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

Aim: 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. Methods: 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). Results: 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. Conclusion: The profile of albaconazole and posaconazole compared to current first-line therapies should be further investigated in well-designed trials.