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Tinea Pedis
Meta-analyses Comparing a Single Application of Terbinafine 1%
Film-forming Solution with Other Topical Treatments for Tinea Pedis
Jean-Paul Ortonne,
1
Martine Feuilhade de Chauvin,
2
Hans Christian Korting,
3
Mahmoud A Ghannoum,
4
Boni E Elewski,
5
Roderick J Hay,
6
Pascal Mallefet,
7
Laurence Poignon Cahen
8
and Jean-Marie Grouin
9
1. Dermatology Department, University Hospital, Nice; 2. Mycology Department, Saint Louis Hospital APHP, University Paris VII;
3. Dermatology Department, University Hospital, Munich; 4. University Hospitals Case Medical Center, Cleveland; 5. Dermatology Department,
University of Alabama at Birmingham School of Medicine; 6. Dermatology Department, King’s College Hospital NHS Trust, London;
7. Novartis Consumer Health SA, Nyon; 8. Novartis Santé Familiale, Rueil-Malmaison; 9. University of Rouen
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.
Keywords
Athlete’s foot, tinea pedis, literature review, randomised vehicle-controlled trials, meta-analysis, statistical superiority, statistical non-inferiority,
topical antifungal treatments, allylamines, azoles, ciclopiroxolamine, mycological cure, compliance
Disclosure and Acknowledgements: The authors thank Vincent Fabien, Statistician in Research and Development at Novartis Consumer Health SA, for his contribution, and
Dr Mike Matthews for his help drafting the manuscript in the role of medical writer on behalf of Novartis Consumer Health SA, who supported this study.
Received: 13 March 2009 Accepted: 15 April 2009
jean-marie.grouin@univ-rouen.fr
Athlete’s foot (tinea pedis) is a common foot infection caused by in Europe and other markets internationally. Compliance with a
dermatophyte fungi. Treatment is by the application of topical single application of a topical antifungal is expected to be
antifungals, typically for a period of one to four weeks. Non- considerably better than compliance with a treatment requiring
compliance with treatment of this duration is an issue and may be daily applications for anything from one to four weeks. If
one of the reasons why the condition has a high rate of recurrence. equivalent efficacy could be shown for FFS compared with
In a survey of 900 patients conducted in Germany, France and the reference treatments (whether other formulations of terbinafine or
UK, half of respondents applied antifungal treatment for less than other agents), there would be an advantage for the simpler single-
13 days, even though commonly available antifungal drugs require use treatment.
three to four weeks’ use.
There are only two published randomised controlled clinical trials
Antifungal agents can be classified as fungicidal or fungistatic. with terbinafine FFS,
2,3
and both of them compared it with its vehicle.
Fungicidal agents such as the allylamines (including terbinafine) In order to compare FFS with other clinically available active
are compounds that kill fungi, whereas fungistatic agents (for treatments, one must rely on an indirect method of comparison. A
example the azole class of compounds) inhibit the growth of recent meta-analysis
1
compared various formulations of terbinafine
fungi.
1
Terbinafine is fungicidal against dermatophytes at with each other and found that this agent is very well tolerated in
concentration levels (minimum inhibitory concentrations any topical pharmaceutical formulation (cream, gel, solution, FFS)
1–10ng/ml) well below those achieved by oral or topical and also has high efficacy as a cure for tinea pedis, irrespective of
administration, and is widely used as a topical agent in the the type of pharmaceutical formulation, treatment duration and
treatment of tinea pedis. It is available in a variety of topical frequency of application, including the single-application FFS. This
formulations (Lamisil
®
, Novartis Consumer Health SA, Nyon, report aims to assess the efficacy of terbinafine 1% FFS compared
Switzerland). Recently, the film-forming solution (FFS) terbinafine with other topical formulations of terbinafine 1% (gel, cream,
1%, which is intended to be applied only once, was made available solution) and other topical antifungal treatments for tinea pedis
© TOUCH BRIEFINGS 2009 19
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