lifestyle changes (67% men; 58% women) with consistent use of condoms cited most frequently. Nearly half of the patients (46% men; 45% women) reported knowing enough about genital warts, but actual statements about the disease suggested some misinformation. Since physicians were globally cited as the most common source of information about genital warts, this qualitative research has practical implications and outlines the important psychosexual component of genital warts which physicians must address along with the disease.
IP335
Two vehicle-controlled trials of topical imiquimod for the treatment of genitaNperianal condylomata acuminate
K. Trofatter ’ , K. Beutner2, L. Edwards3, S. Tyring4, M. Owens 5, T. Fox 5, A. Hougham 5, K. Gayoso 5 and the Study Group 5. ’ University of Tennessee, Knoxville, TN; 2Solano Medical Studies, USA
Dermatology Associates, Vallejo, CA: 3Carolinas Center, Charlotte, NC; 4UTMR Centerfor Clinical Nassau Bay, TX; 5 CM Pharmaceuticals, St. Paul MN,
Imiquimod (IQ) is a new immune response enhancer which stimulates the production of interferon-or and other cytokines. The effect of IQ5%, IQl% and vehicle was compared in 2 multi-center, double-blind, vehicle-controlled, parallel group trials. In the 1st trial, 279 pts (154M, 125F) were enrolled and treated daily for up to 16 wks or until wart clearance. In the 2nd trial 3 11 pts (I 80M, 13 1F) were enrolled and treated 3xlwk for up to 16 wks or until wart clearance. In both trials, pts with complete wart clearance entered a 12wk treatment-free follow-up period. Total wart clearance rates were higher for females than for males in both trials. In the 1st trial, 84% of the female IQ5% pts, 28% of the IQ1 % pts and 9% of the vehicle pts had complete wart clearance (p < 0.0001). Of the male pts 59% of the IQ5% pts, 5% of the IQl% pts and 0% of the vehicle pts had complete wart clearance (p < 0.0001). In the 2nd trial, 77% of the female IQ5% pts, 46% of the IQl% pts and 28% of the vehicle pts had complete wart clearance (p=O.OOOl). Of the male pts 40% of the IQ5% patients, 10% of the IQl% pts and 6% of the vehicle pts had complete wart clearance (p < 0.0001). In both studies, IQS% had a significantly higher clearance rate than IQl% and vehicle. IQl% and vehicle were not significantly different. In the 1st trial, recurrence rates were
-
S231
Therapy
low: 19% of IQ5% pts, 17% of IQl% pts and 0% of vehicle pts. In the 2nd trial, 13% of IQS% pts, 0% of IQl% pts and 10% of vehicle pts had a wart recurrence during follow-up. Local skin reactions associated with IQ occurred in both studies but were more common and of greater severity with daily dosing. There were no statistically significant differences among treatment groups for systemic adverse experiences. Daily treatment with IQ5% cream increased the wart clearance rate compared to 3xlweek dosing in females, males and all pts, with local skin reactions being more common. Both IQ regimens are effective and have acceptable safety profiles.
P336 czl
A novel topical immune response modifier induces cytokine productlon in human keratinocytes and skin
M.A. Tomai ’ , R.L. Miller’, H.B. Slade ‘, H. Fujisawa2, G.M. Shivji’, B. Wang2, D.N. Sauder’. ‘3M Pharmaceuticals, St. Paul, MN, USA, 2 University of Toronto, Sunnybrook Health Science Centre, Toronto, Canada
A new topically effective immune response modifier agent, imiquimod has been shown to have significant antiviral antitumor activity in animal models. Imiquimod has completed phase III clinical trials for the treatment of papilloma virus infections. To further delineate the local immunomodulatory effect of imiquimod, we evaluated the effects of imiquimod on normal human keratinocyte cytokine gene expression in vitro and on skin cytokine induction in vivo. Cytokine gene expression was analyzed by reverse transcriptase PCR. The optical density of each cytokine was normalized relative to G3PDH signals. Interferon-a, IL-6 and IL-8 gene expression in human keratinocytes were upregulated with 1 @g/ml and with IO~g/ml of imiquimod. Increases in protein were also seen for IL-8. Topical application of 5% imiquimod cream on the skin of hairless mice resulted in interferon-a message induction within one hour after topical application with peak message induction at four hours. This peak in interferon-a mRNA was paralleled by an increase in interferon protein as well as tumor necrosis factor protein. These results further confirm that imiquimod has potent immune response enhancing properties locally in the skin. The augmentation of proinflammatory and immunoregulatory cytokines likely contribute to effectiveness of imiquimod in the treatment of cutaneous papilloma virus infections.
Therapy
IP337
Lichenoid drug eruption due to ethambutol
M.S. Marques, T.E. Correia. Clinica Dermatologia e Venereologia, Lisboa, Portugal
Hospital
Universitdria de Pulido
de Valente,
A 77 year - old Caucasian male patient developed a disseminated papulosquamous dermatosis during treatment of lung tuberculosis with ethambutol and rifampicin. The dermatological picture was consistent with lichen planus and has been supported by histological findings of a lichenoid reaction with significant numbers of eosinophils in the infiltrate.
Posters
appointment. Anonymous questionnaires were sent to these patients and their referring physicians. 34% of patients and 88% of physicians replied. Mean patient age was 53; range 26-74. 69% of patients were married; 17% single; 6% separated and 6% divorced. 47% claimed problems, long distance, work commitments or travel abroad; 27% had spontaneous resolution of erectile dysfunction. Deteriorating health was a factor in 21% and 6% had a relationship termination. 25% claimed embarrassment and 31% anxiety. Partners objected to attendance in 6%. Patient deaths accounted for 5%. Only 6% received other treatment. Further appointments were requested by 52%. 80% of physicians had been informed of non-attendance. Physician referrals were made after one consultation in 53% of patients; after 2 in 31%; after 3 in 8% and after 4 or more in 5%. 23% of non-attenders subsequently saw their physician regarding erectile dysfunction and 8% were referred elsewhere. 0 P331 Liquorodiagnosis of early neurosyphilis A.Y. Beskrovnaya, K.A. Yuldashev. Research Institute of Dermatology
and Venereology,
Tashkent,
Uzbekistan
Increase in blood-brain barrier (BBB) permeability in 29% of patients with primary, 46% - with secondary fresh, 59% with recurrent syphilis accompanied by FTA positivity in spinal fluid (SF) has been registered. By FfA positivity 2 types of SF immuno-pathologies have been revealed: absence of A-, M-, G- treponematous antibodies was remarkable for the 1. type, absence of solely G-antibodies - for the 2. type. An early neurosyphilis has been determined in 60% of patients with the 1. type of SF immunopathology. It is discussed a matter of diagnosis of early neurosyphilis and necessity to correct specific treatment in patients with syphilis of the 1. type of SF immunopathology. ElP332 Optimal genital herpes management has
been curtailed by the lack of availability of HSV II serology tests
S. Bentley. Molecules to Market, Centre,
BlackstaflRoad,
Belfast
Unit BTll
5 Kennedy 9DT, UK
Enterprise
Despite the availability of effective therapeutics for treating genital herpes for over 10 years, the majority (> 70%) of those infected with HSV II remain untreated. A diagnosis based on clinical symptoms or antigen testing alone does not capture at risk groups within STD patients and pregnancy management. A marriage of serological screening of at risk groups with public awareness campaigns may begin to significantly impact the spread of genital herpes. The POCKIT HSV II test is the world’s first specific rapid serology test to aid the detection of genital herpes amongst the asymptomatic populations. It is an immunoassay designed to aid with the detection of HSV II amongst pregnant women and in STD clinics. Extensive clinical testing has shown the POCKIT test to have sensitivity and specificity greater than 95% with a result within 6 minutes. References
[1] Lange&erg et al. 1989: Ann. Intern. Med. 40,882-887.
- STD/HIV
[2] Pober et al. 1988: 15, 1031-S. 131 Wald et al. NEJM, 1995: Sept. 21, 770-775. [4] Barton et al. 1996: Int. J. of STD & AIDS, 7,229.232. [5] Arvin and Prober 1994: Infect. Agents and Disease, 375382.
ElP333 A safety assessment of topical imiquimod M.L. Owens, K.I. Tygum, T.A. Senta, J.A. Myers, T.L. Fox, M.H. Smith. 3M Pharmaceuticals, St. Paul, MN, USA Imiquimod (IQ) is a new immune response enhancer which stimulates the production of interferon-alpha and other cytokines. Topically applied IQ 5% cream has proven effective as a patient-applied treatment for genitabperianal warts. The safety of the market formulation of IQ 5% cream was assessed in a series of three clinical trials. The first trial was conducted in 40 healthy subjects and assessed irritation using a 21-day cumulative irritation protocol. Hill Top chambers’” containing IQ 5% cream, vehicle cream and Vaseline Intensive Care Lotion’” (VICL) were applied daily to the same test sites for 21 consecutive days to the back. Test sites were graded daily on a 7-point scale. The second trial assessed the sensitization potential using a modified Draize sensitization protocol; 139 healthy subjects were enrolled. During the 3-week induction phase, Hill Top chambers containing IQ 5% cream and vehicle cream were applied three-times-per-week to the same test sites on the upper arm. After a 14-day rest period, each subject was challenged with both materials and test sites were graded for sensitization. The third trial was conducted in 6 healthy subjects and assessed the percutaneous penetration from a single 8-hour application of radiolabelled IQ 5% cream. Blood, urine and feces were collected an analyzed for total radio-activity. In the first trial, IQ 5% and vehicle creams were shown to be significantly less irritating than the control VICL based on pairwise analysis of the test site scores. In the second trial, IQ 5% and vehicle creams were identical in sensitization potential; both have demonstrated minimal sensitization potential. The extent of percutaneous penetration in the third trial was < 0.9% of the single IQ dose. No radioactivity was detectable in serum over the 48-hour collection period. As demonstrated in these three trials, IQ, formulated as a 5% cream for topical application, is minimally absorbed and has a minimal irritation and sensitization potential. As a patient-applied treatment with low systemic absorption and minimal irritation potential, IQ 5% cream provides advantages over existing therapies for the treatment of external genital/perianal warts. 0 P334 Genital warts: Global patient perspective D. Brussee’, S. Labram 2 . ‘3M Pharmaceuticals, St. Paul, MN, USA, 2Taylor
Nelson
Healthcare,
London,
UK
Although genital warts are one of the most common sexuallytransmitted diseases, patients’ perceptions about this disease have not been widely studied. Our objective of this research was to better understand patient perceptions concerning genital warts, treatment, and the impact infection has on lifestyle. We interviewed 166 patients who had been treated for genital warts within the previous 6 months in five countries in North America (Canada, US) and Europe (France, Germany, UK) during 1993-1994. In each country 30 to 36 patients were
Posters
interviewed, with efforts made to divide equally by gender and age. Questionnaires were administered individually in the local language to patients in person. Although two-thirds of patients consulted a physician at first discovery of genital warts, among the remaining one-third, the greatest percentage (40%) did not do so because they thought the warts would go away. Patients reported that infection with genital warts was a concern - 85% of men and 91% of women indicated that they were at least slightly concerned. A greater level of concern was expressed among those in Canada, US and the UK with more patients “quite” or “very” concerned (Canada 70%, US 72%, UK 64%) than patients in France (36%) and Germany (42%) The most frequently cited concerns of both men and women were transmission (37%), recurrence (36%), pain (28%), emotional/sexual concerns (26%) and treatment efficacy (24%). When asked if genital warts had changed their lifestyle, approximatley two-thirds of patients reported lifestyle changes (67% men; 58% women) with consistent use of condoms cited most frequently. Nearly half of the patients (46% men; 45% women) reported knowing enough about genital warts, but actual statements about the disease suggested some misinformation. Since physicians were globally cited as the most common source of information about genital warts, this qualitative research has practical implications and outlines the important psychosexual component of genital warts which physicians must address along with the disease.
IP335
Two vehicle-controlled trials of topical imiquimod for the treatment of genitaNperianal condylomata acuminate
K. Trofatter ’ , K. Beutner2, L. Edwards3, S. Tyring4, M. Owens 5, T. Fox 5, A. Hougham 5, K. Gayoso 5 and the Study Group 5. ’ University of Tennessee, Knoxville, TN; 2Solano Medical Studies, USA
Dermatology Associates, Vallejo, CA: 3Carolinas Center, Charlotte, NC; 4UTMR Centerfor Clinical Nassau Bay, TX; 5 CM Pharmaceuticals, St. Paul MN,
Imiquimod (IQ) is a new immune response enhancer which stimulates the production of interferon-or and other cytokines. The effect of IQ5%, IQl% and vehicle was compared in 2 multi-center, double-blind, vehicle-controlled, parallel group trials. In the 1st trial, 279 pts (154M, 125F) were enrolled and treated daily for up to 16 wks or until wart clearance. In the 2nd trial 3 11 pts (I 80M, 13 1F) were enrolled and treated 3xlwk for up to 16 wks or until wart clearance. In both trials, pts with complete wart clearance entered a 12wk treatment-free follow-up period. Total wart clearance rates were higher for females than for males in both trials. In the 1st trial, 84% of the female IQ5% pts, 28% of the IQ1 % pts and 9% of the vehicle pts had complete wart clearance (p < 0.0001). Of the male pts 59% of the IQ5% pts, 5% of the IQl% pts and 0% of the vehicle pts had complete wart clearance (p < 0.0001). In the 2nd trial, 77% of the female IQ5% pts, 46% of the IQl% pts and 28% of the vehicle pts had complete wart clearance (p=O.OOOl). Of the male pts 40% of the IQ5% patients, 10% of the IQl% pts and 6% of the vehicle pts had complete wart clearance (p < 0.0001). In both studies, IQS% had a significantly higher clearance rate than IQl% and vehicle. IQl% and vehicle were not significantly different. In the 1st trial, recurrence rates were
-
S231
Therapy
low: 19% of IQ5% pts, 17% of IQl% pts and 0% of vehicle pts. In the 2nd trial, 13% of IQS% pts, 0% of IQl% pts and 10% of vehicle pts had a wart recurrence during follow-up. Local skin reactions associated with IQ occurred in both studies but were more common and of greater severity with daily dosing. There were no statistically significant differences among treatment groups for systemic adverse experiences. Daily treatment with IQ5% cream increased the wart clearance rate compared to 3xlweek dosing in females, males and all pts, with local skin reactions being more common. Both IQ regimens are effective and have acceptable safety profiles.
P336 czl
A novel topical immune response modifier induces cytokine productlon in human keratinocytes and skin
M.A. Tomai ’ , R.L. Miller’, H.B. Slade ‘, H. Fujisawa2, G.M. Shivji’, B. Wang2, D.N. Sauder’. ‘3M Pharmaceuticals, St. Paul, MN, USA, 2 University of Toronto, Sunnybrook Health Science Centre, Toronto, Canada
A new topically effective immune response modifier agent, imiquimod has been shown to have significant antiviral antitumor activity in animal models. Imiquimod has completed phase III clinical trials for the treatment of papilloma virus infections. To further delineate the local immunomodulatory effect of imiquimod, we evaluated the effects of imiquimod on normal human keratinocyte cytokine gene expression in vitro and on skin cytokine induction in vivo. Cytokine gene expression was analyzed by reverse transcriptase PCR. The optical density of each cytokine was normalized relative to G3PDH signals. Interferon-a, IL-6 and IL-8 gene expression in human keratinocytes were upregulated with 1 @g/ml and with IO~g/ml of imiquimod. Increases in protein were also seen for IL-8. Topical application of 5% imiquimod cream on the skin of hairless mice resulted in interferon-a message induction within one hour after topical application with peak message induction at four hours. This peak in interferon-a mRNA was paralleled by an increase in interferon protein as well as tumor necrosis factor protein. These results further confirm that imiquimod has potent immune response enhancing properties locally in the skin. The augmentation of proinflammatory and immunoregulatory cytokines likely contribute to effectiveness of imiquimod in the treatment of cutaneous papilloma virus infections.
Therapy
IP337
Lichenoid drug eruption due to ethambutol
M.S. Marques, T.E. Correia. Clinica Dermatologia e Venereologia, Lisboa, Portugal
Hospital
Universitdria de Pulido
de Valente,
A 77 year - old Caucasian male patient developed a disseminated papulosquamous dermatosis during treatment of lung tuberculosis with ethambutol and rifampicin. The dermatological picture was consistent with lichen planus and has been supported by histological findings of a lichenoid reaction with significant numbers of eosinophils in the infiltrate.