The EVerT2 (Effective Verruca Treatments 2) trial: a randomized controlled trial of needling vs. nonsurgical debridement for the treatment of plantar verrucae.

BACKGROUND: Verrucae are a common foot skin pathology, which can in some cases persist for many years. Plantar verrucae can be unsightly and painful. There are a range of treatment options including needling. OBJECTIVES: The EVerT2 (Effective Verruca Treatments 2) trial aimed to evaluate the clinical and cost-effectiveness of the needling procedure for the treatment of plantar verrucae, relative to callus debridement. METHODS: This single-centre randomized controlled trial recruited 60 participants (aged ≥ 18 years with a plantar verruca). Participants were randomized 1 : 1 to the intervention group (needling) or the control group (debridement of the overlying callus). The primary outcome was clearance of the index verruca at 12 weeks after randomization. Secondary outcomes included recurrence of the verruca, clearance of all verrucae, number of verrucae, size of the index verruca, pain and participant satisfaction at 12 and 24 weeks. A cost-effectiveness analysis was carried out from the National Health Service perspective over 12 weeks. RESULTS: Sixty eligible patients were randomized (needling group n = 29, 48%; debridement group n = 31, 52%) and 53 were included in the primary analysis (needling n = 28, 97%; debridement n = 25, 81%). Clearance of the index verruca occurred in eight (15%) participants (needling n = 4, 14%; debridement n = 4, 16%; P = 0·86). The needling intervention costs were on average £14·33 (95% confidence interval 5·32-23·35) more per patient than for debridement. CONCLUSIONS: There is no evidence that the needling technique is more clinically or cost-effective than callus debridement. The results show a significant improvement in pain outcomes after needling compared with the debridement treatment alone.

A multicenter, randomized, open-label, controlled study comparing the efficacy, safety and cost-effectiveness of a sequential therapy with RV4104A ointment, ciclopiroxolamine cream and ciclopirox film-forming solution with amorolfine nail lacquer alone in dermatophytic onychomycosis.

BACKGROUND: The efficacy of topical antifungals is controversial. OBJECTIVE: To compare the efficacy and safety of a sequential(SEQ) treatment with chemical nail avulsion and topical antifungals to amorolfine nail lacquer in dermatophytic onychomycosis. METHODS: This was a randomized,parallel-group, controlled study comparing a 36-week SEQ treatment with chemical nail avulsion with RV4104A ointment(class I medical device containing 40% urea) followed by ciclopirox cream for 8 weeks and ciclopirox nail lacquer for 25 weeks (SEQ group) to amorolfine nail lacquer for 36 weeks (AMO group). Patients had to have a big toenail onychomycosis,sparing the matrix. The primary efficacy criterion was complete cure at week 48. A cost-effectiveness analysis was performed. RESULTS: A total of 142 patients were randomized. The complete cure rate at week 48 was significantly higher in the SEQ group than in the AMO group (36.6 vs. 12.7%, p = 0.001). Clinical cure at week 48 was observed in 53.5% of patients in the SEQ group versus 17% in the AMO group (p < 0.01). The cost of cure per patient was 50% lower with SEQ treatment (EUR 33) compared with amorolfine(EUR 76). CONCLUSION: A treatment of onychomycosis comprising chemical avulsion of the pathological nail, ciclopirox cream and nail lacquer is significantly more effective than amorolfine nail lacquer.

Reliability of self-reported willingness-to-pay and annual income in patients treated for toenail onychomycosis.

BACKGROUND: Willingness-to-pay (WTP) is a health economics measure that has recently been used for skin diseases to evaluate patients' quality of life. However, the reliability of this measure has not been investigated in the dermatology literature and is essential in validating its use in health services research. OBJECTIVES: This study evaluated the test-retest reliability of self-reported annual income and WTP, a health economics measure of disease impact, in patients with toenail onychomycosis. METHODS: Forty-six patients enrolled in a randomized clinical trial comparing two different dosing regimens of terbinafine completed a self-administered questionnaire at baseline and 1 month later. The questionnaire asked: (i) how much patients would be willing to pay for a theoretical treatment with a cure rate of 85% for their current onychomycosis (10 categories: $0-50, $51-100, to > $800); and (ii) annual income (10 categories: $0-10,000 to > $200,000). RESULTS: Forty-four patients reported WTP at both visits, and 55% reported the same WTP. The quadratic-weighted (Fleiss-Cohen) kappa statistic indicated moderate agreement (kappa = 0.50, 95% confidence interval, CI 0.24-0.75, P < 0.01) as did the Spearman rank-order correlation coefficient (r(s) = 0.57, P < 0.01; median difference = 0, P = 0.50). Strong agreement was shown among the 42 patients who reported income at both visits; 71% reported the same annual income category (kappa = 0.72, 95% CI 0.47-0.96, P < 0.01; r(s) = 0.68, P < 0.01; median difference = 0, P = 0.77). Age, disease severity and duration, previous therapy, self-reported annual income, and medication side-effects were not statistically associated with the reliability of WTP. CONCLUSIONS: WTP and annual income demonstrated moderate and strong test-retest reliability, respectively. Self-reported WTP can serve as a reliable measure for future health economics research on onychomycosis.

Cost-effectiveness of diagnostic tests for toenail onychomycosis: a repeated-measure, single-blinded, cross-sectional evaluation of 7 diagnostic tests.

OBJECTIVE: Our purpose was to estimate and compare the cost-effectiveness of the most commonly used diagnostic tests for onychomycosis: potassium hydroxide preparation (KOH), interpreted both by a dermatologist (KOH-CLINIC) and a laboratory technician (KOH-LAB); KOH with dimethyl sulfoxide (KOH-DMSO) and with chlorazol black E (KOH-CBE), interpreted by a dermatologist; culture using dermatophyte test medium, culture with Mycobiotic and Inhibitory Mold Agar (Cx); and histopathologic analysis using periodic acid-Schiff stain (PAS). METHODS: This was a repeated-measure, blinded, cross-sectional study conducted at the Minneapolis Veterans Affairs Medical Center. Inclusion criteria included: at least one toenail with 25% or more clinical disease, which was defined as subungual debris with onycholysis and/or onychauxis. Exclusion criteria included other nail dystrophies, use of oral antifungal medication for 2 months or longer within the past year, or topical ciclopirox lacquer within 6 weeks of enrollment. The main outcome measure was the cost-effectiveness (Medicare and non-Medicare costs) of 7 diagnostic tests. Sensitivity (at least 3 positive tests) was the unit of effectiveness. RESULTS: Two hundred four participants were enrolled; their average age was 69.5 years and 95.5% were male. PAS was the most sensitive test (98.8%); it was statistically significantly more sensitive than all other diagnostic tests except KOH-CBE (94.3%). Dermatophye test medium was the least sensitive test (57.3%). KOH-CBE was statistically significantly more cost effective than any other test, with the exception of KOH-CLINIC and KOH-LAB. PAS was the least cost effective. LIMITATIONS: Test specificities were not evaluated. CONCLUSION: KOH-CBE should be the test of choice for practitioners confident in interpreting KOH preparations because of its combination of high sensitivity and cost-effectiveness.

Onychomycosis in primary school children: association with socioeconomic conditions.

Onychomycosis in childhood is reported to be unusual. The aim of this study was to determine the prevalence of onychomycosis in primary school children and to make comparison between different socioeconomic status in the rural and urban areas of the city. Hand and foot nails of 23235 children aged 7-14 were examined. Onychomycosis was suspected and nail scrapings for mycological examination were taken in 116 of them. Hyphae or spores were seen in 41 (0.18%) by direct microscopic examination, and mycological cultures were positive in 24 (0.1%) of them. Toenails were affected in all of the fungal culture positive cases. Trichosporon spp, Trichophyton rubrum, Candida albicans and Candida glabrata grew in 11, 6, 5 and 2 of the cultures respectively. Onychomycosis prevalence was significantly higher in the children living in the rural areas (p = 0.016) [Odds ratio = 3.43 (%95 CI 1.11

Utility of histopathologic analysis in the evaluation of onychomycosis.

Onychomycosis is a common problem seen in clinical practice. Given the differential diagnosis of dystrophic nails, it is helpful to obtain a definitive diagnosis of dermatophyte infection before initiation of antifungal therapy. Potassium hydroxide preparation and fungal culture, which are typically used in the diagnosis of these infections, often yield false-negative results. Recent studies have suggested that nail plate biopsy with periodic acid-Schiff stain may be a very sensitive technique for the diagnosis of onychomycosis. In this article, we review the literature on the utility of histopathologic analysis in the evaluation of onychomycosis. Many of these studies indicate that biopsy with periodic acid-Schiff is the most sensitive method for diagnosing onychomycosis. We propose that histopathologic examination is indicated if the results of other methods are negative and clinical suspicion is high; therefore, it is a useful complementary technique in the diagnosis of onychomycosis.

Treatment costs of three nail lacquers used in onychomycosis.

OBJECTIVE: To assess the daily treatment costs and the average cost-effectiveness of three topical onychomycosis therapies - amorolfine 5% and ciclopirox 8% nail lacquers and tioconazole 28% nail solution - when used as indicated in France, the UK, Germany and Italy. METHODS: The quantity of drug required and nail size measurements were investigated and, knowing the cost per bottle of each study drug, used to calculate the average treatment cost per patient. Using the prevalence of infection data, the weighted average total treatment cost per patient and hence the weighted average daily treatment cost and cost per patient cured, were calculated. RESULTS: Amorolfine was consistently more cost-effective in terms of weighted average daily treatment cost and cost per patient cured than ciclopirox and tioconazole, when all therapies were used as indicated to treat onychomycosis. In France, for example, the weighted average daily treatment cost of amorolfine was found to be euro 0.23 and euro 0.40 when used once and twice a week, respectively; the cost per patient cured for amorolfine was euro 84. By comparison, the weighted average daily treatment cost of ciclopirox was found to be euro 0.81; the cost per patient cured was euro 252. CONCLUSIONS: When used as indicated, amorolfine 5% nail lacquer is more cost-effective than ciclopirox 8% and tioconazole 28% for onychomycosis of toenail, fingernail or both in males and females in France, UK, Germany and Italy.

Treatment of dermatophyte toenail onychomycosis in the United States. A pharmacoeconomic analysis.

This study attempted to determine the cost-effectiveness of therapies for dermatophyte toenail onychomycosis in the United States in 2001. The antimycotic agents evaluated were ciclopirox 8% nail lacquer and the oral agents terbinafine, itraconazole (pulse), itraconazole (continuous), fluconazole, and griseofulvin. A treatment algorithm for the management of onychomycosis was developed, and a meta-analysis was carried out to determine the average mycologic and clinical response rates for the various agents. The cost of the regimen was figured as the sum of the costs of drug acquisition, medical management, and management of adverse effects. The expected cost of management and disease-free days were determined, and a sensitivity analysis was conducted. It was concluded that ciclopirox 8% nail lacquer, which has recently become available in the larger size of 6.6 mL, is a cost-effective agent for the management of toenail onychomycosis.

Pharmacoeconomic analysis of ciclopirox nail lacquer solution 8% and the new oral antifungal agents used to treat dermatophyte toe onychomycosis in the United States.

BACKGROUND: Recently a novel topical nail lacquer, ciclopirox solution 8%, has been approved for the treatment of onychomycosis. OBJECTIVE: This was undertaken to determine the most cost-effective treatment for the treatment of dermatophyte onychomycosis of the toes in the United States in 2000. METHODS: The nature of the problem was defined. The drug comparators were ciclopirox nail lacquer, terbinafine, itraconazole (pulse), itraconazole (continuous), fluconazole, and griseofulvin. A decision analytic model that reflected the manner in which pedal tinea unguium is managed was produced. Studies that have evaluated the efficacy of the nail lacquer and the oral antifungal agents for this indication were identified. Appropriate studies were used in a meta-analysis to determine the mycologic and clinical response rates when the drug comparators are used for the treatment for toe dermatophyte onychomycosis. For each drug comparator a cost of regimen analysis was carried out. This is the sum of the drug acquisition cost, the cost of medical management, and the cost of managing adverse effects. Next, the expected cost of management was calculated, disease free days were determined, and a sensitivity analysis was conducted. RESULTS: For each comparator the meta-analytic average mycologic cure (MC) rate and clinical response (CR) rates were: ciclopirox nail lacquer (MC: 52.6 +/- 4.2%, CR: 52.4 +/- 9.0%), griseofulvin (MC: 41.1 +/- 20.4%, CR: 33.7 +/- 14.1%), itraconazole (continuous) (MC: 66.3 +/- 4.2%, CR: 70.3 +/- 4.2%), itraconazole (pulse) (MC: 70.8 +/- 5.7%, CR: 73.6 +/- 4.6%), terbinafine (MC: 77.2 +/- 4.0%, CR: 75.3 +/- 2.9%), and fluconazole (MC: 65.6 +/- 7.1%, CR: 66.5 +/- 11.7%). The cost of regimen for the drug comparators was: ciclopirox nail lacquer $325.2, griseofulvin $1413.1, itraconazole (continuous) $1410.2, itraconazole (pulse) $811.7, terbinafine $890.1, and fluconazole $966.8. The cost/mycologic cure rate and expected cost/expected symptom free day were, ciclopirox nail lacquer ($618.2, 1.69), griseofulvin $3438.2, 5.3), itraconazole (continuous) ($2126.9, 3.52), itraconazole (pulse) ($1146.4, 2.01), terbinafine ($1153.0, 2.14), and fluconazole ($1473.7, 2.10). The relative cost-effectiveness was ciclopirox nail lacquer 1.00, itraconazole (pulse) 1.19, fluconazole 1.24, terbinafine 1.27, itraconazole (continuous) 2.08, and griseofulvin 3.13. Sensitivity analysis indicated that ciclopirox nail lacquer was a cost effective alternative compared with the oral regimens of terbinafine, itraconazole (continuous), and griseofulvin when clinical response rate was used as the primary efficacy parameter. CONCLUSION: Ciclopirox nail lacquer solution 8% is a recent addition to the armamentarium of therapies available to the physician and patient for the treatment of onychomycosis. The nail lacquer is a cost effective agent compared with the oral antifungal therapies, terbinafine, itraconazole, fluconazole, and griseofulvin.

Onychomycosis: current treatment and future challenges.

Onychomycosis is a fungal infection of the nails, more often of the toenails. It is a common condition, with an estimated overall prevalence of 3-10% in European populations. Dermatophytes, especially Trichophyton rubrum and Trichophyton mentagrophytes, are the usual pathogens. Some 50% of infected patients fail to seek medical advice. Medically confirmed onychomycosis should be treated. This recommendation is based on several disease-specific considerations: cosmetic and functional disability, lack of spontaneous remission, impairment of health and wellbeing in elderly patients and the need to reduce contamination in communal bathing places. Current treatments for onychomycosis include oral antifungal agents such as terbinafine (Lamisil) and itraconazole (Sporanox). They offer significantly improved rates of cure, shorter treatment regimens and a lower level of adverse events than was previously the case. Comparative studies have shown that terbinafine is more effective than griseofulvin, fluconazole or itraconazole in the treatment of this condition, providing a cure rate of 70-80% and an excellent tolerability profile. Terbinafine is also the most cost-effective agent. However, several problems remain that will provide future challenges in the treatment of onychomycosis, not least the consistent treatment failure rate of 20%. In many of these cases, surgery may need to precede drug therapy in order to maximise the prospects of clinical and mycological cure. In addition, duration of treatment also needs to be more closely adjusted to the individual case by prior identification of severity and extent of toenail infection, and combined oral and topical therapy also requires further investigation.

Effect of onychomycosis on quality of life.

BACKGROUND: Onychomycosis impairs normal nail functions, causes considerable pain, interferes with daily activities, and has negative psychosocial effects. OBJECTIVE: Our purpose was to determine patients' perception of onychomycosis on the quality of life. METHODS: A total of 258 patients with confirmed onychomycosis were surveyed by telephone at three centers. Responses to a standardized quality-of-life questionnaire were analyzed for patient demographics, physical and functional impact, psychosocial impact, and economic impact. RESULTS: Highest positive responses were nail-trimming problems (76%), embarrassment (74%), pain (48%), nail pressure (40%), and discomfort wearing shoes (38%). Ability to pick up small objects was impaired in 41% of subjects with fingernail involvement. More than 58 onychomycosis-related sick days and 468 medical visits (1.8 per subject) were reported during a 6-month period. CONCLUSION: Onychomycosis has significant social, psychologic, health, and occupational effects. Relevance of quality-of-life issues to overall health, earning potential, and social functioning should prompt reconsideration of the value of aggressive treatment of and financial coverage for onychomycosis.

Pharmacoeconomic analysis of oral antifungal therapies used to treat dermatophyte onychomycosis of the toenails. A US analysis.

Until a few years ago, griseofulvin and ketoconazole were the only 2 oral agents available for the treatment of dermatophyte onychomycosis of the toenails. With the availability of the newer antifungal agents, such as itraconazole, terbinafine and fluconazole, the armamentarium of drugs available to treat onychomycosis has expanded. The objective of this study was to determine the relative cost effectiveness of the most commonly used oral antifungal agents in the US for the treatment of dermatophyte onychomycosis of the toenails from the perspective of a third-party payer. The time horizon was 3 years. A 5-step approach was used in this pharmacoeconomic analysis. First, the purpose of the study, the comparator drugs and their dosage regimens were defined. In step II, the medical practice and resource-consumption patterns associated with the treatment of onychomycosis were identified. In step III, a meta-analysis was performed on all studies meeting prespecified criteria, and the mycological cure rates of the comparator drugs were determined. In step IV, the treatment algorithm for the management of onychomycosis was constructed for each drug. The cost-of-regimen analysis for each comparator incorporated the drug acquisition cost, medical-management cost and cost of managing adverse drug reactions. The expected cost per patient, number of symptom-free days (SFDs), cost per SFD and the relative cost effectiveness for the comparator drugs were calculated. In step V, a sensitivity analysis was performed. The drug comparators for this study were griseofulvin, itraconazole (continuous and pulse), terbinafine and fluconazole. The mycological cure rates [mean +/- standard error (SE)] from the meta-analysis were griseofulvin 24.5 +/- 6.7%, itraconazole (continuous) 66.4 +/- 6.1%, itraconazole (pulse) 76 +/- 9.3%, terbinafine 74 +/- 7% and fluconazole 59%. The cost per mycological cure was griseofulvin $US8089, itraconazole (continuous) $US1877, itraconazole (pulse) $US991, terbinafine $US1125 and fluconazole $US1506. The corresponding cost per SFD was griseofulvin $US7.05, itraconazole (continuous) $US2.18, itraconazole (pulse) $US1.26, terbinafine $US1.28 and fluconazole $US2.12. The resulting ratios of cost per SFD relative to itraconazole (pulse) [1.00] were terbinafine 1.02, itraconazole (continuous) 1:73, fluconazole 1.69 and griseofulvin 5.62. In conclusion, in this analysis, itraconazole (pulse) and terbinafine were the most cost-effective therapies for dermatophyte onychomycosis of the toenails, both being substantially more cost effective than griseofulvin.

A multinational pharmacoeconomic analysis of oral therapies for onychomycosis. The Onychomycosis Study Group.

Due to increased interest in economic evaluation and the rapid international spread of new healthcare technologies across borders, there is a need to interpret economic evaluations on a worldwide basis. We conducted a multinational cost-effectiveness analysis, from a government payer perspective, comparing four primary oral treatment regimens for onychomycosis of the fingernails and toenails: griseofulvin, itraconazole, ketoconazole and terbinafine. We used a four-step pharmacoeconomic research model which includes all relevant factors affecting costs in 13 countries: Austria, Belgium, Canada, Finland, France, Germany, Greece, Italy, The Netherlands, Portugal, Spain, Switzerland and the U.K. A worldwide meta-analysis of published clinical data served as the statistical input for the pharmacoeconomic model, and demonstrated that terbinafine had the highest success rates (95.0% and 78.3%) of the clinical comparators for fingernails and toenails, respectively. We found that terbinafine was the most effective therapy in relation to cost (therefore giving it the lowest cost-effectiveness ratio) for both infections in all health-care systems analysed.