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Toenail fungal infections account for half of all nail disease cases, and a highly negative impact on patient quality of life. Our aim was to compare the efficacy and safety of commercially available oral antifungals for onychomycosis. A systematic review was performed in PubMed and Scopus. Randomized controlled trials evaluating the effect of oral antifungals on mycological cure, discontinuation and adverse events were included. Network meta-analyses were built for each outcome. Results were reported as odds ratios (OR) with 95% credibility intervals (CrI). Ranking probabilities were calculated by surface under the cumulative ranking analysis (SUCRA). We included 40 trials ( n  = 9568). Albaconazole 400 mg (OR 0.02 [95% CrI 0.01–0.07]  versus  placebo), followed by posaconazole 200–400 mg and terbinafine 250–350 mg were considered the best therapies (SUCRA probabilities over 75%). For the networks of discontinuation and individual adverse events, few significant differences among treatments were observed, but itraconazole 400 mg was considered the safest drug (SUCRA around 25%). Albaconazole 400 mg, posaconazole 200–400 mg, and terbinafine 250–350 mg were the most effective therapies for onychomycosis, while itraconazole 400 mg was the safest. The profile of albaconazole and posaconazole compared to current first-line therapies should be further investigated in well-designed trials.

Oral antifungal therapies for toenail onychomycosis: a systematic review with network meta-analysis toenail mycosis: network meta-analysis