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Evidence-Based Dermatology: Review |

Efficacy of Topical Antifungals in the Treatment of Dermatophytosis:  A Mixed-Treatment Comparison Meta-analysis Involving 14 Treatments

Inajara Rotta, MSc; Patricia K. Ziegelmann, PhD; Michel F. Otuki, PhD; Bruno S. Riveros, BPharm; Noemia L. M. C. Bernardo, MSc; Cassyano J. Correr, PhD
JAMA Dermatol. 2013;149(3):341-349. doi:10.1001/jamadermatol.2013.1721.
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Importance Considering that most randomized controlled trials compare antifungals with placebo instead of other antifungals, conventional meta-analysis is insufficient to define superiority between the evaluated strategies. To our knowledge, this is the first mixed-treatment comparison meta-analysis on antifungal treatments in the literature and shows all the evidence available at the time of the study.

Objective To evaluate and compare the efficacy of topical antifungals used in dermatophytosis treatment, using mixed-treatment comparisons.

Evidence Acquisition We performed a comprehensive search (up to July 31, 2012) for all entries in MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, Literatura Latino Americana e do Caribe em Ciências da Saúde, and International Pharmaceutical Abstracts. Randomized controlled trials that compared topical antifungals with one another or with placebo in dermatophytosis treatment were selected for analysis. Methodologic quality of the trials was assessed using the Jadad scale. We excluded studies that scored less than 3 points. The outcomes evaluated were mycologic cure at the end of treatment and sustained cure. A random-effects Bayesian mixed-treatment comparisons model was applied to combine placebo-controlled and direct topical antifungals comparison trials.

Results Pooled data of the 65 trials identified did not show any statistically significant differences among the antifungals concerning the outcome of mycologic cure at the end of treatment. Regarding the sustained cure outcome, butenafine hydrochloride and terbinafine hydrochloride were significantly more efficacious than were clotrimazole, oxiconazole nitrate, and sertaconazole nitrate. Terbinafine also demonstrated statistical superiority when compared with ciclopirox (ciclopiroxolamine), and naftifine hydrochloride showed better response compared with oxiconazole. No inconsistency was detected in the network of evidence for both outcomes, sustaining the validity of the mixed-treatment comparisons results.

Conclusions and Relevance With the outcome mycologic cure at the end of treatment, there was no significant difference among the antifungals. Butenafine, naftifine, and terbinafine might be the best strategies for maintaining cured status. Because of the different costs of the antifungals, pharmacoeconomic analysis is required to identify the most efficient strategy for dermatophytosis management.

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Figure 1. Flowchart of the selection of randomized controlled trials included for the mixed-treatment comparison meta-analysis.

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Figure 2. Network of eligible comparisons for the mixed-treatment comparison meta-analysis. A, Mycologic cure at the end of treatment. B, Sustained cure. AMF indicates amorolfine hydrochloride; BFZ, bifonazole; BTF, butenafine hydrochloride; CPX, ciclopirox; CTL, ketoconazole; CTZ, clotrimazole; ECZ, econazole nitrate; FLZ, flutrimazole; MCZ, miconazole nitrate; NFT, naftifine hydrochloride; OCZ, oxiconazole nitrate; PCB, placebo; STZ, sertaconazole nitrate; TBF, terbinafine hydrochloride; and TCZ, tioconazole.

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Figure 3. Mixed-treatment comparison meta-analysis of topical antifungals. Results are the odds ratios associated with their 95% credible interval. For both efficacy outcomes, an odds ratio higher than 1 favored the first drug in alphabetical order. Results given in boldface type show a statistically significant difference between evaluated drugs. The results were obtained using Addis. AMF indicates amorolfine hydrochloride; BFZ, bifonazole; BTF, butenafine hydrochloride; CLZ, clotrimazole; CPX, ciclopirox; ECZ, econazole nitrate; FLZ, flutrimazole; KTZ, ketoconazole; MCZ, miconazole nitrate; NFT, naftifine hydrochloride; OCZ, oxiconazole nitrate; STZ, sertaconazole nitrate; TBF, terbinafine hydrochloride; and TCZ, tioconazole.

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