Confirmatory Testing Prior to Initiating Onychomycosis Therapy Is Cost-Effective.

BACKGROUND: Onychomycosis can be investigated by sampling. Information gleaned includes nail bed involvement, nail plate penetration, fungal viability, and species identification. Testing samples can confirm a diagnosis. While diagnostic testing is considered useful in directing therapy, a substantial number of clinicians do not confirm diagnosis prior to treatment. OBJECTIVES: The aim of this study is to quantify the benefit of confirmatory testing prior to treating toenail onychomycosis. METHODS: The cost of mycological cure (negative potassium hydroxide and negative culture) and the cost-effectiveness of confirmatory testing were determined using the average cost of potassium hydroxide (KOH), culture, periodic acid-Schiff (PAS), efinaconazole, ciclopirox, terbinafine, and itraconazole. Costs were obtained through literature searches, public domain websites, and telephone surveys to local pharmacies and laboratories. To represent the potential risks of prescribing onychomycosis treatment, the costs associated with liver monitoring, potential life-threatening adverse events, and drug-drug interactions were obtained through public domain websites, published studies, and product inserts. RESULTS: PAS was determined to be the most sensitive confirmatory test and KOH the least expensive. The overall cost of an incorrect diagnosis (no confirmatory test used) ranged between $350 and $1175 CAD per patient for treatment of 3 infected toenails. Comparatively, performing confirmatory testing prior to treatment decreases the overall cost to $320 to $930, depending on the therapy, physician, and test. CONCLUSIONS: It is preferred to diagnose onychomycosis prior to treatment. Furthermore, there are cost savings when confirmatory testing is performed before initiating treatment with both topical and oral antifungals in Canada.

Cost-effectiveness of Confirmatory Testing Before Treatment of Onychomycosis.

IMPORTANCE: Onychomycosis is the most common disease of the nail in adults. International guidelines urge health care professionals to perform confirmatory diagnostic testing before initiating systemic therapy. This approach was determined to be cost-effective in studies from the late 1990s but has not been evaluated more recently. The effect of testing on the costs of efinaconazole, 10%, topical solution treatment is unknown. OBJECTIVE: To evaluate the cost and potential harm associated with 3 approaches to onychomycosis evaluation before treatment with oral terbinafine or efinaconazole, 10%. DESIGN, SETTING, AND PARTICIPANTS: A decision analysis that compared the costs of 3 onychomycosis management algorithms based on recently published data of test statistics, disease prevalence, and relevant costs: (1) empirical therapy without confirmatory testing, (2) pretreatment confirmatory testing with potassium hydroxide (KOH) stain followed by periodic acid-Schiff (PAS) evaluation if KOH testing is negative, and (3) pretreatment testing with PAS. There was no direct patient evaluation. Selection of included studies was based on outcome variables and the quality of study design. The study was conducted from April 1, 2014, to September 1, 2015. MAIN OUTCOMES AND MEASURES: Primary outcomes included direct cost of onychomycosis testing and therapy and cost to avoid harm when treating patients with oral terbinafine. RESULTS: At a disease prevalence of 75%, per-patient cost savings of empirical terbinafine therapy without confirmatory testing was $47 compared with the KOH screening model and $135 compared with PAS testing. The cost of testing necessary to prevent a single case of clinically relevant liver toxic effects related to terbinafine at a prevalence of 75% was between $18.2 million and $43.7 million for KOH screening and between $37.6 million and $90.2 million for PAS testing. At a prevalence of 75%, KOH screening and PAS testing before treatment with efinaconazole, 10%, saved $272 and $406 per patient per nail, respectively. CONCLUSIONS AND RELEVANCE: These results show that empirical treatment with terbinafine for patients with suspected onychomycosis is more cost-effective than confirmatory testing across all prevalence of disease, with minimal effect on patient safety. In contrast, confirmatory testing before treatment with efinaconazole, 10%, is associated with reduced costs. Blanket recommendations for confirmatory testing before systemic therapy should be reconsidered and replaced with recommendations tailored to specific therapies.

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.

A multicentre, randomized, controlled study of the efficacy, safety and cost-effectiveness of a combination therapy with amorolfine nail lacquer and oral terbinafine compared with oral terbinafine alone for the treatment of onychomycosis with matrix involvement.

BACKGROUND: Onychomycosis is common, accounting for up to 50% of all nail disorders. Toenail onychomycosis can cause nail deformity, embarrassment, pain and walking difficulties. Some populations, such as individuals with diabetes, are at higher risk for developing secondary complications such as infections. Treatment takes many months and therapeutic choices can increase clinical effectiveness, lower toxicity and minimize healthcare costs. OBJECTIVES: Based on the results of a previous pilot study, the objective of the present study was to show, in a larger population, the enhanced efficacy of a combination of amorolfine nail lacquer and oral terbinafine in the treatment of onychomycosis with matrix involvement. In addition, a cost-effectiveness analysis was performed. METHODS: In this multicentre, randomized, open-label, parallel group study, patients were randomized to receive either a combination of amorolfine hydrochloride 5% nail lacquer once weekly for 12 months plus terbinafine 250 mg once daily for 3 months (AT group) or terbinafine alone once daily for 3 months (T group). The study duration was 18 months including a 6-month treatment-free phase following the 12-month active treatment phase for the AT group and a 15-month treatment-free phase following the 3-month active treatment phase for the T group. The primary efficacy criterion was overall response, dichotomized into success or failure, success being the combination of clinical cure and negative mycology at month 18. This criterion was used as the effectiveness measure in the pharmacoeconomic analysis, conducted from a payer perspective. RESULTS: In total, 249 patients were included into the study: 120 in the AT group and 129 in the T group. A significantly higher success rate was observed for patients in the AT group relative to those in the T group at 18 months (59.2% vs. 45.0%; P = 0.03). Both treatment regimens were safe and well tolerated. Treatment cost per cured patient was lower for the combination than for terbinafine alone in all countries. CONCLUSIONS: Study results confirmed that, in the treatment of dermatophytic toenail onychomycosis with matrix involvement, amorolfine nail lacquer in combination with oral terbinafine enhances clinical efficacy and is more cost-effective than terbinafine alone.

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

Evaluating costs for onychomycosis treatments: a practitioner's perspective.

Onychomycosis is a common problem. The desired outcome of treatment for patients and clinicians is complete cure (negative culture and negative potassium hydroxide examination results plus a completely normal nail). This cost analysis sought to determine the cost-effectiveness of treatments for onychomycosis using complete cure as a unit of effectiveness. A simplified cost-effectiveness analysis was conducted using complete cure rates from randomized, blinded clinical trials involving at least 50 participants. Trials were identified by searching the literature, manually searching for review articles, and reviewing medication package inserts. For each trial that met the entry criteria, three levels of cost were used to calculate medication cost per complete cure: commercial price, average wholesale price, and Veterans Affairs pharmacy price. In addition, a computerized economic model was used to determine total cost per complete cure, including all medical costs. The most cost-effective treatments were those that involved terbinafine: pulse, continuous, or in combination with other agents. Itraconazole, griseofulvin, and fluconazole were less cost-effective. Ciclopirox nail lacquer was at least three times more expensive than all other agents when evaluating total costs per complete cure. Overall, the lowest cost per complete cure resulted from terbinafine treatment, with most evidence supporting 3 months of continuous therapy.

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.

Pharmacoeconomic issues in onychomycosis.

The importance of health economics (the application of economics to healthcare and medicine) has grown significantly in recent years as the need to maximize the use of limited healthcare resources has increased. The role of pharmacoeconomics (the application of health economics to pharmaceuticals) is to provide a method that evaluates outcomes and costs of treatment at the same time, thus providing an aid to better decision-making. However, there remains some uncertainty within the medical community about the usefulness of pharmacoeconomic data. Reasons for this include a poor understanding of the purpose and outcome of pharmacoeconomic studies, inconsistent use of terminology, and a perception that freedom of choice of prescriptions is restricted. To optimize the medical management of patients with severe onychomycosis, two pharmacoeconomic evaluations of amorolfine were undertaken. In a comparison of topical amorolfine + oral terbinafine vs. oral terbinafine alone, treatment with the topical/oral combination for a period of up to 12 weeks resulted in an improved outcome compared with the oral drug alone. A second study with topical amorolfine + oral itraconazole showed that treatment for a period of 6 weeks was the preferred cost-effective treatment option. While combination therapy might seem to be a more costly option, pharmacoeconomic studies have clearly shown that treatment of onychomycosis with amorolfine, in combination with either oral terbinafine or oral itraconazole, is both cost-saving and cost-effective compared with oral treatment alone.

Economic analysis of oral and topical therapies for onychomycosis of the toenails and fingernails.

OBJECTIVE: Several antifungal agents are indicated for onychomycosis, a fungal infection of the toenails and fingernails. These agents differ in their dosing regimen, efficacy, adverse events profile, potential for drug interaction, and cost. We conducted a pharmacoeconomic analysis of oral and topical therapies for onychomycosis from the perspective of a hypothetical managed care payer to determine the most cost-effective agent. DESIGN: A decision analytic model was developed to evaluate the pharmacoeconomic profiles of itraconazole-continuous (Sporanox, Janssen Pharmaceutica), itraconazole-pulse (Sporanox, Janssen Pharmaceutica), terbinafine (Lamisil, Novartis Pharmaceuticals), and ciclopirox (Penlac, Dermik Laboratories) in the treatment of fingernail and toenail onychomycosis. METHODOLOGY: We conducted a meta-analysis of the available literature to populate the decision analytic model with clinical point estimates for success, failure, and relapse. A panel of expert dermatologists defined resources consumed during the onychomycosis treatment process. These resources were then assigned values, using publicly available data sources, to reflect the U.S. managed care perspective. These clinical and economic data elements were integrated in the decision analytic model to arrive at the expected cost of treatment for each drug. Additionally, incremental cost-effectiveness was calculated for treatment success and disease-free days achieved by each therapy. Finally, a policy-level analysis of the budgetary impact of using the therapies for onychomycosis in a managed care setting was conducted. RESULTS: The meta-analysis demonstrated terbinafine to be the therapeutic alternative with the highest success rate for both fingernails (96.55 percent) and toenails (81.15 percent). Terbinafine also had the lowest relapse rate (6.42 percent) and the highest number of disease-free days for both fingernails and toenails. Subsequently, in terms of cost-effectiveness, terbinafine dominated all other comparators for fingernails and toenails. CONCLUSIONS: Based on the patient-level analysis, we concluded that terbinafine is the most cost-effective therapy in the treatment of onychomycosis from a managed care perspective. Furthermore, at the policy level, increased utilization of terbinafine among onychomycosis patients is likely to reduce the managed care organizations' per member per month cost.

[Pharmacoeconomic aspects of the treatment of onychomycosis]. / Aspects pharmaco-économiques des onychomycoses.

The clinical management of severe onychomycosis is known to be a long and difficult task. When deciding which treatment to prescribe to our patients we may be tempted to use the efficacy rate as the only objective measurement or on the other hand to assess treatment costs only by looking at the drug acquisition cost. The role of pharmacoeconomics is to provide a method that evaluates outcomes and costs at the same time; it is an aid to better decision making. Cost effectiveness studies take into account the efficacy of each treatment regimen balanced against the global cost of treatment. So we can assess the number of patients cured for a given health care budget. Two recent studies presenting the results of a combination therapy of an antifungal therapy and antifungal lacquer give us the opportunity to illustrate some pharmacoeconomic principals.