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Abstract

The objective of this study was to assess the efficacy of a single application of terbinafine 1% film-forming solution (FFS) compared with other topical antifungal treatments for tinea pedis using meta-analytical methods. Randomised, double-blind, vehicle-controlled clinical trials were identified using a comprehensive literature search, and mycological cure rates were meta-analysed by treatment type: FFS versus vehicle and other active treatments versus vehicle. Treatment effects were estimated on a rate difference scale. The difference in treatment effect between FFS and other topical agents was then estimated to derive an indirect estimate of the effect of FFS versus each comparator with its 95% confidence interval [CI]. Terbinafine FFS gave consistent results and the meta-analysis provided a difference from vehicle in mycological cure rate of 53.5+-4.4% and a 95% CI of 44.9-62%. This cure rate was non-inferior to that found with other agents (including the azoles) when used for many weeks of treatment, and was even superior to some (clotrimazole, oxiconazole). A single application of terbinafine 1% FFS was also non-inferior to other allylamines (butenafine, naftifine) and to ciclopiroxolamine when used for many weeks of treatment. A single application of terbinafine FFS is non-inferior to multiple applications of other formulations of terbinafine and of all the other approved topical agents in medical use that yielded randomised vehicle-controlled trials on a comprehensive literature search.

Athlete's foot (tinea pedis) is a common foot infection caused by dermatophyte fungi. Treatment is by the application of topical antifungals, typically for a period of one to four weeks. Noncompliance with treatment of this duration is an issue and may be one of the reasons why the condition has a high rate of recurrence. In a survey of 900 patients conducted in Germany, France and the UK, half of respondents applied antifungal treatment for less than 13 days, even though commonly available antifungal drugs require three to four weeks' use.

Antifungal agents can be classified as fungicidal or fungistatic. Fungicidal agents such as the allylamines (including terbinafine) are compounds that kill fungi, whereas fungistatic agents (for example the azole class of compounds) inhibit the growth of fungi.1 Terbinafine is fungicidal against dermatophytes at concentration levels (minimum inhibitory concentrations 1-10ng/ml) well below those achieved by oral or topical administration, and is widely used as a topical agent in the treatment of tinea pedis. It is available in a variety of topical formulations (Lamisil, Novartis Consumer Health SA, Nyon, Switzerland). Recently, the film-forming solution (FFS) terbinafine 1%, which is intended to be applied only once, was made available in Europe and other markets internationally. Compliance with a single application of a topical antifungal is expected to be considerably better than compliance with a treatment requiring daily applications for anything from one to four weeks. If equivalent efficacy could be shown for FFS compared with reference treatments (whether other formulations of terbinafine or other agents), there would be an advantage for the simpler singleuse treatment.

There are only two published randomised controlled clinical trials with terbinafine FFS,2,3 and both of them compared it with its vehicle. In order to compare FFS with other clinically available active treatments, one must rely on an indirect method of comparison. A recent meta-analysis1 compared various formulations of terbinafine with each other and found that this agent is very well tolerated in any topical pharmaceutical formulation (cream, gel, solution, FFS) and also has high efficacy as a cure for tinea pedis, irrespective of the type of pharmaceutical formulation, treatment duration and frequency of application, including the single-application FFS. This report aims to assess the efficacy of terbinafine 1% FFS compared with other topical formulations of terbinafine 1% (gel, cream, solution) and other topical antifungal treatments for tinea pedis using meta-analytical methods on all available good-quality randomised vehicle-controlled clinical trials.