Clinical Question

What is the preferred monotherapy for the treatment of toenail onychomycosis?

Bottom Line

For toenail onychomycosis, continuous terbinafine (Lamisil), 250 mg, and continuous itraconazole (Sporanox), 200 mg, for 12 to 24 weeks are the preferred therapies. (Level of Evidence = 1a−)

Synopsis

Network meta-analyses can include direct comparisons (drug A vs. drug B in individual trials) and indirect comparisons (comparing drug A with drug C by linking studies of A vs. B and B vs. C). The researchers performed an appropriate search, and, of the 10,845 studies initially identified, 75 met the inclusion criteria, but only 26 reports of 31 clinical trials provided outcome data regarding cure rates or adverse events that could be used in the analysis. The included studies had a total of 8,136 patients and reported eight treatment regimens, including some with the same drug given continuously or in a pulsed fashion (i.e., daily for one week of a month). Most studies treated patients for 12 to 24 weeks, and the study drugs included ciclopirox 8% solution (Loprox), efinaconazole 10% solution (Jublia), fluconazole (Diflucan), itraconazole, terbinafine, and tavaborole 5% solution (Kerydin). The researchers used conventional methods for data abstraction, quality assessment, and analysis.

Of the 31 trials, only five were judged to be at overall low risk of bias. Most studies failed to describe randomization procedures or allocation concealment, 52% failed to mask participants, and 64% failed to mask outcome assessors. Itraconazole, 200 mg, and terbinafine, 250 mg, were most effective, based on placebo-controlled trials. Continuous regimens were more effective than pulsed regimens. This is consistent with the results based on direct and indirect comparisons. Continuous terbinafine and continuous itraconazole were most likely to be effective for mycologic cure. Adverse events did not differ much among the drugs; itraconazole was the safest.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Self-funded or unfunded

Setting: Various (meta-analysis)

Reference: Gupta AK, Foley KA, Mays RR, et al. Monotherapy for toenail onychomycosis: a systematic review and network meta-analysis. Br J Dermatol. 2020;182(2):287–299.

Editor's Note: Dr. Ebell is deputy editor for evidence-based medicine for AFP and cofounder and editor-in-chief of Essential Evidence Plus, published by Wiley-Blackwell.