Relative impact of traditional vs. newer oral antifungals for dermatophyte toenail onychomycosis: a network meta-analysis study

Abstract Background There is a paucity of evidence regarding the relative therapeutic efficacy of treatments for onychomycosis. Objectives We determined the relative efficacy of monotherapies for dermatophyte toenail onychomycosis with Bayesian network meta-analyses (NMAs). Methods We searched PubMed, Scopus, EMBASE (Ovid) and CINAHL to identify studies that investigated the efficacy of monotherapy with oral antifungals for dermatophyte toenail onychomycosis in adults. In this paper, ‘regimen’ corresponds to a given agent and its dosage. The relative effects and surface under the cumulative ranking curve (SUCRA) values of the various regimens were estimated; evidence quality was assessed at the study level and across networks. Results Data from 21 studies were used. Our two efficacy-related endpoints were: (i) mycological and (ii) complete cure at 1 year; safety-­related endpoints were: (i) 1-year count of any adverse event (AE), (ii) 1-year odds of discontinuation due to any AE, (iii) 1-year odds of discontinuation due to liver issues. Thirty-five regimens were identified; the newer agents among these included posaconazole and oteseconazole. We compared the efficacy of newer regimens with traditional ones like ‘terbinafine 250 mg daily for 12 weeks’ and ‘itraconazole 200 mg daily for 12 weeks. We found that an agent’s dosage was associated with its efficacy; for example, the 1-year odds of mycological cure with terbinafine 250 mg daily for 24 weeks (SUCRA = 92.4%) were significantly greater than those of terbinafine 250 mg daily for 12 weeks (SUCRA = 66.3%) (odds ratio 2.62, 95% credible interval 1.57–4.54). We also found that booster regimens can increase efficacy. Our results showed that some triazoles could be more effective than terbinafine. Conclusions This is the first NMA study of monotherapeutic antifungals – and their various dosages – for dermatophyte toenail onychomycosis. Our findings could provide guidance for the selection of the most appropriate antifungal agent, especially amid the growing concerns about terbinafine resistance.