The role of topical antifungal therapy for onychomycosis and the emergence of newer agents.

Onychomycosis is a common infection of the nail unit that is usually caused by a dermatophyte (tinea unguium) and most frequently affects toenails in adults. In most cases, onychomycosis is associated with limited treatment options that are effective in achieving complete clearance in many cases. In addition, recurrence rates are high in the subset of treated patients who have been effectively cleared, usually with an oral antifungal agent. There has been a conspicuous absence of medical therapies approved in the United States since the introduction of topical ciclopirox (8% nail lacquer), with no new effective agents introduced for more than 10 years. Fortunately, newer agents and formulations have been under formal development. While patients might prefer a topical therapy, efficacy with ciclopirox 8% nail lacquer, the only available agent until the very recent approval of efinaconazole 10% solution, has been disappointing. The poor therapeutic outcomes achieved with ciclopirox 8% nail lacquer were not unexpected as the cure rates achieved in the clinical trials were unimpressive, despite concomitant nail debridement, which was an integral part of the pivotal trials with ciclopirox 8% nail lacquer. Efinaconazole 10% solution and tavaborole 5% solution are new topical antifungals specifically developed for the treatment of dermatophyte onychomycosis. In Phase 3 clinical trials, both newer agents were applied once daily for 48 weeks without concomitant nail debridement. Mycologic cure rates with efinaconazole 10% solution are markedly superior to what was achieved with ciclopirox 8% nail lacquer. To add, they appear to be nearly comparable to those achieved with oral itraconazole in pivotal clinical trials. However, it is important to remember that direct comparisons between different studies are not conclusive, are not generally considered to be scientifically sound, and may not be entirely accurate due to differences in study design and other factors. Well-designed and properly powered head-to-head studies are needed in order to draw definitive conclusions about efficacy comparisons between therapies, at least based on academic and regulatory standards. Although tavaborole 5% solution is in an earlier phase of development for onychomycosis, treatment success rates reported thus far for both efinaconazole 10% solution and tavaborole 5% solution are superior to ciclopirox 8% nail lacquer. As a result, a new era of onychomycosis appears to be upon us that incorporates topical therapy more effectively than in the past. Not only may these newer topical agents provide viable monotherapy alternatives to oral therapy for onychomycosis, topical therapy for onychomycosis that is effective, well tolerated, and easy to use may also find a role in combination therapy, and/or as continued therapy after initial clearance to reduce recurrence or re-infection.