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Pulse vs. continuous terbinafine for treatment of toenail onychomycosis: results of a double-blind controlled trial
P386
P388
A FATAL CASE OF TRICHOSPORONOSIS IN A RENAL-TRANSPLANT PATIENT Jeffery C Weeks, MD, University of Alabama at Birmingham, Birmingham, AL, United States, Sate Hamza, MD, University of Alabama at Birmingham, Birmingham, AL, United States, Boni Elewski, MD, University of Alabama at Birmingham, Birmingham, AL, United States Trichosporonosis is a disseminated, often lethal, infection caused by Trichosporon species that most often affects immunocompromised patients. Trichosporon species can be part of the normal flora of the skin and the respiratory tract. Prior to 2000, Trichosporon beigelii was the name given to the pathogen causing both deep infections as well as the superficial white nodules found on hair shafts known as white piedra. The taxonomy has changed and Trichosporon ovoides and Trichosporon inkin are now the causative agents of white piedra of the scalp and of pubic hair, respectively. Trichosporon ashaii, and less commonly, Trichosporon mucoides are the usual pathogens in trichosporonosis. This infection has a poor prognosis, with a mortality rate of up to 83%. We describe the case of a 70-year-old white male kidney transplant patient who died from multiple organ failure following Trichosporon asahii fungemia.
PULSE VS. CONTINUOUS TERBINAFINE FOR TREATMENT OF TOENAIL ONYCHOMYCOSIS: RESULTS OF A DOUBLE-BLIND CONTROLLED TRIAL Erin M Warshaw, MD, University of Minnesota, Mpls, MN, United States, Debra Fett, MD, Indiana University, Indianapolis, IN, United States, Joseph Grill, MS, University of Minnesota, Mpls, MN, United States, Dave Nelson, PhD, University of Minnesota, Mpls, MN, United States Objective: The primary objective of this study was to determine if pulse dosing of terbinafine is as effective as standard, continuous dosing for treatment of toenail onychomycosis. Methods: Study design was that of a double blind, randomized, noninferiority trial of individuals with culture-proven dermatophyte toenail infection involving at least 25% of one toenail. The pulse group received 500 mg of terbinafine once daily for one week per month for three months. The standard, continuous group received 250 mg of terbinafine daily for three months. Endpoints were measured at 18 months. Primary endpoint was mycological cure of the target toenail, defined as a negative culture for dermatophytes and an absence of hyphae in a potassium hydroxide preparation. Secondary endpoints included complete cure of the target toenail (mycological cure plus 100% normal nail) and complete cure of all ten toenails. A total sample size of 300 patients was needed to provide at least 80% power to demonstrate the noninferiority of pulse dosing, using a one-sided 97.5% confidence interval, if it were at least as effective as continuous dosing. Results: The 306 participants were primarily male (96.4%), over 50 years of age (85.9%.), had 100% involvement of the target toenail (54.2%), and had an average of 8 toenails and less than 1 fingernail affected. An intent-to-treat analysis failed to demonstrate that pulse terbinafine is not inferior to standard, continuous terbinafine in achieving mycological cure of the target toenail (58.7% vs. 71.0%), complete cure of the target toenail (28.0% vs. 40.5%), and complete cure of all ten toenails (14.7% vs. 25.2%). Sensitivity analyses were consistent with the intent-to-treat analysis, using “per protocol,” as well as “best,” and “worse” case scenarios for individuals lost to follow-up. Tolerability of the regimens, as measured by a global rating scale, did not differ between the groups (X2 ⫽ 1.63, p ⫽ .65). Acknowledgements: This study is supported by the Minneapolis VAMC and its Center of Excellence on Chronic Disease Outcomes Research
Disclosure not available at press time.
Dr Warshaw has served on the speakers’ bureau for Novartis Pharmaceuticals and has received research grants from Novartis. This study was not funded by Novartis.
P389
P387 PREVALENCE AND EPIDEMIOLOGY OF ONYCHOMYCOSIS IN PATIENTS VISITING PHYSICIANS’ OFFICES: A MULTICENTER CANADIAN SURVEY OF 35,000 PATIENTS Aditya K Gupta, MD, PhD, University of Toronto, London, ON, Canada, Aditya Gupta, MD, PhD, University of Toronto, London, ON, Canada Onychomycosis is a common nail disorder, however few large-scale surveys of onychomycosis prevalence have been made. A multicenter study to assess the prevalence of onychomycosis in the Southwestern Ontario region of Canada has been ongoing from 1995 to the present. Over 35, 000 dermatology patients have been included in this survey, which expands on initial data previously reported (N ⫽ 15000). This will be the largest epidemiology survey reported on the prevalence of onychomycosis, to our knowledge. Consenting patients attending dermatology clinics were inspected by the investigating physicians for signs of nail abnormalities, particularly onychomycosis. Patients referred for onychomycosis or other nail diagnoses were excluded from the survey. Both toenails and fingernails were inspected. Where fungal infection was suspected, the type of infection was noted, as well as how many nails were involved. If fungal infection was suspected, the nail(s) was cultured to confirm the presence of a fungal infection, and if possible, identify the infecting organism. Patients with no abnormalities were noted as ‘normal’, and were not sampled. Other conditions which may influence nail presentations, such as psoriasis, were recorded. Where nail trauma was suspected, this was also recorded. Patients of all ages were surveyed. Abnormal toenails were noticed in approximately 4500 patients (13%). Mycological examination of samples taken from those patients with abnormal toenails showed evidence of fungal infection in approximately 2000 patients (47% of patients sampled). Distal lateral subungual onychomycosis (DLSO) was the diagnosis most frequently noted in surveyed patients. Disclosure not available at press time.
MARCH 2004
COST ANALYSES OF TWO NAIL LACQUERS USED FOR THE TREATMENT OF ONYCHOMYCOSIS INFECTION Line Hamel, formerly Galderma International, La De´fense, France, Lucie Adjadj, formerly Galderma International, La De´fense, France Objectives: The principle aim of this study was to assess the daily treatment cost of two topical therapies-amorolfine 5% nail lacquer and ciclopirox 8% nail lacquer-that are currently available in France, based on their licensed treatment regimens. The secondary aim of this study was to estimate the average cost-effectiveness of the treatments, based on results of clinical studies previously published. Methodology: We used three complementary routes of investigation: measurement of the quantity of drug required to cover the nail, nail size measurements, the distribution of the infected nail and the frequency of nail infections. These data were provided from studying the synthetic nails, investigations of the nail sizes of human volunteers and from the re-examination of data from clinical trails, respectively. Knowing the cost of one bottle of each study drug, these data were combined to calculate the average treatment cost per patient. This information was weighted according to prevalence of infection to show the weighted average total treatment cost per patient. From this, the weighted average daily treatment cost, and the cost per patient cured were calculated. Results: The weighted daily treatment cost of amorolfine, used as indicated to treat onychomycosis infections was found to be 0.22€ when used once a week and 0.38€ when used twice a week. The weighted daily treatment cost of ciclopirox, used as indicated to treat onychomycosis infections, was found to be 0.77€. The cost per cured patient was estimated to be 79.72€ for amorolfine when used once weekly and 239.57€ for ciclopirox. Conclusion: We conclude that, in addition to a lower daily treatment cost, amorolfine 5% nail lacquer is more cost-effective than ciclopirox 8% when used as a topical monotherapy for onychomycosis. Disclosure not available at press time. Study granted by Galderma.
J AM ACAD DERMATOL
P101
P388
A FATAL CASE OF TRICHOSPORONOSIS IN A RENAL-TRANSPLANT PATIENT Jeffery C Weeks, MD, University of Alabama at Birmingham, Birmingham, AL, United States, Sate Hamza, MD, University of Alabama at Birmingham, Birmingham, AL, United States, Boni Elewski, MD, University of Alabama at Birmingham, Birmingham, AL, United States Trichosporonosis is a disseminated, often lethal, infection caused by Trichosporon species that most often affects immunocompromised patients. Trichosporon species can be part of the normal flora of the skin and the respiratory tract. Prior to 2000, Trichosporon beigelii was the name given to the pathogen causing both deep infections as well as the superficial white nodules found on hair shafts known as white piedra. The taxonomy has changed and Trichosporon ovoides and Trichosporon inkin are now the causative agents of white piedra of the scalp and of pubic hair, respectively. Trichosporon ashaii, and less commonly, Trichosporon mucoides are the usual pathogens in trichosporonosis. This infection has a poor prognosis, with a mortality rate of up to 83%. We describe the case of a 70-year-old white male kidney transplant patient who died from multiple organ failure following Trichosporon asahii fungemia.
PULSE VS. CONTINUOUS TERBINAFINE FOR TREATMENT OF TOENAIL ONYCHOMYCOSIS: RESULTS OF A DOUBLE-BLIND CONTROLLED TRIAL Erin M Warshaw, MD, University of Minnesota, Mpls, MN, United States, Debra Fett, MD, Indiana University, Indianapolis, IN, United States, Joseph Grill, MS, University of Minnesota, Mpls, MN, United States, Dave Nelson, PhD, University of Minnesota, Mpls, MN, United States Objective: The primary objective of this study was to determine if pulse dosing of terbinafine is as effective as standard, continuous dosing for treatment of toenail onychomycosis. Methods: Study design was that of a double blind, randomized, noninferiority trial of individuals with culture-proven dermatophyte toenail infection involving at least 25% of one toenail. The pulse group received 500 mg of terbinafine once daily for one week per month for three months. The standard, continuous group received 250 mg of terbinafine daily for three months. Endpoints were measured at 18 months. Primary endpoint was mycological cure of the target toenail, defined as a negative culture for dermatophytes and an absence of hyphae in a potassium hydroxide preparation. Secondary endpoints included complete cure of the target toenail (mycological cure plus 100% normal nail) and complete cure of all ten toenails. A total sample size of 300 patients was needed to provide at least 80% power to demonstrate the noninferiority of pulse dosing, using a one-sided 97.5% confidence interval, if it were at least as effective as continuous dosing. Results: The 306 participants were primarily male (96.4%), over 50 years of age (85.9%.), had 100% involvement of the target toenail (54.2%), and had an average of 8 toenails and less than 1 fingernail affected. An intent-to-treat analysis failed to demonstrate that pulse terbinafine is not inferior to standard, continuous terbinafine in achieving mycological cure of the target toenail (58.7% vs. 71.0%), complete cure of the target toenail (28.0% vs. 40.5%), and complete cure of all ten toenails (14.7% vs. 25.2%). Sensitivity analyses were consistent with the intent-to-treat analysis, using “per protocol,” as well as “best,” and “worse” case scenarios for individuals lost to follow-up. Tolerability of the regimens, as measured by a global rating scale, did not differ between the groups (X2 ⫽ 1.63, p ⫽ .65). Acknowledgements: This study is supported by the Minneapolis VAMC and its Center of Excellence on Chronic Disease Outcomes Research
Disclosure not available at press time.
Dr Warshaw has served on the speakers’ bureau for Novartis Pharmaceuticals and has received research grants from Novartis. This study was not funded by Novartis.
P389
P387 PREVALENCE AND EPIDEMIOLOGY OF ONYCHOMYCOSIS IN PATIENTS VISITING PHYSICIANS’ OFFICES: A MULTICENTER CANADIAN SURVEY OF 35,000 PATIENTS Aditya K Gupta, MD, PhD, University of Toronto, London, ON, Canada, Aditya Gupta, MD, PhD, University of Toronto, London, ON, Canada Onychomycosis is a common nail disorder, however few large-scale surveys of onychomycosis prevalence have been made. A multicenter study to assess the prevalence of onychomycosis in the Southwestern Ontario region of Canada has been ongoing from 1995 to the present. Over 35, 000 dermatology patients have been included in this survey, which expands on initial data previously reported (N ⫽ 15000). This will be the largest epidemiology survey reported on the prevalence of onychomycosis, to our knowledge. Consenting patients attending dermatology clinics were inspected by the investigating physicians for signs of nail abnormalities, particularly onychomycosis. Patients referred for onychomycosis or other nail diagnoses were excluded from the survey. Both toenails and fingernails were inspected. Where fungal infection was suspected, the type of infection was noted, as well as how many nails were involved. If fungal infection was suspected, the nail(s) was cultured to confirm the presence of a fungal infection, and if possible, identify the infecting organism. Patients with no abnormalities were noted as ‘normal’, and were not sampled. Other conditions which may influence nail presentations, such as psoriasis, were recorded. Where nail trauma was suspected, this was also recorded. Patients of all ages were surveyed. Abnormal toenails were noticed in approximately 4500 patients (13%). Mycological examination of samples taken from those patients with abnormal toenails showed evidence of fungal infection in approximately 2000 patients (47% of patients sampled). Distal lateral subungual onychomycosis (DLSO) was the diagnosis most frequently noted in surveyed patients. Disclosure not available at press time.
MARCH 2004
COST ANALYSES OF TWO NAIL LACQUERS USED FOR THE TREATMENT OF ONYCHOMYCOSIS INFECTION Line Hamel, formerly Galderma International, La De´fense, France, Lucie Adjadj, formerly Galderma International, La De´fense, France Objectives: The principle aim of this study was to assess the daily treatment cost of two topical therapies-amorolfine 5% nail lacquer and ciclopirox 8% nail lacquer-that are currently available in France, based on their licensed treatment regimens. The secondary aim of this study was to estimate the average cost-effectiveness of the treatments, based on results of clinical studies previously published. Methodology: We used three complementary routes of investigation: measurement of the quantity of drug required to cover the nail, nail size measurements, the distribution of the infected nail and the frequency of nail infections. These data were provided from studying the synthetic nails, investigations of the nail sizes of human volunteers and from the re-examination of data from clinical trails, respectively. Knowing the cost of one bottle of each study drug, these data were combined to calculate the average treatment cost per patient. This information was weighted according to prevalence of infection to show the weighted average total treatment cost per patient. From this, the weighted average daily treatment cost, and the cost per patient cured were calculated. Results: The weighted daily treatment cost of amorolfine, used as indicated to treat onychomycosis infections was found to be 0.22€ when used once a week and 0.38€ when used twice a week. The weighted daily treatment cost of ciclopirox, used as indicated to treat onychomycosis infections, was found to be 0.77€. The cost per cured patient was estimated to be 79.72€ for amorolfine when used once weekly and 239.57€ for ciclopirox. Conclusion: We conclude that, in addition to a lower daily treatment cost, amorolfine 5% nail lacquer is more cost-effective than ciclopirox 8% when used as a topical monotherapy for onychomycosis. Disclosure not available at press time. Study granted by Galderma.
J AM ACAD DERMATOL
P101